A number of animal and human studies have been conducted over the decades to investigate the toxicodynamics of asbestos. In generally, these studies can be classified into two categories:
1) Acute exposure: This type of study is based on animal experiments. They provide a reliable estimate about the rapid clearance of asbestos from the lungs.
2) Chronic exposure: This type of study has been done with both animal experiment and long-term follow-up on asbestos-exposed workers. They are useful for studying the slow clearance of asbestos from the lungs.
Different asbestos fibers can stay in the lungs with a highly variable time-span. The estimated half life T1/2 varies from minutes to years. Several investigators have used multi-compartment mathematical models to describe the dynamic behaviors of asbestos in the lung. A typical model may consist of 4 clearance compartments:
1) Fast clearance compartment: T1/2 = minutes to hours
2) Medium clearance compartment: T1/2 = days
3) Slow clearance compartment: T1/2 = months
4) Very-slow clearance compartment: T1/2 = years
The inter-relationship among the compartments is complex. One proposed diagram is illustrated below (Vincent et al. 1985):
The most consistent finding reported from the researches is that the highly variable clearance rates are related to the fiber’s physical characteristics (for example, see the following table; the half life T1/2 is estimated for the very-slow clearance compartment only; human data are used; Finkelstein and Dufresne 1999). The “rule of thumb” is that longer fibers have a longer half life (slower clearance rate) and that amphiboles have a longer half life than chrysotile.
| Fiber Length |
Chrysotile |
Tremolite |
| <5_m |
T1/2=4 years |
T1/2=14 years |
| 5-10_m` |
T1/2=6 years |
T1/2=16 years |
| >10_m |
T1/2=8 years |
T1/2=150 |
|
|
|
When human subjects are concerned, the very-slow clearance compartment is most important. Dose contributions from other faster clearance compartments are considered negligible. In this case, a simple mathematical expression can be written down:
Here is the amount of asbestos in the lungs, the deposition rate, the clearance rate, and the exposure duration. If the exposure time is sufficiently long, this equation predicts that a plateau will be reached. In available human-epidemiological data (Finkelstein and Dufresne 1999), such a plateau phenomenon is observed, but only transiently. Possible explanations for this inconsistency include incorrect exposure-history assessment (e.g., is not a constant and has decreased over time) and the existence of a very-very-slow clearance compartment (also see Finkelstein and Dufresne 1999 for more discussions).
If the exposure to asbestos was discontinued at time , the lung burden is then expected to decrease:
Here is the time since the exposure cessation (see the figure below; some human-epidemiological data reported by Finkelstein and Dufresne are also enclosed for comparison).
In summary, asbestos toxicodynamics are best described by a multi-compartment model although some discrepancy with available human data is noted and needs to be resolved with further investigation in the future.
