title: Attenuation of perfluoropolymer fume pulmonary toxicity: effect of filters, combustion method, and aerosol age.
abstract: Thermal decomposition products of some perfluorinated polymers are toxic to experimental animals in small-scale combustion toxicity tests; the toxicity is dependent upon the heating procedure, combustion temperature, and other experimental conditions. In the current studies we investigated the time course of fume generation and exposure on pulmonary effects in rats following a 30-min exposure to perfluoropolymer decomposition products (i.e., fume concentration = 0.2 mg/m3 of tetrafluoroethylene/hexafluoropropylene copolymer (FEP)) pyrolyzed with either static or dynamic airflows. In the first set of experiments, five different groups of rats were exposed to FEP fumes in a static combustion toxicity test system. Three groups were exposed to unfiltered FEP fumes during 0- to 15-, 15- to 30-, and 0- to 30-min intervals, respectively, and one to a filtered (particle-free) atmosphere of combusted FEP for 30 min. Sham-exposed rats constituted the control group. Immediately after exposure, the rats were sacrificed and their lungs weighed and lavaged or perfused to assess indices of cytotoxicity. Our results showed that lung weights, markers of inflammation, and pulmonary hemorrhage and alkaline phosphatase, beta-glucuronidase, lactate dehydrogenase, and protein levels in bronchoalveolar lavage fluids were significantly elevated in all unfiltered FEP-exposed groups compared to those in either the rates exposed through filters or controls (P less than 0.01). In a second set of experiments using a dynamic pyrolysis toxicity test system, rats were exposed for 30 min to FEP-pyrolyzed fumes which were either freshly generated or aged for 1 or 5 min prior to delivery to the animal's breathing zone. Subsequently, lung cytotoxicity parameters were measured. Rats exposed directly to the fresh fumes demonstrated toxic effects consistent with those described above (P less than 0.01), but the pulmonary toxicity of aged (i.e., 1 or 5 min delay) FEP fumes was diminished in a time-dependent manner, suggesting that the toxicant was unstable. Histopathological studies correlated with biochemical results and revealed that inhalation of unfiltered or freshly generated FEP fumes produced a severe lung injury characterized by the development of alveolar and interstitial edema, intraalveolar hemorrhage, congestion, and fibrin deposition. Electron microscopy studies demonstrated severe damage to terminal bronchiolar cells and detachment of Type I epithelial and endothelial cells in pulmonary regions. The severity of pathology observed in lungs of rats exposed to 1-min aged fumes was intermediate between unfiltered/unaltered fume-exposed animals and sham controls. The results of these studies demonstrate that the lung toxicity of perfluoropolymer fumes is associated with the aerosol phase generated in perfluoropolymer pyrolysis.
authors.affiliation: Central Research and Development Department, Haskell Laboratory for Toxicology and Industrial Medicine, E.I. du Pont de Nemours and Company, Inc., Newark, Delware 19714.
authors.forename: D B
authors.initials: DB
authors.lastname: Warheit
authors.forename: W C
authors.initials: WC
authors.lastname: Seidel
authors.forename: M C
authors.initials: MC
authors.lastname: Carakostas
authors.forename: M A
authors.initials: MA
authors.lastname: Hartsky
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000201:enzymology; D005466:Fluorocarbons / Q000633:toxicity*; D006470:Hemorrhage / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009929:Organ Size; D010587:Phagocytosis; D011108:Polymers / Q000633:toxicity*; D011138:Polytetrafluoroethylene / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D001617:beta-Glucosidase / Q000378:metabolism
chemical_list: D005466:Fluorocarbons; D011108:Polymers; D011138:Polytetrafluoroethylene; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D001617:beta-Glucosidase