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Environmental Health Criteria
Updated February 2002
Environmental Health Criteria, No. 188
1997, xxiv + 550 pages [E, with summaries in F, S]
ISBN 92 4 157188 8; order no. 1160188
Sw.fr. 92./US $82.80; in developing countries: Sw.fr. 64.40
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.
Environmental Health Criteria, No. 189
1997, 205 pages [E, with summaries in F, S]
ISBN 92 4 157189 6; order no. 1160189
Sw.fr. 42./US $37.80; in developing countries: Sw.fr. 29.40
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.
Environmental Health Criteria, No. 190
1997, xvi + 147 pages [E, with summaries in F, S]
ISBN 92 4 157190 X; order no. 1160190
Sw.fr. 30./US $27.00; in developing countries: Sw.fr. 21.
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.
Environmental Health Criteria, No. 191
1997, xviii + 106 pages [E, with summaries in F, S]
ISBN 92 4 157191 8; order no. 1160191
Sw.fr. 27./US $24.30; in developing countries: Sw.fr. 18.90
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.
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; order no. 1160192; in developing countries: Sw.fr. 20.30
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.
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.
Environmental Health Criteria, No. 193
1997, xvii + 70 pages [E, with summaries in F, S]
ISBN 92 4 157193 4; order no. 1160193
Sw.fr. 21./US $18.90; in developing countries: Sw.fr. 14.70
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.
Environmental Health Criteria, No. 194
1997, xx + 282 pages [E, with summaries in F, S]
ISBN 92 4 157194 2; Order no. 1160194
Sw.fr. 60./US $54.00; in developing countries: Sw.fr. 42.
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 9095% 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.
Environmental Health Criteria, No. 195
1997, xviii + 160 pages [E, with summaries in F, S]
ISBN 92 4 157195 0; order no. 1160195
Sw.fr. 36./US $32.40; in developing countries: Sw.fr. 25.20
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.
Environmental Health Criteria, No. 196
1997, xviii + 180 pages [E, with summaries in F, S]
ISBN 92 4 157196 9; order no. 1160196
Sw.fr. 42./US $37.80; in developing countries: Sw.fr. 29.40
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.
Environmental Health Criteria, No. 197
1997, xviii + 83 pages [E, with summaries in F, S]
ISBN 92 4 157197 7; order no. 1160197
Sw.fr. 26./US $23.40; in developing countries: Sw.fr. 18.20
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.
Environmental Health Criteria, No. 198
1998, xx + 140 pages [E, with summaries in F, S]
ISBN 92 4 157198 5; order no. 1160198
Sw.fr. 30./US $27.00; in developing countries: Sw.fr. 21.
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.
Environmental Health Criteria, No. 199
1998, xix + 159 pages [E, with summaries in F, S]
ISBN 92 4 157199 3; order no. 1160199
Sw.fr. 36./US $32.40; in developing countries: Sw.fr. 25.20
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.
Summary of main findings and conclusions
Environmental Health Criteria, No. 200
1998, xxii + 360 pages (English with summaries in French and Spanish)
ISBN 92 4 157200 0
Sw.fr. 72./US $64.80; in developing countries: Sw.fr. 50.40
Order no. 1160200
A section on environmental behaviour discusses what is know about the fate of copper released to the atmosphere, water, and land. Data indicate that most copper is released to land; major sources are mining operations, agriculture, solid waste, and sludge from treatment works. Bioaccumulation, which occurs if the copper is biologically available, can lead to exceptionally high body burdens in certain animals and terrestrial plants. A review of levels detected in different environmental compartments supports the conclusion that, for healthy members of the general population, the major route of exposure is oral, with substantial exposure possible when drinking-water is contaminated with copper.
A section on kinetics and metabolism cites evidence that copper is mainly absorbed through the gastrointestinal tract, where part is excreted through the faeces and the remainder is transported to the liver bound to serum albumin. The liver is the critical organ of copper homoeostasis. When copper exceeds homoeostatic control, its biological toxicity arises from its effects on the structure and function of biomolecules such as DNA, membranes, and proteins.
A review of abundant findings from studies in laboratory animals and in vitro test systems shows wide species variations in toxic effects. Rats exposed to single doses by the oral route showed alterations in blood biochemistry and haematology, and adverse effects on the liver, kidney, and lungs. Long-term exposure in rats and mice demonstrated no overt signs of toxicity other than a dose-related reduction in growth. Studies of chronic toxicity and carcinogenicity were judged inadequate for assessment. Limited data on immunotoxicity suggest some impairment of humoral and cell-mediated immune functions in mice. While studies of neurotoxicity have failed to demonstrate behavioural effects, some neurochemical changes have been reported after oral administration.
An assessment of health effects in humans draws on numerous investigations of copper's role as both an essential and a toxic element, and abundant evidence that adverse effects may arise from both deficient and excessive intakes. Clinically evident deficiency, which is rare in the general population, is characterized by anaemia, neutropenia, and bone abnormalities. Copper toxicity, likewise rare in the general population, usually arises following the consumption of contaminated beverages, including drinking-water, or from accidental or suicidal ingestion of high quantities of copper salts. Symptoms include vomiting, lethargy, acute haemolytic anaemia, renal and liver damage, neurotoxicity, and increased blood pressure and respiratory rates.
The evaluation gives particular attention to the clinical features of population groups known to be especially sensitive to copper toxicity. These include premature infants fed on cow's milk, infants recovering from severe malnutrition, haemodialysis patients, patients suffering from chronic liver disease, and patients with genetically determined disorders of copper homoeostasis, such as Menkes disease, Wilson disease, and hereditary aceruloplasminaemia. The report also cites evidence from several recent dietary surveys indicating suboptimal copper intake in the mean population. Health effects arising from insufficient copper intake, which may have a role in the pathogenesis of cardiovascular disease, were judged to be more important than adverse effects associated with excessive ingestion.
Selected Chloroalkyl Ethers
Environmental Health Criteria, No. 201
1998, xviii + 95 pages
ISBN 92 4 157201 9
Sw.fr. 26.-/US $23.40; in developing countries: Sw.fr. 18.20
Order no. 1160201
This book evaluates the risks to human health and the environment posed by exposure to bis(2-chloroethyl) ether (BCEE), bis(chloromethyl) ether (BCME), and chloromethyl methyl ether (CMME). These three ethers, which are part of the large class of chloroalkyl ethers, are used as solvents and in several industrial processes, including the manufacture of polymers. BCEE is also used in the textile industry, as an intermediate in the manufacture of pharmaceuticals and other chemicals, and as a soil fumigant, insecticide and acaricide. While data on risks to the environment are limited, the report draws on a considerable body of evidence, from laboratory animals and epidemiological studies of exposed workers, indicating that BCME and CMME are potent human carcinogens.
