ARCHIVED - Bis(Chloromethyl) Ether and Chloromethyl Methyl Ether - PSL1

Environment Canada
Health Canada
1993
ISBN: 0-662-20377-1
Cat. No.: En40-215/8E

Canadian Environmental Protection Act

Table of Contents

Synopsis

Data gathered under the authority of Section 16 of CEPA indicate that bis(chloromethyl) ether (BCME) and chloromethyl methyl ether (CMME) are not currently used or produced in Canada. If these substances were to enter the environment, they would both be rapidly broken down by hydrolysis and photo-oxidation. Data were not found concerning concentrations of BCME and CMME in the ambient environment in Canada.

Based on the fate of these substances in the environment and the lack of exposure, there is no reason to suspect that adverse effects on aquatic and terrestrial organisms would occur. For the same reason, these substances are not considered to be associated with depletion of stratospheric ozone or with global warming, and are not expected to contribute significantly to ground level ozone formation.

Bis(chloromethyl) ether and technical grade CMME [which contains bis(chloromethyl) ether] have been demonstrated to cause cancer in experimental animals and in humans. These substances are, therefore, considered to be "non-threshold toxicants" (substances for which there is believed to be some chance of adverse health effects at any level of exposure). For such substances, where data permit, estimated exposure is compared to quantitative estimates of cancer potency to characterize risk and provide guidance in establishing priorities for further action under CEPA. For BCME and CMME, such values would be expected to be extremely low owing to the lack of exposure in the general environment.

Based on these considerations, the federal Minister of the Environment and the federal Minister of National Health and Welfare have concluded that the substances BCME and CMME are not entering the environment in a quantity or concentration or under conditions that constitute a danger to the environment or to the environment on which human life depends. However, if these non-threshold toxicants were to enter the Canadian environment (as a consequence of their commercial use), they may constitute a danger in Canada to human life and health. Therefore, BCME and CMME are considered to be "toxic" as defined under Paragraph 11(c) of the Canadian Environmental Protection Act.

1.0 Introduction

The Canadian Environmental Protection Act (CEPA) requires the federal Minister of the Environment and the federal Minister of National Health and Welfare to prepare and publish a Priority Substances List that identifies substances, including chemicals, groups of chemicals, effluents, and wastes that may be harmful to the environment or constitute a danger to human health. The Act requires both Ministers to assess these substances and determine whether they are "toxic" as defined under Section 11 of the Act which states:

"... a substance is toxic if it is entering or may enter the environment in a quantity or concentration or under conditions

  1. having or that may have an immediate or long-term harmful effect on the environment;
  2. constituting or that may constitute a danger to the environment on which
    human life depends; or
  3. constituting or that may constitute a danger in Canada to human life or
    health."

Substances that are assessed as "toxic" according to Section 11 may be placed on Schedule I of the Act. Consideration can then be given to possible development of regulations, guidelines, or codes of practice to control any aspect of their life cycle, from the research and development stage through manufacture, use, storage, transport, and ultimate disposal.

The assessment of whether bis(chloromethyl) ether (BCME) and chloromethyl methyl ether (CMME) are "toxic", as defined in CEPA, was based on the determination of whether they enter or are likely to enter the Canadian environment in a concentration or quantities or under conditions that could lead to exposure of humans or other biota to levels that could cause harmful effects. Both BCME and CMME are considered in this report since technical grade CMME contains small amounts (1 to 8%) of BCME (Travenius, 1982; ATSDR, 1989). Unless otherwise noted in this Assessment Report, "CMME" refers to technical grade CMME which contains small amounts of BCME as a contaminant.

