Retention Modeling of Refractory Ceramic Fibers (RCF) in Humans

Yu, C.P.; Ding, Yuanyuan; Zhang, L.; Oberdörster, G.; Mast, Richard; Maxim, Laura; Utell, Mark J.

doi:10.1006/rtph.1996.1064

Cited by 18 publications

(4 citation statements)

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“…( 104 ) Models of fiber cle-arance from the respiratory tract in rats have been developed; ( 101 , 103 , 104 ) and similar model structures are now addressing fiber deposition and clearance in humans. ( 49 , 102 ) The latter model shows different regional dose estimates by fiber properties and breathing patterns. ( 49 , 97 )…”

Section: Agent-specific Dosimetry and Model Selectionmentioning

confidence: 99%

Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

Kuempel

Sweeney

Morris

et al. 2015

Journal of Occupational and Environmental Hygiene

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The purpose of this article is to provide an overview and practical guide to occupational health professionals concerning the derivation and use of dose estimates in risk assessment for development of occupational exposure limits (OELs) for inhaled substances. Dosimetry is the study and practice of measuring or estimating the internal dose of a substance in individuals or a population. Dosimetry thus provides an essential link to understanding the relationship between an external exposure and a biological response. Use of dosimetry principles and tools can improve the accuracy of risk assessment, and reduce the uncertainty, by providing reliable estimates of the internal dose at the target tissue. This is accomplished through specific measurement data or predictive models, when available, or the use of basic dosimetry principles for broad classes of materials. Accurate dose estimation is essential not only for dose-response assessment, but also for interspecies extrapolation and for risk characterization at given exposures. Inhalation dosimetry is the focus of this paper since it is a major route of exposure in the workplace. Practical examples of dose estimation and OEL derivation are provided for inhaled gases and particulates.

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Section: Agent-specific Dosimetry and Model Selectionmentioning

confidence: 99%

Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

Kuempel

Sweeney

Morris

et al. 2015

Journal of Occupational and Environmental Hygiene

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show abstract

“…In a human lung kinetic model, the inclusion of a sequestration process (thought to include particle interstitialization) was required to adequately predict the end-of-life lung burdens in U.S. and United Kingdom coal miners, whereas a rat-based overload model provided a poor fit to these human data (Kuempel, 2000;Tran & Buchanan, 2000). In a one-compartment kinetic lung model, based on both human and rat extrapolated data, overloading was predicted not to occur in humans at the estimated fiber exposures and observed lung burdens in three individuals (Yu et al, 1997).…”

Section: Toxicokinetics Of Particles and Fibersmentioning

confidence: 99%

Toxicity of Fibers and Particles—report of the Workshop Held in Munich, Germany, 26–27 October 2000

Greim¹,

Borm²,

Schins³

et al. 2001

Inhalation Toxicology

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110

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“…It assumes that the sensitivity of the two species, at the cell level, is identical. Moolgavkar et al relied on the Yu et al dosimetry models (Yu et al, 1995(Yu et al, , 1997 to estimate the human lung burden resulting from an exposure to 1 fiber/ml. The initiation rate for humans was then applied to this lung burden using Markov-chain Monte Carlo methods to estimate the unit risk.…”

Section: A Dose-response Model For Rcf 1107mentioning

confidence: 99%

“…In a series of reports, Yu and his colleagues (Yu et al, 1995(Yu et al, , 1997 developed models for predicting the number of RCF fibers retained in the human lung for a given exposure. These models explicitly consider fiber clearance due to their dissolution in the lung environment, their tendency to break under lung forces, and macrophage clearance as a function of fiber dimensions.…”

Section: Extrapolation From High To Low Dosementioning

confidence: 99%

A Dose-Response Model for Refractory Ceramic Fibers

Turim¹,

Brown²

2003

Inhalation Toxicology

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Refractory ceramic fibers (RCFs) are man-made vitreous fibers commonly used in insulation applications above 1000 degrees C. Although they have been subjected to considerable toxicologic evaluation, only the pooled results from two rat inhalation studies provide data that may be suitable for performing a numerical risk assessment. Even in these inhalation studies, good evidence exists that the maximum tolerated dose (MTD) was exceeded and that pulmonary overload occurred, a condition that will cause tumors whatever the dust responsible. Indeed, a significant yield of tumors was only obtained at the highest dose tested. If these results are omitted, there is no statistically significant evidence of carcinogenicity within the RCF results. Although there is little evidence that overload-related tumors are relevant to human risk, we adopted a conservative approach to obtain the estimates of risk regardless of overload, using a biologically based model, the two-stage clonal expansion model, as well as various statistical models, including the benchmark dose model. We argue that the data favor the use of a biologically based model, which gives the best fit when the highest dose RCF exposures are omitted. Continuing with this model, we show that available data from the RCF experiment, less outliers, coupled with results from other experiments with man-made mineral fibers (MMVFs), demonstrate that all MMVFs are potentially carcinogenic, with any risk mediated by the fibers' biopersistence. Application of this "all MMVF data set" model yields a maximum likely estimate for RCF excess unit risk of 4.6 x 10(-5) (95% upper confidence limit = 9.2 x 10(-5) per fiber/ml). This implies that the risk from occupational exposure to RCFs at 1 fiber/ml for a typical working lifetime would not exceed 10(-4).

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Retention Modeling of Refractory Ceramic Fibers (RCF) in Humans

Cited by 18 publications

References 1 publication

Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

Toxicity of Fibers and Particles—report of the Workshop Held in Munich, Germany, 26–27 October 2000

A Dose-Response Model for Refractory Ceramic Fibers

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