Document Detail


Report of the IWGT working group on strategies and interpretation of regulatory in vivo tests I. Increases in micronucleated bone marrow cells in rodents that do not indicate genotoxic hazards.
MedLine Citation:
PMID:  17116417     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In vivo genotoxicity tests play a pivotal role in genotoxicity testing batteries. They are used both to determine if potential genotoxicity observed in vitro is realised in vivo and to detect any genotoxic carcinogens that are poorly detected in vitro. It is recognised that individual in vivo genotoxicity tests have limited sensitivity but good specificity. Thus, a positive result from the established in vivo assays is taken as strong evidence for genotoxic carcinogenicity of the compound tested. However, there is a growing body of evidence that compound-related disturbances in the physiology of the rodents used in these assays can result in increases in micronucleated cells in the bone marrow that are not related to the intrinsic genotoxicity of the compound under test. For rodent bone marrow or peripheral blood micronucleus tests, these disturbances include changes in core body temperature (hypothermia and hyperthermia) and increases in erythropoiesis following prior toxicity to erythroblasts or by direct stimulation of cell division in these cells. This paper reviews relevant data from the literature and also previously unpublished data obtained from a questionnaire devised by the IWGT working group. Regulatory implications of these findings are discussed and flow diagrams have been provided to aid in interpretation and decision-making when such changes in physiology are suspected.
Authors:
D J Tweats; D Blakey; R H Heflich; A Jacobs; S D Jacobsen; T Morita; T Nohmi; M R O'Donovan; Y F Sasaki; T Sofuni; R Tice;
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Publication Detail:
Type:  Journal Article     Date:  2006-11-20
Journal Detail:
Title:  Mutation research     Volume:  627     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-15     Completed Date:  2007-03-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  78-91     Citation Subset:  IM    
Affiliation:
Centre for Molecular Genetics and Toxicology, University of Wales, Swansea, UK. djtweats@fish.co.uk
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MeSH Terms
Descriptor/Qualifier:
Aniline Compounds / toxicity
Animals
Body Temperature
Bone Marrow Cells / drug effects*
Erythropoietin / genetics,  toxicity
Guidelines as Topic
Hyperthermia, Induced
Micronucleus Tests
Mutagenicity Tests / methods*
Mutagens / toxicity*
Naphthoquinones / toxicity
Phenol / toxicity
Phenylhydrazines / toxicity
Pyridines / toxicity
Reserpine / toxicity
Rodentia
Sensitivity and Specificity
Triazoles / toxicity
Chemical
Reg. No./Substance:
0/Aniline Compounds; 0/E 5842; 0/Mutagens; 0/Naphthoquinones; 0/Phenylhydrazines; 0/Pyridines; 0/Triazoles; 100-63-0/phenylhydrazine; 108-95-2/Phenol; 11096-26-7/Erythropoietin; 50-55-5/Reserpine; 62-53-3/aniline; 83-72-7/lawsone

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


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