Data from: A rat liver transcriptomic point of departure predicts a prospective liver or non-liver apical point of departure

Identifying a toxicity point of departure (POD) is a required step in
human health risk characterization of crop protection molecules, and this
POD has historically been derived from apical endpoints across a battery
of animal-based toxicology studies. Using rat transcriptome and apical
data for 79 molecules obtained from Open TG-GATES (Toxicogenomics
Project-Genomics Assisted Toxicity Evaluation System) (632 datasets), the
hypothesis was tested that a short-term exposure, transcriptome-based
liver biological effect POD (BEPOD) could estimate a longer-term exposure
“systemic” apical endpoint POD. Apical endpoints considered were body
weight, clinical observation, kidney weight and histopathology and liver
weight and histopathology. A BMDExpress algorithm using Gene Ontology
Biological Process gene sets was optimized to derive a liver BEPOD most
predictive of a systemic apical POD. Liver BEPODs were stable from 3 hours
to 29 days of exposure; the median fold difference of the 29 day BEPOD to
BEPODs from earlier time points was approximately 1 (range of 0.7-1.1).
Strong positive correlation (Pearson R = 0.86) and predictive accuracy
(root mean square difference = 0.41) were observed between a concurrent
(29 day) liver BEPOD and the systemic apical POD. Similar Pearson R and
root mean square difference values were observed for comparisons between a
29 day systemic apical POD and liver BEPODs derived from 3 hours to 15
days of exposure. These data across 79 molecules suggest that a
longer-term exposure study apical POD from liver and non-liver
compartments can be estimated using a liver BEPOD derived from an acute or
subacute exposure study.