COMPARATIVE EFFECTS OF HALOACETIC ACIDS IN WHOLE-EMBRYO CULTURE

A major class of disinfection by-products in drinking water are the ha loacetic acids. Both dichloro- and trichloroacetic acids are teratogen ic when administered to rats throughout organogenesis. However, there is little information regarding the developmental toxicity of other ha loacetic acids. Therefore, 3-6 somite staged CD-1 mouse embryos were e xposed to acetic acid (AA) or mono- (M), di- (D), and tri- (T) substit uted fluoro- (F), chloro- (C), or bromo- (B) acetic acids in whole emb ryo culture in order to evaluate the effects of these agents on develo pment. A 24 hour exposure to the haloacetic acids produced dysmorphoge nesis. Effects on neural tube development ranged from prosencephalic h ypoplasia to non-closure defects throughout the cranial region. Exposu re to the haloacetic acids affected optic development, produced malpos itioned and/or hypoplastic pharyngeal arches, and resulted in perturba tion of heart development. In order to determine the relative toxiciti es of these agents, benchmark concentrations were calculated as the lo wer 95% confidence interval of the concentration that produced a 5% in crease in neural tube defects. The benchmark concentrations occurred o ver a wide range with DFA (5912.6 mu M) and MBA (2.7 mu M) at the extr emes. Using the benchmark concentrations to compare the chemicals give s a ranking of the agents in order of increasing potency as: DFA < TFA < DCA < AA < TEA less than or equal to TCA < DBA < MCA < MBA. TCA and DCA have demonstrated ability to disrupt development in vivo but were among the least potent haloacetic acids in vitro. Because of the pote ntial for widespread exposure to haloacetic acids in drinking water an d the incomplete toxicity profile of these chemicals, further work on their developmental effects is warranted. (C) 1996 Wiley-Liss, Inc.