A section on sources of these chemicals in the environment notes that BCEE may enter the environment as a by-product from the chlorination of waste streams containing ethylene or propylene, and as a contaminant in the fungicide metam-sodium. BCME and CMME are released, in small amounts, from industrial activities. Concerning environmental behaviour, the report concludes that BCEE is rapidly volatilized from surface water, does not adsorb to soil or sediment, and may reach groundwater. The chemical may be persistent due to the relative stability of b-chloroalkyl ethers. The report found no evidence that BCEE bioaccumulates or biomagnifies to any significant extent. For BCME and CMME, evidence pointing to extremely short residence times supports the conclusion that levels in the environment are extremely low if not nonexistent.
A section on sources of human exposure draws on limited data indicating that occupational exposure to BCEE may occur, via inhalation or dermal contact, in the dry cleaning and textile industries, or during the processing of gum, lacquer, oil, paint, soap, and tar. For BCME and CMME, data suggest that occupational exposure may occur in laboratory and textile workers, and during the production of anion-exchange resins, selected organic chemicals, and polymers. In occupational settings where vapours of formaldehyde and hydrochloric acid co-exist, BCME may form spontaneously in air. The report also found evidence that the general population may be exposed to BCME and CMME through the use of mosquito coils.The most extensive section evaluates the large number of studies, in laboratory animals and in vitro test systems, conducted to assess toxic effects. BCEE is noted to be acutely toxic by the oral, inhalation and dermal routes. Exposure via inhalation to high concentrations resulted in eye irritation, and congestion, oedema, and haemorrhage in the lungs. Inhalation of BCME resulted in irritation of the eyes and respiratory tract, and necrotizing bronchitis. Exposure to CMME produced similar effects. In vitro testing for mutagenicity produced positive results for all three chemicals. In carcinogenicity studies, animals exposed to BCME showed a significantly elevated incidence of pulmonary adenomas and respiratory tumours. Studies of CMME toxicity have shown an increased incidence of tracheal metaplasia and bronchial hyperplasia in a dose-dependent manner.
The evaluation of effects on human health concentrates on evidence of an increased risk of lung cancer demonstrated in eight epidemiological studies of workers exposed to BCME and CMME. In all of these studies, the type of lung cancer, the standardized mortality ratios, the latency periods, and average age when lung cancer appeared were remarkably consistent. Moreover, the report notes that the type and incidence of lung cancer, seen in relatively young individuals after latency periods as short as two years, are distinct from those caused by tobacco. On the basis of this evidence, the report recommends that exposure to BCME and CMME should be eliminated.
This book evaluates the risks to human health and the environment posed by exposure to 33 non-heterocyclic polycyclic aromatic hydrocarbons (PAH), of which benzo[a]pyrene is the most extensively investigated. Compounds from this large class were selected for evaluation on the basis of abundant data documenting toxic effects, including carcinogenicity. More than 2,000 references to the recent literature are included.
The book opens with a discussion of physical and chemical properties of PAH relevant to their toxicological and ecotoxicological evaluation. Chapter two, on sources of human and environmental exposure, notes that PAH are ubiquitous in the environment, with the largest emissions resulting from incomplete combustion of organic materials during industrial processes and other human activities. The most important sources are identified as coal coking; production of aluminium, iron, and steel; heating in power plants and residences; cooking; motor vehicle traffic; environmental tobacco smoke; and the incineration of refuse. Data on the environmental behaviour of PAH are discussed in chapter three, which cites evidence that PAH accumulate in organisms in water and sediment and in their food, and that sediment and soil are the principal environmental sinks. Since most organisms have a high biotransformation potential for PAH, the report concludes that biomagnification is unlikely to occur.
A chapter on environmental levels and human exposure summarizes results from numerous studies aimed at detecting concentrations in the general environment, in indoor air, and in various occupational settings. For the general population, the main sources of exposure are identified as polluted ambient air, smoke from open fireplaces and cooking, environmental tobacco smoke, contaminated food and drinking-water, and the use of PAH-contaminated products. Evidence shows that PAH are formed during food processing, roasting, frying, and baking. In occupational settings, exposure occurs via the lung and skin, with the highest exposures occurring during the processing and use of coal and mineral oil products, such as in coal coking, petroleum refining, road paving, asphalt roofing, and impregnation of wood with creosotes. High concentrations have also been detected in the air of aluminium production plants using coal/pitch electrodes, and steel and iron foundries.
A review of data on kinetics and metabolism cites evidence that PAH are absorbed through the pulmonary tract, the gastrointestinal tract, and the skin, and are widely distributed throughout the organism following administration by any route. Although these lipophilic compounds have been detected in almost all internal organs, levels are highest in organs rich in lipids. Knowledge about the complex metabolism of PAH, which sheds light on mechanisms of carcinogenic action, is also considered in detail.
The most extensive chapters assess the large number of studies of toxic effects in laboratory mammals, in vitro test systems, and humans, giving particular attention to evidence of carcinogenicity. Findings from animal studies and in vitro tests, which have assessed the toxicity of single PAH, confirm the carcinogenicity of 17 compounds. Many others are known to be mutagenic. While data indicate a relationship between the site of tumour development and the route of administration, PAH can induce tumours at other sites as well, since tissues such as the skin can metabolize PAH to their ultimate metabolites, and metabolites formed in the liver can reach various sites via the blood stream. Current theoretical explanations for the carcinogenic action of PAH are considered in detail. The report also cites animal studies demonstrating the immunotoxic potential of a number of PAH.
In view of the paucity of data on human exposure to single, pure PAH, the chapter on health effects in humans draws on findings from epidemiological studies of occupational and environmental exposures to mixtures of PAH. These studies confirm the association between exposure to PAH and an increased risk of cancer in humans. Increased lung tumour rates linked to exposure were found in coke-oven workers, asphalt workers, and workers in Söderberg potrooms of aluminium reduction plants. The highest risk was found for coke-oven workers. In aluminium plants, adverse effects included increased risk of urinary bladder cancer, asthma-like symptoms, lung function abnormalities, and chronic bronchitis. Adverse effects on the immune system were also documented in several studies of exposed workers. The report further concludes that PAH are almost certainly one of the carcinogenic agents responsible for lung cancers in cigarette smokers.
This book evaluates the risks to human health and
the environment posed by exposure to chrysotile asbestos. Also referred to as white
asbestos, chrysotile is a naturally occurring fibrous hydrated magnesium silicate mineral
having many commercial applications. Chrysotile is released to the environment from
industrial sources. In addition, natural weathering of serpentine rock results in
emissions to air and water.
