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 topic is of substantial practical importance because most quantitative risk analyses 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 disease) is summarized. Dosimetry models indicate that, on a normalized basis, fiber deposition and clearance rates are lower in humans than rats. Potency is less well understood than dosimetry, in part because the source of relevant human data is asbestos studies, which are adequate to demonstrate hazard, but are problematic in other regards. There are significant interspecies 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 microm length) fibers per gram of dry lung] to those in humans. This analysis concludes that, on a weight-of-evidence basis, there is no reason to conclude that humans are more sensitive to fibers than rats with respect to the development of lung cancer.
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Everest Consulting Associates, Cranbury, New Jersey, 08512, USA.
McConnell
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D000818:Animals; D001194:Asbestos / Q000009:adverse effects* / Q000493:pharmacokinetics; D001195:Asbestosis / Q000209:etiology / Q000473:pathology* / Q000662:veterinary; D002273:Carcinogens / Q000009:adverse effects* / Q000493:pharmacokinetics; D002455:Cell Division; D006224:Cricetinae; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation; D008175:Lung Neoplasms / Q000209:etiology; D008420:Manufactured Materials / Q000009:adverse effects; D051379:Mice; D019016:Mineral Fibers / Q000009:adverse effects*; D011634:Public Health; D051381:Rats; D015203:Reproducibility of Results; D018570:Risk Assessment; D014018:Tissue Distribution
D002273:Carcinogens; D019016:Mineral Fibers; D001194:Asbestos