Appendices of the Screening Assessment Report Ethene, 1,1-dichloro- (1,1-Dichloroethene) Chemical Abstracts Service Registry Number 75-35-4 Environment Canada Health Canada June 2013

Lowest inhalation LC₅₀ (mouse) = 200 mg/m³ (Zeller et al. 1979a, 1979b, 1979c, 1979d)

[Additional studies: Carpenter et al. 1949; Siegel et al. 1971; Jaeger et al. 1973, 1974; Klimisch and Freisberg, 1979a, 1979b; Zeller et al. 1979a, 1979b, 1979c, 1979d]

Lowest oral LD₅₀ (mouse) = 194 mg/kg-bw (Jones and Hathway 1978a)

[Additional studies: Jenkins et al. 1972; Andersen and Jenkins 1977; Ponomarkov and Tomatis 1980]

Lowest inhalation LOEC (rat) = 200 mg/m³: fatty changes and focal liver cell necrosis (4 weeks) (Plummer et al. 1990); changes to the liver and kidneys (7 days, with observation period to 28 days) (Maltoni and Patella 1983)

[Additional studies: Gage 1970; Short et al. 1977; Oesch et al. 1983; Norris and Reitz 1984]

Lowest oral LOEL (gavage) (rat) = 200 mg/kg-bw (2 times per week): increased serum sorbitol dehydrogenase and aminotransferases indicative of hepatotoxicity (4 weeks) (Siegers et al. 1983)

[Additional studies: NTP 1982; Maltoni and Patella 1983]

Lowest inhalation LOEC (rat) = 100 mg/m³: minimal, reversible liver cell cytoplasmic vacuolation (90 days) (Norris 1977; Quast et al. 1977)

[Additional studies: Lazarev 1960; Prendergast et al. 1967]

Lowest oral LOEL (rat) = 19 mg/kg-bw per day: minimal, recoverable liver cell cytoplasmic vacuolation (90 days) (Norris 1977; Quast et al. 1977)

[Additional studies: NTP 1982; Quast et al. 1983]

Lowest inhalation LOAEC (mice) = 40 mg/m³: significant increases in kidney damage (regressive changes and/or abscesses and nephritis in males) (52 weeks) (Maltoni et al. 1984, 1985)

[Additional studies: Lee et al. 1977; Rampy et al. 1977, 1978; Viola and Caputo 1977; Hong et al. 1981; Quast et al. 1986; Cotti et al. 1988]

Lowest oral LOEL (rat) = 5 mg/kg-bw per day: increased incidence of chronic renal inflammation in male and female F344/N rats, 2-year gavage study (NTP 1982)

[Additional studies: Ponomarkov and Tomatis 1980; Quast et al. 1983; Maltoni et al. 1984, 1985]

Inhalation study in Swiss mice: 0, 10 or 25 ppm (0, 40 or 100 mg/m³; conversion by IPCS 1990) for 52 weeks; significantly increased incidence of renal adenocarcinomas (0/126, 0/25 and 28/119 for the control, low and high concentrations, respectively) in males at 100 mg/m³; mammary carcinomas (3/185, 6/30 and 16/148 for the control, low and high concentrations, respectively) in females and pulmonary adenomas (12/331, 14/58 and 41/288 for the control, low and high concentrations, respectively) in males and females were not clearly exposure-related (Maltoni et al. 1984, 1985)

No significant increases in tumours considered to be related to exposure were observed in rats or hamsters in inhalation bioassays or in any species in studies by oral, dermal or subcutaneous routes of exposure (Lee et al. 1977, 1978; Rampy et al. 1977, 1978; Viola and Caputo 1977; Van Duuren et al. 1979; Hong et al. 1981; NTP 1982; Quast et al. 1983, 1986; Maltoni et al. 1984, 1985).

Dermal initiation–promotion study in female mice: initiation with 1,1-DCE; promotion by phorbol myristate acetate for 428–576 days, beginning 14 days after exposure to 1,1-DCE; 8/30 treated mice with lung papillomas versus 9/120 controls (Van Duuren et al. 1979)

Lowest inhalation LOAEC (mouse) = 60 mg/m³: significant increase in the mean number of fetuses with an unossified incus and incompletely ossified sternebrae (gestation days 6–16); maternal LOEC = 119 mg/m³, based upon decrease in weight gain (Short et al. 1977)

[Additional studies: Murray et al. 1979]

Lowest oral LOEL (maternal, rat) = 14 mg/kg-bw per day; dams: minimal hepatocellular fatty change; reversible, accentuated hepatic lobular pattern; pups: no effects were observed (three-generation study) (Nitschke et al. 1983)

Note: Although 0.02 mg/kg-bw per day (rat) was the lowest identified oral LOAEL (Dawson et al. 1993), based on several factors, the US EPA (2002a) could not conclude that exposure to 1,1-DCE caused these effects.

