Wolkowski-Tyl R, Phelps M, Davis J K
Teratology. 1983 Apr;27(2):181-95. doi: 10.1002/tera.1420270206.
One hundred bred Fischer-344 female rats were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 25 females per exposure concentration, from gestation day (gd) 7 through gd 19. On gd 20, the females were sacrificed for evaluation of maternal reproductive and fetal parameters. Maternal and fetal toxicity was apparent at the highest exposure concentration. There were no methyl chloride-induced external, skeletal, or visceral abnormalities seen in the fetuses. One hundred thirty-two C57BL/6 female mice bred to C3H males to produce B6C3F1 offspring were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 33 females per exposure concentration, from gd 6 through gd 17. Exposure to the entire 1,500-ppm group was terminated on gd 10-14, with the animals killed in extremis. Selective necrosis of neurons in the internal granular layer of the cerebellum, ranging from individual cell involvement to focal areas comprising large numbers of neurons, was found in all females. On gd 18, the females from the other treatment groups, all of which survived, were killed for evaluation of maternal reproductive and fetal parameters. No evidence was seen of maternal or fetal toxicity in these exposure groups. There were no significant alterations in external appearance in fetuses from any of the exposure groups. Visceral examination of mouse fetuses revealed a small, but statistically significant, incidence of heart defects in litters of the 500-ppm group. The anomaly, a reduction or absence of the atrioventricular valve, chordae tendineae, and papillary muscle, was observed on the left side (bicuspid valve) in three fetuses and the right side (tricuspid valve) in six fetuses: three males and six females. It is concluded that methyl chloride inhalation exposure in pregnant rats, during critical periods of embryo and fetal development, is not teratogenic at concentrations which elicit maternal and fetal toxicity. In pregnant mice, methyl chloride was severely toxic to dams following 4 days or more of exposure to 1,500 ppm in air. Methyl chloride, at 500, but not 100 ppm, was teratogenic in mice, leading to a malformation in the heart. No embryo-fetal toxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 100 ppm of ethyl chloride.
100只繁殖用Fischer-344雌性大鼠从妊娠第7天（gd7）至gd19，每天6小时暴露于含有0、100、500或1500 ppm氯甲烷的环境中，每个暴露浓度有25只雌性大鼠。在gd20，处死雌性大鼠以评估母体生殖和胎儿参数。在最高暴露浓度下，母体和胎儿毒性明显。在胎儿中未观察到氯甲烷诱导的外部、骨骼或内脏异常。132只与C3H雄性小鼠交配以产生B6C3F1后代的C57BL/6雌性小鼠从gd6至gd17，每天6小时暴露于含有0、100、500或1500 ppm氯甲烷的环境中，每个暴露浓度有33只雌性小鼠。1500 ppm组的所有动物在gd10 - 14时因极度虚弱而被处死。在所有雌性小鼠中均发现小脑内颗粒层神经元的选择性坏死，范围从单个细胞受累到包含大量神经元的局灶区域。在gd18，其他存活的处理组雌性小鼠被处死以评估母体生殖和胎儿参数。在这些暴露组中未发现母体或胎儿毒性的证据。任何暴露组的胎儿外观均无明显改变。对小鼠胎儿的内脏检查显示，500 ppm组的窝仔中心脏缺陷的发生率虽低，但具有统计学意义。这种异常表现为房室瓣、腱索和乳头肌减少或缺失，在3只胎儿的左侧（二尖瓣）和6只胎儿的右侧（三尖瓣）观察到：3只雄性和6只雌性。结论是，在胚胎和胎儿发育的关键时期，怀孕大鼠吸入氯甲烷，在引起母体和胎儿毒性的浓度下不会致畸。在怀孕小鼠中，暴露于空气中1500 ppm氯甲烷4天或更长时间后，氯甲烷对母鼠具有严重毒性。氯甲烷在500 ppm时对小鼠具有致畸性，可导致心脏畸形，但在100 ppm时无此作用。在胚胎和胎儿发育的关键时期，小鼠暴露于100 ppm氯乙烷未出现胚胎 - 胎儿毒性或致畸性。
