Internal exposure to perfluoroalkyl substances (PFASs) and biological markers in 101 healthy 1-year-old children: associations between levels of perfluorooctanoic acid (PFOA) and vaccine response

Abstract

Perfluoroalkyl substances (PFASs) are a complex group of man-made chemicals with high stability and mobility leading to ubiquitous environmental contamination and accumulation in the food chain. In human serum/plasma samples, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are the lead compounds. They are immunotoxic in experimental animals, and epidemiological studies provided evidence of a diminished production of vaccine antibodies in young children. However, information on children of the first year of age is missing but relevant, as they have a relatively high exposure if breastfed, and may have a higher susceptibility as their immune system is developing. In a cross-sectional study with 101 healthy 1-year-old children, internal levels of persistent organic pollutants and a broad panel of biological parameters were investigated at the end of the 1990s. Additional analysis of PFASs resulted in plasma levels (mean ± SD) of PFOA and PFOS of 3.8 ± 1.1 and 6.8 ± 3.4 µg/L, respectively, in the 21 formula-fed children, and of 16.8 ± 6.6 and 15.2 ± 6.9 µg/L in the 80 children exclusively breastfed for at least 4 months. The study revealed significant associations between levels of PFOA, but not of PFOS, and adjusted levels of vaccine antibodies against Haemophilus influenza type b (Hib, r = 0.32), tetanus (r = 0.25) and diphtheria (r = 0.23), with no observed adverse effect concentrations (NOAECs) determined by fitting a 'knee' function of 12.2, 16.9 and 16.2 µg/L, respectively. The effect size (means for PFOA quintiles Q1 vs. Q5) was quantified to be − 86, − 54 and − 53%, respectively. Furthermore, levels of PFOA were inversely associated with the interferon gamma (IFNɣ) production of ex-vivo lymphocytes after stimulation with tetanus and diphtheria toxoid, with an effect size of − 64 and − 59% (means Q1 vs. Q5), respectively. The study revealed no influence of PFOA and PFOS on infections during the first year of life and on levels of cholesterol. Our results confirmed the negative associations of PFAS levels and parameters of immune response observed in other epidemiological studies, with high consistency as well as comparable NOAECs and effects sizes for the three vaccine antibodies investigated, but for PFOA only. Due to reduction of background levels of PFASs during the last 20 years, children in Germany nowadays breastfed for a long duration are for the most part not expected to reach PFOA levels at the end of the breastfeeding period above the NOAECs determined.

Outcome of a public consultation on the draft risk assessment of perfluoroalkyl substances in food

“…The NTP concludes that PFOS/PFOA is presumed to be an immune hazard to humans based on a high level of evidence that PFOS/PFOA NTP performed a meta-analysis on immunotoxicity associated with exposure to PFOA and PFOS (NTP 2016). We suggest integrating this analysis into EFSA's new risk assessment; this would be supportive for EFSA's conclusion, especially as the key study (Abraham et al, 2020) was not considered by NTP. The NTP concludes that PFOS/PFOA is presumed to be an immune hazard to humans based on a high level of evidence that PFOS/PFOA suppressed the antibody response from animal studies and a moderate level of evidence from studies in humans.…”

“…In this case, due to data protection, the CONTAM Panel was unable to obtain individual data but, on request, additional aggregated data were obtained on the sum of the 4 PFASs and these were described in the draft Opinion. The paper by Abraham et al (2020), which focuses on PFOA, is published.…”

“…It was concluded that the assumed maternal levels at birth (measured values of mothers not having breastfed) are too high, and possible explanations were discussed. However, this is misleading as it was not realized that the breastfed children of the study (Abraham et al 2020) received mother's milk for 7.4 months only (mean), and not for 12 months. To test the model, the levels of mothers not having breastfed the child (PFOA 4.9 ng/mL, PFOS 17.2 ng/mL) were taken for the maternal levels before pregnancy.…”

“…EFSA agrees with the notion that the developing immune system may be vulnerable to the effects of exposure to immunotoxic chemicals. The study by Abraham et al (2020) is addressing this population group. We are a little surprised to read that PFOA still seems to have an impact on birthweight, while it has been prohibited since 2011 and we recently read that the exposure to PFOA has diminished considerably.…”

Is There a Role for Environmental and Metabolic Factors Predisposing to Severe COVID-19?

“…In essence, it is confirmed for humans and animals, that levels of PFOS and PFOA are inversely linked to functionality of the immune system. The most significant concern regards the strong inverse association of PFAS blood levels and antibody response for example, following booster vaccinations to diphtheria and tetanus, particularly in children as shown on the Faroe Islands [51] and in Germany [52]. Supporting information from animal studies is available [53].…”