The importance of fiber biopersistence and lung dose in determining the chronic inhalation effects of X607, RCF1, and chrysotile asbestos in rats.
The chronic inhalation effects in rats of X607 (a rapidly dissolving synthetic vitreous fiber) were compared with those previously reported for RCF1 (a refractory ceramic synthetic vitreous fiber) and chrysotile asbestos. Of primary concern was the importance of biopersistence as a mechanism of fiber toxicity. Fischer rats were exposed to fiber aerosol by nose-only inhalation for 6 h/day, 5 days/week for 2 years. X607 and RCF1 aerosols were similar in concentration (approximately 200 fibers/cc) and average dimensions (approximately 20 x 1 microns). Chrysotile aerosol was higher in concentration (10,600 fibers/cc) and an order of magnitude smaller in average dimensions. Lung fiber deposition after 6 h inhalation was greater for X607 than for RCF1. However, at later time points, fibers/lung (especially long fibers) were much lower for X607 than for RCF1, suggesting less biopersistence for X607. X607 was neither fibrogenic nor tumorigenic and induced only minimal lung cellularity that reversed after exposure was terminated. In contrast, RCF1 and chrysotile asbestos induced pulmonary fibrosis and thoracic neoplasms (chrysotile induced 32% more pulmonary neoplasms than RCF1). Lung deposition and fiber lengths did not explain the toxicologic differences between the three fibers. Fiber biodurability, including chemical and physical parameters, appears to be a major toxicologic determinant here. Chemical analysis of lung fibers revealed rapid leaching of X607 compared to RCF1. In in vitro dissolution tests, X607 underwent rapid dissolution (kdis = 990 ng/cm2/h) and transverse fragmentation, RCF1 dissolved slowly (kdis = 6 ng/cm2/h) and did not fragment, and chrysotile dissolution was negligible (< 0.1 ng/cm2/h).
Hesterberg
T W
TW
Johns Manville Technical Center, Littleton, Colorado, USA.
Hart
G A
GA
Chevalier
J
J
Miiller
W C
WC
Hamilton
R D
RD
Bauer
J
J
Thevenaz
P
P
D000818:Animals; D017632:Asbestos, Serpentine / Q000008:administration & dosage / Q000633:toxicity*; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D002516:Ceramics / Q000633:toxicity*; D019570:Inhalation Exposure; D007616:Kaolin / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000209:etiology*; D019016:Mineral Fibers / Q000633:toxicity*; D009929:Organ Size; D051381:Rats
D017632:Asbestos, Serpentine; D002273:Carcinogens; D019016:Mineral Fibers; C103119:RCF-1 fiber; C116511:X607 fiber; D007616:Kaolin