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.
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Pure and Applied Chemistry
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Volume 55 (1983)
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Volume 54 (1982)
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Volume 53 (1981)
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- Nuclear receptor superfamily: Principles of signaling
- Nuclear receptor coregulators
- Function and mode of action of nuclear receptors: Estrogen, progesterone, and vitamin D
- Biological function and mode of action of the androgen receptor
- Genetic dissection of gluco- and mineralocorticoid receptor function in mice
- Functions of RARs and RXRs in vivo: Genetic dissection of the retinoid signaling pathway
- Biological function and mode of action of nuclear xenobiotic receptors
- Molecular mechanisms of cross-talk between growth factors and nuclear receptor signaling
- Estrogen receptor action through target genes with classical and alternative response elements
- Nuclear receptor action involved with sex differentiation
- Human disorders caused by nuclear receptor gene mutations
- Interactions of exogenous endocrine active substances with nuclear receptors
- Transcriptional roles of AhR in expression of biological effects induced by endocrine disruptors
- Nonmammalian nuclear receptors: Evolution and endocrine disruption
- Analysis of endocrine active substances in food and the environment
- Naturally produced steroid hormones and their release into the environment
- Concentration of phytohormones in food and feed and their impact on the human exposure
- Pharmaceuticals and personal care products - A source of endocrine disruption in the environment?
- Endocrine active industrial chemicals: Release and occurrence in the environment
- Release of pesticides into the environment and initial concentrations in soil, water, and plants
- Role of metabolism in the endocrine-disrupting effects of chemicals in aquatic and terrestrial systems
- Critical factors in exposure modeling of endocrine active substances
- Environmental fate and metabolism: Issues and recommendations
- Interactions of xenobiotics with the steroid hormone biosynthesis pathway
- Organochlorine compounds and breast cancer risk
- Prevention of ambiguous genitalia by prenatal treatment with dexamethasone in pregnancies at risk for congenital adrenal hyperplasia
- Male reproductive disorders and the role of endocrine disruption: Advances in understanding and identification of areas for future research
- Brominated flame retardants and endocrine disruption
- Toxicity vs. beneficial effects of phytoestrogens
- Evaluation of thyroid function in neonatal and adult rats: The neglected endocrine mode of action
- Modification of endocrine active potential by mixtures
- Experience with new testing guidelines with endocrine-sensitive end-points
- Critical evaluation of observed adverse effects of endocrine active substances on reproduction and development, the immune system, and the nervous system
- Significance of experimental studies for assessing adverse effects of endocrine-disrupting chemicals
- Determination of acceptable exposure levels for humans for endocrine active substances: Use of animal models
- Use of NOAEL, benchmark dose, and other models for human risk assessment of hormonally active substances
- Endocrine active substances and dose response for individuals and populations
- Endocrine disruption occurring at doses lower than those predicted by classical chemical toxicity evaluations: The case bisphenol A
- Environmental estrogens and sperm counts
- Historical perspective on endocrine disruption in wildlife
- Endocrine disruption in invertebrates
- Endocrine disruption in wild freshwater fish
- Effects of endocrine disruptors in aquatic mammals
- Endocrine disruption in marine fish
- Deformed frogs and environmental retinoids
- Contaminant-induced endocrine and reproductive alterations in reptiles
- Review of the effects of endocrine-disrupting chemicals in birds
- Wildlife as models for the study of how mixtures, low doses, and the embryonic environment modulate the action of endocrine-disrupting chemicals
- Interactions of endocrine-disrupting chemicals with stress responses in wildlife
- Effects of endocrine active substances in wildlife species: Genetic, biochemical, and physiological factors in variable susceptibility to endocrine disruptors
- Development of fish tests for endocrine disruptors
- Endocrine disruption in wildlife: The future?
