title: Comparison of Calidria chrysotile asbestos to pure tremolite: inhalation biopersistence and histopathology following short-term exposure.
abstract: The differences between chrysotile asbestos, a serpentine mineral, and amphibole asbestos have been debated extensively. Many studies have shown that chrysotile is cleared from the lung more rapidly than amphibole. In order to quantify the comparative clearance of chrysotile and the amphibole asbestos tremolite, both fibers were evaluated in an inhalation biopersistence study that followed the European Commission recommended guidelines. In addition, the histopathological response in the lung was evaluated following the short-term exposure. This article presents the results of this study through 90 days after cessation of exposure. Following the termination of the study, a subsequent article will provide the complete results through 12 mo after cessation of exposure. In order to quantify the dynamics and rate by which these fibers are removed from the lung, the biopersistence of a sample of commercial grade chrysotile from the Coalinga mine in New Idria, CA, of the type Calidria RG144 and of a long-fiber tremolite were studied. For synthetic vitreous fibers, the biopersistence of the fibers longer than 20 microm has been found to be directly related to their potential to cause disease. This study was designed to determine lung clearance (biopersistence) and the histopathological response. As the long fibers have been shown to have the greatest potential for pathogenicity, the aerosol generation technique was designed to maximize the number of long respirable fibers. The chrysotile samples were specifically chosen to have 200 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. These longer fibers were found to be largely composed of multiple shorter fibrils. The tremolite samples were chosen to have 100 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. Calidria chrysotile fibers clear from the lung more rapidly (T1/2, fibers L > 20 microm = 7 h) than any other commercial fiber tested including synthetic vitreous fibers. With such rapidly clearing fibers, the 5-day exposure would not be expected to result in any pathological change in the lung, and the lungs of animals that inhaled Calidria chrysotile showed no sign of inflammation or pathology and were no different than the lungs of those animals that breathed filtered air. Following this 5-day exposure to tremolite, the tremolite fibers once deposited in the lung parenchyma do not clear and almost immediately result in inflammation and a pathological response in the lung. At the first time point examined, 1 day after cessation of exposure, inflammation was observed and granulomas were already formed. By 14 days postexposure these microgranulomas had turned fibrotic, and by 90 days postexposure the severity of the collagen deposits had increased and interstitial fibrosis was observed in one of the rats. These findings provide an important basis for substantiating both kinetically and pathologically the differences between chrysotile and the amphibole tremolite. As Calidria chrysotile has been certified to have no tremolite fiber, the results of the current study together with the results from toxicological and epidemiological studies indicate that this fiber is not associated with lung disease.
authors.affiliation: Consultant in Toxicology, 40 chemin de la Petite-Boissiere, 1208 Geneva, Switzerland. davidb@itox.ch
authors.forename: David M
authors.initials: DM
authors.lastname: Bernstein
authors.forename: Jörg
authors.initials: J
authors.lastname: Chevalier
authors.forename: Paul
authors.initials: P
authors.lastname: Smith
mesh_terms: D000336:Aerosols; D000818:Animals; D017636:Asbestos, Amphibole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D017632:Asbestos, Serpentine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D019570:Inhalation Exposure; D008168:Lung / Q000473:pathology*; D008297:Male; D019016:Mineral Fibers; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology; D051381:Rats
chemical_list: D000336:Aerosols; D017636:Asbestos, Amphibole; D017632:Asbestos, Serpentine; D019016:Mineral Fibers; C005846:tremolite