Pulmonary Responses to Inhaled Para-Aramid Fibrils in Exposed Rats and Hamsters

Abstract

This multifunctional study was designed to (1) compare the pulmonary effects of size-separated vs. chrysotile asbestos inhalation exposure in rats; and (2) to compare the effects of inhalation in rats and in hamsters following exposures to aerosolised, size-separated fibrils. A new term to characterise para-fibrils is also introduced herein. Respirable-sized, fibre-shaped particulates (RFP) have recently been described as the respirable component of para-aramid fibres (ECETOC). Para-aramid fibres are nonrespirable, having a diameter of 12-15 urn. Henceforth, the term RFP will be used interchangeably with the term p-aramid and these denote the respirable-sized fraction of para-aramid fibres. Rats were exposed nose-only for 2 weeks to design fibre concentrations of 400 and 750 f ml RFP or chrysotile asbestos fibres, while hamsters were exposed whole-body to for 2 weeks to design fibre concentrations of 350 and 700 f ml. Following completion of exposures, the lungs of sham and fibre-exposed rats were evaluated immediately after (time 0), as well as 5 days, 1, 3, 6 and 12 months postexposure. The hamster study is currently ongoing; thus, sham and fibril-exposed animals have been evaluated immediately after 2 week exposures as well as 10 days, 1 and 3 months postexposure. The major endpoints of this study are assessments of (1) fibre deposition and clearance; (2) biopersistence of inhaled fibrils; and (3) cellular proliferation of terminal bronchiolar, pulmonary parenchymal, subpleural and mesothelial cells. The mean fibre concentrations over the 2 week period were 458 and 782 f ml for chrysotile asbestos; mean RFP concentrations were 419 and 772 f mP 1 for nose-only exposed rats and 358 and 659 f ml for exposed hamsters. p-Aramid fibrils were recovered from the lungs of exposed animals using a diluted Clorox digestion technique. Fibre lung burdens for the two groups of exposed rats immediately after exposure were 4.8 x 10 and 7.6 x 10 fibrils/lung, respectively; similar numbers of chrysotile fibres > 5 urn were recovered from the lungs of asbestos exposed rats. The lung burden for the high dose hamster group was approximately 8 x 10 fibrils/lung. Biopersistence studies in rats indicated that there was an initial decrease (relative to asbestos) in the numbers of cleared fibrils and this corresponded to a reduction in the mean lengths of inhaled fibrils during this time period, signifying biodegradability of inhaled fibrils. Clearance of fibrils was more rapid after the first month