title: Influence of characteristics of inhaled fibres on development of tumours in the rat lung.
abstract: The objective was to examine and quantify the influence of fibre dimensions, persistence in the lung, and dissolution and cell toxicity in vitro, on the risks of developing lung tumours in rats. Data were brought together from the studies carried out at the IOM under the Colt Fibre Research Programme, and from studies carried out in Switzerland and the USA under the programme of the Thermal Insulation Manufacturers Association. In both studies, groups of rats were exposed by inhalation to a range of airborne fibres. At the end of their lives they were examined for the presence of benign and malignant lung tumours and mesothelioma. The studies differed in a number of details, but were combined on the basis of approximate equivalence of cumulative exposure to airborne fibres. Logistic regression models were used to relate differences in carcinogenicity to fibre characteristics; dimensions, persistence in the lung after intratracheal injection, dissolution rates from bench-top flow-through experiments, measures of inflammation, and other cell responses to fibres in vitro. Despite the small number of data points, the results suggested a primary influence of the airborne concentrations of the numbers of fibres thinner than 1 micron diameter and longer than 20 microns, and of the measured dissolution rate of the fibres. While these results are based on only a small number of fibre types, the statistical model fits the data reasonably well, and enables some cautious insights into the quantitative influences of dimensions and biopersistence. Results were broadly consistent with those from intraperitoneal injection studies of the same fibres, in that the responses were dependent on both the durability of the fibres and the numbers of long thin fibres. In vitro and in vivo cell responses did not predict significantly the risk of cancer following inhalation.
authors.affiliation: Institute of Occupational Medicine, Edinburgh, UK.
authors.forename: B G
authors.initials: BG
authors.lastname: Miller
authors.forename: A D
authors.initials: AD
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Searl
authors.forename: D
authors.initials: D
authors.lastname: Buchanan
authors.forename: R T
authors.initials: RT
authors.lastname: Cullen
authors.forename: C A
authors.initials: CA
authors.lastname: Soutar
authors.forename: J M
authors.initials: JM
authors.lastname: Davis
authors.forename: K
authors.initials: K
authors.lastname: Donaldson
mesh_terms: D000395:Air Pollutants, Occupational / Q000009:adverse effects* / Q000032:analysis* / Q000737:chemistry; D000818:Animals; D004195:Disease Models, Animal; D001239:Inhalation; D016015:Logistic Models; D008175:Lung Neoplasms / Q000209:etiology*; D019016:Mineral Fibers / Q000009:adverse effects* / Q000032:analysis*; D009374:Neoplasms, Experimental / Q000209:etiology*; D051381:Rats; D012307:Risk Factors
chemical_list: D000395:Air Pollutants, Occupational; D019016:Mineral Fibers