Fiber Science

Why do Fibers Differ in Biological Effect?

Now that we have shown that there is a difference among different fibers, we would like to know what properties of the fibers contribute to these differences in their biological response. Recent scientific research has clarified that a fiber must possess all of the following properties for disease to result:

Dose It is an axiom of toxicology that a sufficient dose must be present for disease to occur as a result.

Historical exposures of workers to asbestos fibers were at concentrations of tens to hundreds of fibers per cubic centimeter (f/cc), whereas workplace concentrations of modern synthetic vitreous (glass) fibers are below 1 f/cc and, for most products, below 0.1 f/cc.

Fairly comprehensive information about exposure of residential insulation workers is given in this publication and in the references cited there, and information about exposure in manufacturing is available here, as well as in the papers cited there.

Dimension It is the long, thin fibers that are implicated in disease.

The fibers must be thin to be inhaled into the deep lung - less than 3 µm in diameter for humans. If the thin fibers are short enough, less than 10 or 20 µm long for humans, then they are efficiently removed by the lung macrophages in the same way as ordinary dust particles are removed.

However, if the fibers are long, longer than about 20 µm, then they are too long to be enveloped and effectively transported by macrophages even though they are thin enough to be inhaled to the deep lung. This process is illustrated in these animations.

Durability Fibers, even if they are present as a large dose, even if they are long, are not associated with disease if they dissolve or break down in the lung rapidly.

How rapidly a fiber dissolves is captured in its dissolution rate constant, which can be measured in animal biopersistence studies as described this paper or measured in laboratory experiments using simulated lung fluid as described in these papers, as well as in papers by many other scientific groups, most of which are cited in the papers shown here.

There is a movie made of time lapse photomicrographs of dissolving fibers that you may view here.

The effect of fiber dissolution rate on its biological properties may be made quantitative with a predictive model that allows one to predict the incidence of disease after exposure to a given dose of long fibers with a given dissolution rate. A paper describing the model and verifying it against three different diseases in a series of inhalation and injection studies is available here. An animation of this application of the predictive model may be viewed here.

How is fiber durability engineered and controlled?

The rate at which a fiber dissolves in the lung is determined mainly by its composition, which is fixed essentially forever when the fiber is manufactured. Therefore, the dissolution rate of a fiber is the most important biological property for a manufacturer of synthetic vitreous fibers. An extensive series of laboratory investigations of many fiber compositions combined with the results of animal biopersistence studies of many different fiber compositions, which are summarized here, have allowed the dependence of dissolution rate on fiber composition to be determined.

For a wide range of synthetic vitreous fiber compositions, it is now possible to estimate the dissolution rate directly from the oxide composition. A paper that develops this method for borosilicate glass insulation fiber compositions may be read here. A further extension of the method to rock, slag, and other fibers is available here These methods are implemented in a calculator that runs in these web pages that you may use by clicking here.

The resolution of these scientific questions allows fibers to be designed and modified so that they have dissolution rates high enough to minimize the chance that that disease would occur even in laboratory animal studies at extremely high exposures.

Vitreous Fibers Compared to Vitreous Fibers in Chronic Inhalation Studies

One set of convincing evidence that different fiber compositions can have significantly different biological effects even when the doses and dimensions of the fibers are the same comes from chronic inhalation studies in rats performed at the Research and Consulting Company (RCC) in Switzerland. References to the original publications of these studies are given in this paper.

The following table compares the response of three distinct compositions of synthetic vitreous fibers. All three fibers had virtually the same airborne concentrations of the same size distribution, both in length and diameter, as shown in the bottom section of the table. But the disease incidences, shown in the top section, could scarcely have been more different.

RCF Glass Slag
Lung Tumors (%) 13 3 3
Fibrosis (%) 100 0 0
WHO Fibers (f/cc) 190 250 210
Average Diameter (µm) 1.0 0.9 1.0
Average Length (µm) 22 18 21
Long Fibers (f/cc) 60 80 90

Asbestos Compared to Vitreous Fibers in Chronic Inhalation Studies

One set of convincing evidence that different fiber compositions can have significantly different biological effects even when the doses and dimensions of the fibers are the same comes from chronic inhalation studies in rats performed at the Research and Consulting Company (RCC) in Switzerland. References to the original publications of these studies are given in this paper.

The following table compares the response of three distinct compositions of synthetic vitreous fibers. All three fibers had virtually the same airborne

Crocidolite Chrysotile Glass Slag
Lung Tumors (%) 13 19 3 3
Fibrosis (%) 100 100 0 0
WHO Fibers (f/cc) 1600 11000 250 210
Average Diameter (µm) 0.3 0.1 0.9 1.0
Average Length (µm) 6 2 18 21
Long Fibers (f/cc) 160 330 80 90

Although there is once again a great difference in the disease incidences (top section of the table), there is also a great difference in the exposures, no matter how expressed, caused by the great difference in fiber sizes. One cannot be sure from data like these alone whether different fibers have different biological effects or whether dose and fiber size could explain it.

*Churg, Wright, Bilks, and Dai, J. "Pathogenesis of fibrosis produced by asbestos and man-made mineral fibers: What makes a fiber fibrogenic?". Inhalation Toxicology 12 (Suppl. 3), 15-26, (2000)