- Mechanism-based QSAR approach to the study of the toxicity of endocrine active substances
- Regulatory application of SAR/QSAR for priority setting of endocrine disruptors: A perspective
- QSAR prioritization of chemical inventories for endocrine disruptor testing
- The nature of the ligand-binding pocket of estrogen receptor alpha and beta: The search for subtype-selective ligands and implications for the prediction of estrogenic activity
- Fragment molecular orbital study of the binding energy of ligands to the estrogen receptor
- Toxicogenomics: Impact on human health
- Temporal responses to estrogen in the uterus
- Application of toxicogenomics to the endocrine disruption issue
- Transcript profiles elicited by developmental exposure to endocrine-mediated toxicants
- Use of gene expression profiling to understand the transcriptional program associated with estrogen-induced uterine growth
- Need for establishing integrated programs to monitor endocrine active compounds
- Search for the evidence of endocrine disruption in the aquatic environment; Lessons to be learned from joint biological and chemical monitoring in the European project COMPREHEND
- Biomonitoring: Integration of biological end-points into chemical monitoring
- Identifying the causative agents: The use of combined chemical and biological strategies in monitoring programs
- Closing the gap between exposure and effects in monitoring studies
- Simple, rapid assays for conventional definite testing of endocrine disruptor hazard: Summary and recommendations
- Testing of endocrine active substances using an enhanced OECD test guideline 407: Experiences from studies on flutamide and ethinylestradiol
- Application of rat medium-term bioassays for detecting carcinogenic and modifying potentials of endocrine active substances
- Enhanced one-generation reproductive toxicity study in rats for detecting endocrine-disrupting effects of chemicals
- Making decisions in the 21st century: Scientific data, weight of evidence, and the precautionary principle
- Precautionary principle and endocrine active substances
- Why epidemiology of endocrine disruptors warrants the precautionary principle
- General process for the risk assessment of pesticides that interact with or affect the endocrine system
- Role of the precautionary principle in the EU risk assessment process on industrial chemicals
- Differing perspectives on the use of scientific evidence and the precautionary principle
- Risk management options for endocrine disruptors in national and international programs
- Hormonally active agents and plausible relationships to adverse effects on human health
- Government view of endocrine disruption in wildlife
- Risk perception: A chemical industry view of endocrine disruption in wildlife
- Endocrine active substances and the need to improve environmental protection: An environmentalist's perspective
- Endocrine disruption and the USFDA's Center for Drug Evaluation and Research
- Relevant activities for risk management of endocrine disruptors in Japanese government agencies
- Advancing the testing and assessment of chemical substances for endocrine disruption: OECD activities
Use of NOAEL, benchmark dose, and other models for human risk assessment of hormonally active substances
R. W. Setzer Jr.
- Corresponding author
- 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
- Other articles by this author:
- De Gruyter OnlineGoogle Scholar
- Corresponding author
- 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
- Other articles by this author:
- De Gruyter OnlineGoogle Scholar
Published Online: 2009-01-01 | DOI: https://doi.org/10.1351/pac200375112151
Free Access
About the article
Published Online: 2009-01-01
Published in Print: 2003-01-01
Citation Information: Pure and Applied Chemistry, Volume 75, Issue 11-12, Pages 2151–2158, ISSN (Online) 1365-3075, ISSN (Print) 0033-4545, DOI: https://doi.org/10.1351/pac200375112151.
© 2013 Walter de Gruyter GmbH, Berlin/Boston.
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- Nuclear receptor superfamily: Principles of signaling
- Nuclear receptor coregulators
- Function and mode of action of nuclear receptors: Estrogen, progesterone, and vitamin D
- Biological function and mode of action of the androgen receptor
- Genetic dissection of gluco- and mineralocorticoid receptor function in mice
- Functions of RARs and RXRs in vivo: Genetic dissection of the retinoid signaling pathway
- Biological function and mode of action of nuclear xenobiotic receptors
- Molecular mechanisms of cross-talk between growth factors and nuclear receptor signaling
- Estrogen receptor action through target genes with classical and alternative response elements
- Nuclear receptor action involved with sex differentiation
- Human disorders caused by nuclear receptor gene mutations
- Interactions of exogenous endocrine active substances with nuclear receptors
- Transcriptional roles of AhR in expression of biological effects induced by endocrine disruptors
- Nonmammalian nuclear receptors: Evolution and endocrine disruption
- Analysis of endocrine active substances in food and the environment
- Naturally produced steroid hormones and their release into the environment
- Concentration of phytohormones in food and feed and their impact on the human exposure
- Pharmaceuticals and personal care products - A source of endocrine disruption in the environment?
