Toxicity and carcinogenicity of nitrofurazone in F344/N rats and B6C3F1 mice.
Toxicology and carcinogenesis studies were conducted by feeding diets containing nitrofurazone (99% pure) to groups of F344/N rats and B6C3F1 mice for 14 days, 13 wk or 2 yr. In the 14-day studies, in which doses ranged from 630 to 10,000 ppm, nitrofurazone was more toxic to mice than to rats. Accordingly, in the 13-wk studies, doses for rats ranged from 150 to 2500 ppm and for mice from 70 to 1250 ppm. At the higher doses, convulsive seizures and gonadal hypoplasia were observed in both species. Evidence of toxicity in rats also included degenerative arthropathy. For the 2-yr studies, rats were exposed to 0, 310 or 620 ppm nitrofurazone and the survival of male rats given 620 ppm was lower than that of controls (33/50, 30/50 and 20/50 in the control, 310- and 620-ppm groups, respectively). Nitrofurazone administration increased the incidences of mammary gland fibroadenomas in female rats (8/49, 36/50 and 36/50 in the control, 310- and 620-ppm groups, respectively). In male rats it was associated with a marginal increase in sebaceous gland adenomas and trichoepitheliomas of the skin, mesotheliomas of the tunica vaginalis, and tumours of the perputial gland. Nitrofurazone caused testicular degeneration (atrophy of germinal epithelium and aspermatogenesis) in rats, and degeneration of vertebral and knee articular cartilage in rats of both sexes. In mice, dietary concentrations of nitrofurazone for the 2-yr studies were 0, 150 or 310 ppm. In mice of each sex, nitrofurazone administration induced stimulus-sensitive convulsive seizures, primarily during the first year of study. In male mice, there was no evidence of any chemically-related carcinogenic effects, but there was a treatment-related decrease in survival (39/50, 31/50 and 27/50 in the control, 150- and 310-ppm groups, respectively). In female mice nitrofurazone induced ovarian lesions with increased incidences of benign mixed tumours (0/47, 17/50 and 20/50 in control, low- and high-dose groups, respectively) and granulosa cell tumours (1/47, 4/50 and 9/50 in control, low- and high-dose groups, respectively).
Kari
F W
FW
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Huff
J E
JE
Leininger
J
J
Haseman
J K
JK
Eustis
S L
SL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced; D051379:Mice; D009583:Nitrofurazone / Q000633:toxicity*; D010051:Ovarian Neoplasms / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344
D009583:Nitrofurazone