Reproduction studies with mabuterol in rats

In the reproduction studies with dl-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-etha nol hydrochloride (mabuterol), a new beta 2-selective adrenoceptor stimulant, two trials were done: Segment (Seg.) I, fertility tests in male and female rats dosed before and during mating and the first week of gestation with 0.1, 2 and 40 mg/kg, and Seg. III, peri- and postnatal tests in pregnant rats dosed with 0.003, 0.01, 0.03, 0.1, 2 and 40 mg/kg from 17th day of gestation through 21st day of lactation. In Seg. III, cross-fostering was also done. The "maximum non-effective oral doses" of mabuterol from the viewpoint of parental toxicity were in Seg. I, 2 mg/kg and in Seg. III, 0.03 mg/kg, respectively. Doses above these non-effect levels were moderately toxic for the parent generation as shown by clinical signs (only at 40 mg/kg) and influence on food intake and body weight. In Seg. I, no adverse effects on fertility occurred. In Seg. III, doses of 0.1 mg/kg and above affected dose-dependently the body weight of viable pups. Additionally, 40 mg/kg decreased their perinatal survival rate.