Predicting EMP hazard: Lessons from studies with inhaled fibrous and non-fibrous nano- and micro-particles

Our plain-English summary of Predicting EMP hazard: Lessons from studies with inhaled fibrous and non-fibrous nano- and micro-particles, by G. Oberdörster, U. Graham (Toxicology and Applied Pharmacology, 2018).

The study

• Authors: G. Oberdörster, U. Graham
• Journal: Toxicology and Applied Pharmacology
• Published: 2018;361:50-61
• Type of article: Review
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhalation exposure to elongated cleavage fragments occurring at mineral and rock mining and crushing operations raises important questions regarding potential health effects given their resemblance to fibers with known adverse health effects like amphibole asbestos. Thus, a major goal for establishing a toxicity profile for elongate mineral particles (EMPs) is to identify and characterize a suspected hazard and characterize a risk by examining together results of hazard and exposure assessment. This will require not only knowledge about biokinetics of inhaled EMPs but also about underlying mechanisms of effects induced by retained EMPs. In vitro toxicity assays with predictive power for in vivo effects have been established as useful screening tools for toxicological characterization of particulate materials including EMPs. Important determinants of physiological/toxicological mechanisms are physico-chemical and functional properties of inhaled particulate materials. Of the physico-chemical (intrinsic) properties, size, shape and surface characteristics are well known to affect toxicological responses; functional properties include (i) solubility/dissolution rate in physiological fluid simulants in vitro and following inhalation in vivo; (ii) ROS-inducing capacity in vitro and in vivo determined as specific particle surface reactivity; (iii) bioprocessing in vivo. A key parameter for all is the dose and duration of exposure, requiring to establish exposure-dose-response relationships. Examples of studies with fibrous and non-fibrous particles are discussed to illustrate the relevancy of evaluating extrinsic and intrinsic particle properties for predicting in vivo responses of new particulate materials. This will allow hazard and risk ranking/grouping based on a comparison to toxicologically well-characterized positive and negative benchmarks. Future efforts should be directed at developing and validating new approaches using in vitro (non-animal) studies for establishing a complete risk assessment for EMPs. Further comparative in-depth analyses with analytical and ultra-high resolution technology examining bioprocessing events at target organ sites have proven highly successful to identify biotransformations in target cells at near atomic level. In the case of EMPs, such analyses can be essential to separate benign from harmful ones.

Copyright © 2018 Elsevier Inc. All rights reserved.

In plain English

This article was a review, not a new study. The authors discussed how the hazard of inhaled elongate mineral particles (EMPs) might be predicted. EMPs are elongated fragments released by mining and rock crushing. The authors drew on earlier studies of fibrous and non-fibrous particles. They described a 1991 rat study by Davis and colleagues in which adding quartz to asbestos inhalation increased lung tumors and mesothelioma. They cited a rat study in which only refractory ceramic fibers shorter than 5 micrometers and thinner than about 0.5 micrometers reached the pleura. They also cited a study of South African asbestos miners in which fiber surface area appeared to link fibrosis across asbestos types. They discussed cell-free laboratory tests of particle surface reactivity and dissolution whose results correlated with results in animals. The authors concluded that EMPs are not yet well characterized. They wrote that predictive laboratory tests, measured against benchmark particles such as amphibole and quartz (positive) and titanium dioxide (negative), would help rank EMPs before animal testing. They stated that these tests still need validation in living animals.

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 and discussion of earlier published studies (narrative review / perspective); no new data collected
• Who was studied: No study population of its own. The authors discussed earlier studies in rats, dogs, mice and hamsters, and a study of asbestos miners from four locations in South Africa.
• Exposure: Elongate mineral particles (asbestiform and non-asbestiform mineral fragments from mining and crushing). Studies discussed involved crocidolite, chrysotile and amosite asbestos, refractory ceramic fibers, synthetic vitreous fibers, titanium dioxide, quartz, amorphous silica nanoparticles, carbon nanoparticles and nanoceria.
• Main results:
  • Reviewed study (Davis et al., 1991, rats, 12-month inhalation): compared with asbestos alone, co-exposure of asbestos with quartz significantly increased lung tumors and mesothelioma.
  • The authors cautioned that in the Davis study the titanium dioxide exposure concentration caused lung overload in rats.
  • Reviewed study (Gelzleichter et al., 1996, rats, 5 days of inhalation of refractory ceramic fibers): only fibers shorter than 5 micrometers and thinner than about 0.5 micrometers reached the pleura. The pleural fiber number was about 0.1% of retained lung fibers.
  • Reviewed study (Oberdörster et al., 1988, 4 dogs, instilled UICC amosite): only fibers shorter than about 6 to 9 micrometers were cleared into the blood circulation via post-nodal lymph.
  • Reviewed study (Timbrell et al., 1988, South African asbestos miners from 4 locations): fiber surface area appeared to be a unifying dose measure for fibrosis across asbestos types and mining locations.
  • Reviewed study (Rushton et al., 2010, 8 nanomaterials, rats): cell-free reactive oxygen species activity per unit surface area correlated significantly with lung inflammation per unit surface area.
  • Reviewed studies (Eastes et al., 2000; Potter, 2000, synthetic vitreous fibers): laboratory dissolution rates correlated with in vivo dissolution in rat inhalation studies.
  • Reviewed study (Oberdörster et al., 2016, rats, 4-week inhalation of amorphous silica nanoparticles): the estimated in vivo dissolution rate was 0.0195 per day, a dissolution half-time of 35.5 days.
• The authors' conclusion: The authors concluded that EMPs have not been well characterized for toxicity or carcinogenicity. They wrote that predictive in vitro assays for screening and ranking EMPs against positive benchmarks (e.g., amphibole, quartz) and negative benchmarks (e.g., titanium dioxide) would be a valuable tool for deciding on later animal testing.
• Limitations the authors state:
  • The authors stated that more validation studies comparing in vitro and in vivo surface reactivity are needed.
  • The authors stated that the proposed cell-free screening assays still require proper in vivo validation.
  • The authors stated that how bioprocessing of EMPs affects toxic outcomes has not yet been determined.
  • The authors noted that exposure limits derived from rodent studies must account for humans always being co-exposed to other materials.

Topics

Medical terms in this study, explained in our Lexicon: Cleavage Fragment, Amphibole Asbestos, elongate mineral particles (EMPs), Surface Reactivity, Bioprocessing, Dose-response relationship.

Related studies

• Dosimetry of inhaled elongate mineral particles in the respiratory tract: The impact of shape factor — B. Asgharian, T.P. Owen, et al. (2018)
• Analysis and identification of elongated mineral particles in road coated aggregates — E. Leocat, C. Rielland, et al. (2018)
• A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans — D.H. Garabrant, S.T. Pastula (2018)
• A case study of the translocation, bioprocessing and tissue interactions of EMP following inhalation exposure — U.M. Graham, G. Oberdörster, et al. (2018)
• The epidemiologic evidence for elongate mineral particle (EMP)-related human cancer risk — P. Boffetta, K.A. Mundt, 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)

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