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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

✍ Scribed by Shigeki Nakano; Kazumasa Yamashita; Yoshinobu Kirihara; Masahiko Kuwata; Ken'ichi Morita


Publisher
John Wiley and Sons
Year
1984
Tongue
English
Weight
689 KB
Volume
4
Category
Article
ISSN
0260-437X

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✦ Synopsis


In order to study the safety of 1,3,3,5, 5-pentaziridino-l-thia-2,4,6-triaza-3,5-diphosphorine-l-oxide (SOAz), a new antitumor agent, acute toxicity studies by intravenous administration were performed in ddY mice, Wistar rats and beagle dogs. The LDso values in rodents were 325 mg kg-' for male mice, 450 mg kg-' for female mice, 100 mg kg-' for male rats and 82 mg kg-' for female rats. In dogs, the LDsO values were 12 mg kg-' for males and 18 mg/kg-' 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.