Differential relative effect potencies of some dioxin-like compounds in human peripheral blood lymphocytes and murine splenic cells

Autor: Van Ede, Karin I., Gaisch, Konrad P J, Van den Berg, Martin, Van Duursen, Majorie B M, Sub IRAS Tox CMT/ETX, LS IRAS EEPI GRA (Gezh.risico-analyse), LS IRAS Tox Algemeen, Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA1
Přispěvatelé: Sub IRAS Tox CMT/ETX, LS IRAS EEPI GRA (Gezh.risico-analyse), LS IRAS Tox Algemeen, Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA1
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Polychlorinated Dibenzodioxins
Polychlorinated dibenzodioxins
Aryl hydrocarbon receptor repressor
010501 environmental sciences
Toxicology
01 natural sciences
Mice
chemistry.chemical_compound
Blood serum
Basic Helix-Loop-Helix Transcription Factors
Lymphocytes
PCBs
Cells
Cultured
Risk assessment
0303 health sciences
biology
Chemistry
General Medicine
Middle Aged
Polychlorinated Biphenyls
medicine.anatomical_structure
Congener
Cytochrome P-450 CYP1B1
Environmental Pollutants
Female
Aryl Hydrocarbon Hydroxylases
Dibenzofurans
Polychlorinated dibenzofurans
Adult
Spleen
Dioxins
Gene Expression Regulation
Enzymologic
Young Adult
03 medical and health sciences
Species Specificity
Toxicity Tests
Cytochrome P-450 CYP1A1
medicine
Animals
Humans
Toxic equivalency factor
Dibenzodioxins
Aged
Benzofurans
030304 developmental biology
0105 earth and related environmental sciences
Dose-Response Relationship
Drug
REPs
Cytochrome P450
Dibenzofurans
Polychlorinated
Molecular biology
Mice
Inbred C57BL
Receptors
Aryl Hydrocarbon
biology.protein
Zdroj: Toxicology Letters, 226(1), 43. Elsevier Ireland Ltd.
ISSN: 0378-4274
DOI: 10.1016/j.toxlet.2014.01.026
Popis: Human risk assessment for dioxin-like compounds is typically based on the concentration measured in blood serum multiplied by their assigned toxic equivalency factor (TEF). Consequently, the actual value of the TEF is very important for accurate human risk assessment. In this study we investigated the effect potencies of three polychlorinated dibenzo- p-dioxins (PCDDs), six polychlorinated dibenzofurans (PCDFs) and 10 polychlorinated biphenyls (PCBs) relative to the reference congener 2,3,7,8-tetrachloro-dibenzo- p-dioxin (TCDD) in in vitro exposed primary human peripheral blood lymphocytes (PBLs) and mouse splenic cells. REPs were determined based on cytochrome P450 (CYP) 1A1, 1B1 and aryl hydrocarbon receptor repressor (AhRR) gene expression as well as CYP1A1 activity in human PBLs and Cyp1a1 gene expression in murine splenic cells. Estimated median human REPs for 1,2,3,4,6,7,8-heptachlorodibenzo- p-dioxin (1234678-HpCDD), 2,3,4,7,8,-pentachlorodibenzofuran (23478-PeCDF), 1,2,3,4,7,8-hexachlorodibenzofuran (123478-HxCDF) and 1,2,3,4,7,8,9-heptachlorodibenzofuran (1234789-HpCDF) were with 0.1, 1.1, 1 and 0.09, respectively, significantly higher compared to those estimated for mouse with REPs of 0.05, 0.45, 0.09 and 0.04, respectively. Opposite to these results, the estimated median human REP of 3,3',4,4',5-pentachlorobiphenyl (PCB 126), was with 0.001 30-fold lower compared to the mouse REP of 0.03. Furthermore, human REPs for 1234678-HpCDD, 23478-PeCDF, 123478-HxCDF, 1234789-HpCDF and PCB 126 were all outside the ± half log uncertainty range that is taken into account in the WHO-assigned TEFs. Together, these data show congener- and species-specific differences in REPs for some, but not all dioxin-like congeners tested. This suggests that, more emphasis should be placed on human-tissue derived REPs in the establishment of a TEF for human risk assessment.
Databáze: OpenAIRE
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