Cargando…

A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data

BACKGROUND: Risk assessment of human environmental exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) and other dioxin-like compounds is complicated by several factors, including limitations in measuring intakes because of the low concentrations of these compounds in foods...

Descripción completa

Detalles Bibliográficos
Autores principales: Aylward, Lesa L., Goodman, Julie E., Charnley, Gail, Rhomberg, Lorenz R.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569093/
https://www.ncbi.nlm.nih.gov/pubmed/18941576
http://dx.doi.org/10.1289/ehp.11514
_version_ 1782160064872710144
author Aylward, Lesa L.
Goodman, Julie E.
Charnley, Gail
Rhomberg, Lorenz R.
author_facet Aylward, Lesa L.
Goodman, Julie E.
Charnley, Gail
Rhomberg, Lorenz R.
author_sort Aylward, Lesa L.
collection PubMed
description BACKGROUND: Risk assessment of human environmental exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) and other dioxin-like compounds is complicated by several factors, including limitations in measuring intakes because of the low concentrations of these compounds in foods and the environment and interspecies differences in pharmacokinetics and responses. OBJECTIVES: We examined the feasibility of relying directly on human studies of exposure and potential responses to PCDD/PCDFs and related compounds in terms of measured lipid-adjusted concentrations to assess margin of exposure (MOE) in a quantitative, benchmark dose (BMD)–based framework using representative exposure and selected response data sets. METHODS: We characterize estimated central tendency and upper-bound general U.S. population lipid-adjusted concentrations of PCDD/PCDFs from the 1970s and early 2000s based on available data sets. Estimates of benchmark concentrations for three example responses of interest (induction of cytochrome P4501A2 activity, dental anomalies, and neonatal thyroid hormone alterations) were derived based on selected human studies. RESULTS: The exposure data sets indicate that current serum lipid concentrations in young adults are approximately 6- to 7-fold lower than 1970s-era concentrations. Estimated MOEs for each end point based on current serum lipid concentrations range from < 10 for neonatal thyroid hormone concentrations to > 100 for dental anomalies—approximately 6-fold greater than would have existed during the 1970s. CONCLUSIONS: Human studies of dioxin exposure and outcomes can be used in a BMD framework for quantitative assessments of MOE. Incomplete exposure characterization can complicate the use of such studies in a BMD framework.
format Text
id pubmed-2569093
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher National Institute of Environmental Health Sciences
record_format MEDLINE/PubMed
spelling pubmed-25690932008-10-21 A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data Aylward, Lesa L. Goodman, Julie E. Charnley, Gail Rhomberg, Lorenz R. Environ Health Perspect Research BACKGROUND: Risk assessment of human environmental exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) and other dioxin-like compounds is complicated by several factors, including limitations in measuring intakes because of the low concentrations of these compounds in foods and the environment and interspecies differences in pharmacokinetics and responses. OBJECTIVES: We examined the feasibility of relying directly on human studies of exposure and potential responses to PCDD/PCDFs and related compounds in terms of measured lipid-adjusted concentrations to assess margin of exposure (MOE) in a quantitative, benchmark dose (BMD)–based framework using representative exposure and selected response data sets. METHODS: We characterize estimated central tendency and upper-bound general U.S. population lipid-adjusted concentrations of PCDD/PCDFs from the 1970s and early 2000s based on available data sets. Estimates of benchmark concentrations for three example responses of interest (induction of cytochrome P4501A2 activity, dental anomalies, and neonatal thyroid hormone alterations) were derived based on selected human studies. RESULTS: The exposure data sets indicate that current serum lipid concentrations in young adults are approximately 6- to 7-fold lower than 1970s-era concentrations. Estimated MOEs for each end point based on current serum lipid concentrations range from < 10 for neonatal thyroid hormone concentrations to > 100 for dental anomalies—approximately 6-fold greater than would have existed during the 1970s. CONCLUSIONS: Human studies of dioxin exposure and outcomes can be used in a BMD framework for quantitative assessments of MOE. Incomplete exposure characterization can complicate the use of such studies in a BMD framework. National Institute of Environmental Health Sciences 2008-10 2008-06-16 /pmc/articles/PMC2569093/ /pubmed/18941576 http://dx.doi.org/10.1289/ehp.11514 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Aylward, Lesa L.
Goodman, Julie E.
Charnley, Gail
Rhomberg, Lorenz R.
A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data
title A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data
title_full A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data
title_fullStr A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data
title_full_unstemmed A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data
title_short A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data
title_sort margin-of-exposure approach to assessment of noncancer risks of dioxins based on human exposure and response data
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569093/
https://www.ncbi.nlm.nih.gov/pubmed/18941576
http://dx.doi.org/10.1289/ehp.11514
work_keys_str_mv AT aylwardlesal amarginofexposureapproachtoassessmentofnoncancerrisksofdioxinsbasedonhumanexposureandresponsedata
AT goodmanjuliee amarginofexposureapproachtoassessmentofnoncancerrisksofdioxinsbasedonhumanexposureandresponsedata
AT charnleygail amarginofexposureapproachtoassessmentofnoncancerrisksofdioxinsbasedonhumanexposureandresponsedata
AT rhomberglorenzr amarginofexposureapproachtoassessmentofnoncancerrisksofdioxinsbasedonhumanexposureandresponsedata
AT aylwardlesal marginofexposureapproachtoassessmentofnoncancerrisksofdioxinsbasedonhumanexposureandresponsedata
AT goodmanjuliee marginofexposureapproachtoassessmentofnoncancerrisksofdioxinsbasedonhumanexposureandresponsedata
AT charnleygail marginofexposureapproachtoassessmentofnoncancerrisksofdioxinsbasedonhumanexposureandresponsedata
AT rhomberglorenzr marginofexposureapproachtoassessmentofnoncancerrisksofdioxinsbasedonhumanexposureandresponsedata