A review of inhalation toxicology studies with para-aramid fibrils

Our plain-English summary of A review of inhalation toxicology studies with para-aramid fibrils, by D.B. Warheit (The Annals of Occupational Hygiene, 1995).

The study

• Author: D.B. Warheit
• Journal: The Annals of Occupational Hygiene
• Published: 1995;39(5):691-7
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The paper summarizes the results of inhalation toxicology studies associated with para-aramid (p-aramid) fibrils. The review is subdivided into two categories: the results of inhalation toxicity studies and mechanistic inhalation studies. Keratin-associated lesions were observed in the lungs of female rats following chronic exposure to high concentrations of p-aramid. These lesions were originally interpreted as cystic keratinizing squamous cell carcinomas (CKSCC). In recent years, this keratinizing lesion has been observed in the lungs of rats with greater regularity in numerous chronic inhalation studies following exposures to a variety of dusts. In an attempt to reach a consensus on an appropriate diagnosis for this lesion, an international panel of pathologists was convened to evaluate the morphological aspects of this lesion. The panel considered that the most appropriate diagnosis for this lesion was 'proliferative keratin cyst' (PKC), the biological potential of the PKC remains controversial, but it appears to be unique to the rat species and has little relevance for humans. Mechanistic studies with p-aramid have demonstrated that acute inhalation of high concentrations of fibrils produces a potent but transient pulmonary inflammatory and cell labelling response. The inhaled fibrils have low durability in the lungs of rats as evidenced by a progressive decrease in median fibre lengths with increasing residence time in the lung. In contrast, in a comparative study, size-separated chrysotile asbestos produced a sustained increase over controls in cellular proliferation responses of terminal airways, parenchyma, subpleural and mesothelial regions.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This article was a review, not a new experiment. The author summarized rat inhalation studies of para-aramid fibrils, using Kevlar as the representative fibre. In a 2-year rat study by Lee and colleagues, four out of 69 female rats exposed to 100 fibrils per cubic centimetre developed lung lesions first called cystic keratinizing squamous cell carcinomas. The same effect was not seen in similarly exposed males. An international panel of pathologists later agreed these lesions were not malignant and named them proliferative keratin cysts. The panel said it had never observed the lesion in human lungs, and the review stated that the lesions' biological potential remained controversial. Other reviewed rat studies reported that inhaled fibrils caused short-lived inflammation and became shorter while in the lung. In a comparison study by Warheit and colleagues, size-separated chrysotile asbestos raised cell proliferation, with many effects lasting through 3 months after exposure. Para-aramid caused only a transient increase. Long chrysotile fibres were retained in the lung. The author concluded that inhaled chrysotile asbestos is likely to produce greater long-term lung effects than para-aramid fibrils.

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 inhalation toxicology studies (animal experiments in rats) with para-aramid fibrils, including a pathology panel re-evaluation and mechanistic studies
• Who was studied: Rats (male and female) in the reviewed inhalation studies, including a chronic 2-year study and shorter mechanistic studies
• Exposure: Inhaled para-aramid (p-aramid) fibrils, with Kevlar used in all reviewed studies. One comparative study also used size-separated chrysotile asbestos fibres. In the 2-year study, concentrations were 2.5, 25 and 100 fibrils per cubic centimetre for 2 years, or 400 fibrils per cubic centimetre for 1 year followed by 1 year of recovery.
• Main results:
  • In the 2-year study (Lee et al., 1988), four out of 69 female rats exposed to 100 fibrils per cubic centimetre developed lesions originally called cystic keratinizing squamous cell carcinomas (CKSCC). The effect was not observed in similarly exposed male rats.
  • In the 400 fibrils per cubic centimetre group of the 2-year study, one male and six female rats developed CKSCC; the table gives six out of 56 females.
  • An international panel of pathologists reached consensus that the cystic keratinizing lesions were not malignant neoplasms.
  • The panel considered 'proliferative keratin cyst' (PKC) the most appropriate diagnosis. A minority of panel members (three out of 13) characterized the lesions as benign tumours.
  • The pathologists reached consensus that they had never observed this lesion in the lungs of humans.
  • In rats from the chronic study (Kelly et al., 1993), median lengths of retained fibrils became progressively shorter, from 11 micrometres early in exposure to approaching 4 micrometres by the end of the 2-year exposure.
  • In a short-term study (Warheit et al., 1992), inhaled p-aramid fibrils showed low biodurability in rat lungs and produced transient inflammatory and cell labelling responses. Mean lengths of retained fibrils fell from 12.5 micrometres immediately after exposure to 7.5 micrometres at 6 months.
  • In the comparative study (Warheit et al.), both p-aramid and chrysotile produced minimal to mild inflammatory responses in rats. These peaked at 1 month after exposure and were essentially reversible by 6 months.
  • In the comparative study, chrysotile asbestos produced significant increases in cell proliferation in terminal bronchiolar, proximal alveolar, visceral pleural-subpleural and mesothelial cells of rats. Many of these effects remained increased over controls through 3 months after exposure.
  • In the comparative study, high-dose p-aramid fibrils produced only a transient increase in terminal bronchiolar and visceral pleural-subpleural cell labelling immediately after exposure, with no further significant increases at any later time.
  • In the comparative study, rats exposed to p-aramid retained a greater dose (2-3 times) of long fibres (longer than 5 micrometres) than rats exposed to chrysotile.
  • Median lengths of chrysotile fibres recovered from rat lungs increased over time, indicating that short fibres were cleared and long fibres were retained. Median lengths of p-aramid fibrils decreased over time.
• The authors' conclusion: The author concluded that inhalation of chrysotile asbestos fibres is likely to produce greater long-term pulmonary toxic effects than para-aramid fibrils. The author also concluded that the keratin-related lesions seen in rats were re-diagnosed as proliferative keratin cysts.
• Limitations the authors state:
  • The author states that the biological potential of the proliferative keratin cysts remains controversial.
  • The pathology panel was unwilling to speculate or predict whether the lesions would progress.
  • The biopersistence findings in the comparative study are described as preliminary.

Topics

Medical terms in this study, explained in our Lexicon: Fibril, Squamous Cell Carcinoma, Chrysotile, Parenchyma.

Related studies

• The inhalation toxicology of p-aramid fibrils — K. Donaldson (2009)
• 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)
• A comparative study of the clearance of respirable para-aramid, chrysotile and glass fibres from rat lungs — A. Searl (1997)
• Cytotoxic effects of aramid fibres on rat pulmonary macrophages: comparison with chrysotile asbestos — J. Dunnigan, D. Nadeau, et al. (1984)
• Assessments of lung digestion methods for recovery of fibers — D.B. Warheit, H.C. Hwang, et al. (1991)

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