U.S. Environmental Protection Agency
Date of this Version
2016
Citation
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART B 2016, VOL. 19, NOS. 5–6, 266–288 http://dx.doi.org/10.1080/10937404.2016.1195326
Abstract
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 acidleached 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 μm. 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.
Supplementary Table 1 - EP Physical Characterizations.xlsx (12 kB)
Supplementary Table 2 - Full AIC Table.xlsx (34 kB)
Supplementary Table 5 - Master Correlation Table Unique Samples 1mg.xlsx (357 kB)
Supplementary Table 6 - IP tissue bar Graphs.xlsx (126 kB)
Supplementary Tables 3 & 4 - Leached & Unleached Sample Characterizations.xlsx (41 kB)
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Comments
This document is a U.S. government work and is not subject to copyright in the United States.