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

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 endpoint. 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 from the JRC website. 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

BENIGNI Romualdo;  BOSSA Cecilia;  WORTH Andrew; 

2010-06-15

OXFORD UNIV PRESS

JRC54422

0267-8357,   

http://mutage.oupjournals.org/,    https://publications.jrc.ec.europa.eu/repository/handle/JRC54422,   

10.1093/mutage/geq010,