Asbestos exposure, lung fiber burden, and mesothelioma rates: Mechanistic modelling for risk assessment

Abstract

Context

Relationships among asbestos exposure, lung burden, and mesothelioma risks have been previously evaluated, but it would be useful to validate published epidemiological observations with a mathematical model describing deposition and elimination of various mineral types of fibers.

Objective

(a) To develop a mechanistical model demonstrating uptake and removal of fibers from human lungs, (b) To test the model on the results of a British case-control study, (c) To quantify the updated values for elimination coefficient of various mineral types of asbestos fibers.

Methods

A mechanistic model utilizing the first-order kinetic relationship is proposed that relates levels of exposure to mineral fibers, elimination coefficients, and lung burden at certain points of time. The behaviour of the model was explored for different exposure scenarios. Elimination coefficients for various mineral types were estimated based on the observed proportion of asbestos minerals in exposure vs observed lung burden.

Results

Based on the proposed model, the average elimination coefficient was estimated for crocidolite as 0.099 vs average published value of 0.092, for amosite as 0.169 vs 0.19, and for chrysotile as 6.45 vs average published value of 6.36 (years⁻¹). Lung burden level was demonstrated to change linearly with exposure intensity, and supra-linearly with exposure duration. The simulation of three separate exposure events during three decades showed that lung burden level prevailingly depends on the most recent event (R = 0.967, p < 0.05) and only weakly correlates with the most remote event (R = 0.032, p < 0.05).

Conclusion

In spite of potential limitations, mechanistical modelling of asbestos exposure can serve as an effective tool for risk assessment purposes.