Fiber toxicology

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Fiber toxicology

  1. 1. Fiber Toxicology Rhian Cope
  2. 2. Concepts in Fiber ToxicologyClassification Natural Asbestos Amosite (brown) Crocidolite (blue) Amphibole - composed of double chain SiO4 tetrahedra Tremolite “needle like” Anthophyllite Actinolite Chrysotile Serpentine – composed of chains of Si2O5 and forms spirals – long fibers, can be woven Erionite Wollastonite Attapulgite
  3. 3. Crocidolite
  4. 4. Wittenoom - A report by consultants GHD and Parsons Brinckerhoff in November 2006 evaluated the continuing risks associated with asbestos contamination in the town andsurrounding areas and classed the risk to visitors as medium and to residents as extreme.
  5. 5. Concepts in Fiber ToxicologyClassification Synthetic vitreous fibers Fiberglass Mineral wool (slag wool, rock wool) Refractory ceramic fiber Organic fibers
  6. 6. Concepts in Fiber ToxicologyPhysical Properties Key phisical factors are: Length Length Aspect ratio: Diameter Length Short fibers (< 5 μm length) cause no pathology Long fibers (20 μm length) cause considerable pathology Long fibers (20 μm length) cannot be cleared from the lungs by macrophages and have greater biocidal activity
  7. 7. Concepts in Fiber ToxicologyPhysical Properties Aspect ratio Length Diameter Primary criteria that distinguish fibers from nonfibrous particulates Aspect ratio > 3 = fiber
  8. 8. Concepts in Fiber ToxicologyAerodynamic diameter Aerodynamic diameter of a fiber = equivalent to the diameter of a sphere with a specific gravity of 1 that settles in air at the same rate as the fiber Determines where in the lung the fiber will deposit 1 5 1 D A = 1.3 p x d x L 2 6 6p = density, d = diameter, L = lengthActual diameter is more important than actual length in terms of aerodynamic diameter
  9. 9. Concepts in Fiber ToxicologyAerodynamic diameter Respirable = able to reach the gas exchange areas of the lung (bronchioles and alveoli) Fibers with AD > 12 μm are generally not respirable in humans Fibers with AD > 6 μm are generally not respirable in rodents Fibers with actual diameter > 3 μm – deposit in upper airways Fibers with actual diameters ≤ 3 μm are respirable in humans even with lengths up to 200 μm
  10. 10. Concepts in Fiber ToxicologyMechanisms of deposition in the lung Impaction – areas of high air flow – larger airways – classically the carina Sedimentation – areas of low air flow + long residence time + small airway size – classically respiratory bronchioles and alveolar duct bifurcations Interception – probability increases with increasing fiber length
  11. 11. Concepts in Fiber ToxicologyDeposition in humans Most common site of deposition and pathology are larger bronchial airway bifurcations Little information on deposition in the respiratory bronchiolar and alveolar areas Initial lung disease is strongly dependent on initial patterns of fiber deposition in the lung
  12. 12. Concepts in Fiber ToxicologyDeposition in rodents Alveolar deposition decreases with increasing fiber length Alveolar deposition decreases with increasing AD Tracheobronchial deposition increases with increasing fiber length In the deep lung, deposition is primarily at the junctions of the terminal bronchioles and alveolar ducts
  13. 13. Concepts in Fiber ToxicologyFiber Migration and Clearance Diameter > 3 μm – deposit in upper airways and are rapidly cleared and swallowed Fibers with length < 5 μm can be phagocytosed by alveolar macrophages and can be cleared to some degree by the mucociliary elevator Fibers with length > 5 μm tend to be incompletely phagocytosed by alveolar macrophages Long fibers (20 μm length) cannot be cleared from the lungs by macrophages and have greater biocidal activity
  14. 14. Concepts in Fiber ToxicologyFiber Migration and Clearance Shape is important – serpentine fibers are Long fibers (20 μm length) cannot be cleared from the lungs by macrophages and have greater biocidal activity Fibers phagocytosed by alveolar macrophages are translocated through the alveolar walls into the interstitial areas and through the lymphatic drainage (including into the pleura and peritoneum) Linked to the concept of “biopersistence”
  15. 15. Concepts in Fiber ToxicologyFiber biopersistence Biopersistence = ability of inhaled fibers to resist changes in number, dimension, surface chemistry, chemical composition, surface area and other characteristics
  16. 16. Concepts in Fiber ToxicologyFiber biopersistence Biopersistence depends on:  Macrophage mediated clearance i.e. fibers < 5 μm in actual length  Dissolution rate  Tendency for transverse fragmentation, which depends on leaching – rapid leaching and TF = low biopersistence  Tendency for longitudinal splitting – have high biopersistence plus fibers with actual diameter < 3 μm can penetrate cell membranes  Tendency of long non-phagocytosible fibers to migrate into other areas of the thoracic cavity
  17. 17. Mean actual fiber length Time Biopersistent Fibers
  18. 18. Mean actual fiber length Time Non-Biopersistent Fibers
  19. 19. Concepts in Fiber ToxicologyFiber biopersistence T90 for long fibers (> 20 μm actual length) T 90 are based on 2-pool 1st order kinetics (slow clearance and fast clearance pools) Reflects a later phase of fiber clearance and is mechanistically related to the pathogenesis of lung and serous membrane disease Easy to determine
  20. 20. 1 μm diameter x 20 μm length fibers

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