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DEVELOPMENTAL CONSEQUENCES OF EXPOSURE TO DISINFECTION BY-PRODUCTS IN ANIMAL MODELS
Citation:
Hunter III, E S., M G. Narotsky, AND J E. Andrews. DEVELOPMENTAL CONSEQUENCES OF EXPOSURE TO DISINFECTION BY-PRODUCTS IN ANIMAL MODELS. Presented at Society of Toxicology, Nashville, TN, March 17 - 21, 2002.
Description:
Developmental consequences of exposure to disinfection by-products in animal models
Sid Hunter, Michael Narotsky, James Andrews
Reproductive Toxicology Division, NHEERL, ORD, US EPA, RTP, NC, 27711
Disinfection by-products (DBPs) are formed by the reaction of disinfectants (e.g. chlorine) with naturally occurring molecules found in source water. Administration of DBPs to pregnant animals produces a variety of adverse developmental effects. The trihalomethanes do not produce high rates of dysmorphogenesis, but selected members of this family cause pregnancy loss, i.e. full-litter resorptions (FLR) in rats. Following administration of bromodichloromethane a decrease in luteinizing hormone is observed in a susceptible rat strain suggesting that perturbation of the endocrine axis may be responsible for the FLR. The haloacetic acids (HAs) are another group of DBP that alter development. Trichloroacetate and dichloroacetate (DCA) induce heart, eye and kidney defects in rats. Dibromoacetate (DBA) produced small/absent kidneys in mice, eye defects in rats and skeletal abnormalities in both species. Bromochloroacetate (BCA) produced a decrease in total implants and live fetuses in the NTP 35-Day screen study design. In Chernoff-Kavlock assays DCA produced no adverse effects, BCA reduced day 6 pup weights, and DBA induced pre-and postnatal loss and reduced pup weight on PND 1 and 6. When compared in mouse whole embryo culture (WEC) the relative potency of the HAAs are MBA>BCA>MCA>DBA>BDCA>DBCA>TCA>TBA>DCA. Dose additivity of DCA, DBA and BCA was observed in rat WEC. Pathogenesis studies of embryos in vitro show induction of cell death with little concurrent effect on the cell cycle. Mechanistic studies have focused on HA-induced alteration in signal transduction pathways. Haloacetonitriles are another class of DBP that induce FLR (dichloroacetonitrile (DCAN) and trichloroacetonitrile (TCAN)), decreased birth weight (chloroacetonitrile, DCAN, TCAN, bromochloroacetonitrile (BCAN), dibromoacetonitrile (DBAN)), decreased postnatal weight gain (DCAN, BCAN, DBAN) and increased postnatal mortality (DCAN, TCAN). Although most DBPs produce effects on development and neonatal growth, many of these agents are only effective at doses that also produce maternal toxicity. This abstract does not necessarily present the views of the US EPA.