Document Detail


Genotoxicity, metabolism and blood kinetics of epichlorohydrin in mice.
MedLine Citation:
PMID:  6877269     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epichlorohydrin (ECH), a direct mutagen in vitro, did not induce chromosomal aberrations in bone-marrow cells of CD1 mice given single oral doses of 50 and 200 mg/kg in water. The ECH diol derivative (3-chloro-1,2-propanediol) was tested in vitro by a forward-mutation assay on the yeast Schizosaccharomyces pombe and showed a weak but significant mutagenic effect. The failure of ECH to induce mutagenic effects appears to be due to the rapid metabolic clearance of the compound in vivo. ECH blood kinetics at both doses, and at the same time the concentration of the diol, were determined. ECH rapidly disappeared from mouse blood, being no longer detectable 20 min after treatment. In contrast, 3-chloro-1,2-propanediol was measurable up to 5 h after dosage. No difference was observed in the kinetic and metabolic behavior of ECH after single and repeated doses (50 and 200 mg/kg/day for 7 days). When 3-chloro-1,2-propanediol was tested, neither glutathione depletion nor epoxide hydrolase inhibition (evaluated with both styrene-7,8-oxide and ECH as substrates) could be detected in mouse liver. Finally, no difference in ECH blood kinetics or metabolism were observed in experiments in which the compound was administered (200 mg/kg) intraperitoneally in water or orally as a solution in dimethyl sulfoxide.
Authors:
A M Rossi; L Migliore; D Lascialfari; I Sbrana; N Loprieno; M Tortoreto; F Bidoli; C Pantarotto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mutation research     Volume:  118     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  1983 Aug 
Date Detail:
Created Date:  1983-09-20     Completed Date:  1983-09-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  213-26     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Biotransformation
Bone Marrow / drug effects
Chlorohydrins / toxicity*
Chromosome Aberrations
Epichlorohydrin / blood,  metabolism,  toxicity*
Mice
Microsomes, Liver / metabolism
Mutagenicity Tests
Mutagens*
Mutation
Schizosaccharomyces / drug effects
Chemical
Reg. No./Substance:
0/Chlorohydrins; 0/Mutagens; 106-89-8/Epichlorohydrin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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