The effect of dietary administration of Disperse Blue 1 on the urinary system of the Fischer 344 rat.
Disperse Blue 1 (containing 50% lignosulphonate dispersants) was fed to Fischer 344 rats at dietary levels of 0.01 and 0.1% for 19 months and at 1.0% for 6 months. Fischer 344 rats were also given the dye by gavage at 1 g/kg for 1-3 days or in the diet at 0.5 or 1% for 4 days, and corresponding dietary levels of the colouring without dispersant were also fed for 4 days. Bladders and kidneys were examined after the 1-4 day treatments, in animals dying or killed from month 6 to termination (19 months) in the chronic study and in those killed at wk 5, 9 and 17. At the latter three times, autoradiography following injection of tritiated thymidine showed increased DNA synthesis in the urothelium of high-dose rats, but no other increased labelling in any group. Bladder lesions were seen only at the 1.0% level, epithelial erosion with adhering dye particles being seen by day 4, calculi and hyperplasia by wk 5 and squamous metaplasia by wk 9. The calculi contained more dye in males than in females and more calcium in females. By month 6, dye particles were embedded in the bladder wall, with some evidence of histiocyte accumulation in their vicinity. Two papillomas and one carcinoma, but no leiomyosarcomas, were diagnosed. The earliest tumours, two papillomas, were detected at wk 17. Tumour incidence following surgical removal of calculus was about double that in rats not subjected to surgery and the incidence of normal bladders at month 19 was higher in the latter group. Compound-related effects in the kidneys--inflammation, pelvic epithelial hyperplasia and tubular degeneration and regeneration with interstitial fibrosis--were seen only in the high-dose group. Dye present in the tubules and renal pelvis persisted in many rats for a year after cessation of treatment.
D000284:Administration, Oral; D000818:Animals; D000880:Anthraquinones / Q000633:toxicity*; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced; D007680:Kidney Neoplasms / Q000139:chemically induced; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D001744:Urinary Bladder Calculi / Q000139:chemically induced; D014551:Urinary Tract / Q000187:drug effects* / Q000473:pathology; D014571:Urologic Neoplasms / Q000139:chemically induced*
D000880:Anthraquinones; C048853:Disperse Blue 1