WHO/SDE/WSH/03.04/64 English only
Trihalomethanes in Drinking-water Background document for development of WHO Guidelines for Drinking-water Quality
______________________________ “Brominated trihalomethanes” and “Total trihalomethanes” originally published in Guidelines for drinking-water quality, 2nd ed. Vol. 2. Health criteria and other supporting information. Geneva, World Health Organization, 1996; “Chloroform” originally published in Guidelines for drinking-water quality, 2nd ed. Addendum to Vol. 2. Health criteria and other supporting information. Geneva, World Health Organization, 1998.
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Preface One of the primary goals of WHO and its member states is that “all people, whatever their stage of development and their social and economic conditions, have the right to have access to an adequate supply of safe drinking water.” A major WHO function to achieve such goals is the responsibility “to propose ... regulations, and to make recommendations with respect to international health matters ....” The first WHO document dealing specifically with public drinking-water quality was published in 1958 as International Standards for Drinking-water. It was subsequently revised in 1963 and in 1971 under the same title. In 1984–1985, the first edition of the WHO Guidelines for Drinking-water Quality (GDWQ) was published in three volumes: Volume 1, Recommendations; Volume 2, Health criteria and other supporting information; and Volume 3, Surveillance and control of community supplies. Second editions of these volumes were published in 1993, 1996 and 1997, respectively. Addenda to Volumes 1 and 2 of the second edition were published in 1998, addressing selected chemicals. An addendum on microbiological aspects reviewing selected microorganisms was published in 2002. The GDWQ are subject to a rolling revision process. Through this process, microbial, chemical and radiological aspects of drinking-water are subject to periodic review, and documentation related to aspects of protection and control of public drinkingwater quality is accordingly prepared/updated. Since the first edition of the GDWQ, WHO has published information on health criteria and other supporting information to the GDWQ, describing the approaches used in deriving guideline values and presenting critical reviews and evaluations of the effects on human health of the substances or contaminants examined in drinkingwater. For each chemical contaminant or substance considered, a lead institution prepared a health criteria document evaluating the risks for human health from exposure to the particular chemical in drinking-water. Institutions from Canada, Denmark, Finland, France, Germany, Italy, Japan, Netherlands, Norway, Poland, Sweden, United Kingdom and United States of America prepared the requested health criteria documents. Under the responsibility of the coordinators for a group of chemicals considered in the guidelines, the draft health criteria documents were submitted to a number of scientific institutions and selected experts for peer review. Comments were taken into consideration by the coordinators and authors before the documents were submitted for final evaluation by the experts meetings. A “final task force” meeting reviewed the health risk assessments and public and peer review comments and, where appropriate, decided upon guideline values. During preparation of the third edition of the GDWQ, it was decided to include a public review via the world wide web in the process of development of the health criteria documents.
During the preparation of health criteria documents and at experts meetings, careful consideration was given to information available in previous risk assessments carried out by the International Programme on Chemical Safety, in its Environmental Health Criteria monographs and Concise International Chemical Assessment Documents, the International Agency for Research on Cancer, the joint FAO/WHO Meetings on Pesticide Residues and the joint FAO/WHO Expert Committee on Food Additives (which evaluates contaminants such as lead, cadmium, nitrate and nitrite, in addition to food additives). Further up-to-date information on the GDWQ and the process of their development is available on the WHO internet site and in the current edition of the GDWQ.
Acknowledgements The work of the following coordinators was crucial in the development of Trihalomethanes in Drinking-water, Background document for development of WHO Guidelines for Drinking-water Quality: Brominated Trihalomethanes J.K. Fawell, Water Research Centre, United Kingdom (inorganic constituents) U. Lund, Water Quality Institute, Denmark (organic constituents and pesticides) B. Mintz, Environmental Protection Agency, USA (disinfectants and disinfectant by-products) Chloroform P. Chambon, Health Environment Hygiene Laboratory of Lyon, Lyon, France (inorganic constituents) U. Lund, Water Quality Institute, Horsholm, Denmark (organic constituents) H. Galal-Gorchev, Urban Environmental Health, World Health Organization, Geneva, Switzerland (pesticides) E. Ohanian, Environmental Protection Agency, Washington, DC, USA (disinfectants and disinfection by-products) The WHO coordinators for the second edition (brominated trihalomethanes) were as follows: Headquarters: H. Galal-Gorchev, International Programme on Chemical Safety R. Helmer, Division of Environmental Health Regional Office for Europe: X. Bonnefoy, Environment and Health O. Espinoza, Environment and Health The coordinators for the overall administrative and technical aspects of the Addendum to the second edition (chloroform) were, respectively, J. Kenny and H. Galal-Gorchev, Urban Environmental Health, WHO, Geneva, Switzerland. The convening of the experts meetings for the second edition (brominated trihalomethanes) was made possible by the financial support afforded to WHO by the Danish International Development Agency (DANIDA), Norwegian Agency for Development Cooperation (NORAD), the United Kingdom Overseas Development Administration (ODA) and the Water Services Association in the United Kingdom, the Swedish International Development Authority (SIDA), and the following sponsoring countries: Belgium, Canada, France, Italy, Japan, Netherlands, United Kingdom and USA.
