Mesothelioma dose response following intraperitoneal injection of mineral fibres.
The relationship between injected dose and the development of peritoneal mesotheliomas has been examined in rats using the UTCC standard reference samples of chrysotile, crocidolite and amosite as well as a sample of fibrous erionite from Oregon. Doses injected into the peritoneal cavity ranged from 0.005 to 25 mg and with each dust a clear dose response was found. The proportion of animals developing tumours increased with the amount of dust injected while the tumour induction period was reduced. When times to death from mesothelioma were analysed using standard hazard models, erionite was the most carcinogenic dust by mass followed by chrysotile, amosite and crocidolite. The hazard slopes for erionite, chrysotile and crocidolite, over the range of doses examined, were parallel while the slope for amosite was shallower. The relative hazards for the various dust types were also examined with dose expressed as the number of injected fibres in a range of sizes as measured by SEM. No combination of fibre dimensions was found at which the hazard for the four dust types was equal although when dose was expressed as the number of long fibres injected (> 8 microns in length) the hazard slopes for chrysotile, crocidolite and amosite were relatively close. The hazard level of erionite remained well above the other dust types regardless of how the dose was expressed.
Davis
J M
JM
Institute of Occupational Medicine Ltd, Edinburgh.
Bolton
R E
RE
Miller
B G
BG
Niven
K
K
D000818:Animals; D001194:Asbestos / Q000008:administration & dosage / Q000145:classification / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008654:Mesothelioma / Q000209:etiology*; D010316:Particle Size; D010534:Peritoneal Neoplasms / Q000209:etiology*; D016016:Proportional Hazards Models; D051381:Rats; D012306:Risk
D001194:Asbestos