Benchmark calculations in risk assessment using continuous dose-response information: The influence of variance and the determination of a cut-off value

Abstract

A benchmark dose (BMD) is the dose of a chemical that corresponds to a predetermined increase in the response (the benchmark response, BMR) of a health effect. In this article, a method (the hybrid approach) for benchmark calculations from continuous dose-response information is investigated. In the formulation of the methodology, a cut-off value for an adverse health effect has to be determined. It is shown that the influence of variance on the hybrid model depends on the choice of determination of the cut-off point. If the cut-off value is determined as corresponding to a specified tail proportion of the control distribution, P(0), the BMD becomes biased upward when the variance is biased upward. On the contrary, if the cutoff value is directly determined to some level of the continuous response variable, the BMD becomes biased upward when the variance is biased downward. A simulation study was also performed in which the accuracy and precision of the BNID was compared for the two ways of determining the cut-off value. In general, considering BMRs of 1, 5, and 10% (additional risk) the precision of the BMD became higher when the cut-off value was estimated by specifying P(0), relative to the case with a direct determination. Use of the square-root of the maximum-likelihood estimator of the variance in BMD estimation may provide a bias that is reflected by the cut-off formulation (downward bias if specifying P(0), and upward bias if specifying the cut-off, c, directly). This feature may be reduced if an unbiased estimator of the standard deviation is used in the calculations

Published in

Risk Analysis
2003, volume: 23, number: 5, pages: 1059-1068
Publisher: BLACKWELL PUBLISHERS

SLU Authors

• von Rosen, Dietrich

  • Department of Energy and Technology, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Forest Science
Fish and Aquacultural Science
Horticulture

Publication identifier

• DOI: https://doi.org/10.1111/1539-6924.00381

Permanent link to this page (URI)

https://res.slu.se/id/publ/4525