Perfluoroalkyl substance serum concentrations and immune response to FluMist vaccination among healthy adults

Stein, Cheryl R.; Ge, Yongchao; Wolff, Mary S.; Ye, Xiaoyun; Calafat, Antònia M.; Kraus, Thomas; Moran, Thomas M.

doi:10.1016/j.envres.2016.05.020

Cited by 37 publications

(41 citation statements)

References 29 publications

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“…Observed associations between PFAS exposure and methylation of genes involved in immune response and inflammation are consistent with the results of some previous epidemiological studies reporting altered immune system-related outcomes in adults and children exposed to PFAS (Chang et al 2016;Rappazzo et al 2017). Previous studies have generally focused on one or more of the following outcomes: allergy and atopic disease (Goudarzi et al 2016;Stein et al 2016b;Timmermann et al 2017), reduced antibody response to vaccination (Grandjean et al 2017;Looker et al 2014;Stein et al 2016a), frequency of infectious disease in children (Dalsager et al 2016;Goudarzi et al 2017;Impinen et al 2018), and inflammatory or autoimmune disease (Steenland et al 2013(Steenland et al , 2018Webster et al 2014Webster et al , 2016. Evidence from animal studies also indicates that PFOA is immunotoxic, and dietary exposure has resulted in a variety of immune system effects, including reduced weight of lymphoid organs and impaired antibody responses (DeWitt et al 2009).…”

Section: Discussionsupporting

confidence: 88%

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Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study

Starling

Liu

Shen

et al. 2020

Environ Health Perspect

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Background: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype. Objectives: We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators. Methods: Among 583 mother–infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate and differentially methylated regions (DMRs) were identified using comb-p (Šidák-adjusted ). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin. Results: Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correlations were observed between PFAS concentrations ( ). Methylation at one DMP (cg18587484), annotated to the gene TJAP1 , was associated with perfluorooctanoate (PFOA) at . Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth ( RPTOR ), lipid homeostasis ( PON1 , PON3 , CIDEB , NR1H2 ), inflammation and immune activity ( RASL11B , RNF39 ), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively ( ). Discussion: DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888

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Section: Discussionsupporting

confidence: 88%

“…2017 ; Looker et al. 2014 ; Stein et al. 2016a ), frequency of infectious disease in children ( Dalsager et al.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study

Starling

Liu

Shen

et al. 2020

Environ Health Perspect

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“…This effect size is larger than later studies and can be attributed to different exposure levels, different vaccine strains, and different times elapsed since vaccination (peak antibodies vs residual antibodies). Other studies have not examined tetanus and diphtheria, but similar associations have been found in PFAS exposure and other childhood vaccinations such as rubella and mumps, 125, 126 and adult influenza vaccination such as FluMist 127 and anti-H3N2. 128…”

Section: Health Effects Associated With Exposure To Pfassmentioning

confidence: 54%

A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects

Sunderland

Dassuncao

et al. 2018

J Expo Sci Environ Epidemiol

1,611

871

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Here we review present understanding of sources and trends in human exposure to poly- and perfluoroalkyl substances (PFASs) and epidemiologic evidence for impacts on cancer, immune function, metabolic outcomes, and neurodevelopment. More than 4000 PFASs have been manufactured by humans and hundreds have been detected in environmental samples. Direct exposures due to use in products can be quickly phased out by shifts in chemical production but exposures driven by PFAS accumulation in the ocean and marine food chains and contamination of groundwater persist over long timescales. Serum concentrations of legacy PFASs in humans are declining globally but total exposures to newer PFASs and precursor compounds have not been well characterized. Human exposures to legacy PFASs from seafood and drinking water are stable or increasing in many regions, suggesting observed declines reflect phase-outs in legacy PFAS use in consumer products. Many regions globally are continuing to discover PFAS contaminated sites from aqueous film forming foam (AFFF) use, particularly next to airports and military bases. Exposures from food packaging and indoor environments are uncertain due to a rapidly changing chemical landscape where legacy PFASs have been replaced by diverse precursors and custom molecules that are difficult to detect. Multiple studies find significant associations between PFAS exposure and adverse immune outcomes in children. Dyslipidemia is the strongest metabolic outcome associated with PFAS exposure. Evidence for cancer is limited to manufacturing locations with extremely high exposures and insufficient data are available to characterize impacts of PFAS exposures on neurodevelopment. Preliminary evidence suggests significant health effects associated with exposures to emerging PFASs. Lessons learned from legacy PFASs indicate that limited data should not be used as a justification to delay risk mitigation actions for replacement PFASs.

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“…Results from six vaccination response studies in children and adults have been reported to date (Grandjean et al., ; Granum et al., ; Looker et al., ; Kielsen et al., 2016; Stein et al., 2016b; Abraham et al., ). Three of these studies show, for several PFASs, relatively strong inverse associations with antibody response following booster vaccination to tetanus and diphtheria in both children (Abraham et al., ; Grandjean et al., ) and adults (Kielsen et al., 2016).…”

Section: Assessmentmentioning

confidence: 99%

Risk to human health related to the presence of perfluoroalkyl substances in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

332

265

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The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances ( PFAS s) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFAS s: PFOA , PFNA , PFH xS and PFOS . These made up half of the lower bound ( LB ) exposure to those PFAS s with available occurrence data, the remaining contribution being primarily from PFAS s with short half‐lives. Equal potencies were assumed for the four PFAS s included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/ mL for the sum of the four PFAS s in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/ mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake ( TWI ) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI , which is of concern.

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Perfluoroalkyl substance serum concentrations and immune response to FluMist vaccination among healthy adults

Cited by 37 publications

References 29 publications

Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study

Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study

A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects

Risk to human health related to the presence of perfluoroalkyl substances in food

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