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Cited by 84Occupational and environmental lung diseasesFree Radicals and AntioxidantsInterstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

Free radical generation in the toxicity of inhaled mineral particles: the role of iron speciation at the surface of asbestos and silica

Open access
Fenoglio, I., Prandi, L., Tomatis, M., Fubini, B.·2001·Redox Report
DOI 10.1179/135100001101536382
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Abstract

Free radical generation at the particle/biological fluid interface is one of the chemical processes that contributes to pathogenicity. In order to investigate the role played by iron, fibres of crocidolite asbestos have been modified by thermal treatments to alter their surface iron content. Two radical mechanisms, HO* from H2O2 and cleavage of a C-H bond, which are both active on the original fibres, have been tested on the modified fibres. C-H cleavage is dependent on Fe(II) abundance and location and is suppressed by surface oxidation while HO* release appears independent of the oxidation state of iron. Quartz specimens with different levels of iron impurities have been tested in a similar manner. A commercially available quartz (Min-U-Sil 5) containing trace levels of iron is also active in both tests, but reactivity is not fully suppressed by treatment with desferrioxamine, which should remove/inactivate iron. The radical yield attained is close to the level produced by a pure quartz dust, suggesting the presence of active sites other than iron. Ascorbic acid reacts with both crocidolite and quartz, with subsequent depletion of the level of antioxidant defences when particle deposition occurs in the lung lining layer. Following treatment with ascorbic acid the radical yield increases with quartz, but decreases with asbestos. Selective removal of iron and silicon from the surface may account for the differences in behaviour of the two particulates.

AI snapshot

Written from the paper’s full text.

TL;DR

This study examines how surface iron speciation controls radical production by crocidolite asbestos and quartz dusts. It finds two distinct radical pathways—one peroxide-dependent and largely independent of iron oxidation state, and one requiring Fe(II) for carbon-hydrogen cleavage—and shows ascorbic acid alters particle reactivity and is consumed by both minerals.

Key findings

  • Crocidolite and quartz both showed sustained radical release. For crocidolite, vacuum heating at 400°C raised Fe(II) and increased formate-derived carboxylate radical yield about threefold; air heating suppressed that pathway, while HO• release with H₂O₂ remained independent of Fe(II) content. Table 1 reports ferrozine removed 1.3 nmol/mg Fe(II) from original crocidolite, 1.1 from air-heated, and 29 from vacuum-heated; desferrioxamine removed 155, 145, and 130 nmol/mg total iron, respectively.
  • For quartz, Min-U-Sil 5 (0.075% Fe₂O₃) was active in both HO• and CO₂•− assays; desferrioxamine lowered HO• to the level of pure quartz and completely inhibited CO₂•− generation. Pure quartz produced HO• but not CO₂•−, suggesting non-iron sites for HO• and iron traces for C–H cleavage.
  • Ascorbic acid incubation increased the ascorbyl radical signal after 10 min with crocidolite but decreased it with quartz; after 6 days ascorbate was consumed in both supernatants. Radical yield after ascorbic acid increased for quartz but decreased for crocidolite. Supernatant from crocidolite/ascorbic acid (200 nmol/ml iron) gave no CO₂•− after iron chelation and only traces of HO•, ruling out mobilized iron in that case.
  • The authors conclude that surface iron coordination and redox state, rather than total iron, drive most radical mechanisms; detoxification by changing iron state or content alone is likely to fail, and ascorbate depletion may add to oxidative stress.

Methods

  • Samples included UICC crocidolite (SSA 8 m²/g), Min-U-Sil 5 quartz (SSA 5.2 m²/g, 0.075% Fe₂O₃), and pure quartz QA (99.999% SiO₂, SSA 4.5 m²/g). Thermal treatments were 400°C vacuum outgassing or 400°C air heating for 2 h. Chelator incubations used 1 mM ascorbic acid for 6 days at pH 7.4 or 1 mM desferrioxamine for 24 h; iron mobilization used desferrioxamine or ferrozine for 30 days at 37°C and was measured spectrophotometrically.
  • Radical detection used DMPO spin trapping with EPR in aqueous buffered suspensions, with 78 mM H₂O₂ for HO• or 1.0 M sodium formate for CO₂•−, following kinetics for at least 1 h. A supernatant from crocidolite incubated in 10 mM ascorbic acid (iron concentration 200 nmol/ml) was also tested for radical generation.

