title: Long-term toxicity of naturally occurring asbestos in male Fischer 344 rats.
abstract: Naturally occurring asbestos (NOA) fibers are found in geologic deposits that may be disturbed by mining, earthworks, or natural processes, resulting in adverse health risks to exposed individuals. The toxicities of Libby amphibole and NOA samples including Sumas Mountain chrysotile (SM), El Dorado tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON) were compared in male Fischer 344 (F344) rats 15 mo after exposure. Rat-respirable fractions of LA and SM displayed greater mean lengths and aspect ratios than ED and ON. After a single intratracheal (IT) instillation (0.5 or 1.5 mg/rat), persistent changes in ventilatory parameters and a significant increase in lung resistance at baseline and after methacholine aerosol dosing were found only in rats exposed to 1.5 mg SM. High-dose ED significantly elevated bronchoalveolar lavage lactate dehydrogenase (LDH) activity and protein levels, while high-dose SM increased γ-glutamyl transferase and LDH activities. A moderate degree of lung interstitial fibrosis after exposure to 1.5 mg SM persisted 15 mo after exposure, unchanged from previous findings at 3 mo. LA induced mild fibrosis, while ED and ON produced minimal and no apparent fibrosis, respectively. Bronchioloalveolar carcinoma was observed 15 mo after exposure to LA or ED. Data demonstrated that SM, given by bolus IT dosing on an equivalent mass basis, induced greater pulmonary function deficits, airway hyperresponsiveness, and interstitial fibrosis than other NOA, although unlike LA and ED, no apparent evidence for carcinogenicity was found. All NOA samples except ON cleavage fragments produced some degree of long-term toxicity.
authors.affiliation: a Curriculum in Toxicology , University of North Carolina School of Medicine , Chapel Hill , North Carolina , USA.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Cyphert
authors.affiliation: b Oak Ridge Institute for Science and Education , Oak Ridge , Tennessee , USA.
authors.forename: Marie A
authors.initials: MA
authors.lastname: McGee
authors.affiliation: c National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park , North Carolina , USA.|d Sackler School of Medicine , Tel Aviv University , Timrat , Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.affiliation: e Environmental Public Health Division , National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency , Research Triangle Park , North Carolina , USA.
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.affiliation: e Environmental Public Health Division , National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency , Research Triangle Park , North Carolina , USA.
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
authors.affiliation: e Environmental Public Health Division , National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency , Research Triangle Park , North Carolina , USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gavett
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D017636:Asbestos, Amphibole; D017632:Asbestos, Serpentine; D001195:Asbestosis / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D019570:Inhalation Exposure; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012129:Respiratory Function Tests; D016019:Survival Analysis; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D017636:Asbestos, Amphibole; D017632:Asbestos, Serpentine; D016085:Bronchoconstrictor Agents; D002273:Carcinogens; D016210:Methacholine Chloride; C036431:ferroactinolite; D001194:Asbestos; C005846:tremolite; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase