tailieunhanh - PREDICTIVE TOXICOLOGY - CHAPTER 9

Các ứng dụng của SAR-Based Hạ tầng cơ sở trong chất độc Việc chấp nhận gia tăng của các kỹ thuật SAR trong lĩnh vực quản lý để dự đoán sức khỏe và các mối nguy hiểm sinh thái (1-6) đã dẫn đến sự phát triển và tiếp thị của một số chương trình SAR (7). Các cách tiếp cận có tính hữu dụng tối ưu khi họ được tuyển dụng hỗ trợ cho những thích hợp Các tác giả không có lợi ích thương mại trong bất kỳ của các công nghệ được mô tả trong tổng quan này | 9 Applications of Substructure-Based SAR in Toxicology HERBERT S. ROSENKRANZ Department of Biomedical Sciences Florida Atlantic University Boca Raton Florida . BHAVANI P. THAMPATTY Department of Environmental and Occupational Health Graduate School of Public Health University of Pittsburgh Pittsburgh Pennsylvania . 1. INTRODUCTION The increased acceptance of SAR techniques in the regulatory arena to predict health and ecological hazards 1-6 has resulted in the development and marketing of a number of SAR programs 7 . The approaches are of optimal usefulness when they are employed as adjuncts to the appropriate The authors have no commercial interest in any of the technologies described in this review. 309 2005 by Taylor Francis Group LLC 310 Rosenkranz and Thampatty human expertise. In addition to predicting specific toxicological endpoints these methodologies in the hands of an expert can also be used to gain insight into the mechanistic basis of the action of toxicants and thereby allow a more refined health or ecological risk assessment 8 9 . This review deals with aspects of SAR methodologies that are based upon substructural analyses that are driven primarily by statistical constraints . MULTICASE 10 12 as opposed to satisfying predetermined rules . DEREK 13-15 ONCOLOGlC 16 17 Structural Alerts 18 . It must however be made clear that human expertise is very much involved in most aspects of these knowledgebased substructural methods 8 9 . Thus the inclusion of experimental data into the learning set that forms the basis of any SAR model must adhere to previously agreed upon protocols and data handling procedures Fig. 1 . Moreover prior to SAR modeling the context in which the resulting model will be used has to be defined as it will affect the manner in which the biological toxicological activities are encoded and the derived SAR model interpreted. Thus it is commonly recognized 7 19 that the induction of cancers in rodents is one of the most .