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Metabolism of trichloroethylene and chloral hydrate by the Japanese medaka (Oryzias latipes) in vitro.

Authors
Lipscomb-JC; Confer-PD; Miller-MR; Stamm-SC; Snawder-JE; Bandiera-SM
Source
Environ Toxicol Chem 1998 Feb; 17(2):325-332
NIOSHTIC No.
20033965
Abstract
Trichloroethylene (TRI), a common groundwater contaminant, is readily metabolited by mammals to produce chloral hydrate (CH), trichloroacetic acid (TCA), and trichloroethanol (TCOH). Cytochrome P450 (CYP) and other enzymes are responsible for formation of these metabolites, which are implicated in TRI's toxicity and carcinogenicity. To establish the validity of the Japanese medaka (Oryzias latipes) as an alternate test species for TRI, we examined the metabolism of TRI and CH, as well as CYP expression, in medaka liver preparations. Trichloroethylene was incubated with medaka microsomal protein, and metabolites were extracted and analyzed using gas chromatography. Microsome-mediated metabolism of TRI was observed, and a K-m value for TRI oxidation of 540 mu M and a V-max value of 213 pmol/min.mg(-1) protein were obtained. Conversion of TRI to CH, TCA, and TCOH was found with medaka hepatic subcellular fractions. In addition, a sex difference in hepatic microsomal TRI metabolism, specific CYP content, and ethoxyresorufin O-deethylase activity was noted. The lower specific activity of preparations from the livers of female medaka is compensated for by increased total protein in the larger liver mass of the female. Immunochemical analysis showed that CYP1A was readily detectable in medaka liver, but CYP2E1 was present at very low levels. These data suggest that TRI metabolism in medaka liver preparations mimics that observed in mammalian systems and supports their use as an alternative test species in the evaluation of the toxicity of TRI.
Keywords
Epidemiology; Risk-analysis; Risk-factors; Metabolites; Toxic-effects; Toxins; Carcinogenesis; Carcinogens; Chemical-hypersensitivity; Chemical-properties; Chemical-synthesis
Contact
John C. Lipscomb, USAF, Armstrong Lab, Div Toxicol, Wright Patterson AFB, OH 45433
CODEN
ETOCDK
CAS No.
76-03-9; 79-01-6
Publication Date
19980201
Document Type
Journal Article
Email Address
jlipscomb@al.wpafb.mil
Fiscal Year
1998
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0730-7268
NIOSH Division
DBBS
Source Name
Environmental Toxicology and Chemistry
State
OH
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