Use of NOAEL, benchmark dose, and other models for human risk assessment
of hormonally active substances
R. W. Setzer, Jr. and C. A. Kimmel
USEPA, Office of Research and Development, National
Health and Environmental Effects Research Laboratory, Experimental Toxicology
Division, Pharmacokinetics Branch, MD B143-01 109 TW Alexander Drive,Research
Triangle Park, NC 27711, USA;
USEPA Office of Research and Development, National Center for Environmental
Assessment (8623D), Ariel Rios Building, 1200 Pennsylvania Ave. NW,
Washington, DC 20460, USA
Abstract: The benchmark dose (BMD) is the dose of a substance
that is expected to result in a prespecified level of effect, the benchmark
response level or BMR. It is a general approach to characterizing dose
response, applicable to any toxicant and endpoint. A BMD is conceptually
superior to a "no observed adverse effect level" (NOAEL) for this purpose
because of being less determined by experimental design, because it
is a precisely defined entity, and because its precision can be estimated.
Since a BMD is a single number, just as an NOAEL, it is tempting to
use the BMD as a straightforward replacement for the NOAEL in the assessment
process for calculating allowable daily intakes. However, the level
of toxic response at a NOAEL is unknown, while that at a BMD is well
defined. Use of the BMD approach potentially adds consistency and objectivity
to the process of deriving reference values (RfDs, RfCs, or ADIs) for
setting regulatory levels. To take advantage of this, BMRs need to be
selected in a consistent way across studies and endpoints. This paper
discusses some issues affecting the selection of BMRs, and presents
an example of a BMD calculated for the effects of peripubertal exposure
to the fungicide vinclozolin.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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