1. Fiber Toxicology
Rhian Cope

2. Concepts in Fiber Toxicology
Classification
 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. Crocidolite

4. Wittenoom - A report by consultants GHD and Parsons
Brinckerhoff in November 2006 evaluated the continuing risks
associated with asbestos contamination in the town and
surrounding areas and classed the risk to visitors as medium and
to residents as extreme.

9. Concepts in Fiber Toxicology
Classification
 Synthetic vitreous fibers
Fiberglass
Mineral wool (slag wool, rock wool)
Refractory ceramic fiber
 Organic fibers

10. Concepts in Fiber Toxicology
Physical 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

11. Concepts in Fiber Toxicology
Physical Properties
 Aspect ratio
Length
Diameter
Primary criteria that distinguish fibers from nonfibrous particulates
Aspect ratio > 3 = fiber

12. Concepts in Fiber Toxicology
Aerodynamic 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 6
p = density, d = diameter, L = length
Actual diameter is more important than actual length in terms of
aerodynamic diameter

13. Concepts in Fiber Toxicology
Aerodynamic 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

14. Concepts in Fiber Toxicology
Mechanisms 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

15. Concepts in Fiber Toxicology
Deposition 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

16. Concepts in Fiber Toxicology
Deposition 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

17. Concepts in Fiber Toxicology
Fiber 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

18. Concepts in Fiber Toxicology
Fiber 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”

19. Concepts in Fiber Toxicology
Fiber biopersistence
 Biopersistence = ability of inhaled fibers to resist changes in number,
dimension, surface chemistry, chemical composition, surface area
and other characteristics

20. Concepts in Fiber Toxicology
Fiber 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

21. Mean actual fiber length
Time
Biopersistent Fibers

22. Mean actual fiber length
Time
Non-Biopersistent Fibers

23. Concepts in Fiber Toxicology
Fiber 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

24. 1 μm diameter x 20 μm length fibers