Current practice and recommendations for advancing how human variability and susceptibility are considered in chemical risk assessment

Julia R Varshavsky; Swati D G Rayasam; Jennifer B Sass; Daniel A Axelrad; Carl F Cranor; Dale Hattis; Russ Hauser; Patricia D Koman; Emily C Marquez; Rachel Morello-Frosch; Catherine Oksas; Sharyle Patton; Joshua F Robinson; Sheela Sathyanarayana; Peggy M Shepard; Tracey J Woodruff

doi:10.1186/s12940-022-00940-1

Current practice and recommendations for advancing how human variability and susceptibility are considered in chemical risk assessment

Environ Health. 2023 Jan 12;21(Suppl 1):133. doi: 10.1186/s12940-022-00940-1.

Authors

Julia R Varshavsky¹, Swati D G Rayasam², Jennifer B Sass³, Daniel A Axelrad⁴, Carl F Cranor^{5

6}, Dale Hattis⁷, Russ Hauser⁸, Patricia D Koman⁹, Emily C Marquez¹⁰, Rachel Morello-Frosch^{11

12}, Catherine Oksas¹³, Sharyle Patton¹⁴, Joshua F Robinson^{2

15}, Sheela Sathyanarayana^{16

17}, Peggy M Shepard¹⁸, Tracey J Woodruff²

Affiliations

¹ Department of Health Sciences and Department of Civil and Environmental Engineering Northeastern University, Boston, MA, 02115, USA. j.varshavsky@northeastern.edu.
² Department of Obstetrics, Program on Reproductive Health and the Environment, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
³ Natural Resources Defense Council, Washington, DC, USA.
⁴ Independent consultant, Washington, DC, USA.
⁵ Department of Philosophy, University of California, Riverside, Riverside, CA, USA.
⁶ Environmental Toxicology Graduate Program, College of Natural and Agricultural Sciences, University of California, Riverside, Riverside, CA, USA.
⁷ The George Perkins Marsh Institute, Clark University, Worcester, MA, USA.
⁸ Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁹ Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
¹⁰ Pesticide Action Network, Berkeley, CA, USA.
¹¹ School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
¹² Department of Environmental Science, Policy and Management, University of California, Berkeley, Berkeley, CA, USA.
¹³ University of California, San Francisco School of Medicine, San Francisco, CA, USA.
¹⁴ Commonweal, Bolinas, CA, USA.
¹⁵ Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
¹⁶ Department of Pediatrics, University of Washington, Seattle, WA, USA.
¹⁷ Seattle Children's Research Institute, Seattle, WA, USA.
¹⁸ WE ACT for Environmental Justice, New York, NY, USA.

Abstract

A key element of risk assessment is accounting for the full range of variability in response to environmental exposures. Default dose-response methods typically assume a 10-fold difference in response to chemical exposures between average (healthy) and susceptible humans, despite evidence of wider variability. Experts and authoritative bodies support using advanced techniques to better account for human variability due to factors such as in utero or early life exposure and exposure to multiple environmental, social, and economic stressors.This review describes: 1) sources of human variability and susceptibility in dose-response assessment, 2) existing US frameworks for addressing response variability in risk assessment; 3) key scientific inadequacies necessitating updated methods; 4) improved approaches and opportunities for better use of science; and 5) specific and quantitative recommendations to address evidence and policy needs.Current default adjustment factors do not sufficiently capture human variability in dose-response and thus are inadequate to protect the entire population. Susceptible groups are not appropriately protected under current regulatory guidelines. Emerging tools and data sources that better account for human variability and susceptibility include probabilistic methods, genetically diverse in vivo and in vitro models, and the use of human data to capture underlying risk and/or assess combined effects from chemical and non-chemical stressors.We recommend using updated methods and data to improve consideration of human variability and susceptibility in risk assessment, including the use of increased default human variability factors and separate adjustment factors for capturing age/life stage of development and exposure to multiple chemical and non-chemical stressors. Updated methods would result in greater transparency and protection for susceptible groups, including children, infants, people who are pregnant or nursing, people with disabilities, and those burdened by additional environmental exposures and/or social factors such as poverty and racism.

Keywords: Adjustment factors; Chemicals; Cumulative risk; EPA; Environmental justice; NAMs; Risk assessment; Susceptibility; Variability; Vulnerability.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Child
Environmental Exposure*
Female
Humans
Infant
Poverty*
Pregnancy
Risk Assessment / methods

Grants and funding

P30 ES030284/ES/NIEHS NIH HHS/United States