A protocol to evaluate the fibrogenic potential of inhaled materials

Our plain-English summary of A protocol to evaluate the fibrogenic potential of inhaled materials, by I.P. Bennett, G.H. Pigott, K. Isaacs (Journal of Applied Toxicology, 1988).

The study

• Authors: I.P. Bennett, G.H. Pigott, K. Isaacs
• Journal: Journal of Applied Toxicology
• Published: 1988;8(6):423-9
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A protocol to provide a more rapid assessment of the fibrogenic potential of an inhaled particulate has been developed. Young rats are exposed nose-only for 6 h/day, 7 days a week for 28 days to a respirable aerosol of the test compound. After exposure the rats are kept for up to 1 year, followed by histopathological assessment of the lung. Interim sacrifices could allow an estimate of the rate and severity of the development of any fibrogenic lesion. The protocol has been evaluated for chrysotile asbestos, alpha-quartz and titanium dioxide using rats of both sexes and two different ages at first exposure. The results indicate that there are no significant differences in either the rate, type or extent of lesion provoked by a 28-day exposure period when compared with the more conventional 1-year exposure period studies. It can be concluded that neither sex nor age at first exposure cause any biologically significant differences in response, although young rats would be used in practice. Only one sex need be investigated. The protocol offers considerable benefits over conventional inhalation studies for fibrogenicity (where a 1-year exposure period followed by a further 1-year holding period is usual) by virtue of time, specificity (in the absence of continued exposure the development of any lesion can be studied free from initial inflammatory response) and cost, and could be incorporated into a standard subacute inhalation study design. The results obtained are also of more physiological relevance than studies based on intratracheal instillation.

In plain English

This animal experiment tested a shorter way to check whether inhaled dusts cause lung scarring (fibrosis). Rats of both sexes, aged 8 or 13 weeks at the start, breathed chrysotile asbestos, alpha-quartz, titanium dioxide or clean air through the nose for 4 weeks. Each of the eight experimental groups had 20 males and 20 females, and rats were examined at intervals up to 56 weeks after first exposure. In all asbestos-exposed rats, inflammation was seen right after exposure; by Week 34 there was increased collagen, and by Week 56 interstitial fibrosis. Fibrosis was similar in both age groups, except slightly greater in older females at Week 56. Quartz also caused lesions, more severe in older rats, with lungs up to six times as heavy as controls. Titanium dioxide caused only a minimal response, which the authors did not regard as toxic. No sex-related differences were seen. The authors concluded the design could reliably predict fibrogenicity and that 16 weeks of follow-up would suffice for strongly fibrogenic materials, though less fibrogenic ones may need longer.

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: Animal experiment (inhalation study in rats) evaluating a test protocol: 4 weeks of nose-only exposure followed by a holding period of up to 12 months, with interim sacrifices
• Who was studied: Specific pathogen-free Alpk:AP rats from the colony at Alderley Park, UK (ICI Central Toxicology Laboratory). There were eight experimental groups, each of 20 male and 20 female rats. Groups 1-4 were 8 weeks old ('younger') and groups 5-8 were 13 weeks old ('older') at the start of exposure. Each age set had an air control group and one group for each test material. Rats were housed ten per cage, with the sexes kept separately. Dates of the study are not given.
• Exposure: UICC Chrysotile A (Rhodesian) asbestos, alpha-quartz (Min-u-Sil, mean particle size 5 micrometres) and commercial titanium dioxide, compared with air controls. Exposure was nose-only, 6 hours a day, 7 days a week, for 28 days. The target was about 6000 mg.m-3.h total dust. Cumulative exposures for chrysotile were 5775 mg.m-3.h in the younger group and 8606 (8608 in Table 2) in the older group.
• Main results:
  • Asbestos-exposed rats (both age groups): granulomatous inflammation in the alveolar ducts and terminal bronchioles of all rats immediately after 4 weeks' exposure, increased collagen by Week 34, and interstitial fibrosis by Week 56
  • Asbestos-exposed rats: the degree of interstitial fibrosis was similar in younger and older rats throughout, except that older females showed slightly greater fibrosis at 56 weeks
  • Asbestos-exposed rats, lung weights: in younger rats lungs were about double control values at Week 17, falling to about 1.5 times control later. Older rats showed a fairly constant 25-35% excess over controls.
  • Alpha-quartz-exposed rats: lesions were similar in type in both age groups but more severe in older rats, especially at later time points. In older rats, lung weights were double control values by Week 17, five times by Week 34 and six times by Week 56. In younger males they were elevated about 300% at Week 34.
  • Titanium dioxide-exposed rats: no change in lung weight at any time point. The minimal microscopic response was interpreted by the authors as activation of normal defence mechanisms, not a toxic reaction.
  • No sex-related differences were seen in any group
  • Only two animals showed a possibly treatment-related abnormality during exposure. An older male exposed to asbestos had severe respiratory distress after the final exposure and recovered. An older female exposed to alpha-quartz was found dead on Day 16.
  • The authors judged that, for strongly fibrogenic materials such as asbestos or quartz, a 16-week holding period would be sufficient to predict fibrogenicity
• The authors' conclusion: The authors concluded that the study design can reliably predict the fibrogenicity of inhaled particulates and offers benefits over 12-month inhalation studies. They also concluded that age differences were not enough to rule out using younger rats, and that one sex would be sufficient in further work.
• Limitations the authors state:
  • The authors stated that a longer holding period may be needed for less fibrogenic materials, and that the present results cannot accurately predict how long it should be

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Fibrogenic, Chrysotile.

Related studies

• An assessment of the fibrogenic potential of very short 4T30 chrysotile by intratracheal instillation in rats — I. Lemaire, D. Nadeau, et al. (1985)
• Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall — J. Dai, B. Gilks, et al. (1998)
• Characterization of the bronchoalveolar cellular response in experimental asbestosis. Different reactions depending on the fibrogenic potential — I. Lemaire (1985)
• Patterns of histopathological change determined by the point counting method and its application for the hazard assessment of respirable dust — A. Ogami, Y. Morimoto, et al. (2004)
• Fibrogenic effect of wollastonite compared with asbestos dust and dusts containing quartz — E.E. McConnell (1995)
• Studies on the deposition of inhaled fibrous material in the respiratory tract of the rat and its subsequent clearance using radioactive tracer techniques. 1. UICC crocidolite asbestos — J.C. Evans, R.J. Evans, et al. (1973)

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