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Acute toxicity study of 1,3,3,5,5‐pentaziridino‐1‐thia‐2,4,6‐triaza‐3,5‐diphosphorine‐1‐oxide (a new antitumor agent with an inorganic ring) in mice, rats and dogs
Author(s) -
Nakano Shigeki,
Yamashita Kazumasa,
Kirihara Yoshinobu,
Kuwata Masahiko,
Morita Ken'ichi
Publication year - 1984
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550040102
Subject(s) - beagle , atrophy , emaciation , toxicity , bone marrow , medicine , lethal dose , pathology , median lethal dose , acute toxicity , endocrinology , biology , toxicology
In order to study the safety of 1,3,3,5,5‐pentaziridino‐1‐thia‐2,4,6‐triaza‐3,5‐diphosphorme‐1‐oxide(SOAz), a new antitumor agent, acute toxicity studies by intravenous administration were performed in ddY mice, Wistar rats and beagle dogs. The LD 50 values in rodents were 325 mg kg −1 for male mice, 450 mg kg −1 for female mice, 100 mg kg −1 for male rats and 82 mg kg −1 for female rats. In dogs, the LD 50 values were 12 mg kg −1 for males and 18 mg/kg −1 for females. The dosed animals showed diarrhoea and decreased movement in the three species, and emaciation and loss of body weight in mice and rats. Dogs also showed signs of pneumonia. Histopathological examination revealed bone marrow suppression, atrophy of lymphoid organs and testes, and damage to the digestive tract mucosa in the three species. The main causes of death from single‐dose administration were bone marrow aplasia and atrophy of lymphoid tissue in all species, together with gastro‐intestinal ulceration in rats and dogs, and infection in mice and dogs.