Scientific Studies Supporting Development of Transcriptomic Points of Departure for EPA Transcriptomic Assessment Products (ETAPs)

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posted on 2024-03-11, 13:06 authored by Daniel Chang, John Cowden, Sarah Davidson-Fritz, Jeffry Dean, Michael Devito, Logan Everett, Alison Harrill, Susan Hester, Michael Hughes, Jason Lambert, Lucina Lizarraga, Roman Mezencev, Grace Patlewicz, Russell Thomas, Leah Wehmas, Kelsey Vitense, Scott Auerbach, Warren Casey, Reeder Sams, Sid Hunter, John Bucher, Timothy Buckley, Peter Egeghy, Katie Paul Friedman, Joshua Harrill, Kristin Isaacs, Richard Judson, Jonathan Kaiser, Scott V. Masten, Fred Parham, Dan Petersen, Allison Phillips, Jon Sobus, Dan Villeneuve, Paul White, Antony Williams, George M. Woodall, Jay Zhao

Current estimates of the size of worldwide and domestic chemical inventories are substantial, with increasing trends in future chemical production and release. Relatively few of the chemicals in commerce, as well as those found in the environment, various waste streams, and the human body, have traditional toxicity data or human health assessments. Given historical, current, and future trends in chemical production and the disparity in toxicity testing data and human health assessments, the U.S. Environmental Protection Agency (EPA) is frequently faced with making decisions with limited or no data when evaluating potential human health risks.

This document details the methods used to develop transcriptomic reference values (TRV) for use in EPA Transcriptomic Assessment Products (ETAP) by the Office of Research and Development (ORD), EPA. The scientific rationale underlying ETAP is provided in the EPA report entitled Scientific Studies Supporting Development of Transcriptomic Points of Departure for EPA Transcriptomic Assessment Products (ETAPs) (EPA 2023). The TRV is defined as an estimate of a daily oral dose that is likely to be without appreciable risk of adverse effects following chronic exposure. The TRV is intended to protect both the individual and population from adverse effects other than cancer or related to cancer if a necessary key precursor event does not occur below a specific exposure level. While a TRV is expressly defined as a chronic value in an ETAP, it may also be applicable across other exposure durations of interest including short-term and subchronic. This generalization has been previously used by EPA in certain risk assessment applications [e.g., Provisional Peer-Reviewed Toxicity Value (PPRTV) assessments] where a chronic non-cancer reference value has been adopted as a conservative estimate for a subchronic non-cancer reference value when data quality and/or lack of duration-relevant hazard and dose-response data preclude direct derivation.

The ETAP is intended to be applied to data poor substances with no existing or publicly accessible repeated dose toxicity studies or suitable human evidence. ETAPs may be updated to incorporate new data or methodologies that might impact the estimated reference values or retired if traditional toxicity studies and an associated human health assessment are published.

Science Inventory, CCTE products: https://cfpub.epa.gov/si/si_public_search_results.cfm?advSearch=true&showCriteria=2&keyword=CCTE&TIMSType=&TIMSSubTypeID=&epaNumber=&ombCat=Any&dateBeginPublishedPresented=07/01/2017&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&DEID=&personName=&personID=&role=Any&journalName=&journalID=&publisherName=&publisherID=&sortBy=pubDate&count=25