Transcriptomic points of departure for Orcinus orca and Homo sapiens primary dermal fibroblast cells exposed to six organic contaminants

Building upon the vision for Toxicity Testing in the 21st century (Krewski et al., 2010), which proposed the use of mechanistically oriented high-throughput assays with human cell lines as an alternative to traditional toxicity testing involving exposures of surrogate animal models as a basis for chemical safety assessment, we propose to evaluate the use of orca cells for deriving points of departure (PODs) relevant for orca. The objective of the present research was to examine whether PODs derived from high content transcriptomics data (tPODs) collected from exposed orca cells yield substantially different PODs than those derived from high throughput transcriptomic assays (e.g., Harrill et al. 2021) with human cell lines. Orca and human primary dermal fibroblasts were exposed for 24 h to seven different concentrations of test chemical, plus controls. RNA was extracted from cell lysates and subjected to RNA sequencing. Raw fastq files were submitted to NCBI's Sequence Read Archive (Orca - PRJNA126653; Human - PRJNA1266253). Raw counts files (_counts_matrix_updated.txt), normalized and filtered counts with a pseudo count of 1 added (_counts.norm.filt+1.txt), and normalized count files formatted for using in BMDExpress 3 (_BMDExpress_counts.txt) are provided here. Test chemicals: BPA = bisphenol A (CAS 80-05-7; DTXSID7020182) PBDE = 2,2’,4,4’,5-pentabromodiphenyl ether (CAS 60348-60-9; DTXSID9030048) ppDDE = p,p’-dichlorodiphenyldichloroethane (DDE; CAS 72-55-9; DTXSID9020374) 4NP = 4-nonylphenol (CAS 104-40-5; DTXSID5033836) EE2 = 17alpha-ethinylestradiol (CAS 57-63-6; DTXSID5020576) PFOS = perfluorooctane sulfonate (1763-23-1; DTXSID3031864) Concentrations are nominal concentrations in mg/L in the test wells.