Data relevant to the assessment of whether either BCME or CMME are "toxic" under CEPA were identified through evaluation of existing review documents (ASTDR, 1989; Durkin et al., 1975; U.S. EPA, 1980; 1987; and 1991) supplemented with information from published reference texts and literature identified through on-line searches of databases conducted between April and November, 1991 These databases included: AQUIRE, AQUALINE, AQUAREF, BIOSIS Previews, CAS ONLINE, CAB, CCINFO, Chemical Evaluation Search and Retrieval System (CESARS), Cooperative Documents Project (CODOC), Chemical Hazard Response Information System (CHRIS), DOBIS, Environment Canada Departmental Library Catalogue (ELIAS), ENVIROLINE, Federal Register, Hazardous Substances Data Bank (HSDB), Integrated Risk Information System (IRIS) (U.S. EPA, 1991), MEDLINE, MICROLOG, Pollution Assessment Report Abstracts, Registry of Toxic Effects of Chemical Substances (RTECS), TOXLINE, TOXLIT, and TRI (TOXNET). Reviews of the environmental fate and effects, and effects on human health of these substances were prepared under contract by Monenco Consultants Ltd., and Cambridge Environmental Inc. (Croy and DeVoto, 1991), respectively. In addition, a number of officials within federal and provincial governments were asked to provide any available (unpublished) monitoring data on the levels of these substances in the Canadian environment, including drinking water. Data relevant to the assessment of the effects of BCME and CMME on the environment and human health obtained after June 1992 were not considered for inclusion.

Review articles were consulted where appropriate. However, all original studies that form the basis for determining whether BCME and CMME are "toxic" under CEPA have been critically evaluated by the following Environment Canada staff (entry, and environmental exposure and effects) and Health and Welfare Canada staff (human exposure and effects on human health):

Environment Canada

  • D. Boersma
  • C. Fortin
  • S. Walker

Health and Welfare Canada

  • S. Basavaraj
  • I. Caldwell
  • R.G. Liteplo
  • M.E. Meek

In this report, a synopsis concerning BCME or CMME that will appear in the Canada Gazette is presented. Section 2.0 is an extended summary of the technical information that is critical to the assessment. The assessment of whether BCME or CMME are "toxic" is presented in Section 3.0. A Supporting Document that presents the technical information in greater detail has also been prepared.

As part of the review and approvals process established by Environment Canada, the environmental sections of this Assessment Report were peer reviewed by the following scientists: Dr. Derek Muir (Fisheries and Oceans Canada, Winnipeg, Manitoba) and Dr. Keith Solomon (Centre for Toxicology, Guelph, Ontario). Sections related to the assessment of effects on human health were approved by the Standards and Guidelines Rulings Committee of the Bureau of Chemical Hazards of Health and Welfare Canada. The entire Assessment Report was reviewed and approved by the Environment Canada/Health and Welfare Canada CEPA Management Committee.

Copies of this Assessment Report and the unpublished Supporting Document are available upon request from:

Commercial Chemicals Branch
Environment Canada
14th Floor, Place Vincent Massey
351 St. Joseph Boulevard
Hull, Quebec
K1A 0H3

Environmental Health Centre
Room 104
Health and Welfare Canada
Tunney's Pasture
Ottawa, Ontario
K1A 0L2

2.0 Summary of Information Critical to Assessment of "Toxic"

2.1 Identity, Properties, Production, and Uses

Bis(Chloromethyl) Ether - Bis(chloromethyl) ether (BCME) is an a-chloroalkyl ether with the Chemical Abstracts Service (CAS) registry number 542-88-1; the molecular formula C2H4C120; and the structural formula CICH2OCH2Cl (Sittig, 1981; U.S.EPA, 1980). Synonyms for BCME include: chloro(chloromethoxy) methane, sym-dichloro-dimethyl ether, dimethyl-1, 1'-dichloroether, oxybis(chloromethane), dichloromethyl ether, and bichloromethyl ether (Sax, 1984; Verschueren, 1983).