Environmental Health Criteria, No. 203
1998, xxi + 197 pages
ISBN 92 4 157203 5
Sw.fr. 42.-/US $37.80; in developing countries: Sw.fr. 29.40
Order no. 1160203
Summary of main findings and conclusions
Although the health risks associated with mixed exposures to the main commercial forms of asbestos (crocidolite, amosite, and chrysotile) are well known, the evaluation was undertaken in response to the continuing widespread production and use of chrysotile following the International Labour Organisation's recommendation to discontinue the use of crocidolite asbestos, and taking into consideration that amosite is virtually no longer exploited. The asbestos cement industry is singled out as by far the largest current global user of chrysotile fibres. Main applications include the production of corrugated sheets, flat sheets and building boards, slates, moulded goods, including low-pressure pipes, and high-pressure water pipes. Chrysotile is also used, in much smaller quantities, in the manufacturing of friction products, gaskets, and asbestos paper.
In assessing the health risks posed by chrysotile asbestos, the evaluation faced a number of methodological problems, including the industry-specific nature of exposure-response relationships, and difficulties with the interpretation of exposure data from older studies, which did not differentiate between exposures to amphiboles (crocidolite, amosite) and serpentine (chrysotile) fibres. Conclusions and recommendations reflect the consensus reached by a large group of scientists selected solely on the basis of their contribution to the open scientific literature. Some 500 references to the literature are included in this carefully documented assessment.The report opens with a review of methods used for collecting and analysing samples, followed by a discussion of sources of occupational and environmental exposure. Studies indicate that exposure may occur during mining and milling, processing of asbestos into products, construction and repair activities, and the transportation and disposal of waste products containing chrysotile. Exposure to chrysotile fibres during the construction, maintenance, or demolition of buildings is judged likely to entail high risks. Subsequent sections summarize the levels of chrysotile detected in the environment and in various occupational settings, and review what is known about the uptake, clearance, retention, and translocation of inhaled or ingested fibres.
The most extensive sections review the results of toxicity studies conducted in laboratory mammals and in vitro test systems and of epidemiological studies in occupationally exposed workers. For humans, the report concludes that exposure to chrysotile asbestos poses increased risks for asbestosis, lung cancer, and mesothelioma in a dose-dependent manner, and confirms previous findings that asbestos exposure and cigarette smoking interact to greatly increase the risk of lung cancer. The report did not identify a threshold for carcinogenic risks. Evidence that exposure to chrysotile increases the risk of cancer at sites other than the lung was judged inconclusive.
To reduce the health risks posed by exposure, the report calls for the use of engineering and other control measures in workplace settings where occupational exposure continues to occur, and further concludes that, where safer substitute materials are available, these should be considered for use.
See also: Asbestos and Other Natural Mineral Fibres (Environmental Health Criteria, No. 53)
This book evaluates the risks to human health and
the environment posed by boron, a naturally occurring element widely distributed, in the
form of various inorganic borates, in the oceans, sedimentary rocks, coal, shale, and some
soils. Boron is also used in laundry bleach and in the manufacture of glass, glass
products, fertilizers and herbicides, antiseptics, and pharmaceuticals. Since boron is
widely detected in drinking-water and occurs naturally in fruits, nuts, and vegetables,
the report gives particular attention to health risks associated with exposure of the
general population through diet and drinking-water.
Environmental Health Criteria, No. 204
1998, xviii+ 201 pages (English, with summaries in French and Spanish)
ISBN 92 4 157204 3
Sw.fr. 42.-/US $37.80; in developing countries: Sw.fr. 29.40
Order no. 1160204
Summary of main findings and conclusions
A section on sources of human and environmental exposure cites evidence that boron enters the environment mainly through volatilization from seawater, volcanoes, geothermal steam, and natural weathering of clay-rich sedimentary rock. Although industrial uses account for much smaller releases, the report notes that all of the boron from the sodium perborate contained in detergents ultimately enters the wastewater system, and is not removed by standard water treatment procedures.
The environmental behaviour of boron is covered in the next section, which concludes that boron does not persist in the atmosphere to a significant degree, adsorbs onto soil particles, accumulates in aquatic and terrestrial plants, but does not magnify through the food chain. Numerous findings indicate that boron is an essential micronutrient for higher plants. A section on environmental levels and human exposure cites diet and drinking-water as the principal sources of exposure for the general population. Occupational exposure to boron compounds is judged to be potentially significant, with inhalation of dusts singled out as the most significant route of exposure. Concerning kinetics and metabolism in laboratory animals and humans, numerous studies demonstrate that boric acid and borax are readily absorbed from the gastrointestinal and respiratory tracts, widely distributed, and rapidly excreted in urine.
The most extensive section reviews findings from toxicity studies in laboratory mammals and in vitro test systems. General clinical signs of exposure are described as depression, ataxia, occasional convulsions, decreased body temperature, and violet-red colour of skin and mucous membrances. The review found unequivocable evidence that the male reproductive tract is the principal target of toxicity. The review also cites several recent reports indicating that boron in physiological amounts is beneficial to, if not essential for, higher animals.
An evaluation of the few human studies of toxicity concludes that exposure is associated with short-term and reversible irritant effects on the upper respiratory tract, nasopharynx, and eye. The most frequently observed symptoms involve the gastrointestinal tract and include vomiting, abdominal pain, diarrhoea, and nausea. Less frequently observed symptoms include lethargy, rash, headache, light-headedness, fever, irritability, and muscle cramps. Data on carcinogenicity were judged inadequate for evaluation. In line with findings from animal studies, the review found several recent studies demonstrating that boron is a dynamic trace element that can affect the metabolism or utilization of numerous substances essential to life processes.
On the basis of all evidence considered, the report established a tolerable intake for boron of 0.4 mg/kg body weight per day.
Polybrominated Dibenzo-p-dioxins and Dibenzofurans
Environmental Health Criteria, No. 205
1998, xxi + 303 pages (English, with summaries in French and Spanish)
ISBN 92 4 157205 1
Sw.fr. 66.-/US $59.40; in developing countries: Sw.fr. 46.20
Order no. 1160205
Summary of main findings and conclusions
This book evaluates the risks to human health and the environment posed by exposure to polybrominated dibenzo-p-dioxins (PBDDs) and polybrominated dibenzofurans (PBDFs). Of no commercial use, these compounds are generated as unwanted by-products in various industrial and combustion processes and have been detected as contaminants in a number of brominated organic chemicals, many of which are used as flame retardants.
Thermolysis of brominated flame retardants is an important source of emissions, as is the incineration of products containing these flame retardants, most notably scrap computers and business machines. PBDDs and PBDFs have also been detected in emissions of motors using both leaded petrol and unleaded petrol, with and without catalytic converters, and in emissions of diesel engines.
