title: Bioassay of Michler's Ketone for Possible Carcinogenicity (CAS No. 90-94-8).
abstract: Michler's ketone, a dye intermediate and derivative of dimethylaniline, was selected for bioassay by the National Cancer Institute because of the elevated incidence of bladder cancer noted among dye manufacturing industry workers. A bioassay for the possible carcinogenicity of technical-grade Michler's ketone was conducted using Fischer 344 rats and B6C3F1 mice. Michler's ketone was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of Michler's ketone were respectively, 500 and 250 ppm for male rats, 1,000 and 500 ppm for female rats, and 2,500 and 1,250 ppm for mice of both sexes. The compound was administered to rats and mice for 78 weeks. The period of compound administration was followed by an observation period of 28 weeks for male and high dose female rats, 29 weeks for low dose female rats and 13 weeks for mice. There were significant positive associations between the concentrations of Michler's ketone administered and mortality in rats and mice of both sexes. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. There was distinct dose-related mean body weight depression in female rats and in mice of both sexes, and the mean body weight among dosed male rats was slightly lower than that in controls, indicating that the concentrations of Michler's ketone administered tothese animals in this bioassay may have approximated the maximum tolerated concentrations. There were significant positive associations between the concentrations of Michler's ketone administered and the incidences of hepatocellular carcinomas in both sexes of rats and in female mice and hemangiosarcomas in male mice. In all of these cases the high dose to control Fisher exact comparison was also significant. Under the conditions of this bioassay, dietary administration of Michler's ketone was carcinogenic to male and female Fischer 344 rats and female B6C3F1 mice, causing hepatocellular carcinomas, and to male B6C3F1 mice, causing hemangiosarcomas. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonyms: bis[4-(dimethylamino)phenyl]methanone; 4,4'-bis(dimethylamino)benzophenone; p,p'-bis(dimethylamino)benzophenone; bis[p-(N,N'-dimethylamino)phenyl]ketone; tetramethyldiaminobenzophenone