Genotoxicity structure

Genotoxicity studies are required to identify compounds that can induce genetic damage ranging from single point gene mutations to gross alterations of chromosomal structure. Such effects are taken as indicative of the potential to cause cancer or heritable defects in humans. A standard battery of three types of test is recommended ... 

Rosenkranz HS, Klopman G. 1994. Structural implications of the ICPEMC method for quantifying genotoxicity data. Mutat Res 305 99-116. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of affected cells, can be expressed as a mutagenic, clastogenic or carcinogenic event because of specific alteration of the molecular structure of the genome. 

The structures of some PAHs of environmental interest are given in Figure 9.1. Naphthalene is a widely distributed compound consisting of only two fused benzene rings. It is produced commercially for incorporation into mothballs. Many of the compounds with marked genotoxicity contain 3-7 fused aromatic rings. Benzo[a] pyrene is the most closely studied of them, and will be used as an example in the following account. 

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. 

Ashby, J., Tennant, R. W. Chemical structure, Salmonella mutagenicity and extent of carcinogencity as indicators of genotoxic carcinogenesis among 222... 

Genotoxic Effects. Evaluation of the genotoxicity of lead in humans has focused on evaluations of lymphocytes from occupationally or environmentally exposed persons (Table 2-10) and in vitro studies of structural chromosomal aberrations and sister chromatid exchange in cultures of lymphocytes taken from healthy individuals (Table 2-11). Results of studies with human lymphocyte cultures exposed in vitro to lead acetate were nearly equally divided between positive (Beek and Obe 1974 Niebuhr and Wulf 1984) and negative (Beek and Obe 1975 Deknudt and Deminatti 1978 Gasiorek and Bauchinger 1981 Schmid etal. 1972). 

ACD/Tox Suite is a collection of software modules that predict probabilities for basic toxicity endpoints. Predictions are made from chemical structure and based upon large validated databases and QSAR models, in combination with expert knowledge of organic chemistry and toxicology. ToxSuite modules for Acute Toxicity, Genotoxicity, Skin Irritation, and Aquatic Toxicity have been used. 

Baeten, A., Tafazoli, M., Kirsch-Volders, M., and Geerlings, P. 1999. Use of the HSAB principle in quantitative structure-activity relationships in toxicological research Application to the genotoxicity of chlorinated hydrocarbons. Int. J. Quantum Chem. 74 351-355. 

A. R. Jones, W. C. Mackrodt, Structure-Genotoxicity Relationship for Aliphatic Epoxides , Biochem. Pharmacol. 1983, 32, 2359 - 2362 A. R. Jones, W. C. Mackrodt, Structure-Mutagenicity Relationships of Chlorinated Ethylenes A Model Based on the Stability of the Metabolically Derived Epoxides , Biochem. Pharmacol. 1982, 31, 3710 -3712. 

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