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World Health Organization Publications
1991-2002

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Chemical toxicology, carcinogenicity
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Acetaldehyde

Environmental Health Criteria, No. 167
1995, 129 pages [E, with summaries in F, S]
ISBN 92 4 157167 5
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30 Order no. 1160167

Evaluates the risks to human health and the environment posed by exposure to acetaldehyde, a metabolic intermediate in humans and higher plants and a product of alcohol fermentation. As a commercially manufactured chemical, acetaldehyde has important uses as an intermediate in the production of acetic acid, ethyl acetate, and other organic chemicals. The compound is also used as a flavouring agent in beverages, ice cream and ices, candy, baked goods, gelatin desserts, and chewing gum.

Although acetaldehyde formed during the metabolism of ethanol provides the greatest source of human exposure, the report is primarily concerned with the consequences of direct exposure to the chemical. The general population may be exposed via cigarette smoke, air, and a wide range of foodstuffs, with especially high levels detected in some fruit juices, alcoholic beverages, and vinegar. Compared with these sources, exposure through drinking-water was noted to be negligible. In view of the rapid biodegradation of the compound, the report concludes that adverse effects on the aquatic and terrestrial environments should be low.

The remaining sections review the results of toxicity studies and assess the effects of exposure on human health. Toxic effects observed in animals include degenerative changes in the olfactory epithelium and trachea and, at higher concentrations, degenerative changes in the respiratory epithelium and larynx. The limited data in humans are restricted to reports of mild irritation to the eyes and upper respiratory tract.


Acetonitrile

Environmental Health Criteria, No. 154
1993, 110 pages [E, with summaries in F, S]
ISBN 92 4 157154 3
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160154

Evaluates the risks to human health and the environment posed by acetonitrile, a by-product of acrylonitrile manufacture which is widely used as an extractive distillation solvent in the petrochemical industry and as a solvent for polymer spinning and casting. In laboratories, acetonitrile is widely used in high-performance liquid chromatographic analysis and as a solvent for DNA synthesis and peptide sequencing. These practical uses are identified as the major source of human exposure.

Concerning the effects of acetonitrile on organisms in the environment, the report concludes that this chemical has low toxicity due to its rapid volatilization and biodegradation. Studies of kinetics and metabolism indicate that acetonitrile is readily absorbed by all routes and rapidly distributed throughout the body, where it is converted to cyanide. A review of studies conducted in laboratory mammals concludes that acetonitrile induces toxic effects similar to those observed in acute cyanide poisoning, with prostration followed by seizures identified as the main symptoms. No animal studies on chronic or carcinogenic effects have been reported.

In humans, studies of accidental poisoning in occupationally-exposed workers have identified the symptoms and signs of acute acetonitrile intoxication as chest pain, tightness in the chest, nausea, emesis, tachycardia, hypotension, short and shallow respiration, headache, restlessness, semiconsciousness, and seizures. In view of the hazards of poisoning, the report concludes that acetonitrile and mixtures containing this chemical should be clearly labelled with a warning about the danger of poisoning.

"... an invaluable source of reference ... all safety aspects are critically and extensively examined..."
— Journal of the Royal Society of Health


Acrolein

Environmental Health Criteria, No. 127
1992, 119 pages [E, with summaries in F, S]
ISBN 92 4 157127 6
Sw.fr. 24.-/US $21.60; in developing countries: Sw.fr. 16.80
Order no. 1160127

Evaluates the risks to human health and the environment posed by exposure to acrolein, a chemical produced in large quantities and used as an intermediate in the synthesis of several chemicals, most notably acrylic acid and its esters and DL-methionine, an essential amino acid used as a feed supplement for poultry and cattle. Acrolein also has direct application as an aquatic biocide used against algae, molluscs, and herbs in recirculating process water systems, irrigation channels, cooling water towers, and water treatment ponds. Acrolein accounts for about 3 to 10% of total automobile exhaust aldehydes, 1 to 13% of total wood-smoke aldehydes, and up to 7% of the aldehydes in cigarette smoke.

The report notes that exposure of the general population occurs mainly via air, with mainstream and sidestream tobacco smoke representing the most important source. Other sources of exposure include inhalation of air polluted by vehicle exhausts, direct contact with acrolein-treated water, and consumption of alcoholic beverages and certain food items. Concerning effects on the environment, the report cites studies documenting adverse effects on crops grown on soil irrigated by acrolein-treated water, and a very high toxicity for bacteria, algae, crustacea, and fish, with bacteria being the most sensitive species. Acrolein is noted to threaten aquatic life at or near sites of industrial discharge or spills and in areas where acrolein is used as a biocide.

The most extensive section reviews the large number of studies of toxicological effects conducted in laboratory mammals and in vitro test systems. Studies support the conclusion that acrolein is acutely cytotoxic, produces teratogenic and embryotoxic effects, and is weakly mutagenic. Data on carcinogenicity were judged inadequate. In humans, case reports of accidental exposures and suicidal intoxication confirm the high toxicity of this chemical.


Acrylic Acid

Environmental Health Criteria, No. 191
1997, xviii + 106 pages [E, with summaries in F, S]
ISBN 92 4 157191 8
Sw.fr. 27.-/US $24.30; in developing countries: Sw.fr. 18.90
Order no. 1160191

Evaluates the risks to human health and the environment posed by exposure to acrylic acid. Acrylic acid is used primarily in the production of acrylic esters, as a monomer for polyacrylic acid and salts, and as a co-monomer with acrylamide for polymers used as flocculants, with ethylene for ion-exchange resin polymers, with methyl ester for polymers, and with itaconic acid for other co-polymers.

Inhalation and dermal exposures occurring in occupational settings were judged to be the most important exposures affecting human health. Exposure via food was determined to be unlikely. An evaluation of findings from toxicity studies in experimental animals and in vitro test systems concludes that acrylic acid shows, in most studies, low to moderate acute toxicity by the oral route and moderate acute toxicity by the inhalation and dermal routes. Studies also confirm that acrylic acid is corrosive or irritant to the skin and eyes and strongly irritant to the respiratory tract. Available data indicate that the chemical is not teratogenic and has no adverse effects on reproduction. Data on carcinogenic potential were judged inadequate to support firm conclusions.

The evaluation of effects on human health was limited by the absence of any epidemiological studies of occupationally exposed workers and any reports of accidental poisonings. On the basis of animal studies and knowledge about the chemical and biological behaviour of the chemical, the report concludes that acrylic acid does not pose any obvious risks to the health of the general population. Risks associated with occupational exposure were judged to be low, provided good industrial practice is followed.

Because toxicity occurs at the site of contact, the report recommended separate health-based guidance values for oral and inhalation exposure. Proposed guidance values for the general population are 9.9 mg/litre for drinking-water and 54 mg/m3 for ambient air.


Aldicarb

Environmental Health Criteria, No. 121
1991, 130 pages [E, with summaries in F, S]
ISBN 92 4 157121 7
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160121

Evaluates risks to human health and the environment posed by aldicarb, a carbamate insecticide applied, exclusively in granular form and below the soil surface, to control certain insects, mites, and nematodes. Aldicarb has been approved for use on a wide range of crops; ingestion of contaminated food is the main route of exposure for the general population.

Because aldicarb is applied to the subsoil, the evaluation of environmental fate concentrates on mobility and persistence in soil and on the circumstances under which aldicarb may contaminate shallow wells. The rapid uptake of aldicarb and its residues by food crops is another consistently reported finding. Studies in experimental animals point to the efficient absorption of aldicarb from the gastrointestinal tract and its wide distribution to all tissues, including the developing fetus. Concerning risks to human health, the book draws on reports of several widespread outbreaks of aldicarb poisoning following the ingestion of contaminated cucumbers, melons, watermelons, and drinking water. In each of these cases, poisoning resulted from the use of aldicarb on a non-approved crop.

The book concludes that aldicarb is one of the most potent and acutely toxic pesticides in use, that most cases of poisoning and toxicity arise from the use of aldicarb on non-approved crops or the failure to follow recommended safety precautions, that the symptoms of poisoning are transient and rarely fatal, and that aldicarb poses no risk to the general population when applied at recommended rates and using current techniques. The need to use protective equipment during manufacture, formulation, and application is stressed.


Aluminium

Environmental Health Criteria, No. 194
1997, xx + 282 pages [E, with summaries in F, S]
ISBN 92 4 157194 2
Sw.fr. 60.-/US $54.00; in developing countries: Sw.fr. 42.-
Order no. 1160194

Evaluates the risks to human health and the environment posed by exposure to aluminium. In view of recent evidence suggesting a role of aluminium exposure in the development or progression of Alzheimer's disease, the report gives particular attention to the methodological strengths and weaknesses of epidemiological studies and the relevance to humans of animal data demonstrating neurotoxicity in several species. Over 700 studies were assessed in an effort to resolve current uncertainties about risks to the general population, exposed workers, the elderly, and several other susceptible subpopulations

Background information is provided in the opening sections, which summarize what is known about sources of environmental and human exposure and discuss the main routes and levels of exposure. The report notes that aluminium is released to the environment both by natural processes and from anthropogenic sources. As aluminium is a major constituent of the earth's crust and the third most common element, natural processes far outweigh the contribution of anthropogenic sources.

Concerning sources of human exposure, ingestion of aluminium present in food is identified as the main source for the general population, with food and beverages accounting for 90-95% of total daily intake. Much higher exposures are noted to occur in certain occupations and in people taking antacids and buffered analgesics. The report also cites recent evidence indicating that drinking-water is a minor source of human exposure.

A review of human and animal data on kinetics and metabolism concludes that aluminium and its compounds are poorly absorbed in humans; the highest levels have been detected in the lungs. In animals, aluminium is distributed in most organs within the body, with accumulation occurring mainly in bone at high dose levels.

An evaluation of the large body of data from toxicity studies in experimental animals found no evidence that aluminium is carcinogenic and no evidence of fetotoxicity or adverse effects on reproduction. Considerable evidence indicates that aluminium is neurotoxic, with adverse effects on neurological development and brain function. Studies have also demonstrated toxic effects on bone, and osteomalacia, as it presents in man, has been consistently observed. The report found no evidence that exposure induces a neurological pathology with the morphological and biochemical characteristics of Alzheimer's disease.

The evaluation of effects on human health gives particular attention to several epidemiological studies carried out to test the hypothesis that aluminium in drinking-water is a risk factor for the development or acceleration of Alzheimer's disease and a possible cause of impaired cognitive function in the elderly and in occupationally-exposed workers. Following a critical assessment of the design of these studies, all of which have flaws, the report concludes that, while a possible association cannot be totally dismissed, currently available evidence does not support a causal relationship between Alzheimer's disease and exposure to aluminium in drinking-water. The hypothesis that particular exposures, either occupational or via drinking-water, may be associated with non-specific impaired cognitive function was likewise judged to be inadequately supported by available data.

While aluminium has not been shown to pose a risk to healthy, non-occupationally exposed humans, abundant studies demonstrate that patients with renal failure are at risk of neurotoxicity and other disorders from aluminium present in haemodialysis fluid and pharmaceutical products. As iatrogenic aluminium exposure has been shown to pose a hazard to patients with chronic renal failure and to premature infants, the report concludes that every effort should be made to limit exposure in these groups.

Concerning risks to the environment, the report concludes that concentrations of aluminium can increase to levels resulting in adverse effects on both aquatic organisms and terrestrial plants in some areas subject to strong acidifying inputs.


Amitrole

Environmental Health Criteria, No. 158
1994, 123 pages [E, with summaries in F, S]
ISBN 92 4 157158 6
Sw.fr. 28.-/US $25.20; in developing countries: Sw.fr. 19.60
Order no. 1160158

Evaluates the risks to human health and the environment posed by exposure to amitrole, a herbicide with a very wide spectrum of activity against annual and perennial broad leaf and grass type weeds. Amitrole, which appears to act by inhibiting the formation of chlorophyll, is widely used around orchard trees, on fallow land prior to sowing, along roadsides and railway lines, and for weed control in ponds. The herbicide is not approved for direct application to food crops.

A review of studies on the environmental fate of amitrole concludes that the compound is relatively rapidly degraded in the environment, with no evidence of either bioaccumulation or entry into the food chain. Exposure of the general public is expected to be minimal. Studies in both humans and animals show that amitrole is rapidly absorbed and rapidly excreted in urine in an unchanged form.

The most extensive section evaluates the large number of experimental studies that have demonstrated toxic effects on the thyroid. These findings support the conclusion that amitrole is goitrogenic, causing thyroid hypertrophy and hyperplasia, depletion of colloid, and increased vascularity. Experiments indicate that these changes precede the development of thyroid neoplasia; the precise mechanism triggering the change from hyperplasia to neoplasia remains to be elucidated. Although studies of occupationally-exposed workers are largely reassuring, the book recommends annual monitoring of thyroid function in workers regularly handling amitrole at either the formulation or application stage. The book further concludes that amitrole poses no significant threat to the environment, that levels in food and drinking-water should be extremely low, and that the herbicide poses no threat to the health of workers or the general population when manufactured and used as recommended.


Anticoagulant Rodenticides

Environmental Health Criteria, No. 175
1995, 121 pages [E, with summaries in F, S]
ISBN 92 4 157175 6
Sw.fr. 28.-/US $25.20; in developing countries: Sw.fr. 19.60
Order no. 1160175

Evaluates the risks to human health and the environment posed by the use of anticoagulants for rodent control in urban and agricultural settings. Warfarin, which was introduced in the late 1940s, is considered together with the more potent second-generation anticoagulants, including the single dose "superwarfarins". Because warfarin is widely used in the clinical management of thromboembolic disease, its effects on human health are well documented. Abundant information is also provided on the mechanisms by which these anticoagulants act as vitamin K antagonists.

An evaluation of effects on laboratory animals and in vitro test systems demonstrates high acute toxicity by oral, percutaneous, and inhalation routes. Anticoagulant rodenticides are noted to disrupt the normal blood-clotting mechanisms, resulting in increased tendency to bleed and, at higher exposures, in profuse haemorrhage. The second generation anticoagulant rodenticides differ from warfarin in their greater toxicity, their longer retention times in the liver, and their corresponding tendency to induce bleeding for weeks instead of days.

An evaluation of effects on human health draws on the large number of case reports of accidental and intentional poisoning, a few case reports of intoxication following occupational exposure, and extensive experience in the clinical use of warfarin. Following exposure to second generation anticoagulants, symptoms of human poisoning include haematomas, haematemesis, haematuria, and easy bruising. Teratogenic effects have been demonstrated following the administration of warfarin during pregnancy. The report found no evidence that anticoagulant rodenticides are mutagenic or carcinogenic, but did cite evidence that long-term exposure to low levels may have an adverse effect on bone metabolism.

Arsenic and Arsenic Compounds
Second Edition

Environmental Health Criteria Series, No. 224
2001, 521 pages [E]
ISBN 92 4 157224 8
Swiss francs: 108.—/US $97.20
In developing countries: Swiss francs 75.60
Order no. 1160224

This book evaluates the risks to human health and the environment posed by arsenic and arsenic compounds. Arsenic is widely distri-buted in the earth's crust and is emitted into the atmosphere by coal-fired power generation plants and volcanic activity. Inorganic arsenic of geological origin is found in groundwater used as drinking-water in several parts of the world, e.g., Bangladesh. In these areas, drinking-water is the main source of arsenic intake, but elsewhere food is the principal source.

 


Assessing Human Health Risks of Chemicals: Derivation of Guidance Values for Health-based Exposure Limits

Environmental Health Criteria, No. 170
1994, 73 pages [E, with summaries in F, S]
ISBN 92 4 157170 5
Sw.fr. 21.-/US $18.90l in developing countries: Sw.fr. 14.70
Order no. 1160170

Outlines methods and procedures for the derivation of guidance values for protecting the health of humans exposed to chemical substances. Guidance values provide quantitative information from risk assessment for regulatory authorities and other risk managers, and provide a basis for the establishment of national or local exposure limits and standards. The approach described relates primarily to long-term exposure of the general population in the ambient environment. Addressed to all involved in chemical safety, the book aims to promote consistency in the methods used when evaluating the health effects of environmental chemicals and formulating credible conclusions. Information ranges from guidance on the use of uncertainty factors when human data are lacking to advice on how to establish a tolerable intake when a chemical shows more than one adverse effect.

The first section introduces key terms and explains the two principal methodological concepts: development of a tolerable intake on the basis of interpretation of available toxicity data, and allocation of the proportions of the tolerable intake to various environmental media. The second section describes procedures for determining a tolerable intake on the basis of toxicity data. Section three sets out a series of steps to be followed when extrapolating from a toxicity data base to a tolerable intake, moving from selection of a pivotal study and critical effects, through interspecies extrapolation, to a final review of the total uncertainty factor. The concluding section offers advice on the allocation of tolerable intakes to derive guidance values.

"... recommended for all those unfamiliar with the processes of risk assessment..."
— Annals of Occupational Hygiene


Bacillus thuringiensis

Environmental Health Criteria, No. 217
1999, xv + 105 pages (English, with summaries in French and Spanish)
ISBN 92 4 157217 5
Sw.fr. 27.–/US $24.30; in developing countries: Sw.fr. 11.20
Order no. 1160217


This book evaluates the risks to human health and the environment posed by the use of Bacillus thuringiensis (Bt) as a microbial agent for pest control. Products containing various Bt subspecies are increasingly used worldwide to control the larvae of several insect pests that threaten major agricultural crops and forests. Bt products are also being used to control the insect vectors of malaria, onchocerciasis, and other diseases of major public health importance. The bacterium is also a key source of genes for transgenic expression to provide pest resistance in plants and microorganisms.


The report opens with an overview of the biological properties of Bt and commercial Bt products. Particular attention is given to the mechanisms by which sporulation produces inclusion bodies, containing insecticidal crystalline proteins, which are selectively toxic for insect species in the orders Coleoptera, Diptera, and Lepidoptera. Tables show the current classification of 67 Bt subspecies and the large number of genes coding for the insecticidal crystalline proteins. A review of Bt metabolites found in commercial products concludes that they pose no hazards to humans or the environment.


Chapter two reviews data elucidating the mechanisms by which Bt exerts its toxic action on susceptible insect larvae. Data on insect populations that are resistant to Bt are also briefly considered. Chapter three, which focuses on the survival and activity of Bt in the environment, compares habitats where Bt subspecies occur naturally with treated habitats. Particular attention is given to the ability of Bt to form endospores that are resistant to inactivation by heat and desiccation and that persist in the environment under adverse conditions. A chapter on commercial production describes methods of production and general patterns of use in agriculture and forestry, and in large-scale programmes to control the vectors of malaria and onchocerciasis.


The most extensive chapter evaluates the large number of studies conducted to assess the toxicity of various preparations containing insecticidal crystalline proteins, spores, and vegetative cells. Laboratory studies in a range of species have failed to demonstrate toxic or pathogenic effects. Field studies have likewise failed to demonstrate adverse effects on birds, earthworms, fish, other aquatic vertebrates, and non-target aquatic invertebrates. An evaluation of effects on humans draws on studies in volunteers, case reports from occupationally-exposed workers, and extensive data from countries where Bt products are added to drinking-water for mosquito control or used to treat rivers for blackfly control.


On the basis of this review, the report concludes that Bt products are unlikely to pose any hazard to humans or other vertebrates or to the great majority of non-target invertebrates, provided the commercial product is free from non-Bt microorganisms and biologically active products other than the insecticidal crystalline proteins. The report further concludes that Bt products can be safely used for the control of insect pests of agricultural and horticultural crops and forests. These products are likewise judged safe for use in aquatic environments, including drinking-water reservoirs, for the control of mosquito, black fly, and nuisance insect larvae. The report stresses, however, that vegetative Bt has the potential to produce Bacillus cereus-like toxins whose significance as a possible cause of human gastrointestinal disease remains unknown.
"...one of the most thorough published reviews of Bacillus thuringiensis ... provides an array of pertinent background material..."
-- Integrated Pest Management Network

Barium

Environmental Health Criteria, No. 107
1990, 148 pages [E]
ISBN 92 4 157107 1
Sw.fr. 28.-/US $25.20; in developing countries: Sw.fr. 19.60
Order no. 1160107

Evaluates the risks to human health and the environment posed by the mining, processing, and industrial use of barium. The opening sections review both natural and man-made sources of release into the environment, including nuclear fallout following the testing of weapons. A section on environmental behaviour notes the contribution of industrial emissions, especially from the combustion of coal and diesel oil, to the presence of barium in air. Particular concern centres on concentrations found in water, where barium may have a residence time of several hundred years. Water supplies and food are identified as the most important routes of exposure for the general population.

Other sections review what is known about the kinetics and metabolism of barium, discuss its capacity to mimic the role of calcium in many physiological processes, and consider effects on organisms in the environment, including effects on the infectivity of several viruses.

The most extensive section evaluates experimental studies of barium toxicity, with particular attention given to reported effects on cardiovascular functions. The final section, devoted to effects on human health, evaluates findings from large-scale outbreaks of barium poisoning and from epidemiological studies designed to determine whether high barium concentrations in drinking-water are linked to disturbances in cardiovascular function. On the basis of these evaluations, the book concludes that barium poses no special risk for the general population. Potassium-deficient individuals, the elderly, exposed workers, and populations consuming high concentrations of barium in drinking water may experience adverse effects on health.

"... most impressive..."
— Annals of Occupational Hygiene


Benomyl

Environmental Health Criteria, No. 148
1993, 135 pages [E, with summaries in F, S]
ISBN 92 4 157148 9
Sw.
Order no. 1160148

Evaluates the risks to human health and the environment posed by benomyl, a fungicide registered for use in 50 countries on over 70 crops, including cereals, cotton, soybeans, tobacco, mushrooms, grapes, bananas and other fruits. One of the most widely used members of the benzimidazole family of fungicides, benomyl is effective, at low usage rates, against more than 190 different fungal diseases. Because benomyl is rapidly converted to carbendazim in the environment and is extensively metabolized to carbendazim by experimental animals, data from studies of carbendazim, which is a fungicide in its own right, are also considered when evaluating the hazards of benomyl.

Concerning hazards to environmental organisms, the report cites data from laboratory and field studies indicating that benomyl, applied at recommended rates, has little effect on soil microbial activity, but some adverse effects on groups of fungi. Benomyl is toxic to earthworms in laboratory experiments at realistic exposure concentrations and as a result of recommended usage in the field; earthworm populations may take more than two years to recover. Although high toxicity to aquatic organisms has been demonstrated in laboratory tests, the report concludes that this effect is unlikely to be seen in the field, due to the low bioavailability of sediment-bound residues.

For the general population, the main source of potential exposure is noted to be through the ingestion of food crops containing residues of benomyl and carbendazim. Though benomyl has been shown to cause contact dermatitis and dermal sensitization in some farm workers, the report found no evidence that either of these compounds can cause systemic toxic effects in occupationally exposed subjects or the general population. The report cites findings suggesting that both compounds pose a very low risk for acute poisoning in humans.


Benzene

Environmental Health Criteria, No. 150
1993, 156 pages [E, with summaries in F, S]
ISBN 92 4 157150 0
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.00
Order no. 1160150

Evaluates the risks to human health and the environment posed by exposure to benzene, a naturally occurring chemical found in crude petroleum and manufactured in extremely large quantities worldwide. The presence of benzene in gasoline and in cigarette smoke, combined with its widespread use as an industrial solvent, has resulted in the presence of this chemical in the environment. Because benzene is a well-established human carcinogen, the book gives particular attention to data relating patterns, levels, and duration of exposure to health hazards in both the general population and exposed workers.

A section on sources of exposure identifies emissions from motor vehicles as the largest source of this chemical detected in the general environment. For indoor environments, data show that cigarette smoke results in the exposure of non-smokers as well as smokers to important levels of benzene. The report concludes that most humans are exposed to trace levels, with much higher levels seen in cigarette smokers, those exposed to sidestream smoke, residents in areas of heavy automobile traffic, and workers involved in the production, handling, and use of benzene and its derivatives.

The most extensive section reviews the large number of toxicity studies of benzene. Particular attention is given to the numerous animal studies demonstrating carcinogenicity and exploring the mechanisms by which benzene damages bone marrow and exerts its other toxic effects. The remaining sections assess the risks to human health posed by benzene in both the general population and in exposed workers, giving particular attention to the numerous epidemiological and case studies that have established benzene as a human leukaemogen. Because the health risk of low-level benzene exposure is not yet clearly established, the report concludes that exposure should be avoided as much as possible.

Benzoic Acid and Sodium Benzoate

Concise International Chemical Assessment Document, No. 26
2000, iv + 48 pages [E, with summaries in F, S]
ISBN 92 4 153026 X
Sw.fr. 17.–/US $15.30
In developing countries: Sw.fr. 11.90
Order no. 1380026

A concise assessment of the risks to human health and the environment posed by exposure to benzoic acid and sodium benzoate. Benzoic acid is used as an intermediate in the synthesis of several compounds, including phenol and caprolactam. The compound is increasingly used in the production of diethylene and dipropylene glycol dibenzoate plasticizers in adhesive formulations, and to improve the properties of alkyd resins for paints and coatings. Most releases of benzoic acid and sodium benzoate into the environment result from their use as preservatives in food, beverages, mouthwashes, dentifrices, and cosmetics. For sodium benzoate, the largest use is as an anticorrosive added to antifreeze coolants. Processed foodstuffs and soft drinks are considered the main sources of exposure for the general population.

Concerning behaviour in the environment, both compounds are readily biodegraded under aerobic conditions and are unlikely to bioaccumulate. In laboratory animals, exposure to high concentrations caused weight gain and adverse effects on the central nervous system, liver, and kidney. While data are limited, studies suggest that the compounds do not cause adverse effects on development or reproduction and are not carcinogenic.

In humans, reports of adverse effects are largely confined to cases of urticaria, asthma, rhinitis, and anaphylactic shock following oral, dermal, or inhalation exposure to these compounds, including for medical purposes. No evaluation of long-term effects on health was possible in view of the limited data available.

 


Beryllium

Environmental Health Criteria, No. 106
1990, 210 pages [E, with summaries in F, S]
ISBN 92 4 157106 3
Sw.fr. 37.-/US $33.30; in developing countries: Sw.fr. 25.90
Order no. 1160106

Evaluates risks to human health and the environment posed by the use of beryllium, a brittle metal having major applications in the electronics and micro-electronics industries, in nuclear energy, and in the production of military devices, including satellites, missiles, atomic bombs, and other weapons. Beryllium has also proved its superiority as a structural material for aircraft and spacecraft.

An evaluation of sources of exposure cites the combustion of fossil fuels as the most important source of atmospheric beryllium, with coal singled out as the main pollutant source. For humans, the report notes that toxicologically relevant exposure is almost exclusively confined to the workplace. Only two applications pose a risk to the general population: mantle-type camping lanterns and the use of beryllium in dental prostheses and cements.

The most extensive section evaluates data from the large number of toxicological studies documenting the development of acute chemical pneumonitis and a highly species-specific induction of pulmonary cancer. An evaluation of effects on humans, which concentrates on occupational exposures, summarizes findings on the occurrence of both acute and chronic beryllium disease. The review also yields clinically useful information on exposure levels, characteristic signs and symptoms, and the most reliable diagnostic tests. In view of the controversy concerning the carcinogenicity of beryllium, particularly careful attention was given to several studies repor-ting a significantly elevated risk of lung cancer in exposed workers. Evidence was judged sufficient to confirm the role of beryllium in the development of human lung cancer. The report further concludes that the potential of beryllium to provoke contact allergic reactions, supported by several reports of allergic contact stomatitis in dental patients, calls for a reconsideration of the use of this metal in dentistry.


Beryllium, Cadmium, Mercury, and Exposures in the Glass Manufacturing Industry

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 58
1993, 444 pages [E]
ISBN 92 832 1258 4
Sw.fr. 75.-/US $67.50; in developing countries: Sw.fr. 52.50
Order no. 1720058

Evaluates the carcinogenic risk to humans posed by exposure to selected metals and their compounds. Separate monographs are presented for beryllium and beryllium compounds, cadmium and cadmium compounds, and mercury and inorganic and methylmercury compounds. Because several metallic salts and pigments are used in the manufacture and colouring of certain glass products, the book also evaluates the carcinogenic risk posed by exposures in the glass manufacturing industry. More than 1,200 references to the recent literature are included.

The first monograph evaluates biological and epidemiological data on metallic beryllium, beryllium-aluminium and -copper alloys, and some beryllium compounds. Data from studies in humans and several well-designed animal investigations support the conclusion that beryllium and beryllium compounds are carcinogenic to humans. The monograph on cadmium and cadmium compounds gives particular attention to new analyses of epidemiological cohorts and new studies in experimental animals. These data support the conclusion that cadmium and cadmium compounds are carcinogenic to humans. The monograph on mercury and mercury compounds classifies methylmercury compounds as possibly carcinogenic to humans. Metallic mercury and inorganic mercury compounds could not be classified.

Citing evidence from recent cohort studies, the monograph on exposures in the glass manufacturing industry concludes that the manufacture of art glass, glass containers, and pressed ware entails exposures that are probably carcinogenic to humans. Occupational exposures in flat-glass and special glass manufacture could not be classified as to their carcinogenicity to humans.


Biomarkers and Risk Assessment: Concepts and Principles

Environmental Health Criteria, No. 155
1993, 92 pages [E, with summaries in F, S]
ISBN 92 4 157155 1
Sw.fr. 24.-/US $21.60; in developing countries: Sw.fr. 16.80
Order no. 1160155

A guide to the concepts and principles governing the use of biomarkers to assess the risks to human health posed by exposure to chemical agents. Emphasis is placed on criteria for the selection and validation of appropriate biomarkers of exposure, of toxic effect, and of susceptibility in either individuals or sub-populations. The book also explains how the use of validated biomarkers to monitor exposed populations can provide the basis for early public health interventions.

The book opens with background information on the uses of biomarkers for health risk assessment, clinical diagnosis, and the monitoring of exposure, followed by a discussion of the principles and methods governing their selection and validation. The ethical and social issues that need to be considered when designing research projects are also discussed.

The main part of the book sets out guidelines, supported by examples from recent research, for the selection and use of biomarkers of exposure, of effect, of carcinogenicity, and of susceptibility. For biomarkers of effect, the book concentrates on biomarkers that are currently used or under development to assess toxic effects on the hepatic, renal, haematological, immune, pulmonary, reproductive, developmental and nervous systems. For biomarkers of genotoxic carcinogens, the book describes currently available techniques using DNA adducts, protein adducts, cytogenic methods, chromosome damage, sister chromatid exchange, micronuclei, aneuploidy, and mutation. Biomark-ers for non-genotoxic carcinogens are also briefly discussed. The concluding chapter, on susceptibility, alerts researchers to the many factors that can affect individual susceptibility to the toxic effects of chemicals.


Biomarkers in Risk Assessment: Validity and Validation

Environmental Health Criteria, No. 222
2001, 238 pages
ISBN 92 4 157222 1
Swiss francs 42.—
In developing countries:Sw.fr. 29.40
Order no. 1160222

This publication seeks to provide a framework for selecting and validating biomarkers for risk assessment. Initial chapters consider the role of biomarkers in risk assessment and their validity.

