Brown-Woodman P D, Hayes L C, Huq F, Herlihy C, Picker K, Webster W S
Department of Biochemical Sciences, Faculty of Health Sciences, University of Sydney, Lidcombe, N.S.W., Australia.
Teratology. 1998 Jun;57(6):321-33. doi: 10.1002/(SICI)1096-9926(199806)57:6<321::AID-TERA5>3.0.CO;2-Z.
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.
卤代烃在工业、实验室和家庭中广泛使用。在本研究中，使用大鼠胚胎培养来检测三种此类溶剂——氯仿、二氯甲烷和二溴乙烷——的胚胎毒性/致畸潜力。结果表明，每种溶剂在体外对发育中的大鼠胚胎都有浓度依赖性的胚胎毒性作用。所测试的每种卤代烃的效应浓度和无效应浓度（以μmol/ml培养基表示）分别为：二溴乙烷——0.33，<0.18；氯仿——2.06，1.05；二氯甲烷——6.54，3.46。将本研究中发现具有胚胎毒性的氯仿和二氯甲烷水平与报告的人体在受控暴露后达到的血液水平进行了比较。在工业环境中，如果遵守当前的暴露水平，氯仿和二氯甲烷对人类似乎几乎没有生殖毒性潜力。母亲需要达到致命或接近致命的溶剂水平才能达到胚胎毒性水平。对于二溴乙烷，由于其致癌性，没有关于人体受控暴露后的报告。为了阐明胚胎毒性的机制，在将大鼠胚胎暴露于所研究的每种卤代烃的胚胎毒性水平后，进行了组织学研究，暴露时间逐渐增加，直至达到标准的40小时培养时间。在暴露于这些溶剂的胚胎毒性水平达16小时或更长时间的所有胚胎中，发育中的神经管神经上皮细胞明显死亡是一个突出特征。
