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COMPARING ENVIRONMENTALLY RELEVANT PCBS TO TCDD
Citation:
Burgin, D. E., J J. Diliberto, AND L S. Birnbaum. COMPARING ENVIRONMENTALLY RELEVANT PCBS TO TCDD. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, Utah, March 9-13, 2003.
Description:
COMPARING ENVIRONMENTALLY RELEVANT PCBS TO TCDD. D E Burgin1, J J Diliberto2 and L S Birnbaum3.1UNC, Chapel Hill, NC, USA; 2USEPA/ORD/NHEERL, ETD, RTP, 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 examine the interactions of TCDD 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 TCDD and NDL PCBs in both wildtype C57BL/6J (WT) and CYP1A2 null (KO) male and female mice. These chemical groups are: TCDD alone; DL Mix A; NDL Mix B; and Mix C - a combination of Mixes A and B. No effects were seen in body weight or other tissues, in male or female WT or KO 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, WT and KO. No effects were observed in levels of glutathione or uric acid, markers of oxidative stress. Both male WT and KO showed greater decreases in levels of total triiodothyronine (TT3) while Mix A and Mix C resulted in a 50% reduction in levels of total thyroxine in all groups. With exposure to TCDD and DL mixes, but not to NDL PCBs, there is an increase in ascorbate levels. Based on these findings, there does not appear to be a strain difference in response to chemical exposure, indicating CYP1A2 is not necessary for these responses. There does appear to be a gender difference, reflecting a possible endogenous estrogenic component to maintenance of levels of TT3 and ascorbic acid cycling. 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. DB supported by EPA CT902908 and NIEHS T32-ES07126)