Single and subacute local and systemic toxicity studies of benzalazine

Benzalazine (2-hydroxy-5-[(4carboxyphenyl) azo]benzoic acid, CAS 64896-26-0), a new agent for the treatment of ulcerative colitis and Crohn's disease of the large intestine, was investigated regarding its toxicological properties following single and subacute local and systemic applications. After single oral application of the maximum dose of 10 g benzalazine/kg b.w. to rats no pathological findings concerning clinical signs, body weight, food consumption and macroscopical post mortem findings could be observed (LD50 > 10000 mg/kg b.w.). The 24-h LD50 values for benzalazine after single intraperitoneal application were determined as 755 mg/kg b.w. in female rats and 1200 mg/kg b.w. in male rats. The oral administration of benzalazine at 2000 mg/kg b.w./d or more for 4 weeks to rats gave rise to slight sedation, a reduction in body weight increase, increased organ weights (heart, kidneys, suprarenal glands, spleen) and dose-related histopathological findings (liver, kidneys, heart, thyroid gland, duodenum, spleen, suprarenal glands, testes). The daily dose of 500 mg benzalazine/kg b.w. for 4 weeks was without any effects under these experimental conditions. In acute local tolerance studies in rabbits, benzalazine is to be considered as a mild irritant agent for skin (employing an occlusive patch for 24 h) and eye. After a 10-day intra-rectal application of benzalazine to rabbits no substance-related changes at the application sites in the colon were observed.