Biopersistence of synthetic mineral fibers as a predictor of chronic intraperitoneal injection tumor response in rats

In December 1997 the European Commission (EC) adopted Directive 97/69/EC (O .J. L 343/19 of 13 December 1997), in which criteria were established for t he classification and labeling of synthetic mineral fibers. This directive was derived based upon an extensive program evaluating current scientific k nowledge on fiber pathogenicity and its relationship to the biopersistence of long fibers. Within this context, the biopersistence of fibers longer th an 20 mum was found to be a good predictor of the lung burden and early pat hological changes in chronic inhalation studies with fibers as well as of t he tumor response in chronic intraperitoneal studies with fibers. The analy sis that provided the scientific basis for the relationship of biopersisten ce to the chronic intraperitoneal (ip) results is presented in detail. Anal ysis of the relationship of biopersistence clearance half-times to ip tumor response shows a statistically significant relationship of ip tumor respon se to not only the number of fibers injected, but also the median length of the fibers injected and their solubility ( clearance half-time). The resul ts show that the biopersistence half-times as determined by intratracheal i nstillation (T-1/2 of WHO fibers or weighted T-1/2 of fibers with L > 20 mu m) and as determined by inhalation ( weighted T-1/2 of fibers with L > 20 m um) are equivalent predictors of the ip results. From these ip studies, fib ers that can be exonerated from classification as carcinogens in Europe hav e a relative tumorigenic potency in the ip cavity of between 66 and 2500 ti mes less than fibers that have been shown to produce a significant increase in tumors following chronic inhalation exposure. In addition, based upon t he ip results, there is no statistical difference between the EC and the ot her fiber exoneration criteria, such as the German Gefahrstoffverordnung of 1999.