Short-term exposures to dihaloacetic acids produce dysmorphogenesis in mouse conceptuses in vitro.

Abstract

The haloacetic acids (HAAs) are a family of xenobiotics found in tap water as a result of drinking water disinfection. Administration of HAAs to rats produces a variety of adverse effects, including developmental toxicity. The dysmorphogenic potencies of all nine bromo/chloro-acetic acids have been determined in rodent whole embryo culture using standard 26-h exposure. Since the half-lives of the HAAs in vivo are typically <8 h, the developmental effects of short-term exposures to dihaloacetates were evaluated. Gestation day 8 (3-6 somite pairs) CD-1 mouse conceptuses were exposed to 11,000 microM dichloroacetic acid (DCA), 300 microM dibromoacetic acid (DBA) or 300 microM bromochloroacetic acid (BCA) for culture periods of 1, 3, 6 or 26 h. Following 1, 3 or 6 h of exposure to HAAs, conceptuses were transferred to control medium to complete a 26-h culture period. The amounts of HAAs present in embryos after 1, 3 and 6h of exposure were determined. Increased incidences of dysmorphic embryos were produced by 6 or 26-h exposures to DCA; a 26-h exposure to DBA; or 3, 6 or 26-h exposures to BCA. The dysmorphology produced was dependent upon the length of exposure and chemical. The embryonic concentration of each HAA (104.5, 2.5 and 2.6 pmol/microg protein for DCA, DBA and BCA, respectively) was reached by 1h of exposure and did not change at the subsequent time points examined. The current studies demonstrate that BCA is more potent than DBA or DCA at disrupting embryogenesis since shorter exposures alter morphogenesis. Since the embryonic HAA concentrations were the same at the three time points measured, the time-dependence in dysmorphogenesis does not appear to be a simple function of increasing embryonic concentration of these chemicals. These studies demonstrate that for these dihaloacetic acids relatively high concentrations and long exposures are needed to alter rodent development in vitro.