A biomarker is any substance, structure or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease. Biomarkers can be classified into markers of exposure, effect and susceptibility. If biomarkers are to contribute to environmental and occupational health risk assessments, they have to be relevant and valid. Relevance refers to the appropriateness of biomarkers to provide information on questions of interest and importance to public and environmental health authorities and other decision-makers.

The validity of a biomarker is a function of intrinsic qualities of the biomarker and characteristics of the analytic procedures. Additionally, three broad categories of validity can be distinguished: measurement validity, internal study validity and external validity. Measurement validity is the degree to which a biomarker indicates what it purports to indicate. Internal study validity is the degree to which inferences drawn from a study actually pertain to study subjects and are true. External validity is the extent to which findings of a study can be generalized to apply to other populations.

Subsequent chapters examine the validation of specific types of biomarkers and cross-species comparability.Supporting the main text are four extensive appendices covering the following subjects:

Biomarkers of exposure and effect for carcinogenicity
Biomarkers of exposure and effect for non-carcinogenic end-points
Measurement of drug metabolizing enzyme polymorphisms as indicators of susceptibility

Validation of biomarkers for environmental health research and risk assessment



Brominated Diphenyl Ethers

Environmental Health Criteria, No. 162
1994, 347 pages [E, with summaries in F, S]
ISBN 92 4 157162 4
Sw.fr. 62.-/US $55.80; in developing countries: Sw.fr. 43.40
Order no. 1160162

Evaluates the risks to human health and the environment posed by exposure to ten brominated diphenyl ethers. Of these, three (decabromodiphenyl ether, octabromodiphenyl ether, and pentabromodiphenyl ether) are widely manufactured and used as additive flame retardants. The remaining seven compounds occur as contaminants or impurities in commercial brominated flame retardants.

Because of their success in reducing fire hazards for the general public, brominated biphenyl ethers are used in increasing quantities in a wide range of products. Concern about potential risks to human health and the environment has centered on the persistence of these chemicals in the environment, their tendency to bioaccumulate, their detection in several food items and in human adipose tissue and milk, their tendency to leach or escape from finished products during normal operation, and the release of polybrominated dibenzofurans and polybrominated dibenzodioxins as breakdown products under certain conditions.

For decabromodiphenyl ether, which is the most important of these products, the report cites evidence of persistence in the environment, accumulation in sediment and soil, occupational exposure during manufacturing and formulation, and an insignificant exposure of the general population. Similar risks to the environment were found for octabromodiphenyl ether. For pentabromodiphenyl ether, evidence of environmental hazards and potential human exposure via the food chain supports the conclusion that this product should not be used.

In its conclusions, the report stresses the need to minimize environmental contamination with these persistent compounds and their breakdown products. Introduction of such chemicals into widely used products may create a considerable long-term diffuse source of emissions into the environment.


Cadmium

Environmental Health Criteria, No. 134
1992, 280 pages [E, with summaries in F, S]
ISBN 92 4 157134 9
Sw.fr. 50.-/US $45.00; in developing countries: Sw.fr. 35.00
Order no. 1160134

Evaluates the large body of experimental and epidemiological evidence linking cadmium exposure to adverse effects on the health of workers and the general population. In view of the global importance of cadmium as a potentially dangerous environmental pollutant, the book makes a special effort to establish a dose-response relationship for the widely documented adverse effects on the kidney and other organs observed in chronically exposed populations. Findings from over 700 investigations were critically appraised.

The report notes that most human uptake of cadmium occurs via the inhalation of air and the ingestion of contaminated food and drinking-water, with other sources contributing only small amounts to the total uptake. A review of data on the kinetics and metabolism of cadmium in laboratory mammals and humans concludes that exposure via inhalation is more important than exposure via the gastrointestinal route, that the highest cadmium concentrations are generally found in the renal cortex and that, as exposure levels increase, a greater proportion of the absorbed cadmium is stored in the liver.

The second half of the report evaluates investigations of cadmium toxicity. Data from experimental studies support the conclusion that long-term exposure to cadmium leads to renal dysfunction with proteinuria, glucosuria, aminoacid-uria, and histopathological changes in the kidney. The evaluation of effects on humans draws upon epidemiological and clinical studies conducted in occupationally exposed workers and in populations from environments polluted with cadmium. The report concludes that exposure to cadmium produces a wide variety of effects involving many organs and systems. From the point of view of preventive medicine, the detection of early effects on the kidney is regarded as crucial to the prevention of more severe effects on the kidney, lungs, and bones.


Cadmium - Environmental Aspects

Environmental Health Criteria, No. 135
1992, 156 pages [E, with summaries in F, S; R]
ISBN 92 4 157135 7
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.00
Order no. 1160135

Evaluates the threat to ecosystems posed by contamination of the environment with cadmium from natural and industrial sources. More than 350 investigations were critically assessed. The opening sections outline the most important natural and industrial sources of environmental contamination, describe mechanisms of environmental transport, and summarize data on concentrations of cadmium found in various biota. Natural sources identified include zinc, lead, and copper ore and volcanic activity. Noting a major shift in industrial applications over the past few decades, the report cites a decline in the use of cadmium for electroplating and a significant increase in its use in batteries. Other important sources of environmental contamination include steel production and the use of phosphate fertilizers.

Kinetics and metabolism are reviewed in the third section, which concentrates on the many environmental variables, such as temperature, salinity, pH, and the chemical composition of water and soil, that influence cadmium uptake in different aquatic and terrestrial systems and determine the toxic impact on organisms and microorganisms. The remaining sections evaluate data on toxicity to microorganisms, aquatic organisms, and terrestrial organisms, and review the results of field investigations. Documented consequences of environmental contamination with cadmium from either natural or man-made sources include the development of cadmium tolerance in some species, reduced breakdown of leaf litter and recycling of nutrients, physiological abnormalities in fish, and kidney damage in sea-birds. Because of flaws in the design of many investigations, the book concludes that the impact of cadmium on ecosystems may have been underestimated.

"... a well-balanced and up-to-date appraisal..."
— Annals of Occupational Hygiene


Cancer Risk from Occupational Exposure to Wood Dust
A Pooled Analysis of Epidemiological Studies

P.A. Demers and P. Boffetta
IARC Technical Report,
No. 30
1998, iii + 97 pages [E]
ISBN 92 832 144 7
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1770030

Describes the design and findings of a pooled re-analysis of epidemiological studies investigating carcinogenicity in workers exposed to wood dust. The analysis included a large number of studies whose results have not been fully explored due to limitations, mainly linked to small size, inherent in each study. By pooling these studies, the IARC analysis allowed a more powerful interpretation of previously published case-control studies of sino-nasal cancer and cohort studies of workers in wood-related industries. The result is the largest data set ever assembled to examine the relationship between exposure to wood dust and human cancer.

Although exposure to wood dust has long been associated with a very high excess of sino-nasal cancer, the IARC analysis aimed to answer several remaining questions concerning the possible excess risk of cancer at other sites, the level of wood dust exposure needed to cause cancer, the differences between exposure to dust from soft- and hardwood, and the reasons for the wide range of relative risks for sino-nasal cancer and the results observed for other cancers. A uniform exposure assessment strategy was applied in order to classify study subjects according to levels of exposure.

The opening chapters explain the methodology of the pooled re-analysis and provide a detailed description for each of the twelve case-control studies of sino-nasal cancer and five cohorts of workers in wood-related industries. In addition to the predicted excess of sino-nasal cancer, the analysis found an excess of nasopharyngeal cancer and lymphatic and haematopoietic cancer, particularly multiple myeloma. No evidence was found for an excess risk of deaths from lung cancer.


Carbaryl

Environmental Health Criteria, No. 153
1994, 358 pages [E, with summaries in F, S]
ISBN 92 4 157153 5
Sw.fr. 67.-/US $60.30; in developing countries: Sw.fr. 46.90
Order no. 1160153

Evaluates the design and findings of over 700 studies in an effort to determine the risks to human health and the environment posed by carbaryl. This broad spectrum contact and ingestion insecticide has been widely used for over 30 years to control various insect pests on food and fibre crops, trees, and ornamentals. In veterinary practice, carbaryl is used to control flies, mosquitos, ticks, and lice in cattle, poultry, and pets. The compound is also used to treat body louse infestation in humans. Carbaryl is currently processed by more than 290 formulators into over 1,500 different registered products. The general population may be exposed through food or following pest control operations in the home and in camping, picnic, and other recreational areas. Workers can be exposed during manufacturing, formulation, packing, transportation, storage, and during and after application.

The most extensive section reviews the large number of experiments designed to assess the toxic effects of carbaryl and elucidate its mechanisms of action. These studies, supported by limited data on humans, confirm that carbaryl poses no risk of inducing genetic changes in either the somatic or the germinal tissue of humans, that toxic effects are consistent with the signs and symptoms of cholinesterase inhibition, and that signs of intoxication develop quickly, appear well before a dangerous dose is absorbed, and disappear rapidly when exposure ends.

The book concludes that, under normal conditions of use, carbaryl poses a low risk to the environment and to the health of the general population. Levels detected in food and drinking-water are unlikely to endanger health. When reasonable safety precautions and measures for personal protection are enforced, occupational exposure to carbaryl during manufacture, formulation and application will not create health hazards for workers.


Carbendazim

Environmental Health Criteria, No. 149
1993, 132 pages [E, with summaries in F, S]
ISBN 92 4 157149 7
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160149

Evaluates the risks to human health and the environment posed by exposure to carbendazim, a systemic fungicide which is the most widely used compound in the benzimidazole family of fungicides. Carbendazim is used to control a wide range of fungi responsible for several important plant diseases. Plants protected by this fungicide include cereals, cotton, sugar beet, soybeans, vegetables, fruits, and many other food crops. Because carbendazim is the main metabolite of benomyl in mammals and the degradation product of benomyl in the environment, data from studies of both compounds are considered in the report.

The most extensive section reviews the large number of experimental studies designed to investigate the toxicity of carbendazim. Although data on human exposure are limited to two studies, the report draws on the large body of experimental work, supported by knowledge of how carbendazim exerts its toxic effects in both target and non-target species, to conclude that the likelihood of systemic toxicity following exposure in either the gene-ral population or workers is remote. Given current occupational exposures and the low rate of dermal absorption, the report further concludes that, when proper protective clothing is worn, health risks of agricultural exposure are low.

Concerning effects on organisms in the environment, the report cites evidence that both benomyl and carbendazim are highly toxic to certain aquatic organisms in laboratory tests, but concludes that this toxicity is not likely to occur under field conditions due to the compound's low bioavailability in surface waters. The report also cites evidence, from both laboratory and field investigations, that benomyl and carbendazim, applied at recommended rates, cause deaths and sublethal reproductive effects on earthworms. The compound has shown low toxicity for birds and is classified as "relatively non-toxic" to honey-bees.


Chloral Hydrate

Concise International Chemical Assessment Document, No. 25
2000, iv + 34 pages [E, with summaries in F, S]
ISBN 92 4 153025 1
Sw.fr. 16.–/US $14.40
In developing countries: Sw.fr. 11.20
Order no. 1380025

A concise assessment of the risks to human health and the environment posed by exposure to chloral hydrate, a chemical used in human and veterinary medicine as a sedative and hypnotic drug. Chloral hydrate and its metabolites are also formed as by-products when water is disinfected with chlorine.

Release to the environment occurs from wastewater treatment facilities, from the manufacture of pharmaceutical-grade chloral hydrate, and from the waste stream during the manufacture of insecticides and herbicides that use chloral hydrate as an intermediate. For the general public, the most important source of exposure is from treated drinking-water. When used as a pharmaceutical agent in humans, the chemical often causes gastric distress, nausea, and vomiting at the recommended clinical dose. While persons surviving near-lethal acute overdoses show some signs of hepatic injury, no convincing evidence indicates that hepatic injury results from intake at the recommended dose.

Concerning kinetics and metabolism, studies show that chloral hydrate is completely absorbed and rapidly metabolized following oral administration. Laboratory studies of toxic effects found no evidence of behavioural changes or of histopathological changes in nervous tissue. Limited data suggest that significant adverse effects on reproduction and development are unlikely. While some animal carcinogenicity studies show an increased risk of liver tumours, data were considered inadequate for an assessment of carcinogenic risk in humans. No long-term studies of exposed humans were available for evaluation. The report found no convincing evidence that exposure causes direct damage to DNA. Available data were judged inadequate to assess risks to the environment caused by chloral hydrate.

Chlordimeform

Environmental Health Criteria, No. 199
1998, xix + 159 pages [E, with summaries in F, S]
ISBN 92 4 157199 3
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160199

Evaluates the risks to human health and the environment posed by chlordimeform, a broad-spectrum acaricide active against motile forms of mites and ticks and against the eggs and early instars of some Lepidoptera insects. Introduced in the late 1960s, the compound was initially used in numerous countries to protect a wide variety of food crops. Application was later restricted to cotton and, in one country, to rice. Although worldwide production and use ceased a decade ago, concern continues to centre on evidence that exposure is linked to an increased risk of urinary bladder cancer in humans.

Concerning risks for the general population, the main sources of previous exposure are identified as the consumption of residues in food. Of greater importance is the large number of workers exposed to higher levels during the compound's manufacturing or application, particularly in view of the long latency period of urinary bladder cancer.

The most extensive section evaluates the results of toxicity studies in laboratory mammals and in vitro test systems. Following short- and long-term exposure, treatment-related changes observed include haematological abnormalities and, at high doses, hyperplasia of the epithelium of the bile duct and urinary bladder. Studies in mice, but not in rats, produced evidence of a dose-related increase in haemorrhagic malignant tumours of vascular origin. The report found no evidence of teratogenic potential or adverse effects on reproduction.

The evaluation of effects on human health draws on epidemiological studies of exposed workers as well as close to 1,000 case reports of accidental or intentional poisoning. These studies support the conclusion that chlordimeform has significant potential to cause both immediate and long-term toxicity in exposed humans. Current evidence also supports the conclusion that exposure to the metabolite, 4-chloro-o-toluidine and, to a lesser extent, chlordimeform is associated with an increased risk of urinary bladder cancer in humans. In view of the long latency period for this cancer, the report calls for the continued screening of previously exposed workers in programmes that include urinary cytology and tests for haematuria.


Chlorendic Acid and Anhydride

Environmental Health Criteria, No. 185
1996, 74 pages [E, with summaries in F, S]
ISBN 92 4 157185 3
Sw.fr. 21.-/US $18.90; in developing countries: Sw.fr. 14.70
Order no. 1160185

Evaluates the risks to human health and the environment posed by chlorendic acid and anhydride. These closely related compounds are important reactive flame retardants used in polyester resins and plasticizers for electrical systems and paints, and in fibreglass-reinforced resins for process equipment in the chemical industry. As all flame retardants are eventually released to the environment, either directly or as breakdown products, the review gives particular attention to studies of the environmental behaviour and ultimate fate of these chemicals. Firm conclusions were limited by the paucity of data and the inadequate design of several studies.

A review of studies in experimental animals and in vitro test systems indicates low acute oral toxicity; no mutagenic potential or teratogenic effects have been observed. Both compounds have been shown to be skin irritants and severe eye and respiratory tract irritants. Long-term studies have produced evidence of an association between exposure to high concentrations of chlorendic acid and tumours in the rat and mouse, supporting the conclusion that this compound has carcinogenic potential.

The report concludes that exposure of the general population to chlorendic acid, chlorendic anhydride and products derived from them should be minimized. The report further recommends caution in the disposal of these chemicals and their waste products to prevent exposure of the general population and minimize environmental risks.


Chlorinated Drinking-Water; Chlorination By-products; Some Other Halogenated Compounds; Cobalt and Cobalt Compounds

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 52
IARC 1991, 544 pages [E]
ISBN 92 832 1252 5
Sw.fr. 88.-/US $79.20; in developing countries: Sw.fr. 61.60
Order no. 1720052

Evaluates the carcinogenic risk to humans posed by the consumption of chlorinated drinking-water, by two chemicals used in the chlorination of drinking-water, by a number of halogenated by-products formed when chlorine interacts with organic matter in water, and by a selection of other halogenated compounds found in drinking-water. Chlorination was selected for evaluation because of its widespread use and because potentially carcinogenic by-products have been measured in chlorinated water. The book also includes a separate monograph on cobalt and cobalt compounds.

The volume opens with a discussion of the many methodological problems that complicate efforts to assess the carcinogenicity of chlorinated water. Against this background, the book evaluates the design and findings of all studies relevant to the carcinogenicity assessment of chlorinated drinking-water, two chemicals (sodium chlorite and hypochlorite salts) used in the chlorination of water, eight of the by-products most frequently measured in drinking-water, and three additional halogenated chemicals detected in drinking-water. Because of the formidable methodological obstacles faced by all investigations, only one of these substances could be classified: bromodichloromethane was classified as possibly carcinogenic to humans.

The final monograph considers data on metallic cobalt, cobalt alloys, including cobalt-containing surgical implants and dental devices, and cobalt compounds. In view of the strength of evidence linking cobalt metal powder and cobalt[II] oxide to cancer in experimental animals, cobalt and cobalt compounds were classified as possibly carcinogenic to humans.


Chlorinated Paraffins

Environmental Health Criteria, No. 181
1996, 181 pages [E, with summaries in F, S]
ISBN 92 4 157181 0
Sw.fr. 40.-/US $36.00; in developing countries: Sw.fr. 28.-
Order no. 1160181

Evaluates the risks to human health and the environment posed by exposure to chlorinated paraffins. These complex mixtures are widely used throughout the world as a secondary plasticizer in polyvinyl chloride, as extreme pressure lubricant additives in the metal-working industry, and in fire-retardant and water-repellent fabric treatment. Chlorinated paraffins are also added to paints, coatings, and sealants to improve resistance to water and chemicals.

The most extensive section assesses findings from toxicity studies in experimental mammals and in vitro test systems. Studies demonstrate low acute oral toxicity and suggest that acute toxicity by the inhalation and dermal routes is also low. Repeated dose toxicity studies by the oral route consistently show that the liver, kidney and thyroid are the primary targets of toxic action. Long-term carcinogenicity studies in rodents have demonstrated increases in the incidence of hepatic, renal, and thyroid tumours following exposure to a short-chain compound. Following exposure to a long-chain compound, an increased incidence of malignant lymphomas and tumours of the adrenal gland has been observed.

In reviewing the limited data on human health effects, the report notes that, despite widespread use of these compounds, no case reports of skin irritation or sensitization have been recorded. This observation is supported by studies of dermal exposure in human volunteers. The report concludes that, when proper personal hygiene and safety procedures are followed, risks to the health of exposed workers should be minimal. Since chlorinated paraffins bioaccumulate and are toxic to environmental organisms, the report recommends that use and disposal of these compounds should be controlled to avoid release to the environment.


Chlorobenzenes Other than Hexachlorobenzene

Environmental Health Criteria, No. 128
1991, 252 pages [E, with summaries in F, S]
ISBN 92 4 157128 4
Sw.fr. 45.-/US $40.50; in developing countries: Sw.fr. 31.50
Order no. 1160128

Evaluates the risks to human health and the environment posed by exposure to monochlorobenzene, dichlorobenzenes, trichlorobenzenes, tetrachlorobenzenes, and pentachlorobenzene. These chemicals are produced in huge quantities for use as intermediates in the synthesis of pesticides and in the production of a wide range of consumer and commercial products.

A review of data on sources of environmental exposure notes that release to the environment occurs primarily during manufacture and that incineration of chlorobenzenes may lead to the emission of polychlorinated dibenzo-p-dioxins and dibenzofurans. Sections concerned with sources and levels of human exposure conclude that the general population is exposed to the lower chlorinated congeners mainly through inhalation, whereas a greater proportion of the total daily intake of the higher chlorinated compounds is ingested in food; breast-fed babies may receive a higher dose than adults. Particular concern centres on risks of human exposure arising from the ingestion of contaminated fish and from contaminated indoor air linked to use of these compounds as moth repellents and air fresheners. The report was unable to predict the environmental impact of low-level contamination, but noted the need to avoid discharge of chlorobenzenes into the aquatic environment, as this can result in the buildup of persistent residues.

Concerning risks to human health, findings from case reports in occupationally exposed populations point to transient effects on the central nervous system, and irritation of the eyes and upper respiratory tract as the principal health effects of exposure.

"... a useful, sensible and well-referenced assessment..."
— Annals of Occupational Hygiene


Chloroform

Environmental Health Criteria, No. 163
1994, 174 pages [E, with summaries in F, S]
ISBN 92 4 157163 2
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160163

Evaluates the risks to human health and the environment posed by exposure to chloroform, a volatile liquid used in pesticide formulations and as a solvent and chemical intermediate. Its use as an anaesthetic and in proprietary medicines has been discontinued in many countries following well-documented reports of adverse effects on respiratory, cardiac and liver function. Exposure of the general public occurs via food, drinking-water, and indoor air, with water use in homes making a substantial contribution to levels in indoor air. Studies have demonstrated significant dermal absorption while showering.

The most extensive chapter reviews the results of toxicity studies in laboratory animals and in vitro test systems. While both the liver and the kidneys are target organs, the most universally observed toxic effect is damage to the liver. Studies indicate that cytotoxicity followed by cell proliferation is the most important cause for the development of liver and kidney tumours following experimental exposure to chloroform. The severity of toxic effects was observed to vary according to species, vehicle, and route of administration.

A chapter on health effects in humans notes disturbances in respiratory and cardiovascu-lar functions observed following short-term exposure. As in animals, liver and kidney damage was the most frequently reported adverse effect of long-term exposure. Data were judged inadequate to implicate chloroform exposure via drinking-water as a cause of human cancer. Concerning effects on the environment, the report concludes that the low levels of chloroform in surface water should not pose a hazard to aquatic organisms.

"... produced with the usual conciseness and readability..."
— International Journal of Environmental Studies


Chlorothalonil

Environmental Health Criteria, No. 183
1996, 145 pages [E, with summaries in F, S]
ISBN 92 4 157183 7
Sw.fr. 35.-/US $31.50; in developing countries: Sw.fr. 24.50
Order no. 1160183

Evaluates the risks to human health and the environment posed by exposure to chlorothalonil, a fungicide widely used in agriculture to protect pome and stone fruit, citrus, currants, berries, bananas, tomatoes, green vegetables, coffee, peanuts, potatoes, onions, and cereals. Chlorothalonil, which has a broad spectrum of activity, is also used on turf, lawns, and ornamental plants, and in wood preservatives and anti-fouling paints. Particular attention is given to crop residue studies.

The most extensive section evaluates the results of toxicity studies conducted in laboratory mammals and in vitro test systems. Studies show that chlorothalonil has low acute oral and dermal toxicity; the main effects of repeated oral dosing are on the stomach and kidney. The evaluation gives particular attention to several feeding studies which demonstrated a rapid onset of toxic effects on the forestomach and kidney, and a rapid induction of forestomach and renal tumours in rodents, but not in other species, including the dog. Most studies failed to demonstrate mutagenicity; the limited data available indicate that the compound is not teratogenic and shows no reproductive toxicity.

Data on effects on human health are confined to case reports of contact dermatitis following occupational or accidental exposure. In interpreting the relevance of experimental findings to human health, particularly the evidence of carcinogenic potential in rodent models, the report notes important species differences in metabolic pathways and postulates that chlorothalonil probably exerts its carcinogenic effects in rodents via a non-genotoxic mechanism. Concerning effects on other organisms in the laboratory and field, the report cites evidence that chlorothalonil is highly toxic to fish and aquatic invertebrates in laboratory studies, but is not phytotoxic and should not pose a risk to wild mammals.


Chromium, Nickel and Welding

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 49
IARC 1990, 677 pages [E]
ISBN 92 832 1249 5
Sw.fr. 105.-/US $94.50; in developing countries: Sw.fr. 73.50
Order no. 1720049

Evaluates the carcinogenic risk to humans posed by industrial exposure to chromium and its compounds, nickel and its compounds, and welding fumes and gases. Occupational exposures, principally by inhalation, are noted to affect about three million workers worldwide. The first and most extensive monograph evaluates the carcinogenicity of chromium and its compounds. The monograph is divided into subsections based on the oxidation state and solubility of the compounds, with separate evaluations made for metallic chromium, chromi-um[III] compounds, chromium [VI] compounds, and for a fourth group of tested agents that were of mixed or unknown oxidation states. The most extensive sections evaluate the design and findings of over 500 investigations of carcinogenicity in animals and experimental systems, studies of metabolic fate in animals and humans, and case reports and epidemiological studies in human populations. On the basis of this evaluation, the monograph concludes that chromium[VI] is carcinogenic to humans. The carcinogenicity of chromium[III] and of metallic chromium could not be determined on the basis of available evidence.

The second monograph presents similar information for metallic nickel and nickel alloys, nickel oxides and hydroxides, nickel sulfides, nickel salts, and other nickel compounds. Nickel carbonyl is identified as the most acutely toxic nickel compound, causing severe damage to the respiratory system in experimental animals and in humans. The evaluation concludes that nickel compounds are carcinogenic to humans and that metallic nickel is possibly carcinogenic to humans.

The final monograph evaluates the carcinogenic risk posed by exposure to welding gases and fumes. On the basis of evidence from human and animal studies, welding fumes are classified as possibly carcinogenic to humans.


Coffee, Tea, Mate, Methylxanthines and Methylglyoxal

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 51
IARC 1991, 513 pages [E]
ISBN 92 832 1251 7
Sw.fr. 88.-/US $79.20; in developing countries: Sw.fr. 61.60
Order no. 1720051

Reports the deliberations of a working group convened to evaluate the strength of evidence linking the drinking of coffee, tea, and mate to the development of human cancer. Separate evaluations are also provided for caffeine, theophylline, theobromine and methylglyoxal, which are chemical constituents of coffee, tea, and several other popular beverages.

The first and most extensive monograph evaluates the large number of studies designed to assess the carcinogenic potential of coffee. On the basis of available data, the working group concluded that coffee is possibly carcinogenic to the human urinary bladder. Evidence further suggests that coffee may actually protect humans against cancer of the colon and rectum. The risk for breast cancer was shown, with remarkable consistency, to have no association with coffee drinking.

The second monograph evaluates the carcinogenicity of black and green teas. Although available data were judged inadequate to classify tea according to its carcinogenic risk, the analysis uncovered evidence suggesting that the temperature at which tea is drunk may be a more important determinant of risk than the chemical composition of the beverage.

This observation is further supported in the monograph on mate, a South American beverage which is usually drunk very hot following repeated addition of almost boiling water to the infusion. While mate could not be classified on the basis of available data, hot mate drinking was judged to have a probable association with the development of oesophageal and oral cancers. Evidence was inadequate to assess the carcinogenicity of caffeine, theophylline, theobromine, and methylglyoxal.


Combined Analyses of Cancer Mortality Among Nuclear Industry Workers in Canada, the United Kingdom and the United States of America

E. Cardis, E.S. Gilbert, L. Carpenter and others
IARC Technical Report, No. 25
1995, iii + 147 pages [E]
ISBN 92 832 1440 4
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1770025

Reports the results of an analysis of combined mortality data on 95,673 nuclear industry workers at seven facilities in the USA, UK and Canada. Workers at these facilities, which include both atomic energy stations and nuclear weapons plants, have been monitored in previous studies to determine the health effects of external exposure to ionising radiation. By combining and assessing data from previous studies, the present analysis aimed to develop more precise estimates of the risk of radiation-induced cancer and thus to strengthen the scientific basis for setting radiation protection standards.

The study also compared risk estimates among workers with estimates obtained in high-dose studies, including investigations of atomic bomb survivors and of patients irradiated for therapeutic purposes. The results represent the most comprehensive and precise direct assessment to date of the carcinogenic risk of protracted external exposure to generally low doses of ionising radiation.

The combined analysis of data on nuclear industry workers found a significant increase in the risk of leukaemia, and of myeloid leukaemia in particular, at relatively low dose levels. The study also provided an opportunity to examine some of the previously reported associations between low doses of ionising radiation and mortality from specific cancer types. Of the 36 cancer types or groupings considered, most showed little or no association with radiation exposure. Apart from leukaemia, multiple myeloma was the only cancer to exhibit a statistically significant association with radiation dose.


Cresols

Environmental Health Criteria, No. 168
1995, 144 pages [E, with summaries in F, S]
ISBN 92 4 157168 3
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160168

Evaluates the risks to human health and the environment posed by exposure to cresols. Commercial cresols have a wide variety of uses as solvents and disinfectants and as chemical intermediates for pharmaceuticals, fragrances, antioxidants, dyes, pesticides, and resins. Cresols are also used in the production of lubricating oils, motor fuels and rubber polymers and in the manufacture of explosives. The general population may be exposed to cresols present in air, drinking-water, food and beverages, and consumer products, such as soaps and disinfectants.

The most extensive sections evaluate data on toxic effects linked to different routes and levels of exposure. In laboratory animals, toxic effects, including damage to the respiratory and gastrointestinal tracts, are associated with the strong irritant and corrosive activity of cresols. Although acute poisoning via inhalation is judged unlikely due to the low vapour pressure of cresols, dermal exposure causes irreversible tissue damage in experimental animals and can be fatal at high concentrations.

In humans, toxic effects and clinical signs following accidental or intentional ingestion are identified as burning of the mouth and throat, abdominal pain, and vomiting. Studies of acute poisoning in workers indicate that occupa-tional exposure is usually the result of dermal contact, which can result in severe burns and scarring of the skin, haematological changes, kidney failure, coma and death. Data were judged inadequate to evaluate potential reproductive effects and carcinogenic risk. The report concludes that, at concentrations normally detected in the environment, cresols do not pose a significant risk to the general population.

"... a thorough and well-documented account..."
— International Journal of Environmental Studies


Crystalline Silica, Quartz

Concise International Chemical Assessment Document, No. 24
2000, iv + 50 pages [E, with summaries in F, S]
ISBN 92 4 153024 3
Sw.fr. 17.–/US $15.30
In developing countries: Sw.fr. 11.90
Order no. 1380024

A concise assessment of the adverse effects on human health caused by exposure to quartz, the most common form of crystalline silica. Quartz is a frequently occurring solid component of most natural mineral dusts. Human exposure occurs most often during occupational activities involving movement of earth, disturbance of silica-containing products, such as masonry and concrete, or use or manufacture of silica-containing products. As respirable quartz dust particles can be inhaled and deposited in the lung, the report gives particular attention to evidence of an increased risk of lung cancer in occupationally exposed workers.

Most studies in laboratory animals have concentrated on adverse effects associated with long-term inhalation of particles. Effects observed include cellular proliferation, nodule formation, suppressed immune function, and alveolar proteinosis. While exposure clearly induces pulmonary tumours in one species, other species show less or no malignant tumour response.