Limitations

  • Stated: the authors call for further research to identify the surface characteristics responsible for toxicity, and some quartz CO₂•− data were omitted for brevity.
  • Evident: all experiments are cell-free aqueous suspensions using model reactants (H₂O₂, formate), so relevance to in vivo lung lining fluid, cells, proteins, and lipids is inferential; no cellular or animal toxicity endpoints are reported, and EPR radical yields are not direct measures of pathogenicity.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1179/135100001101536382

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

2 of 20 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

  • Findingcitation

    Heating crocidolite at 400°C does not modify its crystal structure.

    “At this temperature, the crystal structure is not modified, as confirmed by X-ray and IR spectra.24”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] source
  • Findingown data

    Thermal treatment of crocidolite at 400°C slightly reduces the extent of iron mobilised by chelators compared with original fibres.

    “The thermal treatment slightly reduces the extent of iron mobilised in comparison with the original fibres.”
    Quote in the paperNot a substantial claim
  • Findingcitation

    H abstraction from formate by crocidolite requires the presence of Fe(II).

    “In contrast, H abstraction requires the presence of Fe(II), as previously proposed.27,36,37”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [27] source
    • cites [36] source
    • cites [37] source
  • Findingown data

    Treatment with desferrioxamine completely inhibited the ability of Min-U-Sil quartz to generate CO2•- radicals.

    “Treatment with desferrioxamine completely inhibited the ability of quartz (MIN) to generate CO 2 •-radicals.”
    Quote in the paperSubstantial claim
  • Findingown data

    After 10 min incubation, the ascorbyl radical signal was decreased in quartz suspensions.

    “It is noteworthy, however, that when recorded after 10 min incubation this signal was increased in the case of crocidolite and decreased in the case of quartz, suggesting that a one electron oxidation of ascorbate, yielding the ascorbyl radical, rapidly occurs on crocidolite, while a different reaction seems to be responsible for the ascorbic acid consumption on quartz.”
    Quote in the paperSubstantial claim
  • May combine two claims. 16
  • The quote only partly states this claim. 2
  • Classified as probably not a substantial claim. 4

  • May combine two claims.

    Premisecitation

    Iron is implied in free radical generation from asbestos, but the effects elicited are unrelated to total iron content, suggesting the presence of specific iron active sites.

    “Iron is implied in free radical generation from asbestos but the effects elicited are unrelated to total iron content, suggesting the presence of specific iron active sites.[21][22][23][24]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [21] source
    • cites [22] Pollak H, 1993, Suid-Afrikaanse Tydskrif vir Wetenskap

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [23] source

      The introductory passage (page unavailable) links iron to free-radical generation and reports greater free-radical activity in long than short amosite fibres. The Discussion (page unavailable) speculates that a particular iron coordination site may be important in damaging processes. The paper does not establish the broader claim that the effects are unrelated to total iron content. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    On the surface of crocidolite, ascorbic acid may both reduce surface iron or remove it from the solid into the solution.

    “On the surface of crocidolite, ascorbic acid may both reduce surface iron or remove it from the solid into the solution.11,30,33”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [11] source
    • cites [30] Gold J, Amandusson H, Krozer A et al. Chemical characterisation and reactivity of iron chelator-treated amphibole asbestos. Environ Health Perspect 1997; 105 (Suppl. 5): 1021-1030. source
    • cites [33] source

  • May combine two claims.

    Findingown data

    All quartz samples tested (Min-U-Sil, pure quartz, DFX-treated Min-U-Sil) are active in HO• generation and radical release appears sustained with time.

    “All samples are active and radical 238 Fenoglio, Prandi, Tomatis, Fubini release appears sustained with time.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The commercial quartz (MIN) was active in CO2•- generation via cleavage of the C-H bond of formate, while the pure quartz dust (QA) was not.

    “The commercial quartz (MIN) was active whilethe pure quartz dust (QA) was not.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    The release of radicals from asbestos or silica in the presence of H2O2 is slow and sustained with time, with radical concentration increasing for 1 h or more.

