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Richard E Peterson - One of the best experts on this subject based on the ideXlab platform.
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relative potencies of individual polychlorinated dibenzo p dioxin dibenzofuran and biphenyl congeners and congener mixtures based on induction of cytochrome p4501a mrna in a rainbow trout gonadal cell line rtg 2
Environmental Toxicology and Chemistry, 1996Co-Authors: Erik W Zabel, Richard Pollenz, Richard E PetersonAbstract:Cytochrome P450-catalyzed enzyme activity in cell culture was investigated as a bioassay for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents in environmental mixtures of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners. A problem with the use of enzyme induction is that certain congeners are unable to induce P4501A enzyme activity to the same maximal level as TCDD. We sought to eliminate this problem by measuring mRNA induction rather than enzyme activity. Rainbow trout gonadal cells (RTG-2) were exposed to PCDD, PCDF, and PCB congeners and congener mixtures, and induction of cytochrome P4501A mRNA was measured. A high level of induction in cells treated with only a medium change was seen and was due to a component of the fresh medium. 2,3,7,8-Substituted PCDD and PCDF congeners and four non-ortho-substituted PCBs caused dose-related induction of P4501A mRNA. Di-ortho-substituted PCBs did not induce P450 mRNA, but three mono-ortho-substituted PCBs caused significant induction. Toxic equivalency factors determined in RTG-2 cells were generally higher than those in rainbow trout early life stages. Rainbow trout gonadal cell (RTG-2) bioassay TCDD equivalents (TEqs) for three environmental extracts were lower than those predicted by addition of individual congener TEqs, and the synthetic congener mixture acted additively.
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additive interactions between pairs of polybrominated dibenzo p dioxin dibenzofuran and biphenyl congeners in a rainbow trout early life stage mortality bioassay
Toxicology and Applied Pharmacology, 1996Co-Authors: Michael W Hornung, Erik W Zabel, Richard E PetersonAbstract:Abstract Use of fish-specific toxic equivalency factors (TEFs) to estimate the risk that exposure to polybrominated dibenzo- p -dioxins (PBDDs), dibenzofurans (PBDFs), and biphenyls (PBBs) pose to fish early life stage survival depends on validation of the hypothesis that these chemicals act additively to produce mortality. A rainbow trout early life stage bioassay was used to determine how pairs of PBDD, PBDF, and PBB congeners interact to produce 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD)-like toxicity associated with sac fry mortality. The congener pairs tested were 2,3,7,8-tetra- bromodibenzo- p -dioxin (2,3,7,8-TBDD)/1,2,3,7,8-pentabromodi- benzo p -dioxin (1,2,3,7,8-PBDD); 2,3,7,8-TBDD/1,2,3,7,8-penta- bromodibenzofuran (1,2,3,7,8-PBDF); 1,2,3,7,8-PBDD/2,3,4,7,8-pentabromodibenzofuran (2,3,4,7,8-PBDF); and 2,3,4,7,8-PBDF/3,3′,4,4′-tetrabromobiphenyl (3,3′,4,4′-TBB). Graded doses of each congener alone, or graded doses of fixed ratios of paired congeners were injected into newly fertilized rainbow trout eggs. In all cases, interactions between congener pairs were additive as tested by a probit model. Isobolographic analysis also supported the hypothesis that the PBDD, PBDF, and PBB congeners act additively. Thus, the use of fish-specific TEFs to convert fish tissue concentrations of individual PBDD, PBDF, and PBB congeners to TCDD equivalents (TEs) and then adding the TEs contributed by the various congeners to give the total TCDD equivalents concentration (TEC) in the tissue is supported by these results. By comparing the TEC in feral fish eggs to the fish egg TCDD no-observed-effect level (NOEL) and lowest-observed-effect level (LOEL) for early life stage mortality, the risk that complex mixtures of these polybrominated chemicals in eggs pose to sac fry survival can be estimated.