In view of the complexity of these compounds, the problems with analytical procedures, and substantial gaps in the experimental database, the report makes a special effort to determine the extent to which the environmental behaviour and toxic effects of PBDDs and PBDFs resemble those of their better characterized chlorinated analogues, polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). An effort is also made to determine the extent to which PBDDs and PBDFs contribute to the overall hazard posed by environmental "dioxins".
The opening sections consider currently available analytical methods for detection and analysis, and discuss the principal sources of human and environmental exposure. Although data are limited, the available evidence confirms formation of PBDDs and PBDFs during fire accidents, especially when electrical appliances are involved, during the use of flame retardants and fire extinguishers, during waste disposal and treatment, and during combustion processes in engines. Current environmental levels are judged to be much lower than those for the ubiquitous PCDDs and PCDFs. Evidence suggests that occupational exposure may occur in a variety of workplaces. Workers at greatest risk are those employed in the plastic and recycling industry, where brominated flame retardants or products containing them are used, firemen, and clean-up personnel associated with fires. Some monitoring results are also available for exposures in workplaces equipped with a number of electrical appliances continually in use, such as displays and computer monitors.
A section on environmental behaviour cites evidence that these compounds are similar to their chlorinated analogues, with preferential distribution to carbon- or fat-rich compartments and long persistence. Data on kinetics and metabolism are assessed in the next section, which concludes that these compounds are distributed throughout the body, with major deposits found in liver and adipose tissue, followed by skin and muscle.
Data from experimental studies of toxicity support the conclusion that the thymus, lymphatic tissue, and liver are the principal targets of toxic action. Thymus atrophy and other signs of immunotoxicity were the effects most consistently seen in laboratory animals. Data on human exposures and health effects were judged inadequate to support an assessment of hazards for the general population or a recommended safe level of exposure.
In view of the growing worldwide production and use of brominated flame retardants as additives to a series of polymers, the report concludes that the amount of bromine-containing waste will be increasing in the future, and that electronic scrap from casings and printed circuit boards of computers, flame-retarded with brominated compounds, will reach the waste streams as a potentially major source of release to the environment. As the potential for toxic action of these compounds is judged similar to that of their chlorinated analogues, the report recommends that every effort should be made to prevent environmental pollution with PBDDs and PBDFs. To avoid release to the environment, the report further concludes that brominated flame retardants should be phased out and that all products flame-retarded with bromine compounds should be labelled and disposed of only in properly constituted waste incinerators designed to minimize emissions.
Methyl tertiary-butyl Ether
Environmental Health Criteria, No. 206
1998, xix + 199 pages
ISBN 92 4 157206 X
Sw.fr. 42.-/US $37.80; in developing countries: Sw.fr. 29.40
Order no. 1160206
Summary of main findings and conclusions
This book evaluates the risks to human health and the environment posed by exposure to methyl tertiary-butyl ether (MTBE). Used almost exclusively as a fuel additive, MTBE is blended with gasoline to provide both octane enhancement and an increase in oxygen content. MTBE currently numbers among the 50 chemicals produced in the highest volume worldwide. Production and use are expected to increase, particularly in countries where oxygenated or reformulated gasolines are required in national programmes aimed at reducing ambient air levels of carbon monoxide and ozone or benzene and other volatile hydrocarbons.
A summary of sources of human and environmental exposure is followed by an assessment of what is known about the chemical's environmental behaviour and fate. Studies demonstrate that, after discharge into air, MTBE largely remains in the air, with smaller amounts entering soil and water. Although atmospheric MTBE can partition into rain, data indicate that atmospheric transformation by hydroxyl radicals is a more important pathway of removal.
Concerning environmental levels and human exposure, evaporative emissions from oxygenated gasoline are identified as the main source of exposure for the general population. Widespread exposure via inhalation is noted to occur during time spent at service stations, while driving cars, in public parking garages, and in homes with attached garages. The report also cites data on exposure levels obtained in numerous studies of urban air, in facilities where MTBE is manufactured or blended, and in such occupational settings as service stations, garages, and the transportation of neat MTBE and fuel mixtures through pipelines, barges, railroad cars, and trucks.
A review of the kinetics and metabolism of MTBE draws on toxicokinetic data derived from controlled studies in healthy adult volunteers and in occupationally exposed workers. Data indicate that MTBE is rapidly absorbed into the circulation following inhalation. In rodents, the compound is likewise rapidly absorbed and distributed following exposure by both inhalation and oral routes.
From studies in laboratory animals, the report identifies the principal signs of intoxication as depression of the central nervous system, ataxia, and laboured respiration. Most effects on the central nervous system are transient. From the few studies available, the report concludes that MTBE is moderately irritating to the skin and eyes and induces slight to severe respiratory irritation. Repeated exposure results primarily in increases in organ weights and histopathological effects in the kidney of rats and the liver of mice. The report found no evidence of adverse effects on reproduction, genotoxicity, or mutagenicity. Although limited carcinogenicity studies showed significant increases in tumour incidence, the report judged these findings inconclusive and thus inadequate to support an assessment of carcinogenic risk in humans.
An evaluation of health effects in humans gives major attention to several recent "outbreaks" of health complaints in the USA which occurred shortly after the introduction of MTBE-blended gasoline. Symptoms most widely reported by consumers include headache, eye and nose irritation, cough, nausea, dizziness, and disorientation. The report also draws on findings from epidemiological studies of occupationally exposed workers and experimental studies of volunteers exposed in inhalation chambers. Based on this evaluation, the report concludes that MTBE alone, under common conditions of inhalation exposure, is not likely to induce adverse acute health effects in the general population. In making this conclusion, the report also notes that the potential effects of mixtures of gasoline and MTBE, as well as the manner in which most people are exposed to MTBE via oxygenated fuels, have not been examined experimentally or in prospective epidemiological studies.
Environmental Health Criteria, No. 207
1998, xviii + 159 pages (English with summaries in French and Spanish)
ISBN 92 4 157207 8
Sw.fr. 36./US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160207
Summary of main findings and conclusions
This book evaluates the risks to human health and the environment posed by exposure to acetone. Acetone is widely used as an intermediate in chemical production and as a solvent for resins, paints, inks, varnishes and lacquers and in adhesives, thinners, and clean-up products. Pharmaceutical applications include use as an intermediate and solvent for drugs, vitamins, and cosmetics. Acetone is also used in food processing as an extraction solvent for oils and fats and as a precipitation agent in the purification of starches and sugars.
