Acute toxicity study of 1,3,3,5,5-pentaziridino-1-thia-2,4,6-triaza-3,5-diphosp horine-1-oxide (a new antitumor agent with an inorganic ring) in mice, rats and dogs

J Appl Toxicol. 1984 Feb;4(1):1-7. doi: 10.1002/jat.2550040102.

Abstract

In order to study the safety of 1,3,3,5,5-pentaziridino-1-thia-2,4,6-triaza-3,5-diphospho rine-1-oxide (SOAz), a new antitumor agent, acute toxicity studies by intravenous administration were performed in ddY mice, Wistar rats and beagle dogs. The LD50 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 LD50 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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Azirines / toxicity*
  • Body Weight / drug effects
  • Dogs
  • Eating / drug effects
  • Female
  • Injections, Intravenous
  • Lethal Dose 50
  • Male
  • Mice
  • Organ Size / drug effects
  • Rats
  • Rats, Inbred Strains
  • Species Specificity
  • Time Factors

Substances

  • Antineoplastic Agents
  • Azirines
  • pentazirinocyclodiphosphathiazene