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interactions of polychlorinated dibenzo p dioxin dibenzofuran and biphenyl congeners for producing rainbow trout early life stage mortality
Toxicology and Applied Pharmacology, 1995Co-Authors: Erik W Zabel, Mary K Walker, Michael W Hornung, M K Clayton, Richard E PetersonAbstract:Fish-specific toxic equivalency factors (TEFs), which relate the toxic potency of polyhalogenated aromatic hydrocarbons (PHAHs) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on the endpoint of early life stage mortality, have been used in assessing the risk to fish early life stage survival of complex mixtures of PHAHs in feral fish eggs. Use of TEFs assumes that PHAH congeners act additively. However, this has not been unequivocally determined. Isobolograms and a probit model were used to assess the validity of the additivity assumption by determining the significance of interactions between pairs of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners when injected into newly fertilized rainbow trout eggs in ratios bracketing those found in feral lake trout eggs from the Great Lakes. The majority of congener pairs tested acted additively in causing rainbow trout early life stage mortality: [1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PCDD)/TCDD]; [2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF)/1,2,3,7,8-PCDD]; (2,3,4,7,8-PCDF/TCDD), (2,3,7,8-tetrachlorodibenzofuran/2,3,4,7,8-PCDF); [3,3′,4,4′-tetrachlorobiphenyl (PCB 77)/ 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126)]; [2,3,3′,4,4′-pentachlorobiphenyl (PCB 105)/TCDD]; (2,2′,4,4′,5,5′-hexachlorobiphenyl/TCDD); (PCB 105/PCB 126); and (2,3′,4,4′,5-pentachlorobiphenyl/PCB 126). The only pairs showing evidence of a statistically significant interaction that deviated from additivity were (TCDD/PCB 77) and (TCDD/PCB 126). Taken together, these results suggest that the use of fish-specific TEFs to determine TCDD equivalents contributed by individual congeners in a fish egg sample and then adding these TCDD equivalents to determine the total amount contributed by all congeners may not exactly predict the mortality risk posed to fish early life stages by the mixture of TCDD-like congeners in the eggs. However, the relatively small deviations from additivity in the rainbow trout sac fry mortality test (1- to 4-fold) are less than traditional uncertainty factors used in noncancer risk assessments (10-fold/factor) and are not sufficient to warrant a change away from the additivity assumption in assessing the risk to fish early life stage mortality posed by TCDD and related compounds in eggs.
Erik W Zabel - One of the best experts on this subject based on the ideXlab platform.
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relative potencies of individual polychlorinated dibenzo p dioxin dibenzofuran and biphenyl congeners and congener mixtures based on induction of cytochrome p4501a mrna in a rainbow trout gonadal cell line rtg 2
Environmental Toxicology and Chemistry, 1996Co-Authors: Erik W Zabel, Richard Pollenz, Richard E PetersonAbstract:Cytochrome P450-catalyzed enzyme activity in cell culture was investigated as a bioassay for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents in environmental mixtures of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners. A problem with the use of enzyme induction is that certain congeners are unable to induce P4501A enzyme activity to the same maximal level as TCDD. We sought to eliminate this problem by measuring mRNA induction rather than enzyme activity. Rainbow trout gonadal cells (RTG-2) were exposed to PCDD, PCDF, and PCB congeners and congener mixtures, and induction of cytochrome P4501A mRNA was measured. A high level of induction in cells treated with only a medium change was seen and was due to a component of the fresh medium. 2,3,7,8-Substituted PCDD and PCDF congeners and four non-ortho-substituted PCBs caused dose-related induction of P4501A mRNA. Di-ortho-substituted PCBs did not induce P450 mRNA, but three mono-ortho-substituted PCBs caused significant induction. Toxic equivalency factors determined in RTG-2 cells were generally higher than those in rainbow trout early life stages. Rainbow trout gonadal cell (RTG-2) bioassay TCDD equivalents (TEqs) for three environmental extracts were lower than those predicted by addition of individual congener TEqs, and the synthetic congener mixture acted additively.
