The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental toxicity criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
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.