# Sources, Transport, Exposure and Effects of PFASs (STEEP)

> **NIH NIH P42** · UNIVERSITY OF RHODE ISLAND · 2020 · $281,167

## Abstract

PROJECT SUMMARY/ABSTRACT
Project 3 is one of two biomedical projects proposed for new URI-led Center – Sources, Transport, Exposure
and Effects of PFASs (STEEP) – that is being created to aid the Superfund Research Program (SRP) in
addressing the emerging problem of poly- and perfluorinated alkyl substances (PFASs) contamination. PFASs
are considered emerging environmental pollutants, notably found at high concentrations at sites contaminated
by aqueous fire fighting foams, such as Cape Cod. Human exposure to PFASs has been linked to
immunotoxicity, cancer, as well as metabolic and dyslipidemia. Specific to metabolic disorders, PFASs are
known to highly partition to the liver and links have been established between PFAS serum levels, specifically
perfluorooctanic acid (PFOA) and perfluorosulfonic acid (PFOS), and liver injury. While insightful, these two
common PFASs represent only a fraction of PFASs that exist within the contaminated sites and have been
detected in humans (for example by Grandjean, STEEP Project 2; and Sunderland, STEEP Project 1).
Understanding the mechanisms driving the biological response to PFASs are still emerging. The goal of this
work is to (i) address whether environmental exposure to PFASs contributes an additional increase risk for
obesity-induced fatty liver disease and metabolic disorders, and (ii) identify the physicochemical and
partitioning behavior of PFASs that contribute to bioaccumulation. The overarching hypotheses are (1) that
PFAS exposure will increase diet-induced hepatic steatosis and inflammation, which is potentially via
increased adiposity and altered adipokine secretion, and (2) that the biological responses (e.g. liver weight)
and biomarkers (e.g. oxidative stress gene expression) can be correlated with the protein, lipid, and/or
membrane partitioning behavior of PFASs. These hypotheses will be tested by (Aim 1) evaluating the potential
of PFASs to impact hepatic lipid accumulation, adipogenesis and adipokine secretion, (Aim 2) evaluating
postnatal and adult PFAS exposure as an additional risk factor for obesity-induced hepatic steatosis and
adipocyte dysfunction, and (Aim 3) determining the physicochemical properties of PFASs and their partitioning
behavior to fat and in protein phases. Furthermore, through this project significant gaps in ATSDR guidance
related to PFASs will be addressed pertaining to (i) outcomes with early in life PFAS exposure, (ii) mechanistic
biomarkers for PFAS exposure in addition to liver endpoints, (iii) risk factors common to the United States
population that might impact response to PFAS exposure (i.e. diet; obesity), and (iv) accurate measurements
of physicochemical properties that are needed to predict bioaccumulation and toxicity.

## Key facts

- **NIH application ID:** 9904672
- **Project number:** 5P42ES027706-04
- **Recipient organization:** UNIVERSITY OF RHODE ISLAND
- **Principal Investigator:** Angela L Slitt
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $281,167
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904672

## Citation

> US National Institutes of Health, RePORTER application 9904672, Sources, Transport, Exposure and Effects of PFASs (STEEP) (5P42ES027706-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9904672. Licensed CC0.

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