Bioassay of 4'-(Chloroacetyl)-acetanilide for Possible Carcinogenicity (CAS No. 140-49-8)
Chemical Formula: C10H10Cl N O2
4'-(Chloroacetyl)-acetanilide, an intermediate in the synthesis of dyes and pharmaceutical compounds, was selected for bioassay by the National Cancer Institute because of the increased incidence of bladder cancer observed among dye manufacturing industry workers. Aromatic amines, such as 4'-(chloroacetyl)-acetanilide, are among several classes of chemicals thought to contribute to the increased cancer risk in this industry, and 4'-(chloroacetyl)-acetanilide is especially suspect because it is structurally similar to the possible human renal pelvic carcinogen, phenacetin.
A bioassay for the possible carcinogenicity of 4'-(chloroacetyl)-acetanilide was conducted using Fischer 344 rats and B6C3F1 mice. 4'-(Chloroacetyl)-acetanilide 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 4'-(chloroacetyl)-acetanilide were, respectively, 2,000 and 1,000 ppm for rats and 10,000 and 5,000 ppm for mice. The compound was administered for 87 weeks of a 102-week period in rats and for 90 weeks of a 105-week period in mice. Mice were killed at the end of the last week of compound administration, while rats were observed for 1 week after compound administration ceased.
There were no significant positive associations between the concentration of 4'-(chloroacetyl)-acetanilide administered and mortality in rats or mice of either sex. Adequatenumbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Dose-related mean body weight depression was observed for males and females of both species, indicating that the concentrations of 4'-(chloroacetyl)-acetanilide administered to the animals in this bioassay may have approximated the maximum tolerated concentrations.
None of the statistical tests for any site in rats of either sex or in male mice indicated a significant positive association between compound administration and tumor incidence. Although there was a significant positive association between the concentration of the compound administered and the incidences of hepatocellular adenomas in female mice, the Fischer exact comparisons were not significant.
Under the conditions of this bioassay, 4'-(chloroacetyl)-acetanilide was not carcinogenic when administered in the diet to Fischer 344 rats or B6C3F1 mice of either sex.
Synonyms: N'-(Chloroacetyl)-N-phenylacetamide; 4-(Cl-acetyl)acetanilide
Report Date: 1979