Bis(chloromethyl) ether is a colourless, volatile liquid with a "suffocating" odour (Sittig, 1981; Verschueren, 1983). No experimental values for the vapour pressure of BCME were found in the literature. There are no experimental values for water solubility and Henry's Law Constant for BCME, as this substance hydrolyses very rapidly in water (see Subsection 2.3.1). This substance is miscible with most organic solvents (Weast, 1984). Analytical methods used to quantify BCME involve gas chromatography/mass spectrometry or gas chromatography with electron capture detection (Collier, 1972; Evans et al., 1975; Frankel and Black, 1976).

Chloromethyl Methyl Ether - Chloromethyl methyl ether (CMME) is an a-chloroalkyl ether with the CAS registry number 107-30-2; the molecular formula C2H5ClO; and the structural formula CH3OCH2C1 (Sittig, 1981; U.S. EPA, 1980). Synonyms for CMME include: chloromethoxymethane, dimethylchloro ether, monochlorodimethyl ether, and methoxymethyl chloride (Sax, 1984; Verschueren, 1983; Sittig, 1981). Technical grade CMME contains from 1 to 8% BCME (Travenius, 1982). Available data for CMME permit evaluation only of the technical grade material (referred to as "CMME", unless otherwise specified).

Chloromethyl methyl ether is a colourless liquid with an "irritating" odour (Verschueren, 1983). No experimental values for the vapour pressure of CMME were found in the literature. There are no experimental values for water solubility and Henry's Law Constant for CMME as this substance is hydrolyzed very rapidly in water (Radding et al., 1977; Verschueren, 1983). This substance is soluble in most organic solvents (Weast, 1984). Analytical methods used to quantify CMME include gas chromatography with electron-capture detection (Kallos et al., 1977; Langhorst et al., 1981; Sittig, 1981).

Information provided in response to a Notice published under Section 16(1) of CEPA indicated that there was no commercial activity involving more than one kilogram of either BCME or CMME in Canada during 1990 or 1991 (Environment Canada, 1992). However, each of these compounds was reported to be used in Canada between 1984 and 1986 (Canada Gazette, 1991).

Since the early 1980s, industrial use of both BCME and CMME in the United States has been restricted to specific intermediate chemical reactions (Travenius, 1982).

2.2 Entry into the Environment

Neither BCME or CMME occurs naturally in the environment. However, BCME can be formed as a by-product when formaldehyde reacts with chloride ions in an acidic medium (Travenius, 1982). Moderate to high concentrations (mg/L or mg/m3) of the reactants are required to produce low concentrations (µg/L) of BCME (Tou and Kallos, 1974; Travenius, 1982; Kallos and Tou, 1977).

Information showing that CMME may be formed as a by-product during the production of other industrial chemicals was not found.

It was reported in the Toxic Release Inventory (U.S. EPA, 1990) that less than 1 kg of BCME and 50 kg of CMME were released to the atmosphere in the United States from industrial producers and users during 1989. No releases were reported in other media (water, soil, underground injection).

2.3 Exposure-related Information

2.3.1 Fate

Bis(chloromethyl) ether and CMME hydrolysis rapidly in water. At 20°C, half-lives in water of 38 seconds for BCME and <1 second for CMME have been reported (U.S. EPA, 1980; Tou et al., 1974; Radding et al., 1977). Although BCME may be degraded by oxidation, the extremely rapid hydrolysis of BCME in an aqueous medium precludes any oxidative degradation of this substance from taking place in aquatic systems (Callahan et al., 1979). Bis(chloromethyl) ether is hydrolyzed to formaldehyde and hydrogen chloride (ASTDR, 1989). Chloromethyl methyl ether is hydrolyzed to hydrogen chloride, methanol, and formaldehyde (Travenius, 1982).

Owing to their rapid hydrolysis in an aqueous medium, the volatilization of BCME and CMME from surface water is likely to be insignificant. Callahan et al. (1979) suggested that BCME could volatilize rapidly from an aquatic system only if it were discharged in a water-immiscible solvent that had a high vapour pressure. Once in the atmosphere, these substances would be degraded by photo-oxidation or hydrolysis. Cupitt (1980) reported atmospheric half-lives of <2.9 days for BCME and <3.9 days for CMME. Tou and Kallos (1974) reported half-lives for atmospheric hydrolysis as >1 day for BCME and between 0.0024 (Nichols and Merritt, 1973) and 0.27 days for CMME, in humid air. At low humidity levels, however, BCME may be degraded by oxidative as well as hydrolytic pathways (Callahan et al., 1979).

