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Characterizing non-constant relative potency.

ABSTRACT: Relative potency plays an important role in toxicology. Estimates of relative potency are used to rank chemicals by their effects, to calculate equivalent doses of test chemicals compared to a standard, and to weight contributions of constituent chemicals when evaluating mixtures. Typically relative potency is characterized by a constant dilution factor, even when non-similar dose-response curves indicate that constancy is inappropriate. Improperly regarding relative potency as constant may distort conclusions and potentially mislead investigators or policymakers. We consider a more general approach that allows relative potency to vary as a function of dose, response, or response quantile. Distinct functions can be defined, each generalizing different but equivalent descriptions of constant relative potency. When two chemicals have identical response limits, these functions all carry fundamentally equivalent information; otherwise, relative potency as a function of response quantile is distinct and embodies a modified definition of relative potency. Which definition is preferable depends on whether one views any differences in response limits as intrinsic to the chemicals or as extrinsic, arising from idiosyncrasies of data sources. We illustrate these ideas with constructed examples and real data. Relative potency functions offer a unified and principled description of relative potency for non-similar dose-response curves.

SUBMITTER: Dinse GE

PROVIDER: S-EPMC3134169 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Characterizing non-constant relative potency.

Dinse Gregg E GE Umbach David M DM

Regulatory toxicology and pharmacology : RTP 20110513 3

Relative potency plays an important role in toxicology. Estimates of relative potency are used to rank chemicals by their effects, to calculate equivalent doses of test chemicals compared to a standard, and to weight contributions of constituent chemicals when evaluating mixtures. Typically relative potency is characterized by a constant dilution factor, even when non-similar dose-response curves indicate that constancy is inappropriate. Improperly regarding relative potency as constant may dist ...[more]

PMID: 21601607

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Project description:Hydromechanical and structural properties of compacted loess have a significant impact on the stability and reliability of subbase and subgrade, which needs to be quickly determined in the field and laboratory. Hence, an electrical resistivity method was used to characterize the hydromechanical and structural properties of compacted loess during constant rate of strain compression. In the present work, compacted loess samples with a dry density of 1.7 g/cm3, a diameter of 64 mm, a height of 10 mm and different water content ranging from 5-25% were prepared. The constant rate of strain (CRS) tests were conducted by a developed oedometer cell equipped with a pair of horizontal circular electrodes (diameter of 20 mm) and vertical rectangular electrodes (width of 3.5 mm) to determine the electrical resistivity of compacted loess. The results showed that as average water content increases, plastic compression indices increase from 0.220 to 0.350 and the elastic compression indices increase from 0.0152 to 0.030, but they decrease to 0.167 and 0.010 and yield stress decreases from 381.28 kPa to 72.35 kPa. Moreover, as vertical strain increases, the variation trend of average formation factor and average shape factor for the lower water content decreases but increases for the maximum water content, and the anisotropy index first decrease and then tend to increase slightly, which indicates that the structural properties of unsaturated and saturated samples during compression exhibits different trend and the anisotropy of samples tend to be stable as vertical strain increases. As the water content increases, the average formation factor and average shape factor decrease, but the anisotropy index first decreases then increases, suggesting that water content has a significant impact on these electrical indices. More important, The coefficients of average formation factor decrease from 33.830 to -1.698 and the coefficients of average shape factor decrease from 8.339 to -0.398 as water content increases, whereas there is less variation for the coefficient of anisotropic index with a value of 2.190. An equation correlating average formation factor and water content and vertical strain is regressed to characterize the hydromechanical properties of compacted loess by measuring its impedance, which can be used to evaluate the stability of compacted loessic ground and subgrade.

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Characterizing non-constant relative potency.

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Characterizing non-constant relative potency.

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