[Additional studies: Murray et al. 1979]

Chromosomal aberrations

Positive results:
Hamster, bone marrow (Hofmann and Peh 1976) [inhalation; 120 or 400 mg/m³, 6 hours/day, 5 days/week, 6 weeks]

Negative results:
Rat, bone marrow (Rampy et al. 1977) [inhalation; 100 or 300 mg/m³, 6 hours/day, 5 days/week, 6 months]; mouse, bone marrow (Cerna and Kypenova 1977)[intraperitoneal injection for 5 days]

DNA adduct formation
Positive results:
CD1-mice [inhalation; 40 or 200 mg/m³, 6 hours], Sprague-Dawley rats [inhalation, 40 mg/m³, 6 hours], liver and kidney (Reitz et al. 1980)

Dominant lethal test
Negative results:
Mouse (Andersen and Jenkins 1977) [inhalation; 50 ppm (198 mg/m³), 6 hours/day, 5 days]; rat (Short et al. 1977)[inhalation; 55 ppm (218 mg/m³), 6 hours/day, 5 days/week, 11 weeks]

Micronuclei test
Negative results:
Mouse, bone marrow [oral, 200 mg/kg-bw]; mouse, fetal erythrocytes [oral, 100 mg/kg-bw] (Sawada et al. 1987)

Non-mammalian sex-linked recessive lethal assay

Negative results:
Drosophila (Foureman et al. 1994) [oral, 20 000 or 25 000 ppm, 72 hours; or injection, 5000 ppm, 24 hours]

Unscheduled DNA synthesis
Positive results:
CD-1 mice, liver and kidney (Reitz et al.1980) [inhalation; 200 mg/m³, 6 hours]

Aneuploidy
Positive results:
Saccharomyces cerevisiae,with and without activation (K_och et al. 1988)

Chromosomal aberrations
Positive results:
Chinese hamster lung cells, with activation (Sawada et al. 1987)

Negative results:
Chinese hamster lung cells, without activation (Sawada et al.1987); Chinese hamster fibroblast CHL cells (Ishidate 1983); Chinese hamster DON-6 cells (Sasaki et al. 1980)

Gene conversion
Positive results:
S. cerevisiae,without activation(K_och et al.1988); S. cerevisiae,with activation(Bronzetti et al.1981)

Negative reults:
S. cerevisiae,without activation(Bronzetti et al. 1981); S. cerevisiae, with activation(K_och et al.1988)

Mutagenicity
Positive results:
Salmonella typhimurium BA13/BAL13, with activation (Roldan-Arjona et al.1991)
S. typhimurium TA100, with activation (Bartsch et al. 1975, 1979; Baden et al. 1976, 1978, 1982; Jones and Hathway 1978b; Simmon and Tardiff 1978; Waskell 1978; Oesch et al.1983; Strobel and Grummt 1987; Malaveille et al.1997)
S. typhimurium TA100, without activation (Baden et al. 1976, 1978, 1982; Cerna and Kypenova 1977; Waskell 1978; Strobel and Grummt 1987)
S. typhimurium TA1535, with activation (Baden et al.1977; Jones and Hathway 1978b; Oesch et al.1983)
S. typhimurium TA1535, without activation (Cerna and Kypenova 1977)
S. typhimurium TA1537, with activation (Oesch et al.1983)
S. typhimurium TA1538, without activation (Cerna and Kypenova 1977)
S. typhimurium TA98, with activation (Oesch et al.1983; Strobel and Grummt 1987)
S. typhimurium TA98, without activation (Cerna and Kypenova 1977)
S. typhimurium TA92, with activation (Oesch et al.1983)
S. typhimurium TA97, with activation (Strobel and Grummt 1987)
Escherichia coli K12, with activation (Oesch et al.1983)
E. coli K12, without activation (Greim et al. 1975)
E. coli WP2,with activation (Oesch et al.1983)
S. cerevisiae, with activation (Bronzetti et al.1981; K_och et al.1988);
S. cerevisiae, without activation (K_och et al.1988)
Mouse lymphoma L5178Y T/K +/- cells, with activation (McGregor et al.1991)

