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

• Published in: Environmental health perspectives 1997-09, Vol.105 (suppl 5), p.1219-1222
• Main Authors: Warheit, David B., Snajdr, Suzanne I., Hartsky, Mark A., Frame, Steven R.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Animals; Antimetabolites - toxicity; Asbestos; Asbestos, Serpentine - administration & dosage; Asbestos, Serpentine - pharmacokinetics; Asbestos, Serpentine - toxicity; Biodegradation; Biodegradation, Environmental; Bromodeoxyuridine - toxicity; Carcinogens - administration & dosage; Carcinogens - pharmacokinetics; Carcinogens - toxicity; Cell Division - drug effects; Cell growth; Chemical hazards; Cricetinae; Hamsters; Inhalation; Lung - metabolism; Lung - pathology; Lungs; Male; Mesocricetus; Models/Mechanisms; Polymers - administration & dosage; Polymers - pharmacokinetics; Polymers - toxicity; Rats; Rats, Inbred Strains; Solar fibrils; Toxicology
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.97105s51219

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× 107and 7.6× 107fibrils/lung, with similar numbers of chrysotile fibers > 5 μm recovered from the lungs of asbestos-exposed rats. In comparison, 1.4× 106fibrils/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.