Intrapleural administration of fibres induces mesothelioma in rats in the same relative order of hazard as occurs in man after exposure.
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.
Carthew
P
P
MRC Toxicology Unit, MRC Laboratories, Carshalton, Surrey, UK.
Hill
R J
RJ
Edwards
R E
RE
Lee
P N
PN
D000818:Animals; D001194:Asbestos / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D008654:Mesothelioma / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D001194:Asbestos