A discussion of sources of human and environmental exposure covers both natural and anthropogenic sources. In the mammalian body, studies show that acetone is formed endogenously from fatty acid oxidation, is found as a natural metabolic component in blood, urine, and human breath, and is exhaled. Acetone has been detected in a variety of plants and foods and is emitted, in vapour form, from several tree species. Acetone also occurs naturally as a biodegradation product of sewage, solid wastes, and alcohols, and as an oxidation product of humic substances. Concerning man-made sources of emissions, the report identifies the most important sources as wastewater discharges from many industries, leaching from industrial and municipal landfills, and evaporation of acetone solvent from coating products such as paints, cleaners, varnishes, and inks. Acetone may also be emitted from the combustion of wood and in exhaust from automobile, diesel, and turbine engines.
A review of data on environmental behaviour and fate cites evidence from several studies of acetone levels detected in air, water, soil, and biological samples. Studies indicate that atmospheric acetone is degraded by a combination of photolysis and reaction with hydroxyl radicals. Acetone is readily biodegradable in soil and water. A discussion of kinetics and metabolism draws on extensive data from absorption and tissue distribution studies, radiolabelled metabolic and kinetic studies, and studies of elimination and excretion. Abundant evidence shows that acetone is rapidly absorbed via the respiratory and gastrointestinal tracts and mainly distributed to non-adipose tissues. Under normal circumstances, metabolism is the predominant route of elimination. Studies in humans confirm the importance of such variables as diet, exercise, and alcohol consumption as factors affecting kinetics.
A review of toxicity studies in laboratory mammals and in vitro test systems concludes that acetone is only mildly toxic to the liver, unless physiological processes are compromised, as in diabetes mellitus. Some adverse effects on development and reproductive function have been reported. One of the major adverse effects identified is acetone's ability to potentiate the toxicity of other chemicals. Extensive studies on the mechanisms of toxic action help elucidate the possible mechanisms by which acetone enhances the neurotoxicity of ethanol.
A section on health effects in humans evaluates findings from numerous case reports of accidental or intentional poisoning, studies conducted in healthy volunteers, and studies of occupationally exposed workers. The most commonly reported effects include irritation to the nose, eyes, throat, and trachea. Studies also show that acetone can produce neurobehavioural and other changes, including headache, dizziness, confusion and, at high vapour concentrations, central nervous system depression and narcosis. The report found no evidence that acetone is either a skin or a respiratory tract sensitizer. Human studies confirm the ability of acetone to potentiate, and in some instances antagonize, the toxic effects of other chemicals. Those at greatest risk include diabetics, alcoholics, and those undergoing prolonged fasting. The report found no evidence that acetone is genotoxic or carcinogenic.
Concerning effects on the environment, the report concludes that acetone, even in the case of accidental spills, is unlikely to have a major or lasting adverse effect on the ecosystem.
Environmental Health Criteria, No. 208
1999, xviii + 177 pages (English, with summaries in French and Spanish)
ISBN 92 4 157208 6
Sw.fr. 42.-/US $37.80; In developing countries: Sw.fr. 29.40
Order no. 1160208
Summary of main findings and conclusions
Flame Retardants: Tris(chloropropyl) Phosphate and Tris(2-chloroethyl) Phosphate
Environmental Health Criteria, No. 209
1998, xix + 106 pages (English with summaries in French and Spanish)
ISBN 92 4 157209 4
Sw.fr. 27./US $24.30; in developing countries: Sw.fr. 18.90
Order no. 1160209
Summary of main findings and conclusions
This book evaluates the risks to human health and the environment posed by exposure to three flame retardants: tris(1-chloro-2-propyl) phosphate (TCPP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and tris(2-chloroethyl) phosphate (TCEP). In view of their many similarities, TCPP and TDCPP are covered together. Data on all three flame retardants are extremely limited and largely confined to studies of environmental levels and adverse effects detected in experimental animals and in vitro test systems.
The monograph on TCPP and TDCPP describes manufacturing processes and summarizes current uses. The vast majority of TCPP is used in rigid polyurethane foams, with main applications in insulation for buildings and in refrigerator casings. TDCPP is likewise added as a flame retardant to polyurethane foam and has some additional applications as a flame retardant for non-woven fabrics. For both chemicals, studies show that residues are found infrequently and at low concentrations in food items. For TCPP, traces have been detected in industrial and domestic effluents but not in surface water or drinking-water. Traces of TDCPP have been detected in sewage effluent, river water, seawater, drinking-water, and water sediment, and in fish. In view of the low volatility of both chemicals, the report concludes that human exposure from these sources will be very low and will not present an acute health hazard for the general population. Likewise, no adverse effects on the environment are anticipated from the use of either of these flame retardants.
Experimental studies of TCPP in laboratory animals demonstrate low to moderate toxicity by the oral, dermal, and inhalation routes. Tests indicate that the chemical is neither a skin nor an eye irritant. No studies were available to evaluate reproductive toxicity, immunotoxicity, or carcinogenic potential. In vitro and in vivo mutagenicity studies produced negative results.
Toxicity studies of TDCPP show low to moderate acute toxicity by the oral route and low acute toxicity by the dermal route. The report found no evidence of teratogenicity or mutagenicity. A single carcinogenicity study found an increased occurrence of several tumours at all exposure levels tested in both male and female rats. In the absence of data on the mechanisms of carcinogenic action, the relevance of these findings to humans could not be assessed. The limited studies of occupationally exposed workers were judged inadequate for evaluation.
The second monograph evaluates TCEP, a flame retardant with declining uses in the production of liquid polyester resins and in textile back-coating formulations. Traces have been detected in river water, seawater, drinking-water, sediment, fish and shellfish, and a few food items. Experimental studies show low to moderate acute oral toxicity. In repeat dose experiments, TCEP caused adverse effects on the brain, liver and kidneys. The report concludes that TCEP is not an irritant to the eye or skin and is not teratogenic, although some adverse effects on the fertility of male rats and mice have been demonstrated. Data indicating low environmental exposures support the conclusion that TCEP poses a very low risk of adverse health effects for the general population. Use of TCEP is not expected to cause any adverse effects on the environment.
A state-of-the-art review of methods
and procedures for assessing the risks to human health posed by environmental chemicals.
Addressed to regulatory authorities, risk managers and other decision-makers, the book
aims to demystify the principles of risk assessment and thus encourage wider use of this
powerful tool for protecting populations. Since the detection of chemical hazards may have
socioeconomic and political consequences, the book gives particular attention to methods
for the accurate identification of risks and determination of their severity.
Principles for the Assessment of Risks to Human Health from Exposure to Chemicals
Environmental Health Criteria, No. 210
1999, xx + 110 pages [E, with summaries in F, S]
ISBN 92 4 157210 8
Sw.fr. 29.-/US $26.10; in developing countries: Sw.fr. 20.30
Order no. 1160210
The book has four chapters covering each logical step in the process of risk assessment. The first, on hazard identification, explains how data on a chemical's toxicity and mode of action can be used to determine whether the chemical will cause adverse effects on health. The strengths and limitations of different types of data are discussed together with criteria commonly used to establish causality. Methods for assessing dose-response relationships are reviewed in chapter two, which explains how to characterize the relationship between the dose administered or received and the incidence of an adverse effect.
