title: Identification of developmentally toxic drinking water disinfection byproducts and evaluation of data relevant to mode of action.
abstract: Reactions between chemicals used to disinfect drinking water and compounds present in source waters produce chemical mixtures containing hundreds of disinfection byproducts (DBPs). Although the results have been somewhat inconsistent, some epidemiological studies suggest associations may exist between DBP exposures and adverse developmental outcomes. The potencies of individual DBPs in rodent and rabbit developmental bioassays suggest that no individual DBP can account for the relative risk estimates reported in the positive epidemiologic studies, leading to the hypothesis that these outcomes could result from the toxicity of DBP mixtures. As a first step in a mixtures risk assessment for DBP developmental effects, this paper identifies developmentally toxic DBPs and examines data relevant to the mode of action (MOA) for DBP developmental toxicity. We identified 24 developmentally toxic DBPs and four adverse developmental outcomes associated with human DBP exposures: spontaneous abortion, cardiovascular defects, neural tube defects, and low birth weight infancy. A plausible MOA, involving hormonal disruption of pregnancy, is delineated for spontaneous abortion, which some epidemiologic studies associate with total trihalomethane and bromodichloromethane exposures. The DBP data for the other three outcomes were inadequate to define key MOA steps.
authors.affiliation: Chemical, Biological and Environmental Center, SRC, Inc., Syracuse, NY 13212, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Colman
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Rice
authors.forename: J Michael
authors.initials: JM
authors.lastname: Wright
authors.forename: E Sidney
authors.initials: ES
authors.lastname: Hunter
authors.forename: Linda K
authors.initials: LK
authors.lastname: Teuschler
authors.forename: John C
authors.initials: JC
authors.lastname: Lipscomb
authors.forename: Richard C
authors.initials: RC
authors.lastname: Hertzberg
authors.forename: Jane Ellen
authors.initials: JE
authors.lastname: Simmons
authors.forename: Margaret
authors.initials: M
authors.lastname: Fransen
authors.forename: Mark
authors.initials: M
authors.lastname: Osier
authors.forename: Michael G
authors.initials: MG
authors.lastname: Narotsky
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced / Q000453:epidemiology* / Q000378:metabolism; D000818:Animals; D018376:Cardiovascular Abnormalities / Q000139:chemically induced / Q000453:epidemiology* / Q000378:metabolism; D004202:Disinfectants / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight / Q000254:growth & development / Q000378:metabolism; D007231:Infant, Newborn; D009436:Neural Tube Defects / Q000139:chemically induced / Q000453:epidemiology* / Q000378:metabolism; D011247:Pregnancy; D018570:Risk Assessment; D018508:Water Purification / Q000379:methods; D014881:Water Supply / Q000032:analysis
chemical_list: D004202:Disinfectants