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DOI | 10.1080/10937404.2016.1195326 |
Quantitative structure-mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study | |
Cook, Philip M.1; Swintek, Joseph2; Dawson, Timothy D.2; Chapman, David3; Etterson, Mathew A.1; Hoff, Dale1 | |
发表日期 | 2016 |
ISSN | 1093-7404 |
卷号 | 19期号:5-6页码:266-288 |
英文摘要 | Cancer potencies of mineral and synthetic elongated particle mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. An extensive rat intrapleural dose characterization data set with a wide variety of elongated particles physicochemical properties facilitated statistical analyses of pleural mesothelioma response data combined from several studies for evaluation of alternative dose-response models. Utilizing logistic regression of individual elongated particle dimensional variations within each test sample, four major findings emerged: (1) Mild acid leaching provides superior prediction of tumor incidence compared to samples that were not leached; (2) sum of the elongated particle surface areas from mildly acid-leached samples provides the optimum holistic dose-response model; (3) progressive removal of dose associated with very short and/or thin elongated particles significantly degrades the resultant particle count and surface area dose-based predictive model fits; and (4) alternative biologically plausible model adjustments provide evidence for reduced potency of elongated particles with aspect ratios less than 8 and lengths greater than 80 mu m. Regardless of these adjustments, the optimum predictive models strongly incorporate potency attributable to abundant short elongated particles in proportion to their surface area. Transmission electron microscopy analyses of low-temperature-ashed pleural membrane and lung tissues 5.5 mo post intrapleural exposures do not support hypotheses that short elongated particles that reach the pleural space are rapidly eliminated. Low-aspect-ratio elongated particles were still abundant in pleural membrane tissues but may have reduced potencies due to aggregation tendencies and therefore lower potential for intracellular presence. |
语种 | 英语 |
WOS记录号 | WOS:000387788000009 |
来源期刊 | JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS |
来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/57257 |
作者单位 | 1.US EPA, ORD, NHEERL, Midcontinent Ecol Div, 6201 Congdon Blvd, Duluth, MN 55804 USA; 2.Badger Tech Serv BTS, Duluth, MN USA; 3.Wilson Environm Labs, Duluth, MN USA |
推荐引用方式 GB/T 7714 | Cook, Philip M.,Swintek, Joseph,Dawson, Timothy D.,et al. Quantitative structure-mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study[J]. 美国环保署,2016,19(5-6):266-288. |
APA | Cook, Philip M.,Swintek, Joseph,Dawson, Timothy D.,Chapman, David,Etterson, Mathew A.,&Hoff, Dale.(2016).Quantitative structure-mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study.JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS,19(5-6),266-288. |
MLA | Cook, Philip M.,et al."Quantitative structure-mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study".JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS 19.5-6(2016):266-288. |
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