Benchmark dose lower bound

Once the BMD is identified, the one-sided lower 95th confidence interval on the BMD called the BMDL (benchmark dose lower bound) is used as the POD. Similar to noncancer risk assessment, the POD is then divided by uncertainty factors to account for potential interspecies differences, intraindividual variability, and so on. The current risk assessment paradigm has accepted that, by accounting for uncertainty through use of the BMDL and other uncertainty factors, the resulting dose is either below a toxic threshold or so low as to constitute a virtually safe dose (Bogdanffy et al. 2001). 

Similarly, in order to avoid any quantitative estimate, an MOE approach has been recommended by, e.g., JECFA (the Joint FAO/WHO Expert Committee on Food Additives) and EFSA (the European Food Safety Authority) in the assessment of compounds that are both genotoxic and carcinogenic by using a benchmark dose (BMD) approach to estimate the BMDLio (benchmark dose lower limit) representing the lower bound of a 95% confidence interval on the BMD corresponding to a 10% tumor incidence (see Section 6.4). 

In many respects, the foundations and framework of the proposed risk-based hazardous waste classification system and the recommended approaches to implementation are intended to be neutral in regard to the degree of conservatism in protecting public health. With respect to calculations of risk or dose in the numerator of the risk index, important examples include (1) the recommendation that best estimates (MLEs) of probability coefficients for stochastic responses should be used for all substances that cause stochastic responses in classifying waste, rather than upper bounds (UCLs) as normally used in risk assessments for chemicals that induce stochastic effects, and (2) the recommended approach to estimating threshold doses of substances that induce deterministic effects in humans based on lower confidence limits of benchmark doses obtained from studies in humans or animals. Similarly, NCRP believes that the allowable (negligible or acceptable) risks or doses in the denominator of the risk index should be consistent with values used in health protection of the public in other routine exposure situations. NCRP does not believe that the allowable risks or doses assumed for purposes of waste classification should include margins of safety that are not applied in other situations. 

Benchmark dose (BMD). The BMD is used as an alternative to the NOAEL for reference dose calculations. The dose response is modeled and the lower confidence bound for a dose at a specified response level is calculated. For a further description, see the section on BMD calculation. 

Benchmark An exposure level that corresponds to a statistical lower bound on a dose — standard probability of an effect, such as 10% of people affected. 

The BMD approach has been put forward as an alternative to the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) approach for health effects because it provides a more quantitative alternative point of departure for the first step in the dose-response assessment (International Programme on Chemical Safety, in press). The BMD approach is based on a mathematical model being fitted to the experimental data within the observable range and estimates the dose that causes a low but measurable response (the benchmark response) typically chosen at a 5% or 10% incidence above the control. The BMD lower limit (BMDL) refers to the corresponding lower limit of a one-sided 95% confidence interval on the BMD. Using the lower bound takes into account the uncertainty inherent in a given study and assures (with 95% confidence) that the chosen benchmark response is not exceeded. 

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