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COMPARING MIXTURES OF DIOXIN-LIKE AND NON DIOXIN-LIKE PCBS TO TCDD
Citation:
Burgin, D. E., J J. Diliberto, AND L S. Birnbaum. COMPARING MIXTURES OF DIOXIN-LIKE AND NON DIOXIN-LIKE PCBS TO TCDD. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
COMPARING MIXTURES OF DIOXIN-LIKE AND NON DIOXIN-LIKE PCBS TO TCDD. D E Burgin1, J J Diliberto2 and L S Birnbaum3.1University of North Carolina/Toxicology, Chapel Hill, NC, USA; 2USEPA/ORD/NHEERL, ETD, Research Triangle Park, NC, USA; 3USEPA/ORD/NHEERL, HSD, Chapel Hill, NC, USA.
Environmental exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) always occur as part of a complex mixture. In order to assess the potential risk associated with these exposures, the Toxic Equivalency Factor (TEF) method was developed, and uses toxic equivalents (TEQ) to relate a chemical to TCDD. While this method adequately accounts for the effects of mixtures of TCDD or dioxin-like (DL) chemicals, there are almost always non-dioxin-like (NDL) chemicals present, in particular, the NDL polychlorinated biphenyls (PCBs). To further examine the interactions of dioxin with NDL PCBs, the present study compared the effects on multiple responses of different laboratory-defined mixtures, based on mass ratios found in food, of dioxin and NDL PCBs in both wild type C57BL/6J and CYP1A2 null male and female mice. These chemical groups are: 1) TCDD alone; 2) DL Mix A containing TCDD, 1,2,3,7,8 Pentachlorodibenzo-p-dioxin, 2,3,4,7,8 Pentachloro-dibenzofuran, PCB 126; 3) NDL Mix B containing PCB 118, PCB 138, PCB 153, PCB 180; and 4) Mix C - a combination of Mixes A and B. The dose levels used were 0.0, 0.001, 0.01, 0.1, 1.0, and 10.0 ug TEQ/kg body weight for Mix A, B and C, and the same plus 100.0 ug /kg for TCDD. No effects were seen in body weight or other tissues, in male or female wildtype or knockout mice. Although we expected an increase in liver weights in Mix B and Mix C, liver weight was increased only in Mix C in both male and female, wildtype and knockout. The effect appears to be synergistic, not additive. No effects were observed in levels of glutathione, a marker of oxidative stress, in either wildtype or knockout, although this is not surprising due to the large pools of glutathione in the body. Based on these findings, it appears that these mixtures have a synergistic effect greater than the sum of the individual congeners, or TCDD alone. (This abstract does not reflect EPA policy. This research was supported by EPA CT902908)