The inhalation toxicology of p-aramid fibrils

Our plain-English summary of The inhalation toxicology of p-aramid fibrils, by K. Donaldson (Critical Reviews in Toxicology, 2009).

The study

• Author: K. Donaldson
• Journal: Critical Reviews in Toxicology
• Published: 2009;39(6):487-500
• Type of article: Review
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The pandemic of lung disease caused by asbestos has cast suspicion on any industrial fibrous material that can become airborne in respirable form in workplaces, such that the respirable fibres might be inhaled. Fibre toxicology arose as a sub-specialty of particle toxicology to address the specialised nature of fibre effects and has evolved substantially in the last 25 years. It has yielded valuable information on the dosimetry, structure-activity relationships, and mechanism involved in toxicological effects of a range of fibrous materials, including asbestos, other naturally occurring fibrous materials, and synthetic vitreous fibres. A robust structure/activity paradigm has emerged from this research that highlights fibre length, thinness, and biopersistence as major factors in determining the pathogenicity of a fibre. p-Aramid is a manufactured fibre composed of synthetic polyamide (poly paraphenylene terephthalamide) manufactured on a commercial scale since 1970 by polymerisation and spinning steps. It is used as an advanced composite and in fabrics, body armour, friction materials, etc. Respirable fibrils of p-aramid can be released from the fibres during working and can become airborne. A considerable body of research has been carried out into the hazard posed by inhaled p-aramid fibrils, and this review considers this body of literature and summarises the state-of-the-science in the toxicology of p-aramid fibrils in the light of the existing overarching fibre toxicology paradigm. The peer-reviewed studies demonstrate that p-aramid fibrils can be long and thin but that the fibrils are not biopersistent. Residence in the milieu of the lungs leads to fibre shortening, allowing efficient and complete phagocytosis and effective clearance. Subsequently the p-aramid hazard is low, and this is confirmed in animal studies. The mechanism of shortening of p-aramid fibrils is not well-understood, but may involve the action of macrophages on the fibrils following phagocytosis.

In plain English

This article was a review, commissioned and funded by DuPont, of around 30 papers on the toxicology of inhaled p-aramid fibrils, the tiny respirable fibres that can come off p-aramid. In the reviewed rat studies, fibrils got shorter and cleared from the lungs. In one study, median fibril length roughly halved within 20 days. In another, long fibres (over 15 micrometres) had a clearance half-time of 3.1 weeks for p-aramid and 6.8 weeks for chrysotile asbestos in weeks 1 to 24, and 46.2 weeks for chrysotile later on. Increased cell division in the lungs after p-aramid was brief, while chrysotile caused sustained increases. In a 2-year rat study, 9 of 10 lesions first named carcinomas were unanimously re-evaluated by 4 pathologists as benign keratinizing cysts. Two injection studies found no significant increase in mesothelioma. The author noted that no worker disease from p-aramid has been documented, that animal exposures were often hundreds of times workplace levels, and that the shortening mechanism is not understood. The author concluded that p-aramid fibres present a very low hazard to workers.

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: Narrative review of published toxicology studies, commissioned and funded by DuPont
• Who was studied: Published research on p-aramid fibrils, around 30 papers, mostly peer reviewed and mostly rat studies, done in laboratories in the United States and Europe
• Exposure: Respirable p-aramid (poly paraphenylene terephthalamide) fibrils. Some reviewed studies compared them with chrysotile asbestos and synthetic vitreous (glass) fibres.
• Main results:
  • In a rat inhalation study (Bellmann et al., 2000) with exposures of 50, 200 or 800 fibrils/ml for 3 months, retained fibril mass had cleared completely by 9 months at the 50 fibrils/ml exposure. Clearance was slower but effective at the higher exposures.
  • After a single 6-hour exposure of rats to 400 fibrils/ml (Kelly et al., 1993), median fibril length roughly halved by 20 days, to 5 micrometres. Fibrils shorter than 5 micrometres were not counted.
  • In another rat study (Warheit et al., 1994), the median length of fibrils in the lungs fell from 12.5 micrometres to an average of 7.45 micrometres after 6 months.
  • In a rat comparison study (Searl, 1997), clearance half-times for long (over 15 micrometre) fibres over weeks 1 to 24 were 3.1 weeks for p-aramid fibrils, 2.5 weeks for synthetic vitreous fibres and 6.8 weeks for chrysotile.
  • In the same study, from 6 to 12 months too few long p-aramid fibres remained to calculate a half-time. Half-times over this period were 6.6 weeks for synthetic vitreous fibres and 46.2 weeks for chrysotile.
  • In rat studies by Warheit et al. (1996, 1997), p-aramid inhalation caused no significant increase in cell proliferation in the alveolar region or the pleurae.
  • In the same studies, chrysotile caused sustained proliferation in all lung compartments that resolved fully only at 6 months.
  • In a 2-year rat inhalation study (Lee et al., 1988), the lowest exposure (2.5 fibres/ml) produced only a dust reaction.
  • In the same 2-year study, the higher exposures produced type 2 cell hyperplasia, granulomas, alveolar wall fibrosis and bronchiolisation.
  • Of the 10 lesions in the Lee study originally named cystic keratinizing squamous-cell carcinomas, 9 were unanimously re-evaluated as benign pulmonary keratinizing cysts by 4 independent pathologists (Frame et al., 1997).
  • Two intraperitoneal injection studies in rats were negative, with no significant increase in mesotheliomas compared to controls.
  • The author stated that there is no documented case of disease from p-aramid exposure in any worker.
• The authors' conclusion: The author concluded that the available data suggest p-aramid fibres present a very low hazard to workers exposed to them in the workplace.
• Limitations the authors state:
  • The review does not deal with exposure or risk, except in passing.
  • The animal exposures in the reviewed studies were often hundreds, and sometimes thousands, of times higher than measured workplace exposures.
  • How p-aramid fibrils are shortened in the lung is not understood.
  • The author knew of no studies on how branched fibres such as p-aramid fibrils deposit in the lungs.
  • The 1-year exposure and 1-year recovery group in the Lee study was not a classic lifetime carcinogenicity study, in which more pathology could have developed.

Topics

Medical terms in this study, explained in our Lexicon: Fibril, Vitreous, biopersistence, Phagocytosis, Macrophage.

Related studies

• A review of inhalation toxicology studies with para-aramid fibrils — D.B. Warheit (1995)
• Pulmonary effects in rats inhaling size-separated chrysotile asbestos fibres or p-aramid fibrils: differences in cellular proliferative responses — D.B. Warheit, M.A. Hartsky, et al. (1996)
• Lung proliferative and clearance responses to inhaled para-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibers — D.B. Warheit, S.I. Snajdr, et al. (1997)
• Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure — E.E. McConnell, C. Axten, et al. (1999)
• Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the syrian golden hamster. Part I. Results of a subchronic study and dose selection for a chronic study — T.W. Hesterberg, C. Axten, et al. (1999)
• Cytotoxic effects of aramid fibres on rat pulmonary macrophages: comparison with chrysotile asbestos — J. Dunnigan, D. Nadeau, et al. (1984)

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