Nitrofen, a substituted diphenyl ether, is one of several agricultural pesticides selected for bioassay by the National Cancer Institute because of a lack of carcinogenicity data.
A bioassay for the possible carcinogenicity of nitrofen was conducted using Fischer 344 rats and B6C3F1 mice. Nitrofen 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 nitrofen were 6000 and 3000 ppm for both species. The compound was administered to rats and mice for 78 weeks, followed by a period of no compound administration of 26 weeks for rats and 13 weeks for mice.
There were no significant positive associations between the concentrations of nitrofen administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Dose-related mean body weight depression, relative to controls, was observed for males and females of both species, indicating that the concentrations of nitrofen 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 indicated a significant positive association between compound administration and tumor incidence. There was a significant positive association between the concentrationof nitrofen administered and the incidences of hepatocellular carcinomas in mice of both sexes.
In another bioassay of nitrofen for possible carcinogenicity, the compound was found to induce hepatocellular carcinomas in B6C3F1 mice of both sexes and hemangiosarcomas of the liver in male B6C3F1 mice. In addition, adenocarcinomas of the pancreas were induced in female Osbourne-Mendel rats.
Under the conditions of this bioassay, dietary administration of nitrofen was carcinogenic to B6C3F1 mice, causing hepatocellular carcinomas in both sexes. There was no evidence for carcinogenicity in Fischer 344 rats.
Note: Nitrofen was previously studied by administration in feed to Osborne-Mendel rats and B6C3F1 mice (See TR-26, reported 1979).