# Environmental-use chemicals that target pathways linked to autism and other neurodevelopmental disorders

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $852,030

## Abstract

PROJECT SUMMARY
While significant progress has been made in identifying de novo gene mutations linked to autism risk, much
less attention has been paid to environmental risks and the extent to which these risks cause autism pathology
in susceptible individuals. Environmental factors, including gestational exposure to pyrethroid pesticides and
valproic acid, are implicated in risk for autism. Prenatal exposure to pyrethroids is also linked to risk for
developmental delay and attention deficit hyperactivity disorder (ADHD)—one of the most common
neurodevelopmental disorders. However, these environmental risks were identified retrospectively, after a
large number of people were exposed. Thousands of chemicals are registered for use in the environment, and
humans are potentially exposed to many of these chemicals to varying degrees, including chemicals in plastics
and building materials. We currently lack a way to systematically evaluate which environmental-use chemicals
have the greatest potential to harm the developing brain. The inability to identify environmental threats to the
brain early—before they cause disease—represents one of the major public health challenges of our time.
This challenge is particularly relevant to autism, which now affects 1 in 59 individuals in America, and where
heritability studies indicate that genetic and environmental factors contribute to autism risk. Our research
program is guided by the hypothesis that “candidate” environmental risks for autism and other
neurodevelopmental disorders can be identified rationally, by identifying chemicals and mixtures that
target molecular pathways implicated in these disorders. Our long term goals are to 1) identify
environmental-use chemicals and mixtures that target molecular pathways implicated in neurodevelopmental
disorders. These studies will utilize primary human neural progenitor cells (phNPCs), primary neurons, and
endpoints that are compatible with high-throughput screening. 2) Assess real world exposure to these
chemicals/mixtures. If environmental sampling and biomonitoring data are not available for these
chemicals/mixtures, we will work with a network of Environmental Health Science (EHS) researchers to collect
these data. 3) Evaluate exposure risk in vivo using wild-type and CRISPR/Cas9-engineered mice that model
human de novo autism-linked mutations. We will prioritize chemicals/mixtures that a) impact one or more
phNPC/neuron assay endpoints, b) are verified exposure risks to humans, and c) enter the placenta and/or
developing brain following maternal exposure. While the specific projects will evolve over time, we plan to
initially focus on individual and joint exposures to pyrethroids and strobilurins—a new class of fungicides that
inhibits mitochondria. Both chemical classes impair neuronal functions and co-occur in the home environment.
We will evaluate the extent to which prenatal exposure to these and other prioritized chemicals and mixtures
exacerbate brain ...

## Key facts

- **NIH application ID:** 10402265
- **Project number:** 5R35ES028366-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Mark J. Zylka
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $852,030
- **Award type:** 5
- **Project period:** 2019-06-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402265

## Citation

> US National Institutes of Health, RePORTER application 10402265, Environmental-use chemicals that target pathways linked to autism and other neurodevelopmental disorders (5R35ES028366-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10402265. Licensed CC0.

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