Toxicology and Carcinogenesis Studies of p-Nitrophenol (CAS No.100-02-7)inSwiss Webster Mice (Dermal Studies)
Chemical Formula: C6H5NO3
p-Nitrophenol is used in the production of acetaminophen, methyland ethylparathion insecticides, fungicides, and dyestuffs. Toxicology andcarcinogenesis studies of p-nitrophenol (greater than 97% pure) wereconductedby dermal application to male and female Swiss-Webster mice for 18 months.Dermal application was selected as the route of chemical administrationbecauseof possible skin absorption from p-nitrophenol-treated leather footwear.Genetic toxicology studies were conducted in Salmonella typhimurium,Chinesehamster ovary cells, and Drosophila melanogaster.
Groups of 60 Swiss-Webster mice of each sexreceivedp-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 perweek for 78weeks. At the end of the study, survival rates of mice receiving 0, 40, 80, or160 mg/kg p-nitrophenol were 29/60, 17/60, 26/60, and 24/60 formales and35/60, 26/60, 33/60, and 27/60 for females.
Deaths after 60 weeks were caused by generalized amyloidosis andsecondarykidney failure. The severity of amyloidosis was similar among dosed andcontrol animals. At the end of the study, the final mean body weights of thedosed groups of each sex were similar to those of the controls. Nobiologically significant lesions were observed that were related to the dermaladministration of p-nitrophenol.
p-Nitrophenol was not mutagenic inSalmonella typhimurium(strains TA100, TA1535, TA1537, and TA98) with or without exogenousmetabolic(S9) activation, or in germ cells of male Drosophila melanogasteradministeredp-nitrophenol in feed or by injection. In Chinese hamster ovary cells, noinduction of sister chromatid exchanges was observed with or without S9, butasignificant increase in chromosomal aberrations occurred in trials conductedwith S9.
Under the conditions of these 18-month dermal studiesthere wasno evidence of carcinogenic activity in male or female Swiss-Webster micereceiving 40, 80, or 160 mg/kg p-nitrophenol.
Synonyms: 4-hydroxynitrobenzene, p-hydroxynitrobenzene,4-nitrophenol,paranitrophenol, PNP, Niphen
Report Date: April 1993