Intrapleural administration of fibres induces mesothelioma in rats in the same relative order of hazard as occurs in man after exposure

Our plain-English summary of Intrapleural administration of fibres induces mesothelioma in rats in the same relative order of hazard as occurs in man after exposure, by P. Carthew, R.J. Hill, R.E. Edwards, et al (Human & Experimental Toxicology, 1992).

The study

• Authors: P. Carthew, R.J. Hill, R.E. Edwards, P.N. Lee
• Journal: Human & Experimental Toxicology
• Published: 1992;11(6):530-4
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

1. The dose-response data for the induction of mesothelioma, in rats, by the intrapleural administration of the fibrous zeolite, erionite, has been compared to the published data for the crocidolite and chrysotile forms of asbestos. Erionite is more than two orders of magnitude more carcinogenic than either of the two forms of asbestos examined. 2. The relative sensitivity of the intrapleural and intraperitoneal routes of injection were also examined. The sensitivity of the intraperitoneal over the intrapleural route of administration was considerably greater for all the forms of asbestos examined but not for erionite. 3. The relationship for different fibres, between the number of fibres required to give animals mesothelioma, at the 50% or 10% observable tumour effect level (OTEL) was examined, and a ranking of relative carcinogenicity was made. 4. This showed that the data derived from the dose responses obtained by the intrapleural administration of fibres to rats ranked the relative carcinogenicity of erionite, crocidolite and chrysotile in accord with the known clinical mesothelioma induction in man after exposure to these fibres. Examination of the carcinogenicity ranking from data derived from intraperitoneal injections of fibres was not in accord with the known clinical mesothelioma induction in man for the various asbestos types examined.

In plain English

This was an analysis of existing rat data rather than a human study. The authors combined eight dose-response experiments, one their own and the others from three other groups, in which fibres were injected into rats' chest cavities (the intrapleural route) or abdominal cavities (the intraperitoneal route). The fibres were erionite, a fibrous zeolite mineral, and crocidolite and chrysotile asbestos. Amosite had data only for the abdominal route. Using a statistical model, the authors estimated how many long, thin fibres were needed to produce mesothelioma in 10% or 50% of rats. By the chest route, erionite was more than two orders of magnitude more carcinogenic than either asbestos type. The abdominal route was much more sensitive than the chest route for crocidolite and chrysotile, but only slightly for erionite. Chest-route results ranked erionite above crocidolite above chrysotile, the order the authors described as seen in humans. Abdominal-route results did not. The authors concluded the chest route may be more appropriate for comparing fibres' relative hazard to people. They noted few fibre types and small groups of rats.

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: Statistical reanalysis (probit dose-response modelling) of eight rat injection experiments, one of them the authors' own erionite study
• Who was studied: Rats in eight dose-response experiments conducted by the authors and three other research groups. Studies differed in rat sex and strain, age at dosing and study length. The text does not give the numbers of rats, because the data table is missing.
• Exposure: Intrapleural or intraperitoneal injection of erionite (a fibrous zeolite), crocidolite and chrysotile. Amosite was tested only by the intraperitoneal route. Doses were converted to numbers of fibres longer than 8 micrometres and thinner than 0.25 micrometres, using factors of 1.4 (erionite), 3.4 (crocidolite), 27.0 (chrysotile) and 0.9 (amosite) million per mg. The authors' own erionite came from the same batch used in earlier inhalation studies.
• Main results:
  • Erionite was more than two orders of magnitude more carcinogenic than crocidolite or chrysotile (intrapleural comparison).
  • Compared with the intrapleural route, the intraperitoneal route was only slightly more sensitive for erionite but much more sensitive for crocidolite and chrysotile.
  • The intrapleural route ranked erionite well above crocidolite, and crocidolite above chrysotile. The authors said this agreed with the order seen in humans.
  • The intraperitoneal route did not match that order. Erionite was not clearly more carcinogenic than amosite, and was somewhat less so at the 10% level. Crocidolite was not clearly more carcinogenic than chrysotile, and was less so at the 50% level.
  • The dose-response slope differed between fibres, being steeper for erionite than for crocidolite and amosite. As a result, relative hazard values shifted somewhat between the 10% and 50% levels. The authors said their general conclusions did not change.
• The authors' conclusion: The authors concluded that the intraperitoneal route's failure to predict the known human order of hazard casts serious doubt on its results for ranking fibres. They said it may still be used to see whether a fibre causes mesothelioma, but the intrapleural route may be more appropriate for assessing fibres' relative carcinogenicity to man. They called for more dose-response data.
• Limitations the authors state:
  • Few fibre types had data allowing comparison of rat and human findings.
  • Groups of rats at each dose level were small, so the fitted curves were not precise.
  • Survival differences could only be handled by dropping very high doses from the analysis, a method the authors called somewhat arbitrary.
  • The studies differed in rat sex and strain, age at dosing and study length.
  • Exact fibre comparisons depended on which tumour level (10% or 50%) was used, which the authors called unsatisfactory. No human dose-response data were available to resolve this.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Dose-response relationship, Zeolite, erionite, Crocidolite, Chrysotile, Carcinogenic.

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