Structural analysis and predictive value of the rodent in vivo micronucleus assay results.

Abstract:

:In vivo genotoxicity studies-shortly followed by carcinogenicity-are posing high demand for test-related recourses in terms of animal lives and resources. Among those, the micronucleus test in rodents is the most widely used as a follow-up to positive in vitro mutagenicity results; therefore, the development and extensive use of estimation techniques based on the concept of Structure-Activity Relationships-such as (Quantitative) Structure-Activity Relationships, read-across and grouping of chemicals-might have a huge saving potential for this end point. In this paper, we present a newly derived compilation of Structural Alerts for the rodent in vivo micronucleus assay, thus providing a coarse-grain filter for preliminary screening of potentially in vivo mutagens. The compilation has been implemented as computerized rule of the expert system Toxtree and is freely available: http://ecb.jrc.ec.europa.eu/qsar/qsar-tools/index.php?c=TOXTREE. In addition, analyses on the performance of the micronucleus assay as pre-screening tool for carcinogenesis indicate that this assay is prone to give false-negative predictions and point to the need of improving the in vivo component of the present testing schemes.

journal_name

Mutagenesis

journal_title

Mutagenesis

authors

Benigni R,Bossa C,Worth A

doi

10.1093/mutage/geq010

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

335-41

issue

4

eissn

0267-8357

issn

1464-3804

pii

geq010

journal_volume

25

pub_type

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