    “Conversely, the release of radicals from asbestos or silica is slow and sustained with time.The radical concentration increases for 1 h or more, suggesting the presence of active iron species bound at the surface which give rise to slow, probably catalytic, processes.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingnone given

    Heating crocidolite in air at 400°C decreases its Fe(II) content.

    “When heating in air, conversely, the amount of Fe(II) decreases.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Heating crocidolite in vacuum at 400°C increases its Fe(II) content.

    “Upon contact with a ferrozine solution, the samples heated in vacuum triggered the immediate development of the typical violet colour of the Fe(II) ferrozine complex.”
    • Also stated in: § Asbestos modified by thermal treatments · plain
      “The major effect of the thermal treatment, however, is the increase in Fe(II) content of the samples.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No CO2•- radical generation was found with the ascorbate supernatant after iron chelation, while only few traces of HO• were detectable.

    “Note that no CO 2 •-radical generation was found with the ascorbate supernatant after iron chelation, while only few traces of HO • were detectable.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Ascorbic acid reacts with both quartz and crocidolite, although in different ways, being consumed by the particulates.

    “Ascorbic acid reacts with both quartz and crocidolite, although in different ways, being consumed by the particulates.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The sustained radical generation on the three quartz samples may be assigned to a non-iron driven mechanism, possibly involving silicon-based surface radicals arising from reaction of broken Si-O bonds with oxygen (e.g. SiOO•).

    “It is tempting to assign the latter sustained radical generation on the three samples to a non-iron driven mechanism.Silicon-based surface radicals, arising from reaction of the broken Si-O bonds with oxygen (e.g.SiOO • ), may be implicated.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted).

    Premisecitation

    Iron has been claimed to act as a source of radicals on silica.

    “Iron also has been claimed to act as a source of radicals on silica.25,26”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [25] Castranova V, 1997

      Not checked in the free run.

    • cites [26] Ghio AJ, 1992, Am J Physiol source

  • Classified as probably not a substantial claim.

    Premisecitation

    The important role of reactive oxygen and nitrogen species (ROS, RNS) in the pathogenicity of inhaled particles is well documented for both mineral fibers and particles.

    “The important role of reactive oxygen and nitrogen species (ROS, RNS) in the pathogenicity of inhaled particles is, however, well documented in the recent literature for both mineral fibers 4 and particles.5”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] Hardy JA, 1995, Chem Rev source
    • cites [5] IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Silica, some silicates, coal dusts and para-aramid fibrils. Lyon: IARC, 1997; 68.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Selective removal of Fe(II) by chelators eliminates generation of carboxylate radicals from formate but does not substantially influence production of HO•.

    “This is in agreement with results previously reported which demonstrated that selective removal of Fe(II) by chelators eliminated the generation of carboxylate radicals from formate, but did not substantially influence the production of HO • .16”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] source

  • May combine two claims.

    Interpretationown data

    The balance in Fe(II)/Fe(III) at the surface appears to be determined by the mineral structure and any modification resulting from physicochemical treatments is bound to be short-lived.

    “The balance in Fe(II)/Fe(III) at the surface appears to be determined by the mineral structure and any modification, resulting from physicochemical treatments, is bound to be short-lived”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The removal of silicon by ascorbic acid may reveal active sites on the quartz surface, either silicon-associated radicals previously buried in subsurface layers, or reduced iron traces strongly associated to silanols.

    “This removal may reveal some active sites on the surface, which may be either siliconassociated radicals, previously buried in subsurface layers, or reduced iron traces strongly associated to silanols.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Such reactions may take place in vivo, and may contribute to silica pathogenicity by depleting ascorbate antioxidant defences in the lung lining layer while enhancing free radical yield in the proximity of target cells.

    “Such reactions may take place in vivo, and may contribute to silica pathogenicity by depleting ascorbate antioxidant defences in the lung lining layer while enhancing free radical yield in the proximity of target cells.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The inhaled particle will be primarily in contact with the lung lining layer and with type II cells which contain ascorbic acid.

  • May combine two claims.

    Interpretationown data

    A one-electron oxidation of ascorbate, yielding the ascorbyl radical, rapidly occurs on crocidolite, while a different reaction seems responsible for ascorbic acid consumption on quartz.

