NSC-121 210 Dehydroepiandrosterone Mustard: Preclinical Toxicological Evaluation in Dogs.

摘要

Androst-5-en-17-one, 3beta-hydroxy-, (p-(bis (2-chloroethyl) amino) phenyl)-acetate; (Dehydroepiandrosterone mustard) was submitted to a p.o. preclinical pharmacological evaluation in 16dogs. Treatments included 14oral daily consecutive doses of 21.4to 300mg/kg and single doses of 100and 750mg/kg. One dog treated with 14 x 300mg/kg and another treated with 14 x 75mg/kg was sacrificed in fair condition at termination of treatment;the remaining dogs survived in good condition. Toxicity was non dose related and included severe anorexia (7/16),weight loss (10/16),severe salivation (2/16),abdominal pain (2/16),emesis (1/16) and diarrhea (1/16). Most dogs exhibited moderate to marked lymphopenia (10/16) and several showed neutropenia (3/16). Dogs necropsied immediately after post treatment usually exhibited marked to moderate hypocellularity of the lymphoid tissues (6/7) and often hypocellularly of the bone marrow (4/7). In 5/8female dogs androgenic effects included endometrial hyperplasia and progestational effects,and acinar development and secretion of the mammary glands. One dog showed abnormal cell division of the spermatogenic cells. Intestinal toxicity was not important.