Negative results:
S. typhimurium BA13/BAL13, without activation (Roldan-Arjona et al.1991)
S. typhimurium TA100, with activation (Mortelmans et al. 1986)
S. typhimurium TA100, without activation (Bartsch et al. 1975, 1979; Simmon and Tardiff 1978; Oesch et al.1983; Mortelmans et al. 1986)
S. typhimurium TA104, with and without activation(Strobel and Grummt 1987)
S. typhimurium TA1535, with activation (Mortelmans et al. 1986)
S. typhimurium TA1535, without activation (Baden et al.1977; Oesch et al.1983; Mortelmans et al. 1986)
S. typhimurium TA1537, with activation (Mortelmans et al. 1986)
S. typhimurium TA1537, without activation (Oesch et al.1983; Mortelmans et al. 1986)
S. typhimurium TA98, with activation (Mortelmans et al. 1986)
S. typhimurium TA98, without activation (Oesch et al.1983; Mortelmans et al. 1986; Strobel and Grummt 1987)
S. typhimurium TA92, without activation (Oesch et al.1983)
S. typhimurium TA97, without activation (Strobel and Grummt 1987)
E. coli K12, without activation (Oesch et al.1983)
E. coli WP2,without activation (Oesch et al.1983)
Chinese hamster lung V79 cells, hprt locus, with and without activation (Drevon and Kuroki 1979)
Chinese hamster lung V79 cells, ouabain resistance, with and without activation (Drevon and Kuroki 1979)

Sister chromatid exchange
Positive results:
Chinese hamster lung cells, with activation (Sawada et al.1987); Chinese hamster ovary cells (McCarroll et al.1983)

Negative results:
Chinese hamster lung cells, without activation (Sawada et al.1987)

Unscheduled DNA synthesis

Positive results:
Rat, hepatocytes (Costa and Ivanetich 1982)  

Cohort of 138 U.S. workers exposed to 1,1-DCE, where vinyl chloride was not used as a copolymer. Twenty-seven workers were lost to follow-up but considered to be alive in the analyses. Fifty-five people had less than 15 years since first exposure, and only five deaths were observed. The authors indicate no finding was statistically attributable to exposure to 1,1-DCE (Ott et al. 1976).

Cohort of 629 males (447 German and 182 foreign workers) employed at two plants in the Federal Republic of Germany that had produced 1,1-DCE since 1955. Vital status was ascertained for 97% of the 447 German workers. Of the 182 foreign workers, 65 had worked for less than one year, and only 24% (44) were traced. Observed deaths were compared with local and regional rates, without making allowance for a latent period. Within the study period (approximately 20 years), 39 deaths were observed, where 57 [local] and 36 [regional] would have been expected. Five cases of lung carcinoma were observed, whereas 3.9 [local] and 2.2 [regional] were expected; this result was not statistically significant. Workers in the factory were also potentially exposed to vinyl chloride and acrylonitrile (Thiess et al. 1979).

The International Agency for Research on Cancer Working Group noted that both Ott et al. (1976) and Thiess et al. (1979) suffered from the limited size of cohorts, the short observation period and the small numbers of deaths from specific causes. The fact that no allowance was made for latent period may have resulted in an overestimation of the expected numbers and an underestimation of risk.

In an attempt to identify the specific exposure associated with an excess lung cancer risk noted previously in a U.S. synthetic chemicals plant, Waxweiler et al. (1981) considered 19 chemicals, one of which was 1,1-DCE. Company personnel assigned a rank of exposure to 1,1-DCE (from 0 to 5) to each job in the plant for each year since its opening in 1942. These exposure data were then linked with detailed, individual work histories to obtain an individual estimate for each of the 4806 male workers employed at the plant. The doses calculated were the product of the exposure rank of the job and the number of days worked at that job. Cumulative doses for 45 workers who had died of lung cancer during the study period of 1942–1973 were then compared to expected doses based on the cumulative exposure of subcohorts of fellow workers matched individually to the cases by year of birth and age of hire into the plant. This comparison failed to suggest any specific association between exposure to 1,1-DCE in the plant and excess lung cancer risk.