The toxicity of ddI was assessed in CD-1 male and female mice at dose levels of 500, 1000, and 2000 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 or Day 5 of lactation. A second group of female mice (20/group) was dosed on 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 weight, and hematologic parameters. Offspring from each group were evaluated for viability, external anomalies, and weight.
Administration of ddI at a dosage of 2000 mg/kg/day may have slightly increased the incidence of resorbed conceptuses but the difference from the control value was not statistically significant. No other toxicity was observed. In males, the no observable adverse effect level for toxicity was greater than 2000 mg/kg/day. In females, the approximate NOAEL for maternal toxicity was greater than 2000 mg/kg/day and the NOAEL for developmental and reproductive toxicity was approximately 2000 mg/kg/day.