Publication related to RSI or an RSI staff member
Database-calibrated toxicity values for human health assessment based on existing toxicology data for one thousand chemicals.
The US Environmental Protection Agency (US EPA) and other regulatory agencies routinely assess whether certain chemical exposures might result in harmful health effects. Traditional human health assessments rely upon expert judgment of dose-effect linkages observed in animal toxicology or human studies. Because both collection of toxicology data and synthesis of information might take multiple years to complete, there are relatively few available assessments for decision-making. Identifying methods that yield significant time and resource efficiencies to the process will have scalable public health benefits. To address the need, US EPA developed the database-calibrated assessment process (DCAP) to generate oral, non-cancer human health toxicity values that builds on previously published approaches and guidance. The approach uses the US EPA Toxicity Values Database (ToxValDB) that contains dose-response summary values (DRSVs) from in vivo toxicity studies. The DRSVs are converted to an oral, chronic, human equivalent dose using a series of standard conversion factors. A point-of-departure (POD) is then calculated across a distribution of studies for a given chemical using a calibration percentile that is benchmarked to critical effect PODs from published human health assessments. Traditional and process-specific uncertainties are incorporated to derive a calibrated toxicity value (CTV), defined as an estimate of a daily oral dose to the human population that is likely to be without appreciable risk of adverse non-cancer health effects over a lifetime. This review presents the rationale and methods for the approach, resulting in reporting of 1001 CTVs for chemicals that currently lack a human health assessment.
Authors
- Harrill, Alison H, Harrill AH, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Hagiwara, Shintaro, Hagiwara S, Risk Sciences International, Ottawa, ON, Canada
- Weitekamp, Chelsea A, Weitekamp CA, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Stanish, Paul C, Stanish PC, Risk Sciences International, Ottawa, ON, Canada
- Wall, Jonathan T, Wall JT, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Sayre, Risa R, Sayre RR, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Davidson-Fritz, Sarah E, Davidson-Fritz SE, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Vitense, Kelsey, Vitense K, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Chang, Daniel T, Chang DT, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Devito, Michael J, Devito MJ, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Gonzales, Chris J, Gonzales CJ, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Groover, Maxwell, Groover M, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Hughes, Michael F, Hughes MF, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Judson, Richard S, Judson RS, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Lambert, Jason C, Lambert JC, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Lowe, Charles N, Lowe CN, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Mutlu, Esra, Mutlu E, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Friedman, Katie Paul, Friedman KP, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Watkins, Andrew M, Watkins AM, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Williams, Antony J, Williams AJ, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
- Krewski, Daniel, Krewski D, Risk Sciences International, Ottawa, ON, Canada
- Paoli, Greg M, Paoli GM, Risk Sciences International, Ottawa, ON, Canada
- Thomas, Russell S, Thomas RS, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
YEAR OF PUBLICATION: 2025 September 17
JOURNAL TITLE ABBREVIATION: J Toxicol Environ Health B Crit Rev
JOURNAL TITLE: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
ISSN: 1521-6950
PAGES: 1-40
ABSTRACT:
The US Environmental Protection Agency (US EPA) and other regulatory agencies routinely assess whether certain chemical exposures might result in harmful health effects. Traditional human health assessments rely upon expert judgment of dose-effect linkages observed in animal toxicology or human studies. Because both collection of toxicology data and synthesis of information might take multiple years to complete, there are relatively few available assessments for decision-making. Identifying methods that yield significant time and resource efficiencies to the process will have scalable public health benefits. To address the need, US EPA developed the database-calibrated assessment process (DCAP) to generate oral, non-cancer human health toxicity values that builds on previously published approaches and guidance. The approach uses the US EPA Toxicity Values Database (ToxValDB) that contains dose-response summary values (DRSVs) from in vivo toxicity studies. The DRSVs are converted to an oral, chronic, human equivalent dose using a series of standard conversion factors. A point-of-departure (POD) is then calculated across a distribution of studies for a given chemical using a calibration percentile that is benchmarked to critical effect PODs from published human health assessments. Traditional and process-specific uncertainties are incorporated to derive a calibrated toxicity value (CTV), defined as an estimate of a daily oral dose to the human population that is likely to be without appreciable risk of adverse non-cancer health effects over a lifetime. This review presents the rationale and methods for the approach, resulting in reporting of 1001 CTVs for chemicals that currently lack a human health assessment.
The US Environmental Protection Agency (US EPA) and other regulatory agencies routinely assess whether certain chemical exposures might result in harmful health effects. Traditional human health assessments rely upon expert judgment of dose-effect linkages observed in animal toxicology or human studies. Because both collection of toxicology data and synthesis of information might take multiple years to complete, there are relatively few available assessments for decision-making. Identifying methods that yield significant time and resource efficiencies to the process will have scalable public health benefits. To address the need, US EPA developed the database-calibrated assessment process (DCAP) to generate oral, non-cancer human health toxicity values that builds on previously published approaches and guidance. The approach uses the US EPA Toxicity Values Database (ToxValDB) that contains dose-response summary values (DRSVs) from in vivo toxicity studies. The DRSVs are converted to an oral, chronic, human equivalent dose using a series of standard conversion factors. A point-of-departure (POD) is then calculated across a distribution of studies for a given chemical using a calibration percentile that is benchmarked to critical effect PODs from published human health assessments. Traditional and process-specific uncertainties are incorporated to derive a calibrated toxicity value (CTV), defined as an estimate of a daily oral dose to the human population that is likely to be without appreciable risk of adverse non-cancer health effects over a lifetime. This review presents the rationale and methods for the approach, resulting in reporting of 1001 CTVs for chemicals that currently lack a human health assessment.
LANGUAGE: English
DATE OF PUBLICATION: 2025 September 17
DATE OF ELECTRONIC PUBLICATION: 2025 September 17
DATE REVISED: 2025 September 18
EDAT: 2025 September 18
STATUS: Publisher
PUBLICATION STATUS: Ahead of print
PUBLISHING MODEL: Print-Electronic
Related RSI Experts
Chief Risk Scientist
Dr. Daniel Krewski is Chief Risk Scientist and co-founder of Risk Sciences International (RSI), a firm established in 2006 to bring evidence-based, multidisciplinary expertise to the challenge of understanding, managing, and communicating risk. As RSI’s inaugural CEO and long-time scientific...
CEO, Principal Risk Scientist
Greg Paoli is the CEO and Principal Risk Scientist at Risk Sciences International (RSI), a firm he co-founded in 2006 following the integration of his earlier consultancy, Decisionalysis Risk Consultants, with the consulting activities of the McLaughlin Centre for Population...
Risk Analyst, Statistician
Dr. Shintaro Hagiwara is a Risk Analyst and Statistician at Risk Sciences International (RSI), where he contributes cutting-edge statistical insight to risk assessments, particularly in chemical safety and public health. Since joining RSI’s technical team in 2018 and transitioning to...
Risk Analyst
Dr. Paul Stanish joined Risk Sciences International (RSI) in 2021 as a Risk Analyst, where he plays an essential role in advancing data-driven risk practices. Leveraging his strong background in chemistry and nanotechnology, he supports clients in building modern data...