Exposure assessment is covered in the next chapter, which describes methods for determining the nature and extent of contact with chemical substances and discusses the characteristics of exposure in the general environment, in the workplace, and from consumer products. The final chapter explains the procedure of risk characterization as a decision-making tool that brings together estimates of exposure levels and risks and summarizes sources of uncertainty in the scientific data. Practical options for risk management are presented as a range of regulatory, non-regulatory, economic, and technological measures.
Evaluates the findings of close to
600 studies aimed at determining whether the health risks associated with tobacco use are
enhanced by co-exposure to numerous chemical, biological, and physical agents commonly
found in the workplace. Co-exposures in the domestic and general environment, which are
especially important in newly industrializing countries, are also considered in this
comprehensive review. Although all forms of tobacco use are covered, particular attention
is given to risks arising from exposure to mainstream and sidestream smoke from
Health Effects of Interactions between Tobacco Use and Exposure to Other Agents
Environmental Health Criteria, No. 211
1999, xx + 149 pages [E, with summaries in F, S]
ISBN 92 4 157211 6
Sw.fr. 36.-/US $32.40; in developing countries: Sw.fr. 25.20
Order no. 1160211
The book has four chapters. The first summarizes what is known about the health risks caused by tobacco use. A brief overview of the history of tobacco use is followed by a detailed explanation of the chemistry of processed tobacco and the many toxic compounds found in tobacco and in mainstream and sidestream smoke. The chapter also includes an overview of all documented acute and chronic adverse effects of tobacco, including smokeless tobacco.
The second and most extensive chapter evaluates the evidence on health effects caused by interactions between tobacco smoke and asbestos, non-asbestos fibres, seven inorganic chemicals, five organic chemical agents, including ethanol, four physical agents, and seven biological agents, including two widespread infectious agents. The chapter also includes an explanation of the concept of interaction and how it can be measured, a discussion of vector effects, whereby cigarettes become contaminated with toxic chemicals in the workplace, and a review of data indicating that tobacco smoking can alter the metabolism of therapeutic drugs and other chemicals.
Chapter three considers whether adverse effects following co-exposure to tobacco smoke and other agents are separate effects or possible interactions. The report found evidence for synergism in the production of adverse effects, including cancer, between tobacco smoking and exposure to asbestos, ethanol, silica, and radiation. The report also found evidence that tobacco smoking affects the health risks of exposure in coal mining, pesticide handling, and in the rubber and petroleum industries. In addition, tobacco smoking can increase the risk of byssinosis produced by exposure to cotton dust, and nasal cancer caused by exposure to wood dusts.
On the basis of this evaluation, the final chapter concludes that all possible measures should be taken to eliminate tobacco use, particularly smoking. To avoid interaction with occupational exposure and to eliminate hazards arising from exposure to environmental tobacco smoke, the report concludes that smoking in the workplace should be prohibited.
Summarizes current understanding of
the complex interactions between chemicals, the immune system, and target organs that lead
to manifestations of allergic hypersensitivity and autoimmunity. Noting that the incidence
of allergic disorders has increased significantly in many countries, the book responds to
the urgent need to improve methods for detecting potential allergens and predicting their
effects in both individuals and populations. The need for better preventive strategies and
therapeutic options is also considered, particularly in view of the high costs of allergic
disorders in terms of health care and time lost from work.
Principles and Methods for Assessing Hypersensitization Associated with Exposure to Chemicals
Environmental Health Criteria, No. 212
1999, xxix + 399 pages [E, with summaries in F, S]
ISBN 92 4 157212 4
Sw.fr. 84.-/US $75.60; in developing countries: Sw.fr. 58.80
Order no. 1160212
Addressed to researchers, the book concentrates on what is known about the mechanisms of sensitization and autoimmunity elicited by numerous industrial chemicals, adjuvant environmental factors, such as air pollution, tobacco smoke, and ultraviolet radiation, and food allergens with a proven involvement of the immune system. Although a large number of allergies are covered, particular attention is given to asthma and contact dermatitis as major occupational diseases undergoing intensive investigation. Throughout, a special effort is made to identify lines of investigation that will lead to a better understanding of fundamental mechanisms and thus improve the prospects for treatment and prevention. Over 1000 references to the literature are included.
The book opens with a detailed explanation of the structure and functional processes of the immune system, followed by a discussion of the mechanisms by which chemicals can disrupt these functions. Also discussed are fundamental concepts of immunosuppression, immunodeficiency, and immunological tolerance that help explain the mechanistic basis of sensitization, allergic responses, and autoimmunity.
Chapter two provides an overview of mechanisms involved in four major types of hypersensitivity and in autoimmunity. Mechanisms are illustrated with examples of diseases from occupational asthma, through myasthenia gravis, to chronic beryllium disease where exposure to environmental chemicals might play a role. The numerous hypotheses put forward to explain the mechanisms of autoimmune reactions are also critically assessed. Factors influencing allergenicity are covered in chapter three, which concentrates on the many complex endogenous and exogenous factors that govern the induction of allergic responses.
Against this background, chapter four discusses clinical aspects of the most important allergic diseases. These include allergic contact dermatitis, atopic eczema, allergic rhinitis and conjunctivitis, allergic asthma caused by contact with chemicals, food allergy, and autoimmune diseases associated with drugs, chemicals, and environmental factors. Each disease is profiled in terms of its epidemiology, clinical manifestations, etiology, pathogenesis, diagnosis, and strategies for treatment and prevention.
The remaining chapters review the epidemiology of asthma and allergic disease, including trends over time in different geographical regions, describe procedures for hazard identification through the demonstration of allergenicity, and explain how the principles of risk assessment can be applied to allergy.
The book concludes with a glossary of terms, followed by 15 precise recommendations for the protection of human health and a list of priorities for further research.
Environmental Health Criteria, No.
1999, xxiv + 464 pages [E, with summaries in F, S]
ISBN 92 4 157213 2
Sw.fr. 96./US $86.40; in developing countries: Sw.fr. 67.20
Order no. 1160213
Evaluates the risks to human health and the environment posed by exposure to carbon monoxide, a colourless, odourless gas produced by both natural and anthropogenic processes. Concerns about the potential health effects of exposure have been addressed in extensive studies with both humans and a range of animal species. Although studies of carbon monoxide poisoning are included, the report gives major attention to possible health risks linked to the relatively low concentrations that characterize most exposures. The report also aims to identify subpopulations that may be especially susceptible to adverse health effects. Close to 1000 references are included in this comprehensive assessment.
