title: Pregnancy loss and eye malformations in offspring of F344 rats following gestational exposure to mixtures of regulated trihalomethanes and haloacetic acids.
abstract: Chlorination of drinking water yields hundreds of disinfection by-products (DBPs). Among the DBPs, four trihalomethanes (THMs; chloroform, bromodichloromethane, chlorodibromomethane, bromoform) and five haloacetic acids (HAAs; chloroacetic, dichloroacetic, trichloroacetic, bromoacetic, and dibromoacetic acid) are U.S. EPA regulated. We assessed the combined toxicity of these DBPs. F344 rats were treated with mixtures of the four THMs (THM4), the five HAAs (HAA5), or nine DBPs (DBP9; THM4+HAA5). Mixtures were administered in 10% Alkamuls(®) EL-620 daily by gavage on gestation days 6-20. Litters were examined postnatally. All three mixtures caused pregnancy loss at ≥ 613 μmol/kg/day. In surviving litters, resorption rates were increased in groups receiving HAA5 at 615 μmol/kg/day and DBP9 at 307 μmol/kg/day. HAA5 caused eye malformations (anophthalmia, microphthalmia) at ≥ 308 μmol/kg/day. Thus, both HAAs and THMs contributed to DBP9-induced pregnancy loss. The presence of THMs in the full mixture, however, appeared to reduce the incidence of HAA-induced eye defects.
authors.affiliation: Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. narotsky.michael@epa.gov
authors.forename: Michael G
authors.initials: MG
authors.lastname: Narotsky
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Best
authors.forename: Anthony
authors.initials: A
authors.lastname: McDonald
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Godin
authors.forename: E Sidney
authors.initials: ES
authors.lastname: Hunter
authors.forename: Jane Ellen
authors.initials: JE
authors.lastname: Simmons
mesh_terms: D000085:Acetates / Q000633:toxicity*; D000818:Animals; D004202:Disinfectants / Q000633:toxicity*; D004338:Drug Combinations; D020964:Embryo Loss / Q000139:chemically induced* / Q000473:pathology; D005124:Eye Abnormalities / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced* / Q000473:pathology; D006219:Halogens / Q000633:toxicity; D018811:Maternal Exposure / Q000009:adverse effects; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D022882:Trihalomethanes / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000085:Acetates; D004202:Disinfectants; D004338:Drug Combinations; D006219:Halogens; D022882:Trihalomethanes; D014874:Water Pollutants, Chemical