In air, the decomposition products for BCME include hydrogen chloride, formaldehyde, and chloromethylformate, while those for CMME include chloromethyl and methyl formate (Cupitt, 1980).

Very little information was found concerning the behaviour of BCME or CMME in soil. For BCME, Mabey et al. (1982) calculated a log organic carbon partition coefficient (log K??) of 1.2. On the basis of this value, BCME appears to have minimal potential to adsorb to soil. However, it is also unlikely that BCME and CMME are mobile in soil as both compounds are hydrolyzed rapidly in an aqueous environment. No information on the biodegradation of either BCME or CMME in soil was identified.

The high rates of hydrolysis preclude any possibility of BCME or CMME bioaccumulating in organisms.

2.3.2 Concentrations

No data on levels of BCME or CMME in the ambient Canadian environment or in industrial effluents were identified.

2.4 Effects-related Information

2.4.1 Experimental Animals and In Vitro

Bis(chloromethyl) ether and CMME are acutely toxic following inhalation, oral, or dermal exposure. The LC50 for the exposure (by inhalation) of experimental animals to BCME ranges from 5.3 ppm (25 mg/m3) to 10.3 ppm (48 mg/m3) (Drew et al., 1975; Union Carbide, 1968; Leong et al., 1971). The LD50 for the oral administration of BCME to rats was 0.21 mL/kg body weight (b.w.) (278 mg/kg b.w.) (Union Carbide, 1968). The LC50 for the exposure (by inhalation) of rats and hamsters to CMME was 55 ppm (182 mg/m3) and 65 ppm (215 mg/m3), respectively (Drew et al., 1975). It should be noted that since CMME contains between 1 to 8% BCME, the toxic effects produced by CMME may be due, at least in part, to BCME.

Information is limited on the toxicological effects produced following short-term exposure of experimental animals to BCME or CMME. The repeated exposure by inhalation of male rats or hamsters to 1 ppm (4.7 mg/m3) BCME over periods of up to 30 days, produced a marked reduction in survival, hyperplastic changes within the trachea and bronchus, and subarachnoid haemorrhage, compared to unexposed controls (Drew et al., 1975). In male rats exposed (duration not specified) by inhalation to 10 ppm (33 mg/m3) CMME, there was a reduction in survival in addition to alterations in lung/body weight ratios, and regenerative hyperplasia of the bronchial epithelium, compared to unexposed controls (Drew et al., 1975).

Studies on the toxicological effects produced following long-term inhalation exposure to BCME and CMME have been restricted primarily to limited carcinogenesis bioassays in mice, rats, and hamsters. Following exposure (inhalation) of male mice to 5 mg/m3 BCME over a period of 82 days, there was a marked reduction in survival, and increased incidence of pulmonary tumors (adenomas) compared to unexposed controls (26/47 versus 20/49, respectively). The statistical significance of this increase, however, was not specified (Leong et al., 1971). The number of lung tumors per animal in the BCME-exposed mice was slightly higher than in unexposed controls (5.2 versus 2.2, respectively). In male mice exposed to 1, 10, or 100 ppb (0.0047, 0.047, or 0.47 mg/m3) BCME over a period of 6 months, there was a reduction in survival (compared to unexposed controls), although after 6 months, a significant increase in the incidence of pulmonary adenomas was observed only in surviving mice exposed to the highest concentration (Leong et al., 1981).

