Morphological and chemical mechanisms of elongated mineral particle toxicities

Our plain-English summary of Morphological and chemical mechanisms of elongated mineral particle toxicities, by A.E. Aust, P.M. Cook, R.F. Dodson (Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 2011).

The study

• Authors: A.E. Aust, P.M. Cook, R.F. Dodson
• Journal: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
• Published: 2011;14(1-4):40-75
• Type of article: Review
• Cited by: 98 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This article was a review, not a new study. The authors brought together published research on how 'respirable elongated mineral particles' (REMP), a term not limited to the six regulated asbestos fibers, may cause disease. They discussed how particle size affects lung clearance and movement elsewhere, how surface area relates to reactions with cells, and iron chemistry in several minerals. Reviewed findings included that asbestos fibers can generate reactive oxygen species through iron on or released from the fibers. In one cited study, crocidolite's toxicity to human lung epithelial (A549) cells tracked their low-molecular-weight iron. Across cited tissue studies, most asbestos fibers reaching the parietal pleura were shorter than 5 µm. A cited rat study reported peritoneal mesotheliomas from tremolite samples that appeared to be largely cleavage fragments. The authors concluded that iron released from the particles inside cells is responsible for most of the chemical properties of the most carcinogenic forms of asbestos. They noted it is not known whether iron on 'asbestos bodies' in the lung is released and reacts this way in the body.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published cell-free, cell-culture, animal and human tissue studies on how elongated mineral particles, mainly asbestos, cause toxicity; no new data were reported
• Who was studied: No study population; the review covered published experiments in cell-free systems, cultured cells (for example human lung epithelial A549 cells), animals, and analyses of human lung, lymph node and pleural tissue
• Exposure: Respirable elongated mineral particles (REMP), including asbestos (crocidolite, amosite, chrysotile, tremolite), amphibole cleavage fragments, erionite, and, briefly, carbon nanotubes
• Main results:
  • The authors stated that particle sizes affect the clearance and translocation of dust particles reaching the lung
  • The reviewed studies supported that asbestos fibers can generate reactive oxygen species, and that this activity is due to iron, either on the fibers or, more likely, released from them
  • In a cited study of human lung epithelial (A549) cells treated with crocidolite, toxicity to the cells was linearly related to the amount of low-molecular-weight iron in the cells, but not to the total iron released
  • In cited studies of A549 cells, crocidolite exposure led to release of iron from the fibers inside the cells and a fall in the cells' glutathione
  • A comparison across several cited human tissue studies suggested that most asbestos fibers reaching the parietal pleura are shorter than 5 µm
  • A cited rat study of 6 tremolite samples injected into the abdominal cavity (Davis et al., 1991b) reported peritoneal mesotheliomas for 3 samples that appeared to be largely tremolite cleavage fragments
• The authors' conclusion: The authors concluded that iron, either part of the particle or acquired by it, which is released from the particles inside cells, is responsible for most of the chemical and some of the biochemical properties of the most carcinogenic forms of asbestos
• Limitations the authors state:
  • The authors stated that iron deposited on fibers to form asbestos bodies can be released and generate reactive oxygen species in laboratory tests, but whether this happens in the living body is not known
  • The authors stated that because most comparative studies compare fibers by weight, no reliable information on relative reactivities is available

Topics

Medical terms in this study, explained in our Lexicon: Aspect Ratio (Length-to-diameter ratio), Reactive Oxygen Species (ROS), Reactive Nitrogen Species (RNS).

Related studies

• Analysis and identification of elongated mineral particles in road coated aggregates — E. Leocat, C. Rielland, et al. (2018)
• Does qualitative examination of Elongated Mineral Particles (EMP) recovered from human and animal lungs provide reliable information on their carcinogenic and other effects? — B.W. Case (2018)
• Biological mechanisms of non-linear dose-response for respirable mineral fibers — L.A.T. Cox (2018)
• Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms — A. Valavanidis, T. Vlachogianni, et al. (2013)
• Measurement of elongate mineral particles: What we should measure and how do we do it? — E.J. Chatfield (2018)
• Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos — B.T. Mossman, M. Lippmann, et al. (2011)

Browse more research in Journal of Toxicology and Environmental Health. Part B, Critical Reviews, or return to medical research.