A Technic for Testing Acnegenic Potency in Rabbits, Applied to the Potent Acnegen, 2,3,7,8-Tetrachlorodibenzo-P-Dioxin

Abstract

Follicular hyperkeratosis is an important feature of the occupational disease known as chloracne, which is characterized by the appearance of papules, comedones and cysts after exposure to industrial materials containing highly chlorinated diphenyls, highly chlorinated naphthalenes, and other chlorinated aromatic compounds. A characteristic epithelial hyperplasia and hyperkeratosis can be produced on the inner surface of the rabbit ear by such compounds (1, 2), and a difference in intensity of response has been noted and suggested as a basis for comparative tests (2). Experimental studies heretofore (1-7) have been, however, directed chiefly to the ability or the failure of various materials to produce this effect in experimental animals and in man, and in delineating its gross and its histological features; these studies have used either material of unstated origin, or else mixtures (e.g. Halowax, 1014). We have attempted to study the phenomenon of acnegen-induced hyperkeratinization on the rabbit ear in a quantitative fashion by recovering and weighing the keratin formed after applying known amounts of a single, well-characterized chemical compound under controlled conditions. To recover keratin a new technic was developed based on the resistance of this material to digestion by pepsin. As test compound we have chosen 2,3,7,8-tetrachlorodibenzo-p-dioxin, which has been reported to be so potent that painting the rabbit ear three times with a 0.05%-0.001% solution was sufficient to produce the acneform response (7). With a compound of such potency, the expected effects could be produced without the necessity of applying the material in an ointment or as a crust, circumstances which would have made very uncertain the quantity actually in contact with the skin.