ENVR 99 |
| Methods to predict the expected outcome of combination exposures are critical both to risk assessment and to an accurate judgment of synergism or antagonism. The toxic equivalency factor (TEF) method used to assess the joint effects of dioxin-like chemicals is a special case of the method of concentration addition (CA). However, TEF implicitly assumes that the individual agents are full agonists with parallel dose-response curves. We have derived a generalization of concentration addition (GCA) to more accurately describe interactions of combinations including partial agonists. GCA and TEF models were compared to AhR-dependent gene expression by combination doses of TCDD with a partial agonist PCB and with the flavanoid galangin. In each case, the GCA model fit experimental data better than TEF. The TEF method overpredicts combination effects at the highest combination doses, but may underpredict the joint effects of lower (environmentally relevant) doses depending on the specific TEF values chosen. |
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Environmental Contaminants: Low-Level and Complex Mixtures
1:30 PM-4:50 PM, Wednesday, August 22, 2007 Boston Park Plaza -- Stanbro Rm, Oral
Division of Environmental Chemistry |