Characterizing Non-constant Relative Potency
Overview
Toxicology
Authors
Affiliations
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.
Hertzberg R, Teuschler L, McDonald A, Sey Y, Simmons J Toxics. 2024; 12(5).
PMID: 38787084 PMC: 11125920. DOI: 10.3390/toxics12050305.
Kassotis C, Phillips A Toxics. 2023; 11(6).
PMID: 37368587 PMC: 10303128. DOI: 10.3390/toxics11060487.
Mwanza P, Jukes M, Dealtry G, Lee M, Moore S Viruses. 2022; 14(1).
PMID: 35062232 PMC: 8780862. DOI: 10.3390/v14010028.
Escher B, Neale P, Villeneuve D Environ Toxicol Chem. 2018; 37(9):2273-2280.
PMID: 29846006 PMC: 6150494. DOI: 10.1002/etc.4178.
Parameterizing dose-response models to estimate relative potency functions directly.
Dinse G, Umbach D Toxicol Sci. 2012; 129(2):447-55.
PMID: 22700543 PMC: 3491959. DOI: 10.1093/toxsci/kfs209.