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COMPARING IMMUNOTOXICITY IN RATS AFTER IN UTERO VERSUS AN ADULT EXPOSURE: IS DEVELOPMENTAL EXPOSURE MORE SENSITIVE?
Citation:
GOFF, K., W. C. WILLIAMS, AND R. J. SMIALOWICZ. COMPARING IMMUNOTOXICITY IN RATS AFTER IN UTERO VERSUS AN ADULT EXPOSURE: IS DEVELOPMENTAL EXPOSURE MORE SENSITIVE? . Presented at 45th Annual Society of Toxicology Meeting 2006, San Diego, CA, March 05 - 09, 2006.
Description:
Using a known immunosuppresant, dexamethasone (DEX), pregnant Sprague Dawley (SD) rats were given subcutaneous (s.c.) injections of DEX (0.0, 0.0375, 0.075, 0.15, 0.3 mg/kg) during gestation days 6 to 21. Both male and female offspring were tested for immune dysfunction. In a separate study, non pregnant adult females and males were given s.c. injections of the same DEX doses for 16 days. This study explored the hypothesis that exposure to immunotoxicants produces long lasting immune suppression at or below levels seen in adults. Immune assays were performed starting 5-6 weeks after treatment ended and thereafter every 2-3 months up to 9 months for both adults and offspring. Immune assays included the delayed type hypersensitivity (DTH) response, which is mediated via T cells and the anti -SRBC ELISA which quantitates IgM and IgG antibody production. The DTH response in non - pregnant female adults was significantly suppressed up to 6 weeks after DEX treatment while the response in female offspring was significantly suppressed up to 17 weeks after DEX treatment. Dams used in the in utero exposure to DEX were significantly suppressed up to 34 weeks after DEX treatment. ED50 values for the DTH response were similar in female offspring and adults. Male offspring and adults showed little or no significant immunosuppression. We conclude that adult females and female offspring are more sensitive to long lasting immune dysfunction after DEX treatment compared to males. (This abstract does not reflect EPA policy and is supported, in part, by the American Chemistry Council under CRADA 0215-02).