Kikkawa, Rie (2016) A Case of Drug-Induced Cutaneous Toxicity Observed in Cynomolgus Monkeys. Toxicologic Pathology .

Abstract

The purpose of this presentation is to demonstrate a case of drug-induced cutaneous toxicity observed in cynomolgus monkeys and to introduce approaches we attempted to elucidate mechanisms. The test-article was a small molecule with a ubiquitously distributed target, especially in rapidly dividing cells, and which modulated cell cycle regulation. After seven consecutive days of oral dosing, animals developed multifocal skin lesions. The lesions were characterized clinically by vesicles and scabs formation and were distributed mainly in thin-skinned areas of the body including the cheek, chest, abdomen and inner limbs. Microscopically, the lesions were confirmed as epidermal vesicle formation and ulceration. Immunohistochemical staining revealed that the levels within the epidermis where separation (vesicle formation) occurred were not consistent. The differential diagnoses for vesicular skin lesions and our efforts to elucidate the mechanism of toxicity using in-house database searches and immunohistochemistry are presented and discussed.
To the best of our knowledge, similar cutaneous toxicity has not been reported previously, although there are reports of other types of cutaneous toxicities. Understanding the mechanisms of the toxicity is very important when assessing human relevancy during drug development. Our investigative approach can be utilized when unusual skin toxicities are observed in the future.

Item Type:	Article
Keywords:	skin lesions; vesicle formation, small molecule; cutaneous toxicity; cynomolgus monkeys; bioinformatics; computational toxicology
Date Deposited:	13 Jun 2016 23:45
Last Modified:	13 Jun 2016 23:45
URI:	https://oak.novartis.com/id/eprint/27798