BIOLOGICAL STUDIES ON AN ADRENOCORTICOLYTIC AGENT AND THE ISOLATION OF THE ACTIVE COMPONENTS123

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Abstract
Pure p,p -DDD, (2,2-bis (parachlorophenyl) 1,1-dichloroethane) technical DDD, and various fractions isolated from the technical compound were compared in effectiveness as adrenocorticolytic agents. Each of the fractions was tested by a four-day oral administration in normal dogs. Active fractions were obtained which were effective at doses of 4 mg/ kg/day. The fractions were assayed by the effect on the eosinophil response of the dog following ACTH administration, and by the excretion of 17-hydroxycorticoids in dogs fed the desired fraction. Further evidence was secured by observation of the physical conditions of treated dogs and by histological examination of the adrenal glands at autopsy. Conclusive evidence that p,p''-DDD is ineffective as an adrenocorticolytic agent was obtained. The technical material was active in producing adrenal cortical atrophy in about three weeks while the pure p,p''-DDD was ineffective after 10 weeks. Systematic fractionation of technical DDD and biological evaluation of each fraction led to the isolation of a strongly active component. This material possessed the same chemical and physical properties reported in the literature for o,p''-DDD.