Chronic Inhalation Toxicity of a Kaolin-Based Refractory Ceramic Fiber in Syrian Golden Hamsters

Abstract

Kaolin-based refractory ceramic fiber (RCF) is a man-made vitreous fiber used primarily in industrial high-temperature applications, especially for insulation of furnaces and kilns. Because of its increasing use and potential for human exposure, a chronic toxicity/ carcinogenicity inhalation study was conducted in Syrian golden hamsters. Two groups of 140 weanling male hamsters were exposed via nose-only inhalation to either HEPA-filtered air (chamber controls) or 30 mg/m³ (-220 fibers/cm³) of “size-selected” RCF fibers (1 µm in diameter and -25 /jm in length) for 6 h/day, 5 dayslwk for 18 mo. They were then held unexposed until -20% survival (20 mo). A positive control group of 80 hamsters was exposed to 10 mg/m³ chrysotile asbestos (0.09 µm average diameter and 2.2 µm average length). Groups of 3 hamsters were sacrificed at 3, 6, 9, 12, 15, and 18 mo to follow the progression of lesions. Additional groups of 3 hamsters were removed from exposure at 3, 6, 9, and 12 mo and were held until 18 mo (recovery groups). Treatment-related lesions were restricted to the lungs. RCF exposure resulted in macrophage infiltration, bronchiolization of proximal alveoli, and microgranuloma formation by 3 mo of exposure. Interstitial and focal pleural fibrosis were observed at 6 mo. The pulmonary lesions progressed in severity until 12 mo after which they plateaued. In contrast, pleural fibrosis progressed until the end of the study. In recovery animals, there was no further progression of either pulmonary or pleural lesions following cessation of exposure. While no pulmonary neoplasms were observed in the RCF exposed hamsters, 42 of 102 (41.2%) had pleural mesotheliomas. A greater severity of fibrosis was observed in the lungs of the positive (chrysotile asbestos) controls, but no neoplasms were observed in either the lung or pleura. No neoplasms were found in the lungs or pleura of the chamber air controls.