Subchronic toxicity of aniline hydrochloride in rats

Hematological, biochemical and histopathological responses of subchronic exposure to aniline hydrochloride (AH) have been investigated in rats. Male Sprague-Dawley rats were given 600 ppm of AH in drinking water while the control rats received tap water only. Five rats from each group were sacrificed at 30, 60, and 90 days of treatment. Organ-to-body weight ratio for spleen in the AH-treated rats was 56, 61, and 53% higher than controls at days 30, 60, and 90, respectively. Liver showed a biphasic pattern for this ratio, a decrease at 30 days and then an increase at 60 days. Among other organs, testes showed a significant decrease in this ratio at 60 days. Hematological analysis showed 65% increase in WBC counts at 30 days in the AH-treated rats, whereas, no changes were recorded at later time points. Erythrocyte counts in the AH-treated rats showed very significant decreases at all the time points, whereas, hemoglobin and hematocrit decreased at 30 and 90 days of treatment. Mean corpuscular volume and mean corpuscular hemoglobin increased in the AH-treated rats at 60 and 90 days of treatment. Methemoglobin content showed significant increases of 89, 59 and 45% at days 30, 60, and 90, respectively. Among serum immunoglobulins, IgA in the AH-treated groups showed 24 and 51 % increases at days 60 and 90, respectively. Analysis of splenic lymphocyte subpopulation showed a decrease in the T-helper (CD4⁺/CD8^-) sub-set at 90 days whereas, other subpopulations were not affected. Aniline hydroxylase activity in the liver microsomes of the AH-treated rats was significantly higher at 60 days of treatment. At all times, spleen demonstrated striking histopathological changes including marked red pulp expansion due to increased sinusoidal cells, fibroblasts, and markedly increased light brown pigment of heme origin. Focal pericapsular fibrosis was found at all times, with no evidence of neoplasia. These histological changes were greatly accentuated with the progression of exposure. Our data, apart from indicating toxicity to the hemopoietic system, show a good interrelationship between damage to erythrocytes and splenic lesions associated with aniline exposure.