Hamm T E, Raynor T H, Phelps M C, Auman C D, Adams W T, Proctor J E, Wolkowski-Tyl R
Fundam Appl Toxicol. 1985 Jun;5(3):568-77. doi: 10.1016/0272-0590(85)90104-6.
Male and female Fischer-344 rats were exposed to methyl chloride by inhalation (0, 150, 475, or 1500 ppm, 6 hr/day, 5 days/week, 40 males and 80 females per group). The only treatment-related clinical signs were a 10 to 20% body weight gain depression (BWGD) in both males and females exposed to 1500 ppm at all weekly weighings after 2 weeks of exposure and a 5-7% BWGD in 475-ppm exposed animals after Day 57. After 10 weeks the exposure schedule was changed to 6 hr/day, 7 days/week and each male was mated to two exposed females. The mating period was ended after 2 weeks, at which point 10 males/group were necropsied. The only treatment-related lesions found were severe bilateral testicular degeneration (10/10) and granulomas in the epididymis (3/10) in the 1500-ppm males. The remaining 30 males per group were then removed from exposure and mated during a 2-week period with 60 unexposed females. The exposed females were continued on exposure from the start of mating to Postnatal Day 28 (6 hr/day, 7 days/week). The females were not exposed from Gestation Day 18 to Postnatal Day 4, and the pups were never directly exposed prior to weaning. There were no significant differences between groups in the number of exposed or unexposed females that mated, as evidenced by copulation plugs. No litters were born to exposed or unexposed females mated to the 1500-ppm males. There was no significant difference in the number of litters produced by the 150-ppm groups when compared to the control groups. Fewer litters were born in the 475-ppm groups than in the control groups. No differences in litter size, sex ratio, pup viability, or pup growth were found among the 475-ppm, 150-ppm, or control F0 groups. When bred 10 weeks after the cessation of exposures, 5 to 20 1500-ppm F0 males had regained the ability to sire normal litters. The same number of 475-ppm F0 males proved as fertile (15/20) as control F0 males (13/20). After weaning, F1 pups from the 475-, 150-, and 0-ppm groups were exposed to the same concentrations of methyl chloride for 10 weeks and then mated. A trend toward decreased fertility was found in the 475-ppm F1 group.
将雄性和雌性Fischer - 344大鼠通过吸入方式暴露于氯甲烷中（浓度分别为0、150、475或1500 ppm，每天6小时，每周5天，每组40只雄性和80只雌性）。唯一与处理相关的临床体征是，暴露2周后，在所有每周称重时，暴露于1500 ppm的雄性和雌性大鼠体重增加均下降10%至20%（体重增加抑制，BWGD），以及在第57天后，暴露于475 ppm的动物体重增加下降5 - 7%。10周后，暴露时间表改为每天6小时，每周7天，每只雄性与两只暴露的雌性大鼠交配。2周后交配期结束，此时每组处死10只雄性大鼠。在暴露于1500 ppm的雄性大鼠中，唯一发现的与处理相关的病变是严重的双侧睾丸退化（10/10）和附睾肉芽肿（3/10）。然后每组剩余的30只雄性大鼠停止暴露，并在2周内与60只未暴露的雌性大鼠交配。暴露的雌性大鼠从交配开始到产后第28天持续暴露（每天6小时，每周7天）。雌性大鼠在妊娠第18天至产后第4天不暴露，幼崽在断奶前从未直接暴露。通过交配栓证明，交配的暴露或未暴露雌性大鼠数量在各组之间没有显著差异。与暴露于1500 ppm雄性大鼠交配的暴露或未暴露雌性大鼠均未产仔。与对照组相比，暴露于150 ppm组产仔数没有显著差异。暴露于475 ppm组的产仔数少于对照组。在暴露于475 ppm、150 ppm或对照组的F0代中，窝仔数、性别比例、幼崽存活率或幼崽生长方面均未发现差异。在停止暴露10周后进行繁殖时，5至20只暴露于1500 ppm的F0代雄性大鼠恢复了生育正常窝仔的能力。相同数量的暴露于475 ppm的F0代雄性大鼠（15/20）与对照组F0代雄性大鼠（13/20）一样具有生育能力。断奶后，将来自475 ppm、150 ppm和0 ppm组的F1代幼崽暴露于相同浓度的氯甲烷中10周，然后进行交配。在暴露于475 ppm的F1代组中发现生育能力有下降趋势。
