Evaluation of the developmental and reproductive toxicity of chlorpyrifos in the rat
Evaluation of the developmental and reproductive toxicity of chlorpyrifos in the rat
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DOI：
10.1006/faat.1996.0013
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Quast, JF
中科院分区：
文献类型：
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作者：
Breslin, WJ;Liberacki, AB;Quast, JF
毒死蜱（O，O-二乙基-O-（3，5，6-三氯-2-吡啶基）-硫代磷酸酯）是一种有机磷杀虫剂，经口染毒后，对大鼠的发育和生殖毒性进行了评价。在妊娠第6天至第15天，通过灌胃给予妊娠Fischer 344大鼠0（玉米油溶剂）、0.1、3.0或15 mg毒死蜱/kg/天的剂量。在两个较高剂量水平下观察到的母体效应包括3.0 mg/kg/天剂量下胆碱酯酶水平降低和15 mg/kg/天剂量下胆碱能体征（过度流涎和震颤）、胆碱酯酶水平降低和体重增加减少。在0.1 mg/kg/天剂量下未观察到明显的母体效应。尽管在这两个较高暴露水平下观察到母体毒性，但在任何剂量下均未观察到发育影响。在一项两代生殖研究中，Sprague-Dawley大鼠的饮食中每天摄入0、0.1、1.0或5.0 mg毒死蜱/kg。对父母的影响包括1.0 mg/kg/天剂量下血浆和红细胞胆碱酯酶降低，5.0 mg/kg/天剂量下血浆、红细胞和脑胆碱酯酶降低以及肾上腺束状带的组织病理学改变。肾上腺的组织病理学变化特征为雄性动物极轻微至轻微空泡化（与脂肪变化一致），雌性动物极轻微空泡化和/或着色特性改变。在任何剂量水平下均未观察到对生殖或生育力指数或生殖组织的组织病理学的影响，在F1或F2窝中，在0.1或1.0 mg/kg/天剂量下均未观察到新生儿影响。仅在F1窝中，高剂量下的亲代毒性伴随幼仔体重下降和幼仔死亡率增加。这些数据表明，大鼠经口给予非肠道毒性剂量的毒死蜱不会导致胚胎死亡、胚胎/胎儿毒性或致畸性，也不会对生育能力或生殖器官的功能或结构产生不利影响。虽然在一代母体毒性剂量水平下观察到对新生儿生长和存活的影响，但在下一代中未观察到这种影响，因此可能与给药无关。(C)1996年毒理学学会
Chlorpyrifos (O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)-phospho rothioate), an organophosphate insecticide, was evaluated for its potential to produce developmental and reproductive toxicity in rats following oral exposure. Pregnant Fischer 344 rats were given doses of 0 (corn oil vehicle), 0.1, 3.0, or 15 mg chlorpyrifos/kg/day, by gavage, on Gestation Days 6 through 15. Maternal effects noted at the two higher dose levels included decreased cholinesterase levels at 3.0 mg/kg/day and cholinergic signs (excessive salivation and tremors), decreased cholinesterase levels, and decreased body weight gain at 15 mg/kg/day. No maternal effects were apparent at 0.1 mg/kg/day. Although maternal toxicity was observed at these two higher exposure levels, no developmental effects were noted at any dose. In a two-generation reproduction study, Sprague-Dawley rats were maintained on diets supplying 0, 0.1, 1.0, or 5.0 mg chlorpyrifos/kg/day. Parental effects included decreased plasma and erythrocyte cholinesterase at 1.0 mg/kg/day, and decreased plasma, erythrocyte, and brain cholinesterase and histopathologic alterations of the adrenal zona fasciculata at 5.0 mg/kg/day. The histopathologic alterations of the adrenal were characterized as very slight to slight vacuolation (consistent with fatty change) in males, and very slight vacuolation and/or altered tinctorial properties in females. No effects on the reproductive or fertility indices or on the histopathology of reproductive tissues were observed at any dose level, and no neonatal effects were observed at 0.1 or 1.0 mg/kg/day in the F1 or F2 litters. Parental toxicity at the high dose was accompanied by decreased pup body weight and increased pup mortality in the F1 litters only. These data show that oral administration of chlorpyrifos to rats at parentally toxic dose levels was not embryolethal, embryo/fetotoxic, or teratogenic and did not adversely affect fertility or the function or structure of the reproductive organs. Although effects on neonatal growth and survival were observed at a maternally toxic dose level in one generation, this effect was not observed in the subsequent generation and, therefore, may not have been related to treatment. (C) 1996 Society of Toxicology