Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”

Use of the dioxin toxic equivalency factor (TEF) approach in human risk assessments assumes that the combined effects of dioxin-like compounds in a mixture can be predicted based on a potency-adjusted dose-additive combination of constituents of the mixture. In this study, we evaluated the TEF appro...

Full description

Bibliographic Details
Main Authors:	Walker, Nigel J., Crockett, Patrick W., Nyska, Abraham, Brix, Amy E., Jokinen, Michael P., Sells, Donald M., Hailey, James R., Easterling, Micheal, Haseman, Joseph K., Yin, Ming, Wyde, Michael E., Bucher, John R., Portier, Christopher J.
Format:	Online
Language:	English
Published:	National Institue of Environmental Health Sciences 2005
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1253708/

id	pubmed-1253708
recordtype	oai_dc
spelling	pubmed-12537082005-11-08 Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds” Walker, Nigel J. Crockett, Patrick W. Nyska, Abraham Brix, Amy E. Jokinen, Michael P. Sells, Donald M. Hailey, James R. Easterling, Micheal Haseman, Joseph K. Yin, Ming Wyde, Michael E. Bucher, John R. Portier, Christopher J. Research Use of the dioxin toxic equivalency factor (TEF) approach in human risk assessments assumes that the combined effects of dioxin-like compounds in a mixture can be predicted based on a potency-adjusted dose-additive combination of constituents of the mixture. In this study, we evaluated the TEF approach in experimental 2-year rodent cancer bioassays with female Harlan Sprague-Dawley rats receiving 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of the three compounds. Statistically based dose–response modeling indicated that the shape of the dose–response curves for hepatic, lung, and oral mucosal neoplasms was the same in studies of the three individual chemicals and the mixture. In addition, the dose response for the mixture could be predicted from a combination of the potency-adjusted doses of the individual compounds. Finally, we showed that use of the current World Health Organization dioxin TEF values adequately predicted the increased incidence of liver tumors (hepatocellular adenoma and cholangiocarcinoma) induced by exposure to the mixture. These data support the use of the TEF approach for dioxin cancer risk assessments. National Institue of Environmental Health Sciences 2005-01 2004-10-19 /pmc/articles/PMC1253708/ /pubmed/15626646 http://dx.doi.org/10.1289/ehp.7351 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Walker, Nigel J. Crockett, Patrick W. Nyska, Abraham Brix, Amy E. Jokinen, Michael P. Sells, Donald M. Hailey, James R. Easterling, Micheal Haseman, Joseph K. Yin, Ming Wyde, Michael E. Bucher, John R. Portier, Christopher J.
spellingShingle	Walker, Nigel J. Crockett, Patrick W. Nyska, Abraham Brix, Amy E. Jokinen, Michael P. Sells, Donald M. Hailey, James R. Easterling, Micheal Haseman, Joseph K. Yin, Ming Wyde, Michael E. Bucher, John R. Portier, Christopher J. Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”
author_facet	Walker, Nigel J. Crockett, Patrick W. Nyska, Abraham Brix, Amy E. Jokinen, Michael P. Sells, Donald M. Hailey, James R. Easterling, Micheal Haseman, Joseph K. Yin, Ming Wyde, Michael E. Bucher, John R. Portier, Christopher J.
author_sort	Walker, Nigel J.
title	Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”
title_short	Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”
title_full	Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”
title_fullStr	Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”
title_full_unstemmed	Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”
title_sort	dose-additive carcinogenicity of a defined mixture of “dioxin-like compounds”
description	Use of the dioxin toxic equivalency factor (TEF) approach in human risk assessments assumes that the combined effects of dioxin-like compounds in a mixture can be predicted based on a potency-adjusted dose-additive combination of constituents of the mixture. In this study, we evaluated the TEF approach in experimental 2-year rodent cancer bioassays with female Harlan Sprague-Dawley rats receiving 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of the three compounds. Statistically based dose–response modeling indicated that the shape of the dose–response curves for hepatic, lung, and oral mucosal neoplasms was the same in studies of the three individual chemicals and the mixture. In addition, the dose response for the mixture could be predicted from a combination of the potency-adjusted doses of the individual compounds. Finally, we showed that use of the current World Health Organization dioxin TEF values adequately predicted the increased incidence of liver tumors (hepatocellular adenoma and cholangiocarcinoma) induced by exposure to the mixture. These data support the use of the TEF approach for dioxin cancer risk assessments.
publisher	National Institue of Environmental Health Sciences
publishDate	2005
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1253708/
_version_	1611378523546583040

Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”

Similar Items