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Toxicological Responses of Fischer Rats to Naturally Occurring Asbestos Samples from the United States and Canada
Cyphert, J., A. Nyska, R. Mahoney, M. Schladweiler, U. Kodavanti, AND S. Gavett. Toxicological Responses of Fischer Rats to Naturally Occurring Asbestos Samples from the United States and Canada. Presented at NC SOT PARC Award meeting, October 04, 2012.
To support risk assessment efforts, a comparative study was designed to provide understanding of the toxicity of different types of fibers encountered in EPA clean-up efforts. Physico-chemical properties, and consequentially toxicity, are likely to be different among various fiber types. NOA samples representing different types of asbestiform fibers or non-asbestiform cleavage fragments included Libby Amphibole (LA; composed of winchite/richterite/tremolite and served as a positive control), chrysotile from Whatcom County/Sumas Mountain, Washington (SM), tremolite from El Dorado Hills, California (ED) and ferroactinolite cleavage fragments from Ontario, Canada (ON) which served as a negative control. Rat-respirable fractions (aerodynamic equivalent diameter ≤ 2.5 μm) of each NOA were prepared by water elutriation, resuspended in dispersion media (containing albumin and surfactant), and delivered via a single intratracheal (IT) instillation to 9-10 wk old male Fischer rats at doses of 0.5 mg/rat and 1.5 mg/rat. Bronchoalveolar lavage fluid (BALF) biomarkers of inflammation and lung injury, gene expression arrays, lung histology, and baseline pulmonary function were analyzed 1 day, 3 months, or 15 months post-IT to determine both the acute and long-term toxicity of each NOA sample compared to a vehicle (dispersion media, DM) control. The majority of significant changes were seen 1 day post-instillation. BALF cellularity was significantly increased in all asbestos-exposed groups. Low-dose (0.5 mg/rat) exposure to all samples resulted in a 3-4 fold increase in total cells compared to controls, whereas high-dose (1.5 mg/rat) exposure had a more severe effect on lung inflammation which varied by source of the fiber. Exposure to high-dose LA resulted in a 4 fold increase in total cells, SM a 7 fold increase and both ON and ED exposure resulted in a 9 fold increase compared to DM controls. Although inducing less acute inflammation, exposure to either LA or
Comparison of pulmonary toxicity of 4 samples of naturally occurring asbestos (NOA) fibers showed that Sumas Mountain chrysotile (SM) was more fibrogenic than Libby amphibole (LA), El Dorado Hills tremolite (ED) and Ontario ferroactinolite cleavage fragments (ON) in rats 3 months after exposure. The results suggest that environmental exposure to NOA in the absence of mining has the potential for adverse health effects and highlights the need for further study of more sites within the United States.
URLs/Downloads:NCSOT PARC AWARD 2012.DOCX
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH