Application of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effects
Abstract Human health risk assessment currently uses the reference dose or reference concentration (RfD, RfC) approach to describe the level of exposure to chemical hazards without appreciable risk for non-cancer health effects in people. However, this “bright line” approach assumes that there is mi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-01-01
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| Series: | Environmental Health |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12940-022-00918-z |
| _version_ | 1828063559340261376 |
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| author | Greylin H. Nielsen Wendy J. Heiger-Bernays Jonathan I. Levy Roberta F. White Daniel A. Axelrad Juleen Lam Nicholas Chartres Dimitri Panagopoulos Abrahamsson Swati D. G. Rayasam Rachel M. Shaffer Lauren Zeise Tracey J. Woodruff Gary L. Ginsberg |
| author_facet | Greylin H. Nielsen Wendy J. Heiger-Bernays Jonathan I. Levy Roberta F. White Daniel A. Axelrad Juleen Lam Nicholas Chartres Dimitri Panagopoulos Abrahamsson Swati D. G. Rayasam Rachel M. Shaffer Lauren Zeise Tracey J. Woodruff Gary L. Ginsberg |
| author_sort | Greylin H. Nielsen |
| collection | DOAJ |
| description | Abstract Human health risk assessment currently uses the reference dose or reference concentration (RfD, RfC) approach to describe the level of exposure to chemical hazards without appreciable risk for non-cancer health effects in people. However, this “bright line” approach assumes that there is minimal risk below the RfD/RfC with some undefined level of increased risk at exposures above the RfD/RfC and has limited utility for decision-making. Rather than this dichotomous approach, non-cancer risk assessment can benefit from incorporating probabilistic methods to estimate the amount of risk across a wide range of exposures and define a risk-specific dose. We identify and review existing approaches for conducting probabilistic non-cancer risk assessments. Using perchloroethylene (PCE), a priority chemical for the U.S. Environmental Protection Agency under the Toxic Substances Control Act, we calculate risk-specific doses for the effects on cognitive deficits using probabilistic risk assessment approaches. Our probabilistic risk assessment shows that chronic exposure to 0.004 ppm PCE is associated with approximately 1-in-1,000 risk for a 5% reduced performance on the Wechsler Memory Scale Visual Reproduction subtest with 95% confidence. This exposure level associated with a 1-in-1000 risk for non-cancer neurocognitive deficits is lower than the current RfC for PCE of 0.0059 ppm, which is based on standard point of departure and uncertainty factor approaches for the same neurotoxic effects in occupationally exposed adults. We found that the population-level risk of cognitive deficit (indicating central nervous system dysfunction) is estimated to be greater than the cancer risk level of 1-in-100,000 at a similar chronic exposure level. The extension of toxicological endpoints to more clinically relevant endpoints, along with consideration of magnitude and severity of effect, will help in the selection of acceptable risk targets for non-cancer effects. We find that probabilistic approaches can 1) provide greater context to existing RfDs and RfCs by describing the probability of effect across a range of exposure levels including the RfD/RfC in a diverse population for a given magnitude of effect and confidence level, 2) relate effects of chemical exposures to clinical disease risk so that the resulting risk assessments can better inform decision-makers and benefit-cost analysis, and 3) better reflect the underlying biology and uncertainties of population risks. |
| first_indexed | 2024-04-10T22:46:30Z |
| format | Article |
| id | doaj.art-deb40711a1e340668c5ed4d9b60a1eed |
| institution | Directory Open Access Journal |
| issn | 1476-069X |
| language | English |
| last_indexed | 2024-04-10T22:46:30Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Environmental Health |