The evaluation of risks to human health draws on a large number of epidemiological studies of workers exposed to respirable quartz dust. Occupational exposure has been linked to an increased incidence of silicosis, lung cancer, and pulmonary tuberculosis. Studies have also documented statistically significant increases in cases of bronchitis, emphysema, chronic obstructive pulmonary disease, autoimmune-related diseases, including scleroderma, rheumatoid arthritis, and systemic lupus erythematosus, and renal disease. In reviewing these findings, the report underscores several uncertainties, inherent to the study of respiratory diseases in occupational populations, that complicate the assessment of risks associated with exposure to quartz dust. The need for improved methods of exposure assessment and data analysis is stressed.

Cyhalothrin

Environmental Health Criteria, No. 99
1990, 106 pages [E, with summaries in F, S]
ISBN 92 4 154299 3
Sw.fr. 23.-/US $20.70; in developing countries: Sw.fr. 16.10
Order no. 1160099

Evaluates the risks to human health and the environment posed by the use of cyhalothrin, a synthetic pyrethroid insecticide having a high level of activity against a wide range of agricultural pests. Cyhalothrin is also used in public health and animal health, where it effectively controls a broad spectrum of insects, including cockroaches, flies, mosquitos, and ticks.

Residues in food are identified as the most important potential hazard for the general population, though a review of available studies indicates that residues in excess of the established acceptable daily intake are very unlike-ly to occur. Concerning effects on organisms in the environment, the report cites laboratory evidence of high toxicity to fish, aquatic arthro-pods, and honey bees, but concludes that this high toxicity in the laboratory is not translated into a significant field hazard for these species.

The most extensive section reviews data from experimental toxicity studies. The review uncovered no evidence of carcinogenicity, mutagenicity, or disturbed reproductive functions, and no evidence of adverse effects on any aspect of fetal development at any of the experimental doses used. The final section, devoted to effects on humans, considers the clinical significance of a subjective facial sensation reported in laboratory workers, workers in manufacturing plants, and field operators handling cyhalothrin. While noting the documented occurrence of this syndrome, the report concludes that it is a transient phenomenon, that symptoms are not associated with objective physical signs, and that recovery is complete. On the basis of these evaluations, the report concludes that, when recommended safety precautions and rates of application are followed, cyhalothrin is highly unlikely to pose a risk to the health of the environment, the general public, or occupationally-exposed workers.


alpha-Cypermethrin

Environmental Health Criteria, No. 142
1992, 112 pages [E, with summaries in F, S]
ISBN 92 4 157142 X
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160142

Evaluates risks to human health and the environment posed by the use of alpha-cyper-methrin, a potent and versatile pyrethroid insecticide used against a wide range of pests encountered in agriculture. Main agricultural applications include the protection of oilseeds, pome fruits, peaches, fruiting vegetables, berries, leafy vegetables, maize, hops, and tobacco. Marketed since late 1983, alpha-cypermethrin is also used against disease-carrying insects and in the control of parasites of veterinary importance.

In view of the uses of this pesticide, an evaluation of sources of human exposure draws upon crop residue data obtained from a large number of supervised trials conducted throughout the world. The report concludes that exposure of the general population is negligible when the pesticide is used in keeping with good agricultural practice. Toxicity studies conducted in laboratory mammals and in vitro test systems indicate that alpha-cypermethrin has a moderate to high acute oral toxicity and is 3-4 times more toxic than cypermethrin. Short-term exposures have not been shown to cause toxic effects. Several studies provide evidence that alpha-cypermethrin is non-mutagenic. No data on long-term toxicity, teratogenicity, carcinogenicity, or immunotoxicity were available for evaluation.

The report concludes that, when good work practices, hygiene measures, and safety precautions are followed, use of alpha-cyper-methrin is unlikely to pose a hazard to occupationally exposed workers. Though laboratory studies have documented high toxicity for fish, studies show that this toxicity is not realized under field conditions, where the rapid loss of alpha-cypermethrin from water facilitates the complete recovery of affected populations.


Deltamethrin

Environmental Health Criteria, No. 97
1990, 133 pages [E, with summaries in F, S; R]
ISBN 92 4 154297 7
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160097

Evaluates the risks to human health and the environment posed by the use of deltamethrin, a synthetic pyrethroid insecticide mainly used against agricultural pests. Marketed since 1977, deltamethrin is most commonly used on cotton, on fruit and vegetable crops, and on cereals, corn, and soybean. Deltamethrin is also used for the post-harvest protection of stored cereals, grains, coffee beans, and dry beans. Major public health applications include use in the control of Chagas disease and malaria.

Dietary residues, particularly following post-harvest treatment, are identified as the most important source of exposure for the general population. While deltamethrin has been shown to be highly toxic to fish, aquatic arthropods, and honey bees in laboratory investigations, field studies and observations following widespread use indicate that this insecticide, when used according to good agricultural practice, is unlikely to have lasting effects on these species.

The main part of the book examines investigations of the toxic effects of deltamethrin on experimental animals and in vitro test systems. The review found no evidence of mutagenicity, teratogenic or reproductive effects, though it did cite evidence that the combined use of deltamethrin with some organophosphorus compounds can potentiate toxicity. The final section evaluates effects on humans as observed following poisoning, occupational accidents, and both short- and long-term occupational exposure. The book concludes that exposure of the general population to deltamethrin is very low and that, provided recommended rates of application are followed, use of this insecticide is unlikely to present a hazard to either occupationally-exposed workers or the environment.


Demeton-S-methyl

Environmental Health Criteria, No. 197
1997, xviii + 83 pages [E, with summaries in F, S]
ISBN 92 4 157197 7
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160197

Evaluates the risks to human health and the environment posed by exposure to demeton-S-methyl, a systemic and contact organophosphorus insecticide and acaricide having high acute toxicity. The compound has been used for over 30 years to protect cereals, fruits, vegetables, and ornamental plants.

Studies of the environmental behaviour of demeton-S-methyl indicate that the compound is rapidly metabolized in soil, plants, and mammals, does not persist, and is not accumulated by organisms. Workers may be exposed during manufacturing or application via the dermal or inhalation routes. Residues in food crops are identified as the principal source of exposure for the general population. Although data on dietary levels are limited, the report concludes that exposure of the general population to residues in food is unlikely to cause adverse effects on health.

Concerning effects on experimental animals and in vitro test systems, the report cites abundant evidence that demeton-S-methyl causes cholinergic toxicity. The report found no evidence of embryotoxic or teratogenic potential, adverse effects on reproduction or development, or carcinogenic action.

The evaluation of effects on human health draws on several reports of accidental and suicidal poisoning in the general population, and episodes of poisoning in inadequately protected workers. These findings confirm the high acute toxicity demonstrated in experimental studies. The report concludes that demeton-S-methyl should be handled and applied only by well-trained and closely-supervised operators. When good work practices, hygienic measures, and recommended safety precautions are followed, exposure to the compound during manufacturing or application was judged unlikely to cause adverse effects on health.


Diazinon

Environmental Health Criteria, No. 198
1998, xx + 140 pages [E, with summaries in F, S]
ISBN 92 4 157198 5
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1160198

Evaluates the risks to human health and the environment posed by diazinon, a contact organophosphorus insecticide with a wide range of insecticidal activity. Diazinon has been used since the early 1950s to control adult and juvenile forms of flying insects, crawling insects, ticks, mites, and spiders. Applications include the protection of food crops, the control of indoor pests, and the control of ectoparasites in veterinary medicine. Although diet is identified as the principal route of exposure for the general population, levels detected in edible crops and food animals have been far below the acceptable daily intake.

Concerning effects on experimental animals and in vitro test systems, the report notes that manufacturing practices during the past two decades have significantly reduced the content of highly toxic impurities, resulting in low acute toxicity for currently marketed formulations. The report found no evidence of embryotoxic or teratogenic potential, adverse effects on reproduction function, or carcinogenic action. The principal adverse effect of concern was judged to be dose-related inhibition of acetyl cholinesterase activity.

The evaluation of effects on human health draws on several reports of accidental and intentional poisoning. Acute poisoning was noted to cause signs and symptoms consistent with inhibition of plasma cholinesterase activity. Acute pancreatitis has also been observed in cases of severe poisoning. Although fatalities in occupationally-exposed workers have occurred, most have been linked to the former presence of highly toxic impurities or associated with poor hygienic practices. The report concludes that, when good work practices, safety precautions, and hygienic measures are followed, diazinon is unlikely to present a hazard to occupationally-exposed workers. The report further concludes that diazinon does not pose a significant health hazard for the general population.


1,2-Dibromoethane

Environmental Health Criteria, No. 177
1996, 148 pages [E, with summaries in F, S]
ISBN 92 4 157177 2
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1160177

Evaluates the risks to human health and the environment posed by 1,2-dibromoethane. This highly volatile chemical is used as a lead scavenger in antiknock gasoline, as a fumigant for soil, grains, and fruits, as an intermediate in the synthesis of dyes and pharmaceuticals, and as a solvent for resins, gums, and waxes. Although world demand has been reduced substantially following bans on the use of leaded gasoline and on agricultural applications, 1,2-dibromoethane is still used in large amounts for many industrial purposes in industrialized countries.

Studies in laboratory mammals and in vitro test systems demonstrate acute toxicity to animals, with the main effects observed in the liver and kidneys. Exposure via inhalation has been shown to cause nasal irritation and depression of the central nervous system is several studies. Adverse effects on reproductive function have also been observed. Concerning carcinogenicity, studies have shown that long-term exposure causes tumours, in rats and mice, in a variety of organs.

An evaluation of effects on human health draws on case studies of accidental and intentional poisoning as well as epidemiological studies of occupationally exposed workers. In humans, 1,2-dibromoethane is strongly irritant to the eyes, skin, and respiratory tract. Symptoms of poisoning are identified as headache, severe vomiting, diarrhoea, respiratory tract irritation, and death, usually caused by pneumonia following damage to the lungs. Other targets of toxic action include the liver and kidneys. Reports of adverse effects on reproductive function in occupationally exposed workers were judged inconsistent. Although carcinogenicity studies in humans are extremely limited, strong and consistent evidence from animal studies supports the conclusion that 1,2-dibromoethane is a potential human carcinogen.


Di-n-butyl Phthalate

Environmental Health Criteria, No. 189
1997, 205 pages [E, with summaries in F, S]
ISBN 92 4 157189 6
Sw.fr. 42.-/US $37.80; in developing countries: Sw.fr. 29.40
Order no. 1160189

Evaluates the risks to human health and the environment posed by exposure to di-n-butyl phthalate (DBP). DBP is used as a speciality plasticizer for nitrocellulose, polyvinyl acetate, and polyvinyl chloride, in adhesives, in coatings, and in miscellaneous applications, including paper coating. The compound is also used as a lubricant for aerosol valves, an antifoaming agent, a skin emollient, and a plasticizer in hair spray, fingernail polish, and numerous other cosmetic products. Although DBP has low volatility, its widespread use in many thin polymeric sheets and coatings provides large surface areas for volatilization during the manufacture, use, and disposal of these products.

An evaluation of studies on environmental presence and behaviour notes that DBP is rapidly and completely eliminated by aerobic degradation. Concerning sources of exposure for the general population, food is identified as the principal source, followed by much lower exposures from indoor air and drinking-water. Ingestion was identified as by far the most important route of exposure for the general population.

The most extensive section examines the results of toxicity studies conducted in laboratory mammals and in vitro test systems, concentrating on the numerous studies of oral exposure in rodent models. Toxic effects observed include hepatomegaly, increased numbers of hepatic peroxisomes, fetotoxicity, teratogenicity, and testicular damage. Alterations in the liver were judged to be indicative of metabolic stress. On the basis of these findings, the report concludes that DBP is teratogenic in certain species at high doses and that susceptibility to teratogenesis varies with developmental stage and period of administration. The report further noted that toxic effects on development and reproduction occurred at concentrations well above those to which people are normally exposed in the general environment. The report found no evidence that DBP is genotoxic.

Concerning effects on humans, the report considered findings from isolated case reports of skin sensitization, a single case of accidental poisoning, and epidemiological studies of workers exposed to mixtures of phthalates. Although limited, these data, combined with findings from extensive animal studies, support the conclusion that exposure to DBP, at levels currently found in the general environment, is unlikely to cause adverse effects on human health. Carcinogenic effects were also judged unlikely. The report further urges the continuation of current measures to limit the release of DBP into the environment and to control its use in food packaging materials.


2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123)

Concise International Chemical Assessment Document, No. 23
2000, iv + 31 pages [E, with summaries in F, S]
ISBN 92 4 153023 5
Sw.fr. 16.–/US $14.40
In developing countries: Sw.fr. 11.20
Order no. 1380023

A concise assessment of the risks to human health and the environment posed by exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123), a volatile liquid used as a refrigerant in commercial and industrial air-conditioning installations, in gaseous fire extinguishers, as a foam-blowing agent, and in metal and electronics cleaning. Although HCFC-123 is known to contribute to ozone depletion, the significance of its role in global warming is far smaller than that of chlorofluorocarbons and bromofluorocarbons, which are being phased out in compliance with the 1987 Montreal Protocol on Substances that Deplete the Ozone Layer.

Releases of HCFC-123 to the environment are primarily to ambient air. In the atmosphere, the chemical has an estimated lifetime of less than two years. The risk to aquatic organisms is considered low. While exposure of the general public is expected to be minimal, occupational exposures during manufacture and use of products containing the chemical are of concern.

In laboratory animals, exposure via inhalation has been shown to cause liver lesions, central nervous system depression, and adrenaline-induced cardiac arrhythmia. In studies involving repeated exposure, the principal targets of toxicity were the liver, the hypothalamic-pituitary-gonadal endocrine system, and the central nervous system. Although an increased incidence of benign tumours of the liver and other organs has been observed in one species, the relevance of these findings to carcinogenicity in humans could not be clarified. Adverse effects on the liver have been detected in some studies of exposed workers. Central nervous system depression and an increased likelihood of adrenaline-induced cardiac arrhythmia are the principle effects in humans of brief exposure.

3,3�-Dichlorobenzidine

Concise International Chemical Assessment Document, No. 2
1998, iv + 21 pages [E, with summaries in F, S]
ISBN 92 4 153002 2
Sw.fr. 13.-/US $11.70; in developing countries: Sw.fr. 9.10
Order no. 1380002

A concise assessment of the risks to human health and the environment posed by 3,3�-dichlorobenzidine, a chemical used primarily as an intermediate in the manufacture of pigments for printing inks, textiles, paints, and plastics. The document is part of a new series of brief reports aimed at the characterization of hazards and dose-response for exposure to selected industrial chemicals. With this goal in mind, documents in the series focus on studies and findings considered critical for risk characterization.

Several properties of 3,3�-dichlorobenzidine, including its relatively low volatility, very short persistence, and low concentrations in the atmosphere, support the conclusion that the chemical will not contribute to the greenhouse effect, depletion of the ozone layer, or the formation of ground-level ozone. The assessment of toxic effects in experimental animals found sufficient evidence of carcinogenicity in several species, and substantial evidence of genotoxicity. The very limited epidemiological studies were considered inadequate to access the chemical's carcinogenicity to humans.


1,2-Dichloroethane
Second edition

Environmental Health Criteria, No. 176
1995, 148 pages [E, with summaries in F, S]
ISBN 92 4 157176 4
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1160176

Evaluates the risks to human health and the environment posed by exposure to 1,2-dichloroethane, an industrial chemical mainly used in the synthesis of vinyl chloride. The compound is also used in the manufacture of various chlorinated solvents, as a fumigant, and in the manufacture of anti-knock additives for gasoline.

Most emissions during production are to air, with the stratosphere providing the predominant environmental sink. Though photolysis may produce chlorine radicals which may, in turn, react with ozone, 1,2-dichloroethane is judged to have a low ozone-depleting potential. Studies show that 1,2-dichloroethane present in indoor and outdoor air is the main source of human exposure. Levels detected in drinking-water are low, and food is judged to be an unlikely source of exposure.

The most extensive section evaluates studies of toxicity in laboratory mammals and in vitro test systems. Particular concern centred on several animal studies that produced convincing evidence of increases in both common and rare tumours at several sites. 1,2-Dichloroethane has also been shown to be genotoxic in in vitro and in vivo assays.

An evaluation of effects on humans draws on case reports of poisoning as well as epidemiological studies of occupationally exposed workers. The report cites findings from limited epidemiological studies indicating an increased risk of pancreatic cancer and leukaemia. On the basis of these and other findings, the report concludes that 1,2-dichloroethane is a probable human carcinogen. Since a safe level for human exposure by any route could not be established, the report further concludes that all appropriate measures should be taken to eliminate or minimize human exposure to 1,2-dichloroethane.


1,2-Dichloroethane

Concise International Chemical Assessment Document, No. 1
1998, iv + 28 pages [E, with summaries in F, S]
ISBN 92 4 153001 4
Sw.fr. 13.-/US $11.70; in developing countries: Sw.fr. 9.10
Order no. 1380001

A concise assessment of the risks to human health and the environment posed by exposure to 1,2-dichloroethane, an industrial chemical mainly used in the synthesis of vinyl chloride. The compound is also used in the manufacture of various chlorinated solvents, as a fumigant, and in the manufacture of anti-knock additives for gasoline. The document is the first in a new series aimed at the characterization of hazards and dose-response for exposures to selected industrial chemicals. With this goal in mind, documents in the series focus on studies and findings considered critical for risk characterization.

A review of findings from studies in laboratory animals and limited epidemiological studies in humans supports the conclusion that 1,2-dichloroethane is a probable human carcinogen, and that exposure should be reduced as much as possible. Using the results of gavage studies in experimental animals, the carcinogenic potency, expressed as the dose associated with a 5% increase in tumour incidence, was calculated to be 6.2-34 mg/kg body weight per day. As humans are exposed primarily via the inhalation route, guidance values for air of 3.6-20 micrograms/m3 or 0.36-2.0 micrograms/m3 were derived, calculated on the basis of a margin of 5,000-fold or 50,000-fold less than the estimated carcinogenic potential. This margin of 5,000 to 50,000 affords protection similar to that associated with the range for low-dose risk estimates generally considered to be "essentially negligible". The report notes, however, that the calculation, based on the results of gavage studies, probably overestimates the risks of human exposure, as 1,2-dichloroethane is less potent when inhaled.


1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures

Environmental Health Criteria, No. 146
1993, 261 pages [E, with summaries in F, S]
ISBN 92 4 157146 2
Sw.fr. 50.-/US $45.00; in developing countries: Sw.fr. 35.00
Order no. 1160146

Evaluates the risks to human health and the environment posed by 1,3-dichloropropene, 1,2-dichloropropane and mixtures of these chemicals. Since the two compounds and mixtures have been widely used in agriculture as pre-plant fumigants applied by soil injection, the report gives particular attention to studies investigating behaviour in soil, risks of leaching and groundwater contamination, uptake by food crops, residues detected in drinking-water and food, and risks to agricultural workers and the general population. Over 300 studies, including proprietary toxicological data from the manufacturers, were critically assessed.

The report concludes that, when used at the recommended rate, 1,3-dichloropropene is unlikely to attain levels of environmental significance. Risks to the general population were judged negligible. Concerning occupational hazards, the report cites evidence, largely from case reports of poisoning, underscoring the need to follow appropriate safety precautions.

The report concludes that 1,2-dichloropropane poses a negligible risk to the general population. When used at the recommended rate, the compound is unlikely to attain levels of environmental significance. For workers, the compound is judged unlikely to pose a hazard, provided good work practices, hygienic measures, and safety precautions are followed.

Data on mixtures of dichloropropenes and dichloropropane are evaluated in the final monograph. This technical mixture previously enjoyed wide use as a soil nematocide before planting. Citing evidence of a significant potential for 1,2-dichloropropane derived from this mixture to leach from soil and contaminate well water and groundwater, the report recommends that mixtures of dichloropropenes and dichloropropane should not be used as a soil fumigant.


Diesel Fuel and Exhaust Emissions

Environmental Health Criteria, No. 171
1996, xxiii + 389 pages [E, with summaries in F, S]
ISBN 92 4 157171 3
Sw.fr. 90.-/US $81.00; in developing countries: Sw.fr. 63.-
Order no. 1160171

Draws on findings from over 600 studies to evaluate the risks to human health and the environment posed by exposure to diesel fuel and diesel exhaust emissions. The two categories of exposure are evaluated in separate parts.

The evaluation of diesel fuel opens with a discussion of the complexity of these mixtures and the many variables that affect their quality and composition. An evaluation of toxicity studies in laboratory animals and in vitro test systems concludes that diesel fuel has low acute toxicity when administered via oral, dermal, and inhalation routes. Findings on embryotoxicity, teratogenicity, mutagenicity, and genotoxicity were judged to be either negative or equivocal. In view of inadequacies in the few studies of carcinogenic risks, the report concludes that the main effect of exposure on human health is dermatitis following skin contact.

The second and largest part evaluates diesel exhaust emissions. A review of the abundant data demonstrating adverse effects on the environment concludes that the major components of diesel exhaust contribute to acid deposition, tropospheric ozone formation, and global warming. The most extensive sections discuss the epidemiological studies in humans and studies in experimental animals considered useful for the assessment of risks to human health. Although a number of epidemiological studies have indicated an increased risk of lung cancer in bus and railroad workers, all studies suffered from weaknesses. The report concludes that diesel exhaust is probably carcinogenic to humans, and that inhalation of diesel exhaust contributes to both neoplastic and non-neoplastic diseases, including asthma. The report further concludes that the particulate phase has the greatest effect on human health.


Diethylhexyl Phthalate

Environmental Health Criteria, No. 131
1992, 141 pages [E, with summaries in F, S]
ISBN 92 4 157131 4
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160131

Evaluates the risks to human health and the environment posed by the production, processing, use, and disposal of diethylhexyl phthalate (DEHP). DEHP is produced in large quantities for use as a resin-softening plasticizer, with major application in the production of polyvinyl chloride used in the construction and packaging industries and in components of medical devices, including tubes used in transfusions and dialysis. Findings from over 300 recent studies were critically assessed.

The opening sections characterize the beha-viour of DEHP in different environmental media and summarize data indicating concentrations detected in air, precipitation, water, sediment, soil, biota, food, and the workplace environment. These studies show that, while DEHP is rapidly photodegraded in the atmosphere, aerobic biodegradation is slow, and anaerobic degradation is even slower. The report concludes that adverse effects on environmental organisms are likely in areas where water and sediment are highly contaminated.

The most extensive section examines the results of numerous toxicological studies in laboratory animals and in vitro test systems. Significant findings include testicular atrophy and neoplastic effects on the liver in rats and mice. An evaluation of numerous studies on the mechanisms of hepatotoxicity concludes that the livers of rats and mice are exquisitely sensitive to DEHP and other peroxisome proliferators, while the livers of guinea-pigs, monkeys, and humans show minimal or no response.

Determination of the effects of DEHP on human health was limited by the paucity of available data. Case reports of adverse effects linked to haemodialysis and artificial ventilation underscore the need to reduce exposure arising from the use of plastic tubes containing DEHP in such clinical procedures as transfusion, haemodialysis, and artificial respiration.


Diflubenzuron

Environmental Health Criteria, No. 184
1996, 163 pages [E, with summaries in F, S]
ISBN 92 4 157184 5
Sw.fr. 40.-/US $36.00; in developing countries: Sw.fr. 28.-
Order no. 1160184

Evaluates the risks to human health and the environment posed by exposure to diflubenzuron, a synthetic compound used in agriculture, forestry, and public health programmes to control mosquitos and other insect pests and vectors. As this insecticide is usually applied directly to plants and water, particular attention is given to studies of its behaviour in the environment and its effects on ecosystems and aquatic organisms.

Numerous studies support the conclusion that diflubenzuron has minimal or reversible effects on most aquatic invertebrates. Studies of forest spraying found no adverse effects on bird and mammal populations. Concerning sources and levels of human exposure, the report cites evidence that exposure of the general population to diflubenzuron via water or food as a result of its use in agriculture, against forest insects, or in mosquito control is negligible.

Concerning the toxicity of diflubenzuron in experimental animals and in vitro test systems, numerous studies consistently show that the primary manifestation of toxicity is methaemoglobin induction attributable to the metabolite, 4-chloroaniline, which is known to induce methaemoglobin formation in several animals species and in humans. A review of studies of long-term dietary administration supports the conclusion that diflubenzuron is not mutagenic or carcinogenic. Although the main metabolite, 4-chloroaniline, has been reported to cause methaemoglobinaemia in exposed workers and inadvertently exposed neonates, no data on the direct effects of diflubenzuron on human health were available for evaluation. The extensive toxicology studies in animals nonetheless support the conclusion that exposure to 0.02 mg/kg body weight will probably not cause adverse effects in humans by any exposure route.


Dimethylformamide

Environmental Health Criteria, No. 114
1991,124 pages [E, with summaries in F, S]
ISBN 92 4 157114 4
Sw.fr. 24.-/US $21.60; in developing countries: Sw.fr. 16.80
Order no. 1160114

Evaluates risks to human health and the environment posed by the production and use of dimethylformamide, an organic solvent produced in large quantities throughout the world. Dimethylformamide is widely used in the chemical industry as a solvent, an intermediate, and an additive, with the largest quantities used in the production of acrylic fibres and polyurethanes. Dimethylformamide is also used in the production of pharmaceutical products.

The opening sections outline the main sources of human and environmental exposure and review studies of the behaviour of dimethylformamide in the environment. Because of its complete solubility in water, dimethylformamide is noted to move readily through soils; accumulation in the food chain is judged unlikely. Concerning effects on organisms in the environment, the limited data available suggest low toxicity for aquatic organisms.

The second half of the book reviews findings useful in determining the risks to health posed by exposure of workers and of the general population to dimethylformamide. An extensive review of findings from experimental studies reveals consistent evidence that dimethyl-formamide is a hepatotoxic agent. Both teratogenic and embryotoxic effects have been demonstrated in several species. The final section, which evaluates data from human studies, notes that symptoms associated with cases of acute accidental occupational poisoning are transient and followed by complete recovery. Biochemical signs of liver dysfunction are observed to accompany long-term repeated occupational exposure, but evidence suggesting an increased risk of certain cancers in exposed workers was judged inadequate.

"... well written, well-organized and concise..."
— Journal of Toxicology and Environmental Health


Dinitro-ortho-cresol

Environmental Health Criteria, No. 220
2000, xvii + 87 pages [E, with summaries in F, S]
ISBN 92 4 157220 5
Sw.fr. 26.–/US $23.40
In developing countries: Sw.fr. 18.20
Order no. 1160220

Evaluates the risks to human health and the environment posed by exposure to dinitro-ortho-cresol, a chemical used for over a century as an acaricide, larvicide, and ovicide to control the dormant forms of many insects in orchards. The chemical is also sprayed on potatoes to prevent virus and disease contamination of the tubers. Although the chemical's use as a pesticide has been banned in many countries, significant volumes of obsolete stocks are still found in several parts of the world, especially in developing countries. Dinitro-ortho-cresol continues to be used in the plastics industry as an inhibitor of polymerization in styrene and vinyl aromatic compounds.

Concerning environmental behaviour, studies indicate that the chemical is rapidly biodegraded in soil and has no potential to volatilize when released to water. Evidence further suggests that uptake by treated fruit trees or potatoes, leaving residues at harvest time, does not occur. Food is therefore not considered an important source of exposure for the general population. Occupational exposures during agricultural spraying and during manufacturing and formulation are regarded as the principal sources of human exposure.

The most extensive part evaluates the results of toxicity studies in laboratory mammals and in vitro test systems. Short-term dietary administration decreased body-weight gain in some species, usually without significant alteration in food consumption. At high doses, adverse effects on the liver have been observed. Data on embryotoxicity, teratogenicity, mutagenicity, and carcinogenicity were judged inadequate for evaluation.

The evaluation of effects on human health draws on data obtained during the limited use of dinitro-ortho-cresol in the 1930s as a therapeutic agent for the treatment of obesity, and on cases of acute poisoning. Symptoms associated with toxicity include restlessness, flushed skin, sweating, thirst, deep and rapid respiration, severe increase of body temperature, and cyanosis leading to collapse, coma, and death. Concerning adverse effects on occupationally exposed workers, the report cites a dramatic decline over the last 25 years in reported cases of occupational intoxication. The decline is attributed to better education of users, the use of adequate protective equipment, and improvements in application techniques, equipment, and formulations. The report concludes that, when used according to registered recommendations, and when measures for personal protection are followed, exposure to dinitro-ortho-cresol is reduced to levels that do not cause systemic toxicity.

Directory of Agents being Tested for Carcinogenicity
Number 17

Compiled by A. Meneghel and J. Wilbourn
IARC 1996, x + 247 pages [E]
ISBN 92 832 1317 3
Sw.fr. 50.-/US $45.00; in developing countries: Sw.fr. 35.-
Order no. 1740017

A worldwide inventory of on-going research projects involving the long-term carcinogenicity testing, in experimental animals, of chemicals and other agents. In view of the long duration and high costs of carcinogenicity testing, the book aims to help avoid unnecessary duplication of research, to increase communication among scientists, and to provide a guide to research facilities as well as to the specific chemicals and agents being tested. The 1996 directory draws together data on 533 chemicals or agents under investigation at 65 institutes in 21 countries. Also included in a fully-referenced index covering some 200 published studies emanating from projects described in the directory.

Information on current research projects is arranged alphabetically by country, within each country by city, and within each city by institute. For each institute reporting on long-term carcinogenicity testing, the chemicals or complex mixtures being tested are listed in alphabetical order. Reported data are given in a six-column format, including name of substance; use categories of the substance; species, strain and number of animals per treated and control group; exposure route, dose levels, and purity; starting date and stage of experiment; and principal investigators.

The directory also includes a special section giving cross references to some 270 on-going epidemiological studies of 50 substances. Use of the directory is further facilitated through the inclusion of indices of institutes, investigators, chemical abstracts services registry numbers, and a cross index of names.


Disinfectants and Disinfectant By-products

Environmental Health Criteria, No. 216
2000, xxvii + 499 pages (English, with summaries in French and Spanish)
ISBN 92 4 157216 7
Sw.fr. 102.–/US $91.80; in developing countries: Sw.fr. 71.40
Order no. 1160216

This book evaluates the risks to human health posed by disinfectants and disinfectant by-products found in treated drinking-water. Noting that chlorine and other widely-used disinfectants were approved for use almost 100 years ago, when toxicological data were limited, the report responds to the need for reassurance that consumption of treated drinking-water will not have adverse effects on health. Particular concern centres on the potential of chlorine to react with natural organic matter and form a large number of by-products, some of which have been intensively studied as potential human carcinogens. With these concerns in mind, the report evaluates over 800 recent studies in an effort to clarify understanding of the chemistry and toxicology of disinfectants and disinfectant by-products, and provide a balanced assessment of the associated risks to human health.

The report is issued at a time when public health authorities and utilities providers in several countries are considering alternative methods of disinfection aimed at reducing the formation of specific by-products. In this context, the report stresses the overriding importance of microbiological safety, and warns that adequate disinfection must not be compromised by efforts to control chemical by-products.

The first chapter, on the chemistry of disinfectants and disinfectant by-products, examines the many complex factors, including methods of water treatment, that govern the formation of by-products and influence their type and amount. Of special interest to utilities providers, the chapter explains the physical and chemical properties that influence the behaviour of specific by-products in drinking-water and determine their toxic actions. By-products of greatest concern are identified as trihalomethanes, including chloroform and bromodichloromethane, haloacetic acids, including dichloroacetic acid and trichloroacetic acid, bromate, and chlorite. The chapter concludes that the adoption of alternative disinfecting chemicals often amounts to nothing more than a trade-off between one group of by-products and another. Removal of natural organic matter is singled out as the most effective control strategy.

Chapter two reviews what is known about the toxic effects of the principal disinfectants: chlorine and hypochlorite, chloramine, and chlorine dioxide. On the basis of this evaluation, the report concludes that disinfectants probably do not increase the risk of cancer or have other significant adverse effects on health. Chapter three evaluates the toxic effects of fourteen by-products, concentrating on the large number of studies of carcinogenicity and mutagenicity.

Epidemiological studies are reviewed in chapter four, which considers extensive investigations of possible associations with cancer, cardiovascular disease, and adverse effects on reproduction and development. While most studies have concentrated on an increased risk of bladder cancer, risks of colon, rectal, and other cancers have also been investigated. Noting the uncertainties surrounding many of these studies, the report cautions against a simple interpretation of observed associations and concludes that more comprehensive water quality data must be collected to improve exposure assessments. Evidence was considered insufficient to determine whether observed associations are causal and which specific by-products or other contaminants play a role.

In the final chapters, focused on risk characterization and assessment, the report concludes that the risks to health from disinfectant by-products, at the levels at which they occur in drinking-water, are extremely small in comparison with the risks associated with inadequate disinfection. In supporting efforts to minimize the formation of by-products, the report further concludes that protection of source waters, aimed at reducing the presence of natural organic matter, is often the most efficient approach to control.


Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 63
1995, iv + 551 pages [E]
ISBN 92 832 1263 0
Sw.fr. 90.-/US $81.00; in developing countries: Sw.fr. 63.-
Order no. 1720063

Evaluates the carcinogenic risks to humans posed by exposures in the dry cleaning industry, by eight chlorinated solvents and related chemicals, and by an additional group of seven industrial chemicals. Dry cleaning is evaluated in the first and most extensive monograph. Concerning exposures to specific chemicals, tetrachloroethylene is identified as the most commonly used solvent during the last two to three decades. The evaluation also considers exposure to the wide range of chemicals used in the treatment of spots. A review of epidemiological studies on dry cleaning indicates that the risks for cancers at two cites, urinary bladder and oesophagus, may be increased by employment in dry cleaning. The monograph concludes that dry cleaning entails exposures that are possibly carcinogenic to humans.

A second group of monographs evaluates selected chlorinated solvents and related chemicals used in dry cleaning, metal cleaning and degreasing, as chemical intermediates, and in the production of insecticides and herbicides. Trichloroethylene, tetrachloroethylene, and 1,2,3-trichloropropane were classified as probably carcinogenic to humans. 1-Chloro-2-methylpropene was classified as possibly carcinogenic to humans. The remaining chemicals - chloral and chloral hydrate, dichloroacetic acid, trichloroacetic acid, and 3-chloro-2-methylpropene - could not be classified.

For the remaining seven chemicals used in a diversity of industrial applications, vinyl fluoride was classified as probably carcinogenic to humans. Furan, benzofuran, and vinyl acetate were classified as possibly carcinogenic to humans. Acrolein, crotonaldehyde, and furfural could not be classified.


Electromagnetic Fields
(300 Hz-300 GHz)

Environmental Health Criteria, No. 137
1993, 282 pages [E, with summaries in F, S]
ISBN 92 4 157137 3
Sw.fr. 54.-/US $48.60; in developing countries: Sw.fr. 37.80
Order no. 1160137

A critical review of all data relevant to the assessment of human health effects associated with exposure to electromagnetic fields in the frequency range of 300 Hz to 300 GHz. Emphasis is placed on new data that shed light on the interactions of electromagnetic fields with biological systems and on the specific biological effects and responses that result. Over 500 recent studies were rigorously assessed. Sources of exposure considered include broadcasting systems, microwave ovens, induction heating stoves, visual display units, television receivers, dielectric heaters for industrial use, radar installations, and medical devices and procedures.

A chapter devoted to interaction mechanisms reviews the electrical properties of tissues and discusses direct and indirect interaction mechanisms, including the interaction of biological bodies with electrical charges induced on ungrounded or poorly grounded metallic objects such as cars, cranes, wires, and fences. A review of the large body of data from cellular and animal studies considers the strength of evidence pointing to effects on the nervous, endocrine, and immune systems, on reproduction, and on pre- and post-natal development. The report concludes that most of the biological effects of acute exposure are consistent with responses to induced heating

Data on human responses are assessed in the next chapter, which addresses concern about the effects of locally elevated temperatures resulting from the deposition of radiofre-quency energy and the possible dangers, particularly for pregnancy outcome, linked to the use of visual display units. The report concludes that current data provide no clear evidence of detrimental health effects in humans exposed to radiofrequency fields. The remaining chapters provide guidelines for health hazard assessment and standards for protection.


Endrin

Environmental Health Criteria, No. 130
1992, 241 pages [E, with summaries in F, S]
ISBN 92 4 157130 6
Sw.fr. 45.-/US $40.50; in developing countries: Sw.fr. 31.50
Order no. 1160130

Evaluates the risks to human health and the environment posed by endrin, an organochlo-rine insecticide used since the 1950s to protect cotton, rice, sugar cane, maize, and other crops against a wide range of agricultural pests. Because of its high toxicity and persistence in the environment, endrin has been banned in many countries and severely restricted in others. Ingestion of contaminated food is the most important route of human exposure.

A review of levels of endrin detected in the environment, in animals, in food, and in exposed humans draws upon a large number of older studies conducted when endrin was much more widely used. Findings from these studies, which document widespread contamination, indicate the health and environmental consequences arising from the indiscriminate use and disposal of this highly toxic pesticide. Reports of fish kills linked to the use of endrin confirm its environmental hazards, which have also been documented for other species.

Other sections review findings from experimental investigations of toxicity, case reports of accidental and suicidal poisoning, and epidemiological studies of occupationally exposed workers. Findings consistently point to the neurotoxicity of this pesticide and the rapid onset of convulsions following exposure. The report concludes that endrin is unlikely to present a hazard to exposed workers where good work practices and recommended safety precautions are enforced. The occasional presence of low levels of endrin in air, food, and surface and drinking-water is judged to be of little public health significance. Because of the high toxicity of this pesticide, the report recommends that endrin should be used only in cases where no less toxic alternative is available. The report closes with advice on the medical treatment of endrin poisoning and on the emergency management of major status epilepticus.


Ethylbenzene

Environmental Health Criteria, No. 186
1996, 101 pages [E, with summaries in F, S]
ISBN 92 4 157186 1
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1160186

Evaluates the risks to human health and the environment posed by exposure to ethylbenzene, a chemical widely used in the production of styrene and, to a much smaller extent, in technical xylene used as a solvent in paints and lacquers, and in the rubber and chemical manufacturing industries.

Industrial releases and vehicle emissions are identified as the main sources of human and environmental exposure. A review of data on the environmental behaviour and fate of ethylbenzene concludes that the chemical is readily degraded by photo-oxidation and biodegradation. The principal environmental sink is the atmosphere, where photo-oxidation may contribute to photochemical smog formation.

The most extensive section assesses the results of toxicity studies in experimental animals and in vitro test systems. These studies support the conclusion that ethylbenzene has low acute and chronic toxicity and demonstrates no significant mutagenic properties or teratogenicity in the species tested. Data were judged inadequate to assess carcinogenicity and reproductive toxicity.

An evaluation of the limited data on toxicity to humans notes that inhalation is the major route of exposure, though exposure may also occur via skin absorption or ingestion. Toxic effects observed include prenarcotic effects on the central nervous system and limited irritation of the mucous membranes and eyes. As occupational exposure to ethylbenzene alone is rare, the report was unable to reach conclusions concerning the health risks to workers. On the basis of the limited data available, a tentative guidance value for ethylbenzene in inhaled air was established using an uncertainty factor. The report further concludes that ethylbenzene is unlikely to cause adverse effects in aquatic or terrestrial ecosystems except in cases of spills or point-source emissions.


Ethylene Glycol: Environmental Aspects

Concise International Chemical Assessment Document, No. 22
2000, iii + 24 pages [E, with summaries in F, S]
ISBN 92 4 153022 7
Sw.fr. 13.–/US $11.70
In developing countries: Sw.fr. 9.10
Order no. 1380022

A concise assessment of the risks to the environment posed by ethylene glycol. The chemical is produced in large quantities for use as a chemical intermediate, as an antifreeze in engine coolants, and as a de-icer on airport runways and aeroplanes. Most release to the environment is to the hydrosphere, with use for the de-icing of runways and aeroplanes accounting for the largest local release to surface waters.

Concerning behaviour in the environment, studies show little or no capacity to bind to particulates and no mobility in soil. Evidence likewise indicates a low likelihood of bioaccumulation. Rapid biodegradation has been observed under both aerobic and anaerobic conditions in sludge, surface waters, groundwater, and soil. Although data are limited, levels detected in surface water are generally low, with the exception of very high concentrations in runoff water from airports.

Studies of toxic effects indicate generally low toxicity to aquatic organisms when the pure compound was tested, but higher toxicity when tests used a de-icer containing ethylene glycol. Laboratory exposure of aquatic organisms to stream water receiving runoff from airports resulted in toxic effects and death. Terrestrial organisms, which are much less likely to be exposed, generally show low sensitivity to the compound.

The report concludes that the risk to aquatic organisms from the production of ethylene glycol is very low and is probably negligible. Substantially higher concentrations in runoff water at particular airport sites are of much greater concern. The report further concludes that risk assessment and field monitoring of overt effects should be applied on a case-by-case basis to determine the need to apply measures for pollution control.

Fenitrothion

Environmental Health Criteria, No. 133
1992, 184 pages [E, with summaries in F, S]
ISBN 92 4 157133 0
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160133

Evaluates the risks to human health and the environment posed by fenitrothion, a moderately toxic organophosphorus insecticide used since 1959 to control pests on crops, stored grains, and cotton. Fenitrothion is also used in forest spraying and in public health campaigns.

Because residues in food decline very quickly, the report concludes that exposure of the general population via the ingestion of contaminated food does not constitute a health hazard. A review of studies on the kinetics and metabolism of this insecticide shows that fenitrothion is unlikely to remain in the body for a prolonged period.

The remaining sections evaluate investigations of toxicity, case reports of accidental and intentional poisoning in humans, epidemiological studies of exposed workers, studies of spray-men and inhabitants following indoor spraying in large public health campaigns, and studies of effects on organisms in the environment.

The report found no evidence of carcinogenic, mutagenic, embryotoxic, or teratogenic effects, of delayed neurotoxicity, or of an association between exposure to fenitrothion and the development of Reye's syndrome. Evidence supports the conclusion that fenitrothion is unlikely to constitute a health hazard for occupationally exposed workers when good work practices, hygienic measures, and safety precautions are followed. Concerning effects on environmental organisms, particularly following standard forest spraying operations, the report notes that few, if any, adverse effects have been detected despite the widespread use of this insecticide for several decades. Because fenitrothion is highly toxic for non-target arthropods, the report recommends that this insecticide should never be sprayed over water bodies or streams.


Fenvalerate

Environmental Health Criteria, No. 95
1990, 121 pages [E, R]
ISBN 92 4 154295 0
Sw.fr. 24.-/US $21.60; in developing countries: Sw.fr. 16.80
Order no. 1160095

Evaluates the risks to human health and the environment posed by fenvalerate, a synthetic pyrethroid insecticide widely used for crop protection. Marketed since 1976, fenvalerate is also used in homes and gardens and for the control of insect infestation in cattle.

A brief discussion of sources of human exposure concentrates on studies of dietary residues, concluding that residues in crops grown by good agricultural practice are generally low. A section devoted to environmental behaviour cites studies documenting the rapid degradation and decomposition of fenvalerate, the reduced toxicity of its degradation products, and the absence of leaching in soil. Other sections summarize studies of effects on aquatic and terrestrial organisms. Although laboratory tests have demonstrated high toxicity for fish and honey bees, these effects are shown to be markedly reduced under field conditions, where toxicity is mitigated by the adsorption of the compound to sediments and its strong repellent effect.

The remaining sections evaluate effects on health as determined from the results of animal experimentation, in vitro tests, case studies of accidental exposure, and clinical investigations. The book concludes that exposure of the general population is very low, that the effects of occupational exposure are transitory, and that risks to the environment and human health are unlikely when fenvalerate is applied as recommended.

"... highly recommended as a reference book..."
— Environment International


Flame Retardants: A General Introduction

Environmental Health Criteria, No. 192
1997, xvii + 133 pages [E, with summaries in F, S]
ISBN 92 4 157192 6
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160192

Provides a general overview of the properties, mechanisms of action, production, use, and performance of chemicals added to polymeric materials, both natural and synthetic, to enhance flame-retardant properties. Flame-retardant chemicals are most often used with low-to-moderate cost commodity polymers to either lower ignition susceptibility or lower flame spread once ignition has occurred.

The opening chapters explain how flame-retardant systems work and profile the three main families of flame-retardant chemicals in terms of their component chemicals, formulations, distinctive properties and actions, and the corresponding commercial applications. Mechanisms of action are covered in chapter three, which explains the processes involved in polymer flammability and the mechanisms by which flame retardants act to interfere with combustion and retard these processes. Chapter four discusses the strict performance criteria that guide the selection of suitable flame retardants and severely limit the number of acceptable materials.

Data on the production and uses of flame retardants and flame-retardant polymers are summarized in chapter five, which includes several tables depicting the worldwide demand for these chemicals. Chapter six, on the formation of toxic products on heating or combustion, reviews data on some of the major toxic products that can be produced by pyrolysis of flame retardants. The chapter also addresses the important question of whether use of these chemicals creates more toxic smoke and thus increases the risks to human health. The remaining chapters provide an overview of possible routes of exposure and hazards to humans and the environment, and summarize various national regulations pertaining to flame retardants. A 60-page annex lists flame retardants in commercial use or in former use.


Formaldehyde

Environmental Health Criteria, No. 89
1989, 219 pages [E]
ISBN 92 4 154289 6
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160089

Evaluates the risks to human health and the environment posed by formaldehyde, a gas produced industrially in large quantities for a wide range of applications, including the production of glue for particle boards and plywood and the manufacturing of sterilizing and disinfecting agents, medicines, cosmetics, and several consumer goods.

In view of the wide range and diversity of exposure sources, the book makes a clear distinction between outdoor exposures, occupational exposures, and exposures arising from the emission of formaldehyde into indoor air environments. Particular attention is given to the case of hospitals and scientific facilities, where formaldehyde is widely used as a sterilizing and preserving agent, and living spaces, such as schools, kindergartens, and mobile homes, where uncontrolled emissions of formaldehyde from building materials, furniture, and tobacco smoking may pose a particular health hazard.

The book devotes most of its pages to the task of defining exposure levels and relating these to health hazards. The book cites evidence providing a relatively clear suggestion of a possible cancer risk for humans from exposure to formaldehyde. The book concludes that the carcinogenic potential is not high, that only nasal or nasopharyngeal tumours are likely to be causally related to formaldehyde exposure, and that formaldehyde is not teratogenic. The final section presents a series of recommendations, including proposed maximum allowable air concentrations in different settings and precautions to be followed in hospitals.

"... essential reading for anyone concerned about potentially harmful effects associated with the production, use or disposal of formaldehyde..."
— International Journal of Environmental Studies


Fully Halogenated Chlorofluorocarbons

Environmental Health Criteria, No. 113
1990, 164 pages [E]
ISBN 92 4 157113 6
Sw.fr. 32.-/US $28.80; in developing countries: Sw.fr. 22.40
Order no. 1160113

Evaluates the risks to human health and the environment posed by the production and use of fully halogenated chlorofluorocarbons. Eight different commercial compounds, some of which are known to contribute to ozone depletion, are assessed. The opening section summarizes the unique chemical and physical properties that account for the commercial importance of chlorofluorocarbons and explain why their degradation in the upper stratosphere destroys ozone. Subsequent sections summarize data on the global distribution of chlorofluorocarbons and evaluate the strength of evidence suggesting that increased ultraviolet-B radiation, resulting from ozone depletion, will endanger terrestrial and aquatic biota. The report concludes that even small increases in ambient ultraviolet-B exposure can result in significant ecosystem changes.

The second half of the book evaluates health risks associated with both direct exposure, mainly through inhalation during production, and the far more important indirect effects of ozone depletion. A review of extensive experimental data supports the conclusion that direct exposure entails low toxicity and little or no carcinogenic risk. Concerning the consequences of increased exposure to ultraviolet-B radiation, the book notes documented and potential risks that include a virtually undisputed increase in the incidence of non-melanoma skin cancers, an increase in the incidence of cutaneous melanomas, possible suppression of the immune system, and an increase in the incidence of cataracts. The report concludes with an eight-point agenda for further research and a call for cuts of at least 80-90% in the emission of ozone-depleting chlorofluorocarbons.


Fumonisin B1

Environmental Health Criteria, No. 219
2000, xix + 150 pages (English, with summaries in French and Spanish)
ISBN 92 4 157219 1
Sw.fr. 36.–/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160219

This book evaluates the risks to human and animal health posed by the consumption of maize and maize-based products contaminated with fumonisin B1. This naturally occurring mycotoxin, produced by the mould Fusarium verticillioides, is found in high concentrations throughout the world, and is believed to be the most prevalent and toxic of the fumonisins. Consumption is known to cause two fatal diseases in farm animals. Possible adverse effects on human health are of particular importance in several developing countries, where maize and maize-based products are the staple food for large populations.

A section on sources of human exposure considers factors that influence the vulnerability of maize to contamination during growth, storage, and processing. Weather conditions that favour Fusarium kernel rot are noted to cause significant accumulation of fumonisin B1. Studies of the effects of different processing techniques demonstrate the toxin's stability. Dry milling results in its distribution into the bran, germ, and flour. In experimental wet milling, fumonisin has been detected in steep water, gluten, fibre, and germ, but not in the starch.

A review of studies on the environmental fate of fumonisin B1 concludes that fumonisins are heat stable, light stable, water soluble, poorly absorbed, poorly metabolized, and rapidly excreted by animals. As a result, most fumonisin is recycled into the environment in a manner that concentrates its spatial distribution.

A section on environmental levels and human exposure reviews a large number of studies measuring levels of contamination in maize and maize-based foods for human consumption and in animal feeds. The highest levels of contamination have been recorded in Europe, followed by North America, Africa, Asia, and Latin America.

The most extensive section reviews toxicity data from studies in experimental animals and in vitro test systems. Fumonisin B1 has been shown to be hepatotoxic in all animal species tested, and nephrotoxic in several species. The report found no evidence that consumption of fumonisins causes adverse effects on development or reproductive functions in farm animals or humans. Studies in some species indicate an association between exposure and the development of renal and liver cancers. The evaluation also drew on extensive investigations of equine leukoencephalomalacia and porcine pulmonary oedema syndrome, fatal diseases which have been causally linked to the consumption of fumonisin-contaminated feeds. These and other lines of evidence suggest that fumonisin B1 exerts its toxic action by inhibiting cell growth and causing accumulation of free sphingoid bases and alteration of lipid metabolism.

The evaluation of effects on human health draws on limited evidence from correlation studies, in South Africa and China, and an analytical study, from northern Italy, suggesting a link between direct fumonisin exposure and oesophageal cancer. Due to weaknesses in all these studies, no firm conclusions could be reached. No confirmed records of acute fumonisin toxicity in humans were available for evaluation.

A final section draws attention to the urgent need for more knowledge about the effects of food processing and cooking, especially in developing countries, on levels of contamination, for epidemiological studies of adverse health effects, and for better understanding of the mode of toxic action in humans.


2-Furaldehyde

Concise International Chemical Assessment Document, No. 21
2000, iv + 27 pages [E, with summaries in F, S]
ISBN 92 4 153021 9
Sw.fr. 13.–/US $11.70
In developing countries: Sw.fr. 9.10
Order no. 1380021

A concise assessment of the risks to human health and the environment posed by exposure to 2-furaldehyde. The chemical is produced commercially for industrial use in the production of resins, abrasive wheels, and refractories, refining of lubrication oils, and solvent recovery. Although 2-furaldehyde is present in many food items as a natural product or contaminant, emphasis is placed on the more important risks to health that occur in occupational settings.

Concerning presence in the environment, the highest reported emissions are from the wood pulp industry, which releases 2-furaldehyde predominantly in the vapour phase. The chemical has been found in water samples near industrial sites, in air, and in a range of food

items. Data from animal studies indicate that 2-furaldehyde is readily absorbed via the inhalation and dermal exposure routes, and rapidly excreted via the urine. In humans, studies show absorption of the chemical, in vapour form, via the lungs and skin, and excretion via the urine. Studies of toxic effects in animals provide evidence of both carcinogenic and genotoxic effects. The principal neoplastic effects observed include increases in hepatocellular adenomas and hepatocellular carcinomas, and an increased incidence of skin tumours.

The assessment of health effects in humans concentrates on occupational exposures in the petrochemical, distillation, and food flavouring industries, and during the manufacturing of resins, polymers, and abrasive wheels. Data from human studies were judged to be extremely limited and of poor quality. Based on findings from animal studies, the report concludes that a potential risk of carcinogenic and genotoxic effects exists in the occupational environment , and that exposure levels should be reduced as low as possible, using currently available protective technology.

Glyphosate

Environmental Health Criteria, No. 159
1994, 177 pages [E, with summaries in F, S]
ISBN 92 4 157159 4
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160159

Evaluates the risks to human health and the environment posed by glyphosate, a post-emergent, systemic, and non-selective herbicide used, primarily against deep-rooted perennial species, in agriculture and forestry, and for weed-killing in water systems, parks, road verges, and gardens. Roundup is the major formulation of glyphosate. Because of its agricultural uses, concern centres on the possible presence of residues in crops and animal tissues destined for human consumption.

Concerning possible presence of residues in crops and edible animal tissues, the report cites evidence that such residues are negligible. The report further concludes that the low toxicity, low volatility, and low body absorption of glyphosate make its application by backpack sprayer safe when workers wear full protective clothing.

A review of studies in laboratory animals and in vitro test systems supports the conclusion that glyphosate has very low toxicity when administered by the oral and dermal routes, does not induce sensitization, and shows no mutagenic, carcinogenic, or teratogenic activity.

While the formulation Roundup is acutely toxic to humans when ingested intentionally or accidentally, dermal absorption is low, and no adverse effects are expected in properly protected workers. Studies of adverse effects on other organisms in the laboratory and field demonstrate low toxicity for bees, earthworms, and birds. The risk to most aquatic organisms was judged to be small or negligible. While marked changes in populations of birds and small mammals have been documented following glyphosate application, these changes are attributed to alterations in habitat, vegetation cover, and food supply resulting from the herbicide's intended effects.


Hexachlorobenzene

Environmental Health Criteria, No. 195
1997, xviii + 160 pages [E, with summaries in F, S]
ISBN 92 4 157195 0
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160195

Evaluates the risks to human health and the environment posed by exposure to hexachlorobenzene (HCB). HCB has historically had many industrial and agricultural uses, including extensive use as a seed dressing to prevent fungal disease on grains. Although concerns about effects on health and the environment prompted many countries to discontinue production in the 1970s, inadvertent production continues in the form of by-products and impurities generated during the manufacture of chlorinated solvents, chlorinated aromatics, and chlorinated pesticides. Other continuing sources of this highly persistent chemical include application of contaminated pesticides, incomplete incineration of chlorine-containing wastes, and release from old dump sites.

A discussion of the environmental behaviour of HCB cites properties, including its resistance to degradation, mobility, and lipid solubility, that help explain its detection in all environmental compartments and its presence in the adipose tissues of virtually all members of the general population. Studies indicate that HCB undergoes significant bioaccumulation and biomagnification in the food chain. Concerning environmental levels and human exposure, food is determined to be the principal route of exposure for the general population. Although HCB is widely dispersed in ambient air, concentrations are generally low. The contribution of levels in drinking-water to total exposure is likewise estimated to be low. Limited data suggest that, when poor industrial hygiene is practiced, workers in certain occupations may be exposed to higher concentrations than the general population.

A review of data on the kinetics and metabolism of HCB in experimental animals concludes that the chemical is readily absorbed by the oral route and poorly via the skin. Studies demonstrate that HCB is slowly metabolized and eliminated, accumulates in lipid-rich tissues, crosses the placental barrier, and is present in breast-milk.

The most extensive section evaluates findings from the numerous studies of toxic effects in laboratory animals. Convincing studies demonstrate that HCB is carcinogenic in animals and has adverse non-neoplastic effects, at relatively low doses, on a wide range of organs and systems, including the liver, lungs, kidneys, thyroid, reproductive tissues, and nervous and immune systems.

The evaluation of effects on human health draws on numerous reviews of an accidental poisoning incident in Turkey that occurred in 1955-1959, when HCB-treated wheat grain was ground into flour and used to produce bread, and resulted in more than 600 cases of porphyria cutanea tarda with a high mortality rate. In this incident, clinical manifestations of poisoning included disturbances in porphyrin metabolism, dermatological lesions, hyperpigmentation, hypertrichosis, enlarged liver, enlargement of the thyroid gland and lymph nodes, and osteoporosis or arthritis. Nursing infants of exposed mothers developed a disorder called pembe yara, or "pink sore", and most died within a year. Follow-up of survivors at 20 and 30 years revealed persistent abnormalities. The report found no adequate epidemiological studies of cancer in exposed populations, including workers.

On the basis of clinical evidence from the poisoning incident, supported by animal data demonstrating adverse effects at several sites in several species at relatively low doses, the report calls for measures to reduce the environmental burden of HCB and concludes that alternatives should be found for any continuing present uses. The following health-based guidance values for the total daily intake of HCB in humans were proposed: for non-neoplastic effects, 0.17 micrograms/kg body weight/day; for neoplastic effects, 0.16 micrograms/kg body weight/day.


Hexachlorobutadiene

Environmental Health Criteria, No. 156
1994, 136 pages [E, with summaries in F, S]
ISBN 92 4 157156 X
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160156

Evaluates risks to human health and the environment posed by exposure to hexachlorobutadiene. This compound is essentially a waste product formed during the manufacturing of various chlorinated hydrocarbons. Hexachlorobutadiene has limited use as an agricultural fumigant in some parts of the world. The chemical can also be used for the recovery of chlorine-containing gas in chlorine plants and as a wash liquor for removing certain volatile organic compounds from gas streams.

Findings from field and laboratory studies support the conclusion that hexachlorobutadiene has a high potential to accumulate in sediment and to persist in water. Hexachlorobutadiene is noted to be moderately to very toxic to aquatic organisms, with fish species and crustaceans found to be the most sensitive.

A review of experimental studies concentrates on the large body of evidence demonstrating short- and long-term effects on the kidney. These findings support the conclusion that the target organs for toxicity, in humans as well as experimental animals, are the kidney, and to a much lesser extent, the liver. The report also cites evidence supporting the hypothesis that the nephrotoxicity, mutagenicity, and carcinogenicity of hexachlorobutadiene are dependent on the biosynthesis of a reactive sulfur metabolite following conjugation with glutathione.

In view of the shortage of human studies, the evaluation of effects on health draws upon experimental data supported by evidence that the metabolism of hexachlorobutadiene is similar in humans and animals. The report concludes that hexachlorobutadiene should be regarded as a sensitizing agent. Evidence for carcinogenicity is limited in animals and insufficient in humans.

"... concise, clear and authoritative..."
— Environmental Management and Health


alpha- and beta-Hexachlorocyclohexanes

Environmental Health Criteria, No. 123
1992, 170 pages [E, with summaries in F, S]
ISBN 92 4 157123 3
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160123

Evaluates the risks to human health and the environment posed by exposure to alpha- and beta-hexachlorocyclohexanes (HCH). These two isomers are by-products in the manufacturing of lindane, and may be present in this pesticide as impurities. Alpha- and beta-HCH are also present in technical-grade HCH, which is used in agriculture and wood protection. Most environmental releases are linked to the use of technical-grade HCH and to the inappropriate disposal of residues produced when lindane is purified.

Alpha- and beta-HCH are evaluated in separate monographs. Both isomers are noted to be universal environmental contaminants, with concentrations detected in samples of air, rain water, fresh water, sea water, soil, sediment, and numerous plant and animal species, as well as in several important food items.

A review of studies on environmental behaviour and metabolic fate concludes that alpha- and beta-HCH, when compared with lindane, are characterized by a higher bioconcentration in the environment, a slower rate of biodegradation by ultraviolet light, and a slower rate of elimination from organisms. Current exposures via food are judged to be low and gradually decreasing, supporting the conclusion that these isomers pose no serious health threat to the general public. A review of findings from toxicity studies in laboratory animals identifies growth retardation and effects on the liver and kidney as the major consequences of acute exposure.

In its concluding section, the report expresses serious concern over the widespread pollution of the environment with these isomers. As neither has any insecticidal action, the report concludes that use of technical-grade HCH products containing high concentrations of alpha- and beta-HCH is never justified.


Hexachlorocyclopentadiene

Environmental Health Criteria, No. 120
1991, 126 pages [E, with summaries in F, S]
ISBN 92 4 157120 9
Sw.fr. 24.-/US $21.60; in developing countries: Sw.fr. 16.80
Order no. 1160120

Evaluates risks to human health and the environment posed by the production, use, and disposal of hexachlorocyclopentadiene (HEX). HEX is a chemical used in the production of several pesticides, including heptachlor, chlordane, aldrin, dieldrin, endrin, mirex, pentac, and endosulfan. The compound is also used as an intermediate in the manufacturing of flame retardants and dyes.

A section devoted to sources of human and environmental exposure evaluates data on quantities released during production, processing, and use, during the incineration of hazardous waste containing HEX, and from products contaminated with HEX. While exposure of the general population is judged to be very low, risk of exposure can be high in residential areas near HEX production, processing, and disposal sites or hazardous waste incinerators. A discussion of environmental behaviour draws upon studies conducted following chemical accidents at manufacturing sites and waste treatment plants in the USA.

Findings from toxicity studies showed high toxicity for HEX vapour following oral, dermal, and inhalation dosing in all species tested, with dosing via inhalation causing the most acute toxicity. A review of the limited data available on human health effects yields evidence of severe irritation to the eyes, nose, throat, and lungs. Major concern centers on the toxic effects on the human respiratory system. A review of epidemiological studies found no evidence of an increase, attributed to HEX or its metabolites, in the incidence of neoplasms at any site.

