An overload hypothesis for pulmonary clearance of UICC amosite fibres inhaled by rats.

Bolton, Robert; Jones, A. D.; Addison, J.; Beckett, S T

doi:10.1136/oem.40.3.264

Cited by 53 publications

(35 citation statements)

References 30 publications

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“…To avoid double counting, different fiber length limits were set for the counts at each magnification. The size distribution was approximated to log-normal for all fiber types and was classified by the limits for length and diameter of 10,50 …”

Section: Methodsmentioning

confidence: 99%

Comparative investigations of the biodurability of mineral fibers in the rat lung.

Muhle

Bellmann

Pott

1994

Environ Health Perspect

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The biodurability of various glass fibers, rockwool, and ceramic fibers was examined in rat lungs and compared with natural mineral fibers. Experiments were based on studies that have shown that the biodurability of fibers is one of the essential factors of the carcinogenic potency of these materials. Sized fractions of fibers were instilled intratracheally into Wistar rats. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM) or careful examination of the fiber suspension before treatment. After serial sacrifices up to 24 months after treatment, the fibers were analyzed by SEM following low temperature ashing of the lungs. Parameters measured included number of fibers, diameter, and length distribution at the various sacrifice dates, so that analyses could be made of the elimination kinetics of fibers from the lung in relation to fiber length (FL). Size selective plots of the fiber elimination correlated with fiber diameters enables the mechanism of the fiber elimination (dissolution, fiber breakage, physical clearance) to be interpreted. The half-time of fiber elimination from the lung ranges from about 10 days for wollastonite to more than 300 days for crocidolite. The biodurability of man-made vitreous fibers (MMVF) is between these values and is dependent on the chemical composition of the fibers and the diameter and length distribution. Results indicate that the in vivo durability of glass fibers is considerably longer than expected from extrapolation of published data on their in vitro dissolution rates.

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Section: Methodsmentioning

confidence: 99%

Comparative investigations of the biodurability of mineral fibers in the rat lung.

Muhle

Bellmann

Pott

1994

Environ Health Perspect

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“…Observations of the clearance of amosite ®bers in inhalation experiments on rats led to the ®rst use of the term`o verload'' [1]. The ®rst universally accepted de®nition of dust or particle overloading was provided by Morrow [38]:``Overload is a condition of the lungs of rats (and of some other species) caused by an excessive accumulation of a relatively inert insoluble dust, at ®rst characterized by an increased dust retention.…”

Section: Animal Experimental Studiesmentioning

confidence: 99%

Exposure to carbon black: a cancer risk?

Brockmann

Fischer

Müller

1998

International Archives of Occupational and Environmental Health

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Lung cancer is one of the most serious health problems in the industrial nations and is therefore of great public and scientific interest. Although inhalative cigarette smoking is without doubt the main cause for the increasing frequency of lung cancer, during recent years there has been more and more public interest in other substances in the environment or at the work place that are assumed to be potentially carcinogenic especially due to experiences with fibrous particles such as asbestos and their effects. Enhanced attention is also directed to inert or nuisance dusts such as carbon black. Evaluation of the possibly increased risk for humans should first be based on exact epidemiology data. In the absence of those data--as in the case of carbon black--experimental data in animals serve as the point of orientation, especially results gained in rats in long-term inhalation studies. Pathologic anatomy investigations of human lungs under similar exposure conditions, however, render results quite different from those obtained in rats and, thus, preclude ready interpretation of animal results to human risk assessment. This is particularly true for the development of lung tumors in rats under overload conditions as well as for certain tumor types not observed in human lung tissues. It is therefore quite understandable that many researchers propose to interpret the changes observed in rat lung tissues after inhalation of carbon black as rat-specific reaction mechanisms that cannot be applied to human tissues, which in the past have led to the wrong conclusions regarding human risk assessment due, among other factors, to incorrect experimental design and inaccurate nomenclature of tumorous lesions in rats.

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“…fibrosis and cancer'. Although the observation had been made in the 1960s and 1970s that high dust con centrations in animal studies could cause lung changes, the association between excessive exposure and 'overload' was most clearly described by Bolton et al [3] in a rodent study using amosite asbestos. About this time researchers reported the involvement of alveolar macrophages and dust loading related to pulmonary inflammatory re sponses [4].…”

Section: Experimental Findingsmentioning

confidence: 99%

The 'Particle Overload' Phenomenon and Human Assessment

Levy¹

1995

Indoor Built Environ

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The last decade has seen the publication of an increasing number of scientific papers in which lung tumours have been induced in rats following chronic exposure by inhalation to a range of insoluble, respiratory-sized particulate dusts which hitherto have been considered to be biologically inert. Such substances include talc, titanium dioxide, volcanic ash and carbon black. Such particles have generally been considered ‘nuisance dusts’, possibly capable of eliciting fibrogenic changes, but not cancer. The one feature that all these studies in rats have in common is that the experimental exposures induced ‘overloading’ of the lung as evidenced by an increase in lung weight, retention of particles and chronic and marked inflammatory changes. All of this was preceded by an underlying ‘overloading’ of the alveolar macrophages to the point where they stopped removing particles from the lung. This can happen in a number of experimental species, but it is only the rat that appears to respond with lung tumours as an additional pathological response. This points to the lung tumours being a rat-specific response and thus not a very useful end-point for human risk evaluation for such biologically inert particles. In support of this view is the remarkable observation that in the one well-studied occupational group that routinely has ‘particle overload’ in the lungs, namely coal miners, there is no evidence that they experience an excess risk of lung cancer.

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An overload hypothesis for pulmonary clearance of UICC amosite fibres inhaled by rats.

Cited by 53 publications

References 30 publications

Comparative investigations of the biodurability of mineral fibers in the rat lung.

Comparative investigations of the biodurability of mineral fibers in the rat lung.

Exposure to carbon black: a cancer risk?

The 'Particle Overload' Phenomenon and Human Assessment

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