Biopersistence, Fiber Length, and Cancer Risk Assessment for Inhaled Fibers

Moolgavkar, Suresh H.; Brown, R. C.; Turim, Jay

doi:10.1080/089583701316941294

Cited by 49 publications

(26 citation statements)

References 33 publications

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“…1. Fibre content of lung tissue (burden) for a number of fibre types with different abilities to persist as a function of age for rats exposed under the assumption that 12 fibres/mg of lung was deposited each day of exposure (from Moolgavkar et al, 2001a). Note: X607 is a type of AES wool.…”

Section: Principles Of Fibre Toxicity and The Key Role Of Biopersistencementioning

confidence: 99%

“…The relationship between fibre accumulation and clearance has been modelled (see Fig. 1; Moolgavkar et al, 2001a) and related to calculations of human risk (Moolgavkar et al, 2001b, andBrown, 2003) for fibres with different rates of clearance from the lung. This shows, as might be expected, that the dose to the target tissue increases with the ability to persist and hence accumulate.…”

Section: Principles Of Fibre Toxicity and The Key Role Of Biopersistencementioning

confidence: 99%

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Alkaline earth silicate wools – A new generation of high temperature insulation

Brown¹,

Harrison

2012

Regulatory Toxicology and Pharmacology

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Section: Principles Of Fibre Toxicity and The Key Role Of Biopersistencementioning

confidence: 99%

Section: Principles Of Fibre Toxicity and The Key Role Of Biopersistencementioning

confidence: 99%

Alkaline earth silicate wools – A new generation of high temperature insulation

Brown¹,

Harrison

2012

Regulatory Toxicology and Pharmacology

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“…In fact, it is natural to expect unit risk to scale roughly linearly with weighted half-life in the following sense (see, e.g., Moolgavkar et al, 2001):…”

Section: Risk Of Other Synthetic Vitreous Fibersmentioning

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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“…These findings coupled with the finding of no MMVFs in the lung tissue sample suggest that Case 2's MMVF exposure at Plant 17 or elsewhere did not play a role in this case of carcinoma. However, because the absence of MMVF in lung tissue 30 years after cessation of exposure could be the result of the low biopersistence of RSW fibers in the lung 14,15) , we cannot determine how much MMVF may have been present previously.…”

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confidence: 90%

The Role of Smoking and Exposure to Asbestos and Man-Made Vitreous Fibers in a Questionable Case of Mesothelioma

et al. 2003

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A remaining uncertainty in the U.S. cohort study of man-made vitreous fiber (MMVF) workers is whether asbestos exposure contributed to 10 questionable cases of mesothelioma. We report further details on one case from our previous mesothelioma investigation, including results of a recent lung tissue analysis. Case is a 68 year-old white male employed 1951-54 in a rock/slag wool plant where asbestos-containing products were manufactured. Cause of death was recorded as "mesothelioma, malignant, right pleural cavity" (ICD9: 163.9). Analysis for presence of asbestos bodies identified 18,300 asbestos bodies per gram of wet lung tissue (AB/gm), which greatly exceeds the normal range of 0-20 AB/gm. No MMVFs were identified in this sample. We conclude that this patient's tumor was not a mesothelioma, but a carcinoma possibly arising in the lung or mediastinum, and that this case supports the view that the few suspected mesotheliomas found in the U.S. cohort may have been caused by asbestos exposure.

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Biopersistence, Fiber Length, and Cancer Risk Assessment for Inhaled Fibers

Cited by 49 publications

References 33 publications

Alkaline earth silicate wools – A new generation of high temperature insulation

Alkaline earth silicate wools – A new generation of high temperature insulation

A Dose-Response Model for Refractory Ceramic Fibers

The Role of Smoking and Exposure to Asbestos and Man-Made Vitreous Fibers in a Questionable Case of Mesothelioma

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