Indices of fiber biopersistence and carcinogen classification for synthetic vitreous fibers (SVFs).
It is generally accepted that the biopersistence of a synthetic vitreous fiber (SVF) is an important determinant of its biological activity. Experimental protocols have been developed to measure the biopersistence of an SVF from short-term inhalation experiments with rats. Clearance kinetics of long (>20 microm) fibers (those believed to have greatest biological activity) have been approximated by one- or two-pool models. Several measures or indices of biopersistence have been proposed in the literature of which three, the weighted half-time (WT(1/2)), the time required to clear 90% of long fibers (T(0.9)), and the so-called slow-phase half-time (T(2)), have been investigated in some detail. This paper considers both one- and two-pool models for long fiber clearance, characterizes the properties of these candidate indices of fiber biopersistence, identifies measures with potentially superior statistical properties, suggests possible cutoff values based on the relation between biopersistence and the outcome of chronic bioassays, and offers comments on the selection of efficient experimental designs. This analysis concludes that WT(1/2) and T(0.9) are highly correlated, are efficient predictors of the outcome of chronic bioassays, and have reasonable statistical properties. T(2), although perhaps attractive in principle, suffers from some statistical shortcomings when estimated using present experimental protocols. The WT(1/2) is shown to be directly proportional to the cumulative exposure (fiber days) after the cessation of exposure and also the mean residence time of these fibers in the lung.
Maxim
L Daniel
LD
Everest Consulting Associates, Cranbury, New Jersey 08512, USA.
Boymel
Paul
P
Chase
Gerald R
GR
Bernstein
David M
DM
D000818:Animals; D019540:Area Under Curve; D001822:Body Burden; D002273:Carcinogens / Q000145:classification / Q000493:pharmacokinetics* / Q000633:toxicity; D005898:Glass; D006207:Half-Life; D006801:Humans; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D017640:Silicates / Q000145:classification / Q000493:pharmacokinetics* / Q000633:toxicity
D002273:Carcinogens; D017640:Silicates; C009753:fiberglass