"... well-written and concise ... highly recommended..."
— Journal of Toxicology and Environmental Health


n-Hexane

Environmental Health Criteria, No. 122
1991, 164 pages [E, with summaries in F, S]
ISBN 92 4 157122 5
Sw.fr. 32.-/US $28.80; in developing countries: Sw.fr. 22.40
Order no. 1160122

Evaluates the risks to human health and the environment posed by n-hexane, a chemical isolated from natural gas and crude oil and used in food processing to extract vegetable oil from beans, nuts, and seeds. n-Hexane is also used as a solvent, a cleaning agent, in the rubber industry, and in the manufacture of pharmaceuticals.

The opening sections review what is known about the behaviour of this highly volatile chemical in the environment and its metabolic fate in experimental animals and in the human body. A review of investigations in experimental animals and in vitro test systems concentrates on testicular lesions and neurotoxicity as the principal effects of repeated exposure to n-hexane. Studies have also shown that neurotoxicity induced by n-hexane is enhanced by co-exposure to methyl ethyl ketone, methyl isobutyl ketone, and lead acetate; co-exposure to toluene decreases the neurotoxic effects of n-hexane.

These findings are further supported by observations in humans, which draw upon several reports of peripheral neuropathy in workers exposed to n-hexane and in abusers of glues or solvents containing this chemical. The report notes that the majority of occupational cases have occurred in poorly ventilated small industries.

While concluding that n-hexane is not likely to present a hazard to either the general population or the environment, the report stresses the need for precautions in the occupational setting, including the use of suitably designed work processes and engineering controls for reducing atmospheric levels below the recommended occupational exposure limits. The book further recommends the use of protective clothing and the ready availability of respiratory protection for use in enclosed spaces and in emergencies.


Human Exposure Assessment

Environmental Health Criteria, No. 214
2000, xxx + 375 pages (English, with summaries in French and Spanish)
ISBN 92 4 157214 0
Sw.fr. 78.–/US $70.20; In developing countries: Sw.fr. 54.60
Order no. 1160214

This book offers an up-to-date guide to the concepts, procedures, statistical methods, and models used to assess human exposure to environmental chemicals. Noting that exposure assessment is a comparatively new discipline of the environmental sciences, the book aims to encourage its use as a powerful tool for measuring actual levels of exposure and determining whether interventions are needed to protect public health. With this goal in mind, the book gives researchers expert advice on the design and conduct of studies, the interpretation of findings, and the best methods for ensuring the reliability and reproducibility of results. Throughout, emphasis is placed on the ways in which well-designed exposure assessments can enhance the practical value of findings from traditional epidemiological and toxicological investigations.

The book has twelve chapters. The first six cover conceptual and methodological issues. Chapter one introduces basic concepts used in exposure assessment, and describes direct and indirect methods of measuring or estimating actual exposure and determining whether intervention is required. The uses of human exposure data are covered in chapter two, which explains how studies of human exposure can reduce the uncertainty of estimates used in epidemiology, risk assessment, and risk management. Chapter three considers several generic study designs and approaches, and compares their advantages and limitations. Chapter four, on statistical methods, discusses selective applications of descriptive and inferential statistics, using data on lead exposure as an example. Subsequent chapters review methods for the collection and application of time-use data, and introduce the principles, methods, and data requirements of exposure modelling.

Against this background, chapters in the second half of the book offer practical advice on the design and conduct of studies aimed at assessing exposure to chemicals in different environmental media. Separate chapters describe sampling methods used to analyze chemical concentrations in air, water, and food, and in soil and settled dust. Environmental allergens that can contribute to disease or alter susceptibility are considered in chapter nine, which concentrates on methods for measuring particles from house dust mites and their faeces, allergens from pets and cockroaches, and allergens or toxins from fungi, bacteria, and pollen.

Subsequent chapters describe the use of biological markers in exposure assessment, and discuss issues surrounding the quality assurance of exposure studies and results. The final chapter presents brief summaries and examples of exposure studies in order to illustrate different study designs for different objectives, target pollutants, and populations. Studies that show how exposure assessment supports epidemiology and risk management, particularly in developing countries, are also included.


Hydroquinone

Environmental Health Criteria, No. 157
1994, 178 pages [E, with summaries in F, S]
ISBN 92 4 157157 8
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160157

Evaluates the risks to human health and the environment posed by exposure to hydroquinone, a chemical found, in natural form, in a number of plants and animals. Hydroquinone is manufactured for a large variety of commercial applications, including use as a developer in black-and-white photography, in the production of medical and industrial X-ray films, in the manufacture of rubber antioxidants and antiozonants, and antioxidants for food preservation, and as a chemical intermediate for the production of agrochemicals and performance polymers. Hydroquinone and products containing hydroquinone are used in cosmetics and medical skin preparations as a depigmentation agent to lighten small areas of hyperpigmented skin and to treat various other disorders of pigmentation.

The most extensive section evaluates studies of toxic effects in experimental animals and in vitro test systems. Particular attention is given to recent studies indicating that co-exposure to hydroquinone and various other phenolic compounds can greatly potentiate the toxic effects of the individual compounds, causing cytotoxic, immunotoxic, and genotoxic effects.

Although data from human studies were judged inadequate to evaluate carcinogenic potential, the report notes a well-documented association between exposure to hydroquinone and various skin disorders. Long-term exposure to airborne hydroquinone has been observed to cause a range of ocular disorders. Citing evidence that skin-lightening creams containing hydroquinone are frequently inadequately labelled and contain concentrations exceeding the permitted limit, the report recommends that over-the-counter sale of these products be restricted. The report also calls for the development of health education programmes to discourage the use of these creams for whole body skin lightening.


Inorganic Lead

Environmental Health Criteria, No. 165
1995, 300 pages [E, with summaries in F, S]
ISBN 92 4 157165 9
Sw.fr. 56.-/US $50.40; in developing countries: Sw.fr. 39.20
Order no. 1160165

Evaluates the risks to human health posed by exposure to lead and inorganic lead compounds. Reflecting the focus of recent research, the report concentrates on mounting evidence that exposure to low levels of lead can have significant effects on health, particularly for infants and young children. Food, beverages, and water constitute the major source of exposure for the adult general population. Infants and young children are exposed to an additional burden of lead present in soil and household dust.

A review of the kinetics and metabolism of lead draws upon studies using several biological markers of exposure and body burden. Particular attention is given to evidence that host factors, such as age, physiological status, and nutritional condition, can influence lead absorption, metabolism, and retention in tissues and bone, where lead is now known to accumulate throughout the lifespan. Studies indicate that lead is readily transferred to the fetus throughout gestation, with lead metabolised from maternal bone serving as an important exposure source. Evidence also underscores the greater vulnerability of infants and young children, who may absorb as much as 50% of dietary lead, compared with only 10% for adults. Additional evidence shows increased lead absorption when diets are deficient in calcium, phosphate, selenium, or zinc.

An evaluation of effects on human health concentrates on the numerous epidemiological studies designed to investigate the possible neurotoxic effects of lead on the developing child. While noting that several well-designed studies have detected an association between exposure to lead and impaired intellectual performance, the report concludes that existing studies cannot provide definitive evidence of either a causal relationship or a threshold.

"... a very good reference text..."
— Pathology


Inorganic Mercury

Environmental Health Criteria, No. 118
1991,168 pages [E, with summaries in F, S; R]
ISBN 92 4 157118 7
Sw.fr. 32.-/US $28.80; in developing countries: Sw.fr. 22.40
Order no. 1160118

Assesses the risk to human health posed by the use of inorganic mercury in dental amalgam and in soaps and creams used to lighten the skin. Although such skin-lightening products are now banned throughout the European Economic Community, in North America, and in many African states, the report reveals that mercury-containing soap continues to be manufactured in several European countries, is sold as germicidal soap to the Third World, and is illegally re-imported from Africa to European cities having a substantial black population.

Dental amalgam and food, most notably seafood, are identified as the main sources of human exposure. Although exposure of the general population is judged to be low, toxic levels may arise from the mishandling of liquid mercury, mercury dispensed from jars, broken thermometers, fluorescent lamps, and accidental ingestion of mercury batteries. The use of skin-lightening soap and creams results in substantial exposure.

The most extensive sections review findings from toxicology studies in experimental animals and clinical reports and epidemiological studies in humans. Results from experimental studies show that inorganic mercury can induce autoimmune glomerulonephritis in all species tested, but not in all strains, indicating a genetic predisposition which is in good agreement with clinical findings. Experimental evidence of adverse effects on the menstrual cycle and on fetal development is also supported by observations in humans. Clinical manifestations of mercury poisoning are described in full detail. Concerning the health hazards posed by dental amalgam, no firm conclusions could be reached in the light of severe weaknesses in the design of most epidemiological studies. The book also includes information on reported levels of mercury vapour in dental clinics and the corresponding risk to the dental profession.


Isobenzan

Environmental Health Criteria, No. 129
1992, 62 pages [E, with summaries in F, S]
ISBN 92 4 157129 2
Sw.fr. 16.-/US $14.40; in developing countries: Sw.fr. 11.20
Order no. 1160129

Evaluates the risks to human health and the environment posed by exposure to isobenzan. This cyclodiene insecticide was manufactured in the Netherlands from 1958 to 1965 and used from existing stocks for several years thereafter. Present sources of human and environmental exposure are restricted to the original waste-disposal sites and to polders which were built up using mud dredged from contaminated harbour areas. Although recent research on this insecticide has been limited, the report draws heavily on a number of proprietary toxicological studies made available by the manufacturer.

The opening sections summarize the physical and chemical properties of isobenzan and review data on mechanisms of biodegradation in soil and water. A section devoted to environmental levels and human exposure assesses findings from the monitoring of water and soil samples, food crops, dairy products, and terrestrial and aquatic organisms. Other studies reviewed show that isobenzan is readily absorbed through the gastrointestinal wall, accumulates in the tissues and organs of laboratory animals, is very persistent in the environment, and is highly toxic to fish, shrimp, and birds.

Concerning the results of toxicological studies in laboratory animals, the report cites over-stimulation of the central nervous system, resulting in convulsions, as the predominant effect of exposure. This observation is supported by 15 cases of clinical intoxication in exposed workers, including eight cases with convulsions. No studies of teratogenicity or mutagenicity were available for evaluation. Despite the limited number of studies, the report concludes that isobenzan poses a significant hazard to the environment and to exposed workers, and that no human or environmental exposure to this substance, whether used as an insecticide or for any other purpose, should be allowed.


Isophorone

Environmental Health Criteria, No. 174
1995, 84 pages [E, with summaries in F, S]
ISBN 92 4 157174 8
Sw.fr. 24.-/US $21.60; in developing countries: Sw.fr. 16.80
Order no. 1160174

Evaluates the risks to human health and the environment posed by the widespread use of isophorone as a solvent for synthetic resins, polymers, and pesticide formulations. Since these uses create numerous opportunities for environmental contamination, most studies of isophorone have concentrated on its presence and behaviour in the environment. Because isophorone is rapidly volatilized and biodegraded, the report concludes that environmental persistence is low and that significant bioconcentration is unlikely.

Studies of kinetics and metabolism in laboratory animals demonstrate rapid absorption via the oral, dermal, and inhalation routes, and rapid elimination via urine and expired air. Data from animal studies indicate a low acute toxicity. Signs of toxicity following inhalation are noted to be similar to the effects produced by solvents and narcotics: eye and respiratory irritation, lacrimation, ataxia, dyspnoea, diarrhoea, central nervous system depression, and death at high doses. Although some investigations have detected adverse effects on the liver, kidney, and lung, no conclusions could be reached due to weaknesses in study design. Studies in in vitro test systems suggest that isophorone is not mutagenic. Results from carcinogenicity investigations were inconclusive.

The limited data on toxic effects in humans indicate symptoms of eye, nose, and throat irritation at low concentrations, and nausea, headache, dizziness, faintness, and inebriation at higher concentrations. To protect the health of exposed workers, the report recommends the use of adequate engineering controls and appropriate industrial hygiene measures. In view of the low toxicity demonstrated in experimental animals and the low levels detected in environmental samples, the risk posed by isophorone to the general population was judged to be minimal.


Limonene

Concise International Chemical Assessment Document, No. 5
1998, iv + 32 pages [E, with summaries in F, S]
ISBN 92 4 153005 7
Sw.fr. 13.-/US $11.70; in developing countries: Sw.fr. 9.10
Order no. 1380005

A concise assessment of the risks to human health posed by exposure to limonene, a chemical released to the atmosphere in large amounts from certain trees and bushes as well as from anthropogenic sources. In industry, limonene is used as a solvent in degreasing metals prior to industrial painting, for cleaning in the electronic and printing industries, and as a solvent in paint. The compound is also used as a flavour and fragrance additive in food, household cleaning products, and perfumes.

The document is part of a new series of brief reports aimed at the characterization of hazards and dose-response for exposures to selected industrial chemicals. With this goal in mind, documents focus on studies and findings considered critical for risk characterization.

In experimental animals exposed to limonene, the liver is the principal target organ; exposure affects the amount and activity of different liver enzymes, liver weight, cholesterol levels, and bile flow. Studies indicate that limonene is not genotoxic and has no teratogenic or embryotoxic potential. No case reports or epidemiological studies were available for the evaluation of health effects in humans.

For the general population, food is identified the principal source of exposure. The report established a guidance value for the ingestion of limonene of 0.1 mg/kg body weight per day. The report further concluded that, at current estimated levels of intake, limonene in food does not represent a significant risk to human health.


Lindane

Environmental Health Criteria, No. 124
1991, 208 pages [E, with summaries in F, S]
ISBN 92 4 157124 1
Sw.fr. 37.-/US $33.30; in developing countries: Sw.fr. 25.90
Order no. 1160124

Evaluates the risks to human health and the environment posed by lindane, an isomer of hexachlorocyclohexane used, for more than four decades, as a broad-spectrum insecticide. Although most lindane is used in agriculture for the treatment of seeds and soils, other important applications include the protection of wood and timber, the treatment of veterinary ectoparasites, and the treatment of scabies and body lice in humans.

Concerning sources and levels of human exposure, the report cites residues in food as responsible for more than 90% of human exposure, noting that populations throughout the world are exposed to lindane on a daily basis. From the large number of studies that have measured levels in food, the report is able to conclude that such exposures are already below the acceptable daily intake and are gradually decreasing.

The assessment of effects on human health benefits from the large number of recent, well-designed studies conducted in both experimen-tal test systems and a range of different laboratory species and strains. These studies support the conclusion that dietary intake of lindane, at currently measured levels, will not impair the health of the general population, nursing infants, or toddlers. Citing evidence from well-designed studies of exposed workers, the report further concludes that, under normal conditions of use, lindane poses no short- or long-term threats to the health of workers. Reports of severe toxic symptoms following the use of lindane to treat scabies underscore the need for strict adherence to prescribed doses, especially when treating children. Concerning risks to organisms in the environment, the report notes that lindane, even when applied at recommended rates, is highly toxic for bats and should thus be regarded as a major environmental hazard wherever bats might roost on lindane-treated wood.


Linear Alkylbenzene Sulfonates and Related Compounds

Environmental Health Criteria, No. 169
1996, 328 pages [E, with summaries in F, S]
ISBN 92 4 157169 1
Sw.fr. 62.-/US $55.80; in developing countries: Sw.fr. 43.40
Order no. 1160169

Evaluates the risks to human health and the environment posed by exposure to linear alkylbenzene sulfonates and their salts, a-olefin sulfonates, and alkyl sulfates. These surface-active agents are used in large quantities in shampoos, dish-washing products, household cleaners, laundry detergents, and industrial cleaners. Linear alkylbenzene sulfonates (LAS) form the major component of these detergent compounds and, as such, have been the most extensively investigated.

The three groups of surfactants are evaluated in separate monographs. The first and most extensive monograph reviews the large number of studies that have investigated the environmental and biological toxicity of LAS. Adverse effects observed in experimental animals were largely confined to minor histopathological and biochemical changes in the liver. An assessment of toxic effects in humans draws upon studies of dermal exposures, supported by a large number of case reports of accidental or suicidal ingestion. Mild to moderate skin irritation following repeated or prolonged dermal contact was the main adverse effect. The report concluded that the average daily intake of LAS by the general population, from all sources, is many times lower than the levels shown to induce minor effects in experimental animals. Concerning effects on the environment, the report made a number of observations about the use of laboratory findings to predict adverse effects. Under environmental conditions, biodegradation and adsorption result in decreased environmental concentrations, decreased bioavailability, and the production of compounds that are less toxic than the parent compound. The numerous laboratory studies were judged inadequate to support a generally applicable assessment of environmental risks. The remaining monographs provide similar evaluations for a-olefin sulfonates and alkyl sulfates.


Methanol

Environmental Health Criteria, No. 196
1997, xviii + 180 pages [E, with summaries in F, S]
ISBN 92 4 157196 9
Sw.fr. 42.-/US $37.80; in developing countries: Sw.fr. 29.40
Order no. 1160196

Evaluates the risks to human health and the environment posed by exposure to methanol. Although methanol occurs naturally in humans, animals, and plants, anthropogenic sources are far more significant. Methanol is produced in large amounts in many countries and is extensively used as an industrial solvent, a chemical intermediate, mainly in the production of methyl tertiary butyl ether, formaldehyde, acetic acid, and glycol ethers, as a denaturant of ethanol, and in a variety of consumer products. Products containing methanol include paints, shellacs, varnishes, mixed solvents in duplicating machines, antifreeze and gasoline deicers, windshield washer fluids, cleansing solutions, and model and hobby glues and adhesives. The general population is routinely exposed to low levels from metabolic processes and from such dietary sources as fruits, vegetables, fruit juices, and foods and soft-drinks containing the synthetic sweetener aspartame. The most notorious use of methanol is as an adulterant in alcoholic beverages, which has led to large-scale episodes of poisoning and numerous fatalities.

A review of data on environmental levels and human exposure notes that most emissions to the environment arise from the production and use of methanol as a solvent in industrial processes and, to a lesser extent, from a variety of other industrial processes and consumer applications. Concerning the behaviour of methanol in the environment, the report cites abundant evidence that the compound is readily and rapidly degraded in a wide variety of environmental media, and has low bioconcentration and low toxicity. Evidence supports the conclusion that methanol is unlikely to have adverse effects on the environment except in the case of accidental spills. The report also draws attention to the potential large increase in environmental levels associated with the use of methanol as a replacement for gasoline and its predicted role as a major automotive fuel in the next century.

A section on kinetics and metabolism in laboratory animals and humans concludes that inhalation and ingestion are the primary routes of methanol exposure, with dermal exposure currently of much less importance in terms of total daily intake for both the general population and exposed workers. Studies indicate that methanol is readily absorbed by all three routes and widely and rapidly distributed to tissues according to the distribution of body water.

A review of findings from animal studies and in vitro test systems notes the great variation in acute and short-term toxicity observed in different species, with toxicity highest in species, such as humans and non-human primates, characterized by a poor ability to metabolize formate. Studies show that exposure to methanol induces a wide range of concentration-dependent teratogenic and embryolethal effects. Although no evidence from animal studies indicates that methanol is a carcinogen, the report notes the absence of an appropriate animal model for carcinogenicity assessment.

The evaluation of effects on human health draws on numerous reports of acute exposure following deliberate or accidental ingestion of adulterated alcoholic beverages. The clinical features of acute methanol poisoning are identified as transient central nervous system depression, followed by an asymptomatic latent period culminating in metabolic acidosis, severe ocular toxicity, blindness, coma, and death. Although data on the health effects of chronic exposure are limited, the report cites evidence of visual disturbances observed in workers exposed to high concentrations of methanol vapours. The report found no evidence of carcinogenic, genotoxic, reproductive, or developmental effects in humans attributed to methanol exposure.


Methomyl

Environmental Health Criteria, No. 178
1996, 150 pages [E, with summaries in F, S]
ISBN 92 4 157178 0
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1160178

Evaluates the risks to human health and the environment posed by exposure to methomyl, a carbamate pesticide with a well-characterized mechanism of action as a cholinesterase inhibitor. Methomyl is used on a wide range of crops throughout the world, including fruit, vines, hops, vegetables, grain, soya bean, cotton, and ornamentals. The pesticide also has indoor uses to control flies in animal houses and dairies. In view of these uses, many studies have investigated levels detected in food items, including dairy products, and the toxic effects associated with prolonged dietary exposure.

The report concludes that levels in groundwater, food and other crops, and dairy products are either very low or undetectable; total diet studies found either no detectable residues or very low levels. Experimental toxicity studies are evaluated in the most extensive section, which found high toxicity by the oral and inhalation routes, but low dermal toxicity. Signs of toxicity were observed to be consistent with those of cholinesterase inhibitors, including profuse salivation, lacrimation, tremor, and pupil constriction. Studies further show that recovery from these effects is rapid, with no gross pathological effects observed. Repeated dietary administration over longer periods did not lead to accumulation or an increase in toxic effects. The evaluation found no evidence of carcinogenicity, mutagenicity, or neurotoxic effects.

A section on the effects of methomyl exposure on human health draws on findings from cases of accidental and intentional poisoning, including several fatalities. Findings from these case reports confirm the high acute toxicity by the oral route seen in experimental animals, and the quick recovery and reversal of cholinesterase inhibition in survivors.


2-Methoxyethanol, 2-Ethoxyethanol, and their Acetates

Environmental Health Criteria, No. 115
1990, 126 pages [E]
ISBN 92 4 157115 2
Sw.fr. 24.-/US $21.60; in developing countries: Sw.fr. 16.80
Order no. 1160115

Evaluates the risks to human health and the environment posed by exposure to 2-meth-oxyethanol, 2-ethoxyethanol, and their two acetates: 2-methoxyethyl acetate and 2-ethoxyethyl acetate. These glycol ethers have a wide range of uses as solvents with particular application in paints, stains, inks, lacquers, and the production of food-contact plastics.

Sections concerned with sources of exposure note that patterns of use as evaporative solvents result in significant, widespread emissions to the environment, with great potential for direct human exposure in industry, in small work-shops, and during home use of numerous consumer products. A review of data on environmental behaviour points to rapid degradation, supporting the conclusions that the risk of hazardous environmental concentrations is small and that human exposure through food, water, or the ambient air is probably negligible. A review of experimental studies of toxicity reveals strong and consistent evidence, across all species investigated, of adverse effects on the male reproductive system, developmental toxicity, and haematological toxicity. Although studies in humans are scarce, results from case reports and workplace epidemiological studies confirm the findings from animal research, pointing to a clear risk of disturbances in the male reproductive system and of embryotoxicity.

The book concludes with a series of recommendations to authorities, including the need to find less toxic solvents, to alert users to the hazards of these chemicals, and to be aware that air monitoring alone is not an adequate measure of safety conditions at the workplace.


Methyl Bromide

Environmental Health Criteria, No. 166
1995, 324 pages [E, with summaries in F, S]
ISBN 92 4 157166 7
Sw.fr. 62.-/US $55.80; in developing countries: Sw.fr. 43.40
Order no. 1160166

Evaluates the risks to human health and the environment posed by exposure to methyl bromide. This highly toxic gas is present in the environment both as a natural product of biological processes in the environment and as a commercial product widely used as a fumigant for pest control. The compound's ability to penetrate quickly and deeply into sorptive materials makes it an effective and versatile fumigant. Methyl bromide is used to control nematodes and soil-borne fungi in fields and greenhouses, to treat fresh fruits and vegetables in compliance with quarantine regulations, and to control termites and other indoor pests in homes and buildings.

Data support the conclusion that occupational exposure, particularly during fumigation, poses the greatest potential threat to human health. Concerning risks to the environment, evidence points to the presence of methyl bromide in the troposphere and stratosphere, where it contributes substantially to ozone depletion.

The toxic effects of exposure are examined in the most extensive section, which reviews the large number of experimental studies. Findings confirm the high toxicity of methyl bromide for all animal species by all routes of administration investigated. Data on carcinogenicity were judged inadequate.

A section on toxic effects in humans draws on hundreds of case histories of accidental and occupational poisoning, including numerous fatalities. Neurological manifestations are cited as the major clinical signs of toxicity. Exposure may also result in permanent injury commonly characterized by sensory disturbances, weakness, disturbances of gait, irritability, and blurred vision. In view of the high toxicity of this substance, the report stresses the need to follow strict safety precautions, particularly when using methyl bromide to fumigate greenhouses, buildings, and silos and other food storage facilities.


Methyl Ethyl Ketone

Environmental Health Criteria, No. 143
1993, 161 pages [E, with summaries in F, S]
ISBN 92 4 157143 8
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160143

Evaluates risks to human health and the environment posed by exposure to methyl ethyl ketone. Because of its excellent properties as a solvent, methyl ethyl ketone is widely used in the application of protective coatings and adhesives, in magnetic tape production, in the dewaxing of lubricating oil, and in food processing. Methyl ethyl ketone is also a common ingredient in consumer products such as varnishes and glues. Intentional abuse of solvent mixtures containing this chemical is of particular public health concern, since injuries can be severe, permanently disabling, and even fatal.

Although methyl ethyl ketone is a natural component of many foods, the report notes that concentrations are consistently low. Other sources of population exposure include drinking-water, tobacco smoke, and volatilization from building materials and consumer products. The report concludes that methyl ethyl ketone does not pose a significant threat to the environment except in cases of major spills or discharges.

The remaining sections concentrate on evidence, from animal studies, in vitro test systems, and observations in humans, of the toxic effects of this chemical. Evidence from several outbreaks of poisoning linked to solvent abuse is also considered. The report concludes that the principal toxic effects observed with methyl ethyl ketone exposure stem from its well-documented ability to potentiate the toxicity of two classes of organic solvents: unbranched aliphatic hexacarbons and haloalkanes. While methyl ethyl ketone on its own appears to be a relatively safe organic solvent, chronic co-exposure with these other organic solvents represents a significant potential occupational hazard. A concluding section urges industries to take all precautions necessary to ensure that workers are not exposed to both methyl ethyl ketone and solvents whose toxicity is potentiated by this chemical.


Methyl Isobutyl Ketone

Environmental Health Criteria, No. 117
1990, 79 pages [E, with summaries in F, S]
ISBN 92 4 157117 9
Sw.fr. 19.-/US $17.10; in developing countries: Sw.fr. 13.30
Order no. 1160117

Evaluates risks to human health and the environment posed by the widespread production and use of methyl isobutyl ketone as a solvent, with major applications in the production of lacquers and paint solvents, including car and industrial spray paints. Methyl isobutyl ketone also occurs naturally in food, is a permitted flavouring agent, and is used in food contact packaging materials.

Sections concerned with the behaviour of methyl isobutyl ketone in the environment note its rapid evaporation into the atmosphere, rapid photo-transformation, ready biodegradation, and low potential for bioaccumulation. A review of data on metabolic pathways and toxicity to organisms concludes that production and use of this chemical pose no threat to wildlife or the environment, except in the case of accidental spills or inappropriate disposal of wastes.

The most extensive section reviews findings from a large number of studies, conducted in experimental animals and in vitro test systems, designed to test the toxicity of this chemical, including its actions as a skin and respiratory tract irritant, its effects on reproduction, and its embryotoxicity, teratogenicity, carcinogenicity, and mutagenicity. A review of studies conducted in human volunteers and in occupationally-exposed workers concludes that exposure to methyl isobutyl ketone can cause eye and respiratory irritation as well as symptoms of headache, nausea, and vertigo. The review found no evidence that exposure to this chemical causes permanent damage to the nervous system of workers or that its presence in the environment and in food poses any threat to the general population.


Methylene Chloride
Second edition

Environmental Health Criteria, No. 164
1996, 242 pages [E, with summaries in F, S]
ISBN 92 4 157164 0
Sw.fr. 46.-/US $41.40; in developing countries: Sw.fr. 32.20
Order no. 1160164

Evaluates the risks to human health and the environment posed by exposure to methylene chloride. Due to its volatility, stability, and properties as a solvent, methylene chloride is widely used in aerosols, paint removers, the chemical and pharmaceutical industries, polyurethane foam manufacturing, and metal cleaning. Virtually all atmospheric release of this chemical result from its use as an end-product by various industries, combined with the use of paint removers and aerosol products at home. The general public is exposed to methylene chloride primarily through the use of consumer products, such as paint removers, which can result in relatively high indoor levels.

The most extensive sections evaluate the toxicity of methylene chloride in experimental animals and humans, giving particular attention to studies indicating carcinogenic potential in some species. Studies indicate that methylene chloride is rapidly absorbed through the lung and gastrointestinal tract, is distributed throughout the body, and rapidly excreted via the lungs. The main toxic effects in exposed humans are reversible central nervous system depression and carboxyhaemaglobin formation. Studies have also reported liver and renal dysfunctions, haematological effects, and neurophysiological and neurobehavioural disturbances. Although several studies have investigated the link between human exposure to methylene chloride and cardiovascular disease and cancer, the report cites several inadequacies in these studies and concludes that no firm link with either cardiovascular disease or cancer can be made.

Concerning risks to the environment, the report concludes that, with the exception of accidental spills, use of methylene chloride has no significant impact on the environment.


Methylmercury

Environmental Health Criteria, No. 101
1990, 144 pages [E]
ISBN 92 4 157101 2
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160101

Evaluates the risks to adult and fetal health posed by exposure to compounds of mono-methylmercury. In view of the irreversible neurological damage produced in severe cases of poisoning, the book makes a special effort to clarify the ways in which this highly mobile metal enters the food chain and to define the levels that constitute a risk to human health. Close to 400 recent investigations, including numerous clinical studies following outbreaks of poisoning, are critically assessed.

A section on sources of human exposure concentrates on environmental release from man-made sources. Noting that the general population is primarily exposed through the dietary intake of contaminated fish and fish products, the book gives particular attention to the mechanisms by which methylmercury enters the food chain and is metabolized and transported to tissues in the human body.

A review of studies in animals and in in vitro test systems, conducted since 1976, documents the consistent neurotoxicity and fetotoxicity of methylmercury. Chapters devoted to effects in humans draw upon what has been learned from poisoning outbreaks in Minamata, Japan and in Iraq as well as from studies of populations consuming high quantities of fish. An evaluation of effects on developing tissues draws upon the considerable amount of new data available on dose-response relationship, concluding that prenatal life is especially sensitive to methylmercury. The final chapter issues conclusions concerning levels of exposure and associated health risks in the general public, in populations consuming high quantities of fish, and in pregnant women.

"... should be on the bookshelves of all those who may need to know whether methylmercury is likely to be a health hazard in any particular circumstance..."
— Human and Experimental Toxicology


Methyl Methacrylate

Concise International Chemical Assessment Document, No. 4
1998, iv + 40 pages [E, with summaries in F, S]
ISBN 92 4 153004 9
Sw.fr. 16.-/US $14.40; in developing countries: Sw.fr. 11.20
Order no. 1380004

A concise assessment of the risks to human health posed by exposure to methyl methacrylate, a synthetic chemical used primarily in the production of cast acrylic sheet, acrylic emulsions, moulding and extrusion resins, and several consumer and medical products, including dental prostheses, surgical bone cements, and orthotic shoe inserts. The document is part of a new series of brief reports aimed at the characterization of hazards and dose-response for exposures to selected industrial chemicals. With this goal in mind, documents in the series focus on studies and findings considered critical for risk characterization.

