Contribution to comparability of in-vitro and in-vivo man-made mineral fibre (MMMF) durability experiments

Abstract

Toxicologists discuss three major conditions which must be met in order to prevent adverse health effects of dust with regard to three necessary fibre properties: the fibre has to be thin, long, and durable. First definitions concerning the geometric properties thin and long were made already in 1972; however, the criterion durability has not yet been defined. The durability of man-made siliceous fibres has been tested with experimental animals (in-vivo) as well as with purely chemical methods (in-vitro). A reaction of first order was deduced from in-vivo experiments. On the other hand, in-vitro experiments in different setups proved all to follow zeroth-order kinetics. From that, it was postulated sometimes that in-vitro experiments are unsuited to determine the persistence of man-made siliceous fibres. The present study will show that correct mathematical treatment of in-vivo data leads to the same results as obtained from in-vitro experiments. The lg-normal distribution in fine fibrous dust is responsible for the seemingly first-order pattern for mass and fibre number. If the time intervals are chosen to be rather long - as in published in-vivo studies - it is impossible to demonstrate the deviation from the dissolution process at the beginning and at the end. This means the solution of the apparent discrepancy between in-vivo and in-vitro experiments. The mathematical model allows to estimate the lifetime of inhaled fibrous particles from known dissolution velocity and fibre size distribution for the worst case, since the chemical process of dissolution of siliceous fibres is superimposed by accelerating effects as fragmentation or clearance. The validity of the model is shown by comparison with data from an inhalation study [1 to 3]. Also, the model allows the calculation of the accumulated fibre number from dose and duration of exposure.