The current state of knowledge on the use of the benchmark dose concept in risk assessment

Abstract

This review deals with the current state of knowledge on the use of the benchmark dose (BMD) concept in health risk assessment of chemicals. The BMD method is an alternative to the traditional no-observed-adverse-effect level (NOAEL) and has been presented as a methodological improvement in the field of risk assessment. The BMD method has mostly been employed in the USA but is presently given higher attention also in Europe. The review presents a number of arguments in favor of the BMD, relative to the NOAEL. In addition, it gives a detailed overview of the several procedures that have been suggested and applied for BMD analysis, for quantal as well as continuous data. For quantal data the BMD is generally defined as corresponding to an additional or extra risk of 5% or 10%. For continuous endpoints it is suggested that the BMD is defined as corresponding to a percentage change in response relative to background or relative to the dynamic range of response. Under such definitions, a 5% or 10% change can be considered as default. Besides how to define the BMD and its lower bound, the BMDL, the question of how to select the dose-response model to be used in the BMD and BMDL determination is highlighted. Issues of study design and comparison of dose-response curves and BMDs are also covered.

Estimation of the benchmark duration of alternating shift work associated with increased total cholesterol levels among male Japanese workers

“…The BMD concept was introduced by Crump (21) and involves fitting a mathematical model to dose-response data. The BMD is defined as the dose that causes a predetermined change in response (22). This specified change in response is generally referred to as the BMR (22).…”

“…One advantage of the BMDL/BMD approach is that it utilizes the whole dose-response curve (20). While the response or risk level at the "no observed adverse effect level" was not assessed and may vary from case to case, the BMDL corresponds to an explicit response level and therefore introduces consistency (22). Using multiple logistic regression, researchers have also shown that it is possible to take into account the effect of potential covariates (23).…”

Estimation of a Safe Level for Occupational Exposure to Vinyl Chloride Using a Benchmark Dose Method in Central China

“…A 10% benchmark response level (BMR) is conventionally used for dichotomous end points because it is at the low end of the observable range for many common study designs. Various investigations [23][24][25][26][27][28][29][30] have performed risk assessments of the non-cancer effects of toxic exposures using the benchmark dose (BMD) method. A previous study 31) evaluated the effects of occupational exposure to vinyl chloride monomer (VCM) on the micronucleus and estimated a benchmark dose for chromosome damage induced by VCM in VCM-exposed workers.…”

Establishing allowable value of Electric Conductivity for monitoring groundwater based on the benchmark dose concept and its application

“…Various organizations and regulatory agencies in the US and abroad have considered adoption of its use [6]. The BMD approach is being considered in the international arena as part of the effort to develop a standard approach [3,7]. In general, BMD is determined by fitting a dose-response model to data observed in the range of higher doses, or higher risk doses, since it is difficult to observe responses in low doses.…”

“…Murrell et al define a modified BMD for making comparison among various endpoints more meaningful [5]. On the other hand, Sand et al illustrate an epidemiological approach for a continuous response variable based on the definition of the normal range for clinical data [7]. When developing water quality standards, the latter approach seems appropriate for use with our data to show relationships between NO 3 -N and EC, under pristine and uncontaminated environmental conditions, with regards to the standard value of 10 for NO 3 -N as a pre-specified limit of risk.…”