Subchronic oral toxicology of 4-fluoro-3-nitroaniline in the rat

4-Fluoro-3-nitroaniline (4-F-3-NA), an intermediate used in the production of commercial hair dyes, was administered daily for 90 days via po intubation to Charles River CD rats at doses of 40, 120, or 360 mg/kg to determine its subchronic toxicology. All animals receiving 360 mg/kg died prior to termination of the study. The principal effect to rats of 4-F-3-NA exposure was alteration of the hematopoietic system characteristic of hemolytic anemia. Hematocrit, hemoglobin concentration, and erythrocyte count were decreased and reticulocytes increased in a dose-related pattern in both male and female animals. Histopathological change consistent with hemolytic anemia was observed in the bone marrow (erythroid hyperplasia), kidneys (deposition of biliverdin and pigment-laden macrophages in the tubules), liver (pigmented Kupffer cells), and spleen (increased hematopoiesis) in males and females. Heinz bodies and an increase in methemoglobinemia were not observed in this study. In the testes, aspermia and testicular degeneration were seen in isolated tubules, but these changes were significant only at the high dose. Additional pathologic changes noted at the high dose included colloid depletion and follicular cell hypertrophy of the thyroid gland, hypertrophy of the zone fasciculata in the adrenal glands, and lymphoid cell depletion in mesenteric lymph nodes. The calcification of the myocardium and coronary arteries was considered metastatic in nature, secondary to kidney damage. Serum ALT and BUN were elevated in males and AP was elevated in females from the high dose group. Glycosuria, bilirubinuria, and urobilinogenuria were also increased in both sexes at this dose.