| spelling | doaj.art-deb40711a1e340668c5ed4d9b60a1eed2023-01-15T12:20:43ZengBMCEnvironmental Health1476-069X2023-01-0121S111310.1186/s12940-022-00918-zApplication of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effectsGreylin H. Nielsen0Wendy J. Heiger-Bernays1Jonathan I. Levy2Roberta F. White3Daniel A. Axelrad4Juleen Lam5Nicholas Chartres6Dimitri Panagopoulos Abrahamsson7Swati D. G. Rayasam8Rachel M. Shaffer9Lauren Zeise10Tracey J. Woodruff11Gary L. Ginsberg12Department of Environmental Health, Boston University School of Public HealthDepartment of Environmental Health, Boston University School of Public HealthDepartment of Environmental Health, Boston University School of Public HealthDepartment of Environmental Health, Boston University School of Public HealthIndependent ConsultantDepartment of Public Health, California State UniversityProgram on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San FranciscoProgram on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San FranciscoProgram on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San FranciscoDepartment of Environmental and Occupational Health Sciences, University of Washington School of Public HealthOffice of Environmental Health Hazard Assessment, California Environmental Protection AgencyProgram on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San FranciscoDepartment of Environmental Health Sciences, School of Public Health, Yale UniversityAbstract Human health risk assessment currently uses the reference dose or reference concentration (RfD, RfC) approach to describe the level of exposure to chemical hazards without appreciable risk for non-cancer health effects in people. However, this “bright line” approach assumes that there is minimal risk below the RfD/RfC with some undefined level of increased risk at exposures above the RfD/RfC and has limited utility for decision-making. Rather than this dichotomous approach, non-cancer risk assessment can benefit from incorporating probabilistic methods to estimate the amount of risk across a wide range of exposures and define a risk-specific dose. We identify and review existing approaches for conducting probabilistic non-cancer risk assessments. Using perchloroethylene (PCE), a priority chemical for the U.S. Environmental Protection Agency under the Toxic Substances Control Act, we calculate risk-specific doses for the effects on cognitive deficits using probabilistic risk assessment approaches. Our probabilistic risk assessment shows that chronic exposure to 0.004 ppm PCE is associated with approximately 1-in-1,000 risk for a 5% reduced performance on the Wechsler Memory Scale Visual Reproduction subtest with 95% confidence. This exposure level associated with a 1-in-1000 risk for non-cancer neurocognitive deficits is lower than the current RfC for PCE of 0.0059 ppm, which is based on standard point of departure and uncertainty factor approaches for the same neurotoxic effects in occupationally exposed adults. We found that the population-level risk of cognitive deficit (indicating central nervous system dysfunction) is estimated to be greater than the cancer risk level of 1-in-100,000 at a similar chronic exposure level. The extension of toxicological endpoints to more clinically relevant endpoints, along with consideration of magnitude and severity of effect, will help in the selection of acceptable risk targets for non-cancer effects. We find that probabilistic approaches can 1) provide greater context to existing RfDs and RfCs by describing the probability of effect across a range of exposure levels including the RfD/RfC in a diverse population for a given magnitude of effect and confidence level, 2) relate effects of chemical exposures to clinical disease risk so that the resulting risk assessments can better inform decision-makers and benefit-cost analysis, and 3) better reflect the underlying biology and uncertainties of population risks.https://doi.org/10.1186/s12940-022-00918-zHuman health risk assessmentProbabilistic risk assessmentNon-cancer riskUncertaintyPopulation riskProbabilistic |
| spellingShingle | Greylin H. Nielsen Wendy J. Heiger-Bernays Jonathan I. Levy Roberta F. White Daniel A. Axelrad Juleen Lam Nicholas Chartres Dimitri Panagopoulos Abrahamsson Swati D. G. Rayasam Rachel M. Shaffer Lauren Zeise Tracey J. Woodruff Gary L. Ginsberg Application of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effects Environmental Health Human health risk assessment Probabilistic risk assessment Non-cancer risk Uncertainty Population risk Probabilistic |
| title | Application of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effects |
| title_full | Application of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effects |
| title_fullStr | Application of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effects |
| title_full_unstemmed | Application of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effects |
| title_short | Application of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effects |
| title_sort | application of probabilistic methods to address variability and uncertainty in estimating risks for non cancer health effects |
| topic | Human health risk assessment Probabilistic risk assessment Non-cancer risk Uncertainty Population risk Probabilistic |
| url | https://doi.org/10.1186/s12940-022-00918-z |
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