The effect of piroctone olamine on reproduction of male and female rats.

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.