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State of the Science Report for Dibromoethane

Exposure Assessment, Hazard Characterization and Risk Evaluation

An upper-bounding estimate of exposure to 1,2-dibromoethane was calculated to be 0.089 µg/kg-bw per day in non-formula-fed infants (0-6 months), based on maximum concentrations reported in ambient air and limits of detection for other media in which the compound was not detected (i.e., indoor air, drinking water and food; see Table 1). However, indoor and ambient air likely contribute proportionally more to overall exposure than indicated in the upper bounding estimates presented in Table 1 and are likely the principal media of exposure to 1,2-dibromoethane, since it is volatile and readily partitions into air and also since the estimated intakes are based on limits of detection for several media.

Given that these upper-bounding estimates are based on detection limits for analyses of all media other than ambient air, and since the use of 1,2-dibromoethane has dropped significantly, confidence that these values overestimate actual exposures in Canada is high.

The International Programme on Chemical Safety (IPCS, 1996) concluded that 1,2-dibromoethane is a carcinogen in rodents and a potential human carcinogen. The International Agency for Research on Cancer (IARC, 1999) concluded that there is inadequate evidence in humans and sufficient evidence in experimental animals for the carcinogenicity of 1,2-dibromoethane; 1,2-dibromoethane was classified as probably carcinogenic to humans (Group 2A). These conclusions were based on significant increases in tumour incidences in rats and mice exposed via multiple routes (see Table 2 for an overview of the toxicological database). Significant increases in the incidences of squamous cell carcinomas of the forestomach were observed in male and female rats administered 1,2-dibromoethane by gavage at 37 mg/kg-bw per day or more for up to 61 weeks (NCI, 1978). Exposure of rats to 77 mg/m³ or more via inhalation for 103 weeks resulted in significant increases in the incidences of adenocarcinomas and adenomas of the nasal cavity in both sexes, mammary gland fibroadenomas in females and tunica vaginalis mesotheliomas and nasal cavity adenomatous polyps in males (NTP, 1982). Dermal exposure of mice to 25 mg/day for up to 594 days (approximately equivalent to 833 mg/kg-bw per day; Health Canada, 1994) resulted in an increased incidence of papillomas of the lung in female mice (Van Duuren et al., 1979). In each of these bioassays, these significant increases were observed at the lowest exposure level tested.

1,2-Dibromoethane was genotoxic in a large number and variety of assays, including in vivo DNA binding, DNA damage and non-mammalian mutagenicity assays and in vitro mutagenicity, clastogenicity and DNA damage assays (Table 2).

The weight of evidence of mutagenicity and carcinogenicity of 1,2-dibromoethane is supported by rule-based structure-activity analysis (DEREK; LHASA Ltd., 2002).

Male reproductive effects are considered to be the critical non-neoplastic effect. In a short-term longitudinal study in male forestry workers, significantly decreased sperm velocity and semen volume were observed in subjects exposed via inhalation to 0.46 mg/m³ or greater (occupational time-weighted average) levels of 1,2-dibromoethane in conjunction with dermal exposure (Schrader et al., 1988). Male reproductive effects were also observed in multiple species of experimental animals exposed to the lowest doses or concentrations tested. The lowest Lowest-Observed-Effect Level (LOEL) for reproductive effects for the oral route of exposure was 2 mg/kg-bw per day for 12 months (followed by further administration at 4 mg/kg-bw every second day for an additional 10-12 months) in bulls for reversible low sperm density, poor motility and altered spermatozoa morphology (Amir and Volcani, 1965). Testicular degeneration in male rats was observed at an inhalation concentration of 77 mg/m³ in conjunction with other neo-plastic effects including toxic nephropathy in males, retinal atrophy and adrenal cortex degeneration in females and increases in hepatic necrosis in both sexes (NTP, 1982).

Owing to an extensive data set on carcinogenicity and in vivo and in vitro genotoxicity assays, there is high confidence in the health effects database upon which the conclusion that 1,2-dibromoethane is considered to be a genotoxic carcinogen is based.

On the basis of available information, it is concluded that 1,2-dibromoethane induces tumours likely by direct interaction with genetic material. It is, therefore, considered to be a substance for which there may not be a level of exposure below which there is no probability of adverse health effects.