# Predicting the Toxicity of Complex PAH Mixtures

> **NIH NIH P42** · OREGON STATE UNIVERSITY · 2020 · $303,956

## Abstract

PROJECT SUMMARY – TANGUAY PROJECT
Polycyclic aromatic hydrocarbons (PAHs) are near ubiquitous contaminants at Superfund sites. Approximately
16% of the U.S. population, including ~17% of all children in the U.S. under the age of 5, live within 3 miles of a
Superfund site. The physical proximity of so many people to PAH contamination challenges regulatory
agencies to provide accurate risk assessments in order to protect public health. Human exposure to PAHs is
complex; exposures always occur as complex mixtures rather than as individual parent PAHs. The potency
for individual parent PAHs to produce adverse developmental outcomes is fairly well understood, but the
additive antagonistic or synergistic effects of PAHs in mixtures is largely unknown. An added level of
uncertainty is that PAHs are environmentally transformed, and the mobility and toxicity of these transformed
PAHs can be significantly greater than the parent forms. Developmental exposure to PAHs may carry the
greatest risk. Recent epidemiological data indicate strong associations between early life stage PAH exposures
and the increased occurrence of birth defects and increases in significant neurobehavioral deficits and heart
disease. Risk assessors desperately need of relevant in vivo data to develop comprehensive models for
predictive toxicity. By linking biological responses to PAH structures, uptake, and diagnostic gene expression
pathways, the Tanguay Project will establish zebrafish as a biosensor that can provide rapid feedback to SRP
stakeholders responsible for risk assessment and remediation. This approach interrogates all aspects of
development and the molecular pathways that underlie it, in one integrated experiment. We have developed an
effective framework for conveying this high-impact work to stakeholders and for collaborating with
populations to reduce their risk. Our overarching hypothesis is that we can learn to predict the toxicity of
PAH mixtures based on the structural classes, bioactivity profiles and pathway targets of their PAH
components. We will test this hypothesis in four Specific Aims: 1) Determine how the developmental impacts of
PAH exposure depend on the composition of PAH mixtures, the chemical structures of environmentally
transformed PAHs, and the presence of AHR signaling; 2) Measure the uptake and metabolism of biologically
active PAHs in zebrafish; 3) Develop diagnostic gene expression pathways for classes of PAHs, determine how
those pathways vary as a function of dose and associate those pathways with specific adverse effects; 4)
Determine adult and transgenerational consequences of transient developmental exposures to individual PAHs
and mixtures.

## Key facts

- **NIH application ID:** 9841202
- **Project number:** 2P42ES016465-11
- **Recipient organization:** OREGON STATE UNIVERSITY
- **Principal Investigator:** Robyn L Tanguay
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $303,956
- **Award type:** 2
- **Project period:** — → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841202

## Citation

> US National Institutes of Health, RePORTER application 9841202, Predicting the Toxicity of Complex PAH Mixtures (2P42ES016465-11). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9841202. Licensed CC0.

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