Evidence map›Paper›PMID 36635753›Full record

ReviewEnvironmental health : a global access science source2023

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 and 6 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Environmental health : a global access science source, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Incorporating a dermal absorption route into high throughput toxicokinetic modeling.Journal of exposure science & environmental epidemiology · 2026
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. FIGO committee opinion: Environmental drivers of gynecologic and reproductive health.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025
    Article
  12. FIGO committee opinion: Environmental drivers of obstetric health and early childhood development.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025
    Article
  13. Characterizing variability and uncertainty for parameter subset selection in PBPK models.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Mapping assays to the key characteristics of carcinogens to support decision-making.Database : the journal of biological databases and curation · 2025
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Julia R VarshavskyDepartment of Health Sciences and Department of Civil and Environmental Engineering Northeastern University, Boston, MA, 02115, USA. j.varshavsky@northeastern.edu.
Swati D G RayasamDepartment of Obstetrics, Program on Reproductive Health and the Environment, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
Jennifer B SassNatural Resources Defense Council, Washington, DC, USA.
Daniel A AxelradIndependent consultant, Washington, DC, USA.
Carl F CranorDepartment of Philosophy, University of California, Riverside, Riverside, CA, USA.
Dale HattisThe George Perkins Marsh Institute, Clark University, Worcester, MA, USA.
Russ HauserDepartment of Environmental Health, T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Patricia D KomanDepartment of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Emily C MarquezPesticide Action Network, Berkeley, CA, USA.
Rachel Morello-FroschSchool of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Catherine OksasUniversity of California, San Francisco School of Medicine, San Francisco, CA, USA.
Sharyle PattonCommonweal, Bolinas, CA, USA.
Joshua F RobinsonDepartment of Obstetrics, Program on Reproductive Health and the Environment, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
Sheela SathyanarayanaDepartment of Pediatrics, University of Washington, Seattle, WA, USA.
Peggy M ShepardWE ACT for Environmental Justice, New York, NY, USA.
Tracey J WoodruffDepartment of Obstetrics, Program on Reproductive Health and the Environment, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.

Funding

UCSF Environmental Research and Translation for Health Center (EaRTH Center)P30ES030284 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Rashmi Joglekar · 2020 to 2026
$11.2M
NIEHS NIH HHS P30 ES030284
6 · The paper itself

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.

Indexed as

Environmental ExposurePovertyChildFemaleHumansInfantPregnancyRisk AssessmentAdjustment factorsChemicalsCumulative riskEnvironmental justiceEPANAMsRisk assessmentSusceptibilityVariabilityVulnerability

Identifiers

PMID36635753
PMCPMC9835253

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.