Toxicity profile of chloroacetaldehyde

Chloroacetaldehyde, a probable metabolite of 2-chloroethanol (ethylene chlorohydrin), was studied in a number of in vivo animal systems, in in vitro hemolysis tests, and in tissue cultures to obtain a toxicity profile of the compound. Acute toxicity tests were conducted in mice, rats, guinea pigs, and rabbits by one or more routes of administration. Tissue culture tests utilized both the agar-overlay and protein assay methods. Irritant activity was evaluated by intramuscular implantation, intradermal injection, and dermal and ophthalmic applications in the rabbit. Acute cardiovascular effects in rabbits were also determined. Sleeping-time tests in mice were conducted to assess the effect of chloroacetaldehyde pretreatment (inhalation and intraperitoneal) upon drug-metabolizing enzymes. The compound was tested in guinea pigs for its sensitizing potential. Cumulative (30 daily injections) and subacute (three injections per week for 12 weeks) toxicity studies were conducted to evaluate subtle toxic effects (e.g., weight gain, hematology, and histopathology) as well as lethality. Chloroacetaldehyde is a very toxic and irritating compound in acute tests; in tests of longer duration, most of the parameters measured appeared to be normal in animals that survived its lethal activity. The acute toxic effects of chloroacetaldehyde are compared with those of 2-chloroethanol. The former is inherently more toxic and irritating, while the latter exhibits greater ease of quantitative penetration through the GI tract and the intact skin.