title: Developmental toxicity evaluations of whole mixtures of disinfection by-products using concentrated drinking water in rats: gestational and lactational effects of sulfate and sodium.
abstract: A developmental toxicity bioassay was used in three experiments to evaluate water concentrates for suitability in multigenerational studies. First, chlorinated water was concentrated 135-fold by reverse osmosis; select lost disinfection by-products were spiked back. Concentrate was provided as drinking water to Sprague-Dawley and F344 rats from gestation day 6 to postnatal day 6. Maternal serum levels of luteinizing hormone on gestation day 10 were unaffected by treatment for both strains. Treated dams had increased water consumption, and increased incidences of polyuria, diarrhea, and (in Sprague-Dawley rats) red perinasal staining. Pup weights were reduced. An increased incidence of eye defects was seen in F344 litters. Chemical analysis of the concentrate revealed high sodium (6.6 g/l) and sulfate (10.4 g/l) levels. To confirm that these chemicals caused polyuria and osmotic diarrhea, respectively, Na₂SO₄ (5-20 g/l) or NaCl (16.5 g/l) was provided to rats in drinking water. Water consumption was increased at 5- and 10-g Na₂SO₄/l and with NaCl. Pup weights were reduced at 20-g Na₂SO₄/l. Dose-related incidences and severity of polyuria and diarrhea occurred in Na₂SO₄-treated rats; perinasal staining was seen at 20 g/l. NaCl caused polyuria and perinasal staining, but not diarrhea. Subsequently, water was concentrated ∼120-fold and sulfate levels were reduced by barium hydroxide before chlorination, yielding lower sodium (≤1.5 g/l) and sulfate (≤2.1 g/l) levels. Treatment resulted in increased water consumption, but pup weight and survival were unaffected. There were no treatment-related clinical findings, indicating that mixtures produced by the second method are suitable for multigenerational testing.
authors.affiliation: NHEERL-MD-67, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. narotsky.michael@epa.gov
authors.forename: Michael G
authors.initials: MG
authors.lastname: Narotsky
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Pressman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miltner
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Speth
authors.forename: Linda K
authors.initials: LK
authors.lastname: Teuschler
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Rice
authors.forename: Susan D
authors.initials: SD
authors.lastname: Richardson
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Best
authors.forename: Anthony
authors.initials: A
authors.lastname: McDonald
authors.forename: E Sidney
authors.initials: ES
authors.lastname: Hunter
authors.forename: Jane Ellen
authors.initials: JE
authors.lastname: Simmons
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004203:Disinfection; D004327:Drinking Behavior / Q000187:drug effects; D060766:Drinking Water / Q000737:chemistry*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D007774:Lactation / Q000097:blood / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood; D018811:Maternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000633:toxicity*; D012996:Solutions; D013431:Sulfates / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D060766:Drinking Water; D012996:Solutions; D013431:Sulfates; D007986:Luteinizing Hormone; D012964:Sodium