Tumors of the bladder, kidney, and intestine of F344 rats and liver of B6C3F1 mice administered o-nitroanisole in feed.
o-Nitroanisole, a mutagenic intermediate used in the manufacture of azo dyes, was administered in feed for 2 years at concentrations of 0, 222, 666, or 2000 ppm to groups of 60 male and 60 female F344 rats. No significant increase in neoplasms occurred in these groups of rats. Additional (stop exposure) groups of 60 male and 60 female F344 rats received diets containing 0, 6000, or 18,000 ppm for 27 weeks followed by maintenance on control diets for up to an additional 77 weeks. Survival of the stop exposure groups was reduced because of the development of chemical related neoplasms of the urinary bladder. After 13, 28, 40, and 65 weeks on study, 10 rats per group were necropsied and evaluated for the presence of chemical associated lesions. Hyperplasia of the epithelium of the urinary bladder was significantly increased at all interim evaluations. A transitional cell carcinoma was observed at the 13-week evaluation in one male rat that received 18,000 ppm and thereafter transitional cell neoplasms of the bladder were present in male and female rats at each interim evaluation. Adenomatous polyps of the large intestine were significantly increased in groups that received 6000 or 18,000 ppm. In addition carcinomas of the large intestine were present in four males and two females that received 18,000 ppm. Hyperplasia of the transitional epithelium of the renal pelvis was significantly increased in groups of rats that received 6000 or 18,000 ppm and transitional cell papillomas were observed in three males and one female that received 18,000 ppm. Transitional cell carcinomas of the kidney occurred in one male that received 6000 ppm and six males and one female that received 18,000. Groups of 60 male and 60 female B6C3F1 mice received dietary concentrations of 0, 666, 2000, or 6000 ppm o-nitroanisole for 2 years. No stop exposure study was conducted with mice. The only neoplastic response observed in mice was in the liver of males; hepatocellular adenomas or carcinomas were increased in groups of male mice that received 2000 or 6000 ppm. No increase in neoplasms associated with chemical exposure occurred in female mice.
Irwin
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RD
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 12233, USA.
Chhabra
R
R
Eustis
S
S
Pinter
A
A
Prejean
J D
JD
D000821:Animal Feed; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens; D004334:Drug Administration Schedule; D005260:Female; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000401:mortality / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000401:mortality / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000401:mortality / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000401:mortality / Q000473:pathology
D000840:Anisoles; D002273:Carcinogens; C005328:2-nitroanisole