Abstract for TR-417

Toxicology and Carcinogenesis Studies of p-Nitrophenol in Swiss-Webster Mice (Dermal Studies)

CASRN: 100-02-7
Chemical Formula: C6H5NO3
Molecular Weight: 139.11
Synonyms/Common Names: 4-Hydroxynitrobenzene; p-hydroxynitrobenzene; 4-nitrophenol; paranitrophenol; PNP; niphen
Report Date: April 1993

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p-Nitrophenol is used in the production of acetaminophen, methyland ethylparathion insecticides, fungicides, and dyestuffs. Toxicology and carcinogenesis studies of p-nitrophenol (greater than 97% pure) were conducted by dermal application to male and female Swiss-Webster mice for 18 months. Dermal application was selected as the route of chemical administration because of possible skin absorption from p-nitrophenol-treated leather footwear. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary cells, and Drosophila melanogaster.

Eighteen-month studies

Groups of 60 Swiss-Webster mice of each sex received p-nitrophenol in acetone applied to the interscapular skin. Doses of 0, 40, 80, or 160 mg/kg p-nitrophenol were administered to mice 3 days per week for 78 weeks. At the end of the study, survival rates of mice receiving 0, 40, 80, or 160 mg/kg p-nitrophenol were 29/60, 17/60, 26/60, and 24/60 for males and 35/60, 26/60, 33/60, and 27/60 for females.

Deaths after 60 weeks were caused by generalized amyloidosis and secondary kidney failure. The severity of amyloidosis was similar among dosed and control animals. At the end of the study, the final mean body weights of the dosed groups of each sex were similar to those of the controls. No biologically significant lesions were observed that were related to the dermal administration of p-nitrophenol.

Genetic toxicology

p-Nitrophenol was not mutagenic in Salmonella typhimurium (strains TA100, TA1535, TA1537, and TA98) with or without exogenousmetabolic (S9) activation, or in germ cells of male Drosophila melanogaster administered p-nitrophenol in feed or by injection. In Chinese hamster ovary cells, no induction of sister chromatid exchanges was observed with or without S9, but a significant increase in chromosomal aberrations occurred in trials conductedwith S9.


Under the conditions of these 18-month dermal studiesthere was no evidence of carcinogenic activity in male or female Swiss-Webster micereceiving 40, 80, or 160 mg/kg p-nitrophenol.