Dibromoacetic acid is a more potent teratogen than diiodoacetic acid in a developmental toxicity screen with F344 rats
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Dibromoacetic acid (DBA) and diiodoacetic acid (DIA) are drinking water disinfection by-products (DBPs) formed when oxidizing disinfectants (e.g., chlorine) react with organic material in source waters. DBA, but not DIA, is among five haloacetic acids (HAAs) that are regulated by the EPA in drinking water. Many water utilities are using chloramination (chlorine + ammonia) as an alternative to chlorination for disinfection to reduce concentrations of regulated DBPs; consequently, brominated and iodinated DBPs become more prevalent. Iodinated DBPs are expected to be more toxic on a molar basis than their brominated or chlorinated counterparts. Previously, we have shown that another regulated HAA (trichloroacetic acid) causes eye malformations (i.e., micro- or anophthalmia) when administered to F344 rats during pregnancy. Here, we administered DIA (150 or 200 mg/kg; 0.48 or 0.64 mmol/kg) and DBA (100 or 140 mg/kg; 0.46 or 0.64 mmol/kg) in deionized water (adjusted to pH 6.5-7) by gavage to timed-pregnant F344 rats on gestation days (GD) 6-10 (plug = GD 0); controls received deionized water. This exposure period encompasses the critical period for embryonic eye development. Dams were allowed to deliver and litters were examined on postnatal days 1 and 6. Uteri of nongravid rats were stained with 2% ammonium sulfide to confirm cases of full-litter resorption. Maternal toxicity, evidenced by weight loss after the first dose, was observed only in DIA-treated dams. There were no significant effects on prenatal or postnatal viability or pup weight. However, significantly increased incidences of eye malformations were noted at the DIA high dose and at both dosages of DBA. The number of affected litters were 0/14 controls, 2/13 at DIA 0.48 mmol/kg, 5/15 at DIA 0.64 mmol/kg, 8/11 at DBA 0.46 mmol/kg, and 9/12 at DBA 0.64 mmol/kg. Thus, administration of equimolar dosages of DIA and DBA demonstrated that DIA was more potent to the dam, causing maternal toxicity only to DIA-treated dams. In contrast, although both DBPs were teratogenic, DBA was clearly the more potent teratogen, with significantly higher incidences of eye malformations at equimolar doses. [This abstract does not necessarily reflect EPA policy.]