benzalazine and Eye-Diseases

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.

Topics: Administration, Rectal; Administration, Topical; Animals; Benzaldehydes; Blood Cell Count; Blood Chemical Analysis; Eating; Eye Diseases; Female; Hydrazones; Irritants; Lethal Dose 50; Male; Organ Size; Rabbits; Rats; Rats, Wistar; Skin Tests; Weight Gain

A 26-week toxicity study by oral gavage administration was performed in Sprague-Dawley rats with benzalazine (2-hydroxy-5-[(4-carboxyphenyl) azo] benzoic acid, CAS 64896-26-0), a new agent for the treatment of ulcerative colitis and Crohn's disease of the large intestine, as a part of a safety evaluation program. Dosages of 0 (control), 300, 900 and 2700 mg/kg b.w./d were selected for this study. Except slight changes in the urinary status (decreased pH value and increased specific gravity) from 900 mg/kg b.w./d p.o. onwards, which were probably substance related, no further intolerance reactions were observed. The urine had a dark-yellow colour which was probably an indication of metabolites of benzalazine or benzalazine itself which were excreted via the urine. Behaviour, external appearance, body weight gain, food and water consumption, haematology, clinical biochemistry, organ weight analysis, macroscopic and microscopic examinations revealed no substance-related influence. Therefore, on the basis of the results obtained, it is concluded that the non-toxic dose level in this study is considered to be 300 mg benzalazine/kg b.w./d p.o. following daily administration for 26 weeks.

Topics: Animals; Behavior, Animal; Benzaldehydes; Blood Cell Count; Blood Chemical Analysis; Drinking; Eating; Eye Diseases; Female; Hearing Disorders; Hydrazones; Male; Rats; Rats, Sprague-Dawley; Tooth; Urinalysis; Weight Gain

The 26-week oral toxicity of benzalazine (2-hydroxy-5-[(4-carboxyphenyl) 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 in beagle dogs of both sexes. No change was observed in the 160 mg/kg group. A reduction of the aspartate aminotransferase activity was observed from 800 mg/kg b.w./d onwards. In high-dosed dogs (1600 mg/kg b.w./d) liver weights were increased and substance-related neutral fat disposition in liver cells was observed. The non-toxic dose was 160 mg/kg b.w./d under these experimental conditions.

Topics: Animals; Behavior, Animal; Benzaldehydes; Blood Cell Count; Blood Chemical Analysis; Blood Protein Electrophoresis; Dogs; Eating; Eye Diseases; Female; Hearing Disorders; Hydrazones; Male; Organ Size; Weight Gain