Concerning environmental levels arising from human activities, highway vehicle emissions are considered the principal source, followed by emissions from non-highway transportation sources, other fuel combustion sources, industrial processes, and solid waste disposal. Evidence from monitoring stations supports the conclusion that environmental concentrations are declining, reflecting the efficacy of emission control devices on newer vehicles. The report also considers the factors that contribute to indoor concentrations, with cigarette smoke singled out as a major source.
A chapter on environmental distribution and transformation summarizes what is known about the environmental fate of carbon monoxide, its contribution to ozone production in the troposphere, and its possible role in global warming. Sources of personal exposure are considered in the next chapter, which concludes that the most important exposures for the general population occur in the vehicle and indoor macroenvironments. Several occupations involving an increased risk of high exposures are also identified. Toxicokinetics and mechanisms of action are reviewed in the next chapter, which discusses the many factors that influence the concentrations of carboxyhaemoglobin in blood, and summarizes what is known about the primary mechanisms by which carboxyhaemoglobin formation exerts its toxic effects.
The remaining chapters consider adverse effects on health. A review of the abundant findings from animal studies helps elucidate the mechanisms of carbon monoxide toxicity. Studies of developmental toxicity provide strong evidence that maternal exposure produces reductions in birth weight, cardiomegaly, delays in behavioural development, and disruptions in cognitive function.
A chapter on health effects in humans considers numerous investigations of adverse effects linked to typical ambient exposure levels. Findings are summarized in terms of damage to the cardiovascular and respiratory systems, effects on neurobehavioural functions, developmental toxicity, and other systemic effects. Also considered are the effects of exposure at high altitudes, in users of psychoactive drugs, and in combination with exposure to other air pollutants.
An evaluation of high-risk groups concludes that patients with reproducible exercise-induced ischaemia are a sensitive group at increased risk for experiencing adverse health effects. The report also found evidence indicating that exposure may cause an increased risk of sudden death from arrhythmia in patients with coronary artery disease. The report further concludes that exposure during pregnancy and early childhood carries a number of important risks.
Concerning accidental exposure to high concentrations, the report concludes that carbon monoxide poisoning occurs frequently, has severe consequences, including immediate death, involves complications and late sequelae, and is often overlooked.
Among its many other conclusions, the report calls for better education of the general population about the risks of exposure, especially in individuals with cardiovascular and respiratory disease, and better awareness among medical professions of the dangers of carbon monoxide exposure during pregnancy.
Environmental Health Criteria, No. 215
1999, xxi + 356 pages [E, with summaries in F, S]
ISBN 92 4 157215 9
Sw.fr. 72./US $64.80; in developing countries: Sw.fr. 50.40
Order no. 1160215
Evaluates the risks to human health and the environment posed by exposure to vinyl chloride, a colourless, flammable gas manufactured almost exclusively for use in the production of polyvinyl chloride (PVC). PVC is used to produce plastic materials having wide applications in the building sector, packaging, electrical appliances, medical care, agriculture, the automotive industry, and toys.
Conclusive evidence that vinyl chloride causes cancer in humans led to the lowering, in the early 1970s, of occupational exposure limits in several countries. At the same time, many countries imposed restrictions on the levels of residual vinyl chloride permitted in PVC, thus reducing the risk that residues in packaging materials might contaminate food items, pharmaceutical products, and cosmetics.
A chapter on sources of human and environmental exposure covers production levels and processes, noting the recent geographical expansion of production plants to South-east Asia, Eastern Europe, the Indian subcontinent, and oil-producing countries. Production technologies that lead to lower residual levels of PVC are also briefly described. A review of data on the environmental fate of vinyl chloride notes that environmental releases are almost entirely in the vapour phase. Vinyl chloride is rapidly volatilized and removed from surface water and soil, but is not easily biodegraded. Evidence suggests some bioaccumulation within the food chain, but no biomagnification.
Concerning human exposure, the report concludes that atmospheric concentrations in ambient air are low, resulting in very little exposure of the general population. Much higher concentrations have been recorded near industry and waste disposal sites, and following accidental spills, including spills of chlorinated solvents in dry cleaning shops. Findings confirm a reduced risk of exposure for the general population via residues in packaging materials. The report identifies inhalation as the main route for occupational exposure, which occurs primarily in plants producing vinyl chloride and PVC.
A chapter on kinetics and metabolism in laboratory animals and humans concludes that vinyl chloride is rapidly absorbed and widely distributed following exposure via the inhalation and oral routes. Following inhalation, the main metabolic route involves oxidation to form chloroethylene oxide, which is rapidly transformed to chloroacetaldehyde.
Effects on laboratory mammals and in vitro test systems have been extensively studied. The compound shows low acute toxicity when administered by inhalation. Long-term feeding studies in several species show significantly increased incidences of liver angiosarcoma, hepatocellular carcinoma, and tumours at several other organ sites.
An assessment of effects on humans draws on clinical findings following accidental exposures, supported by a large number of well-designed epidemiological studies of occupationally-exposed workers. Apart from defining the symptoms of "vinyl chloride illness", these studies provide strong and consistent evidence that vinyl chloride causes the rare tumour, angiosarcoma of the liver. Brain tumours and hepatocellular carcinoma may also be associated with exposure, though the evidence is less conclusive.
On the basis of this analysis, the report calls for measures to minimize emissions at production sites and sanitary landfills, and to ensure low residual levels in PVC. Moreover, as vinyl chloride is a known carcinogen, the report stresses the need to keep occupational exposures as low as possible and to educate workers about the risks involved and the need for safe working procedures.
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.
Environmental Health Criteria, No. 217
1999, xv + 105 pages [E, with summaries in F, S]
ISBN 92 4 157217 5
Sw.fr. 27./US $24.30; in developing countries: Sw.fr. 11.20
Order no. 1160217
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.
Environmental Health Criteria, No. 218
Tris(2-butoxyethyl) Phosphate, Tris(2-ethylhexyl) Phosphate and Tetrakis(hydroxymethyl) Phosphonium Salts
Evaluates the risks to human health and the environment posed by exposure to selected flame retardants, including chemicals widely used to treat textiles. Although data were inadequate to support a full scientific evaluation, the report reaches several preliminary conclusions concerning the likelihood of risks to human health.
