Exploration of Disinfection Byproduct Mixture Methods in an Epidemiological Study of Birth Defects
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Epidemiological and toxicological studies have shown that disinfection byproducts (DBPs) are associated with some birth defects, e.g., obstructive genitourinary defects (OGDs) and certain cardiac defects. Quantifying risk for birth defects is complicated by the limited number of measured exposure surrogates relative to the extent of DBPs (n>600) to which humans are exposed. We analyzed data from a case-control study of birth defects in Massachusetts from 1999–2004 to examine whether water concentration-based risks for OGD can be differentiated for DBP mixtures. Joint toxicity combinations were examined for the individual components of the regulated four trihalomethanes (THM4) and five haloacetic acids (HAA5). A kinetic prediction model was used to predict the water concentration of more toxic brominated haloacetic acids (HAABr) which allowed additional summary measures (HAA9; DBP13) to be evaluated. We calculated relative potency factor (RPF) weights for the THM/HAA components based on full-litter resorption and/or eye-malformation data from gavage administration in F344 and Long-Evans rats. In unweighted analyses, the highest DBP exposure categories were associated with elevated adjusted odds ratios (aORs) for OGD (range: 1.31-1.99) including chloroform, bromodichloromethane (BDCM), dibromochloromethane, tribromoacetic acid, chlorodibromoacetic acid, bromodichloroacetic acid, bromochloroacetic acid, a trichloroacetic acid/dichloroacetic acid (TCAA/DCAA) joint exposure, and HAABr, DBPBr, and DBP9 mixture measures. We only detected monotonic exposure-response relationships for BDCM and THMBr. When the RPF-based metrics were compared to the unweighted results, aORs for THM4 and the THM4/TCAA measures were slightly higher. In contrast, RPF-based results were null for the highest TCAA/DCAA quartile. The aORs for the RPF-based THMBr measure were slightly lower compared with unweighted results, but still showed a monotonic exposure-response relationship (quartile 4 aOR=1.68; 95%CI: 1.08,2.61). The unweighted TCAA/DCAA/dibromoacetic acid measure showed a slightly increased risk across all exposure quartiles (quartile 4 aOR=1.27) compared to the RPF-weighted results (quartile 4 aOR=1.11). This metric approximated HAA5 as teratogenicity was not observed in toxicological data for the other two HAA5 components (monobromoacetic acid; monochloroacetic acid) tested. The approaches examined here allow for more specificity of potential risks due to better targeting of toxicologically relevant exposure mixture metrics as well as examination of some component DBPs with limited exposure contrasts.
The views expressed in this abstract are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.