Characterizing non-constant relative potency

Regul Toxicol Pharmacol. 2011 Aug;60(3):342-53. doi: 10.1016/j.yrtph.2011.05.002. Epub 2011 May 13.

Abstract

Relative potency plays an important role in toxicology. Estimates of relative potency are used to rank chemicals by their effects, to calculate equivalent doses of test chemicals compared to a standard, and to weight contributions of constituent chemicals when evaluating mixtures. Typically relative potency is characterized by a constant dilution factor, even when non-similar dose-response curves indicate that constancy is inappropriate. Improperly regarding relative potency as constant may distort conclusions and potentially mislead investigators or policymakers. We consider a more general approach that allows relative potency to vary as a function of dose, response, or response quantile. Distinct functions can be defined, each generalizing different but equivalent descriptions of constant relative potency. When two chemicals have identical response limits, these functions all carry fundamentally equivalent information; otherwise, relative potency as a function of response quantile is distinct and embodies a modified definition of relative potency. Which definition is preferable depends on whether one views any differences in response limits as intrinsic to the chemicals or as extrinsic, arising from idiosyncrasies of data sources. We illustrate these ideas with constructed examples and real data. Relative potency functions offer a unified and principled description of relative potency for non-similar dose-response curves.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Carcinogenicity Tests / methods
  • Dose-Response Relationship, Drug
  • Hazardous Substances / toxicity*
  • Risk Assessment / methods
  • Risk Factors
  • Toxicology / methods*
  • Toxicology / standards

Substances

  • Hazardous Substances