# Airborne PCBs and their Metabolites: Risk Factors for Adverse Neurodevelopmental Outcomes in Adolescence

> **NIH NIH P42** · UNIVERSITY OF IOWA · 2020 · $277,852

## Abstract

PROJECT SUMMARY: Project 1 – Neurotoxicity
Studies by the Iowa Superfund Research Program demonstrate that inhalation of indoor air, especially in U.S.
schools contaminated with polychlorinated biphenyls (PCBs), represents a current public health concern for U.S.
adolescents. Although the adolescent brain is vulnerable to the toxicity of PCBs and their metabolites, information
regarding the neurotoxicity of human metabolites of airborne PCBs—which differ significantly from those formed in
rodents—is currently not available. There is, therefore, a critical need to: 1) establish mechanisms by which
human metabolites of PCBs affect neurochemistry (i.e., toxic neurotransmitter metabolites) and subsequent
behavioral outcomes; and 2) determine how metabolism of airborne PCBs and their metabolites in the brain
represents a key event in PCB-mediated neurotoxicity in adolescents exposed to PCBs. The objective of this
project is to inform future risk assessment by defining the link between neurotoxic PCB metabolites present in
the brain and neurotoxic outcomes following exposure during adolescence. Our central hypothesis is that, in
addition to the parent airborne PCBs, metabolites formed in humans are present in the brain and serve as risk
factors for altered neurodevelopment during adolescence. We propose that PCBs, and especially their
metabolites, adversely affect neurotransmitter homeostasis. This hypothesis is based on preliminary studies
showing that metabolites of airborne PCBs: a) are present in the rodent brain; b) cause oxidative stress in vitro
and in vivo; c) alter neurotransmitter homeostasis in dopaminergic neurons in culture, producing ROS and toxic
catecholaldehydes; and d) undergo further metabolism to potentially toxic metabolites in the brain. Guided by
these preliminary data, the novel hypothesis will be tested by 1) identifying cellular sites and targets of airborne
PCB metabolites vs. parent compounds responsible for neurotoxicity in vitro; 2) characterizing the region-
specific biotransformation of PCBs and PCB metabolites with in vitro models and in the adolescent rat brain in
vivo; and 3) determining the effects of human metabolites of airborne PCBs on biochemical markers of PCB
neurotoxicity and behavioral outcomes in rats exposed throughout adolescence in vivo. The proposed research
is innovative because it determines how the disruption of dopamine balance by PCB metabolites disturbs
dopamine levels and/or produces toxic dopamine metabolites detrimental to the brain in adolescence, a period
of vulnerability; and studies localized metabolism in the brain, thus challenging the scientific paradigm that
PCBs are either resistant to metabolism or metabolized only in the liver. Outcomes of the proposed studies will
elucidate the contributions of airborne PCBs and their metabolites to, and their mechanisms of action in,
neurotoxic responses. Thus, the successful completion of this research will impact public health by providing
fundame...

## Key facts

- **NIH application ID:** 9839864
- **Project number:** 2P42ES013661-15
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** HANS-JOACHIM LEHMLER
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $277,852
- **Award type:** 2
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9839864

## Citation

> US National Institutes of Health, RePORTER application 9839864, Airborne PCBs and their Metabolites: Risk Factors for Adverse Neurodevelopmental Outcomes in Adolescence (2P42ES013661-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9839864. Licensed CC0.

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