# Early life ENM-exposure and the impact on neurobehavioral and cardiovascular outcomes and biochemical mechanisms

> **NIH NIH U01** · RESEARCH TRIANGLE INSTITUTE · 2020 · $499,000

## Abstract

Project Summary
This submission is prepared in response to RFA-ES-15-013, which will establish a National Institute of
Environmental Health Sciences - Nanotechnology Health Implications Research (NHIR) Consortium:
Comprehensive Evaluation of Interactions Between Engineered Nanomaterials (ENMs) and Biological System
U01s. The NHIR Consortium will collaborate to investigate the interaction between ENMs and biological
systems to provide comprehensive response profiles of ENM exposures to guide development of benign ENMs
and support safe and sustainable use of nanotechnology. The aim of this proposal is to investigate
Consortium-selected ENMs, with a broad range of physicochemical properties, to reveal how early life ENM
exposure impacts neurobehavioral and cardiovascular outcomes and cause changes in biochemistry. The
developing neonate has immature gastrointestinal function, with a developing barrier function, that may allow
greater uptake of ENMs than in an adult. The developing brain can be impacted by exposure to chemicals
both directly and indirectly. The cardiovascular system has also been shown to be particularly sensitive to the
effects of ENMs.
The project will consist of three inter-related areas of investigation with the following aims:
 1. To investigate the impact of ENMs on the integrity and permeability of the intestinal barrier in vitro. We
will test the Consortium-selected ENMs in two well-established models of the small intestine using 1)
enterocytes and goblet cells, and 2) enterocytes and M cells.
 2. To determine the ENM tissue distribution and cellular localization in exposed neonatal and juvenile rats
with determination of neurobehavioral and cardiovascular effects. The biological response to ENMs will be
studied in female and male neonatal and juvenile rats with daily ENMs administered orally from postnatal day
(PND) 2-20, and euthanized at PND 4, 9, and 21. Comprehensive assessment of the ENM tissue distribution,
functional neurobehavioral observations, cardiovascular measurements, neurotransmitter measurement, and
untargeted and targeted metabolomics analysis (aim 3) will be conducted on PND 4, 9 and 21.
 3. To characterize perturbations in biochemical profiles of serum, brain tissue, and cecal contents
associated with ENM exposure, and with neurological and cardiovascular assessments. Studies will focus on
determining how ENMs perturb the biochemical profiles of the serum, brain tissue, and cecal contents of male
and female rat pups. Assessments will include the use of NMR metabolomics, a 16 channel ECD CoulArray to
simultaneously quantitate 20 neurotransmitters, and a quantitative assay for 188 compounds including
acylcarnitines, amino acids, biogenic amines, hexose, glycerophospholipids, phosphatidylcholines, and
sphingolipids.

## Key facts

- **NIH application ID:** 10005355
- **Project number:** 5U01ES027254-05
- **Recipient organization:** RESEARCH TRIANGLE INSTITUTE
- **Principal Investigator:** TIMOTHY RAYMOND FENNELL
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $499,000
- **Award type:** 5
- **Project period:** 2016-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005355

## Citation

> US National Institutes of Health, RePORTER application 10005355, Early life ENM-exposure and the impact on neurobehavioral and cardiovascular outcomes and biochemical mechanisms (5U01ES027254-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10005355. Licensed CC0.

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