Ono A, Sekita K, Ogawa Y, Hirose A, Suzuki S, Saito M, Naito K, Kaneko T, Furuya T, Kawashima K, Yasuhara K, Matsumoto K, Tanaka S, Inoue T, Kurokawa Y
Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.
J Environ Pathol Toxicol Oncol. 1996;15(1):9-20.
Male and female Sprague-Dawley rats were exposed to toluene vapor at 600 and 2000 ppm for 6 h/day, and effects on their fertility were investigated. Females were exposed from 14 days before mating until day 7 of gestation. Males were exposed for a total of 90 days, including the mating period; treatment was begun 60 days before pairing, and toxicity with respect to testicular and reproductive functions was examined. In females of the 2000 ppm-treated group, salivation and lacrimation that may have been caused by CNS depression were observed starting 20 days after exposure. Although no abnormalities were seen in mating behavior or fertility, fetal mortality and the number of dams with dead fetuses increased in the 2000 ppm group. In the males exposed to 2000 ppm toluene for 90 days, an increase in kidney weights and a decrease in thymus weights were observed. Basophilic changes and necrosis of kidney tubules were greater at the higher exposure level. Additionally, decreases in the weights of the epididymides and spermatic count were observed, indicating toxicity of toluene to the male reproductive system in vivo for the first time. In conclusion, embryo-fetal toxic effects were apparent in female rats exposed to toluene before and during the early stage of pregnancy. Subacute exposure to a high level (2000 ppm) of toluene vapor elicited mild toxic changes in the kidneys, thymus, and reproductive organs of males. Toxic effects on fertility and reproduction were thus demonstrated not only in females but also in males exposed to toluene vapor in the present study.
将雄性和雌性斯普拉格-道利大鼠暴露于浓度为600 ppm和2000 ppm的甲苯蒸气中，每天暴露6小时，并研究其对生育能力的影响。雌性大鼠在交配前14天开始暴露，直至妊娠第7天。雄性大鼠总共暴露90天，包括交配期；在配对前60天开始处理，并检查对睾丸和生殖功能的毒性。在2000 ppm处理组的雌性大鼠中，从暴露后20天开始观察到可能由中枢神经系统抑制引起的流涎和流泪现象。虽然在交配行为或生育能力方面未观察到异常，但2000 ppm组的胎儿死亡率和死胎母鼠数量增加。在暴露于2000 ppm甲苯90天的雄性大鼠中，观察到肾脏重量增加和胸腺重量减少。在较高暴露水平下，肾小管的嗜碱性变化和坏死更为明显。此外，还观察到附睾重量和精子计数下降，这首次表明甲苯对雄性生殖系统在体内具有毒性。总之，在怀孕前和怀孕早期暴露于甲苯的雌性大鼠中，胚胎-胎儿毒性作用明显。亚急性暴露于高水平（2000 ppm）的甲苯蒸气会引起雄性大鼠肾脏、胸腺和生殖器官的轻度毒性变化。因此，在本研究中，不仅在雌性大鼠中，而且在暴露于甲苯蒸气的雄性大鼠中都证明了对生育能力和生殖的毒性作用。
