AbstractA two‐generation reproduction toxicity study was conducted in rats with isopropanol. Thirty rats of each sex per group (P1) were dosed once daily by oral gavage with 0, 100, 500 or 1000 mg isopropanol kg−1for 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 P2adults were selected from the F1litters 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 P2males. There was also accumulation of hyaline droplets and other microscopic findings in the kidneys from the mid‐ and high‐dose P1males and from all treated groups of the P2males. Increased mortality was observed in the high‐dose F1offspring 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 F1males and in the high‐dose F2pups of both sexes. Eighteen out of 70 F1weanlings in the 1000 mg kg−1group died or were euthanized prior to P2selection. 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 P2males 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
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