Agarwal D K, Bose M
Industrial Toxicology Research Centre, Lucknow, India.
Indian J Exp Biol. 1992 Jun;30(6):504-8.
Adult male Wistar rats were exposed to methylisocyanate (MIC, 3.2 mg/l, single inhalation exposure for 8 min under static condition) or ethyl methanesulphonate (EMS, 150 mg/kg, single ip dose) for the assessment of germ cell mutagenicity and reproductive effects. Sequential matings of treated males with normal females on days 1-7, 8-14 and 15-21 post-exposure did not indicate any induction of dominant lethal mutation (increased frequency of preimplantation losses and early fetal deaths) by MIC but it was significantly induced by EMS as compared to respective controls. Males, necropsied after 21 days of exposure, showed no effect of MIC on epididymal sperm density and morphology. EMS also had no effect on sperm density but it significantly induced morphological abnormalities in sperm as compared to untreated controls. There was an acute and transitional reduction in reproductive performance (10-21%) of MIC-exposed males during days 1-14 post-exposure followed by recovery to the normal level during days 15-21 post-exposure. The progeny of MIC-exposed males was also normal in terms of litter size, litter weight, neonatal survival and body weight gain in litters up to 10 days post-partem. It is concluded with the evidence at hand that the observed failure of MIC to cause germ cell mutagenicity is related to its poor biodistribution to the target site(s) and a transient reduction in the reproductive performance of MIC-exposed males is a result of general stress and disconsolate copulation.
成年雄性Wistar大鼠暴露于甲基异氰酸酯（MIC，3.2毫克/升，在静态条件下单次吸入暴露8分钟）或甲磺酸乙酯（EMS，150毫克/千克，单次腹腔注射剂量），以评估生殖细胞致突变性和生殖效应。在暴露后第1 - 7天、8 - 14天和15 - 21天，将处理过的雄性大鼠与正常雌性大鼠进行连续交配，结果表明MIC未诱导任何显性致死突变（着床前损失和早期胎儿死亡频率增加），但与各自的对照组相比，EMS显著诱导了显性致死突变。暴露21天后进行尸检的雄性大鼠显示，MIC对附睾精子密度和形态没有影响。EMS对精子密度也没有影响，但与未处理的对照组相比，它显著诱导了精子形态异常。暴露于MIC的雄性大鼠在暴露后第1 - 14天生殖性能出现急性和过渡性下降（10 - 21%），随后在暴露后第15 - 21天恢复到正常水平。暴露于MIC的雄性大鼠的后代在产后10天内的窝仔数、窝仔体重、新生仔鼠存活率和体重增加方面也均正常。根据现有证据得出结论，观察到的MIC未能引起生殖细胞致突变性与它在靶位点的生物分布不佳有关，而暴露于MIC的雄性大鼠生殖性能的短暂下降是一般应激和交配意愿低落的结果。