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additive interactions between pairs of polybrominated dibenzo p dioxin dibenzofuran and biphenyl congeners in a rainbow trout early life stage mortality bioassay
Toxicology and Applied Pharmacology, 1996Co-Authors: Michael W Hornung, Erik W Zabel, Richard E PetersonAbstract:Abstract Use of fish-specific toxic equivalency factors (TEFs) to estimate the risk that exposure to polybrominated dibenzo- p -dioxins (PBDDs), dibenzofurans (PBDFs), and biphenyls (PBBs) pose to fish early life stage survival depends on validation of the hypothesis that these chemicals act additively to produce mortality. A rainbow trout early life stage bioassay was used to determine how pairs of PBDD, PBDF, and PBB congeners interact to produce 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD)-like toxicity associated with sac fry mortality. The congener pairs tested were 2,3,7,8-tetra- bromodibenzo- p -dioxin (2,3,7,8-TBDD)/1,2,3,7,8-pentabromodi- benzo p -dioxin (1,2,3,7,8-PBDD); 2,3,7,8-TBDD/1,2,3,7,8-penta- bromodibenzofuran (1,2,3,7,8-PBDF); 1,2,3,7,8-PBDD/2,3,4,7,8-pentabromodibenzofuran (2,3,4,7,8-PBDF); and 2,3,4,7,8-PBDF/3,3′,4,4′-tetrabromobiphenyl (3,3′,4,4′-TBB). Graded doses of each congener alone, or graded doses of fixed ratios of paired congeners were injected into newly fertilized rainbow trout eggs. In all cases, interactions between congener pairs were additive as tested by a probit model. Isobolographic analysis also supported the hypothesis that the PBDD, PBDF, and PBB congeners act additively. Thus, the use of fish-specific TEFs to convert fish tissue concentrations of individual PBDD, PBDF, and PBB congeners to TCDD equivalents (TEs) and then adding the TEs contributed by the various congeners to give the total TCDD equivalents concentration (TEC) in the tissue is supported by these results. By comparing the TEC in feral fish eggs to the fish egg TCDD no-observed-effect level (NOEL) and lowest-observed-effect level (LOEL) for early life stage mortality, the risk that complex mixtures of these polybrominated chemicals in eggs pose to sac fry survival can be estimated.
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interactions of polychlorinated dibenzo p dioxin dibenzofuran and biphenyl congeners for producing rainbow trout early life stage mortality
Toxicology and Applied Pharmacology, 1995Co-Authors: Erik W Zabel, Mary K Walker, Michael W Hornung, M K Clayton, Richard E PetersonAbstract:Fish-specific toxic equivalency factors (TEFs), which relate the toxic potency of polyhalogenated aromatic hydrocarbons (PHAHs) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on the endpoint of early life stage mortality, have been used in assessing the risk to fish early life stage survival of complex mixtures of PHAHs in feral fish eggs. Use of TEFs assumes that PHAH congeners act additively. However, this has not been unequivocally determined. Isobolograms and a probit model were used to assess the validity of the additivity assumption by determining the significance of interactions between pairs of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners when injected into newly fertilized rainbow trout eggs in ratios bracketing those found in feral lake trout eggs from the Great Lakes. The majority of congener pairs tested acted additively in causing rainbow trout early life stage mortality: [1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PCDD)/TCDD]; [2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF)/1,2,3,7,8-PCDD]; (2,3,4,7,8-PCDF/TCDD), (2,3,7,8-tetrachlorodibenzofuran/2,3,4,7,8-PCDF); [3,3′,4,4′-tetrachlorobiphenyl (PCB 77)/ 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126)]; [2,3,3′,4,4′-pentachlorobiphenyl (PCB 105)/TCDD]; (2,2′,4,4′,5,5′-hexachlorobiphenyl/TCDD); (PCB 105/PCB 126); and (2,3′,4,4′,5-pentachlorobiphenyl/PCB 126). The only pairs showing evidence of a statistically significant interaction that deviated from additivity were (TCDD/PCB 77) and (TCDD/PCB 126). Taken together, these results suggest that the use of fish-specific TEFs to determine TCDD equivalents contributed by individual congeners in a fish egg sample and then adding these TCDD equivalents to determine the total amount contributed by all congeners may not exactly predict the mortality risk posed to fish early life stages by the mixture of TCDD-like congeners in the eggs. However, the relatively small deviations from additivity in the rainbow trout sac fry mortality test (1- to 4-fold) are less than traditional uncertainty factors used in noncancer risk assessments (10-fold/factor) and are not sufficient to warrant a change away from the additivity assumption in assessing the risk to fish early life stage mortality posed by TCDD and related compounds in eggs.
