Chemical Formula: C10H12N2O4
3-Nitro-p-acetophenetide, a derivative of the analgesic phenacetin, was selected for bioassay by the National Cancer Institute because of the suspected renal pelvic carcinogenicity of the parent compound.
A bioassay for possible carcinogenicity of 3-nitro-p-acetophenetide was conducted using Fischer 344 rats and B6C3F1 mice. 3-Nitro-p-acetophenetide was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species, with the exception of low dose male mice, of which there were 49. Fifty animals of each sex and species were placed on test as controls. The high and low time- weighted average dietary concentrations of 3-nitro-p-acetophenetide were, respectively, 0.36 and 0.18 percent for rats and 1.46 and 0.73 percent for mice. The compound was administered in the diet for 78 weeks, followed by an observation period of up to 30 weeks for rats and 20 weeks for mice.
There were no significant positive associations between the concentrations of 3-nitro-p-acetophenetide administered and mortality in rats or mice of either sex. In addition, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors.
There was a statistically significant increased incidence of a combination of hepatocellular carcinomas and adenomaswhen high dose male mice were compared to controls. No other neoplasm in any other dosed group occurred in significant positive increased incidences when compared to controls.
Under the conditions of this bioassay, dietary administration of 3-nitro-p-acetophenetide was not carcinogenic in Fischer 344 rats of either sex or in female mice. The compound, however, was considered carcinogenic in male B6C3F1 mice based on a significant increase in the combined incidence of hepatocellular carcinomas and hepatocellular adenomas in these animals.
Synonyms: N-(4-ethoxyphenyl)-3'-nitroacetamide; 3'-Nitro-p-acetophenetide; 3'-Nitro-p-acetophenetidin; 4-Acetamino-2-nitrophenetole
Report Date: 1979