A comparison of the results from intra-pleural and intra-peritoneal studies with those from inhalation and intratracheal tests for the assessment of pulmonary responses to inhalable dusts and fibres

Our plain-English summary of A comparison of the results from intra-pleural and intra-peritoneal studies with those from inhalation and intratracheal tests for the assessment of pulmonary responses to inhalable dusts and fibres, by G. Drummond, R. Bevan, P. Harrison (Regulatory Toxicology and Pharmacology, 2016).

The study

• Authors: G. Drummond, R. Bevan, P. Harrison
• Journal: Regulatory Toxicology and Pharmacology
• Published: 2016;81:89-105
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of this paper is to compare results from inhalation studies with those from intraperitoneal and intrapleural tests, where available, for a number of fibrous and particulate test materials. The objective is to determine how well intraperitoneal/intrapleural studies predict the pathological responses observed in more standard in vivo studies of pulmonary toxicity, with a particular focus on carcinogenicity. Published toxicity data was obtained for a number of materials including asbestos, wollastonite, MMVFs (including glass fibres, stone wools and RCF), silicon carbide whiskers, potassium octatitanate, quartz, kevlar, polypropylene and titanium dioxide. For some of the fibrous material reviewed, there is conformity between the results of intraperitoneal and inhalation tests such that they are either consistently positive or consistently negative. For the remaining fibrous materials reviewed, intraperitoneal and inhalation tests give different results, with positive results in the intraperitoneal test not being reflected by positive inhalation results. It is suggested that the intraperitoneal test can be used to exonerate a dust or fibre (because if negative in the intraperitoneal test it is extremely unlikely to be positive in either inhalation or intratracheal tests) but should not be used to positively determine that a dust or fibre is carcinogenic by inhalation. We would argue against the use of intraperitoneal tests for human health risk assessment except perhaps for the purpose of exoneration of a material from classification as a carcinogen.

Copyright © 2016 Elsevier Inc. All rights reserved.

In plain English

This article was a review, not a new experiment. The authors compared published animal studies in which the same dusts or fibres were given by inhalation (and sometimes by instillation into the windpipe) with studies in which they were injected into the abdominal cavity (intraperitoneal) or the chest cavity (intrapleural). Their focus was cancer of the lung and of the mesothelium. The materials included chrysotile, crocidolite and amosite asbestos, man-made vitreous fibres, refractory ceramic fibres, titanium dioxide, quartz, Kevlar and others. For all three asbestos types, the authors reported positive cancer results by inhalation and by intraperitoneal injection, with greater intraperitoneal potency for chrysotile and amosite. In one amosite study, mesothelioma developed in 4.8% of animals exposed by inhalation and 81% of those injected intraperitoneally. Across all materials, results were consistently negative for some and consistently positive for a few. For others, results differed: the intraperitoneal test was positive but inhalation was not. No positive inhalation result was matched by a negative intraperitoneal result. The authors argued against using intraperitoneal tests for human health risk assessment, except perhaps to clear a material from classification as a carcinogen.

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 published animal toxicity studies comparing inhalation and intratracheal results with intraperitoneal and intrapleural injection results for the same materials; not an exhaustive review
• Who was studied: Published animal studies of dusts and fibres given by inhalation (and sometimes intratracheal instillation), compared with studies of the same materials given by intraperitoneal and/or intrapleural injection
• Exposure: Asbestos (chrysotile, crocidolite and amosite), wollastonite, man-made vitreous fibres (including glass fibres, stone and slag wools, and refractory ceramic fibres), titanium dioxide, silicon carbide, potassium octatitanate, quartz, Kevlar and polypropylene
• Main results:
  • Chrysotile asbestos was positive for carcinogenicity in both inhalation and intraperitoneal studies, with much greater potency in the intraperitoneal studies
  • Crocidolite asbestos was positive in both inhalation and intraperitoneal studies, with less difference in potency between routes than for chrysotile
  • Amosite asbestos was positive by both routes, with apparently greater potency by intraperitoneal injection. In the Cullen et al. (2000a) study, 4.8% of animals in the inhalation group developed mesothelioma, compared with 81% in the intraperitoneal group
  • In the Muhle et al. (1987) intraperitoneal study, crocidolite induced malignant tumours in 55% of animals and UICC chrysotile in 84%, compared with 0 to 6% in controls. No significant tumour incidence was reported in the parallel inhalation studies
  • Results were consistently negative or equivocally negative across routes for wollastonite, 104/475 glass fibres, HT stone wool, titanium dioxide (except at extremely high doses), Kevlar and polypropylene
  • Results were consistently positive for both inhalation and injection only for amosite, silicon carbide whiskers and E-Glass, and possibly for crocidolite and quartz
  • Markedly different results between exposure routes were found for chrysotile, various man-made vitreous fibres (including 100/475 and 104E glass fibres and RCF) and potassium octatitanate, with positive intraperitoneal results not reflected by positive inhalation results
  • No positive inhalation study was matched by a negative intraperitoneal study
• The authors' conclusion: The authors concluded that a negative intraperitoneal test makes a positive inhalation result extremely unlikely, but that the intraperitoneal test should not be used to show a material is carcinogenic by inhalation. They argued against using intraperitoneal tests for human health risk assessment, except perhaps to exonerate a material from classification as a carcinogen
• Limitations the authors state:
  • The review was not an exhaustive collection of all published studies
  • Fibre and particle size distribution data were not consistently available
  • Fibres of the same type came from different manufacturers or batches, so chemical compositions may have differed between studies
  • Not all reviewed papers gave enough information on the chemical composition of the test fibres
  • Doses differed greatly between single large injections and long, low-concentration inhalation exposures, making them hard to compare
  • Lung overload can occur at high doses and can produce false positives
  • Relevance of the findings to human exposures remains uncertain

Topics

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

Medical terms in this study, explained in our Lexicon: Wollastonite, Carcinogenic.

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