PFAS and Developmental and Reproductive Toxicity: An EWG Fact Sheet

The toxic fluorinated per-and polyfluoroalkyl chemicals known as PFAS  are a class of thousands of environmentally persistent synthetic chemicals that have been used since the 1940s. They are added as a water-, grease- or stain-repellent in clothing, cookware, furniture, carpets and some cosmetics. PFAS are also found in industrial firefighting foam and in numerous industrial applications.

People can be exposed to PFAS through food, water, household dust and consumer products. Nearly everyone in the U.S already has PFAS in their body. These chemicals readily cross the placenta and have been detected in cord blood, showing direct prenatal exposure to the developing fetus. PFAS are also detected in breast milk, another potential source of infant exposure. 

Exposure to PFAS is linked to developmental and reproductive toxicity, including low birth weight, thyroid disruption, harm to the male reproductive system, pregnancy-induced high blood pressure, and some evidence of infertility and shorter duration of breastfeeding.

The Environmental Protection Agency’s lifetime interim health advisory values, set in 2022, for the two best-known PFAS – PFOA, formerly used to make DuPont’s Teflon, and PFOS, formerly an ingredient in 3M’s Scotchgard – are based on toxicity to the developing immune system. 

Developmental and reproductive health effects associated with exposure to PFAS

Human health harms

Evidence from human and animal studies

Low birth weight

• PFOA levels in maternal serum during pregnancy were associated with lower birth weight.1

• PFOS and PFOA levels in maternal serum during pregnancy were associated with lower birth weight.2-4

• Lower birth weight was associated with increasing PFOA, PFOS, PFNA, PFHxS and PFDA exposure levels during pregnancy.5

• Evidence of reduced fetal weight has also been observed in animal studies.6

• Birth weight was a key developmental health effect selected by the EPA to assess health impacts of lower exposure to PFOA and PFOS in drinking water. Since birth weight is a significant factor to infant survival, the EPA estimated 1,232.7 annual birth-weight-related deaths would be avoided (Table 6.12) if proposed maximum contaminant levels of 4 parts per trillion for PFOA and PFOS and a hazard index for four PFAS were adopted.7

Developmental toxicity to the immune system

• PFOA exposure in young children was linked to suppression of the immune system response to the tetanus vaccine.8, 9

• PFOS exposure in young children was linked to suppression of the immune system response to the diphtheria vaccine.8, 9

Hormone disruption

• Studies in humans found associations among PFAS, PFHxS and PFOS; exposure during pregnancy; and increases in maternal thyroid stimulating hormone, or TSH.10

• Animal studies found PFOA, PFOS, PFBA, PFBS, PFHxA, PFHxS, PFNA and PFDA exposure causes changes in thyroid hormone levels, TSH and thyroxine in adult animals.11, 12

Harm to sperm and the male reproductive system

• In humans, maternal exposure to PFOA was associated with reduced sperm concentrations and count in male offspring.13

• In another human study, semen quality went down in association with maternal exposure to seven PFAS, especially PFHpA.14

• Men living in a region of Italy highly contaminated by PFOA had reduced semen quality, testicular volume and penile length, compared to controls.15

• Animals studies found decreases in serum testosterone and sperm count from exposure to PFOA during developmental and adult stages.16, 17

Pregnancy-induced high blood pressure

• Evidence from the C8 Health Study of 70,000 residents near a DuPont Teflon plant in West Virginia suggests a probable link between PFOA and PFOS and pregnancy-induced high blood pressure.18-20

• Other studies have found no association.21, 22

Shorter duration of breastfeeding and harm to mammary gland development

• Some human studies have reported an association between PFOA and PFOS exposure and shorter duration of breastfeeding.23, 24

• Animal studies found PFOA reduced mammary gland development in females and offspring, though harm to lactation and nursing behavior have not been well assessed.25-27

Increased time to pregnancy

• In human studies, PFOA and PFOS exposure has been associated with longer time to pregnancy, an indicator of infertility.28, 29

• In another human study, exposure to PFDA, followed by PFOS, PFOA, and PFHpA, was associated with lower odds of a confirmed pregnancy.30

• Other studies found no association.31-34

References

1. Johnson, P.I., et al., The Navigation Guide–Evidence-Based Medicine Meets Environmental Health: Systematic Review of Human Evidence for PFOA Effects on Fetal Growth. Environmental Health Perspectives, 2014. 122(10): p. 1028-1039.

2. Chu, C., et al., Are perfluorooctane sulfonate alternatives safer? New insights from a birth cohort study. Environ Int, 2020. 135: p. 105365.

3. Wikström, S., et al., Maternal serum levels of perfluoroalkyl substances in early pregnancy and offspring birth weight. Pediatr Res, 2020. 87(6): p. 1093-1099.

4. Yao, Q., et al., Associations of paternal and maternal per- and polyfluoroalkyl substances exposure with cord serum reproductive hormones, placental steroidogenic enzyme and birth weight. Chemosphere, 2021. 285: p. 131521.

5. Padula, A.M., et al., Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program. Environ Health Perspect, 2023. 131(3): p. 37006.

6. Koustas, E., et al., The Navigation Guide–Evidence-Based Medicine Meets Environmental Health: Systematic Review of Nonhuman Evidence for PFOA Effects on Fetal Growth. Environmental Health Perspectives, 2014. 122(10): p. 1015-1027.

7. Environmental Protection Agency, Economic Analysis for the Proposed Per- and Polyfluoroalkyl Substances National Primary Drinking Water Regulation. 2023. (EPA-822-P-23-001) 

8. Budtz-Jørgensen, E. and P. Grandjean, Application of benchmark analysis for mixed contaminant exposures: Mutual adjustment of perfluoroalkylate substances associated with immunotoxicity. PLoS One, 2018. 13(10): p. e0205388.

