Calculation of benchmark doses for reproductive and developmental toxicity observed after exposure to isopropanol

Regul Toxicol Pharmacol. 1998 Aug;28(1):38-44. doi: 10.1006/rtph.1998.1226.


Reproductive, including developmental, toxicity risk assessment has typically relied on estimation of toxicity criteria values derived from no-observed-adverse-effect levels (NOAELs). The benchmark dose (BMD) approach has been proposed as an alternative that avoids problems with NOAELs. In this analysis of the reproductive and developmental toxicity observed in a multigeneration study of rats exposed to isopropanol, the BMD approach has been applied to all effects exhibiting significant dose-response relationships. The BMD estimates were very consistent across models and across end points; they were within the range of doses (100 to 500 mg/kg/day) that has been suggested as being the NOAEL. The use of the BMD approach for analysis of isopropanol reproductive toxicity is shown to avoid the experiment-specific argument of whether a particular treatment has induced statistically significant differences, compared to controls, in favor of the estimation of experiment-independent doses corresponding to risk levels of interest. The consistency of the BMD estimates, with values of about 420 mg/kg/day, suggests that, for isopropanol, the available multigeneration study data may provide a suitable basis for considering safe exposure.

MeSH terms

  • 2-Propanol / toxicity*
  • Animals
  • Animals, Newborn
  • Dose-Response Relationship, Drug
  • Embryonic and Fetal Development / drug effects*
  • Female
  • Fertility / drug effects
  • Infertility, Male / chemically induced
  • Litter Size / drug effects
  • Male
  • Models, Biological
  • No-Observed-Adverse-Effect Level
  • Pregnancy
  • Rats
  • Risk Assessment / methods
  • Sexual Behavior, Animal / drug effects
  • Solvents / toxicity*
  • Survival Rate


  • Solvents
  • 2-Propanol