Morphological and Chemical Mechanisms of Elongated Mineral Particle Toxicities

Abstract

Much of our understanding regarding the mechanisms for induction of disease following inhalation of respirable elongated mineral particles (REMP) is based on studies involving the biological effects of asbestos fibers. The factors governing the disease potential of an exposure include duration and frequency of exposures; tissue-specific dose over time; impacts on dose persistence from in vivo REMP dissolution, comminution, and clearance; individual susceptibility; and the mineral type and surface characteristics. The mechanisms associated with asbestos particle toxicity involve two facets for each particle's contribution: (1) the physical features of the inhaled REMP, which include width, length, aspect ratio, and effective surface area available for cell contact; and (2) the surface chemical composition and reactivity of the individual fiber/elongated particle. Studies in cell-free systems and with cultured cells suggest an important way in which REMP from asbestos damage cellular molecules or influence cellular processes. This may involve an unfortunate combination of the ability of REMP to chemically generate potentially damaging reactive oxygen species, through surface iron, and the interaction of the unique surfaces with cell membranes to trigger membrane receptor activation. Together these events appear to lead to a cascade of cellular events, including the production of damaging reactive nitrogen species, which may contribute to the disease process. Thus, there is a need to be more cognizant of the potential impact that the total surface area of REMP contributes to the generation of events resulting in pathological changes in biological systems. The information presented has applicability to inhaled dusts, in general, and specifically to respirable elongated mineral particles.

Notes

¹The term “REMP” as used in this article is not restricted to the six types of fibers currently defined under federal asbestos regulations. The term “REMP” is specifically chosen here to avoid confusion associated with interpretations of scientific studies where there is a wide range of particle origins including mineral habits ranging from asbestiform to nonasbestiform in the original rock formations. Historically the term “fiber” has been used to define elongated (length/width ratios ≥3.0) particles per various counting schemes (Millette, 2006). Any of these entities that meet the specific counting definition could be considered morphologically as a “REMP” if sufficiently small to be inhaled. The definition of “respirable” as used in this term (REMP) is based on the theoretical dimensions considered as defining “respirable” particles for humans (Lee, 1985). The upper limit of diameter for a rounded structure has been suggested as >10 μm and for an elongated particle as <3.5 μm (Lee, 1985). In reality, one of the authors (RFD) has evaluated thousands of REMPs from human lung tissue and found that these are rarely >1 μm in diameter.

The authors express their appreciation for the helpful critique of the mineralogical sections of the paper by Gregory Meeker, U.S. Geological Survey, Denver, CO.