Abstract |
Five groups of 10 male and five groups of 10 female mice were fed nutritionally adequate diets containing 0, 50, 350, 2000 or 7000 ppm of the test substance for 28 days. To evaluate the primary humoral immune response, all mice were injected on test day 23 with SRBC and sacrificed on test day 28. Following sacrifice, the spleen and thymus were removed from each animal and weighed and serum was collected and analyzed for SRBC-specific IgM antibody. Sera previously collected from mice injected with SRBC and dosed with the known immunosuppressive agent cyclophosphamide monohydrate were analyzed for SRBC-specific IgM antibody concurrently with the study samples as a positive control. The dietary exposure of male mice to 7000 ppm of the test substance resulted in a statistically significant decrease of 12% compared to control in the primary humoral immune response to SRBC. The biological significance of this decreased humoral immune response in the 7000 ppm male group is equivocal. The lower humoral immune response occurred only at the highest dietary concentration (>1000 mg/kg/day). The 1000 mg/kg/day dose is the limit dose for 28-day oral studies (OECD Guideline for Testing of Chemicals; Health Effects, No. 407 Repeated Dose Oral Toxicity-Rodents: 28-Day or 14-Day Study: 1981). Additionally, no alterations in the humoral immune response occurred in female mice nor in male and female rats in a separate 28-day feeding study with the test substance. Furthermore, the magnitude of the altered humoral immune response was small (i.e., a 12% decrease relative to control). |