Sulfallate, a chlorinated dithiocarbamate derivative used as a preemergence herbicide on vegetable crops, was selected for bioassay by the National Cancer Institute because of its structural relationship to the known tumorigens selenium diethyldithiocarbamate and potassium bis(2-hydroxyethyl) dithiocarbamate and to a number of suspected tumorigens containing the diethyldithiocarbamate or dimethyldithiocarbamate moieties.
A bioassay for possible carcinogenicity of sulfallate was conducted using Osborne-Mendel rats and B6C3F1 mice. Sulfallate was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty mice and 50 rats of each sex were placed on test as controls for the bioassay. The time-weighted average high and low dietary concentrations of sulfallate were, respectively, 410 and 250 ppm for male rats, 404 and 250 ppm for female rats, 1,897 and 949 ppm for male mice, and 1,815 and 908 ppm for female mice. After a 78-week period of chemical administration, there was an additional observation period of 25 to 26 weeks for dosed rats, 33 weeks for control rats, and 12 to 13 weeks for dosed and control mice.
There were significant positive associations between increased sulfallate concentration and accelerated mortality in both sexes of rats and in female mice. However, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors.
Statistical analyses of the incidences of mammary adenocarcinomas in female rats, stomach neoplasms (i.e.,combination of papillomas NOS, squamous-cell papillomas, and squamous-cell carcinomas) in male rats, combined alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas in male mice, and adenocarcinomas of the mammary gland in female mice revealed a significant positive association between dosage and incidence. These associations were all supported by at least one significant Fisher exact comparison.
The incidences of toxic tubular nephropathy observed in male rats and in mice of both sexes increased with the concentration of the compound administered. This nonneoplastic lesion was not observed in control animals.
Under the conditions of this bioassay, dietary administration of sulfallate was carcinogenic to Osborne-Mendel rats and to B6C3F1 mice, inducing mammary gland tumors in females of both species, tumors of the forestomach in male rats, and lung tumors in male mice.