The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Integration of Animal and Human Evidence for PFOA Effects on Fetal Growth
Open accessAbstract
BACKGROUND: The Navigation Guide is a novel systematic review method to synthesize scientific evidence and reach strength of evidence conclusions for environmental health decision making. OBJECTIVE: Our aim was to integrate scientific findings from human and nonhuman studies to determine the overall strength of evidence for the question "Does developmental exposure to perfluorooctanoic acid (PFOA) affect fetal growth in humans?" METHODS: We developed and applied prespecified criteria to systematically and transparently a) rate the quality of the scientific evidence as "high," "moderate," or "low"; b) rate the strength of the human and nonhuman evidence separately as "sufficient," "limited," "moderate," or "evidence of lack of toxicity"; and c) integrate the strength of the human and nonhuman evidence ratings into a strength of the evidence conclusion. RESULTS: We identified 18 epidemiology studies and 21 animal toxicology studies relevant to our study question. We rated both the human and nonhuman mammalian evidence as "moderate" quality and "sufficient" strength. Integration of these evidence ratings produced a final strength of evidence rating in which review authors concluded that PFOA is "known to be toxic" to human reproduction and development based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. CONCLUSION: We concluded that developmental exposure to PFOA adversely affects human health based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. The results of this case study demonstrate the application of a systematic and transparent methodology, via the Navigation Guide, for reaching strength of evidence conclusions in environmental health.
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PFAS are recognized developmental toxicants.
“In utero exposure to per- and polyfluoroalkyl substances (PFAS), which are recognized developmental toxicants, potentially leads to decreased anthropometric measures in infants at birth.”
From Associations between in utero exposure of per- and polyfluoroalkyl substances (PFAS) mixture and anthropometry measures at birth (2025) · cites this paper as Lam et al., 2014
The Results report sufficient evidence of toxicity from increased PFOA exposure and decreased birth weight, and the Discussion describes sufficient evidence of an association in human and mammalian studies (pages not provided). This supports the developmental-toxicity claim for PFOA, but the paper does not establish that PFAS as a whole are recognized developmental toxicants. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTo date, the Navigation Guide method has been used in 3 case studies.
“To date, the Navigation Guide method has been used in 3 case studies [25, 27, 28].”
From A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder (2016) · cites this paper as [25]
Systematic review methods have only recently been developed and utilized in environmental health sciences.
“such methods have only recently been developed and utilized in environmental health sciences [23–30].”
From A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder (2016) · cites this paper as [25]
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- Authors
- Lam, J., Koustas, E., Sutton, P., Johnson, P. I., Atchley, D. S., Sen, S., Robinson, K. A., Axelrad, D. A., & Woodruff, T. J.
- Affiliations
- Environmental Protection Agency (US)
- University of California, San Francisco (US)
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
- Johns Hopkins University (US)
- Corresponding author
- Lam, Juleen
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-06-25
- Volume
- 122
- Issue
- 10
- Pages
- 1040-1051
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC4181930
- OpenAlex
- W1987523543
- Cited by
- 214
- References
- 60
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 10 · 2023: 13 · 2022: 22 · 2021: 26 · 2020: 23 · 2019: 15 · 2018: 15 · 2017: 28 · 2016: 13 · 2015: 16 · 2014: 6
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 1283 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Energy
- U.S. Environmental Protection Agency (RD-83543301)
- New York Community Trust
- Heinz Endowments
- Johnson Family Foundation
- Rose Foundation for Communities and the Environment
- Kaiser Permanente
- Environmental Defense Fund
- Oak Ridge Institute for Science and Education
- U.S. Public Health Service (ESO22841)
- University of California, San Francisco
- National Institute of Environmental Health Sciences (ESO22841, ES018135, P01ES022841, P20ES018135)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- perfluorooctanoic acid, fetal growth, early life exposure, quality of evidence, veterinary toxicology, human epidemiology, evidence integration, perfluorinated compounds, reproductive toxicity
- MeSH terms
- Animals, Birth Weight, Caprylates, Environmental Health, Environmental Pollutants, Female, Fluorocarbons, Humans, Pregnancy, Maternal Exposure, Evidence-Based Medicine, Fetal Development
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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