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Ann. occup. Hyg., Vol. 46, No. suppl_1, pp. 99-101, 2002
© 2002 British Occupational Hygiene Society
Published by Oxford University Press

Mechanistic In Vivo and In Vitro Pulmonary Cellular Studies Demonstrating Biodegradability of Inhaled p-Aramid RFP

D. B. Warheit*, M. A. Hartsky, K. L. Reed and T. R. Webb

DuPont Haskell Laboratory for Health and Environmental Sciences 1090 Elkton Road, PO Box 50, Newark, DE, USA

*Author to whom correspondence should be addressed.

These studies were designed to investigate mechanisms through which inhaled p-aramid respirable-sized fiber-shaped particulates (RFP) are biodegraded in the lungs of exposed rats and hamsters. We have postulated that lung fluids coat/activate inhaled p-aramid RFP which deposit in the lung and promote enzymatic attack and consequent shortening. Aliquots of p-aramid or cellulose (biopersistent control) RFP were instilled into the lungs of rats and the lungs digested 24 h later using two different (KOH or enzymatic) digestion methods. For in vitro studies the two RFP types were incubated with lavage fluid and processed via simulated digestion; in addition, rat lung epithelial cells, macrophages or co-cultures were incubated with p-aramid and digested 1, 24 or 168 h post-exposure. In vivo the enzyme but not the KOH digestion method resulted in shortening of p-aramid but not cellulose RFP recovered from rat lungs. The results of in vitro studies showed that mean lengths of p-aramid RFP incubated with saline and processed by either digestion method were not found to be altered. Indeed, only the preparation of p-aramid RFP that had been incubated with BAL fluid and processed with the enzyme solution resulted in cleavage of p-aramid RFP. In contrast to the in vitro acellular studies with p-aramid RFP, the combination of BAL fluid incubation and enzyme digestion method had no measurable effect on shortening of cellulose RFP, indicating that the results with p-aramid were specific. In vitro cellular studies demonstrated a shortening of p-aramid RFP in exposed macrophages and co-cultures but not in lung epithelial cells 24 h and 1 week post-exposure. These findings demonstrate that lung fluids coat and activate the p-aramid RFP as a prerequisite for cleavage and describe a likely mechanism for the biodegradability of inhaled p-aramid RFP in the lungs of exposed animals.

p-aramid RFP • biodegradability • cellulose RFP • fiber toxicology • man-made organic fibers • respirablesized fiber-shaped particulates


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