Short-term Transcriptomic Studies of 1,2-Dichlorobenzene and 1,4-Dichlorobenzene following Whole-body Inhalation Exposure in Rats and Mice

NIH RePORTER · NIH · N01 · $603,660 · view on reporter.nih.gov ↗

Abstract

The project was initiated by a nomination from the US Environmental Protection Agency (EPA) to leverage DTT's capabilities to conduct short-term inhalation studies for ortho-dichlorobenzene (1,2-DCB) and para-dichlorobenzene (1,4-DCB). The test articles, 1,2-DCB and 1,4-DCB, are both utilized in products like bathroom deodorants (urinal cakes and moth balls) have been extensively studied for the toxicological properties, with significant contributions from DTT. Both chemicals have undergone oral cancer bioassays by the National Toxicology Program (NTP), along with other assessments covering endpoints like reproductive and developmental toxicity. Despite this, a notable data gap exists in inhalation toxicity for 1,2-DCB, highlighted by the EPA. By undertaking short-term in vivo genomic dose-response studies via inhalation, we seek to establish new benchmarks for genomic data collection, address inhalation exposure's unique challenges, and link oral exposure data with findings from inhalation studies. This project emerges as a unique opportunity for the DTT to engage closely with members of the regulatory community, particularly with the EPA. The EPA’s current focus on mandated re-evaluation of the risks of 1,2-DCB and 1,4-DCB under TSCA provides an opportune moment for such a partnership. The collaboration aims to refine the DTT’s genomic analysis methodologies to better fit the nuanced requirements of regulatory groups. Specifically, it is intended to formulate a framework for using the genomic data to go beyond identifying biological potency and to use the data to characterize hazard and mechanism along with developing standards for performing high dimensional similarity analysis to support genomics-based read-across.

Key facts

NIH application ID
11216035
Project number
75N96024C00005-0-9999-2
Recipient
BATTELLE CENTERS/PUB HLTH RES & EVALUATN
Principal Investigator
DAWN FALLACARA
Activity code
N01
Funding institute
NIH
Fiscal year
2024
Award amount
$603,660
Award type
Project period
2024-09-16 → 2025-09-15