Michael W Hornung - One of the best experts on this subject based on the ideXlab platform.
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additive interactions between pairs of polybrominated dibenzo p dioxin dibenzofuran and biphenyl congeners in a rainbow trout early life stage mortality bioassay
Toxicology and Applied Pharmacology, 1996Co-Authors: Michael W Hornung, Erik W Zabel, Richard E PetersonAbstract:Abstract Use of fish-specific toxic equivalency factors (TEFs) to estimate the risk that exposure to polybrominated dibenzo- p -dioxins (PBDDs), dibenzofurans (PBDFs), and biphenyls (PBBs) pose to fish early life stage survival depends on validation of the hypothesis that these chemicals act additively to produce mortality. A rainbow trout early life stage bioassay was used to determine how pairs of PBDD, PBDF, and PBB congeners interact to produce 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD)-like toxicity associated with sac fry mortality. The congener pairs tested were 2,3,7,8-tetra- bromodibenzo- p -dioxin (2,3,7,8-TBDD)/1,2,3,7,8-pentabromodi- benzo p -dioxin (1,2,3,7,8-PBDD); 2,3,7,8-TBDD/1,2,3,7,8-penta- bromodibenzofuran (1,2,3,7,8-PBDF); 1,2,3,7,8-PBDD/2,3,4,7,8-pentabromodibenzofuran (2,3,4,7,8-PBDF); and 2,3,4,7,8-PBDF/3,3′,4,4′-tetrabromobiphenyl (3,3′,4,4′-TBB). Graded doses of each congener alone, or graded doses of fixed ratios of paired congeners were injected into newly fertilized rainbow trout eggs. In all cases, interactions between congener pairs were additive as tested by a probit model. Isobolographic analysis also supported the hypothesis that the PBDD, PBDF, and PBB congeners act additively. Thus, the use of fish-specific TEFs to convert fish tissue concentrations of individual PBDD, PBDF, and PBB congeners to TCDD equivalents (TEs) and then adding the TEs contributed by the various congeners to give the total TCDD equivalents concentration (TEC) in the tissue is supported by these results. By comparing the TEC in feral fish eggs to the fish egg TCDD no-observed-effect level (NOEL) and lowest-observed-effect level (LOEL) for early life stage mortality, the risk that complex mixtures of these polybrominated chemicals in eggs pose to sac fry survival can be estimated.
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interactions of polychlorinated dibenzo p dioxin dibenzofuran and biphenyl congeners for producing rainbow trout early life stage mortality
Toxicology and Applied Pharmacology, 1995Co-Authors: Erik W Zabel, Mary K Walker, Michael W Hornung, M K Clayton, Richard E PetersonAbstract:Fish-specific toxic equivalency factors (TEFs), which relate the toxic potency of polyhalogenated aromatic hydrocarbons (PHAHs) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on the endpoint of early life stage mortality, have been used in assessing the risk to fish early life stage survival of complex mixtures of PHAHs in feral fish eggs. Use of TEFs assumes that PHAH congeners act additively. However, this has not been unequivocally determined. Isobolograms and a probit model were used to assess the validity of the additivity assumption by determining the significance of interactions between pairs of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners when injected into newly fertilized rainbow trout eggs in ratios bracketing those found in feral lake trout eggs from the Great Lakes. The majority of congener pairs tested acted additively in causing rainbow trout early life stage mortality: [1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PCDD)/TCDD]; [2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF)/1,2,3,7,8-PCDD]; (2,3,4,7,8-PCDF/TCDD), (2,3,7,8-tetrachlorodibenzofuran/2,3,4,7,8-PCDF); [3,3′,4,4′-tetrachlorobiphenyl (PCB 77)/ 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126)]; [2,3,3′,4,4′-pentachlorobiphenyl (PCB 105)/TCDD]; (2,2′,4,4′,5,5′-hexachlorobiphenyl/TCDD); (PCB 105/PCB 126); and (2,3′,4,4′,5-pentachlorobiphenyl/PCB 126). The only pairs showing evidence of a statistically significant interaction that deviated from additivity were (TCDD/PCB 77) and (TCDD/PCB 126). Taken together, these results suggest that the use of fish-specific TEFs to determine TCDD equivalents contributed by individual congeners in a fish egg sample and then adding these TCDD equivalents to determine the total amount contributed by all congeners may not exactly predict the mortality risk posed to fish early life stages by the mixture of TCDD-like congeners in the eggs. However, the relatively small deviations from additivity in the rainbow trout sac fry mortality test (1- to 4-fold) are less than traditional uncertainty factors used in noncancer risk assessments (10-fold/factor) and are not sufficient to warrant a change away from the additivity assumption in assessing the risk to fish early life stage mortality posed by TCDD and related compounds in eggs.
