Identification of `genotoxic' and `non-genotoxic' alerts for cancer in mice: the carcinogenic potency database

Genotoxic Impurities in Pharmaceuticals

“…incorrect molecular structure or erroneous data from toxicology studies of a chemical) is introduced into the model, amplification of that error is generated and represented in the prediction (Benigni et al, 2005;Valerio, 2009). Cunningham et al (1998) investigated a SAR analysis of the mouse subset of the carcinogenic potency database (CPDB) which also included chemicals tested by the US national toxicology program (NTP). This database consisted of 627 chemicals tested in mice for carcinogenic activity with the tumorigenicity data being standardized and reported as TD 50 values.…”

“…In fact, it cannot be well approached until some mechanistic understanding of nongenotoxic carcinogenesis is achieved. At this time, this approach is unable to grasp the structural features of non-genotoxic carcinogens (Ashby, 1990;Cunningham et al, 1998;Benigni et al, 2005). The other limitation to currently available QSARs is the lack of models for organometallics, complex mixtures (e.g.…”

Analytical Aspects of Aromatic Amines

“…The QSAR studies on mutagenic and carcinogenic activities of aromatic amines were reviewed 10,11 . QSAR studies based on the Carcinogenic Potency Database 12 found that aromatic amines are among the major genotoxic biophores for cancer causation in rats and mice 13,14 ; however, there seems to be no specific organs targeted by their carcinogenic action 15 . QSAR modeling was proposed for estimation of carcinogenicity of aromatic amines aiming at the synthesis of safer chemicals, for the estimation of the risk posed by such pollutants in the environment, thus reducing the need for animal experimentation.…”

Estimating the extent of the health hazard posed by high-production volume chemicals.

“…SAR models of these databases have also been described (41)(42)(43). We combined the individual projections derived from these different databases using Bayes' theorem, described previously (17,18) to yield a single prediction of carcinogenicity.…”