title: Lung proliferative and clearance responses to inhaled para-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibers.
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 x 10(7) and 7.6 x 10(7) fibrils/lung, with similar numbers of chrysotile fibers > 5 microns recovered from the lungs of asbestos-exposed rats. In comparison, 1.4 x 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.
authors.affiliation: DuPont Haskell Laboratory, Newark, DE 19714, USA. david.b.warheit@usa.dupont.com
authors.forename: D B
authors.initials: DB
authors.lastname: Warheit
authors.forename: S I
authors.initials: SI
authors.lastname: Snajdr
authors.forename: M A
authors.initials: MA
authors.lastname: Hartsky
authors.forename: S R
authors.initials: SR
authors.lastname: Frame
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000963:Antimetabolites / Q000633:toxicity; D017632:Asbestos, Serpentine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D001673:Biodegradation, Environmental; D001973:Bromodeoxyuridine / Q000633:toxicity; D002273:Carcinogens / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008647:Mesocricetus; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000963:Antimetabolites; D017632:Asbestos, Serpentine; D002273:Carcinogens; C039578:Kevlar Aramid fibers; D011108:Polymers; D001973:Bromodeoxyuridine