# Investigating the hepatic toxicity of 3,3’-dichlorobiphenyl (PCB-11) in zebrafish (Danio rerio)

> **NIH NIH F31** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2020 · $32,132

## Abstract

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PROJECT SUMMARY/ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) affects 30-40% of the U.S. population and has an estimated U.S.
economic burden of $103 billion per year. NAFLD is also prevalent in children and adolescents, affecting
34.2% of obese individuals and 7.6% of this population overall. Higher-chlorinated polychlorinated biphenyls
(PCBs) are implicated in the etiology of NAFLD, however, little is known about the hepatic toxicity potential of
lower-chlorinated PCBs, including 3,3’-dichlorobiphenyl (PCB-11), widely detected in environmental and
human samples, including in pregnant women. Preliminary research shows that acute developmental
exposures to PCB-11 alone do not result in overt toxicological outcomes in zebrafish (Danio rerio), however, it
misregulates hepatic-associated genes, stunts liver development, and increases vacuolization in liver tissue.
Further, in combination with Aryl hydrocarbon receptor (Ahr) agonists, PCB-11 can either inhibit Cytochrome
p4501a (Cyp1a) enzyme activity induced by a model PAH, exacerbating toxicity, or prevent toxicity induced by
PCB-126, highlighting the importance of using a mixtures approach. The objective of this proposed study is to
investigate the hepatic toxicity of PCB-11 metabolites, which have longer half-lives in vivo for rodents, and in
preliminary data of low-dose exposures show increased hepatic lipid deposition in 15-day fish. The central
hypothesis of this proposed study is that PCB-11 induced hepatic toxicity is attributed to its metabolites
and is associated with a NAFLD liver phenotype during juvenile development. Aim 1 will determine the
toxicity contribution of phenolic and sulfate PCB-11 metabolites in 4-day old fish. Aim 2 will assess PCB-11
and PCB-11-Sulfate toxicity in 30-day juvenile stage fish after low-dose chronic single and mixture exposures.
The proposed training plan to execute these aims includes learning and/or performing methods such as EROD
assays to measure Cyp1a activity, fluorescence microscopy to assess liver development, histopathology, Oil-
Red-O staining to assess lipid deposition, and Fluorescence-Activated Cell Sorting (FACS) for fatty acid
composition analysis of hepatocytes. In addition, chronic exposures will be carried out using the OECD Fish,
Early-Life Stage (FELS) toxicity test (OECD TG 210) to gain practical experience in regulatory toxicity
approaches and to increase preparation for the career goal of working as a government scientist to assess the
public health impacts of contaminant exposures. This project will yield in vivo mechanistic toxicity data on
PCB-11 and its metabolites at several developmental stages to be of use for public health regulators.
The sponsor, Dr. Alicia Timme-Laragy, has a record of NIH funding, is a recent mentor of an NIH F32
Postdoctoral Fellow (now a faculty member at San Diego State University), has numerous equipment for
fluorescence microscopy, molecular biology and biochemistry work, and is capable of provid...

## Key facts

- **NIH application ID:** 10058206
- **Project number:** 5F31ES030975-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Monika Roy
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,132
- **Award type:** 5
- **Project period:** 2019-09-15 → 2021-06-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058206

## Citation

> US National Institutes of Health, RePORTER application 10058206, Investigating the hepatic toxicity of 3,3’-dichlorobiphenyl (PCB-11) in zebrafish (Danio rerio) (5F31ES030975-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10058206. Licensed CC0.

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