9. Grandjean, P., et al., Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA, 2012. 307(4): p. 391-7.

10. Ballesteros, V., et al., Exposure to perfluoroalkyl substances and thyroid function in pregnant women and children: A systematic review of epidemiologic studies. Environ Int, 2017. 99: p. 15-28.

11. National Toxicology Program, NTP technical report on the toxicity studies of perfluoroalkyl sulfonates (perfluorobutane sulfonic acid, perfluorohexane sulfonate potassium salt, and perfluorooctane sulfonic acid) administered by gavage to Sprague Dawley (Hsd:Sprague Dawley SD) rats. Toxicity Report 96. 2019, National Toxicology Program: Research Triangle Park, N.C.

12. National Toxicology Program, NTP technical report on the toxicity studies of perfluoroalkyl carboxylates (perfluorohexanoic acid, perfluorooctanoic acid, perfluorononanoic acid, and perfluorodecanoic acid) administered by gavage to Sprague Dawley (Hsd:Sprague Dawley SD) rats. Toxicity Report 97. 2019, National Toxicology Program: Research Triangle Park, N.C.

13. Vested, A., et al., Associations of in utero exposure to perfluorinated alkyl acids with human semen quality and reproductive hormones in adult men. Environ Health Perspect, 2013. 121(4): p. 453-8.

14. Hærvig, K.K., et al., Maternal Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Male Reproductive Function in Young Adulthood: Combined Exposure to Seven PFAS. Environ Health Perspect, 2022. 130(10): p. 107001.

15. Di Nisio, A., et al., Endocrine Disruption of Androgenic Activity by Perfluoroalkyl Substances: Clinical and Experimental Evidence. J Clin Endocrinol Metab, 2019. 104(4): p. 1259-1271.

16. Lau, C., et al., Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol Sci, 2007. 99(2): p. 366-94.

17. Song, P., et al., Effects of perfluorooctanoic acid exposure during pregnancy on the reproduction and development of male offspring mice. Andrologia, 2018. 50(8): p. e13059.

18. Darrow, L.A., C.R. Stein, and K. Steenland, Serum perfluorooctanoic acid and perfluorooctane sulfonate concentrations in relation to birth outcomes in the Mid-Ohio Valley, 2005-2010. Environ Health Perspect, 2013. 121(10): p. 1207-13.

19. Savitz, D.A., et al., Perfluorooctanoic acid exposure and pregnancy outcome in a highly exposed community. Epidemiology, 2012. 23(3): p. 386-92.

20. Stein, C.R., D.A. Savitz, and M. Dougan, Serum Levels of Perfluorooctanoic Acid and Perfluorooctane Sulfonate and Pregnancy Outcome. American Journal of Epidemiology, 2009. 170(7): p. 837-846.

21. Savitz, D.A., et al., Relationship of perfluorooctanoic acid exposure to pregnancy outcome based on birth records in the mid-Ohio Valley. Environ Health Perspect, 2012. 120(8): p. 1201-7.

22. Starling, A.P., et al., Perfluoroalkyl substances during pregnancy and validated preeclampsia among nulliparous women in the Norwegian Mother and Child Cohort Study. Am J Epidemiol, 2014. 179(7): p. 824-33.

23. Romano, M.E., et al., Maternal serum perfluoroalkyl substances during pregnancy and duration of breastfeeding. Environ Res, 2016. 149: p. 239-246.

24. Timmermann, C.A.G., et al., Shorter duration of breastfeeding at elevated exposures to perfluoroalkyl substances. Reprod Toxicol, 2017. 68: p. 164-170.

25. Post, G.B., Technical Support Document: Intermine Specific Ground Water Criterion For Perfluorononanoic Acid (PFNA, C9) (CAS #: 375-95-1; Chemical Structure: CF 3(CF 2)7 COOH). 2019: Division of Science and Research, New Jersey Department of Environmental Protection.

26. Tucker, D.K., et al., The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure. Reprod Toxicol, 2015. 54: p. 26-36.

27. White, S.S., et al., Gestational PFOA exposure of mice is associated with altered mammary gland development in dams and female offspring. Toxicol Sci, 2007. 96(1): p. 133-44.

28. Fei, C., et al., Maternal levels of perfluorinated chemicals and subfecundity. Hum Reprod, 2009. 24(5): p. 1200-5.

29. Vélez, M.P., T.E. Arbuckle, and W.D. Fraser, Maternal exposure to perfluorinated chemicals and reduced fecundity: the MIREC study. Hum Reprod, 2015. 30(3): p. 701-9.

30. Cohen, N.J., et al., Exposure to perfluoroalkyl substances and women's fertility outcomes in a Singaporean population-based preconception cohort. Science of The Total Environment, 2023. 873: p. 162267.

31. Bach, C.C., et al., Serum perfluoroalkyl acids and time to pregnancy in nulliparous women. Environ Res, 2015. 142: p. 535-41.

32. Buck Louis, G.M., et al., Persistent environmental pollutants and couple fecundity: the LIFE study. Environ Health Perspect, 2013. 121(2): p. 231-6.

33. Jørgensen, K.T., et al., Perfluoroalkyl substances and time to pregnancy in couples from Greenland, Poland and Ukraine. Environmental Health, 2014. 13(1): p. 116.

34. Vestergaard, S., et al., Association between perfluorinated compounds and time to pregnancy in a prospective cohort of Danish couples attempting to conceive. Hum Reprod, 2012. 27(3): p. 873-80.

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