Assessing particle and fiber toxicology in the respiratory ...
Fiber toxicology
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Transcript of Fiber toxicology
Fiber Toxicology
Rhian Cope
Concepts in Fiber Toxicology
Classification Natural
Asbestos
Amosite (brown)
Crocidolite (blue)
Tremolite
Anthophyllite
Actinolite
Chrysotile Serpentine – composed of chains of Si2O5
and forms spirals – long fibers, can be
woven
Erionite
Wollastonite
Attapulgite
Amphibole - composed of double chain SiO4 tetrahedra“needle like”
Crocidolite
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.
Concepts in Fiber Toxicology
Classification
Synthetic vitreous fibers
Fiberglass
Mineral wool (slag wool, rock wool)
Refractory ceramic fiber
Organic fibers
Concepts in Fiber Toxicology
Physical Properties
Key phisical factors are:
Length
Aspect ratio:
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
Diameter
Length
Concepts in Fiber Toxicology
Physical Properties
Aspect ratio
Primary criteria that distinguish fibers from nonfibrous particulates
Aspect ratio > 3 = fiber
Diameter
Length
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
p = density, d = diameter, L = length
Actual diameter is more important than actual length in terms of aerodynamic diameter
6
1
6
5
2
1
3.1 LxdxpDA
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
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
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
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
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
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”
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
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
Mea
n ac
tual
fib
er le
ngth
Time
Biopersistent Fibers
Mea
n ac
tual
fib
er le
ngth
Time
Non-Biopersistent Fibers
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
1 μm diameter x 20 μm length fibers