Working P K, Bus J S, Hamm T E
Toxicol Appl Pharmacol. 1985 Jan;77(1):144-57. doi: 10.1016/0041-008x(85)90275-3.
Studies were performed to assess the effects of inhaled methyl chloride (MeCl) on sperm quality and testicular histopathology in the Fischer 344 rat. Adult male F-344 rats were exposed to 1000 or 3000 ppm MeCl 6 hr/day for 5 days, or received an ip injection of 0.2 mg triethylenemelamine (TEM)/kg on the afternoon of Day 5. Five males from a control group and each of the three treatment groups were killed weekly for 8 weeks, and five more from the control and 3000 ppm groups at Week 16 postexposure. Male rats from the 1000 ppm MeCl- and TEM-exposed groups exhibited no consistent difference from control males in any parameter measured. In the 3000 ppm MeCl group, over 50% of the males had uni- or bilateral sperm granulomas in the cauda epididymis. Testes weights were significantly depressed in these males by 3 weeks postexposure, and remained depressed as late as 8 weeks after treatment. Testicular spermatid head counts were significantly lower by 2 weeks postexposure, and the testes showed a characteristic cytotoxic response to MeCl exposure, including a delay in spermiation, chromatin margination in round spermatids, epithelial vacuolation, luminal exfoliation of spermatogenic cells, and multinucleated giant cells. Counts of repopulating seminiferous tubule cross sections and of testicular sperm heads at 7 weeks postexposure indicated that 60 to 70% of the spermatogonial stem cells had been killed by MeCl exposure. Sperm isolated from the vasa deferentia had significantly depressed numbers and an elevated frequency of abnormal sperm head morphology by Week 1 postexposure, and significantly depressed sperm motility and an elevated frequency of headless tails by Week 3 postexposure. All parameters measured in the testes and in vasa deferentia sperm showed varying degrees of recovery, and all were near the normal range by Week 16 postexposure except sperm count. These data suggest that the previously reported high preimplantation loss caused by methyl chloride exposure may be primarily due to cytotoxic effects on the testis and epididymal epithelium, rather than to direct genotoxic effects on the sperm.
开展了多项研究，以评估吸入氯甲烷（MeCl）对Fischer 344大鼠精子质量和睾丸组织病理学的影响。成年雄性F-344大鼠每天暴露于1000或3000 ppm的MeCl中，持续6小时，共5天，或者在第5天下午接受腹腔注射0.2 mg三乙烯三聚氰胺（TEM）/kg。对照组以及三个治疗组中的每组各5只雄性大鼠，在8周内每周处死一批，暴露后第16周，再从对照组和3000 ppm组中各处死5只。在任何测量参数方面，暴露于1000 ppm MeCl和TEM的雄性大鼠与对照雄性大鼠均未表现出一致差异。在3000 ppm MeCl组中，超过50%的雄性大鼠在附睾尾部出现单侧或双侧精子肉芽肿。暴露3周后，这些雄性大鼠的睾丸重量显著降低，直至治疗后8周仍保持较低水平。暴露后2周，睾丸精子细胞头部计数显著降低，睾丸显示出对MeCl暴露的典型细胞毒性反应，包括精子排放延迟、圆形精子细胞中的染色质边缘化、上皮空泡化、生精细胞的管腔脱落以及多核巨细胞。暴露后7周，对再填充的生精小管横截面积和睾丸精子头部计数表明，60%至70%的精原干细胞已被MeCl暴露杀死。暴露后第1周，从输精管分离出的精子数量显著降低，精子头部形态异常的频率升高；暴露后第3周，精子活力显著降低，无头尾的频率升高。在睾丸和输精管精子中测量的所有参数均显示出不同程度的恢复，除精子计数外，暴露后第16周时所有参数均接近正常范围。这些数据表明，先前报道的由氯甲烷暴露导致的高着床前损失可能主要是由于对睾丸和附睾上皮的细胞毒性作用，而非对精子的直接遗传毒性作用。
