Citation:

Narotsky, M., L. Fuentes, AND T. Willoughby. Assessment of Chlorodibromomethane Effects on Pregnancy Maintenance in a Developmental Toxicity Screen with F344 Rats. Teratology Society, Clearwater, Florida, June 23 - 28, 2018.

Impact/Purpose:

Abstract reporting the preliminary findings of a developmental toxicity screen in F344 rats of chlorodibromomethane, a regulated disinfection by-product found in drinking water. Consistent with other ttrihalomethanes, this drinking water contaminant caused pregnancy loss in F344 rats at high doses.

Description:

Chlorodibromomethane (CDBM) is a drinking water disinfection by-product (DBP) formed when oxidizing disinfectants (e.g., chlorine) react with organic material in source waters. CDBM is among four trihalomethanes (THMs) that are regulated by the EPA in drinking water. Previously, we have shown that the other regulated THMs (chloroform, bromoform, bromodichloromethane) cause pregnancy loss (i.e., full-litter resorption; FLR) when administered to F344 rats, apparently due to disruption of luteinizing hormone (LH) during the LH-dependent period of pregnancy. Here, we administered CDBM, in corn oil vehicle, by gavage to timed-pregnant F344 rats at 0, 50, 100, 150, and 200 mg/kg/day on gestation days (GD) 6-10 (plug = GD 0); 7-10 dams were treated per group. This exposure period encompasses the maternal LH-dependent period (GD-7-10), as well as 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 FLR. One dam died after administration of 200 mg/kg. Maternal toxicity was also evidenced by weight loss after the first two doses in all treated groups except 100 mg/kg. Pregnancy loss (i.e., FLR) was observed only at 200 mg/kg; four of six dams had fully resorbed litters at this dose level. In surviving litters, gestation lengths were normal and parturition did not appear to be affected by CDBM. There were no significant effects on prenatal or postnatal viability or pup weight. However, one litter at 100 mg/kg showed pup mortality and reduced pup weights on PD 6 that was associated with poor maternal health; it is unclear if this isolated case was CDBM related. Thus, CDBM caused pregnancy loss at 200 mg/kg and no clear effects at lower dose levels. However, further investigation is necessary to confirm these preliminary findings. The finding of CDBM-induced pregnancy loss is consistent with the other regulated THMs; these DBPs have also been shown to cause this effect in F344 rats. [This abstract does not necessarily reflect EPA policy.]

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