Genotoxicity structural alerts

In several studies of toxicity, no adverse effects were documented in monkeys or humans. Taking into account data showing that lutein was not genotoxic, had no structural alert, did not exhibit tumor-promoting activity, and is a natural component of the body (the eye), the Scientific Steering Committee concluded there was no need for a study of carcinogenicity. 

Useful data for the hazard assessment may also be obtained from studies on toxicokinetics (including metabolism), in vitro studies on macromolecule binding, from knowledge of the reactivity and electrophilicity of a substance, and from the presence or absence of structural alerts for genotoxicity. 

The chemical stmcture of a substance may contain structural alerts for genotoxicity and/or carcinogenicity, based on clear evidence for carcinogenicity of structural analogues. 

Table 5.8 Classes of chemicals with structural alerts for genotoxicity that might be present in food contact materials...

Moreover the molecules that contributed to this toxicophore (Fig. 19.7), even though they contain the S—0=N—Q= moiety (Fig. 19.6), also contain functionalities (i.e., "structural alerts") that are associated with carcinogenic-ity/genotoxicity such as nitro, amino, and hy-drazino groups. In fact, these could be responsible for the murine carcinogenicity of these chemicals. Obviously, these latter functionalities are absent in epitholone A. 

Although a great deal of effort was put into battery harmonization, there is no universal agreement on the best combination of tests for all purposes. There are other mutagenicity tests in use that may also be useful (Table 1). The choice of additional test(s) or protocol modification(s) depends on various factors. Compounds that contain structural alerts for genotoxicity are usually detectable in the standard test battery. However, compounds bearing... 

Rosenkranz, H. S. Klopman, G. Structural alerts to genotoxicity the interaction of human and artificial intelligence. Mutagenesis 1990, 5, 333-361. 

Figure 8.4 Functionalities commonly associated with genotoxicity and mutagenicity. These groups are used in structure-activity relationships to alert for possible carcinogenic substances.

Class 3 impurities Alerting structure, unrelated to parent structure and of unknown genotoxic (mutagenic) potential. Class 4 Impurities Alerting structure, related to the parent Arrive Pharmaceutical Ingredient (API). 

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