In male rats exposed (by inhalation) to 1, 10, or 100 ppb (0.0047, 0.047, or 0.47 mg/m3) BCME over a period of 6 months, there was an increase in the incidence of "tumors of the respiratory tract" at the highest concentration (102/111 in BCME-exposed group versus 0/112 in unexposed controls); 94% of which were tumors of the olfactory neural tissue (esthesioneuroepitheliomas)(Leong et al., 1981). In male rats exposed to 0.1 ppm (0.47 mg/m3) BCME for periods ranging up to 20 weeks, there was an increase in the incidence of nasal esthesioneuroepitheliomas and squamous cell carcinomas of the lung with increasing periods of exposure; the incidence of carcinomas of the lung in animals exposed over a 20-week period was 8/30. Survival was reduced by approximately 24% in animals exposed to BCME over periods of 16 and 20 weeks (Kuschner et al., 1975).

In male mice exposed (by inhalation) to 2 ppm (6.6 mg/m3) CMME over a period of 101 days, the incidence of "pulmonary tumors" was not greater than in unexposed controls, although the number of lung tumors per animal in the CMME-exposed group was slightly higher than in the controls (3.1 versus 2.2, respectively) (Leong et al., 1971). In male rats exposed to 1 ppm (3.3 mg/m3) CMME for virtually their entire lives, the incidence of tracheal metaplasia and bronchial hyperplasia was greater than in unexposed controls; two tumors of the respiratory tract (an esthesioneuroepithelioma and lung squamous cell carcinoma) were observed in CMME-exposed animals, while none was reported in unexposed controls (Laskin et al., 1975). In male hamsters exposed to 1 ppm (3.3 mg/m3) CMME for virtually their entire lives, the incidence of tracheal metaplasia and bronchial hyperplasia was increased compared to unexposed controls. One lung adenocarcinoma and a tracheal squamous papilloma were observed in two animals exposed to CMME (information on tumor incidence in controls was not presented) (Laskin et al., 1975).

The incidence of pulmonary adenomas was greater in mice observed for six months after receiving a single subcutaneous injection of 12.5 µL/kg b.w. (16.6 mg/kg b.w.) BCME, or 125 µL/kg b.w. (132.5 mg/kg b.w.) CMME than in mice that received vehicle alone. There were, however, no effects on growth or survival of the animals (Gargus et al., 1969). In female rats administered BCME (3 mg) or "laboratory purified" CMME (3 mg) subcutaneously once a week for approximately 300 days (though the dose and schedule of administration were modified owing to the corrosive effects of BCME around the site of injection), there was an increase in the incidence of tumors (though the statistical significance was not specified) at the site of injection for BCME but not for "laboratory purified" CMME, compared to that in the control group administered vehicle alone (van Duuren et al., 1969). However, in a subsequent study (van Duuren et al., 1972) in which "laboratory purified" CMME (300 µg/animal) was administered once a week to female mice for their entire lives, the number of mice with sarcomas at the site of injection was 0/30 in the (vehicle) control and 10/30 in the (laboratory-purified) CMME-exposed groups. In mice, the incidence of tumors (mainly fibrosarcomas) at the site of injection was increased following 32 subcutaneous injections of 0.3 mg BCME compared to that in a control group administered vehicle alone (Zajdela et al., 1980). The incidence of squamous cell carcinomas of the skin in female mice that received 2 mg of BCME (applied dermally) or solvent, i.e., benzene, alone (controls) three times a week for 325 days was 12/20 and 0/20, respectively. "Laboratory purified" CMME (2 mg), however, was not carcinogenic in this skin tumor bioassay. In two-stage skin tumor carcinogenesis bioassays in which several substances were examined, BCME and CMME had "weak" tumor-initiating activity (van Duuren et al., 1969; Zajdela et al., 1980).

The genotoxicity of BCME and CMME has been examined in a variety of limited in vitro bioassays (Anderson and Styles, 1978; Mukai and Hawryluk, 1973; Agrelo and Severn, 1981; Styles, 1978; Kurian et al., 1990; Goldschmidt et al., 1975; Shooter, 1975; Perocco et al., 1983). The weight of evidence from these investigations in which a range of endpoints was examined indicates that both BCME and CMME are genotoxic. Available studies, however, are limited and generally, poorly documented.