Compounds are covered in separate monographs. Tris(2-butoxyethyl) phosphate (TBEP) is covered in the first. TBEP is used in floor polishes and as a plasticizer in rubber and plastics. Studies of concentrations in various environmental samples show that TBEP is readily biodegradable. Most potential exposure of the general population arises from the use of TBEP in packaging materials for food and from the possible contamination of drinking-water from synthetic rubbers used in plumbing washers. The report concludes that exposure from both sources is very low. The risk to workers, exposed by the dermal route during manufacturing, was likewise judged to be very low. Studies in experimental animals indicate that the liver is the target organ for TBEP toxicity. Data on other toxic effects were judged to be weak or inconsistent.
Tris(2-ethylhexyl) phosphate (TEHP) is covered in the second monograph. TEHP is used as a flame retardant, a plasticizer for polyvinyl chloride and cellulose acetate, and a solvent. While the compound has not been detected in outdoor air, some studies have found concentrations in indoor air. The limited data on environmental fate indicate that the compound is rapidly biodegraded in natural waters. In experimental animals, the compound demonstrates low acute toxicity. Studies conducted in rats revealed no toxic effects. Although some long-term studies suggest carcinogenic potential, the report concludes that TEHP does not represent a significant carcinogenic risk to humans. In studies conducted in human volunteers, no skin irritation was reported. The report concludes that the risk to both the general population and occupationally-exposed workers is very low.
The final and most extensive monograph evaluates tetrakis(hydroxymethyl) phosphonium (THP) salts. These compounds are the major class of chemicals used as flame retardants for cotton, cellulose, and cellulose-blend fabrics. Data were considered inadequate to support an evaluation of effects on the environment. Studies conducted in animals show moderate acute toxicity and low dermal toxicity. The liver is the main target organ for toxic effects in experimental animals. The report found no convincing evidence that fabrics treated with THP salts are mutagenic or carcinogenic. Concerning possible migration from textiles, the report cites evidence that the flame retardant polymer is not released during cleaning processes that would normally be employed by consumers.
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.
Dinitro-ortho-cresolEnvironmental Health Criteria, No. 220
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.
Environmental Health Criteria, No. 221
2001, xxii + 360 pages [E, with summaries in F, S]
ISBN 92 4 157221 3
Sw.fr. 48./US $43.20
In developing countries: Sw.fr. 36.60
Order no. 1160221
Zinc is common element in the natural environment. Apart from artificially reduced zinc metal, it exists in the divalent state Zn (II) in the environment and it is an essential element for most organisms. It is well known that zinc deficiency causes numerous effects in humans, including neurosensory changes, growth retardation and delayed wound healing, but most people obtain sufficient amount of zinc from their diet. On the other hand, it is reported that high doses of zinc causes gastrointestinal distress, nausea and diarrhoea.
This book evaluates the risks to human health and the environment posed by exposures to zinc. Environmental concentrations of zinc are strongly determined by local geological and anthropogenic influences and thus vary substantially. The main anthropogenic sources of zinc are mining, zinc production facilities, iron and steel production, corrosion of galvanized structures, coal and fuel combustion, waste disposal and incineration, and the use of zinc-containing fertilizers and pesticides. Concentrations in plants and animals are higher near anthropogenic point sources of zinc contamination.
A review of animal toxicology studies concludes that the toxicity of zinc to laboratory animals is not high. However, high zinc doses causes weakness, anorexia, anaemia, diminished growth and effects on the liver and kidney. Increases in zinc concentrations in the bodies of experimental animals exposed to zinc are accompanied by reduced levels of copper, suggesting that some of the signs of toxicity ascribed to exposure to excess levels of zinc may be caused by zinc-induced copper deficiency.
Overall evaluation suggests that normal, healthy individuals not exposed to zinc in the workplace are at potentially greater risk from the adverse effects associated with zinc deficiency than from those associated with normal environmental exposure to zinc because of its relatively low toxicity in humans and the limited sources of human exposure.
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
Arsenic and Arsenic Compounds
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.
Environmental Health Criteria Series, No.
2001, 187 pages [E]
ISBN 92 4 157225 6
Swiss francs: 42./US $37.80
In developing countries: Swiss francs 29.40
Order no. 1160225
This publication is intended as a tool for use by public health officials, research and regulatory scientists and risk managers. It seeks to provide a scientific framework for the use and interpretation of reproductive toxicity data from human and animal studies. It also discusses emerging methodology and testing strategy in reproductive toxicity.
The text focuses on approaches to assessing reproductive toxicity in males and females, including sexual dysfunction and infertility, and many aspects of developmental toxicity (following both prenatal and postnatal exposure), from conception to sexual maturation. It is an overview of the major scientific principles underlying hazard identification, testing methods and risk assessment strategies in human reproductive toxicity. It also discusses the evaluation of reproductive toxicity data in the context of the extensive risk assessment methodology that has emerged over the past 10-15 years.
The first two chapters provide an introduction, summary and recommendations for improving the knowledge base to allow effective control and and intervention strategies for preventing reproductive and developmental toxicity. Chapter 3 discusses basic reproductive physiology and the relative vulnerability of specific reproductive structures and processes and provides the scientific background for understanding specific methods and procedures used in reproductive toxicology. Chapter 4 focuses on methods for assessing and evaluating altered sexual function and fertility.
Chapter 5 addresses methodologies for assessing developmental toxicity, defined as any effect interfering with normal development both before and after birth resulting from exposure of either parent prior to conception, exposure during prenatal development or exposure postnatally to the time of sexual maturation. Chapter 6 deals with the general principles of risk assessment for reproductive toxicity and identifies areas where research is needed. An appendix provides working definitions for the terminology used in the monograph.
This book evaluates the risks to human health and the environment posed by exposures to palladium. The general population is primarily exposed to palladium through dental alloys or jewellery. There were case reports referring to palladium sensitivity associated with exposure to palladium-containing dental restorations, the symptoms being contact dermatitis, stomatitis or mucositis and oral lichen planus.
Palladium ions are considered to be highly toxic to aquatic organisms. However, due to palladium’s high economic value, emissions of palladium from point sources are currently minimal. Increased use of catalytic converters may increase palladium emissions from diffuse sources. It was recommended that these emissions should be controlled to be as low as possible.
and Methods for the Assessment of Risk from Essential Trace Elements
Although it includes examples, this monograph is not a compendium of assessments on ETEs, nor is it a textbook detailing the scientific basis of risk assessment of the derivation of dietary reference intakes.
Described in the book is the process of risk assessment which begins with the selection of the database for a particular ETE. A weight-of-evidence approach is then used for hazard identification, selecting relevant end-point of deficient and excess exposures. Next, the probability of risk and the severity of various effects are quantified and critical effects are selected. The AROI is then established by balancing end-points of comparable health significance. At this time, the exposure assessment is conducted. Finally, a risk characterization enumerating the strengths and weaknesses of the databases is performed, integrating the AROI and exposure assessment.
ISBN 92 4 157227 2
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