Reproduction and teratological studies with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in the rat and rabbit.

1-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea (CCNU), one of a group of nitrosoureas used for the treatment of cancer, was evaluated for its effects on various parameters of reproduction and postnatal development in the rat and on embryonal and fetal development in the rat and rabbit. Weekly ip treatment of male rats for 9 weeks with 2.5, 5, or 10 mg/kg/week had no effect on copulatory activity, but untreated females bred to males receiving 5 or 10 mg/kg/week had a significant decrease in numbers of implantations, and the resorption rate was increased at all levels of treatment. Treatment of female rats ip with 0.75, 1.5, or 3.0 mg/kg/day for 14 days prior to breeding and through Day 20 of gestation resulted in a high incidence of intrauterine, perinatal, and postnatal mortality. Doses of 2, 4, or 8 mg/kg/day given ip during different 4-day intervals of organogenesis or 6 mg/kg/day given throughout organogenesis (Days 6–15) were teratogenic in the rat. Major abnormalities such as omphalocele, ectopia cordis, hydrocephalus, syndactyly, anophthalmia, and aortic arch anomalies occurred most frequently in groups given 4 or 8 mg/kg on Days 6–9, or 6 mg/kg on Days 6–15 of gestation. Treatment of female rats ip with doses of 0.75, 1.5, or 3.0 mg/kg/day during the last third of gestation and throughout 21 days of lactation had no effect on prenatal, perinatal, or postnatal survival, but pup weights on Day 21 were reduced at all levels of treatment. Doses of 1.5, 2.25, or 3.0 mg/kg administered iv or ip to rabbits on Days 6–18 of gestation resulted in a high incidence of abortion at 3 mg/kg but no drug-related fetal anomalies were detected.