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On reference dose (RfD) and its underlying toxicity data base.

M L Dourson1, L A Knauf, J C Swartout

  • 1Office of Research and Development, Environmental Protection Agency, Cincinnati, OH 45268.

Toxicology and Industrial Health
|May 1, 1992
PubMed
Summary
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Pesticide toxicity studies in dogs and rats over two years detect harmful effects at lower doses than other bioassays. This data helps estimate safe pesticide exposure levels, known as Reference Doses (RfDs).

Area of Science:

  • Environmental toxicology
  • Comparative toxicology

Background:

  • Pesticide toxicity assessment relies on various animal models and bioassays.
  • Understanding inter-species and inter-bioassay variability is crucial for accurate risk assessment.

Purpose of the Study:

  • To compare the sensitivity of different pesticide toxicity bioassays.
  • To evaluate the adequacy of existing bioassay data for estimating Reference Doses (RfDs).

Main Methods:

  • Quantitative and statistical analysis of existing pesticide toxicity data.
  • Comparison of toxic responses across different animal species (dogs, rats, mice) and bioassay types (chronic, multi-generation, developmental).

Main Results:

  • Two-year dog and rat bioassays detected toxic responses at lower doses compared to rat multi-generation or developmental studies, and two-year mouse studies.

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  • While chronic dog and rat studies identified toxicity at lower doses, the severity of effects was not explicitly compared.

    • Conclusions:

    • A combination of two-year dog and rat studies, along with reproductive and developmental bioassays, provides a sufficient dataset for high-confidence RfD estimation.
    • An additional uncertainty factor is recommended for RfD calculations when fewer than these key bioassays are available, to account for variability.