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TESTING FOR ADDITIVITY IN THE LOW DOSE REGION OF AN ENVIRONMENTALLY RELEVANT MIXTURE OF 18 OLYHALOGENATED AROMATIC HYDROCARBONS.
Citation:
GENNINGS, C., L. STORK, M. J. DEVITO, AND K. M. CROFTON. TESTING FOR ADDITIVITY IN THE LOW DOSE REGION OF AN ENVIRONMENTALLY RELEVANT MIXTURE OF 18 OLYHALOGENATED AROMATIC HYDROCARBONS. Presented at Society of Toxicology, Charlotte, NC, March 25 - 29, 2007.
Description:
A common default assumption in risk assessment of chemical mixtures is that the chemicals combine additively in the low dose region. Under additivity, with information from single chemical dose-response data, the risk associated with the mixture can be estimated. The objective of our research is to evaluate if there is indeed sufficient evidence to claim additivity in a low dose region for the effects of an environmentally relevant mixture of 18 PHAHs on serum total thyroxine (T4). Young female rats were dosed via gavage with 18 different PHAHs [2 dioxins, 4 dibenzofurans, and 12 PCBs], for 4 consecutive days (Crofton et al, EnvHlthPersp, 2005). Serum total T4 was measured via radioimmunoassay. A mixture was custom synthesized with the ratio of chemicals based on the ratios of PHAHs found in breast milk, fish and other sources of human exposure. Following the work of Stork et al (Risk Analysis, 2006) we utilized equivalence testing methodology to test for additivity at three environmentally relevant low dose mixture groups. The ratio of predicted mean responses under additivity based on single chemical data to observed sample means at these mixture points was calculated with the corresponding 95% simultaneous confidence intervals. Two of the three confidence intervals were completely contained within predetermined equivalence bounds of [0.80, 1.25]. In these two cases, we conclude that there is significant evidence to claim that the T4 mean response was equivalent to that predicted from the single chemical data under additivity. In the lowest mixture dose group, there was not enough evidence to claim additivity as the lower limit of the Bonferroni-corrected 95% confidence interval fell below 0.80. (This abstract does not reflect U.S. EPA policy.)