Interspecies comparisons of lung responses to inhaled particles and gases

Our plain-English summary of Interspecies comparisons of lung responses to inhaled particles and gases, by D.B. Warheit (Critical Reviews in Toxicology, 1989).

The study

• Author: D.B. Warheit
• Journal: Critical Reviews in Toxicology
• Published: 1989;20(1):1-29
• Type of article: Review
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Two important challenges for inhalation toxicologists involve the elucidation of mechanisms of lung toxicity caused by inhalation of chemicals or particulate materials, as well as the extrapolation of animal data to humans. Because risk estimates of toxicity generally are dependent upon experimental data for which a variety of species are utilized, a fundamental knowledge of species similarities and differences in lung anatomy, physiology, biochemistry, cell biology, and corresponding disease processes is essential. In the present review, the known mechanisms of particle deposition and clearance among various species have been highlighted and related to structure/function relationships and pathogenetic responses to some selected inhaled toxicants. In the aggregate, there is remarkable homogeneity in form and function among the species. Morphologic aspects of the respiratory tract and lung defense mechanisms are qualitatively similar among species. On the other hand, quantitative differences between humans and experimental animals are known to exist with respect to deposition and mucociliary clearance of inhaled particulates, and these factors are likely to influence the dose that is delivered to specific target sites in the lung. It is interesting to consider that pathologic cellular events following asbestos, ozone, and nitrogen dioxide exposure are likely to occur at similar sites in humans, nonhuman primates, and rodents. In this respect, it has been demonstrated that the early lesions of asbestos-induced lung disease in both rats and humans are initiated at similar anatomical sites, i.e., the junctions of terminal airways and alveolar regions. PMs and complement-mediated mechanisms have been implicated in the development of asbestosis in rats; however, it remains to be determined whether complement activation plays an important role in human asbestosis, although pulmonary and interstitial macrophages clearly are associated with the fibrogenic process associated with this restrictive lung disease. The toxic pulmonary effects following ozone exposure have been well studied in rodents and nonhuman primates. It has been established that distal airway and alveolar epithelial cells are principal targets of oxidant pollutants, and this is well supported by dosimetry considerations, morphologic observations, and morphometric analyses. Chronic ozone exposure in rats and monkeys causes epithelial injury at the level of the terminal bronchiole and proximal alveolar regions of the lung.(ABSTRACT TRUNCATED AT 400 WORDS)

In plain English

This single-author review examined published research comparing how human and laboratory animal lungs respond to inhaled particles and gases. The animals included rats, mice, hamsters, guinea pigs, dogs and monkeys. It covered lung structure, particle deposition and clearance, and the lung's scavenger cells (macrophages). It also covered asbestos, silica, ozone and nitrogen dioxide. Several reviewed experiments came from the author's own laboratory. In rats and mice briefly exposed to chrysotile asbestos, fibers landed mainly on alveolar duct forks, small branching passages deep in the lung. In rats, macrophages gathered at these spots and formed part of an early lesion. Fewer macrophages gathered in mice lacking the complement component C5 and in rats whose complement was depleted with cobra venom factor. The author wrote that the evidence suggests early asbestos-related lesions in animals and humans begin where the terminal airways join the air-sac regions. The author concluded that lung form and function are broadly similar across species, but that amounts of particles deposited and cleared differ. Whether complement matters in human asbestosis remained to be determined.

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 studies, including the author's own laboratory work
• Who was studied: Published experimental and human data across species: humans and laboratory animals including rats, mice, hamsters, guinea pigs, dogs and monkeys
• Exposure: Inhaled particles and gases. In the reviewed rat experiments these included chrysotile and crocidolite asbestos, fiberglass, wollastonite fibers, Mt. St. Helens volcanic ash and carbonyl iron particles. The review also covered silica, ozone and nitrogen dioxide.
• Main results:
  • In reviewed studies, inhaled chrysotile asbestos fibers deposited preferentially on alveolar duct bifurcations in the distal lungs of rats and mice.
  • In a reviewed study of rats, mice, hamsters and guinea pigs exposed to carbonyl iron particles, deposition patterns were similar for all species. Nearly 80% of particles reaching the distal lung landed on or next to alveolar duct bifurcations.
  • In rats briefly exposed to chrysotile asbestos, macrophages gathered at fiber deposition sites. They formed part of an early lesion marked by a twofold increase in the tissue area of the bifurcation.
  • Macrophage accumulation at asbestos fiber deposition sites was significantly reduced in C5-deficient mice and in rats decomplemented with cobra venom factor (CVF).
  • In rats, all particle types tested except Mt. St. Helens ash caused significant macrophage accumulation at deposition sites.
  • The author wrote that the evidence suggests early asbestos-induced lung lesions in both animals and humans begin at the junctions of terminal airways and alveolar regions.
• The authors' conclusion: The author concluded that lung structure and defense mechanisms are qualitatively similar among species. However, quantitative differences between humans and experimental animals exist in how inhaled particles are deposited and cleared by the airway lining.
• Limitations the authors state:
  • It remains to be determined whether complement activation plays an important role in human asbestosis.
  • It remains to be determined whether the rat model is appropriate for extrapolating to humans with respect to macrophage-mediated particle clearance.
  • Chronic asbestos exposure models in animals lack an understanding of the initiating events and mechanisms of fibrosis.
  • Further studies are needed to confirm the findings and to allow direct comparisons of species responses at various doses.

Topics

Medical terms in this study, explained in our Lexicon: Deposition, Mucociliary Clearance, Interstitial, Macrophage, Fibrogenic, Restrictive Lung Disease.

Related studies

• 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)
• Lung health among plumbers and pipefitters in Edmonton, Alberta — P.A. Hessel, L.S. Melenka, et al. (1998)
• Pathogenic effects of inhaled particles and antigens — A.C. Allison (1974)
• Cytotoxic effects of quartz and chrysotile asbestos: in vitro interspecies comparison with alveolar macrophages — J. Schimmelpfeng, A. Seidel (1991)
• Free radical generation in the toxicity of inhaled mineral particles: the role of iron speciation at the surface of asbestos and silica — I. Fenoglio, L. Prandi, et al. (2001)
• Interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers: a weight-of-the-evidence approach — L.D. Maxim, E.E. McConnell (2001)

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