Model systems and organisms for addressing inter- and intra-species variability in risk assessment. Academic Article uri icon

abstract

  • Addressing inter- and intra-species differences in potential hazardous effects of chemicals remains a long-standing challenge in human health risk assessment that is typically addressed heuristically through use of 10-fold default "uncertainty" or "safety" factors. Although it has long been recognized that chemical-specific data would be preferable to replace the "defaults," only recently have there emerged experimental model systems and organisms with the potential to experimentally quantify the population variability in both toxicokinetics and toxicodynamics for specific chemicals. Progress is most evident in the use of population in vitro human cell-based models and population in vivo mouse models. Multiple case studies were published in the past 10-15 years that clearly demonstrate the utility of such models to derive data with direct application to quantifying variability at hazard identification, exposure-response assessment, and mechanistic understanding of toxicity steps of traditional risk assessments. Here, we review recent efforts to develop fit-for-purpose approaches utilizing these novel population-based in vitro and in vivo models in the context of risk assessment. We also describe key challenges and opportunities to broadening application of population-based experimental approaches. We conclude that population-based models are now beginning to realize their potential to address long-standing data gaps in inter- and intra-species variability.

published proceedings

  • Regul Toxicol Pharmacol

altmetric score

  • 1

author list (cited authors)

  • Rusyn, I., Chiu, W. A., & Wright, F. A.

citation count

  • 7

complete list of authors

  • Rusyn, Ivan||Chiu, Weihsueh A||Wright, Fred A

publication date

  • July 2022