Short-term toxicity study of 1-aminobenzotraizole, a CYP inhibitor, in Wistar rats

Abstract

1-Aminobenzotriazole (ABT) is a pan-specific, mechanism-based inhibitor of CYP P450 enzymes, often used as co-treatment to investigate the metabolism-dependent toxicity of drugs or chemicals. To assess the confounding effects of ABT in such kind of mechanistic studies, a repeated dose toxicity study with ABT following 7 days oral administration at 0, 25, 50 and 100 mg/kg/day was performed in Wistar rats (5 rats/sex/group). Wistar rat is selected as a model being one of the well characterized rodent species, widely used for toxicity and toxicokinetics studies. The standard parameters of general toxicity study viz. clinical signs, body weight, feed consumption, clinical, gross and histopathology were evaluated. The ABT was tolerated up to the highest tested dose of 100 mg/kg/day. No clinical signs, mortality or effect on feed consumption at any dose. Slight increase in body weight gain was noted in ABT treated females. Increased reticulocyte, and decreased triglycerides, BUN, A/G ratio and plasma potassium; increased weight of liver, kidneys, adrenals and thyroid was noted in ABT treated animals. Microscopically, hypertrophic findings were noted in liver, thyroid, adrenal glands, pituitary and uterus. Some of these changes were observed at as low as 25 mg/kg/day, therefore, NOEL could not be established. Based on this study, it is concluded that ABT is tolerable up to 100 mg/kg/day with some variations in clinical pathology, organ weight and histopathology; these changes should be considered during the assessment of any mechanistic study with ABT. Findings of this manuscript were presented at 58th meeting of the Society of Toxicology, Baltimore, 11 March 2019.