Biopersistence of synthetic mineral fibers as a predictor of chronic inhalation toxicity 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 inhalation results is presented in detail. Proportional o dds regression techniques were used to determine the relationship between b oth inhalation and intratracheal instillation biopersistence clearance half -times and the collagen deposition at the broncho-alveolar junction as dete rmined following 24 mo in chronic inhalation toxicity studies. The results indicate all the indicators of biopersistence considered are equally good p redictors of the early long-term change that occurs in the lung in response to more durable fibers. This change, the collagen deposition at the bronch o-alveolar junction, is a precursor of interstitial fibrosis, which has bee n shown to be associated with tumor response in fiber-exposed animals. The results show that the clearance half-times set in the EC directive are with in the baseline for this parameter.