The preparation of the chloroform document (Addendum to the second edition) was made possible by the financial support afforded to WHO by Canada, the European Commission, Japan and the USA. The first draft of the chloroform section of this background document was prepared by Ms M.E. Meek, Health Canada, to whom special thanks are due. Ms Marla Sheffer of Ottawa, Canada, was responsible for the scientific editing of the entire document. The efforts of all who helped in the preparation and finalization of this document, including those who drafted and peer reviewed drafts, are gratefully acknowledged.
Acronyms and abbreviations used in the text BDCM CAS CHO DBCM DNA IARC IUPAC LD50 LOAEL NCI NOAEL NOEL NTP SGPT TDI THM USA USP
bromodichloromethane Chemical Abstracts Service Chinese hamster ovary dibromochloromethane deoxyribonucleic acid International Agency for Research on Cancer International Union of Pure and Applied Chemistry median lethal dose lowest-observed-adverse-effect level National Cancer Institute (USA) no-observed-adverse-effect level no-observed-effect level National Toxicology Program (USA) serum glutamate–pyruvate transaminase tolerable daily intake trihalomethane United States of America US Pharmacopeia
Table of contents A. CHLOROFORM.....................................................................................................1 1. GENERAL DESCRIPTION......................................................................................1 1.1 Identity .................................................................................................................1 1.2 Physicochemical properties .................................................................................1 1.3 Organoleptic properties........................................................................................1 1.4 Major uses............................................................................................................1 1.5 Environmental fate...............................................................................................2 2. ANALYTICAL METHODS .....................................................................................2 3. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE..................................2 3.1 Outdoor air ...........................................................................................................2 3.2 Indoor air..............................................................................................................2 3.3 Water....................................................................................................................3 3.4 Food .....................................................................................................................4 3.5 Estimated total exposure and relative contribution of drinking-water.................5 4. KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS ......................................................................................................................6 5. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS.7 5.1 Acute exposure.....................................................................................................7 5.2 Short-term exposure.............................................................................................7 5.3 Long-term exposure .............................................................................................9 5.4 Reproductive and developmental toxicity ...........................................................9 5.5 Mutagenicity and related end-points....................................................................9 5.6 Carcinogenicity ..................................................................................................10 5.6.1 Mechanism of carcinogenicity....................................................................13 5.7 Other special studies ..........................................................................................15 5.8 Factors modifying toxicity.................................................................................15 6. EFFECTS ON HUMANS........................................................................................16 7. GUIDELINE VALUE .............................................................................................17 8. REFERENCES ........................................................................................................18 B. BROMINATED TRIHALOMETHANES ..........................................................23 1. GENERAL DESCRIPTION....................................................................................23 1.1 Identity ...............................................................................................................23 1.2 Physicochemical properties ...............................................................................24 1.3 Organoleptic properties......................................................................................24 1.4 Major uses..........................................................................................................24 1.5 Environmental fate.............................................................................................24
