The toxicity of isoniazid was assessed in CD-1 male and female mice at dose levels of 30, 60, and 90 mg/kg/day. Male mice (10/group) were dosed on Study Days 5 to 24 and sacrificed on Study Day 25. Prior to dosing (Study Days 0-4) the male mice were cohabited with female mice (20/group). The sperm-positive female mice were dosed on Days 6 through 15 of gestation and sacrificed on scheduled Day 4 of lactation. A second group of female mice (20/group) was dosed beginning Study Day 0 and throughout mating on Study Days 9 to 13 until the day prior to scheduled sacrifice on Day 18 of gestation. Adult mice were evaluated for clinical signs, body weights, and clinical pathology parameters. Male mice were subjected to a sperm function evaluation. Liver was a predesignated target organ and was evaluated histopathologically in the adult mice. Offspring from each group were evaluated for viability, external anomalies, and weight.
Administration of isoniazid at a dosage of 90 mg/kg/day may have slightly increased the incidence of resorbed conceptuses, but the difference from the control value was not statistically significant. In the 90 mg/kg/day males, there was a significant decrease in epididymal sperm motility. Marginal decreases in red blood cell counts were present in the 60 mg/kg/day males and 90 mg/kg/day males and females, but overt anemia was not present. No other toxicities were observed. The no-observable-adverse-effect-level for male and female mice for developmental and reproductive toxicity was 90 mg/kg/day, the highest dosage administered.