Johannsen F R, Levinskas G J, Rusch G M, Terrill J B, Schroeder R E
Department of Medicine and Health Sciences, Monsanto Company, St. Louis, Missouri 63167.
J Toxicol Environ Health. 1988;25(3):299-315. doi: 10.1080/15287398809531211.
Repeated inhalation exposure and 1-generation reproduction studies have been conducted in the rat to address the adequacy of the 10 ppm occupational exposure limit established for 1,2,3-trichloropropane (TriCP). Groups of 5 rats per sex were exposed for 6 h/d, 5 d/wk up to 4 wk to target TriCP concentrations of 0-900 ppm. Nine of 10 rats died after a single exposure at 900 ppm. Additional deaths were seen in the 300 (1 death) and 600 (3 deaths) ppm test groups. Mean body weights for all TriCP-treated groups were lower than control values. Liver weights were increased in animals of both sexes at 600 ppm and lower. For females ovary weights for the 300 and 600 ppm groups and spleen weights for the 300 ppm group were lower than those of controls. Males exhibited decreased testes weights only at the 600 ppm TriCP level (not evaluated at 900 ppm). Results of a 13-wk exposure, 6 h/d, 5 d/wk of 15 rats/sex.group to TriCP target vapor concentrations of 5, 15, or 50 ppm also resulted in liver weight increases at all test levels. Histopathologic examination showed hepatocellular hypertrophy in male rats at all TriCP levels. Other microscopic findings related to treatment in rats exposed to 15 ppm and to 5 ppm TriCP included lung hyperplasia (both sexes) and splenic extramedullary hematopoiesis (females only) and parallel observed organ weight increases. No treatment-related deaths were observed in this study, nor were there apparent effects on the hematology or clinical chemistries. Group mean body weights at 50 ppm (both sexes) and 15 ppm (females only) TriCP were reduced when compared to controls. In a 13-wk follow-up study in rats at 0, 0.5, and 1.5 ppm TriCP, no gross or microscopic findings related to treatment were found. Groups of 10 male and 20 female rats were exposed 6 h/d, 5 d/wk to 0, 5, or 15 ppm TriCP vapor during premating and mating. Females also were exposed during gestation. Low mating performance was observed in all groups of female rats including the controls, although fewer females in the 15-ppm group mated than in other study groups. Mating and fertility indices of male rats in both treated and control groups were generally low. All measured progeny indices appeared unaffected by treatment. A follow-up study of the same design was conducted at levels of 0, 0.5, and 1.5 ppm TriCP.(ABSTRACT TRUNCATED AT 250 WORDS)
已在大鼠中进行了重复吸入暴露和一代繁殖研究，以评估为1,2,3 - 三氯丙烷（TriCP）设定的10 ppm职业接触限值是否合适。每组5只大鼠，雌雄各半，每天暴露6小时，每周暴露5天，长达4周，目标TriCP浓度为0 - 900 ppm。10只大鼠中有9只在900 ppm单次暴露后死亡。在300 ppm（1只死亡）和600 ppm（3只死亡）测试组中也出现了额外死亡。所有接受TriCP处理组的平均体重均低于对照组。600 ppm及更低浓度下，雌雄动物的肝脏重量均增加。对于雌性，300 ppm和600 ppm组的卵巢重量以及300 ppm组的脾脏重量低于对照组。雄性仅在600 ppm TriCP水平时睾丸重量降低（900 ppm未评估）。15只大鼠/性别组，每天暴露6小时，每周暴露5天，持续13周，暴露于5、15或50 ppm TriCP目标蒸汽浓度下，结果在所有测试水平下肝脏重量均增加。组织病理学检查显示，在所有TriCP水平下雄性大鼠均有肝细胞肥大。暴露于15 ppm和5 ppm TriCP的大鼠中，与处理相关的其他微观发现包括肺增生（雌雄均有）和脾外造血（仅雌性），并观察到相应器官重量增加。本研究中未观察到与处理相关的死亡，对血液学或临床化学也无明显影响。与对照组相比，50 ppm（雌雄均有）和15 ppm（仅雌性）TriCP组的组平均体重降低。在一项对0、0.5和1.5 ppm TriCP大鼠进行的13周后续研究中，未发现与处理相关的大体或微观发现。10只雄性和20只雌性大鼠在交配前和交配期间每天暴露6小时，每周暴露5天，接触0、5或15 ppm TriCP蒸汽。雌性在妊娠期也暴露。在所有雌性大鼠组包括对照组中均观察到交配性能较低，尽管15 ppm组中交配的雌性比其他研究组少。处理组和对照组雄性大鼠的交配和生育指数普遍较低。所有测量的后代指数似乎均未受处理影响。在0、0.5和1.5 ppm TriCP水平下进行了相同设计的后续研究。（摘要截于250字）
