1-Phenyl-3-methyl-5-pyrazolone, an aromatic heterocycle and widely used dye intermediate, was selected for bioassay by the National Cancer Institute because of the increased incidence of bladder cancer observed among workers in the dye manufacturing industry.
A bioassay of 1-phenyl-3-methyl-5-pyrazolone for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 1-Phenyl-3-methyl-5-pyrazolone was administered in the feed, at either of two concentrations, to groups of 49 or 50 male and 50 female animals of each species. The high and low concentrations of 1-phenyl-3-methyl-5-pyrazolone utilized were, respectively, 5,000 and 2,500 ppm for rats and 15,000 and 7,500 ppm for mice. Twenty animals of each species and sex were placed on test as controls. After a 103-week period of chemical administration, there was an additional observation period of 2 weeks for rats. A 102-week period of chemical administration was followed by an additional 2-week observation period for mice.
In both species adequate numbers of animals survived sufficiently long to be at risk from late-developing tumors. Compound-related mean body weight depression was observed in mice, but not in rats. In addition, no significant accelerated mortality or other signs of toxicity were associated with the dietary administration of 1-phenyl-3-methyl-5-pyrazolone to rats; therefore, it is possible that the compound was not administered to rats at the maximum tolerated concentration.
There were no tumors in either sex of rats or mice for which a significant positive association could be established between chemical administration and incidence.
Under the conditions of this bioassay, there was no evidence for the carcinogenicity of 1-phenyl-3-methyl-5-pyrazolone to Fischer 344 rats or B6C3F1 mice.