2. ANALYTICAL METHODS ...................................................................................25 3. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE................................25 3.1 Air ......................................................................................................................25 3.2 Water..................................................................................................................25 3.3 Food ...................................................................................................................26 3.4 Estimated total exposure and relative contribution of drinking-water...............26 4. KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS ....................................................................................................................26 5. EFFECTS ON LABORATORY ANIMALS AND IN VITRO TEST SYSTEMS ..26 5.1 Bromoform.........................................................................................................26 5.1.1 Acute exposure............................................................................................26 5.1.2 Short-term exposure....................................................................................27 5.1.3 Long-term exposure ....................................................................................27 5.1.4 Reproductive toxicity, embryotoxicity and teratogenicity..........................28 5.1.5 Mutagenicity and related end-points...........................................................28 5.1.6 Carcinogenicity ...........................................................................................28 5.2 Dibromochloromethane .....................................................................................29 5.2.1 Acute exposure............................................................................................29 5.2.2 Short-term exposure....................................................................................29 5.2.3 Long-term exposure ....................................................................................29 5.2.4 Reproductive toxicity, embryotoxicity and teratogenicity..........................30 5.2.5 Mutagenicity and related end-points...........................................................30 5.2.6 Carcinogenicity ...........................................................................................31 5.3 Bromodichloromethane......................................................................................31 5.3.1 Acute exposure............................................................................................31 5.3.2 Short-term exposure....................................................................................31 5.3.3 Long-term exposure ....................................................................................32 5.3.4 Reproductive toxicity, embryotoxicity and teratogenicity..........................32 5.3.5 Mutagenicity and related end-points...........................................................32 5.3.6 Carcinogenicity ...........................................................................................33 6. EFFECTS ON HUMANS........................................................................................33 7. GUIDELINE VALUES ...........................................................................................34 7.1 Bromoform.........................................................................................................34 7.2 Dibromochloromethane .....................................................................................34 7.3 Bromodichloromethane......................................................................................35 8. REFERENCES ........................................................................................................35 C. TOTAL TRIHALOMETHANES........................................................................38 1. GUIDELINE VALUE .............................................................................................38
A. CHLOROFORM 1. GENERAL DESCRIPTION 1.1 Identity CAS No:
67-66-3
Molecular formula:
CHCl3
Chloroform is the most commonly occurring trihalomethane (THM); THMs are halogen-substituted single-carbon compounds with the general formula CHX3. 1.2 Physicochemical properties1 Chloroform is degraded photochemically, is not flammable and is soluble in most organic solvents. However, its solubility in water is limited. Phosgene and hydrochloric acid may be formed by chemical degradation. The most important physical properties of chloroform are presented below (IARC, 1979; Budavari et al., 1989): Property
Value
Physical state
Clear, colourless liquid
Boiling point at 101.3 kPa
61.3 °C
Melting point
-63.2 °C
Relative density (20 °C)
1.484
Auto-ignition temperature
>1000 °C
Water solubility (25 °C)
7.5–9.3 g/litre
Vapour density (101.3 kPa, 0 °C)
4.36 kg/m3
Vapour pressure
8.13 kPa at 0 °C; 21.28 kPa at 20 °C
Stability
Air- and light-sensitive; breaks down to phosgene, hydrogen chloride and chlorine
Log octanol–water partition coefficient
1.97
1.3 Organoleptic properties Chloroform has a characteristic odour and a burning, sweet taste. Its odour threshold values are 2.4 mg/litre in water and 420 mg/m3 in air (Budavari et al., 1989; ATSDR, 1993). 1.4 Major uses Commercial production of chloroform was 440 000 t in 1987. Chloroform has been used primarily in the production of chlorodifluoromethane, although smaller amounts have also been used as solvents, as cleaning agents and in fumigants. Although
1
Conversion factor in air: 1 mg/m3 = 0.20 ppm.
1