Studies of environmental behaviour indicate that methyl methacrylate is emitted mainly to air, does not persist in the atmosphere, and is not expected to contribute to depletion of the ozone layer. Inhalation is identified as the principal route of human exposure. The general population may be exposed to methyl methacrylate through the use of paints, varnishes, lacquers and other consumer products.

In animal studies, methyl methacrylate shows low acute toxicity. The principal effect observed with low doses was irritation of the nasal cavity. Higher doses were associated with adverse effects on the kidney and liver. Well-designed studies indicate that the chemical has no adverse effects on development and is not carcinogenic. In humans, methyl methacrylate is a mild skin irritant and has the potential to induce skin sensitization in susceptible individuals. Although occupational asthma associated with exposure has been reported, evidence that methyl methacrylate is a respiratory sensitizer was judged inadequate. Evidence from epidemiological studies of carcinogenic risk in humans was considered inconclusive. On the basis of toxic effects observed in inhalation studies in animals, the report established a tolerable daily intake of 1.2 mg/kg body weight.


Mononitrophenols

Concise International Chemical Assessment Document, No. 20
2000, iv + 39 pages [E, with summaries in F, S]
ISBN 92 4 153020 0
Sw.fr. 16.–/US $14.40
In developing countries: Sw.fr. 11.20
Order no. 1380020

A concise assessment of the risks to human health and the environment posed by exposure to 2- and 4-nitrophenol. These isomers are used as intermediates in the synthesis of a number of organophosphorus pesticides and some medical products. Environmental releases are primarily to air, water, and soil, and result from diffuse sources, including vehicle traffic and hydrolytic and photolytic degradation of pesticides. Further releases into the hydrosphere and the geosphere are caused by the dry and wet deposition of airborne nitrophenols from the atmosphere.

Concerning behaviour within the environment, volatilization from water to air is expected to be slow or negligible. The report found no evidence that nitrophenols contribute directly to depletion of the stratospheric ozone layer or to global warming. Studies show that nitrophenols released to soil are biodegraded under aerobic conditions, with infiltration into groundwater occurring only under conditions unfavourable to biodegradation.

Limited studies of kinetics and metabolism suggest rapid metabolism and excretion. Concerning toxic effects in laboratory animals, the formation of methaemoglobin is the most critical end-point following exposure by inhalation and, presumably, via the oral route as well. Other toxic effects include decreases in body weight gain, differences in organ weights, focal fatty degeneration of the liver, and haematological changes. Adequate data on carcinogenicity and mutagenicity were not available.

Exposure of the general population to nitrophenol isomers occurs mainly through ambient air and drinking-water. Data on health effects in humans are confined to patch tests demonstrating skin sensitization in some subjects. In view of the extremely limited data, no conclusions concerning effects on human health could be reached.

Methyl Parathion

Environmental Health Criteria, No. 145
1993, 244 pages [E, with summaries in F, S]
ISBN 92 4 157145 4
Sw.fr. 45.-/US $40.50; in developing countries: Sw.fr. 31.50
Order no. 1160145

Evaluates the risks to human health and the environment posed by methyl parathion, a highly toxic organophosphorus ester insecticide. Introduced as a commercial chemical in 1949, methyl parathion is used as a contact insecticide and acaricide for the protection of cotton, soybeans, cereals, tobacco, peanuts, vegetables, citrus fruits, and other crops. The compound is applied as a foliar spray by aircraft or ground equipment.

Because methyl parathion is a non-selective pesticide that kills beneficial species as well as pests, a section devoted to effects on environmental organisms concentrates on several studies documenting high toxicity for honey bees. These studies also show that incidents of bee kills were more severe with this insecticide than with others, underscoring the need to time spraying operations with extreme care. The report concludes that methyl parathion should never be sprayed under windy conditions, and that overspraying of water bodies must be avoided.

The most extensive section evaluates studies of toxic effects observed in experimental animals and in vitro test systems. The report found no evidence of carcinogenicity associated with long-term exposure, and no evidence that this insecticide acts as a primary eye or skin irritant. The final section evaluates effects on humans, drawing on a number of case reports of accidental and sometimes fatal poisoning. The report concludes that the only confirmed effects on humans are the signs and symptoms characteristic of systemic poisoning by cholinesterase-inhibiting organophosphorus compounds. No cases of organophosphorus-induced, delayed peripheral neuropathy have been reported.

"... certainly the first book to consult to obtain an authoritative current review of hazards..."
- Environmental Management and Health


Morpholine

Environmental Health Criteria, No. 179
1996, 163 pages [E, with summaries in F, S]
ISBN 92 4 157179 9
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160179

Evaluates the risks to human health and the environment posed by the widespread industrial use of morpholine. Morpholine is an extremely versatile chemical with major uses as an intermediate in the rubber industry, as a corrosion inhibitor, as a solvent for numerous organic materials, and in the synthesis of optical brighteners, crop protection agents, dyes, and drugs. In some countries, the compound continues to be used in toiletry and cosmetic products and in several direct and indirect food additive applications. The ready conversion of morpholine into N-nitrosomorpholine (NMOR) - a proven animal carcinogen - is of particular concern. The report concludes that consumption of food contaminated with this compound is the main source of exposure for the general population.

The most extensive section, which assessed the results of experimental toxicity studies, concludes that morpholine is not highly toxic under conditions of acute exposure. While the review found no evidence of either mutagenicity or carcinogenicity, the importance of ready conversion to NMOR was underscored.

A review of the limited data on health effects in humans supports the conclusion that morpholine does not create any significant risks of systemic toxic effects as a result of occupational or environmental exposures. However, in view of the compound's conversion to NMOR, the report found it prudent to consider morpholine as increasing the carcinogenic risk in exposed populations. The report further concludes that contamination of food through food packaging and food processing should be avoided, and that morpholine should not be used in rubber products intended for direct contact with humans, or in toiletry or cosmetic preparations. The report also underscores the need for rigorous treatment of industrial effluents to avoid contamination of drinking-water.


Neurotoxicity Risk Assessment for Human Health: Principles and Approaches

Environmental Health Criteria, No. 223
2001, 223 pages
ISBN 92 4 157223 X
Swiss francs 48—
In developing countries: Sw.fr 33.60
Order no. 1160223

This publication summarizes the scientific knowledge base on which principles and methods involved in neurotoxicity risk assessment are based. It is aimed at providing a framework for public health officials, research and regulatory scientists, and risk managers on the use and interpretation of neurotoxicity data from human and animal studies, and it discusses emerging methodological approaches to studying neurotoxicity.

The introductory chapter examines definitions and critical concepts in neurotoxicity and looks at the criteria for quality of data used in risk assessment. This is followed by a detailed discussion of the structure and function of the nervous system, of the special susceptibilities of the human fetus, children and the elderly and of the types of effects on the nervous system.

Recent progress in developing validated methods for detecting neurotoxicity in humans is investigated, as is our understanding of the factors that affect the validity and reliability of human neurotoxicological studies. Sources of human data include accidental and occupational exposures, case-studies, clinical evaluations, epidemiological studies, and field and laboratory studies. Standardized neuropsychological tests, validated computer-assisted test batteries, neurophysiological and biochemical tests, and refined imaging techniques have been improved and become well established.

The most extensive section reviews data derived from experimental animal models. Batteries of functional tests have been developed, validated and used extensively in neurotoxicological studies. Many different types of behavioural tests have been used to assess chemical-induced changes in sensory, motor and cognitive function, whereas neurophysiological measures have been standardized to assess chemical-induced sensory and motor function.

The final chapter examines the steps involved in neurotoxicity risk assessment: hazard identification, dose-response assessment, exposure assessment and risk characterization. The application of risk assessment principles for neurotoxicants is similar to that of other non-cancer end-points, except that issues of reversibility, compensation and recovery of function in the nervous system require special consideration. This document provides guidance on neurotoxicity risk assessment at a broad international level.

Nickel

Environmental Health Criteria, No. 108
1991, 383 pages [E, with summaries in F, S]
ISBN 92 4 157108 X
Sw.fr. 60.-/US $54.00; in developing countries: Sw.fr. 42.00
Order no. 1160108

Evaluates close to 900 studies in an effort to determine the role of various nickel compounds as environmental hazards and causes of human diseases, including cancer. A special effort is made to determine the specific exposure levels for nickel and nickel compounds that pose a threat to the environment, the general public, and workers exposed to nickel-containing dusts and fumes.

A section on sources of exposure evaluates both natural and man-made releases into the environment, offering especially detailed information on emissions associated with the nickel industry, the combustion of fossil fuels, and the incineration of sewage sludge and waste. Exposure of the general population is noted to occur via inhaled air, ingestion of food and drinking-water, and dermal contact, particularly with jewellery and coins.

Because most health hazards associated with occupational exposure have resulted from inhalation, a section devoted to kinetics and metabolism concentrates on mechanisms of deposition, retention, and clearance of nickel from the human respiratory tract. The most extensive section reviews the large body of data from experimental studies of the effects of short- and long-term exposures on the respiratory tract, endocrine system, cardiovascular system, immune system, skin and eye. Tests for mutagenicity, embryotoxicity, teratogenicity, and carcinogenicity are also critically reviewed, with particular attention given to possible mechanisms of nickel carcinogenicity. The final section assesses effects on the human respiratory system, kidney, cardiovascular system, skin and eye. Evaluation of the potential for carcinogenicity draws upon increased rates of nasal and lung cancer reported in several epidemiological studies of exposed workers. These studies provide evidence that inhalation of nickel dust and some soluble and insoluble nickel salts carries a risk of carcinogenicity.


Nitrogen Oxides
Second edition

Environmental Health Criteria, No. 188
1997, xxiv + 550 pages [E, with summaries in F, S]
ISBN 92 4 157188 8
Sw.fr. 92.-/US $82.80; in developing countries: Sw.fr. 64.40
Order no. 1160188

Evaluates the risks to human health and the environment posed by exposure to nitrogen oxides. Combustion processes provide the major source of nitrogen oxides in both indoor and outdoor air. Fossil fuel power stations, motor vehicles, and domestic combustion appliances emit nitrogen oxides, mostly in the form of nitric oxide accompanied by some nitrogen dioxide. Once in indoor or outdoor air, chemical reactions oxidize nitric oxide into nitrogen dioxide and a suite of other nitrogenous species. The evaluation concentrates on nitrogen dioxide, which is the most extensively investigated nitrogenous species, the most toxic, and the one most suitable for risk assessment from a public health perspective.

In view of the complex behaviour of these compounds in the environment, the many factors that affect the conditions of human exposure, and the difficulty of correlating specific exposures with direct effects on health, the report gives particular attention to methodological problems that help resolve inconsistencies in reported results. The overriding aim is to establish reliable health-based guidance values for both peak daily concentrations and average annual exposures that are sufficient to protect public health and susceptible populations. Well over 1300 references to the literature are included in this cautious and carefully documented assessment.

The opening chapter reviews data on both ambient and indoor sources of nitrogenous compounds, their emissions, and the resulting concentrations that may directly affect human health. Also considered are indirect effects that arise from the participation of nitrogen-containing compounds in the production of photochemical smog, ozone generation in the troposphere, and ozone depletion in the stratosphere. The next chapter, concerned with the effects of atmospheric nitrogen compounds on plants, cites abundant evidence that increases in pollution with nitrogen compounds have had major adverse effects on rare plant species and have contributed to a loss of biodiversity.

The most extensive chapter evaluates the large body of evidence from animal studies designed to duplicate, as closely as possible, typical patterns of human exposure. Toxic effects consistently observed in several laboratory species support the conclusion that exposure to nitrogen dioxide causes adverse effects on lung metabolism and biochemistry, lung function and lung structure, and can result in dysfunction of respiratory tract host defences, causing increased susceptibility to infectious respiratory diseases. Animal studies also clearly demonstrate that chronic exposure can cause emphysema of the type seen in human lungs.

The evaluation of effects on human health first considers findings from several well-designed studies of controlled exposure conducted in young, healthy adult males, asthmatics and patients with chronic obstructive pulmonary disease, children, and the elderly. These findings support the conclusion that exposure to nitrogen dioxide causes decrements in lung function and results in increased airway responsiveness to bronchoconstrictive agents. Exposure of asthmatics causes, in some subjects, increased airway responsiveness to a variety of provocative mediators. An evaluation of the large number of epidemiological studies confirms that asthmatics are the population most susceptible to adverse effects on health. Children aged 5 to 12 years were identified as a subpopulation potentially susceptible to increased respiratory morbidity associated with exposure.

The report recommends a 1-hour average daily maximum nitrogen dioxide concentration of 200 micrograms/m3 (0.11 ppm) as a short-term guideline value. An annual guideline value of 40 micrograms/m3 (0.023 ppm) was also proposed, although a no-effect level for subchronic or chronic exposure to nitrogen dioxide concentrations has not yet been determined.


2-Nitropropane

Environmental Health Criteria, No. 138
1992, 108 pages [E, with summaries in F, S]
ISBN 92 4 157138 1
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160138

Evaluates the risks to human health and the environment posed by 2-nitropropane, an important industrial chemical used as a solvent for printing inks, paints, varnishes, adhesives, and other coatings, such as beverage container linings. 2-Nitropropane is also used in printing inks for flexible food packaging and in food processing, primarily for the separation of oleic acid from polyunsaturated fatty acids. Though smokers are regularly exposed to low concentrations, exposure of the general population from other sources is very low.

The most extensive section evaluates data from laboratory studies of toxicity. Studies show moderate acute toxicity for mammals, with considerable variation in the sensitivity of different laboratory animals. Studies conducted in the rat provide clear evidence of destructive changes in the liver, including hepatocellular carcinoma. The report found no conclusive evidence that 2-nitropropane causes cancer in other laboratory species.

Concerning effects on humans, the report notes that exposure to high concentrations, which are acutely toxic, is largely or entirely confined to the occupational setting. An evaluation of toxic effects draws upon seven reports of industrial fatalities attributed to inhalation of 2-nitropropane fumes, with death due to acute hepatic failure in all cases. Although more research on long-term effects is needed, the report notes that available data provide no indication that chronic occupational exposure at concentrations usually encountered in the workplace induces hepatic or other neoplasms, or other long-term effects. Because 2-nitro-propane is a potent carcinogen in rats, the report recommends that occupational exposure to this solvent, and its presence in consumer products, be minimized and replaced with a less toxic solvent whenever practical. The report recommends against the use of 2-nitropropane in food processing.


Occupational Exposures in Insecticide Application, and Some Pesticides

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 53
1991, 612 pages [E]
ISBN 92 832 1253 3
Sw.fr. 105.-/US $94.50; in developing countries: Sw.fr. 73.50
Order no. 1720053

Evaluates the carcinogenic risk to humans posed by occupational exposure during the spraying and application of insecticides. The book also features separate monographs evaluating the carcinogenicity of 17 individual pesticides, including several that have been banned by industrialized countries yet are still used in the developing world. Although some of these pesticides have been in use for more than four decades, evaluations of carcinogenicity were hindered by the sparsity of well-designed epidemiological studies.

The first and most extensive monograph evaluates data from descriptive and ecological studies, cohort studies, and case-control studies suggesting an increased risk of cancer, most notably lung cancer, multiple myeloma and other tumours of B-cell origin, in workers exposed to insecticides during their application. On the basis of this evaluation, the book concludes that the spraying and application of nonarsenical insecticides entail exposures that are probably carcinogenic to humans.

The remaining monographs evaluate the carcinogenicity of aldicarb, atrazine, captafol, chlordane, DDT, deltamethrin, dichlorvos, fenvalerate, heptachlor, monuron, pentachlorophenol, permethrin, picloram, simazine, thiram, trifluralin, and zitram.

Of these, captafol, a fungicide used on plants, for seed treatment, and as a wood preservative, was classified as probably carcinogenic to humans. Atrazine, chlordane, DDT, dichlorvos, heptachlor, and pentachlorophenol were classified as possibly carcinogenic to humans. The remaining pesticides could not be classified on the basis of available data.


Occupational Exposures of Hairdressers and Barbers and Personal Use of Hair Colourants; Some Hair Dyes, Cosmetic Colourants, Industrial Dyestuffs and Aromatic Amines

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 57
1993, 427 pages [E]
ISBN 92 832 1257 6
Sw.fr. 75.-/US $67.50; in developing countries: Sw.fr. 52.50
Order no. 1720057

A detailed assessment of the carcinogenic risk to humans posed by the professional and personal use of hair colourants. An additional 17 monographs evaluate the carcinogenicity of eight hair dyes, one cosmetic colourant, four industrial dyestuffs, and four aromatic amines, three of which are used in dyestuff manufacture.

The first and most extensive monograph considers the carcinogenic risk posed by occupational exposures of hairdressers and barbers and personal exposure to hair colourants. Citing consistent evidence from five large European cohort studies of excess risk for cancer of the urinary bladder in male hairdressers and barbers, the monograph concludes that occupation as a hairdresser or barber entails exposures that are probably carcinogenic. The carcinogenic risk linked to the personal use of hair colourants could not be determined.

Of the eight hair dyes considered, only one, HC Blue No. 1, could be classified as possibly carcinogenic to humans. The cosmetic colourant, D&C Red No. 9 (CI Pigment Red 53:1), could not be classified. Of the four industrial dyestuffs, CI Direct Blue 15, CI Acid Red 114, and magenta containing CI Basic Red 9 were classified as possibly carcinogenic to humans. The manufacture of magenta was classified as entailing exposures that are carcinogenic.

Of the four aromatic amines, 4,4'-methylene bis(2-chloroaniline) (MOCA) was classified as probably carcinogenic to humans. para-Chloroaniline and 2,6-dimethylaniline were classified as possibly carcinogenic; N,N-dimethyl-aniline could not be classified.


Occupational Exposures to Mists and Vapours from Strong Inorganic Acids; and Other Industrial Chemicals

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 54
1992, 336 pages [E]
ISBN 92 832 1254 1
Sw.fr. 72.-/US $64.80; in developing countries: Sw.fr. 50.40
Order no. 1720054

Evaluates the carcinogenic risk to humans posed by occupational exposure to mists and vapours from strong inorganic acids and by other industrial chemicals. The volume features six monographs covering occupational exposures to mists and vapours from sulfuric acid and other strong inorganic acids; sulfur dioxide and some sulfites, bisulfites, and metabisulfites; hydrochloric acid; diethyl sulfate; diisopropyl sulfate, and 1,3-butadiene.

In the first and most extensive monograph, evaluations draw upon numerous studies of occupational exposures in industries where the use of strong inorganic acids is particularly heavy. These include the manufacture of isopropanol, synthetic ethanol, phosphate fertilizers, lead batteries, soap and detergents, sulfuric acid, and nitric acid, and industries involving pickling and other acid treatment of metals. Studies of occupational exposure have demonstrated an excess of nasal sinus cancer, laryngeal cancer, and lung cancer. In all studies considered, sulfuric acid mists were the most common exposure. On the basis of these data, the monograph concludes that occupational exposure to strong-inorganic-acid mists containing sulfuric acid is carcinogenic to humans.

Concerning the other industrial chemicals evaluated in this volume, 1,3-butadiene and diethyl sulfate were classified as probably carcinogenic to humans. Diisopropyl sulfate was classified as possibly carcinogenic to humans. Sulfur dioxide, sulfites, bisulfites, metabisulfites, and hydrochloric acid could not be classified on the basis of currently available data.


Partially Halogenated Chlorofluorocarbons (Ethane Derivatives)

Environmental Health Criteria, No. 139
1992, 130 pages [E, with summaries in F, S]
ISBN 92 4 157139 X
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160139

Evaluates the environmental behaviour, toxicity, and ozone-depleting and global-warming potentials of six partially halogenated ethane derivatives selected as candidates to replace the fifteen fully halogenated chlorofluorocarbons that are being phased out in line with the provisions of the Montreal Protocol on Substances that Deplete the Ozone Layer. The compounds considered are 1,1-dichloro-1-fluoroethane (HCFC 141b), 1-chloro1,1-difluoroethane (HCFC 142b), 1,2-dichloro-1,1-difluoroethane (HCFC 132b), 1-chloro-2,2,2-trifluoroethane (HCFC 133a), 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123), and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124).

All compounds were judged to have ozone-depleting and global-warming potentials considerably lower than those of CFC 11, the fully halogenated chlorofluorocarbon with the highest ozone-depleting and global-warming potential. Estimated atmospheric lifetimes range from 1.6 years for HCFC 123 to 19.1 years for HCFC 142b.

Because studies of HCFC 132b and HCFC 133a have documented a number of toxic effects, these compounds could not be recommended as substitutes. Since the toxicity of HCFC 142b is low and the ozone-depleting and global-warming potentials are lower than those of the fully halogenated chlorofluorocarbons, the report concludes that HCFC 142b can be considered as a transient substitute for the chlorofluorocarbons included in the Montreal Protocol. In view of the paucity of toxicological data on HCFC 141b, HCFC 123, and HCFC 125, no evaluation of their potential effects on human health could be made.


Partially Halogenated Chlorofluorocarbons (Methane Derivatives)

Environmental Health Criteria, No. 126
1991, 97 pages [E, with summaries in F, S; R]
ISBN 92 4 157126 8
Sw.fr. 21.-/US $18.90; in developing countries: Sw.fr. 14.70
Order no. 1160126

Evaluates the risks to human health and the environment posed by two partially halogenated chlorofluorocarbons: dichlorofluoromethane (HCFC 21) and chlorodifluoromethane (HCFC 22). These two methane derivatives were selected for evaluation because of their potential use as substitutes for those fully halogenated chlorofluorocarbons that are being phased out as a result of the 1987 Montreal Protocol on Substances that Deplete the Ozone Layer. The evaluation is intended to assist industry in its urgent search for acceptable substitute chemicals, most notably for use as refrigerants, as propellants in aerosols, and as blowing agents for the production of polystyrene. While data on human toxicity are thoroughly reviewed, the greatest challenge is to find the most accurate models for predicting levels of release to the environment and estimating the potential of these chemicals to deplete the ozone layer.

Because HCFC 21 is no longer produced for any commercial purposes, most data assessed come from studies of HCFC 22. Current environmental levels of both chemicals are judged to be extremely low and highly unlikely to cause direct effects on human health. A review of models for estimating atmospheric residence times and routes of transport to the stratosphere concludes that the ozone-depleting potential of both chemicals is considerably lower than that of the fully halogenated chlorofluorocarbons. While HCFC 21 has the advantage of a much shorter tropospheric lifetime, studies have linked exposure to liver damage. Concerning the toxicity of HCFC 22, evidence from the vast majority of studies is reassuring. The report concludes that HCFC 22 is an acceptable transient substitute for the chlorofluorocarbons included in the Montreal Protocol. HCFC 21 could not be recommended due to its potential toxic effects on the liver.


Permethrin

Environmental Health Criteria, No. 94
1990, 125 pages [E, R]
ISBN 92 4 154294 2
Sw.fr. 24.-/US $21.60; in developing countries: Sw.fr. 16.80
Order no. 1160094

Evaluates the design and findings of over 250 studies concerned with the effects on human health and the environment posed by permethrin, a photostable synthetic pyrethroid insecticide marketed since 1977. Because of its strong repellent properties and effectiveness as a stomach and contact insecticide, perme-thrin is widely used in the protection of several agricultural crops, in the control of insects in households and on cattle, in aerial application for forest pest control, as a fog in mushroom houses, and as a wood preservative. Public health applications include the disinsection of aircraft, treatment of mosquito nets, and human lice control.

In view of the uses of permethrin and its photostable properties, a section devoted to sources of human exposure concentrates on the large number of studies investigating residues in fruits, vegetables, dairy milk, and grains. Findings from laboratory studies, indicating that permethrin is highly toxic to certain beneficial insects and natural enemies of pests, are contrasted with field investigations demonstrating the transitory nature of most toxic and repellent effects on non-target species.

The most extensive section reviews the findings of experimental studies conducted to assess toxicity. Particular attention is given to differences in study design, dose, and mode of administration that can affect the validity of findings when extrapolated to humans. The final section draws upon a limited number of occupational and clinical studies to evaluate direct evidence of adverse effects on health.

On the basis of this review, the book concludes that most toxic effects are transitory, that the likelihood of carcinogenic effects in humans is extremely low or non-existent, and that permethrin, when used as recommended, is not likely to present a hazard to the general public, exposed workers, or the environment.


Peroxisome Proliferation and Its Role in Carcinogenesis
Views and Expert Opinions of an IARC Working Group

IARC Technical Report, No. 24
IARC 1995, v + 85 pages [E]
ISBN 92 832 1439 0
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1770024

A state-of-the-art consensus report on what is known about peroxisome proliferation, the mechanisms involved, and their relevance to carcinogenesis. Peroxisomes are single, membrane-limited, cytoplasmic organelles that are found in cells of animals, plants, fungi, and protozoa. Peroxisome proliferators include certain hypolipidaemic drugs, phthalate ester plasticizers, industrial solvents, herbicides, food flavours, leukotriene D4 antagonists, and hormones. Numerous studies in rats and mice have demonstrated the hepatocarcinogenic effects of peroxisome proliferators, and these compounds have been unequivocally established as carcinogens. Since humans are exposed to peroxisome proliferators to a significant extent, assessment of the adverse biological effects of this group of compounds, and particularly their potential carcinogenicity, has become an important issue.

The report has two parts. The first records the consensus reached by a group of eleven experts, including several of the leading investigators in this field. Questions addressed include the mechanisms by which peroxisome proliferators exert their carcinogenic effects in rodents, the relevance of animal studies to the evaluation of carcinogenic risk in humans, and the potential use of peroxisome proliferation as a biological marker for liver cancer. The report concludes that compounds inducing peroxisome proliferation in rats and mice have little, if any, effect on human liver. The report also issues advice on the interpretation of peroxisome proliferation, demonstrated in animal studies, when evaluating the carcinogenic risk to humans. The second part consists of three background papers presented by members of the working group.


Pharmaceutical Drugs

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 50
IARC 1990, 415 pages [E]
ISBN 92 832 1250 9
Sw.fr. 83.-/US $74.70; in developing countries: Sw.fr. 58.10
Order no. 1720050

Reports the deliberations of a working group convened to evaluate the carcinogenic risk to humans posed by the therapeutic use of 15 pharmaceutical drugs. The volume features separate monographs on five antineoplastic agents, four antimicrobial agents, two diuretics, ciclosporin (an immunosuppressant), cimetidine (used in the treatment of gastric and duodenal ulcers), paracetamol (a popular analgesic and antipyretic drug), and dantron (a laxative). Drugs were selected for inclusion on the basis of published data suggesting carcinogenic effects in experimental animals or in human patients treated with the drug.

The working group identified two of the drugs - ciclosporin and thiotepa - as human carcinogens. Ciclosporin, an immunosuppressant, is widely used in the prevention and treatment of graft-versus-host reactions in bone-marrow transplantation and to prevent the rejection of kidney, heart, and liver transplants. Often given to transplant recipients for several months, ciclosporin has been linked to a remarkably high occurrence of lymphomas, found predominantly in the gastrointestinal tract, as well as to skin cancer and Kaposi's sarcoma. The carcinogenicity of thiotepa, a cytostatic agent used in the treatment of malignant lymphomas and solid tumours, has been clearly demonstrated in both experimental animals and human patients, where treatment with the drug has been linked to the development of leukaemia.

Azacitidine, chloramphenicol, and chlorozotocin were judged to be probably carcinogenic to humans, while dantron and trichlormethine were identified as possible human carcinogens. The remaining substances could not be classified on the basis of currently available evidence. The experts also noted that long-term experiments with paracetamol, nitrofurantoin, and nitrofural have shown reductions in tumour incidence at some sites in some animal species.


Phenol

Environmental Health Criteria, No. 161
1994, 151 pages [E, with summaries in F, S]
ISBN 92 4 157161 6
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1160161

Evaluates risks to human health and the environment posed by exposure to phenol, a constituent of coal tar formed during the natural decomposition of organic materials. Phenol is the basic feedstock from which a number of commercially important materials are made, including resins, bisphenol A, caprolactam, alkyl phenols, and chlorophenols. The most important environmental emissions result from the use of phenolic resins. The presence of phenol in liquid manure, and its formation following the atmospheric degradation of benzene, may contribute significantly to atmospheric levels.

The most extensive section summarizes toxicity data from studies in laboratory animals and in vitro test systems, including special studies of neurotoxicity, myelotoxicity, immunotoxicology, and biochemical effects. Neurotoxicity, liver and kidney damage, respiratory effects, and growth retardation were identified as the main effects of short-term exposure. An evaluation of effects on human health draws upon case reports following accidental or intentional ingestion, outbreaks of poisoning following the accidental contamination of drinking-water, and studies in occupationally exposed workers. While available data do not suggest a strong potential for cumulative health effects following chronic exposure, the report concludes that accidental high exposure can cause a number of local and systemic effects. Evidence of genotoxicity, and inadequate studies of carcinogenic potential, remain areas of concern.

Concerning risks to the environment, the report cites evidence of toxicity to freshwater and marine organisms. While phenol is judged unlikely to persist or bioaccumulate in the environment, the report warns that aquatic organisms may be at risk in any surface or sea water contaminated with this compound.


d-Phenothrin

Environmental Health Criteria, No. 96
1990, 64 pages [E, R]
ISBN 92 4 154296 9
Sw.fr. 16.-/US $14.40; in developing countries: Sw.fr. 11.20
Order no. 1160096

Evaluates the risks to human health and the environment posed by d-phenothrin, a synthetic pyrethroid insecticide used primarily for the household control of head lice and other insects and for the treatment of stored grain.

The opening sections review available data on worldwide industrial production and use and summarize studies conducted to assess residues in stored grain. A section devoted to the behaviour of d-phenothrin in the environment concentrates on investigations of photodegradation and transport, concluding that photodegradation under outdoor conditions is rapid, but that d-phenothrin remains virtually intact for up to 12 months on grains stored in the dark.

The most extensive section evaluates toxicological data from studies in experimental animals and in vitro test systems. The evaluation confirms a low toxicity for d-phenothrin and an absence of mutagenic, teratogenic, embryotoxic, oncogenic, and neurotoxic effects. Concerning effects on human health, the book notes that d-phenothrin has not, during more than a decade of use, been reported to have caused human poisoning or other toxic effects. The book concludes that d-phenothrin, when used as recommended, is not likely to pose a hazard to either human health or the environment.


Phosgene

Environmental Health Criteria, No. 193
1997, xvii + 70 pages [E, with summaries in F, S]
ISBN 92 4 157193 4
Sw.fr. 21.-/US $18.90; in developing countries: Sw.fr. 14.70
Order no. 1160193

Evaluates the risks to human health and the environment posed by exposure to phosgene. Initially important as an agent of chemical warfare, this extremely reactive gas is now widely used as a chemical intermediate, most often at the point of production. The principal use is in the production of aromatic diisocyanates, such as methylene diphenyl diisocyanate and toluene diisocyanate, which are used to produce polyurethane foams and other polymers.

