Clearance of Refractory Ceramic Fibers (Rcf) from the Rat Lung: Development of a Model

This paper provides a review of the relevant literature on refractory ceramic fibers (RCFs), summarizing relevant data and information on the manufacture, processing, applications, potential occupational exposure, toxicology, epidemiology, risk analysis, and risk management. RCFs are amorphous fibers used for high-temperature insulation applications. RCFs are less durable/biopersistent than amphibole asbestos, but more durable/biopersistent than many other synthetic vitreous fibers (SVFs). Moreover, as produced/used, some RCFs are respirable. Toxicology studies with rodents using various exposure methods have shown that RCFs can cause fibrosis, lung cancer, and mesothelioma. Interpretation of these animal studies is difficult for various reasons (e.g., overload in chronic inhalation bioassays). Epidemiological studies of occupationally exposed cohorts in Europe and the United States have demonstrated measurable effects (e.g., mild respiratory symptoms and pleural plaques) but no disease (i.e., no interstitial fibrosis, no excess lung cancer, and no mesothelioma) to date. The RCF industry, working cooperatively with various government agencies in the United States, has developed a comprehensive product stewardship program (PSP) to identify and control risks associated with occupational exposure. One provision of the PSP is the adoption of a voluntary recommended exposure guideline (REG) of 0.5 fibers/milliliter (f/ml). Selected on the basis of prudence and demonstrated feasibility, compliance with the REG should reduce risks to levels between 0.073/1000 and 1.2/1000, based on extrapolations from chronic animal inhalation studies.

Section: Chronic Bioassayssupporting

confidence: 71%

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

Utell

Maxim²

2010

“…To make use of the estimate of A for dose prediction, it is desirable to (Yu et al, 199413) h(M) = a exp(-bM') (day-')…”

Section: Clearance Modeling and Resultsmentioning

confidence: 99%

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

Ding

Zhang

et al. 1995

Self Cite

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-

“…The functional residual capacity (FRC), or lung volume, and breathing condition for rats were not measured in the exper- iment. These parameters are estimated from the following correlations for Fischer rats (Yu et al, 1994;Ding, 1995):…”

Section: Physiological Parametersmentioning

confidence: 99%

A Dosimetry Model of Nickel Compounds in the Rat Lung

Hsieh

Yu²,

Oberdörster³

1999

Experimental data from inhalation studies in rats were used to develop mathematical models of deposition, clearance, and retention kinetics for inhaled Ni compounds (high-temperature [green] NiO, Ni3S2, and NiSO4*6H2O) in the rat lung. For deposition, an updated version of an earlier model (Yu & Xu, 1986) was used in this study. Three major mechanisms of airway deposition-impaction, sedimentation, and diffusion-were considered in the deposition model. In the development of a clearance model, a single compartment model in the lung was used and a general assumption was made that the clearance of the insoluble and moderately soluble nickel compounds (high-temperature [green] NiO and Ni3S2, respectively) depends highly on the volume of retained particles in the lungs. For the highly soluble nickel compound (NiSO4 *6H2O), the clearance rate coefficient was assumed to depend on the retained particle mass and total alveolar surface. The retention half-time, however, was found to increase with the lung burden for high-temperature (green) NiO and NiSO4*6H2O particles but decrease with the lung burden for Ni3S2 particles.