In vitro assessment of the effect of halogenated hydrocarbons: chloroform, dichloromethane, and dibromoethane on embryonic development of the rat.
Halogenated hydrocarbons are widely used in industry, the laboratory, and in the home. In the present study three of these solvents--chloroform, dichloromethane, and dibromoethane--were examined for embryotoxic/teratogenic potential using rat embryo culture. The results showed that each of the solvents had a concentration-dependent embryotoxic effect on the developing rat embryo in vitro. The effect and no-effect concentrations (expressed in mumol/ml culture medium), respectively, for each of the halogenated hydrocarbons tested were: dibromoethane--0.33, < 0.18; chloroform--2.06, 1.05; dichloromethane--6.54, 3.46. The levels of chloroform and dichloromethane found to be embryotoxic in the present study were compared to reported blood levels attained following controlled human exposure. In the industrial situation, if the current exposure levels are adhered to, chloroform and dichloromethane appear to have little potential for reproductive toxicity in the human. Fatal or near fatal solvent levels would be required in the mother for the embryotoxic level to be reached. For dibromoethane, there are no reports following controlled human exposure presumably due to its carcinogenicity. In an attempt to elucidate the mechanism of embryotoxicity, histological studies were performed after exposure of rat embryos to an embryotoxic level of each of the halogenated hydrocarbons studied, for increasing time periods up to the standard 40-hour culture. Marked cell death in the neuroepithelium of the developing neural tube was a prominent feature in all embryos exposed to an embryotoxic level of these solvents for periods of 16 hours of longer.
Department of Biochemical Sciences, Faculty of Health Sciences, University of Sydney, Lidcombe, N.S.W., Australia. P.Woodman@cchs.usyd.edu.au
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D000818:Animals; D002725:Chloroform / Q000633:toxicity; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D015946:Ethylene Dibromide / Q000633:toxicity; D005069:Evaluation Studies as Topic; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008752:Methylene Chloride / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*
D006846:Hydrocarbons, Halogenated; D012997:Solvents; D013723:Teratogens; D015946:Ethylene Dibromide; D008752:Methylene Chloride; D002725:Chloroform