Oncogenicity studies of benzalazine in mice and rats

Oncogenicity studies 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, were carried out in male and female mice and rats. The compound was administered in the diet for 119 weeks (rats) and 120 weeks (mice) at dose levels of 100, 300 and 900/1800 mg/kg b.w./d for mice and of 300, 900 and 2700/1800 mg/kg b.w./d for rats. The administration of benzalazine produced no effects on survival, appearance or behaviour. Body weights of the high-dosed male mice and rats (both sexes) were occasionally significantly decreased when compared to the controls. A slight but in most cases statistically significant reduction of the relative food consumption of the female mice of all treated groups was observed between test weeks 6 and 12. In the high-dosed rats a statistically significant increase of the relative food consumption was found between test weeks 17 and 109. At necropsy, there was no evidence of treatment-related changes, nor were these seen on histopathological examination. All microscopic changes seen in mice and rats were of the usual type commonly occurring in untreated aged NMRI mice and Sprague-Dawley rats. However, an increased incidence of thyroid cystic hyperplasia was found in the rats of the high dose-level group. In addition, an increased incidence of thyroid adenomas was found in the male rats of the high-dosed group only as compared to the control groups. This increased tumour incidence is regarded as a marginal finding and may be of a spontaneous nature within the normal range of the background data. However, a substance-related influence cannot completely be excluded. In conclusion, the administration of benzalazine for more than 24 months to NMRI mice and Sprague-Dawley rats produced only slight effects on body weight in the high-dosed male mice and in rats (both sexes) with a no-effect level of 300 mg/kg b.w./d in the diet for mice or 900 mg/kg b.w./d in the diet for rats. There was no evidence of an oncogenic effect of benzalazine.