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Repeat 5-day in vivo genomic dose response studies

Fred Parham, Michele R Balik-Meisner, William M Gwinn, Matthew D Stout, Suramya Waidyanatha, Esra Mutlu, Brad Collins, Richard S Paules, Bruce Alex Merrick, Stephen Ferguson, Sreenivasa Ramaiahgari, John R Bucher, Barney Sparrow, Heather Toy, Jenni Gorospe, Nick Machesky, Ruchir R Shah, Deepak Mav, Dhiral P Phadke, Georgia Roberts, Michael J DeVito, Scott S Auerbach

DOI: https://doi.org/10.22427/NTP-DATA-002-00099-0001-000-1

BioProject ID: PRJNA926950


Abstract

To assess the replicability of in vivo genomic dose response (GDR) study results and improve analysis pipelines for maximum replicability, three test substances (Perfluorooctanoic acid, Bromodichloroacetic acid, and Furan) were subjected to in vivo GDR studies three times (a primary study and two repeat studies), each with independent sets of animals. Two independent sets of animals were used for GDR studies on a fourth substance, Tetrabromobisphenol A. All studies were conducted on male Harlan Sprague Dawley rats, using 8 different doses administered over a 5-day period, with animals being sacrificed 24 hours after the final dose. The same chemical batches and lab were used for the in-life portion of the study. The Biopsyder Tempo-Seq S1500+ gene expression platform was used to analyze liver and kidney gene expression responses in the animals. The genomic data was generated independently for each study, with RNA isolation, library preparation, and sequencing performed independently, but certain steps were carried out by the same lab. Data for the repeated studies are available in the NCBI short read archive: BioProject ID PRJNA926950. Data from the primary study have been previously published.┬╣ A complete set of data from the primary study is available through Bioproject ID PRJNA612884.

┬╣Gwinn WM, Auerbach SS, Parham F, Stout MD, Waidyanatha S, Mutlu E, Collins B, Paules RS, Merrick BA, Ferguson S, Ramaiahgari S, Bucher JR, Sparrow B, Toy H, Gorospe J, Machesky N, Shah RR, Balik-Meisner MR, Mav D, Phadke DP, Roberts G, DeVito MJ. Evaluation of 5-day In Vivo Rat Liver and Kidney With High-throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes. Toxicol Sci. 2020 Aug 1;176(2):343-354. doi: 10.1093/toxsci/kfaa081. PubMed PMID: 32492150; PubMed Central PMCID: PMC7416315.

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