    “suggesting that a one electron oxidation of ascorbate, yielding the ascorbyl radical, rapidly occurs on crocidolite, while a different reaction seems to be responsible for the ascorbic acid consumption on quartz.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    The Fenton-like radical generation mechanism, requiring H2O2, is confined to lysosomal fluids, whereas the other mechanism may take place in any biological compartment where the particle is located.

    “The Fenton-like one, requiring the presence of H 2 O 2 , is confined to lysosomal fluids whereas the other one may take place in any of the biological compartments where the particle is located.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Adsorbed ascorbic acid held at the quartz surface may act, in the presence of a few iron ions, as a radical releasing centre per se.

    “Alternatively, adsorbed ascorbic acid held at the surface may act, in the presence of a few iron ions, as a radical releasing centre per se.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The increase in ascorbyl radical concentration with crocidolite parallels what was previously observed in plasma when Fe3+/EDTA complex was added, confirming an iron-related process.

    “The increase in the ascorbyl radical concentration with crocidolite parallels what was previously observed in plasma when Fe 3+ /EDTA complex was added, 39 confirming an iron-related process.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] source

  • May combine two claims.

    Premisecitation

    Ascorbic acid has a particular affinity for quartz and is able to attack the silica framework and bring consistent amounts of silicon into the solution.

    “Ascorbic acid has a particular affinity for quartz and, indeed, is able to attack the silica framework and bring consistent amounts of silicon into the solution.9”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] source

  • May combine two claims.

    Interpretationreasoning

    Iron speciates at the surface, giving rise to the two kinds of surface centres where ROS are produced.

    “Iron thus speciates at the surface, giving rise to the two kinds of surface centres where ROS are produced.”
    Quote in the paperSubstantial claim
22 of 22

  • The paper relies on this without support.

    The nature of the free radical generating surface sites on asbestos and crystalline silica is not yet clear.

    “In both cases, the nature of the free radical generating surface sites is not yet clear.”

  • The paper relies on this without support.

    The inhaled particle will be primarily in contact with the lung lining layer and with type II cells which contain ascorbic acid.

    “Considering that the inhaled particle will be primarily in contact with the lung lining layer and with type II cells which contain, among other substances, ascorbic acid”

  • The paper relies on this without support.

    Iron is not present on any silica specimen; traces may be present only as impurities acquired during processing or endogenously.

    “However, iron is not present on any silica specimen.Traces may be present only as impurities acquired during processing or endogenously.”

  • The paper relies on this without support.

    Both macrophages and type II alveolar cells are rich in ascorbate.

    “as both macrophages and type II alveolar cells are rich in ascorbate.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Research works printed but not linked: 7

  1. Kane AB, 1996, IARC Sci Publ, 140, 11
  2. Hardy JA, 1995, Chem Rev, 118, 95
  3. Pollak H, 1993, Suid-Afrikaanse Tydskrif vir Wetenskap, 89, 401
  4. Castranova V, 1997, Environ Health Perspect, 105, 1319
  5. Ghio AJ, 1992, Am J Physiol, 263, 511
  6. Gulumian M, 1993, Suid-Afrikaanse Tydskrif vir Wetenskap, 89, 405
  7. Fubini B, 1990, Toxicol Ind Health, 6, 571

Cited by

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Related

Authors
Fenoglio, I., Prandi, L., Tomatis, M., & Fubini, B.
Affiliations
University of Turin (IT)
ORCID
Venue
Redox Report
Publisher
Informa UK Limited
Published
2001-08
Volume
6
Issue
4
Pages
235-241
ISSN
  • 1351-0002 (ISSN-L)
  • 1743-2928
DOI
10.1179/135100001101536382
OpenAlex
W2048242987
Cited by
84
References
39
Citations by year
2026: 4 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 1 · 2014: 2 · 2013: 5 · 2012: 6
FWCI
3.52
Type
journal article
Language
en
Open access
Locations
  • Redox Report (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
Regione Piemonte
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
  • Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Keywords
free radical generation, asbestos, silica, crocidolite, iron speciation, surface iron, hydroxyl radicals, C-H bond cleavage, thermal modification, quartz, deferoxamine, vitamin C, antioxidant defense, particle toxicity, iron removal
MeSH terms
Administration, Inhalation, Ascorbic Acid, Dust, Free Radicals, Hot Temperature, Iron, Quartz, Suspensions, Asbestos, Crocidolite

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