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University of Rhode Island

Superfund Research Program

Inflammation and Metabolic Changes in Children Developmentally Exposed to PFASs

Project Leader: Philippe Grandjean (Harvard School of Public Health)
Co-Investigator: Qi Sun (Harvard University)
Grant Number: P42ES027706
Funding Period: 2017-2022
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Project Summary (2017-2022)

Poly- and perfluorinated alkyl substances (PFASs) are widely used industrial chemicals, but widespread human PFAS exposures from contaminated sites and bioaccumulation in food-chains were discovered less than 20 years ago, and the full range of adverse health effects is not completely known. While the U.S. Environmental Protection Agency published limits for water contamination in 2009, these limits remain provisional and may be as much as two orders of magnitude too high. Thus, recent evidence suggests that current PFAS exposures may cause adverse effects on the immune system and other sensitive tissues and organs, even at exposures far below provisional exposure limits. Further, recent evidence, including the researchers' own studies, suggests that early-life exposure to PFASs may contribute to the development of metabolic diseases, including obesity and type 2 diabetes, which constitute major public health problems.

Following the researchers' discovery that PFAS exposure is associated with decreased antibody response to certain childhood vaccinations, they hypothesize that PFAS-induced inflammation may be involved in obesogenic effects of PFAS exposure. The researchers also recently discovered that most PFASs are transferred via human milk, thereby resulting in peak exposures at the time of weaning.

As part of the University of Rhode Island-led Sources, Transport, Exposure and Effects of PFASs (STEEP) Superfund Research Program Center, the team is determining the possible links between PFAS exposure profiles, immune dysfunction, and metabolic abnormalities by examining an already established birth cohort from the Faroe Islands at age 9 years. The researchers have chosen this epidemiological setting as close to ideal to explore the associations between age-related PFAS exposure profiles and metabolic abnormalities. Relying on an already established birth cohort that has been supported by NIEHS, the Project is efficiently utilizes exposure and outcome data covering a 9-year span within the project duration, while taking advantage of clinical information, exposure data, and banked serum samples from birth and clinical examinations at ages 18 months and 5 years. Due to the homogeneity of the Faroese population, the wide range of exposures, and the high participation rate in the clinical follow-up, this epidemiological setting represents advantages that would be nearly impossible to match anywhere else. In addition, comparable cohorts are being included in pooled statistical analyses to increase the statistical power.

The data analysis is taking into account important covariates, including exposures to other environmental chemicals, and researchers are exploring the influence of child sex and diet on PFAS-associated effects, as well as conducting benchmark dose calculations for possible use in risk characterization in U.S. populations exposed to PFASs. In the selection and evaluation of biomarkers and interpretation of the results, the team is coordinating with the PFAS compound effects on metabolic abnormalities in rodents project in regard to the causal role of PFASs on metabolic and immune dysfunction. The STEEP project is also linked to other projects and the Community Engagement Core and Research Translation Core by contributing to the development of new biomarkers for application in prevention efforts to protect exposed populations.

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