Bioassay of 2,4-diaminoanisole sulfate for possible carcinogenicity.
A bioassay of technical-grade 2,4-diaminoanisole sulfate for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 2,4-Diaminoanisole sulfate was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The time-weighted average dietary concentrations used in the chronic bioassay were 0.12 percent for the low dose rats and 0.5 percent for the high dose rats. The dietary concentrations used for low and high dose mice were 0.12 and 0.24 percent, respectively. After a 78-week period of chemical administration, observation of the rats continued for an additional 29 weeks and observation of the mice continued for an additional 19 weeks. For each species, 49 or 50 animals of each sex were placed on test as controls. In both species, adequate numbers of animals in all groups survived long enough to be at risk from late-developing tumors. In high dose male and female rats groups, the proportion of animals having one or more of the following malignant follicular-cell thyroid tumors: papillary adenocarcinomas, follicular-cell carcinomas, papillary cystadenocarcinomas, or adenocarcinomas NOS, was significantly greater than the proportion in corresponding control groups. For high dose male rats the proportion of animals having either a C-cell adenoma or a C-cell carcinoma was also significantly increased. The incidence of malignant tumors (squamous-cell carcinomas, basal-cell carcinomas, or sebaceous adenocarcinomas) of the skin and its associated glands were significantly increased among high dose rats of both sexes. Among high dose female mice, the combined incidence of thyroid follicular-cell adenomas and carcinomas was significantly increased. Among high dose male mice, the incidence of thyroid follicular-cell adenomas was significantly increased, but no follicular-cell carcinomas were observed. Under the conditions of this bioassay, technical-grade 2,4-diaminoanisole sulfate was carcinogenic to both sexes of both species. In Fischer 344 rats dietary administration of the chemical induced increased incidences of malignant tumors of the skin and its associated glands and malignant thyroid tumors in each sex. In B6C3F1 mice, dietary administration of 2,4-diaminoanisole sulfate induced thyroid tumors in each sex.