The report notes that most emissions are to the air and arise from the thermal degradation of chlorinated solvents and chlorinated polymers. Knowledge about the chemical properties of phosgene supports the conclusion that this chemical is unlikely to be detected in soil, vegetation, or food. Concerning sources of human exposure, the report concludes that inhalation is the principal route of exposure, that the general population is exposed to extremely low levels, and that occupational exposures, though generally very low, vary greatly depending on industrial hygiene practices.

The most extensive section evaluates findings from experimental studies. The lung is identified as the primary target organ in all species studied, with pulmonary oedema consistently reported as the primary cause of death following acute poisoning. Available data were judged inadequate for the assessment of carcinogenicity, neurotoxicity, and potential adverse effects on reproduction and development.

The review of effects on human health considers the consequences of high-level, short-term exposure to phosgene from reports of industrial accidents involving both individual workers and large numbers of the general population. These studies, in line with the animal data, confirm that the respiratory system is the primary target organ and that pulmonary oedema is the main cause of death following acute severe exposure. Studies show that survivors receiving proper medical support can recover completely.

On the basis of these evaluations, the report concludes that the extremely low levels of phosgene detected in air do not threaten the health of the general population. The report likewise found no evidence of adverse effects on the health of workers in closed-system facilities employing good industrial hygiene. However, firemen, welders, and other occupational groups working with chlorinated solvents or exposed to chlorinated hydrocarbon polymers in contact with flames were noted to risk exposure to levels of phosgene known to cause adverse effects on human health.


Platinum

Environmental Health Criteria, No. 125
1991, 167 pages [E, with summaries in F, S]
ISBN 92 4 157125 X
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160125

Evaluates the risks to human health and the environment posed by the mining, refining, industrial use, and recycling of platinum and selected platinum compounds. Because of its exceptional catalytic properties, resistance to chemical corrosion, and high mechanical strength, platinum is widely used in the chemical and petroleum industries, most notably in the production of catalysts, including devices for reducing hazardous gas emissions. The growing use of catalytic converters to reduce pollution from automobile exhausts has caused a sharp increase in the world demand for this metal. Compounds such as cisplatin also have important therapeutic applications.

The book opens with a review of the many sensitive techniques that can be used to detect and measure platinum in biological and environmental samples. A review of data on sources of human and environmental exposure concludes that all significant human exposures are occupational, with the greatest potential health hazards posed by certain halogenated soluble salts that may be inhaled as dusts or come into contact with skin during the later stages of refining or during the manufacturing of catalysts. The reclamation of platinum from scrap and used equipment may also entail hazardous exposures.

Concern about environmental contamination centres on the possible release of platinum in the exhausts of automobiles equipped with catalytic converters. A review of several well-designed studies of automobile exhausts and roadside dusts supports the conclusion that such emissions are unlikely to damage the environment or threaten the health of the general population. Concerning risks to human health, the book cites platinum salt hypersensitivity as the major health hazard for workers, noting that symptoms of hypersensitivity may persist for a lifetime and that allergic reactions can be provoked by very small quantities.


Polybrominated Biphenyls

Environmental Health Criteria, No. 152
1994, 577 pages [E, with summaries in F, S]
ISBN 92 4 157152 7
Sw.fr. 103.-/US $92.70; in developing countries: Sw.fr. 72.10
Order no. 1160152

Evaluates the risks to human health and the environment posed by exposure to polybrominated biphenyls (PBBs). These chemicals were introduced as flame retardants in the early 1970s and used in the manufacture of small appliances and in automotive applications, coatings, lacquers, and polyurethane foam.

Research on these chemicals has been especially intense following a 1973 poisoning disaster, in Michigan, USA, caused when the flame retardant FireMaster� was inadvertently confused with magnesium oxide-based cattle feed supplement. The flame retardant was added to animal feed and widely distributed to farms within the state. The ensuing contamination of farm animals resulted in the destruction of tens of thousands of cattle, pigs, and sheep, and more than a million chickens. Since the cause of contamination remained undetected for almost a year, thousands of farmers and other consumers were exposed to PBBs through the consumption of contaminated meat, eggs, and dairy products.

Although production of PBBs has been halted or severely restricted in many parts of the world, these chemicals remain of enduring concern due to their extreme persistence in the environment, their concentration in the food chain, their marked tendency to bioaccumulate in living organisms, including humans, and the potential for adverse health effects following long-term exposure to very low levels. Close to 600 studies were critically assessed in an effort to reach definitive conclusions concerning the risks posed by these highly persistent chemicals.

Citing overwhelming evidence from several sources, the report concludes that humans and the environment should not be exposed to PBBs and that commercial use of these compounds should cease.


Polychlorinated Biphenyls and Terphenyls
Second edition

Environmental Health Criteria, No. 140
1993, 682 pages [E, with summaries in F, S]
ISBN 92 4 157140 3
Sw.fr. 110.-/US $99.00; in developing countries: Sw.fr. 77.-
Order no. 1160140

Evaluates the vast body of evidence demonstrating the serious threat to human and environmental health posed by polychlorinated biphenyls (PCBs). These chemicals, which are now ubiquitous in the environment, have been used commercially since 1930 as dielectric and heat-exchange fluids and in a variety of other applications. Over 1,300 studies were critically assessed. The book also contains a brief review of the limited data on polychlorinated terphenyls.

A section on the environment assesses the mechanisms by which these highly persistent chemicals, previously introduced into the environment, are gradually being redistributed towards increased contamination of the marine environment. For the general population, the most important sources of exposure are food items and, for babies, breast-milk. The well-documented signs of poisoning in occupationally-exposed workers are also reviewed. A section on metabolic fate cites evidence of accumulation in the liver and the adipose tissues of various organs, placental transport, fetal accumulation, and distribution to milk.

The most extensive section, which runs some 100 pages, evaluates findings from studies of toxicity in experimental animals and in vitro systems. Findings suggest that PCBs are immunosuppressive and act as tumour promoters. An assessment of effects on humans draws upon studies of two large outbreaks of poisoning from contaminated food, and of occupational exposures. The report cites reproductive failure in sea mammals as the most important environmental hazard, further concluding that the predicted redistribution of residues towards the marine environment will pose an increasing hazard for sea mammals in the future. A review of the hazards of polychlorinated terphenyls concludes the report.


Polychlorinated Dibenzo-para-dioxins and Dibenzofurans

Environmental Health Criteria, No. 88
1989, 409 pages [E, R]
ISBN 92 4 154288 8
Sw.fr. 63.-/US $56.70; in developing countries: Sw.fr. 44.10
Order no. 1160088

Evaluates the risks to human health and the environment posed by exposure to polychlorinated dibenzo-para-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). These compounds, which are not produced intentionally, are formed as an undesired side reaction during the manufacture of chemical products used extensively as insecticides, herbicides, antiseptics, disinfectants, and wood preservatives.

The main part of the book evaluates data linking these compounds, and especially the PCDD 2,3,7,8-tetrachloro-dibenzo-p-dioxin, to adverse effects on health. The assessment also draws upon studies following industrial accidents, mass outbreaks of poisoning caused by consumption of contaminated rice oil in Japan and Taiwan, and the widespread use of contaminated Agent Orange in Viet Nam. Despite the number of clinical and follow-up studies, and despite the high incidence of hepatocellular carcinoma observed in some animal species, the report concludes that, for occupational and accidental exposures, no clear-cut persistent effects other than chloracne have been observed.

"... excellent ...essential reading for all scientists working on these hazardous man-made chemicals..."
— Food Australia

"... of significant interest to environmental toxicologists..."
— Human and Experimental Toxicology


Polychlorinated Dibenzo-para-Dioxins and Polychlorinated Dibenzofurans

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 69
1997, ix + 666 pages [E]
ISBN 92 832 1269 X
Sw.fr. 80.-/US $72.00; in developing countries: Sw.fr. 56.-
Order no. 1720069

Evaluates the carcinogenic risks to humans posed by exposure to polychlorinated dibenzo-para-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). PCDDs are formed as inadvertent by-products, sometimes in combination with PCDFs, during the production of chlorophenols and chlorophenoxy herbicides, and have been detected as contaminants in these products. PCDDs and PCDFs may also be produced in thermal processes such as incineration and metal-processing and in the bleaching of paper pulp with free chlorine. Of the PCDDs, 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3,7,8-TCDD), or "dioxin", has attracted the greatest concern.

PCDDs and PCDFs are ubiquitous in soil, sediment, and air, persist in the environment, and accumulate in animal fat. Excluding occupational and accidental exposures, most human exposure to these compounds occurs from the consumption of meat, milk, eggs, fish, and related products. Occupational exposures at higher levels have occurred since the 1940s as a result of the production and use of chlorophenols and chlorophenoxy herbicides and, for PCDFs, in metal production and recycling. Even higher exposures have occurred in sporadic industrial accidents and following incidents of rice oil contamination.

The evaluation, which considered abundant human and animal carcinogenicity data, found strong evidence from epidemiological studies in humans that exposure to 2,3,7,8-TCDD produces increased risks for all cancer combined, rather than for any specific site, suggesting that 2,3,7,8-TCDD is an unprecedented multi-site carcinogen with no single site predominating. Citing data from animal studies and other lines of evidence, the monograph concludes that 2,3,7,8-TCDD is carcinogenic to humans. Other polychlorinated dibenzo-para-dioxins and dibenzo-para-dioxin could not be classified as to their carcinogenicity to humans.

For PCDFs, the evaluation considered evidence from two large poisoning incidents involving rice oil contamination in Japan and Taiwan. Although excessive mortality from liver cancer was observed in long-term follow-up of the Japanese cases, the report cited other factors, including a high prevalence of chronic hepatitis B infection in the geographical area concerned, as possible explanations. Evidence of carcinogenicity to human was judged inadequate. In the absence of convincing data from experimental animals, PCDFs could not be classified as to their carcinogenicity to humans.


Principles and Methods for Assessing Direct Immunotoxicity Associated with Exposure to Chemicals

Environmental Health Criteria, No. 180
1996, xviii + 390 pages [E, with summaries in F, S]
ISBN 92 4 157180 2 |
Sw.fr. 72.-/US $64.80; in developing countries: Sw.fr. 50.40
Order no. 1160180

A comprehensive guide to general strategies and specific methods for testing the immunotoxicity of chemicals in animal models and humans. Addressed to those seeking a basic introduction to the field as well as specialist researchers, the book takes its focus from growing concern, in scientific and public communities, about the capacity of environmental agents to disrupt normal immune functions and thus increase susceptibility to tumours and infectious diseases. Compounds known to adversely affect the immune system are numerous and include drugs, pesticides, solvents, halogenated and aromatic hydrocarbons, and metals.

The book draws on considerable recent progress in understanding the immunological consequences of chemical insults as well as increasingly sophisticated methodologies for assessing such effects. Close to 1000 references are included in this authoritative guide.

The book opens with a detailed basic introduction to immunotoxicology. An extensive explanation of the function, histophysiology, and pathophysiology of the immune system emphasizes features that can aid the understanding and interpretation of the pathological changes caused by immunotoxic insults. Chapter two, on the health impact of selected immunotoxic agents, gives illustrative examples for some 30 chemicals that have been shown to exert immunotoxic effects in laboratory animals, and for an additional seven groups of chemicals known to disturb immune functions in humans. For each, brief discussions illustrate the chemical's distinct immunosuppressive properties and the mechanisms by which it exerts its toxic effects on the immune system. Chapter three provides detailed descriptions of a number of tests used in a tiered approach to the assessment of immunotoxicity.

Against this background, specific nonfunctional and functional tests for the assessment of immunotoxicology in experimental animals are presented and explained in full detail. Information on individual tests includes an explanation of why the test is important, the types of data it can yield, and exactly how it should be performed. Also included are sections offering advice on assessments in non-rodent species, in vitro approaches, and approaches using biomarkers in epidemiological studies and monitoring. The chapter concludes with a discussion of good laboratory practices for immunotoxicology studies and procedures for the validation of tests.

Chapter five explains the much more complicated procedures needed to assess immunotoxicity in humans. An explanation of general questions to be considered when designing epidemiological studies is followed by presentation of three recommended testing schemes, proposed by WHO and other agencies, for preliminary evaluation of individuals exposed to immunotoxicants. Specific assays for assessing immune status are also described. The final chapter outlines a step-by-step process of risk assessment specific to the evaluation of potentially immunotoxic chemicals.


Principles and Methods for the Assessment of Nephrotoxicity Associated with Exposure to Chemicals

Environmental Health Criteria, No. 119
1991, 266 pages [E, with summaries in F, S; R]
ISBN 92 4 157119 5
Sw.fr. 46.-/US $41.40; in developing countries: Sw.fr. 32.20
Order no. 1160119

Establishes detailed guiding principles for the planning of studies designed to investigate the nephrotoxic effects of exposure to chemicals, whether medicinal, industrial, or environmental. Close to 800 recent reports are cited in order to provide state-of-the-art advice on the design of studies, the interpretation of results, and the extrapolation of data from animals to man. As early renal injury is often masked by the kidney's considerable functional reserve and capacity for repair, the book places special emphasis on the need for improved screening tools and markers that can aid the timely diagnosis of chemically induced renal dysfunction. The book also cites evidence that exposure to chemicals may have a much greater influence on the incidence of nephropathy and chronic renal failure than previously suspected.

The book opens with a thorough discussion of the many factors that must be considered when investigating nephrotoxicity due to chemicals. The second chapter discusses the special features of kidney structure and function, including the mechanisms by which xenobiotic molecules are metabolized, that can affect the interpretation of toxicological data. Other chapters summarize current knowledge on the molecular basis of renal injury, identify specific therapeutic agents and chemicals that can induce nephrotoxicity, and outline the multiplicity of questions that must be asked in order to identify nephrotoxic chemicals and understand their potencies, sites, and mechanisms of toxicity. The concluding chapter evaluates the predictive value and diagnostic validity of new biochemical and immunochemical markers of early renal changes in humans.


Principles for Evaluating Chemical Effects on the Aged Population

Environmental Health Criteria, No. 144
1993, 159 pages [E, with summaries in F, S; R]
ISBN 92 4 157144 6
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1160144

A detailed review of research findings and methodological concepts that can guide efforts to characterize the susceptibility of the aged population to the harmful effects of environmental chemicals. Noting that few, if any, of the hundreds of thousands of environmental chemicals have been tested for increased toxicity in the elderly, the book uses knowledge from the fields of gerontology and toxicology to propose methodological principles for investigating the elderly as a population at special risk. Particular attention is given to methods for determining chronic effects, including cancer, linked to the long-term exposures that may characterize this age group.

The book has four main chapters. The first introduces and discusses the many complex factors that complicate efforts to link chemical exposure to adverse effects on the health of the elderly. Chapter two provides a detailed review of age-related changes at the genetic, molecular and cellular level, and in individual tissues, organs and systems. Emphasis is placed on age-related changes in structure which might alter functional responses to environmental insults, including chemicals. The third chapter explores age-related changes in chemical sensitivity as reflected in altered pharmacokinetics and changes in the pharmacodynamics of the central nervous system, endocrine system, kidney, immune system, and other systems and tissues. Theories for explaining the interactions of chemicals and diseases in the aging organism are also reviewed, together with the influence of modifying factors, such as nutrition, alcohol intake, and smoking. The fourth chapter describes the special methodological requirements of studies in the aged population. Guidelines cover experimental, epidemiological, and clinical approaches, and the development of biomarkers of aging.


Printing Processes and Printing Inks, Carbon Black and Some Nitro Compounds

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 65
IARC 1996, v + 578 pages [E]
ISBN 92 832 1265 7
Sw.fr. 90.-/US $81.00; in developing countries: Sw.fr. 63.-
Order no. 1720065

Evaluates the carcinogenic risks to humans posed by exposures in printing processes and to printing inks, to carbon black, and to selected nitro compounds, many of which are used in the production of dye and colourant intermediates. The first monograph evaluate occupational exposures in printing processes and to printing inks. Exposures in the printing industry are assessed according to their occurrence in printing ink manufacture and in printing operations such as letterpress, lithography, flexography, gravure, and screen printing. Although many epidemiological studies have demonstrated some evidence of cancer risk in printing trades and printing industries, the assessment found several important problems in the design of these studies. Occupational exposures in printing processes were classified as possibly carcinogenic to humans. Printing inks could not be classified.

The second monograph evaluates the carcinogenicity of carbon black, an intense black pigment mainly used in tyres and other rubber automotive products, and in many other rubber products. Although the evaluation found sufficient evidence in experimental animals that exposure to carbon black causes lung tumours, data on carcinogenicity to humans were judged inadequate. Carbon black was classified as possibly carcinogenic to humans.

The remaining monographs evaluate selected nitro compounds. Of these, 3,7- and 3,9-dinitrofluoranthenes, 2,4- and 2,6-dinitro-toluenes, 2-nitroanisole, nitrobenzene, and tetranitromethane were evaluated as possibly carcinogenic to humans. Chloronitrobenzenes, 3,5-dinitrotoluene, nitrotoluenes, 2,4,6-trinitrotoluene, and musk xylene and musk ambrette could not be classified.


Propachlor

Environmental Health Criteria, No. 147
1993, 110 pages [E, with summaries in F, S]
ISBN 92 4 157147 0
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160147

Evaluates the risks to human health and the environment posed by propachlor, a pre-emergence and early post-emergence herbicide in use since 1965. Derived from acetanilide, propachlor is used in agriculture to control annual grasses and some broad-leaved weeds in several crops, including corn, sorghum, pumpkins, flax and flowers.

A section devoted to the environmental behaviour of propachlor cites rapid degradation by microorganisms in soil and water, and concludes that this chemical does not biocon-centrate or biomagnify. Studies of metabolic fate in different mammalian species point to rapid elimination of propachlor and its metabolites.

The remaining sections evaluate findings from toxicological investigations in experimental animals and, for humans, the limited data available from cases of contact and allergic dermatitis reported in farmers and production workers exposed to propachlor. For experimental animals, the liver and kidneys are identified as the target organs. For human exposures, the report found no evidence of symptoms or diseases reported for either occupationally exposed workers or the general population, with the exception of scattered reports of dermatitis in workers.

On the basis of these evaluations, the report concludes that, under conditions of normal use, exposure of the general population is unlikely. For occupationally exposed workers, the report recommends the use of adequate safety and hygienic precautions to protect the skin, eyes, and respiratory tract. Though propachlor is judged to pose a low hazard to birds, earthworms, and honey-bees, evidence indicates high toxicity to some aquatic organisms, supporting the conclusion that direct contamination of water courses should be avoided.


1-Propanol

Environmental Health Criteria, No. 102
1990, 98 pages [E]
ISBN 92 4 157102 0
Sw.fr. 23.-/US $20.70; in developing countries: Sw.fr. 16.10
Order no. 1160102

Evaluates the risks to human health and the environment posed by the production, use and waste disposal of 1-propanol, a colourless, highly flammable liquid used primarily as a multi-purpose solvent in industry and in the home. The compound, which has antiseptic as well as solvent properties, is also used in drugs and cosmetics. The evaluation concludes that, under normal conditions of use, 1-propanol is unlikely to pose a serious threat to either the general population or the environment.


2-Propanol

Environmental Health Criteria, No. 103
1990, 132 pages [E]
ISBN 92 4 157103 9
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160103

Evaluates the risks to human health and the environment posed by the production and use of 2-propanol, a liquid widely used as a low-cost solvent in industry and in the home. Because of its cooling, antipyretic, rubefacient, cleaning, and antiseptic properties, 2-propanol is used to produce a large number of household and personal products, including topically applied pharmaceutical products and cosmetics.

The report notes that the strong-acid production process, which has been causally linked to an increased risk of paranasal sinus cancer in workers, has been largely replaced by a less hazardous process, thus reducing the health risks to workers. Experimental studies point to toxic effects similar to those of acute ethanol intoxication. A review of sources of human exposure draws attention to reports of life-threatening intoxication following the sponging of febrile children with 2-propanol preparations. While noting the need for further studies of carcinogenic activity, the report concludes that 2-propanol is unlikely to pose a serious health risk under normal conditions of exposure.


Quality Management for Chemical Safety Testing

Environmental Health Criteria, No. 141
1992, 112 pages [E, with summaries in F, S; R]
ISBN 92 4 157141 1
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160141

A detailed guide to the principles and specifics of quality management needed to ensure that studies of chemical safety produce accurate and meaningful results. Focused on the management of both the laboratory and the individual studies it conducts, the book stresses the need to establish and follow formal standard procedures for virtually every laboratory practice that can influence the quality of study results. The objective is to help laboratory managers and staff think through all possible sources of error and plan appropriate measures for their control. Details range from a list of the types of records that must be kept to a description of the precautions needed to make certain that chemicals used for cleaning or pest control in animal rooms do not interfere with the study.

The book has three chapters. The first describes the principles of management and organization required for quality assurance, stressing the importance of making quality assurance an integral part of the entire study process. To this end, readers are given advice on the selection and training of personnel, the use of inspections and audits, the design of facilities, the maintenance and calibration of equipment, and the formulation and use of written standard operating procedures. Other sections cover the quality management of specific laboratory routines and procedures, moving from the preparation of the study plan, through the characterization of test, control, and reference substances, to the reporting of results. The second chapter explains how quality management can be applied to procedures for handling animals at all stages of a toxicity study, from the shipping of animals to the transfer of specimens to archives. The final chapter covers the quality control of studies designed to measure the presence of chemicals in humans and the environment, and monitor the effects.


Selected Synthetic Organic Fibres

Environmental Health Criteria, No. 151
1993, 100 pages [E, with summaries in F, S]
ISBN 92 4 157151 9
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160151

Evaluates the risks to human health posed by occupational and environmental exposure to selected synthetic organic fibres. Fibres covered include carbon and graphite fibres, aramid fibres, and polyolefin fibres. Carbon and aramid fibres are used mainly in advanced composite materials to improve strength, stiffness, durability, electrical conductivity, or heat resistance. Since these fibres improve properties without adding much weight, they are used primarily in the aerospace industry, for military purposes, and in the manufacture of sports equipment. Polyolefin fibres are used in carpet pile, upholstery, bedding, curtains, and other household textile applications. The largest use of polyolefin fabric in clothing is in disposable diapers and athletic socks.

Basic information on chemical and physical properties and methods of production is followed by a review of data from studies of exposure in the occupational environment, where operations such as fibre forming, winding, chopping, weaving, cutting, and machining and composite formation release fibre dusts into the workplace. The most extensive chapter, focused on the results of toxicological studies in laboratory animals and in vitro test systems, reviews the many important methodological problems, including choice of exposure route, that make it difficult to assess effects and extrapolate findings to humans. Although data from human studies are limited, the report concludes that occupational exposure to these synthetic organic fibres may have adverse effects on the respiratory system. The report further concludes that the health risk associated with exposure in the general environment is likely to be very low.


Silica, Some Silicates, Coal Dust and Para-Aramid Fibrils

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 68
1997, iv + 506 pages [E]
ISBN 92 832 1268 1
Sw.fr. 80.-/US $72.00; in developing countries: Sw.fr. 56.-
Order no. 1720068

Evaluates the carcinogenic risks to humans posed by exposure to crystalline and amorphous silica, some silicates (palygorskite, sepiolite, wollastonite, and zeolites other than erionite), coal dust, and para-aramid fibrils. The volume opens with a discussion of the many complexities involved in assessing the cancer risks associated with occupational exposure to inhaled mineral dusts, and the special toxicological considerations required when evaluating the results of experimental studies. Against this background, the first and most extensive monograph evaluates human and animal carcinogenicity data on silica, concentrating on evidence of an increased risk for lung cancer. On the basis of this evaluation, crystalline silica inhaled in the form of quartz or cristobalite from occupational sources was classified as carcinogenic to humans. For amorphous silica, evidence from both epidemiological and experimental studies was judged inadequate, and amorphous silica could not be classified.

For palygorskite, the evaluation found sufficient evidence from studies in rats that long fibres were carcinogenic; studies of exposure to short fibres showed no significant increase in the incidence of tumours. The few studies in humans were judged inadequate. Long palygorskite fibres were classified as possibly carcinogenic to humans. Short fibres could not be classified.

For coal dust, several limitations in human studies, largely concerned with excessive mortality from lung and stomach cancer, hindered interpretation of the epidemiological literature. The few adequate experimental studies showed no increase in tumours. Coal dust therefore could not be classified. para-Aramid fibrils likewise could not be classifed in view of inadequates in both the epidemiological and experimental data.


Solar and Ultraviolet Radiation

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 55
1992, 316 pages [E]
ISBN 92 832 1255 X
Sw.fr. 72.-/US $64.80; in developing countries: Sw.fr. 50.40
Order no. 1720055

Evaluates carcinogenic risks associated with human exposure to solar radiation and to ultraviolet radiation from medical and cosmetic devices, general illumination, and industrial sources. The main objective of the evaluation was to determine whether enough evidence is available to decide which segments of the radiation spectrum are responsible for its adverse effects. To this end, particular attention is given to data that shed light on the distinctive carcinogenic activity of ultraviolet A, B, and C radiation. In evaluating carcinogenic potential, the report also considers the importance of human constitutional risk factors, such as skin type, hair and eye colour, and specific subtypes of exposure, such as occupational and recreational exposures. More than 1,000 studies were critically assessed.

On the basis of a large body of evidence from human and experimental studies, the monograph concludes that solar radiation is carcino-genic to humans, causing cutaneous malignant melanoma and nonmelanocytic skin cancer. Evidence for the carcinogenicity of ultraviolet A, B, and C radiation was judged sufficient in experimental animals. All three segments of the radiation spectrum were classified as probably carcinogenic to humans. Use of sunlamps and sunbeds entails exposures that are probably carcinogenic to humans. The carcinogenicity of exposure to fluorescent lighting could not be determined. Studies of topical sunscreens are reviewed in an appendix, which concludes that, although effective in preventing sunburn, little is known about their protective value against harmful immuno-logical changes, photo-ageing, or skin cancer.

"... conforms to the usual high standards of IARC monographs ... a valuable source of information about the neglected areas of radiation pathology and toxicology..."
— Journal of Clinical Pathology


Some Antiviral and Antineoplastic Drugs, and Other Pharmaceutical Agents

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 76
IARC 2000, iv + 521 pages [E]
ISBN 92 832 1276 2
Sw.fr. 56.–/US $50.40
In developing countries: Sw.fr. 38.50
Order no. 1720076

Evaluates the carcinogenic risks to humans posed by the use of four antiretroviral agents, four DNA topoisomerase II inhibitors used in the treatment of cancer, and an additional three pharmaceutical agents (hydroxyures, phenolphthalein, and vitamin K substances). The volume marks the first IARC evaluation of nucleoside analogs that act as antiviral agents. The evaluation responds in part to recent findings that zidovudine (AZT), an effective antiretroviral agent now being given to pregnant HIV-infected women to prevent maternal-to-fetal transmission of the virus, is a transplacental carcinogen in mice.

The opening monograph evaluates the carcinogenicity to humans of the antiretroviral nucleoside analogs zidovudine (AZT), zalcitabine (ddC), and didanosine (ddI), and the antiherpesvirus drug aciclovir. Of these, aciclovir and didanosine could not be classified on the basis of available data. For zidovudine, transplacental administration to mice resulted in an increased incidence and multiplicity of lung and liver tumours and in an increased incidence of female reproductive tract tumours in one study, but not in another involving treatment at a lower dose. Despite observation of toxic effects in some studies of humans, human carcinogenicity data were judged to provide inadequate evidence of carcinogenicity in humans. Zidovudine was classified as possibly carcinogenic to humans. Similar weaknesses in human carcinogenicity data for zalcitabine, which consistently induces thymic lymphomas in mice, resulted in its classification as possibly carcinogenic to humans.

The second monograph evaluates four DNA topoisomerase II inhibitors: etoposide, teniposide, mitoxantrone, and amsacrine. Of these, etoposide – one of the most widely used and effective cytotoxic drugs in combination therapy – was classified as probably carcinogenic to humans, and etoposide in combination with cisplatin and bleomycin was judged to be carcinogenic to humans. Teniposide was classified as probably carcinogenic to humans, and mitoxantrone and amsacrine were classified as possibly carcinogenic to humans.

Of the three pharmaceutical agents evaluated in the final monograph, hydroxyurea, which is widely used in cancer treatment and, increasingly, in combination with didanosine in HIV infection, could not be classified. Phenolphthalein, a widely used laxative now being withdrawn from the market in many countries because of toxicological concerns, was classified as possibly carcinogenic. Vitamin K substances could not be classified on the basis of available evidence.

Some Flame Retardants and Textile Chemicals, and Exposures in the Textile Manufacturing Industry

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 48
IARC 1990, 345 pages [E]
ISBN 92 832 1248 7
Sw.fr. 72.-/US $64.80; in developing countries: Sw.fr. 50.40
Order no. 1720048

Evaluates the carcinogenic risk to humans posed by exposure to selected flame retardants and other chemicals used in the textile manufacturing industry. Agents were selected for evaluation on the basis of the availability of data on carcinogenicity and on human exposure. The book also includes an extensive monograph addressing the question of whether employment in the textile manufacturing industry exposes workers to carcinogenic risks.

Monographs cover six flame retardants (chlorendic acid, chlorinated paraffins, decabromodiphenyl oxide, dimethyl hydrogen phosphite, tetrakis(hydroxymethyl) phosphonium salts, and tris(2-chloroethyl) phosphate), five textile dyes (para-chloro-ortho-toluidine and its strong acid salts, Disperse Blue 1, Disperse Yellow 3, Vat Yellow 4, and 5-nitro-ortho-toluidine), and nitrilotriacetic acid and its salts. Para-chloro-ortho-toluidine and its strong acid salts were classified as probably carcinogenic to humans; and chlorendic acid, chlorinated paraffins, Disperse Blue 1, and nitrilotriacetic acid and its salts were classified as possibly carcinogenic to humans. The remaining chemicals could not be classified.

The most extensive monograph evaluates occupational exposures in the textile manufacturing industry. Evaluations of risk concentrate on epidemiological evidence of carcinogenicity at the oral and pharyngeal, oesophagus and stomach, nasal cavity, larynx, lung, and bladder sites. In view of the strength of findings of bladder cancer among dyers and among weavers and of cancer of the nasal cavity among weavers and other textile workers, the monograph concludes that working in the textile manufacturing industry entails exposures that are possibly carcinogenic to humans.


Some Industrial Chemicals

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 77
IARC 2000, iv + 563 pages [E]
ISBN 92 832 1277 0
Sw.fr. 55.–/US $49.50
In developing countries: Sw.fr. 38.50
Order no. 1720077

Evaluates or re-evaluates the carcinogenic risks to humans posed by exposure to sixteen organic industrial chemicals. These included some aromatic amines (ortho-toluidine, 4-chloro-ortho-toluidine, and 5-chloro-ortho-toluidine), some ethanolamines (di- and triethanolamine and N-nitrosodiethanolamine), and three esters [di(2-ethylhexyl) phthalate (DEHP), di(2-ethylhexyl) adipate, and cinnamyl anthranilate]. Seven of the sixteen compounds were evaluated in previous IARC Monographs and are reconsidered here in the light of new evidence.

