Deposition and Clearance Modeling of Inhaled Kaolin Refractory Ceramic Fibers (RCF) in Hamsters—Comparison Between Species

Abstract

A dosimetry model of refractory ceramic fibers in the hamster lung has been developed based upon the data from recent exposure and recovery experiments conducted by the Research and Consulting Company in Geneva, Switzerland. The modeling results of hamsters showed significant differences from those of an earlier study in rats regarding deposition and clearance of these fibers in the lung. Despite smaller airway size of hamsters, alveolar deposition per breathing cycle in the hamster was found to be higher than that in the rat due to the higher upper airway deposition in rats. The calculated mean deposited fiber size was found to be larger in the hamster, and there were more thin and long fibers deposited in the hamster lung. It was also found that alveolar clearance of refractory ceramic fibers was faster in the hamster. The clearance rate in the hamster did not appear to be fiber size dependent but it varied with lung burden. The higher clearance rate in the hamster resulted in a lower fiber accumulation per unit weight of lung after a long period of exposure. The results of the dosimetry model presented here may contribute to an explanation of different tumorigenic responses observed in the hamster and rat.Recent exposure experiments have shown that hamsters and rats have different tumorigenic responses to kaolin refractory ceramic fibers (RCF) of the same concentration Mast et al., 1994). W h e n these animals inhaled at an exposure concentration of 30 mg/m3, the maximum tolerated dose, 42% of the exposed hamsters developed mesothe-

Refractory ceramic fiber (RCF) toxicity and epidemiology: A review

“…Subsequent analyses of the RCF RCC data were consistent with the hypothesis that "lung overload" occurred (Bellmann et al, 2001;Brown et al, 2000Brown et al, , 2005Mast et al, 2000aMast et al, , 2000bYu and Oberdöster, 2000;Yu et al, 1994aYu et al, , 1994bYu et al, , 1995aYu et al, , 1995bYu et al, , 1996, an unintended artifact of the method used to prepare RCFs for testing and the ratio of particles to fibers was not representative of that found in workplace samples (and significantly higher than those for other SVFs tested). Lung overload may result in retarding the rate of fiber clearance, inflammation, and tumors.…”

Survey of the Biological Effects of Refractory Ceramic Fibres: Overload and Its Possible Consequences

“…Although the study of mixed-length fibre retention will dilute any effect of reduced macrophage clearance, several analyses of RCF burdens in the RCC experiments indicate that overload probably occurred (Yu et al, 1994(Yu et al, , 1995(Yu et al, , 1996Yu and Oberdörster, 2000;Mast et al, 2000a,b). Total particulate volume/lung (mm 3 ) AM clearance rate (1/day) Fig.…”

“…The research component of this programme has included both short and long-term animal studies, development of dosimetry and risk analysis models (e.g. Yu et al, 1995Yu et al, , 1996Moolgavkar et al, 1999Moolgavkar et al, , 2000, development of less biopersistent high temperature fibre wools, industrial hygiene studies of occupational exposure (e.g. Maxim et al, 1994Maxim et al, , 1997Maxim et al, , 1998aMaxim et al, ,b, 2000aRice et al, 1997) and mortality and morbidity studies of worker cohorts in Europe (Trethowan et al, 1995;Cowie et al, 2001) and the United States (Lockey et al, 1996(Lockey et al, , 2002LeMasters et al, 1994LeMasters et al, , 2003Walker et al, 2002).…”