No other relevant information was identified concerning the reproductive, developmental, immunological, or neurological toxicity of BCME or CMME in experimental animals or in humans.

2.4.2 Humans

In several case reports and series, the occurrence of lung cancer, several of which were small (oat) cell cancers, has been reported in workers exposed to BCME (Roe, 1985; Sakabe, 1973) or both compounds (Reznick et al., 1977). In addition, there have been a number of epidemiological studies of populations occupationally exposed to BCME or CMME.

In 136 workers employed at a chemical plant in California where BCME was used in the production of ion-exchange resins (Lemen et al., 1976) and in a population of 35 BCME-exposed workers employed at two dye stuff factories in Japan (Nishimura et al., 1990), the standardized mortality ratios for lung cancer were 9.3 and 21, respectively. The average age of appearance of or death due to a lung cancer was 47 and 46 years, respectively, and the average latency period was 10 years and 13.5 years, respectively.

For CMME, in prospective (cohort) studies of 125 employees of a chemical plant in the United States (Weiss, 1976; 1982), 737 "exposed" and 2120 "unexposed" workers at a chemical plant in Philadelphia (Maher and DeFonso, 1987) and 2460 "exposed" and 3692 "unexposed" workers at seven industrial facilities (Collingwood et al., 1987), the standardized mortality ratios for lung cancer were 20, 2.8, and 3, respectively. In the study reported by Weiss (1982), the standardized mortality ratios for deaths due to lung cancer peaked 15 to 19 years from the onset of exposure; similarly, Maher and DeFonso (1987) reported that the greatest increase in deaths due to cancer of the respiratory tract occurred approximately 10 to 20 years after first exposure.

For BCME, exposure was not assessed in any of the available epidemiological studies; however, a relationship between qualitative measures of exposure to CMME and lung cancer was observed in the only two studies in which it was examined (Collingwood et al., 1987; Maher and DeFonso, 1987).

Sram et al. (1983) reported that the proportion of peripheral lymphocytes with chromosomal aberrations (breaks, exchanges) isolated from 77 workers exposed to BCME and CMME was approximately twofold higher than that observed in lymphocytes isolated from 25 non-exposed controls. Except for information on whether the workers were smokers, which did not influence the results, no other relevant information was provided in this published account.

2.4.3 Ecotoxicology

No studies were found that investigated the toxicity of either BCME or CMME to aquatic or terrestrial organisms.

No information on the effects of BCME or CMME on the ozone layer or global warming was found. In view of their relatively short atmospheric lifetime, however, effects of these substances on the ozone layer or global warming are not anticipated.

3.0 Assessment of "Toxic" under CEPA

3.1 CEPA 11(a) Environment

From 1990 to 1991, in Canada, there was no commercial activity involving more than one kilogram of BCME or CMME and it is highly unlikely that these compounds would be formed from other substances that may be present in the environment. Both substances are readily degraded by hydrolysis in aqueous media or by photo-oxidation in the atmosphere and, therefore, are not likely to accumulate within living organisms. No data were found concerning concentrations of these substances in the ambient environment in Canada. Because of their extremely short residence time, it is believed that levels in the environment are extremely low (if they exist at all), and there is no exposure that could potentially arise from the past use of these substances in Canada. Therefore, even though there is a complete absence of data concerning the environmental toxicity of these substances, as previously noted, there is no reason to suspect that adverse effects due to BCME or CMME could occur in organisms living in the Canadian environment.

Therefore, on the basis of available data, BCME and CMME are not considered to be "toxic" as defined under Paragraph 11(a) of the Canadian Environmental Protection Act.

3.2 CEPA 11(b) Environment on Which Human Life Depends

The short persistence of BCME and CMME in the atmosphere and the extremely low levels of release preclude these substances from contributing to ozone layer depletion, global warming, or photochemical smog formation.

