Environmental Health Perspectives 105, Supplement 5, September 1997

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Lung Proliferative and Clearance Responses to Inhaled para-Aramid RFP in Exposed Hamsters and Rats: Comparisons with Chrysotile Asbestos Fibers

David B. Warheit, Suzanne I. Snajdr, Mark A. Hartsky, and Steven R. Frame

DuPont Haskell Laboratory, Newark, Delaware


Abstract
This study compared pulmonary effects of para-aramid respirable-sized, fiber-shaped particles (RFP) ( p -aramid fibrils) and chrysotile asbestos fiber exposures in rats. Additional p -aramid inhalation studies were conducted in hamsters to compare species responses. The hamster results are preliminary. The parameters studied were clearance/biopersistence of inhaled p -aramid RFP or size-separated asbestos fibers as well as pulmonary cell proliferation and inflammation indices after 2-week inhalation exposures. Rats were exposed nose only to chrysotile asbestos fibers at concentrations of 459 and 782 fibers/ml or to p -aramid RFP at 419 or 772 fibrils/ml. Hamsters were exposed whole body to p -aramid RFP at concentrations of 358 and 659 fibrils/ml. Subsequently, animals were assessed immediately (time 0) as well as 5 days (10 days for hamsters), 1, 3, 6, and 12 months postexposure. Lung burdens for the p -aramid-exposed rats were 4.8 Multiple 10 7 and 7.6 Multiple 10 7 fibrils/lung, with similar numbers of chrysotile fibers >5 µm recovered from the lungs of asbestos-exposed rats. In comparison, 1.4 Multiple 10 6 fibrils/lung were recovered in the high-dose hamster group. Biopersistence studies in p -aramid-exposed rats and hamsters demonstrated an initial increase (relative to time 0) in retained p -aramid fibrils during the first month postexposure, which indicated breakage or shortening of inhaled fibrils. This result was associated with a progressive reduction, and increased residence time in the lung, in the mean lengths of the fibrils, which signified biodegradability of inhaled p -aramid fibrils in both species. In contrast, clearance of short chrysotile asbestos fibers was rapid, but clearance of the long chrysotile fibers was slow or insignificant, as evidenced by a progressive increase over time in the mean lengths of fibers recovered from the lungs of exposed rats. Two-week, high-dose exposures to p -aramid in both rats and hamsters produced transient increases in pulmonary inflammatory and cell proliferative responses. In contrast, inhalation of size-separated chrysotile asbestos fibers in rats produced persistent increases in cell labeling indices of airway, alveolar, and subpleural cells measured through a period of 1 to 3 months postexposure. These results suggest that inhaled p -aramid RFP are biodegradable in the lungs of exposed rats and hamsters. In contrast, exposures to chrysotile asbestos fibers in rats resulted in a selective pulmonary retention of long chrysotile fibers. -- Environ Health Perspect 105(Suppl 5):1219-1222 (1997)

Key words : pulmonary cell proliferation, fiber toxicology, biodegradability of inhaled fibers, chrysotile asbestos fibers, para-aramid fibrils, organic fibers, biopersistence, fiber clearance, interspecies comparisons, pulmonary effects, inhaled fibers, inhalation toxicology, lung effects, hamsters, rats


This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 1 July 1997.

This study was sponsored by the DuPont Company and Akzo Nobel Corporation.

Address correspondence to Dr. D.B. Warheit, DuPont Haskell Laboratory, P.O. Box 50, Elkton Road, Newark, DE 19714. Telephone: (302) 366-5322. Fax: (302) 366-5207. E-mail: david.b.warheit@usa.dupont.com

Abbreviations used: BrdU, bromodeoxyuridine; RFP, respirable-sized, fiber-shaped particulate(s); UICC, Union Internationale Contre le Cancer.


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Last Update: November 18, 1997