Occurrence, synthesis, and mammalian cell cytotoxicity and genotoxicity of haloacetamides: an emerging class of nitrogenous drinking water disinfection byproducts.
The haloacetamides, a class of emerging nitrogenous drinking water disinfection byproduct (DBPs), were analyzed for their chronic cytotoxicity and for the induction of genomic DNA damage in Chinese hamster ovary cells. The rank order for cytotoxicity of 13 haloacetamides was DIAcAm > IAcAm > BAcAm > TBAcAm > BIAcAm > DBCAcAm > CIAcAm > BDCAcAm > DBAcAm > BCAcAm > CAcAm > DCAcAm > TCAcAm. The rank order of their genotoxicity was TBAcAm > DIAcAm approximately equal to IAcAm > BAcAm > DBCAcAm > BIAcAm > BDCAcAm > CIAcAm > BCAcAm > DBAcAm > CAcAm > TCAcAm. DCAcAm was not genotoxic. Cytotoxicity and genotoxicity were primarily determined by the leaving tendency of the halogens and followed the order I > Br > > Cl. With the exception of brominated trihaloacetamides, most of the toxicity rank order was consistent with structure-activity relationship expectations. For di- and trihaloacetamides, the presence of at least one good leaving halogen group (I or Br but not Cl) appears to be critical for significant toxic activity. Log P was not a factor for monohaloacetamides but may play a role in the genotoxicity of trihaloacetamides and possible activation of dihaloacetamides by intracellular GSH and -SH compounds.
Plewa
Michael J
MJ
College of Agricultural, Consumer and Environmental Sciences, Department of Crop Sciences, University of Illinois at Urbana-Champaign, 1101 West Peabody Drive, Urbana, Illinois 61801, USA. mplewa@uiuc.edu
Muellner
Mark G
MG
Richardson
Susan D
SD
Fasano
Francesca
F
Buettner
Katherine M
KM
Woo
Yin-Tak
YT
McKague
A Bruce
AB
Wagner
Elizabeth D
ED
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004202:Disinfectants / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D013058:Mass Spectrometry; D009153:Mutagens / Q000633:toxicity*; D013329:Structure-Activity Relationship; D018675:Toxicity Tests; D018508:Water Purification; D014881:Water Supply
D000081:Acetamides; D004202:Disinfectants; D009153:Mutagens