These are animations of some of the important processes underlying the biological effects of fibers.
These are moving schematic diatrams of the action of lung macrophages when confronted with different kinds of particles that can reach the deep lung. The macrophage is represented by the green blob, the particle or fiber in black, and the enzymes released by the macrophage in red in the final stages of the animation.
Macrophage enveloping a particle. Many billions of such ordinary particles are inhaled into the deep lung with every breath. They can be enveloped as indicated here and safely removed from the lung.
Macrophage enveloping a short fiber. Like ordinary particles, sufficiently short fibers can also be enveloped and safely removed from the lung, too.
Macrophage attempting to envelope a long fiber. Long fibers are the only shape that can be inhaled to the deep lung if it is thin enough in diameter, but cannot be successfully enveloped by the macrophage if it is too long.
The unsuccessful envelopment of example 3 leads to the leakage of potent enzymes from the interior of the cell onto the surface of the lung with consequent lung damage that is thought to lead to lung disease including cancer. Such diseases do not develop if the long fibers can be removed rapidly from the deep lung by dissolution in the lung fluid.*
* Churg, Wright, Bilks, and Dai, "Pathogenesis of fibrosis produced by asbestos and man-made mineral fibers: What makes a fiber fibrogenic?". Inhalation Toxicology 12 (Suppl. 3), 15-26 (2000).
These are time lapse photomicrographs of fibers dissolving in simulated lung fluid in a laboratory experiment. Such experiments provide a good way to measure the dissolution rate of fibers as is described in this paper.
Congruent dissolution over a period of 25 days. This type of fiber dissolves starting at the outside and becomes thinner and thinner. Most fiber compositions dissolve in this manner.
Incongruent dissolution over a period of 42 hours. There are a few compositions of this type that dissolve by leaching out some major components of the fiber, whereas the other components dissolve less rapidly. This leaching starts at the outside of the fiber and moves inward toward the center, dissolving from a thinning core.
These fiber dissolution experiments were carried out and the photomicrographs were made by Cheryl Smith (B.A., Chemistry, Botany, and Microbiology).
A predictive model was developed to describe the incidence of disease following exposure of animals to differing amounts of fibers of different dissolution rates. It expresses mathematically the concept that fibers that dissolve more rapidly reside for a shorter time in the body and result in a lower incidence of disease. This model has no adjustable parameters and thus may be tested by using it to predict the results of animal studies that have been carried out and comparing the predicted with the actual disease incidence. The animations below show the verification of the model by applying it to three different diseases in rats by two different routes of administration. This research was published in 1996 in a paper that you may read here.
Animations of the application of the predictive model to Wagner Grade 4 or higher fibrosis following inhalation of fibers by rats. The data that test the model are from a series of chronic inhalation studies conducted by the RCC Laboratory in Switzerland.Learn More
Animations of the application of the predictive model to intraperitoneal (IP) injection of fibers in rats. The data that test the model are from the extensive studies of Prof. Pott and his colleagues carried out over several decades.Learn More
Animations of application of the predictive model to lung tumors (adenomas plus carcinomas) following inhalation of fibers by rats. The data against which the model is tested in this case are from a series of chronic inhalation studies conducted by the RCC Laboratory in Switzerland.Learn More