title: Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay.
abstract: BACKGROUND
  Trihalomethanes (THMs) and haloacetic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown.
  
  
  OBJECTIVE
  We aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs in a multigenerational reproductive toxicity bioassay.
  
  
  METHODS
  Sprague-Dawley rats were exposed (parental, F1, and F2 generations) from gestation day 0 of the parental generation to postnatal day (PND) 6 of the F2 generation to a realistically proportioned mixture of THMs and HAAs at 0, 500×, 1,000×, or 2,000× of the U.S. Environmental Protection Agency's maximum contaminant levels (MCLs).
  
  
  RESULTS
  Maternal water consumption was reduced at ≥ 1,000×; body weights were reduced at 2,000×. Prenatal and postnatal survival were unaffected. F1 pup weights were unaffected at birth but reduced at 2,000× on PND6 and at ≥ 1,000× on PND21. Postweaning F1 body weights were reduced at 2,000×, and water consumption was reduced at ≥ 500×. Males at 2,000× had a small but significantly increased incidence of retained nipples and compromised sperm motility. Onset of puberty was delayed at 1,000× and 2,000×. F1 estrous cycles and fertility were unaffected, and F2 litters showed no effects on pup weight or survival. Histologically, P0 (parental) dams had nephropathy and adrenal cortical pathology at 2,000×.
  
  
  CONCLUSIONS
  A mixture of regulated DBPs at up to 2,000× the MCLs had no adverse effects on fertility, pregnancy maintenance, prenatal survival, postnatal survival, or birth weights. Delayed puberty at ≥ 1,000× may have been secondary to reduced water consumption. Male nipple retention and compromised sperm motility at 2,000× may have been secondary to reduced body weights.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Narotsky
authors.forename: Gary R
authors.initials: GR
authors.lastname: Klinefelter
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Goldman
authors.forename: Anthony B
authors.initials: AB
authors.lastname: DeAngelo
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Best
authors.forename: Anthony
authors.initials: A
authors.lastname: McDonald
authors.forename: Lillian F
authors.initials: LF
authors.lastname: Strader
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Murr
authors.forename: Juan D
authors.initials: JD
authors.lastname: Suarez
authors.forename: Michael H
authors.initials: MH
authors.lastname: George
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*; D005260:Female; D054879:Halogenation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D022882:Trihalomethanes / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000085:Acetates; D004202:Disinfectants; D022882:Trihalomethanes; D014874:Water Pollutants, Chemical