Haloacetonitriles: metabolism, genotoxicity, and tumor-initiating activity
Haloacetonitriles (HAN) are drinking water contaminants produced during chlorine disinfection. This paper evaluates metabolism, genotoxicity, and tumor-initiating activity of these chemicals. The alkylating potential of the HAN to react with the electrophile-trapping agent, 4-(p-nitrobenzyl)pyridine, followed the order dibromoacetonitrile (DBAN) > bromochloroacetonitrile (BCAN) > chloroacetonitrile (CAN) > dichloroacetonitrile (DCAN) > trichloroacetonitrile (TCAN). When administered orally to rats, the HAN were metabolized to cyanide and excreted in the urine as thiocyanate. The extent of thiocyanate excretion was CAN > BCAN > DCAN > DDAN >> TCAN. Haloacetonitriles inhibited in vitro microsomal dimethylnitrosamine demethylase (DMN-DM) activity. The most potent inhibitors were DBAN and BCAN. The HAN produced DNA strand breaks in cultured human lymphoblastic (CCRF-CEM) cells. TCAN was the most potent DNA strand breaker. DCAN reacted with polyadenylic acid and DNA to form adducts in a cell-free system. None of the HAN initiated ..gamma..-glutamyltranspeptidase (GGT) foci when assayed for tumor-initiating activity in rat liver foci bioassay. In summary, the HAN were demonstrated to possess alkylating activity and genotoxicity in vitro and appeared after oral administration to possess biological activity as indicated by the inhibition of DMN-DM by TCAN but appeared to lack genotoxic and tumor-initiating activity in rat liver. It is proposed that if the HAN found in drinking water pose a carcinogenic hazard it would be limited to the gastrointestinal tract.
- Research Organization:
- Environmental Protection Agency, Cincinnati, OH
- OSTI ID:
- 5777076
- Journal Information:
- Environ. Health Perspect.; (United States), Vol. 69
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CARCINOGENESIS
RISK ASSESSMENT
DRINKING WATER
CHLORINATION
NITRILES
METABOLISM
TOXICITY
ACETONITRILE
ALKYLATION
CELL CULTURES
DNA
DNA ADDUCTS
EXCRETION
GASTROINTESTINAL TRACT
LIVER
LYMPHOCYTES
MAN
NEOPLASMS
ORGANIC HALOGEN COMPOUNDS
PEPTIDE HYDROLASES
STRAND BREAKS
ADDUCTS
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHEMICAL REACTIONS
CLEARANCE
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
DISEASES
ENZYMES
GLANDS
HALOGENATION
HYDROGEN COMPOUNDS
HYDROLASES
LEUKOCYTES
MAMMALS
MATERIALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PATHOGENESIS
PRIMATES
SOMATIC CELLS
VERTEBRATES
WATER
560300* - Chemicals Metabolism & Toxicology