Fiber toxicology

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Fiber Toxicology Rhian Cope

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Transcript of Fiber toxicology

Page 1: Fiber toxicology

Fiber Toxicology

Rhian Cope

Page 2: Fiber toxicology

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”

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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.

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Concepts in Fiber Toxicology

Classification

Synthetic vitreous fibers

Fiberglass

Mineral wool (slag wool, rock wool)

Refractory ceramic fiber

Organic fibers

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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

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Concepts in Fiber Toxicology

Physical Properties

Aspect ratio

Primary criteria that distinguish fibers from nonfibrous particulates

Aspect ratio > 3 = fiber

Diameter

Length

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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

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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

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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

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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

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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

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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

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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”

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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

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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

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Mea

n ac

tual

fib

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ngth

Time

Biopersistent Fibers

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Mea

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fib

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ngth

Time

Non-Biopersistent Fibers

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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

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1 μm diameter x 20 μm length fibers