Thousands of chemicals are currently in commerce in the US and hundreds more are introduced every year as new chemicals through the premanufacture notification (PMN) process. Current toxicity testing is resource intensive and only a small fraction of chemicals have been adequately tested for potential human health effects. Deep sequencing technologies of DNA and RNA can play an important role in describing absorption, distribution, metabolism and excretion (ADME) pathways in order to assess health risks from environmental exposures to new and existing chemicals under the Toxic Substances Control Act (TSCA), as amended by the “Frank R. Lautenberg Chemical Safety for the 21st Century Act”. Section 4(h)(1)(B)(i) of the amended TSCA states that the EPA will encourage and facilitate “…the use of scientifically valid test methods and strategies that reduce or replace the use of vertebrate animals while providing information of equivalent or better scientific quality and relevance that will support regulatory decisions..” For example, chemical companies are developing greener chemicals to potentially avoid persistent and toxic substances (both parent and metabolites). These chemicals may be similar to the chemicals they are intended to replace with limited modifications. The Office of Pollution Prevention and Toxics is exploring approaches wherein human health effects evaluations for certain chemicals may benefit from a toxicogenomics approach to determine mechanism of action and pathway analysis. Applying deep sequencing and alternative testing may improve the sensitivity and comprehensive examination of direct and indirect molecular changes. These advantages could provide key information on the pathway to adverse outcomes. The next goal is to quantify these data, not only in the exposure linked genomic environment, but also on the epigenetic and transgenerational landscapes.<br/>

Adverse outcome pathways: A mechanistic approach for future risk assessments

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.