Allgood G S, Miller J M, Schardein J L
Proctor and Gamble Company, Cincinnati, Ohio 45241-2421.
Fundam Appl Toxicol. 1991 Jan;16(1):31-40. doi: 10.1016/0272-0590(91)90132-n.
The purpose of this study was to determine the effect of piroctone olamine, an antidandruff active, on reproductive performance, fertility, parturition, and neonatal viability and growth. Piroctone olamine was administered orally by gavage to three groups of 35 male Sprague-Dawley rats each beginning 64 days prior to mating and continuing until euthanized and to three groups of 35 female Sprague-Dawley rats each beginning 14 days prior to mating and continuing until euthanized. Animals in the treated groups received piroctone olamine in a combination of 1.0% methylcellulose and polyethylene glycol 400 as a single daily dose at levels of 0, 10, 100, and 250 mg/kg/day, at a volume of 2.5 ml/kg. The control group received the vehicle only. Ten randomly selected females/group were mated and underwent a uterine examination on Gestation Day 13; the remaining females were allowed to deliver. Because earlier studies reported hematological effects, blood samples were collected from all parental animals during acclimation and prior to euthanasia for hematological and blood chemistry (Gestation Day 13 females) characterization. The parental animals were necropsied and tissues were grossly examined. Systemic effects induced by the test article were seen at the mid- and high-dose levels but only among the male rats. These effects were reduced body weight and decreased liver weights. Hematological findings representative of anemia occurred at the high-dose level, as did rales in several animals. Offspring growth was inhibited for the high-dose group as evidenced by significantly reduced mean weight values throughout lactation. The remaining parameters assessed, including mating ability and reproductive performance, were not affected by treatment at any dosage level tested. In summary, the no observable effect level of piroctone olamine with respect to systemic toxicity was considered to be 10 mg/kg/day. Neonatal growth was not affected at 100 mg/kg/day or less, and the no observable effect level with respect to reproductive parameters, including fertility, was 250 mg/kg/day.
本研究的目的是确定去屑活性成分奥麦丁锌对生殖性能、生育力、分娩以及新生仔鼠的活力和生长的影响。从交配前64天开始，通过灌胃法对三组雄性斯普拉格-道利大鼠（每组35只）口服给予奥麦丁锌，持续至实施安乐死；从交配前14天开始，对三组雌性斯普拉格-道利大鼠（每组35只）口服给予奥麦丁锌，持续至实施安乐死。治疗组动物接受以1.0%甲基纤维素和聚乙二醇400为溶剂的奥麦丁锌，每日单次给药，剂量分别为0、10、100和250 mg/kg/天，给药体积为2.5 ml/kg。对照组仅接受溶剂。每组随机选取10只雌性大鼠进行交配，并在妊娠第13天进行子宫检查；其余雌性大鼠任其分娩。由于早期研究报告了血液学影响，因此在适应期以及实施安乐死前，从所有亲代动物采集血样，以进行血液学和血液化学（妊娠第13天的雌性大鼠）特征分析。对亲代动物进行尸检并对组织进行大体检查。在中、高剂量水平观察到受试物诱导的全身效应，但仅在雄性大鼠中出现。这些效应包括体重减轻和肝脏重量减轻。高剂量水平出现了代表贫血的血液学检查结果，几只动物还出现了啰音。高剂量组的仔鼠生长受到抑制，整个哺乳期平均体重值显著降低证明了这一点。所评估的其余参数，包括交配能力和生殖性能，在任何测试剂量水平下均未受到治疗的影响。总之，奥麦丁锌全身毒性的未观察到有害作用水平被认为是10 mg/kg/天。100 mg/kg/天及以下剂量对新生仔鼠生长无影响，包括生育力在内的生殖参数的未观察到有害作用水平为250 mg/kg/天。
