An evaluation of the carcinogenic potential of five man-made vitreous fibers using the intraperitoneal test
Résumé
The objective of this study was to evaluate the potential carcinogenic hazard of five man-made vitreous fibers (MMVF) following the recommendations of the dust subgroup of the German Maximale Arbeitsplatz Konzentration (MAK) Commission. This was done by rating the tumors arising from intraperitoneal injection in the rat, relative to the number of injected fibers with length (L) > 5 mu m, diameter (Di < 2 mu m, and VD > 5 contained in the sample. Fibers from glass and stone wools were selected for this evaluation. At the outset of this study, because of their chemical composition, the substances tested were considered new-generation insulation wool fibers. As an example, their "solubility" as measured in vitro at pH 7.4 was higher than those of insulation wool fibers used at that time. The samples have been specially manufactured and processed in order to improve their concentration in fibers fitting the criteria of length and diameter required by the protocol of this study. This was done for several purposes. The first one was to test fibers that are as similar as possible to those encountered at the workplace (median diameter below I mu m and median length between 10 and 15 mu m), in order to facilitate extrapolation to the human situation. The second one was to allow injection of the highest possible dose of fibers under a tolerable volume, since too large a volume and/or too high a number of injections may increase the risk of artifactual responses. In addition, the highest doses were selected on the basis of the recommendations of the dust subgroup of the German MAK Commission along with our decision to limit the number of injections to two. Female Wistar rats were used as a model. They received an intraperitoneal injection of various masses (from 0.7 to 55 mg) of sample, and then were followed during an observation period of 130 wk. The positive controls (long-fiber crocidolite from 0.005 to 0.5 mg) exhibited a significant dose-related occurrence of mesotheliomas. According to the MAK Commission criteria, a carcinogenic potential was demonstrated for fiber H (at the highest dose, 55 mg). The other fibers (A, C, F, and C) did not show any statistically significant carcinogenic potential at the tested doses.