Determinants of the pathogenicity of man-made vitreous fibers (MMVF).
OBJECTIVE
A number of man-made vitreous fibers (MMVF) have been developed over the years to replace asbestos fibres in its uses as insulating material. Concerns have been raised that these man-made fibers may also pose a significant health hazard when inhaled during their manufacture and application. As will be discussed in this brief overview, dose, dimension and durability of fibrous particles are key parameters with respect to the induction of adverse pulmonary effects, including carcinogenicity as well as non-cancer effects. In particular, fiber biopersistence plays a most important role for pulmonary pathogenicities, and consequently biopersistence receives greatest attention in the search of new fibrous materials.


RESULTS
Tests to evaluate fiber biopersistence include the administration of fibers by a short-term inhalation (5 days) or intratracheal instillation into rats. Advantages of the inhalation methodology include the even distribution throughout the lung administered by a physiological process. A disadvantage of this method is the limited respirability of long fibers in the rat whereas they are well respirable by humans. Such long fibers ( > 20 microm) have the greatest potential for tumorigenicity and need special consideration in connection with the evaluation of fiber biopersistence. Enrichment of the inhaled aerosol by these long fibers needs to be considered in order to deposit enough of them in the lower respiratory tract of the rat. In contrast, the advantage of the instillation technique is that these long fibers can be delivered to the lung. However, the major disadvantages of intratracheal instillations are the potential of the administered fibers to form clumps and aggregates in the airways and the induction of a major inflammatory response when high-bolus doses are administered. This could influence fiber dissolution in the lungs significantly.


CONCLUSIONS
At the same delivered lung dose, a fiber of low biopersistency has the least effect and is, therefore, less likely to induce lung or pleural tumors even under chronic exposure conditions. Respective animal studies with more fibers of different biopersistence have confirmed this general principle. It is very important that, when evaluating and interpreting fiber effects observed in experimental animals, species differences with respect to respirability, lung retention and mechanisms of responses are considered.
Oberdörster
G
G
University of Rochester Medical Center, Department of Environmental Medicine, Rochester, NY 14642, USA. gunter_oberdorster@urmc.rochester.edu
D000818:Animals; D001711:Biotransformation; D002516:Ceramics / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D016273:Occupational Exposure / Q000009:adverse effects*; D010316:Particle Size; D011108:Polymers / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D012142:Respiratory Tract Neoplasms / Q000209:etiology
D011108:Polymers