Therefore, on the basis of available data, BCME and CMME are not considered to be "toxic" as defined under Paragraph 11(b) of the Canadian Environmental Protection Act.

3.3 CEPA 11(c) Human Life or Health

In all of the five cohorts of exposed workers conducted to date, an association has been observed between lung cancer and exposure to either BCME (Lemen et al., 1976; Nishimura et al., 1990) or CMME (Weiss, 1976; Maher and DeFonso, 1987; Collingwood et al., 1987). The type of lung cancer [predominantly small (oat) cell carcinomas], the standardized mortality ratios, the latency periods (10 to 24 years), and the average age of appearance of cancer (35 to 55 years) in populations exposed either to BCME or CMME have been remarkably consistent. The type and incidence of lung cancer in individuals exposed to BCME or CMME [predominantly small (oat) cell carcinomas, occurring in relatively young individuals after short latency periods] is distinct from that caused by tobacco. Tobacco is one of the potential confounders in such studies, where lung tumors are predominantly squamous cell carcinomas, occurring after long latency periods in individuals more than 60 years of age (Weiss, 1976; Pasternack et al., 1977). Moreover, in the study in which tobacco smoking was most extensively addressed, involving a population of workers exposed to CMME, the incidence of lung cancer was inversely related to the use of tobacco (Weiss, 1980). The association between exposure to either BCME or CMME and lung cancer is strong, with standardized mortality ratios ranging up to 21 (Nishimura et al., 1990) and 20 (Weiss, 1982), respectively. For CMME, there is also evidence of a positive relationship between a qualitative measure of exposure and mortality due to lung cancer. In two studies on occupationally exposed individuals, the standardized mortality ratios for deaths due to lung cancer peaked 10 to 20 years from the onset of exposure (Weiss, 1982; Maher and DeFonso, 1987). Furthermore, observation of an association between occupational exposure to BCME and CMME and the development of lung cancer is plausible, based on the results of early, rather limited carcinogenesis bioassays and on available data on the genotoxicity of BCME and CMME. Increases in the incidence of tumors predominantly of the respiratory tract were observed in studies of exposed animal species.

The observed association of lung cancer [predominantly small (oat) cell carcinomas] and occupational exposure to either BCME or CMME, therefore, fulfils the traditional criteria (i.e., consistency, strength, specificity, temporal relationship, exposure-response relationship, and plausibility and supporting experimental data) for assessment of causality in epidemiological studies. Consequently, on the basis of the available data, BCME and CMME have been classified in Group I ("Carcinogenic to Humans") of the classification scheme developed for use in the derivation of the "Guidelines for Canadian Drinking Water Quality" (Health and Welfare Canada, 1989).

Owing to the lack of available information on concentrations in several environmental media to which humans are exposed, it is not possible to quantitatively estimate the total daily intake of BCME or CMME by the general population of Canada. It is also not appropriate to estimate intake on the basis of fugacity modelling, owing to the lack of commercial activity reported for these compounds. Consequently, estimates of total daily intake cannot be compared to quantitative estimates of cancer potency to characterize risk and provide guidance in establishing priorities for further action under CEPA. Such values would be expected to be extremely low owing to the lack of reported use of these compounds in Canada and their rapid degradation in the general environment.

On the basis of available data, BCME and technical grade CMME have been classified as being "Carcinogenic to Humans" and are therefore considered to be "toxic" as defined under Paragraph 11(c) of the Canadian Environmental Protection Act.

This approach is consistent with the objective that exposure to non-threshold toxicants should be reduced wherever possible and obviates the need to establish an arbitrary "de minimis" level of risk for determination of "toxic" under CEPA.

3.4 Conclusion

On the basis of available data, neither BCME or CMME are considered to be "toxic" as defined under Paragraphs 11(a) and 11(b) of the Canadian Environmental Protection Act but both are considered to be "toxic" as defined under Paragraph 11(c) of the Canadian Environmental Protection Act.

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