Exposure to PFOA and PFOS and fetal growth: a critical merging of toxicological and epidemiological data

Abstract

Toxicological and epidemiological evidence on the association between perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) and birth/fetal weight was assessed. An extensive search for toxicological information in rats and mice, and a systematic search for epidemiological evidence were conducted. The linear regression coefficient (LRC) of birth weight (BrthW) on PFOA/PFOS was considered, and separate random effects meta-analyses for untransformed (i.e. not mathematically transformed) and log-transformed values were performed.

Toxicological evidence: PFOA: 12 studies (21 datasets) in mice showed statistically significant lower birth/fetal weights from 5 mg/kg body weight per day. PFOS: most of the 13 studies (19 datasets) showed lower birth/fetal weights following in utero exposure.

Epidemiological evidence: Sixteen articles were considered. The pooled LRC for a 1 ng/mL increase in untransformed PFOA (12 studies) in maternal plasma/serum was −12.8 g (95% CI −23.2; 2.4), and −27.1 g (95% CI −50.6; −3.6) for an increase of 1 log_e ng/mL PFOA (nine studies). The pooled LRC for untransformed PFOS (eight studies) was −0.92 g (95%CI −3.4; 1.6), and for an increase of 1 log_e ng/mL was −46.1(95% CI −80.3; −11.9). No consistent pattern emerged for study location or timing of blood sampling.

Conclusions: Epidemiological and toxicological evidence suggests that PFOA and PFOS elicit a decrease in BrthW both in humans and rodents. However, the effective animal extrapolated serum concentrations are 10²–10³ times higher than those in humans. Thus, there is no quantitative toxicological evidence to support the epidemiological association, thus reducing the biological plausibility of a causal relationship.

Keywords:

• Birth weight
• fetal growth
• PFOA
• PFOS
• systematic review
• meta-analysis
• epidemiology
• toxicology
• perfluoroalkyls
• reproduction
• integration
• evidence

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Acknowledgements

The authors wish to thank Lesley Rushton, Karlene Lavelle, Nicholas Synhaeve, and Alan Poole for their most helpful suggestions as reviewers of our CEFIC Long Range Research Initiative project. The authors are grateful for the help of their research to the chemist Andrea Colombo, Istituto di Ricerche Farmacologiche Mario Negri, for the support on the chemical assessment quality.

The authors gratefully acknowledge the comments provided by five reviewers elected by the Editor and anonymous to the authors. These comments were extremely helpful in revising the final manuscript.

Declaration of interest

The employment affiliation of the authors is as shown on the cover paper. However, the authors preparation of the paper was as independent professional not in their role as employees. The views expressed are not necessarily those of their employer. The authors have not been involved in any legal or regulatory proceedings with regard to the contents of the paper.

Funding

This work was funded under CEFIC Long Range Research Initiative Contract number EMSG58. CEFIC was not involved in the preparation or approval of the manuscript. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the views of CEFIC.

Additional information

Funding

This work was funded under CEFIC Long Range Research Initiative Contract number EMSG58. CEFIC was not involved in the preparation or approval of the manuscript. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the views of CEFIC.