title: Biodegradability of inhaled p-aramid respirable fiber-shaped particulates (RFP): mechanisms of RFP shortening and evidence of reversibility of pulmonary lesions.
abstract: These studies elucidated mechanisms of inhaled p-aramid respirable fiber-shaped particulates (RFP) biodegradation in the lungs of exposed rats and hamsters. We postulate that lung fluids coat/activate inhaled p-aramid RFP which deposits in the lung and promote enzymatic attack and consequent shortening. 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 techniques. In vivo, the enzyme but not the KOH solution produced shortening of p-aramid but not cellulose RFP recovered from the lungs. For in vitro studies, the two RFP-types were incubated with BAL fluids and underwent simulated digestions; also rat lung epithelial cells, macrophages or co-cultures were incubated with p-aramid and digested at 1, 24, or 168 h postexposure. The results of in vitro acellular studies demonstrated that only p-aramid RFP incubated in BAL fluids and digested by the enzyme method were shortened. In vitro cellular studies demonstrated a shortening of p-aramid RFP in macrophages and co-cultures but not in lung epithelial cells at 24 h and 1 week postexposure. These results demonstrate that lung fluids coat and catalyze the p-aramid RFP as a prelude for shortening and describe a likely mechanism for the biodegradability of inhaled p-aramid RFP in the lungs of exposed animals.
authors.affiliation: DuPont Haskell Laboratory, P.O. Box 50, Elkton Road, Newark, DE, USA. david.b.warheit@usa.dupont.com
authors.forename: D B
authors.initials: DB
authors.lastname: Warheit
authors.forename: K L
authors.initials: KL
authors.lastname: Reed
authors.forename: K E
authors.initials: KE
authors.lastname: Pinkerton
authors.forename: T R
authors.initials: TR
authors.lastname: Webb
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001673:Biodegradation, Environmental; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D018920:Coculture Techniques; D004798:Enzymes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006878:Hydroxides / Q000737:chemistry; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011108:Polymers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D017680:Potassium Compounds / Q000737:chemistry; D051381:Rats; D013997:Time Factors
chemical_list: D004798:Enzymes; D006878:Hydroxides; C039578:Kevlar Aramid fibers; D011108:Polymers; D017680:Potassium Compounds; C029943:potassium hydroxide