Abstract
Immune toxicity associated with exposure to 2,4,6-trinitrotoluene (TNT) in a 14-day feeding study was examined in male and female white-footed mice (Peromyscus leucopus). Mice (10/group/sex) were exposed to 0, 0.042, 0.083, 0.165, and 0.330% TNT in feed for 14 days. Based upon average feed consumption and body weight, these diets resulted in approximate daily doses of 66, 145, 275, and 601 mg TNT/kg body weight (bw) for males and 70, 142, 283, and 550 mg/kg/day for females. At the end of the exposure period the mice were euthanized and several indicators of nonspecific immunity were examined. These indicators included primary and secondary lymphoid organ/body weight ratio (spleen and thymus), and characterization of nonspecific immune responses (phagocytesis and radical oxygen intermediate [ROI] production). No deaths occurred, even though the high-dose group approached the reported LD50 in Swiss-Webster mice (Dilley et al. 1982. Toxicol. Environ. Health 9:565–585). Spleen weight was significantly increased in the high-dose group (0.330% TNT) for both sexes, whereas a dose-related trend in thymus cellularity was suggestive for males, but not females. In addition, males, but not females, displayed inhibited splenic macrophage phagocytosis and ROI production. Splenic congestion and extramedullary hematopoiesis were observed in both sexes in the two highest dose groups. These results suggest species-specific differences in relative subacute toxicity between laboratory (genus Mus) and Nearctic (genus Peromyscus) mice. In addition, these immunological indicators appear more sensitive than other toxicological endpoints that have been reported as most descriptive of TNT-related effects in mammals.