Nagao T, Wada K, Kuwagata M, Ono H
Department of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
Reprod Toxicol. 2000 Sep-Oct;14(5):403-15. doi: 10.1016/s0890-6238(00)00098-8.
Styrene dimers and trimers (SDT) were evaluated for reproductive toxicity in Sprague-Dawley rats. SDT was administered orally to rats at doses of 0, 0.04, 0.2, and 1.0 mg/kg from day 6 of gestation through day 21 after delivery. Clinical signs, including pregnancy and lactation, and changes in body weight and food consumption were assessed. All dams underwent a gross necropsy examination. The brain, liver, kidney, ovary, uterus, thyroid gland, and pituitary were weighed. Offspring were evaluated for the effects of the test compound on viability, growth, anogenital distance, preputial separation and vaginal opening, behavioral function, estrous cycling, mating, and fertility. There were no test compound-related clinical signs or effects on body weight or food consumption in dams during any phase of the study. In addition, no abnormalities in delivery or lactation, including gestation length, were noted in any dam. No dose-dependent changes were observed in pup viability or growth. There were no adverse effects of SDT on any developmental landmark, learning, memory, or estrous cycling in offspring. The number of days to inseminations in the 0.2 mg/kg group was significantly greater than that in the control group, but was independent of dose. No test compound-related necropsy findings were seen in either the dams or the offspring. No compound-related histopathologic findings were noted in the reproductive tissues of either the male or female offspring. No compound-related alterations in sperm motion or density were detected in the offspring. Thyroid stimulating hormone levels in the male offspring of the 0.2 mg/kg and 1.0 mg/kg groups were significantly higher than those in the controls, whereas thyroid hormone (T(3), T(4)) levels in these groups were comparable to the controls. In addition, the thyroid glands of males in all groups were similar histologically. These results indicate that SDT administered at doses as high as 1.0 mg/kg (1000 times the estimated human daily intake) did not produce reproductive toxicity in dams or offspring.
对苯乙烯二聚体和三聚体（SDT）进行了Sprague-Dawley大鼠生殖毒性评估。从妊娠第6天至产后第21天，以0、0.04、0.2和1.0mg/kg的剂量给大鼠口服SDT。评估了包括妊娠和哺乳在内的临床体征以及体重和食物摄入量的变化。所有母鼠均接受大体尸检。称量脑、肝、肾、卵巢、子宫、甲状腺和垂体的重量。评估了受试化合物对后代的活力、生长、肛门生殖器距离、包皮分离和阴道开口、行为功能、发情周期、交配和生育能力的影响。在研究的任何阶段，母鼠均未出现与受试化合物相关的临床体征，体重或食物摄入量也未受影响。此外，未观察到任何母鼠在分娩或哺乳方面存在异常，包括妊娠期长度。在幼崽的活力或生长方面未观察到剂量依赖性变化。SDT对后代的任何发育里程碑、学习、记忆或发情周期均无不良影响。0.2mg/kg组的授精天数显著多于对照组，但与剂量无关。在母鼠或后代中均未发现与受试化合物相关的尸检结果。在雄性或雌性后代的生殖组织中未观察到与化合物相关的组织病理学结果。在后代中未检测到与化合物相关的精子运动或密度改变。0.2mg/kg和1.0mg/kg组雄性后代的促甲状腺激素水平显著高于对照组，而这些组中的甲状腺激素（T(3)、T(4)）水平与对照组相当。此外，所有组雄性的甲状腺在组织学上相似。这些结果表明，以高达1.0mg/kg（估计人类每日摄入量的1000倍）的剂量给予SDT不会对母鼠或后代产生生殖毒性。
