To study the mechanism of PG renal toxicity and its translatability to humans in human and dog primary renal proximal tubule epithelial cells (RPTECs), in vitro assessments of PG and its metabolites GA and 4OMGA were performed. A concentration-dependent decrease in cell viability was observed with PG for both dog and human RPTECs (Figure ). The relative difference of PG in sensitivity between human (EC50 ~1529 µM) and dog (EC50 ~46.5 µM) was estimated to be ~33-fold, indicating that dogs may be more sensitive to PG-induced renal toxicity than humans in vivo. PG was more cytotoxic for dog than its metabolites, GA and 4OMGA, as well as 4-O-methyl propyl gallate (4OMPG), a synthetic analog of PG that is unable to form a reactive o-quinone. Compound structures are depicted in Supplemental Figure .