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 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.
Benigni
Romualdo
R
Department of Environment and Health, Istituto Superiore di Sanita', Rome, Italy. romualdo.benigni@iss.it
Bossa
Cecilia
C
Worth
Andrew
A
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000139:chemically induced; D021281:Quantitative Structure-Activity Relationship; D012377:Rodentia
D002273:Carcinogens; D009153:Mutagens