Morrissey R E, Schwetz B A, Hackett P L, Sikov M R, Hardin B D, McClanahan B J, Decker J R, Mast T J
Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Environ Health Perspect. 1990 Jun;86:79-84. doi: 10.1289/ehp.908679.
A series of studies to further evaluate the developmental and reproductive toxicity of inhaled 1,3-butadiene was sponsored by the National Toxicology Program. Pregnant Sprague-Dawley rats (24-28/group) and Swiss (CD-1) mice (18-22/group) were exposed to atmospheric concentrations of 0, 40, 200, or 1000 ppm 1,3-butadiene for 6 hr/day on days 6 through 15 of gestation (dg) and killed on dg 18 (mice) or dg 20 (rats). Subsequently, the uterine contents were evaluated; individual fetal body weights were recorded; and external, visceral, and skeletal examinations were performed. In rats, maternal toxicity was observed in the 1000-ppm group in the form of reduced extragestational weight gain and, during the first week of treatment, decreased body weight gain. Under these conditions, there was no evidence of developmental toxicity in rats. In contrast, results of the mouse developmental toxicity study indicated that the fetus may be more susceptible than the dam to inhaled 1,3-butadiene. Maternal toxicity was observed in mice at the 200- and 1000-ppm 1,3-butadiene exposure levels, whereas 40 ppm and higher concentrations of 1,3-butadiene caused significant exposure-related reductions in the mean body weights of male fetuses. Mean body weights of female fetuses were also reduced at the 200- and 1000-ppm exposure levels. No increased incidence of malformations was observed in either study. Other studies addressing male reproductive and mutagenesis end points were performed with B6C3F1 mice (sperm-head morphology) and Swiss (CD-1) mice (dominant lethal study).(ABSTRACT TRUNCATED AT 250 WORDS)
美国国家毒理学计划赞助了一系列进一步评估吸入 1,3 - 丁二烯发育毒性和生殖毒性的研究。妊娠第 6 至 15 天,将怀孕的斯普拉格 - 道利大鼠(每组 24 - 28 只)和瑞士(CD - 1)小鼠(每组 18 - 22 只)每天暴露于大气浓度为 0、40、200 或 1000 ppm 的 1,3 - 丁二烯中 6 小时,并在妊娠第 18 天(小鼠)或第 20 天(大鼠)处死。随后,评估子宫内容物;记录各胎儿体重;并进行外部、内脏和骨骼检查。在大鼠中,1000 ppm 组出现母体毒性,表现为孕期外体重增加减少,且在治疗的第一周体重增加减少。在这些条件下,没有大鼠发育毒性的证据。相比之下,小鼠发育毒性研究结果表明,胎儿可能比母体对吸入的 1,3 - 丁二烯更敏感。在 200 和 1000 ppm 的 1,3 - 丁二烯暴露水平下观察到小鼠母体毒性,而 40 ppm 及更高浓度的 1,3 - 丁二烯导致雄性胎儿平均体重显著降低,与暴露相关。在 200 和 1000 ppm 暴露水平下,雌性胎儿平均体重也降低。两项研究均未观察到畸形发生率增加。其他针对雄性生殖和诱变终点的研究是用 B6C3F1 小鼠(精子头部形态)和瑞士(CD - 1)小鼠(显性致死研究)进行的。(摘要截断于 250 字)