Abdel G Kafafi - One of the best experts on this subject based on the ideXlab platform.
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relationship between aryl hydrocarbon receptor binding induction of aryl hydrocarbon hydroxylase and 7 ethoxyresorufin o deethylase enzymes and toxic activities of aromatic xenobiotics in animals a new model
Chemical Research in Toxicology, 1993Co-Authors: Sherif A Kafafi, Hussein Y Afeefy, Hakim K Said, Abdel G KafafiAbstract:A new mathematical model relating the affinities of aromatic xenobiotics for the aryl hydrocarbon receptor (AhR) to their potencies as aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase inducers and toxic activities in animals is reported. Taking polychlorinated dibenzo-p-dioxins (PCDDs) as examples, the AHH activity of a PCDD relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is shown to be analytically related to corresponding relative affinities for AhR, and electronic energy gaps of PCDD and TCDD. (The electronic energy gap of a chemical is the difference between its ionization potential and electron affinity)
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relationship between aryl hydrocarbon receptor binding induction of aryl hydrocarbon hydroxylase and 7 ethoxyresorufin o deethylase enzymes and toxic activities of aromatic xenobiotics in animals a new model
Chemical Research in Toxicology, 1993Co-Authors: Sherif A Kafafi, Hussein Y Afeefy, Hakim K Said, Abdel G KafafiAbstract:: A new mathematical model relating the affinities of aromatic xenobiotics for the aryl hydrocarbon receptor (AhR) to their potencies as aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase inducers and toxic activities in animals is reported. Taking polychlorinated dibenzo-p-dioxins (PCDDs) as examples, the AHH activity of a PCDD relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is shown to be analytically related to corresponding relative affinities for AhR, and electronic energy gaps of PCDD and TCDD. (The electronic energy gap of a chemical is the difference between its ionization potential and electron affinity.) The reported model is capable of qualitatively explaining and quantitatively estimating potencies of PCDDs and related xenobiotics as AHH inducers in rat hepatoma H-4-II E cells in culture. Therefore, a PCDD is expected to be a potent AHH inducer if its affinity for AhR is high and has a smaller energy gap than TCDD. In addition, it is shown that the derived equations for AHH induction by PCDDs apply equally well to 7-ethoxyresorufin O-deethylase (EROD) activities; that is, there is a 1:1 correspondence between AHH and EROD activities for PCDDs, in agreement with experimental findings. Furthermore, in harmony with experimental observations, AHH (and EROD) activities of PCDDs relative to TCDD parallel the corresponding toxic equivalency factors and AhR mediated in vivo toxicities of these xenobiotics in animals, such as thymic atrophy, body weight loss, and acute lethalities. Moreover, the developed methodology for AHH and EROD induction by PCDDs is shown to apply to polychlorinated dibenzofurans, thus, eliminating cross-class comparison problem of traditional structure-activity studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Mary K Walker - One of the best experts on this subject based on the ideXlab platform.
