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RELATIVE POTENCY BASED ON HEPATIC ENZYME INDUCTION PREDICTS IMMUNOSUPPRESSIVE EFFECT OF A MIXTURE OF POLYCHLORINATED DIBENZO-P-DIOXINS (PCDDS), DIBENZOFURANS (PCDFS) AND BIPHENYLS (PCBS)
Citation:
Smialowicz, R J., M J. DeVito, W C. Williams, AND L S. Birnbaum. RELATIVE POTENCY BASED ON HEPATIC ENZYME INDUCTION PREDICTS IMMUNOSUPPRESSIVE EFFECT OF A MIXTURE OF POLYCHLORINATED DIBENZO-P-DIOXINS (PCDDS), DIBENZOFURANS (PCDFS) AND BIPHENYLS (PCBS). TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 227(3):477-484, (2008).
Impact/Purpose:
The toxic equivalency factor (TEF) approach was employed to compare the immunotoxic potency of mixtures containing polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), using the antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBCs
Description:
ABSTRACT
). Mixture (MIX)-1 contained TCDD , 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), and 1,2,3,4,6,7,8,9-octachlorodibenzofuran (OCDF). MIX-2 was prepared by adding PCBs to MIX-1, the PCBs added were the following: 3,3 ,4,4 -tetrachlorobiphenyl (IUPAC No.77), 3,3 ,4,4 ,5-pentachlorobiphenyl (126), 3,3 ,4,4 ,5,5 -hexachlorobiphenyl (169), 2,3,3 ,4,4 -pentachlorobiphenyl (105), 2,3 ,4,4 ,5-pentachlorobiphenyl (118), and 2,3,3 ,4,4 ,5-hexachlorobiphenyl (156). The chemical composition of the mixture was based on the relative chemical concentrations in food and human tissues. Dioxin equivalents of the mixture used relative potency factors for hepatic enzyme induction in mice (DeVito et al., 1997, 2000). Groups of female B6C3F1 mice received either 0, 1.5, 15, 150 or 450 ng TCDD/kg/d or approximately 0, 1.5, 15, 150 or 450 ng TCDD equivalents/kg/d of MIX-1 or MIX-2. Chemicals were administered by gavage in corn oil, 5 days per week for 13 weeks. Mice were immunized intravenously (iv) with SRBCs 3 days after the last exposure to chemicals. Four days later body, spleen, thymus and liver weights, and the PFC response to SRBC were determined. Exposure to TCDD, MIX-1 and MIX-2 resulted in significant suppression of the PFC response. Two-way ANOVA indicates that there were no significant differences in the response between TCDD and the two mixtures. Dose response analysis was performed by fitting the Hill model to the PFC data. The estimated dose that produced a 50% response in the PFC response was 1.1, 7.9, and 13 ng TEQ/kg/d for TCDD, MIX-1 and MIX-2, respectively. These data suggest that relative potency values for hepatic enzyme induction can provide reasonable estimates of the immunotoxicity of a mixture of dioxin-like chemicals.