Three chemicals were classified or reclassified as probably carcinogenic to humans: ortho-toluidine, 4-chloro-ortho-toluidine, and glycidol. Four compounds, evaluated here for the first time, namely 2,2-bis(bromomethyl)propane-1,3-diol, 2,3-dibromopropan-1-ol, ethylbenzene, and nitromethane, were classified as possibly carcinogenic to humans. N-Nitrosodiethanolamine, which can readily be formed from either di- or triethanolamine in the presence of inorganic nitrite, remained classified as possibly carcinogenic to humans.

For eight compounds, including 5-chloro-ortho-toluidine, coumarin, pyridine, diethanolamine, triethanolamine, di(2-ethylhexyl) adipate, and cinnamyl anthranilate, evidence was judged inadequate to classify these compounds according to their carcinogenicity in humans.

The most extensive monograph is devoted to an evaluation of di(2-ethylhexyl) phthalate (DEHP), which had previously been classified as possibly carcinogenic to humans. Using assessment criteria recently established for compounds that induce peroxisome proliferation in the liver, the evaluation downgraded DEHP to the group of compounds that cannot be classified. Two other compounds that cause peroxisome proliferation, di(2-ethylhexyl) adipate and cinnamyl anthranilate, were also evaluated as not classifiable as to carcinogenicity to humans.


Some Industrial Chemicals

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 60
1994, 560 pages [E]
ISBN 92 832 1260 6
Sw.fr. 90.-/US $81.00; in developing countries: Sw.fr. 63.-
Order no. 1720060

Evaluates the carcinogenic risk to humans posed by exposure to fourteen industrial chemicals, including several having considerable commercial importance as the building blocks of widely used polymers and copolymers. While some of these chemicals are evaluated for the first time, the majority have been re-evaluated in the light of substantial new data and more precise methodological guidelines for the interpretation of findings. In view of the widespread industrial use of these chemicals, particular emphasis is placed on the risk of cancer in occupationally exposed workers. Over 1,800 studies were critically assessed.

The most extensive monographs cover ethylene oxide, styrene, and acrylamide. Ethylene oxide is an important raw material for making major consumer goods in virtually all industrialized countries. On the basis of evidence of small but consistent excesses of lymphatic and haematopoietic cancer found in both human and animal studies, the monograph concludes that ethylene oxide is carcinogenic to humans.

For styrene, one of the most important monomers worldwide, the evaluation concentrated on evidence of a link between exposure and the risk for lymphatic and haematopoietic cancer, concluding that styrene is possibly carcinogenic to humans. Acrylamide was classified as probably carcinogenic to humans. Among the other chemicals evaluated, styrene-7,8-oxide was classified as probably carcinogenic to humans. Propylene oxide, isoprene, 4-vinylcyclohexene, and 4-vinylcyclo-hexene diepoxide were classified as possibly carcinogenic. The remaining chemicals, ethylene, propylene, vinyl toluene, N-methylol-acrylamide, methyl methacrylate, and 2-ethylhexyl acrylate, could not be classified. For two of these, methyl methacrylate and vinyl toluene, experimental evidence indicated a lack of carcinogenicity.


Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 56
1993, 599 pages [E]
ISBN 92 832 1256 8
Sw.fr. 95.-/US $85.50; in developing countries: Sw.fr. 66.50
Order no. 1720056

Evaluates the carcinogenic risk to humans posed by the ingestion of several naturally occurring substances. Separate monographs are presented for two food items (salted fish and pickled vegetables), two naturally occurring plant substances (caffeic acid and d-limonene), four heterocyclic aromatic amines found in cooked meat and fish, and selected mycotoxins, including aflatoxins.

The monograph on salted fish concentrates on fish as traditionally prepared in southern China, where very high rates of nasopharyngeal carcinoma have been linked to the consumption of salted fish prepared in a manner which involves putrefaction. The monograph concludes that Chinese-style salted fish is carcinogenic to humans. The second monograph concludes that pickled vegetables, prepared according to traditional Asian methods, are possibly carcinogenic to humans. Caffeic acid was judged to be possibly carcinogenic to humans. The report was unable to classify the carcinogenicity of d-limonene. For the heterocyclic aromatic amines present in cooked meat and fish, IQ was classified as probably carcinogenic to humans; MeIQ, MeIQx, and PhIP were classified as possibly carcinogenic.

The most extensive monograph, on aflatoxins, concludes that naturally occurring mixtures of aflatoxins are carcinogenic to humans and that aflatoxin M1 occurring in milk is possibly carcinogenic. Toxins derived from Fusarium moniliforme and ochratoxin A, which has been linked to Balkan endemic nephropathy, were classified as possibly carcinogenic to humans. The remaining mycotoxins could not be classified.


Tetrabromobisphenol A and Derivatives

Environmental Health Criteria, No. 172
1995, 139 pages [E, with summaries in F, S]
ISBN 92 4 157172 1
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160172

Evaluates the risks to human health and the environment posed by tetrabromobisphenol A (TBBPA), the most widely used and commercially important brominated flame retardant. The compound is mainly used as a reactive intermediate in the manufacture of flame-retarded epoxy and polycarbonate resins. Tetrabromobisphenol A is also used as an additive flame retardant in various polymers. Laboratory pyrolysis studies have demonstrated that polymers containing TBBPA can form polybrominated dibenzofurans and, to a lesser extent, polybrominated dibenzodioxins, underscoring the need to ensure cautious disposal by incineration of industrial wastes and consumer products treated with TBBPA.

Findings from studies in experimental animals demonstrate a very low acute and repeated dose toxicity. Citing these and other findings, the report concludes that the health risk for the general population posed by TBBPA is insignificant. Since most of the manufacturing process takes place in enclosed equipment, the report further concludes that occupational hazards are mainly confined to dust exposure during the packing process, and can be minimized through the use of local ventilation and other engineering methods.

The report also summarizes available data on five TBBPA derivatives used as flame retardants (tetrabromobisphenol A dibromopropylether, tetrabromobisphenol A bis(allylether), tetrabromobisphenol A bis(2-hydroxyethyl ether), tetrabromobisphenol A carbonate oligomers, and tetrabromobisphenol A brominated epoxy oligomer) and one derivative (tetrabromobisphenol A dimethylether) having no commercial applications, but detected in environmental samples. For all these compounds, data were judged inadequate for evaluation.


1,1,2,2-Tetrachloroethane

Concise International Chemical Assessment Document, No. 3
1998, iv + 28 pages [E, with summaries in F, S]
ISBN 92 4 153003 0
Sw.fr. 13.-/US $11.70; in developing countries: Sw.fr. 9.10
Order no. 1380003

A concise assessment of the risks to human health posed by exposure to 1,1,2,2,-tetrachloroethane, a chemical used primarily as an intermediate in the synthesis of other chlorinated hydrocarbons. The document is part of a new series of brief reports aimed at the characterization of hazards and dose-response for exposures to selected industrial chemicals.

Studies of environmental behaviour and fate support the conclusion that 1,1,2,2-tetrachloroethane is unlikely to contribution to the depletion of stratospheric ozone or to global warming. Animal studies indicate that 1,1,2,2-tetrachloroethane has slight to moderate acute toxicity; the liver is the principal target organ. Studies of long-term exposure demonstrated a significant increase in the incidence of hepatocellular carcinomas in mice, but not in similarly exposed rats. Because of the chemical's declining use, few recent evaluations of toxic effects in humans were available for evaluation.


Tetramethrin

Environmental Health Criteria, No. 98
1990, 69 pages [E, R]
ISBN 92 4 154298 5
Sw.fr. 19.-/US $17.10; in developing countries: Sw.fr. 13.30
Order no. 1160098

Evaluates the risks to human health and the environment posed by tetramethrin, a synthetic pyrethroid insecticide used in aerosol formulations, emulsifiable concentrates, and mosquito coils exclusively for indoor pest control. A review of data on the environmental behaviour of this insecticide points to rapid abiotic degradation in air and water.

Concerning effects on organisms in the environment, the report cites laboratory data demonstrating that tetramethrin is highly and acutely toxic to fish and toxic to bees, but has very low toxicity for birds. Because tetramethrin is rapidly degraded, and provided its use is limited to buildings, as recommended, this potential for environmental toxicity is unlikely to be realised.

The most extensive section evaluates the results of experimental studies of toxicity and carcinogenicity relevant to the assessment of health effects in humans. The report found no evidence of carcinogenicity or other adverse effects on health. On the basis of this evaluation, the report concludes that tetramethrin, when used as recommended for the indoor control of pests, is highly unlikely to present a hazard to the general population, to workers, or to the environment.


Thallium

Environmental Health Criteria, No. 182
1996, 274 pages [E, with summaries in F, S]
ISBN 92 4 157182 9
Sw.fr. 51.-/US $45.90; in developing countries: Sw.fr. 35.70
Order no. 1160182

Evaluates the risks to human health and the environment posed by thallium, a naturally occurring, ubiquitous heavy metal present at low levels in drinking-water, food, and ambient air. Although the industrial production and uses of thallium are now limited, thallium(I) sulfate was previously used in the treatment of tuberculosis and malaria, and as a depilatory agent, resulting in numerous cases of poisoning.

Thallium has also been used within this century as a rodenticide and insecticide. While such uses have been banned in most parts of the world, thallium continues to be used as a low-cost rodenticide in some developing countries. Moreover, since thallium salts are tasteless, odourless, colourless, highly toxic, and were easily obtained in the past, thallium probably qualifies as the world's most frequently used agent for suicide, homicide, and attempts at illegal abortion, resulting in a vast body of clinical data on toxic effects in humans.

The most extensive sections review findings from toxicity studies in laboratory animals and in vitro test systems, and summarize the large body of clinical data drawn from case reports of accidental, suicidal, and criminal poisoning in humans. These studies support numerous conclusions concerning the mechanisms of toxic action, target organs, the symptoms of acute and chronic intoxication , factors influencing clinical course and the degree of recovery, the effectiveness of different therapies, and estimated lethal doses in children and adults.

The report concludes that, while the limited industrial uses of thallium are unlikely to pose a threat to the general population or the environment, emissions from power-generating plants, smelters, brickworks, and cement plants should be strictly controlled and monitored. The report calls for a worldwide ban on the use of thallium as a rodenticide.


o-Toluidine

Concise International Chemical Assessment Document, No. 7
1998, iv + 18 pages [E, with summaries in F, S]
ISBN 92 4 153007 3
Sw.fr. 13.-/US $11.70; in developing countries: Sw.fr. 9.10
Order no. 1380007

A concise assessment of the risks to human health posed by exposure to ortho-toluidine, a chemical used in the manufacture of dyestuffs and, to a lesser extent, in the production of rubber, chemicals, and pesticides, and as a curing agent for epoxy resin systems. The document is part of a new series of brief reports aimed at the characterization of hazards and dose-response for exposures to selected industrial chemicals. With this goal in mind, documents in the series focus on studies and findings considered critical for risk characterization

The document is primarily concerned with assessing the carcinogenic risk in occupationally exposed workers. A review of findings from studies in rats and mice, where oral administration of o-toluidine has been linked to a significant increase in the incidence of benign and malignant tumours, supports the conclusion that o-toluidine may act as a genotoxic carcinogen. In humans, limited epidemiological evidence suggests an increased risk of bladder cancer in occupationally exposed workers. In view of evidence that the chemical's carcinogenic action involves a genotoxic mechanism, the assessment was unable to identify a threshold at which exposure would not result in some risk to human health.


Tributyltin Compounds

Environmental Health Criteria, No. 116
1990, 273 pages [E, with summaries in F, S]
ISBN 92 4 157116 0
Sw.fr. 46.-/US $41.40; in developing countries: Sw.fr. 32.30
Order no. 1160116

Evaluates risks to human health and the environment posed by the use of tributyltin compounds as molluscicides, as antifoulants on boats, ships, quays, buoys, and equipment in the fishing industry, as wood preservatives, and as slimicides on masonry. These compounds pose a particular threat to the marine environment in view of their documented high toxicity to aquatic organisms, including commercially important shellfish.

Tributyltin compounds are observed to be toxic to microorganisms and highly toxic to oysters, mussels, and other marine molluscs consumed by humans. A review of field observations, which are in good agreement with laboratory findings, confirms the association between use of these compounds in the marine environment and mortality, malformations, and population decline of molluscs. The remaining sections evaluate findings from experimental studies and observations in occupationally exposed humans. The book concludes that tributyltin compounds are a severe irritant to human skin and an extreme irritant to the eye, and that inhalation of aerosols can have especially hazardous effects on the respiratory tract. Despite the large body of experimental studies documenting toxicity, the book was unable to quantify the risk to humans posed by the consumption of contaminated fish and shellfish.

"... of the standard we have come to expect in this series..."
— Environmental Management and Health

"... Those involved in the use of any compound containing TBT need accurate, up-to-date information. This volume is essential reading in this context..."
— International Pest Control


Trichlorfon

Environmental Health Criteria, No. 132
1992, 162 pages [E, with summaries in F, S]
ISBN 92 4 157132 2
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160132

Evaluates the risks to human health and the environment posed by trichlorfon, a broad-spectrum organophosphorus insecticide which acts as a "slow release" source of dichlorvos in the mammalian body. Marketed since the 1950s, trichlorfon is used to protect field and fruit crops, to control forest insects, and to control internal and external parasites in domestic and farm animals. Trichlorfon, formulated as metrifonate, has also been used for the pharmacological treatment of Schistosoma haematobium in millions of patients. The compound is under investigation as a treatment for Alzheimer's disease.

A review of environmental levels and human exposure concentrates on the significance of residues detected in crops, the milk of treated cows, and other food items as possible sources of exposure for the general public. Noting that detected levels are far below the established acceptable daily intake, the report concludes that trichlorfon does not constitute a health hazard for the general population. Concerning effects on environmental organisms, the report cites evidence that trichlorfon is moderately toxic for fish and birds, and moderately to highly toxic for aquatic arthropods, supporting the conclusion that this insecticide should never be sprayed over water bodies or streams.

The remaining sections evaluate data from toxicity studies from several hundred case reports of accidental or intentional human poisoning, and from studies of schistosomiasis patients treated with metrifonate. Though poisoning may have serious effects, including delayed neurotoxicity, the report concludes that, when good work practices and safety precautions are followed, trichlorfon is unlikely to present a hazard for occupationally exposed workers. The report further notes that, in the millions of schistosomiasis patients treated with metrifonate, reported side effects have been mild and rare.


1,1,1-Trichloroethane

Environmental Health Criteria, No. 136
1992, 117 pages [E, with summaries in F, S]
ISBN 92 4 157136 5
Sw.fr. 28.-/US $25.20; in developing countries: Sw.fr. 19.60
Order no. 1160136

Evaluates the risks to human health and the environment posed by 1,1,1-trichloroethane, a chlorinated hydrocarbon widely used in the cleaning and degreasing of metal and as a solvent in many industrial and consumer products. The abuse of this solvent has resulted in a large number of fatalities.

A review of data on the environmental behaviour of 1,1,1-trichloroethane documents its ubiquitous presence in the atmosphere, its rapid transport to the troposphere, its long residence time, its depletion of ozone, and its contribution to global warming. Leaching into ground water and deep aquifers occurs and persistent contamination has been documen-ted. While contamination of the atmosphere is judged to be the most important route of exposure for the general population, the report notes that indoor air may cause considerably higher exposures due to the use of numerous consumer products containing this solvent. Air is also noted to be the main source of exposure at the workplace.

An evaluation of effects on humans draws upon studies of occupationally exposed workers and cases of fatal exposure following accidents and intentional abuse. Both acute and long-term inhalation exposures are noted to affect the central nervous system, with signs ranging from slight behavioural changes to unconsciousness. Exposure may also cause damage to the heart and liver. A review of accidents at the workplace underscores the especially dangerous conditions in poorly ventilated areas and confined spaces, such as tanks and vaults, caused by the compound's greater density than air. The final section evaluates effects on organisms in the field, concluding that environmental contamination is unlikely to pose a significant hazard for environmental organisms. Because of its many other hazards, including its ozone-depleting potential, the report recommends that the release of 1,1,1-trichloroethane be reduced to the greatest extent possible.


Tricresyl Phosphate

Environmental Health Criteria, No. 110
1990, 122 pages [E, with summaries in F, S]
ISBN 92 4 157110 1
Sw.fr. 24.-/US $21.60; in developing countries: Sw.fr. 16.80
Order no. 1160110

Evaluates risks to human health and the environment posed by the production and use of tricresyl phosphate. Tricresyl phosphate is used in industry as a plasticizer in vinyl plastic manufacture, as a flame-retardant, as a solvent for nitrocellulose, in cellulosic molding compositions, and in the manufacture of fire-resistant hydraulic fluids and lubricants.

Because of the physico-chemical properties of tricresyl phosphate and its rapid biodegradation, the report concludes that use of the compound does not threaten the environment, though there is some evidence that crop plants can be affected by tri-o-cresyl phosphate released from plastic coverings. A section devoted to kinetics and metabolism concentrates on mechanisms of absorption, distribution, metabolism, and elimination that can help explain the well-documented neuropathic actions of tricresyl phosphate and, most notably, its highly toxic isomer, tri-o-cresyl phosphate.

The most extensive section assesses findings from toxicity studies, emphasizing the large number of studies documenting neurotoxic effects, often at very low doses. These effects are further characterized through a review of the numerous reported cases of large-scale human poisoning following the ingestion of accidentally or deliberately contaminated medicines and foodstuffs. Readers are given detailed information on the clinical symptoms of poisoning, the characteristics of delayed neuropathy, long-term prognosis, and advice on the first-aid treatment of victims. While the concluding section notes that use of tricresyl phosphate poses very little risk to either the environment or the general population, the report underscores the severity and long-duration of the neuropathology caused by accidental poisoning, noting that some victims never recover.


Tri-n-butyl Phosphate

Environmental Health Criteria, No. 112
1991, 80 pages [E, with summaries in F, S]
ISBN 92 4 157112 8
Sw.fr. 19.-/US $17.10; in developing countries: Sw.fr. 13.30
Order no. 1160112

Evaluates risks to human health and the environment posed by the production and use of tri-n-butyl phosphate. Tri-n-butyl phosphate is widely used worldwide as a solvent for cellulose esters, lacquers, and natural gums, as a primary plasticizer in the manufacture of plastics and vinyl resins, in the formulation of fire-resistant aircraft hydraulic fluids, and as an antifoaming agent, mainly in paper manufacturing plants.

Although tri-n-butyl phosphate has been widely detected in air, water, sediment, and biological tissues, the review notes that concentrations are usually very low. Workers involved in aircraft maintenance and exposed during the manipulation of hydraulic fluids are regarded as the largest occupational group at risk. In view of several weaknesses in available experimental data, the report was unable to reach firm conclusions concerning the risks posed by tri-n-butyl phosphate as a potential carcinogen, neurotoxic agent, or dermal sensitizer, though a neurotoxic effect comparable to organophosphate-induced delayed neuropathy was judged unlikely. The report concludes that the production and use of tri-n-butyl phosphate pose a low risk for the environment and for the general population, and that the likelihood of long-term effects in occupationally exposed workers is small.

"... The WHO series on Environmental Health Criteria has proved a model of presentation of as complete a range of information as possible in a manner that allows easy access to any particular category of data, and to expert interpretation ... excellent..."
— Annals of Occupational Health


Triphenyl Phosphate

Environmental Health Criteria, No. 111
1991, 80 pages [E, with summaries in F, S]
ISBN 92 4 157111 X
Sw.fr. 19.-/US $17.10; in developing countries: Sw.fr. 13.30
Order no. 1160111

Evaluates risks to human health and the environment posed by the production and use of triphenyl phosphate, a compound widely used as a flame retardant in phenolic and phenylene-oxide-based resins for the manufacture of electrical and automobile components. Triphenyl phosphate is also used as a non-flammable plasticizer in cellulose acetate for photographic films, and as a component of hydraulic fluids and lubricant oils.

Main sources of release into the environment are identified as leakage or spills of hydraulic fluid, leaching from plastics, and manufacturing processes. A review of data on effects on organisms in the environment concentrates on risks to the aquatic environment, concluding that triphenyl phosphate is the most acutely toxic of the various triaryl phosphates to fish, shrimp, and daphnids. The remaining sections evaluate toxic effects as determined through studies in experimental models and observations in humans. The book notes that triphenyl phosphate exhibits low toxicity in short-term studies, is not mutagenic, and has not been shown, in several well-designed studies, to cause delayed neuropathy or other neurotoxic changes. Studies of exposed workers found no evidence of neurological disease or other abnormalities. Risks to the environment are likewise judged to be low, though spills of hydraulic fluid could result in fish kills.

"... not only the most extensive, but also one of the best toxicological series in existence ... Books in the Environmental Health Criteria series deserve nothing but praise..."
— International Journal of Environmental Studies


Tris(2,3-dibromopropyl) Phosphate and Bis(2,3-dibromopropyl) Phosphate

Environmental Health Criteria, No. 173
1995, 129 pages [E, with summaries in F, S]
ISBN 92 4 157173 X
Sw.fr. 28.-/US $25.20; in developing countries: Sw.fr. 19.60
Order no. 1160173

Evaluates the risks to human health and the environment posed by tris(2,3-dibromopropyl) phosphate (TBPP), a flame retardant with former widespread use in children's sleepwear. In 1977, concern that TBPP might be a human carcinogen led the USA to ban children's clothing treated with this compound. Several other countries have also banned the use of this flame retardant in textiles and severely restricted its use in other consumer products. Although available data indicate that TBPP is no longer produced for use in textiles, an evaluation of health and environmental hazards was judged important in view of additional commercial applications, including the use of TBPP in polymers.

A discussion of production and uses concentrates on previous applications as a flame retardant for triacetate and polyester fabrics. Release to the environment is noted to occur during the wearing or laundering of treated garments, from textile-finishing plants, and following the disposal of solid wastes containing TBPP. Children wearing treated sleepwear are identified as the main group in the general population exposed to TBPP. In humans, TBPP applied to the surface of fabrics can be extracted by saliva. Absorption through human skin has also been shown to occur.

Several studies in experimental animals have detected toxic effects on the kidney and liver and produced evidence that TBPP is teratogenic, mutagenic, genotoxic, and carcinogenic in rats and mice. On the basis of these and other findings, the report concludes that TBPP should no longer be used commercially. The report also assesses available data on bis(2,3-dibromopropyl) phosphate, a major breakdown product of TBPP which is no longer produced for commercial use. Data were judged inadequate for evaluation.


Ultraviolet Radiation
An Authoritative Scientific Review of Environmental and Health Effects of Ultraviolet Radiation, with Reference to Global Ozone Layer Depletion

Environmental Health Criteria, No. 160
1994, 352 pages [E]
ISBN 92 4 157160 8
Sw.fr. 67.-/US $60.30; in developing countries: Sw.fr. 46.90
Order no. 1160160

A state-of-the-art review of the many lines of evidence - whether at the molecular or the clinical level - linking exposure to ultraviolet (UV) radiation to a range of adverse effects on human health. The report, which responds to concern over the depletion of stratospheric ozone and a corresponding increase in levels of UV radiation, makes a special effort to distin-guish between established biological effects and those that have been reported as preliminary or isolated results, or as hypotheses proposed to explain observed results. By distin-guishing areas of consensus from areas of continuing controversy, the book aims to esta-blish a solid, scientific foundation for identifying precise health hazards, designing targeted programmes for prevention, and making realistic predictions for the future.

Since UV radiation is an established human carcinogen, the report concentrates on the mechanisms by which UV radiation exerts its toxic effects and on the many environmental, constitutional, ethnic, behavioural, and other factors that influence individual risk. The opening chapters describe the physical characteristics of the electromagnetic spectrum and discuss the properties of different sources of UV radiation, including the sun, incandescent sources, gas discharges, electric discharges, fluorescent lamps, lasers, and sunbeds. The second chapter discusses human exposures occurring in various occupations, in medicine and dentistry, and in sunbathing, outdoor recreation, and other elective behaviours. Dosimetric concepts are reviewed in the third chapter, which concentrates on principles important to the design and interpretation of studies.

"... authoritative, concise and clearly structured... highly recommended..."
— International Journal of Biometerology


Vinylidene Chloride

Environmental Health Criteria, No. 100
1990, 187 pages [E]
ISBN 92 4 154300 0
Sw.fr. 32.-/US $28.80; in developing countries: Sw.fr. 22.40
Order no. 1160100

Evaluates the environmental hazards and risks to human health posed by the production and use of vinylidene chloride. Vinylidene chloride/vinyl chloride copolymers are used for the packaging of foods, as metal coatings in storage tanks, building structures, and tapes, and as moulded filters, valves, and pipe fittings. Food packaging applications include both commercial packaging films and household wraps.

The most extensive sections evaluate the design and findings of studies, in experimental animals and in vitro test systems, attempting to link exposure to specific health hazards. Research, including studies of possible carcinogenic and mutagenic effects, indicates that the main health hazards associated with exposure are irritation of the skin and eye and depressed functions of the central nervous system. The report concludes that the general population is exposed to very low levels of this chemical, that risks associated with long-term occupational exposure warrant special precautions, and that an evaluation of carcinogenic risk to humans must await further epidemiological studies. The release of vinylidene chloride into the atmosphere is not considered likely to contribute to the depletion of the stratospheric ozone layer.

"... The authors are to be congratulated for their effort in presenting clearly and concisely the relevant data in the literature on vinylidene chloride ... a good buy..."
— Sozial- und Pr�ventivmedizin

"... well worth its place in libraries concerned with environmental health..."
— South African Medical Journal


White Spirit (Stoddard Solvent)

Environmental Health Criteria, No. 187


996, 186 pages [E, with summaries in F, S]
ISBN 92 4 157187 X
Sw.fr. 40.-/US $36.00; in developing countries: Sw.fr. 28.-
Order no. 1160187

Evaluates the risks to human health and the environment posed by exposure to white spirit, a petrochemical solvent widely used in paints and varnishes, in cleaning products, and as a degreasing and extraction solvent. These widespread uses represent a correspondingly large potential for exposure of the general population, professional painters, and workers in dry cleaning plants and other settings where white spirit is used. The report cites inhalation of vapour as the primary route of human exposure. Exposure of the general population is noted to occur during the domestic use of paints and lacquers, habitation in recently painted rooms, and during the washing of vehicles with products containing white spirit.

The most extensive sections evaluate the large body of data from laboratory experiments and epidemiological studies in humans. In humans, signs of toxicity, identified in epidemiological studies of exposed workers, include central nervous system effects ranging from dizziness and headache to impaired performance of neuropsychological tests. In severe cases, chronic toxic encephalopathy has been diagnosed. In its evaluation of effects on human health, the report gives particular attention to findings from several epidemiological studies of cancer in potentially exposed painters, metal machinists, construction workers, and dry cleaners. Though increased relative risks for cancers of the lung, kidney, and prostate, and for Hodgkin's lymphoma have been reported, the report concludes that inadequacies in the design of these studies preclude the establishment of a causal relationship between exposure to white spirit and an increased risk of cancer in humans.


Wood Dust and Formaldehyde

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 62
1995, viii + 405 pages [E]
ISBN 92 832 1262 2
Sw.fr. 80.-/US $72.00; in developing countries: Sw.fr. 56.-
Order no. 1720062

Evaluates the carcinogenic risk to humans posed by occupational exposures to wood dust and formaldehyde. A number of occupational situations that involve exposure to wood dust also entail exposure to formaldehyde, as in plywood and particle board manufacture, during furniture and cabinet-making, and during parquet floor sanding and varnishing.

The carcinogenic risks of wood dust are evaluated in the first monograph. The highest occupational exposures were noted to occur in wood furniture and cabinet manufacture, especially during machine sanding and similar operations, in the finishing departments of plywood and particle-board mills, and in the workroom air of sawmills and planer mills near chippers, saws, and planers. Citing findings from several recent well-designed case-control studies, the monograph concludes that occupational exposure to wood dust is causally related to adenocarcinoma of the nasal cavities and paranasal sinuses. The evaluation further concluded that the excess risk of cancer is attributable to wood dust per se, rather than to other exposures in the workplace. Wood dust was classified as carcinogenic to humans.

Cancer risk associated with occupational exposure to formaldehyde is assessed in the second monograph. The assessment draws on findings from several cohort and case-control investigations of the relationship between exposure to formaldehyde and cancer of the oral cavity, pharynx, and respiratory tract. Citing inconsistencies in the reported results, the monograph concludes that these epidemiological studies can do no more than suggest a causal role of occupational exposure to formaldehyde in carcinoma of the nasal cavities and paranasal sinuses. The review found no evidence of excess risk for oropharyngeal, laryngeal or lung cancer among exposed workers. Several studies in which formaldehyde was administered to rats by inhalation showed evidence of carcinogenicity. Similar studies in hamsters showed no evidence of carcinogenicity, and studies in mice either showed no effect or were inadequate for evaluation. In rats administered formaldehyde in drinking-water, increased incidences were seen of forestomach papillomas in one study and of leukaemias and gastrointestinal tract tumours in another; two other studies gave negative results. Formaldehyde was classified as probably carcinogenic to humans.


Xylenes

Environmental Health Criteria, No. 190
1997, xvi + 147 pages [E, with summaries in F, S]
ISBN 92 4 157190 X
Sw.fr. 30.-/US $27.00; in developing countries: Sw.fr. 21.-
Order no. 1160190

Evaluates the risks to human health and the environment posed by exposure to xylene and its three isomeric forms: ortho, meta, and para. Xylene is an aromatic hydrocarbon blended into petrol and used in a variety of solvent applications, mainly in the paint and printing industries.

The opening sections, on sources of exposure and behaviour in the environment, note that most xylene present in the environment results from its use as a solvent and its presence in motor vehicle exhaust. The majority of environmental xylene enters the atmosphere directly, where it is readily degraded via photooxidation. The report cites evidence that xylene is rapidly biodegraded in soil and water, though o-xylene is more persistent in soil than the other isomers. Limited evidence suggests low bioaccumulation by fish and invertebrates and low to moderate toxicity, supporting the conclusion that xylene is unlikely to endanger aquatic ecosystems except under the higher exposure conditions found in the vicinity of industrial discharges or following accidental spills.

A section on environmental levels and human exposure summarizes data on concentrations detected in various environmental media, in indoor air, near point sources, and in occupational settings where workers are exposed. Data on levels in food were judged inadequate for evaluation. Inhalation was determined to be the most important route of human exposure. Concerning kinetics and metabolism in laboratory animals and humans, the report cites abundant evidence that xylene is rapidly and efficiently metabolized, with more than 90% biotransformed to methylhippuric acid and excreted in urine.

A review of numerous studies conducted in laboratory animals and in vitro test systems cites evidence of chronic effects on the central nervous system following exposure at moderate concentrations. These findings support the limited data available on humans, where studies suggest that exposure to xylene may have an acute impairing effect on the sensory-motor and information-processing functions of the central nervous system. The report found no evidence that xylene is mutagenic or carcinogenic.


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