Toxicogenomic study of triazole fungicides and perfluoroalkyl acids in rat livers predicts toxicity and categorizes chemicals based on mechanisms of toxicity.

Toxicogenomic analysis of five environmental chemicals was performed to investigate the ability of genomics to predict toxicity, categorize chemicals, and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole, and triadimefon) and two perfluorinated chemicals [perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)] were administered daily via oral gavage for one, three, or five consecutive days to male Sprague-Dawley rats at single doses of 300, 300, 175, 20, or 10 mg/kg/day, respectively. Clinical chemistry, hematology, and histopathology were measured at all time points.

Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action.

Successful drug discovery requires accurate decision making in order to advance the best candidates from initial lead identification to final approval. Chemogenomics, the use of genomic tools in pharmacology and toxicology, offers a promising enhancement to traditional methods of target identification/validation, lead identification, efficacy evaluation, and toxicity assessment. To realize the value of chemogenomics information, a contextual database is needed to relate the physiological outcomes induced by diverse compounds to the gene expression patterns measured in the same animals.