- Endocrine active industrial chemicals: Release and occurrence in the environment
- Release of pesticides into the environment and initial concentrations in soil, water, and plants
- Role of metabolism in the endocrine-disrupting effects of chemicals in aquatic and terrestrial systems
- Critical factors in exposure modeling of endocrine active substances
- Environmental fate and metabolism: Issues and recommendations
- Interactions of xenobiotics with the steroid hormone biosynthesis pathway
- Organochlorine compounds and breast cancer risk
- Prevention of ambiguous genitalia by prenatal treatment with dexamethasone in pregnancies at risk for congenital adrenal hyperplasia
- Male reproductive disorders and the role of endocrine disruption: Advances in understanding and identification of areas for future research
- Brominated flame retardants and endocrine disruption
- Toxicity vs. beneficial effects of phytoestrogens
- Evaluation of thyroid function in neonatal and adult rats: The neglected endocrine mode of action
- Modification of endocrine active potential by mixtures
- Experience with new testing guidelines with endocrine-sensitive end-points
- Critical evaluation of observed adverse effects of endocrine active substances on reproduction and development, the immune system, and the nervous system
- Significance of experimental studies for assessing adverse effects of endocrine-disrupting chemicals
- Determination of acceptable exposure levels for humans for endocrine active substances: Use of animal models
- Use of NOAEL, benchmark dose, and other models for human risk assessment of hormonally active substances
- Endocrine active substances and dose response for individuals and populations
- Endocrine disruption occurring at doses lower than those predicted by classical chemical toxicity evaluations: The case bisphenol A
- Environmental estrogens and sperm counts
- Historical perspective on endocrine disruption in wildlife
- Endocrine disruption in invertebrates
- Endocrine disruption in wild freshwater fish
- Effects of endocrine disruptors in aquatic mammals
- Endocrine disruption in marine fish
- Deformed frogs and environmental retinoids
- Contaminant-induced endocrine and reproductive alterations in reptiles
- Review of the effects of endocrine-disrupting chemicals in birds
- Wildlife as models for the study of how mixtures, low doses, and the embryonic environment modulate the action of endocrine-disrupting chemicals
- Interactions of endocrine-disrupting chemicals with stress responses in wildlife
- Effects of endocrine active substances in wildlife species: Genetic, biochemical, and physiological factors in variable susceptibility to endocrine disruptors
- Development of fish tests for endocrine disruptors
- Endocrine disruption in wildlife: The future?
- Mechanism-based QSAR approach to the study of the toxicity of endocrine active substances
- Regulatory application of SAR/QSAR for priority setting of endocrine disruptors: A perspective
- QSAR prioritization of chemical inventories for endocrine disruptor testing
- The nature of the ligand-binding pocket of estrogen receptor alpha and beta: The search for subtype-selective ligands and implications for the prediction of estrogenic activity
- Fragment molecular orbital study of the binding energy of ligands to the estrogen receptor
- Toxicogenomics: Impact on human health
- Temporal responses to estrogen in the uterus
- Application of toxicogenomics to the endocrine disruption issue
- Transcript profiles elicited by developmental exposure to endocrine-mediated toxicants
- Use of gene expression profiling to understand the transcriptional program associated with estrogen-induced uterine growth
- Need for establishing integrated programs to monitor endocrine active compounds
- Search for the evidence of endocrine disruption in the aquatic environment; Lessons to be learned from joint biological and chemical monitoring in the European project COMPREHEND
- Biomonitoring: Integration of biological end-points into chemical monitoring
- Identifying the causative agents: The use of combined chemical and biological strategies in monitoring programs
- Closing the gap between exposure and effects in monitoring studies
- Simple, rapid assays for conventional definite testing of endocrine disruptor hazard: Summary and recommendations
- Testing of endocrine active substances using an enhanced OECD test guideline 407: Experiences from studies on flutamide and ethinylestradiol
- Application of rat medium-term bioassays for detecting carcinogenic and modifying potentials of endocrine active substances
- Enhanced one-generation reproductive toxicity study in rats for detecting endocrine-disrupting effects of chemicals
- Making decisions in the 21st century: Scientific data, weight of evidence, and the precautionary principle
- Precautionary principle and endocrine active substances
- Why epidemiology of endocrine disruptors warrants the precautionary principle
- General process for the risk assessment of pesticides that interact with or affect the endocrine system
- Role of the precautionary principle in the EU risk assessment process on industrial chemicals
- Differing perspectives on the use of scientific evidence and the precautionary principle
- Risk management options for endocrine disruptors in national and international programs
- Hormonally active agents and plausible relationships to adverse effects on human health
- Government view of endocrine disruption in wildlife
- Risk perception: A chemical industry view of endocrine disruption in wildlife
- Endocrine active substances and the need to improve environmental protection: An environmentalist's perspective
- Endocrine disruption and the USFDA's Center for Drug Evaluation and Research
- Relevant activities for risk management of endocrine disruptors in Japanese government agencies
- Advancing the testing and assessment of chemical substances for endocrine disruption: OECD activities

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