Abstract
A two‐generation reproduction toxicity study was conducted in rats with isopropanol. Thirty rats of each sex per group (P~1~) were dosed once daily by oral gavage with 0, 100, 500 or 1000 mg isopropanol kg^−1^ for at least 10 weeks prior to mating. Parental animals were mated within groups for up to 3 weeks. Parental females were dosed during mating, gestation and lactation; parental males were dosed during mating through delivery of their last litter sired. The P~2~ adults were selected from the F~1~ litters and were dosed for 10–13 weeks before mating to produce a single litter. Findings in the parental animals included increased lactation body weight gain in the mid‐ and high‐dose females, increased liver and kidney weights in the mid‐ and high‐dose groups of both sexes and centrilobular hepatocyte hypertrophy in some P~2~ males. There was also accumulation of hyaline droplets and other microscopic findings in the kidneys from the mid‐ and high‐dose P~1~ males and from all treated groups of the P~2~ males. Increased mortality was observed in the high‐dose F~1~ offspring during the early postnatal period, although no other clinical signs of toxicity were observed in the offspring of either generation. In addition, offspring body weight was reduced during the early postnatal period in the high‐dose F~1~ males and in the high‐dose F~2~ pups of both sexes. Eighteen out of 70 F~1~ weanlings in the 1000 mg kg^−1^ group died or were euthanized prior to P~2~ selection. No treatment‐related post‐mortem findings were observed in the offspring from either generation. A statistically significant reduction was observed in the male mating index of the high‐dose P~2~ males compared with that of the controls. However, no treatment‐related microscopic changes in reproductive tissues or biologically meaningful differences in other reproductive parameters were observed in adults of either generation. The no‐observed‐effect‐level (NOEL) for reproductive effects in this study, based on the reduced male mating index of the high‐dose P~2~ males, is 500 mg kg^−1^ day^−1^.