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Review
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A Toxicological Basis to Derive a Generic Interspecies Uncertainty Factor Edward J. Calabrese and Linda A. Baldwin School of Public Health, University of Massachusetts, Amherst, MA 01003
USA Abstract A new method is proposed to derive the size of the interspecies uncertainty factor (UF) that is toxicologically and statistically based. The method involves quantifying interspecies variation in susceptibility to numerous toxic substances via the use of binary interspecies comparisons that are converted to a 95% UF. This interspecies UF represents an estimate of the upper 95% of the population of 95% prediction intervals (PI) for binary interspecies comparisons within four categories of phylogenetic relatedness (species within genus, genera within family, families within order, orders within class) . The 95% interspecies UFs range from a low of 10 for species within genus up to 65 for orders within class. Most mammalian toxicology studies involving mice, rats, cats, dogs, gerbils, and rabbits are orders-within- class categories for human risk assessment and would be provided a 65-fold UF. Larger or smaller interspecies UF values could be selected on the level of protection desired. Key words: interspecies variation, mammalian toxicology, risk assessment, uncertainty factor. Environ Health Perspect 102:14-17(1994) Address correspondence to E. J. Calabrese. Received 21 June 1993 ; accepted 2 October 1993. The full version of this article is available for free in HTML format. |
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