title: Biodegradability of para-aramid respirable-sized fiber-shaped particulates (RFP) in human lung cells.
abstract: Using both in vivo (inhalation) and in vitro (cell culture) studies, we previously reported that p-aramid respirable fibers (RFP--defined as respirable-sized fiber-shaped particulates) are biodegraded in lungs and lung cells of rats following exposures. The current studies were undertaken to determine whether shortening mechanisms of p-aramid RFP biodegradability are also operative in human lung cells. Cultures of human A549 lung epithelial cells (A549), primary alveolar macrophages (HBAL) (collected via bronchoalveolar lavage [BAL]) from volunteers), and co-cultures (Co) of the A549 and HBAL were incubated with p-aramid RFP for either 1 h, 1 day, or 1 week to assess RFP shortening. Lengths of RFP were measured using scanning electron microscopy (SEM) following fixation, digestion of culture tissue components, and processing. Similar to findings using rat lung cells, only slight RFP shortening was measured in A549 cultures at 1-day and 1-week post-incubation. More importantly, in HBAL and Co groups, greater transverse cleavage of p-aramid RFP was measured at 1-day and 1-week postexposure compared to 1-h HBAL or Co groups, or in any A549 groups. In contrast, cellulose RFP, a biopersistent reference control fiber, were not measurably shortened under similar circumstances. Second, p-aramid RFP were incubated either with phosphate-buffered saline (PBS), or acellular BAL fluids from human volunteers or rats and processed for SEM analysis of RFP lengths. Mean lengths of p-aramid RFP incubated with human or rat BAL fluids were substantially decreased compared to PBS. Similar to our findings with rat lung cells, components of human lung fluids coat the p-aramid RFP as a prerequisite for subsequent enzymatic cleavage by human phagocytic lung cells and this finding reinforces the concept that inhaled p-aramid RFP are likely to be biodegradable in the lungs of humans.
authors.affiliation: DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714-0050, 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: J D
authors.initials: JD
authors.lastname: Stonehuerner
authors.forename: A J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: T R
authors.initials: TR
authors.lastname: Webb
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000818:Animals; D001673:Biodegradation, Environmental; D001711:Biotransformation; D018893:Bronchoalveolar Lavage; D002460:Cell Line; D002482:Cellulose / Q000737:chemistry / Q000493:pharmacokinetics / Q000648:ultrastructure; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats
chemical_list: C039578:Kevlar Aramid fibers; D011108:Polymers; D002482:Cellulose