Interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers: A weight-of-the-evidence approach

This analysis reviews the available literature on interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers (SVFs). This topi c is of substantial practical importance because most quantitative risk ana lyses on the effects of inhalation of SVFs are based upon extrapolation of data from rodent inhalation studies. Available information on interspecies comparisons for both dosimetry (the relation between exposure concentration and fiber lung burden) and potency (the relation between lung burden and d isease) is summarized. Dosimetry models indicate that, on a normalized basi s, fiber deposition and clearance rates are lower in humans than rats. Pote ncy is less well understood than dosimetry, in part because the source of r elevant human data is asbestos studies, which are adequate to demonstrate h azard, but are problematic in other regards. There are significant interspe cies differences between the mouse, hamster, rat, and human. The available evidence suggests that the rat is preferable as a model for the human. Rats develop fibrosis at comparable lung burdens [10(6) long (> 20 mum length) fibers per gram of dry lung] to those in humans. This analysis concludes th at, on a weight-of-evidence basis, there is no reason to conclude that huma ns are more sensitive to fibers than rats with respect to the development o f lung cancer. (C) 2001 Academic Press.