# Biological Response Profiles of Selected Engineered Nanomaterials after Perinatal Exposure

> **NIH NIH U01** · UNIVERSITY OF IOWA · 2020 · $409,323

## Abstract

PROJECT SUMMARY
The steady growth of products containing engineered nanomaterials (ENMs) has outpaced research to
determine their impact on biological systems, most importantly human health. Our goal in this Nanomaterials
Health Implications Research (NHIR) Consortium proposal is to elucidate how physicochemical properties of
ENMs and their molecular interactions affect the immune and hormonal status of exposed animals. We will
accomplish this goal by collaborating with NIEHS project scientists and NHIR Consortium members to test
ENMs provided by the ENM Resource and Coordination Core (ERCC) first in vitro using a novel air-liquid
interface system, and then in vivo for a subset of ENMs using a Pulmonary Tox Protocol and a Developmental
Tox Protocol. Each protocol will employ nose-only and whole-body inhalation exposure and a host of outcome
measures to assess body condition, cytotoxicity, inflammation, oxidative stress, gene expression, immune
modulation, endocrine disruption, and histopathology. We will share our data and methods within the NHIR
Consortium and beyond, thereby contributing to the development of comprehensive biological response
profiles of selected ENMs and identifying those that pose significant hazards for vulnerable populations
including pregnant women and children. Three specific aims will be addressed: AIM 1: Identify which ERCC-
characterized ENMs are most likely to induce cytotoxicity, inflammation, or immunomodulation in airway
epithelial cells using our established in vitro air-liquid interface model system. AIM2: Characterize
comprehensive biological responses to selected ENMs following subchronic inhalation exposure in pregnant
compared to non-pregnant mice. AIM 3: Elucidate biological response profiles in male and female offspring
following exposure to ENMs in utero and then postnatally by inhalation and lactation. These aims will be
accomplished by an experienced research team with expertise in inhalation toxicology of nanomaterials,
developmental toxicology, nanoaerosol generation and characterization, and ENM proteomics. Five primary
hypotheses will be tested: H1) Inhalation of the ENM under study induces significant biological responses at
the selected dose compared with controls. H2) ENM exposure produces adverse effects with a distinct
biological response profile that is dependent on pregnancy status. H3) Maternal ENM inhalation exposure from
pre-conception to delivery produces adverse developmental responses in fetuses. H4) Pups with further post-
natal exposure develop toxicological responses not seen in sham-exposed controls or in ENM-exposed adults.
H5) Following in utero and post-natal ENM exposure, maturation without exposure is associated with disease
progression. The research proposed herein will significantly advance understanding of the dose-specific
toxicity of inhaled ENMs and the operative AOPs and thus, will establish a framework for improving the safety
profile of commercial ENMs and guide their s...

## Key facts

- **NIH application ID:** 9995494
- **Project number:** 5U01ES027252-05
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Peter S Thorne
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,323
- **Award type:** 5
- **Project period:** 2016-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995494

## Citation

> US National Institutes of Health, RePORTER application 9995494, Biological Response Profiles of Selected Engineered Nanomaterials after Perinatal Exposure (5U01ES027252-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9995494. Licensed CC0.

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