TRIHALOMETHANES IN DRINKING-WATER chloroform was used in the past as an anaesthetic and in proprietary medicines, these applications have been prohibited in many countries. 1.5 Environmental fate It is assumed that most chloroform present in water is ultimately transferred to air as a result of its volatility. Chloroform has a residence time in the atmosphere of several months and is removed from the atmosphere through chemical transformation. It is resistant to biodegradation by aerobic microbial populations of soils and aquifers subsisting on endogenous substrates or supplemented with acetate. Biodegradation may occur under anaerobic conditions. Bioconcentration in freshwater fish is low. Depuration is rapid (IPCS, 1994a). 2. ANALYTICAL METHODS There are several methods for the analysis of chloroform in air, water and biological materials. The majority of these methods are based on direct column injection, adsorption on activated adsorbent or condensation in a cool trap, then desorption by solvent extraction or evaporation by heating and subsequent gas chromatographic analysis. In water, detection limits range from 0.02 to 1 µg/litre (IPCS, 1994a; ISO, 1997). 3. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 3.1 Outdoor air Chloroform levels in ambient air in remote areas of the USA range from 0.1 to 0.25 µg/m3. In urban and source-dominated areas, concentrations are 0.3–9.9 µg/m3 and 4.1–110 µg/m3, respectively (ATSDR, 1993). The population-weighted mean concentration of chloroform at 17 urban sites sampled across Canada in 1989 was 0.2 µg/m3 (Environment Canada, 1992). Hourly average concentrations of chloroform in the Netherlands, determined during 1979–1981, were generally 0.15 µg/m3 (estimated detection limit) or less, the maximum value being 10 µg/m3 (den Hartog, 1980, 1981). Average concentrations of chloroform during 1990 in four German cities (Berlin, Tübingen, Freudenstadt and Leipzig) ranged from 0.26 to 0.9 µg/m3; the maximum value was 30 µg/m3, detected in Tübingen (Toxicology and Environmental Health Institute of Munich Technical University, 1992). 3.2 Indoor air Concentrations of chloroform in indoor air are generally higher than those in ambient outdoor air owing primarily to volatilization during water use. In a population survey in the USA, the observed increase was approximately 85%, which was consistent with assumptions concerning daily water use and likely release of chloroform from water into air (Wallace, 1987). 2
TRIHALOMETHANES IN DRINKING-WATER In a nationwide survey of 757 randomly selected one-family houses in Canada sampled over a 10-month period in 1991, the mean level of chloroform in indoor air was 4.1 µg/m3; the maximum value was 69 µg/m3 (Otson et al., 1992). Ullrich (1982) reported comparable concentrations in indoor air (1–3 µg/m3) in Germany. Chloroform levels in the air of enclosed swimming pools are also increased as a result of transfer from water. They vary as a function of several factors, such as the degree of ventilation, the level of chlorination, water temperature, the degree of mixing at the water surface and the quantity of organic precursors present (Lahl et al., 1981a). Over a period of 11 months, the levels of chloroform directly above the water surface in indoor public swimming pools in Bremen, Germany, ranged from 10 to 380 µg/m3, with an average of about 100 µg/m3 (Bätjer et al., 1980; Lahl et al., 1981a). Ullrich (1982) reported a similar mean value in four public swimming pools in Germany. In an experimental study in which the mean concentration of chloroform in water in an indoor swimming pool was increased from 159 to 553 µg/litre, corresponding mean air chloroform levels ranged from 2.9 to 8.0 mg/m3 (Levesque et al., 1994). 3.3 Water Sources of chloroform in the aquatic environment include paper bleaching with chlorine, chlorination of recreational (pool) water, cooling water and wastewater. Chloroform is present in drinking-water through direct contamination of the source and through formation from naturally occurring organic compounds during chlorination. The rate and degree of formation of chloroform during chlorination are a function primarily of the concentrations of chlorine and humic acid, temperature and pH. Levels vary seasonally, with concentrations generally being greater in summer than in winter (IPCS, 1994a). Concentrations of chloroform in groundwater vary widely, depending principally on proximity to hazardous waste sites (ATSDR, 1993). For example, chloroform was detected at levels ranging from 11 to 866 µg/litre in samples from five out of six monitoring wells drilled 64 m apart in a direction perpendicular to the northward flow of groundwater at a contaminated site in Pittman, Nevada, USA (the depth of unconfined groundwater was 2–4 m at this selected site) (Kerfoot, 1987). Finished drinking-water collected in 1988–1989 from 35 US sources, 10 of which were located in California, in all four seasons contained median concentrations of chloroform ranging from 9.6 to 15 µg/litre. The overall median for all four seasons was 14 µg/litre (Krasner et al., 1989). In a 1987–1989 survey conducted in the USA, the mean chloroform concentration in finished water for surface water systems serving more than 10 000 people was 38.9 µg/litre (90th percentile, 74.4 µg/litre). The comparable mean value in the distribution system was 58.7 µg/litre (US EPA, 1992). In a national survey of the water supplies of 70 communities in Canada conducted during the winter of 1976–1977, concentrations of chloroform in treated water of the 3
TRIHALOMETHANES IN DRINKING-WATER distribution system 0.8 km from the treatment plant averaged 22.7 µg/litre (Williams et al., 1980). Concentrations at 10 different locations in southern Ontario sampled in the early 1980s were 4.5–60 µg/litre in water leaving the treatment plant and 7.1–63 µg/litre 1.6 km from the plant (Oliver, 1983). In a more recent survey of samples collected during winter and summer of 1993 at 53 sites in nine provinces of Canada, chloroform was the major THM detected at all but three sites, these being groundwater sources that were treated with minimal chlorination. The contribution of chloroform to total THMs (ranging from 75.5 to 91.4%) was higher in summer than in winter and was slightly higher for chlorine–chlorine versus chlorine–chloramine or ozone–chloramine treatment. Although the majority of treatment facilities had relatively low total THM levels (100 µg/litre), particularly in the summer (except for chlorine–chloramine disinfection) (Health Canada, 1995). Chloroform levels in drinking-water in 100 German cities sampled in 1977 ranged from
