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Long-Term Toxicity of Naturally Occurring Asbestos in Male Fischer 344 Rats
Citation:
Cyphert, J., M. McGee, A. Nyska, M. Schladweiler, U. Kodavanti, AND S. Gavett. Long-Term Toxicity of Naturally Occurring Asbestos in Male Fischer 344 Rats. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, 79(2):49-60, (2016).
Impact/Purpose:
The long-term toxicity of 4 samples of naturally occurring asbestos (NOA) fibers including Sumas Mountain chrysotile (SM), Libby amphibole (LA), El Dorado Hills tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON) was evaluated 15 months after exposure in rats. Results indicate that all NOA except ON have some potential for long-term toxicity, including pulmonary fibrosis or carcinogenesis. The results are informative for risk assessment efforts at EPA remediation sites in Regions 8, 9, and 10. Further research is needed to determine the characteristics of site-specific asbestos which are most important for chronic health effects.
Description:
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 (LOH) activity and protein levels, while high-dose SM increased y-glutamyltransferase 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.
