1,1,2,2-Tetrachloroethane - PSL1

3.0 Assessment of "Toxic" Under CEPA

3.1 CEPA 11(a) Environment

There is no current commercial activity involving 1,1,2,2-tetrachloroethane in Canada. However, 1,1,2,2-tetrachloroethane enters the Canadian environment through air emissions from the incineration of wastes generated during production of vinyl chloride monomer and ethylene dichloride; air emissions and leachates from existing waste disposal sites; or long-range atmospheric transport from other countries.

Low concentrations of 1,1,2,2-tetrachloroethane have been detected in Canadian ambient air; it is not frequently detected in groundwater or surface waters. Although no data were identified on levels of 1,1,2,2-tetrachloroethane in sediments, soil, or biota in Canada, it is not likely to be present in these media, based on its physical and chemical properties and the results of laboratory studies on the fate of 1,1,2,2-tetrachloroethane in various environmental media. Since 1,1,2,2-tetrachloroethane is no longer used or manufactured in Canada, the levels currently found are not likely to increase, and in fact may decrease over time.

The freshwater organism most sensitive to long-term exposure of 1,1,2,2-tetrachloroethane was the flagfish (Jordanella floridae), the 10-day larval survival of which was affected at 7.2 mg/L (LOEC). Using a factor of 0.1 to convert the LOEC to a chronic no-observed-effect-concentration (NOEC) for a non-persistent, non-bioaccumulative substance and to account for differences in species sensitivity and extrapolation from laboratory to field conditions, the estimated effects threshold is 720 µg/L for long-term exposure. The estimated effects threshold concentration for long-term exposure is 180 times greater than the maximum concentration found in Canadian surface waters (4.0 µg/L). Given the large difference between the estimated effects threshold and ambient water concentrations, no adverse effects are expected to result from exposure of freshwater organisms to 1,1,2,2-tetrachloroethane at current levels.

Most 1,1,2,2-tetrachloroethane is released to the atmosphere. Reliable effects data on terrestrial organisms are unavailable. As a result, it is not possible to assess whether current 1,1,2,2-tetrachloroethane concentrations in air will adversely effect terrestrial biota.

Therefore, on the basis of available data, it is not possible to conclude whether 1,1,2,2-tetrachloroethane is "toxic" as defined under Paragraph 11(a) of the Canadian Environmental Protection Act.

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

1,1,2,2-Tetrachloroethane is released to the atmosphere in relatively low amounts in Canada. Furthermore, because of its high volatility, rapid photo-oxidation in the atmosphere, and an atmospheric ozone-depleting potential of less than 0.001 relative to CFC-l 1, 1,1,2,2-tetrachloroethane is not expected to contribute significantly to either the depletion of the stratospheric ozone layer or global warming.

Therefore, on the basis of available data, 1,1,2,2-tetrachloroethane is 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

3.3.1 Population Exposure

Estimated average daily intakes (on a body weight basis) of 1,1,2,2-tetrachloroethane from environmental media for various age groups of the general population in Canada and the assumptions upon which they are based are presented in Table 1. Indoor air is the main source of exposure to 1,1,2,2-tetrachloroethane, with estimated intakes ranging from 0.43 to 0.67 µg/[kg (b.w.)·day]. Intake from ambient air is estimated to range from <0.005 to 0.02 µg/[kg (b.w.)·day]. Drinking water is estimated to contribute from 0.001 to 0.11 µg/[kg (b.w.) day] to the daily intake of 1,1,2,2-tetrachloroethane, although it should be noted that these values very likely overestimate exposure via drinking water, since 1,1,2,2-tetrachloroethane has only rarely been detected in treated drinking water in Canada. 1,1,2,2-Tetrachloroethane was not detected in two surveys of foodstuffs in Canada and one survey conducted in the United States. Food probably does not represent a significant source of 1,1,2,2-tetrachloroethane for the general population in Canada, based on its volatility and low potential for bioconcentration.

Inadequate data were available to estimate exposure to 1,1,2,2-tetrachloroethane via breast milk in infants, or through use of consumer products (including cigarettes) in all age groups. Total average daily intake of 1,1,2,2-tetrachloroethane by the general population in Canada is estimated to range from <0.44 to 0.72 µg/[kg (b.w.) ·day].

3.3.2 Effects

Based on the available data, carcinogenicity is potentially the most sensitive endpoint for determination of "toxic" under Paragraph 11(c) of CEPA. The weight of evidence for carcinogenicity, therefore, has been considered, based on the criteria developed for this purpose for the "Determination of 'Toxic' under Paragraph 11(c) of the Canadian Environmental Protection Act" (Environmental Health Directorate, 1992).

No adequate epidemiological studies have been identified in which the carcinogenicity of 1,1,2,2-tetrachloroethane in humans has been investigated.

The incidence of hepatocellular carcinomas was significantly increased in both male and female B6C3F₁ mice administered 1,1,2,2-tetrachloroethane by gavage for 78 weeks. These tumors also appeared earlier in mice administered the higher dose

Table 1 Estimated Average Total Daily Intake of 1,1,2,2-Tetrachloroethane by the General Population in Canada

Medium	Estimated Intake [µg/(kg b.w.·day)]
	*0 to 6 moa	7 rno to 4yrb	5 to 11 yrc	l2 to l9 yrd	20 to 70 yre
Ambient Airf	<0.005 to 0.01	<0.006 to 0.02	<0.007 to 0.02	<0.006 to 0.02	<0.005 to 0.01
Indoor Airg	0.43	0.58	0.67	0.55	0.49
Drinking Waterh	0.005 to 0.11	0.003 to 0.06	0.002 to 0.03	0.001 to 0.02	0.001 to 0.02
Total Intake	<0.44 to 0.55	<0.59 to 0.66	<0.68 to 0.72	<0.56 to 0.59	<0.50 to 0.52

* Age

1. Assumed to weigh 7 kg, breathe 2 m³ of air per day, and drink 0.75 L of water per day (Environmental Health Directorate, 1992).
2. Assumed to weigh 13 kg, breathe 5 m³ of air per day, and drink 0.8 L of water per day (Environmental Health Directorate, 1992).
3. Assumed to weigh 27 kg, breathe 12 m³ of air per day, and drink 0.9 L of water per day (Environmental Health Directorate, 1992).
4. Assumed to weigh 57 kg, breathe 21 m³ of air per day, and drink 1.3 L of water per day (Environmental Health Directorate, 1992).
5. Assumed to weigh 70 kg, breathe 23 m³ of air per day, and drink 1.5 L of water per day (Environmental Health Directorate, 1992).
6. Based on the range of mean concentrations of 1,l,2,2-tetrachloroethane in ambient air in ten Canadian cities (1988 to 1990) of <0.1 to 0.25 µg/m³ (Environment Canada, 1992), and an average of 4 hours per day spent outdoors (Environmental Health Directorate, 1992).
7. Based on a mean concentration of 1,1,2,2-tetrachloroethane in indoor air from approximately 750 homes in ten Canadian provinces of 1.8 µg/m³ (Otson et al., 1992) and an average of 20 hours per day spent indoors (Environmental Health Directorate, 1992).
8. Based on range of detection limits in survey of 30 water treatment facilities across Canada (Otson et al., 1982) and monitoring programs in Ontario (Lachmaniuk, 1991) and New Brunswick (Ecobichon and Allen, 1990) of 0.05 to 1.0 µg/L; since l,1,2,2-tetrachloroethane has only rarely been detected in treated drinking water in Canada, these estimates likely overestimate exposure in this medium.
   
   Top of Page

(National Cancer Institute, 1978). In a similar bioassay in Osborne-Mendel rats, no statistically significant increases in the incidence of any type of tumor were reported. However, there were two hepatocellular carcinomas (a rare tumor in this strain of rat) and one hepatic neoplastic nodule in male rats in the high-dose group, while none was noted in male controls (National Cancer Institute, 1978). The number of pulmonary adenomas per animal was not increased in a limited bioassay in which mice were administered 1,1,2,2-tetrachloroethane intraperitoneally for 24 weeks, although this study is inadequate even for screening of the carcinogenic potential of 1,1,2,2-tetrachloroethane due to poor survival of mice and the lack of histopathological confirmation of all tumors (Theiss et al., 1977).

1,1,2,2-Tetrachloroethane acted as a potent promoter in an initiation/promotion assay in Osborne-Mendel rats initiated with diethylnitrosamine (Milman et al, 1988; Story et al., 1986). Although not adequately tested in vivo (negative and equivocal results have been reported), 1,1,2,2-tetrachloroethane may have some genotoxic potential in vitro.

Due to the lack of sufficient data on the mechanism of 1,1,2,2-tetrachloroethane-induced cancer in mice, it is not possible to assess, with any degree of confidence, the relevance to humans of the hepatocellular carcinomas observed in the bioassay conducted by the National Cancer Institute (1978). Therefore, on the basis of the observed increase in liver tumors in mice, the non-significant increase in hepatocellular tumors in rats, and the genotoxic potential demonstrated in some in vitro studies, 1,1,2,2-tetrachloroethane is classified in Group III ("Possibly Carcinogenic to Humans") of the classification scheme developed for the determination of "toxic" under Paragraph 11(c) of CEPA (Environmental Health Directorate, 1992).

For substances classified in Group III, a tolerable daily intake (TDI) is generally developed by division of a relevant No-Observed-(Adverse)-Effect Level [NO(A)EL] or Lowest-Observed-(Adverse)-Effect Level [LO(A)EL] in animal species by an uncertainty factor, which takes into account, where appropriate, the limited evidence of carcinogenicity.

Available data are considered inadequate, however, to develop a TDI for 1,1,2,2-tetrachloroethane, as none of the studies identified was of sufficient quality to determine a NO(A)EL or LO(A)EL for non-neoplastic endpoints. Consequently, it is not possible to evaluate whether current concentrations of 1,1,2,2-tetrachloroethane present in the environment constitute a danger in Canada to human life or health.

For compounds classified in Group III, if the weight of evidence of carcinogenicity is considered sufficient, estimates of exposure are sometimes compared to quantitative estimates of cancer potency to provide guidance in establishing priorities for additional research. For 1,1,2,2-tetrachloroethane, this approach was considered inappropriate owing to the minimal weight of evidence for carcinogenicity and the suspicion that the observed tumors may not be relevant to humans.

Therefore, on the basis of available data, it is not possible to conclude whether 1,1,2,2-tetrachloroethane is "toxic" as defined under Paragraph 11(c) of theCanadian Environmental Protection Act.

3.4 Conclusion

Therefore, on the basis of available data, 1,1,2,2-tetrachloroethane is not considered to be "toxic" as defined under Paragraph 11 (b) of CEPA. It has also been concluded that available data are insufficient to conclude whether 1,1,2,2-tetrachloroethane is "toxic" as defined under Paragraphs 11 (a) and (c) of the Canadian Environmental Protection Act.