Dataset Information

Transcriptomic changes and toxicologic potential of per/polyflourinated alkyl substances (pfas) in laboratory animals via gavage

ABSTRACT: The US EPA has identified a number of PFAS and other chemicals of high priority to States and Regional EPA offices that have no available in vivo toxicology data. Based on the list of data-poor chemicals and availability of the chemicals, four were selected for 5-day hepatic and renal transcriptomic assessments in male and female Hsd: Sprague Dawley (SD) rats. These data will be used for determining provisional pathway-based transcriptomic BMDs for use in human health risk estimations. Traditional toxicological endpoints (e.g. organ weights and clinical chemistry) have been added to the studies to provide additional contextualizaing information (i.e., phenotypic anchoring).

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE183705 | GEO | 2022/09/15

REPOSITORIES: GEO

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Project description:Per- and polyfluoroalkyl substances (PFAS) are some of the most prominent organic contaminants in human blood that have the potential to disrupt biological processes and pathways in the liver. Although the toxicological implications from human exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are well established, data on other, lesser-understood PFAS are limited. A challenge for regulatory authorities is to determine acceptable levels of human exposure to large, diverse classes of environmental contaminants. New approach methodologies (NAMs) that apply bioinformatics tools to interpret biological data are being increasingly considered to inform risk assessment when traditional toxicology methodologies are not amenable. The aim of the current investigation was to identify the biological responses relevant to PFAS mode of action as the concentration (benchmark dose) that these effects take place in order to utililze this information to inform/facilitate read-across for risk assessment of data-poor PFAS. A TempO-Seq platform (BioSpyder) measured gene expression changes in human liver microtissues (i.e., spheroids) after 1-day and 10-day exposures to increasing concentrations of PFAS. A bioinformatics framework was applied to 23 PFAS sub-classed into carboxylates (PFCAs), sulfonates (PFSAs), or PFAS precursors that were analyzed for the total altered transcripts, the concentration where effects take place, and identifying target genes of interest. Both PFCAs and PFSAs exhibited a trend toward increased transcriptional changes with carbon chain-length. Specifically, longer-chain compounds (7 to 10 carbons) were more likely to surpass liver-toxic transcriptomic thresholds established from previous studies than shorter chain PFAS. Longer-chain PFAS were also more potent, inducing transcriptional effects at lower concentrations. However, PFOS was the most potent PFAS and of all precursors, only PFOSA (a PFOS precursor) induced a response. The combined high-throughput transcriptomic and bioinformatics analyses revealed the capability of NAMs to assess the effects of PFAS in liver microtissues; such data improves our understanding of PFAS-related effects in humans and facilitates the use of read-across in human health risk assessment for other data-poor chemicals.

Dataset Information

Transcriptomic changes and toxicologic potential of per/polyflourinated alkyl substances (pfas) in laboratory animals via gavage

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