IRIS Toxicological Review and Summary Documents for Chloroethane (External Review Draft)

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Chloroethane (CE) is a gaseous halohydrocarbon under ambient conditions. Its uses include: a topical analgesic, an anesthetic when mixed with nitrous dioxide or trichloroethane, a degreasing agent, and an agent to blow styrene in foaming operations. Anecdotal human reports indicate that recreational CE sniffing causes neurological disturbances. Nothing is known about chronic oral toxicology in animals or humans. The lowest dose effect by chronic inhalation in CF-1 mice suggests a weak fetotoxic effect, a delayed skull foramina closure, at 13,057 mg/m3, while the dams were unremarkable. Using this effect an RfC was derived. CE caused uterine cancer in B6C3F1 female mice at chronic exposures of 39,600 mg/m3 with 90% incidence.

Many females showed metastasis at a number of organ sites and died early due to tumor load. Uterine carcinogenesis is uncommon in rodents, but is more common in humans. The mode of action is suggested by positive genotoxicity and structural similarity to bromoethane which also causes uterine cancers in the B6C3F1 mouse. Metabolic studies show that either chloromethane (CM) or CE can deplete cellular GSH pools by excessive reductive conjugation. CM and CE, when in excess, can be oxidized to formaldehyde and acetaldehyde, respectively, and both intermediates are regarded as posing a hazard to humans. For hazard identification purposes CE is judged to be a likely human carcinogen. An estimate of cancer potency was also derived using a linearized multistage model, though uncertainty exists because of bioassay limitations.

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