A Mathematical Model of fiber Carcinogenicity and Fibrosis in Inhalation and Intraperitoneal Experiments in Rats

AbstractA hypothesis is presented that predicts the incidence of tumors and fibrosis in rats exposed to various types of rapidly dissolving fibers in an inhalation study or in an intraperitoneal (ip) injection experiment, for which the response to durable fibers has been determined. The model takes into account the fiber diameter and the dissolution rate of fibers longer than 20 μm in the lung, and it predicts the measured tumor and fibrosis incidence to within approximately the precision of the measurements. The basic concept of the model is that a rapidly dissolving long fiber has the same response in an animal bioassay as a much smaller dose of a durable fiber. Long, durable fibers are considered to have special significance since no effective mechanism is known by which these fibers may be removed. In particular, the hypothesis is that the effective dose of a dissolving long fiber scales as the residence time of that fiber in the extracellular fluid. For example, a certain dose of a fiber that dissolv...