2,4-diaminoanisole sulfate: early effect on thyroid gland morphology and late effect on glandular tissue of Fischer 344 rats

Abstract

F344 female rats were fed 2,4-diaminoanisole sulfate (2,4-DAA) (a hair dye component) at three concentration levels up to 86 weeks. The administration of hair dye was interrupted after 10 weeks' feeding for 15 animals at the highest concentration level. Both the early effect of 2,4-DAA on the thyroid gland and the late effect on thyroid, mammary, clitoral, and pituitary glands were studied. In a few weeks, 2,4-DAA showed goitrogenic effects on the thyroid gland. However, the nodular phase of the goiter did not develop. Cystic colloid-filled follicles became lined with basophilic flattened epithelium that continued to proliferate and to form adenomatous or papillary neoplasms. Only 10 weeks of feeding at the high level of 2,4-DAA produced a 42% tumor incidence, and one-fourth of the animals had thyroid tumors. Dark pigment in the thyroid epithelium was still present 70 weeks after the feeding of 2,4-DAA had been interrupted. Feeding of high levels of 2,4-DAA for 82 weeks produced a 78% thyroid tumor incidence. Mammary tumor incidence was nearly five times higher at the 0.24% 2,4-DAA feeding level than among controls. At this same feeding level, 45% of the rats had clitoral tumors. Lesions of the pituitary gland were present in all groups, but tumors were encountered only among the 2,4-DAA-fed animals.