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correlation of cardiotoxicity mediated by halogenated aromatic hydrocarbons to aryl hydrocarbon receptor activation
Toxicological Sciences, 2001Co-Authors: Scott E Heid, Mary K Walker, Hollie I SwansonAbstract:In mammals, the toxicity of halogenated aromatic hydrocarbons (HAH) correlates with their ability to activate the aryl hydrocarbon receptor (AHR). To test this correlation in an avian model, we selected six HAHs based on their affinity for the mammalian AHR, including: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD); 2,3,7,8-tetrachlorodibenzofuran (TCDF); 2,3,4,7,8-pentachlorodibenzofuran (PCDF); 3,3',4,4'-tetrachlorobiphenyl (PCB 77); and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153). We determined the ability of these compounds to induce cardiotoxicity, as measured by an increase in heart wet weight on incubation day 10 in the chick embryo (Gallus gallus) and formation of the avian AHR/ARNT/DNA binding complex in chicken hepatoma cells. Relative potency values (RPs) were calculated by dividing the TCDD EC(50) (AHR/ARNT/DNA binding) or ED(50) (15% increase in day-10 heart wet weight) by the HAH congeners EC(50) or ED(50), respectively. The rank order of potencies for inducing cardiotoxicity were TCDD > PCDD = PCDF = TCDF > PCDF > PCB77, PCB 153, no effect. The RP values for inducing AHR/ARNT DNA binding were then correlated with those for inducing cardiotoxicity (the RP values of PCDD were determined to be statistical outliers). This correlation was found to be highly significant (r = 0.94, p = 0.017). The ability of PCDD to act as an AHR agonist was verified using luciferase reporter assays and analysis of cytochrome P4501A1 protein levels. These results indicate that the ability of HAHs to activate the avian AHR signaling pathway, in general, correlates with their ability to mediate cardiotoxicity in the chick embryo.
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interactions of polychlorinated dibenzo p dioxin dibenzofuran and biphenyl congeners for producing rainbow trout early life stage mortality
Toxicology and Applied Pharmacology, 1995Co-Authors: Erik W Zabel, Mary K Walker, Michael W Hornung, M K Clayton, Richard E PetersonAbstract:Fish-specific toxic equivalency factors (TEFs), which relate the toxic potency of polyhalogenated aromatic hydrocarbons (PHAHs) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on the endpoint of early life stage mortality, have been used in assessing the risk to fish early life stage survival of complex mixtures of PHAHs in feral fish eggs. Use of TEFs assumes that PHAH congeners act additively. However, this has not been unequivocally determined. Isobolograms and a probit model were used to assess the validity of the additivity assumption by determining the significance of interactions between pairs of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners when injected into newly fertilized rainbow trout eggs in ratios bracketing those found in feral lake trout eggs from the Great Lakes. The majority of congener pairs tested acted additively in causing rainbow trout early life stage mortality: [1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PCDD)/TCDD]; [2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF)/1,2,3,7,8-PCDD]; (2,3,4,7,8-PCDF/TCDD), (2,3,7,8-tetrachlorodibenzofuran/2,3,4,7,8-PCDF); [3,3′,4,4′-tetrachlorobiphenyl (PCB 77)/ 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126)]; [2,3,3′,4,4′-pentachlorobiphenyl (PCB 105)/TCDD]; (2,2′,4,4′,5,5′-hexachlorobiphenyl/TCDD); (PCB 105/PCB 126); and (2,3′,4,4′,5-pentachlorobiphenyl/PCB 126). The only pairs showing evidence of a statistically significant interaction that deviated from additivity were (TCDD/PCB 77) and (TCDD/PCB 126). Taken together, these results suggest that the use of fish-specific TEFs to determine TCDD equivalents contributed by individual congeners in a fish egg sample and then adding these TCDD equivalents to determine the total amount contributed by all congeners may not exactly predict the mortality risk posed to fish early life stages by the mixture of TCDD-like congeners in the eggs. However, the relatively small deviations from additivity in the rainbow trout sac fry mortality test (1- to 4-fold) are less than traditional uncertainty factors used in noncancer risk assessments (10-fold/factor) and are not sufficient to warrant a change away from the additivity assumption in assessing the risk to fish early life stage mortality posed by TCDD and related compounds in eggs.
