title: Comparative effects of haloacetic acids in whole embryo culture.
abstract: A major class of disinfection by-products in drinking water are the haloacetic acids. Both dichloro- and trichloroacetic acids are teratogenic when administered to rats throughout organogenesis. However, there is little information regarding the developmental toxicity of other haloacetic acids. Therefore, 3-6 somite staged CD-1 mouse embryos were exposed to acetic acid (AA) or mono- (M), di- (D), and tri- (T) substituted fluoro- (F), chloro- (C), or bromo- (B) acetic acids in whole embryo culture in order to evaluate the effects of these agents on development. A 24 hour exposure to the haloacetic acids produced dysmorphogenesis. Effects on neural tube development ranged from prosencephalic hypoplasia to non-closure defects throughout the cranial region. Exposure to the haloacetic acids affected optic development, produced malpositioned and/or hypoplastic pharyngeal arches, and resulted in perturbation of heart development. In order to determine the relative toxicities of these agents, benchmark concentrations were calculated as the lower 95% confidence interval of the concentration that produced a 5% increase in neural tube defects. The benchmark concentrations occurred over a wide range with DFA (5912.6 microM) and MBA (2.7 microM) at the extremes. Using the benchmark concentrations to compare the chemicals gives a ranking of the agents in order of increasing potency as: DFA < TFA < DCA < AA < TBA < or = 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 potential for widespread exposure to haloacetic acids in drinking water and the incomplete toxicity profile of these chemicals, further work on their developmental effects is warranted.
authors.affiliation: Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. EPA, Research Triangle Park, North Carolina 27711, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Hunter
authors.forename: E H
authors.initials: EH
authors.lastname: Rogers
authors.forename: J E
authors.initials: JE
authors.lastname: Schmid
authors.forename: A
authors.initials: A
authors.lastname: Richard
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000473:pathology; D000085:Acetates / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D046508:Culture Techniques; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005124:Eye Abnormalities / Q000139:chemically induced; D006330:Heart Defects, Congenital / Q000139:chemically induced; D051379:Mice; D009436:Neural Tube Defects / Q000139:chemically induced; D051381:Rats; D013329:Structure-Activity Relationship; D013723:Teratogens / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000085:Acetates; D013723:Teratogens