The 1990's have seen significant advances in the understanding of mechanisms of fibre-induced disease. Today it is known that the risk of fibre related disease is determined by essentially 3 factors:
€ Dose - the quantity of dust inhaled over time;
€ Dimension - the length, width and aspect ratio of the fibrous dust; and,
€ Durability - or biopersistence of such dust in the human lung.
In general, long, thin, durable fibres are the most hazardous to health. While here remains debate about the absolute size cut-off, the majority of scientists indicate that fibres shorter than 5 micrometres in length do not present a health risk because of the ability of the body's natural defense mechanisms to deal effectively with contaminants of this size and nature.
The dose makes the poison
Dose is the most obvious and in some ways, the most important factor in evaluating the toxic or carcinogenic risk of exposure to a particular substance . At very high doses, practically any substance can be toxic, and the risk will always decline as the dose declines. However, prolonged, intense exposures to a toxic substance can overwhelm the body's natural defence mechanisms and produce cell injury and ultimately even DNA damage which can lead to tumour growth. Intense short-term exposure to a toxic substance can produce acute toxic reactions. While some researchers believe that short, intense exposures play a role in asbestos-related diseases, evidence to support such claims is lacking.
The challenge for scientists is to attempt to determine whether a substance which is carcinogenic at very high doses is necessarily toxic at much lower doses. The principal point of contention centers around the possibility that even though no health effects may be observed, it is possible that these effects exist, but that the level of risk is too low to detect using current data and methodology.
Other scientists maintain that for the purposes of regulatory policy, the weight of animal and human epidemiological evidence is more important than theoretical postulations. If the risk is too low to detect, then it should not be the source of regulatory restrictions. In the case of chrysotile asbestos there is a large body of evidence that demonstrates that at low levels of exposure, the carcinogenicity risk is zero or undetectably low. Evidence of an occupational threshold level of exposure for chrysotile-related disease is presented in Module 4.
Dimensions
Progress in the study of asbestos and other fibres made during the last 15 years has confirmed that fibre length and diameter are important parameters to consider in evaluating carcinogenic potential. Fibre dimensions are important in that they determine whether a fibre is "respirable". Some particles or fibres are too large to infiltrate into the lungs. They are blocked by the body's natural filtration system. .
Those fibres which are capable of bypassing these physical barriers, generally fibres of 3µm in diameter or smaller, have been termed "respirable". Thus in order for fibres to have carcinogenic potential they must first be of respirable size. Scientists are clear to point out however that respirability, though necessary is not sufficient in explaining carcinogenic potential. Fibres which are respirable are not necessarily carcinogenic. Experimental studies demonstrate that while long, thin fibres are associated with pathological manifestations in animals, no such association is found with fibres shorter than 5 µ long. It appears that short fibres can be cleared by the body's natural defenses without provoking inflammation or mesothelial injury. However, long fibres appear to induce the secretion of inflammatory substances by macrophage cells.
As scientists have continued to unravel the reasons for the pathogenicity of longer, respirable fibres they have discovered that fibre length alone cannot explain the wide variance in the carcinogenic potential of different substances. Different fibres of similar dimensions may vary significantly in their health effects. With the evolution of new techniques of chemical and mineral analysis, referred to as tissue burden, an additional parameter of fibrous materials is now recognized as of paramount importance to our understanding of the pathogenic potential of respirable fibres.
Durability or biopersistence
The length of time which inhaled fibres persist in the lung before they are eventually dissolved and/or cleared is an important determinant of their toxic or carcinogenic potential. In general, the longer an inhaled particle persists in the lung, the more likely it is to adversely affect surrounding tissues. Biopersistence studies have been carried out on a number of different respirable fibres, and it has now become clear that there are vast differences among various respirable fibres presently used in industry. How fibres behave and persist in a biological environment depends on the interaction between their size and their chemical composition.
Biosolubility, a key indicator of the biopersistence of a fibre, is measured as the rate at which a fibre dissolves in a biological environment, varies widely among different respirable fibres. It can be measured physically as the decrease in diameter of fibres with time, or as the rate at which individual chemical elements such as iron, magnesium or silicon are removed from the fibres.
Both in vivo (animal studies) and in vitro (biological fluid simulation) research has been conducted to evaluate the biopersistence of different inhalable fibres. It has been demonstrated that for asbestos fibres, chrysotile has low durability and short persistence, while amphiboles are highly durable and persistent. While chrysotile is cleared within weeks or a few months, it is recognized that amphiboles, in particular crocidolite and amosite have clearance half-times in the range of decades. An analysis of the differences in the toxicity of asbestos fibre types is presented in Module 3.
For man made mineral fibres (MMMF), data has shown wide variability in the biopersistence and solubility of different fibres, depending on their respective manufacturing process and chemical composition. For example, glass fibres with high aluminum (Al) content were shown to be more durable than those with low Al content. Module 10 presents a review of some of the health effects of other natural and man-made fibres.
All fibres are not created equal
Today, scientists view the three D's (dose, dimension and durability) as interactive and interdependent. Moreover, as with durability, the parameters of dose and dimension exist on a continuum of pathogenic potential. At low doses, many fibres produce no detectable health effects. All other things being equal, as the dose increases so too will the potential health risks. Similarly, fibres which are less than 5 µm in length can be easily eliminated by the body's natural defense mechanisms. Fibres of 10, 20 or 30 µm and longer are increasingly likely to escape macrophage elimination and remain in the lungs.
In practical terms, in addition to the nature, dimensions and chemical composition of a fibre, industrial hygienists must also consider the type of products these fibres are being used in, as this can have a considerable impact on their potential to generate inhalable dust. For example, high density applications such as asbestos cement are far less likely to break down and release fibre than are friable (sprayed-on) insulation products. The problems resulting from past use of friable insulation materials is discussed in Module 7.