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DOI10.1080/10937404.2016.1195326
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
ISSN1093-7404
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
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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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