Associations between Disinfection Byproducts and Birth Defect: Use of Relative Potency Factors
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Background and Aim: Toxicological and epidemiological evidence suggest that some disinfection byproducts (DBPs) are teratogenic, but exposure assessment is complicated since few of the >700 DBPs (e.g., trihalomethanes (THMs) and haloacetic acids (HAAs)) are monitored in drinking water. We compared adjusted odds ratios (aORs) for seven birth defect types in relation to first trimester exposures using unweighted mixture sums (e.g., THM3/THM4/HAA5/HAA6/HAA9) and relative potency factor (RPF) weighted sums based on full-litter resorption and/or eye-malformation data from THM and HAA gavage administration in F344 and Long-Evans rats.
Methods: From a registry-based case-control analysis of birth defects in Massachusetts with complete quarterly 1999-2004 DBP data, we calculated and compared RPF-weighted to unweighted adjusted odds ratios (aORs) focusing on exposure quantiles with aORs>1.2.
Preliminary Results: No consistent patterns for comparisons of RPF-weighted to unweighted aORs were detected for the highest quantiles. For HAA5, HAA6, and HAA9, RPF-based aORs were 14 to 30% lower for cleft palate and 15-20% lower for tetralogy of Fallot (TOF). The aOR for diaphragmatic hernia (DH) was also attenuated for HAA6 (10%) but increased for HAA5 (6%). The aOR for DH and THM3 was attenuated (7%) but increased for THM4 (16%). The highest quantile aORs for THM metrics and TOF, limb defects, and cleft palate were largely unchanged. For elevated aORs across all quantiles, average absolute value changes in DH aORs were 10% for THM3, 15% for THM4, 12% for HAA6, and 27% for HAA5. Average changes for TOF were 8% for THM4, 9% for HAA5, and 16% for HAA9.
Conclusions: Exposure rankings that reflect concentrations of more toxicologically relevant mixture components should more accurately reflect potential health impacts of widespread DBP mixture exposures. Despite inconsistent findings across metrics and birth defects, development of outcome-specific RPFs may improve the utility of this exposure assessment approach in future epidemiological studies.