Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

[1]  W. Gardner,et al.  Carcinogenesis , 1961, The Yale Journal of Biology and Medicine.

[2]  S. Rooney Lung surfactant. , 1984, Environmental health perspectives.

[3]  B. N. Gupta,et al.  Toxicological assessment of hexachlorobiphenyl isomers and 2,3,7,8 tetrachlorodibenzofuran in chicks. I. Relationship of chemical parameters. , 1976, Toxicology and applied pharmacology.

[4]  P. Zachariah,et al.  Hepatic Biotransformation of Environmental Xenobiotics in Six Strains of Rainbow Trout (Salmo gairdneri) , 1976 .

[5]  G. Lucier,et al.  Toxicological assessment of hexachlorobiphenyl isomers and 2,3,7,8,-tetrachlorodibenzofuran in chicks. II. Effects on drug metabolism and porphyrin accumulation. , 1976, Toxicology and applied pharmacology.

[6]  E. Glover,et al.  Chlorinated biphenyl induction of aryl hydrocarbon hydroxylase activity: a study of the structure-activity relationship. , 1977, Molecular pharmacology.

[7]  Alan Poland,et al.  STUDIES ON THE MECHANISM OF ACTION OF THE CHLORINATED DIBENZO‐p‐DIOXINS AND RELATED COMPOUNDS * , 1979, Annals of the New York Academy of Sciences.

[8]  J. Bradlaw,et al.  Induction of enzyme activity in cell culture: a rapid screen for detection of planar polychlorinated organic compounds. , 1979, Journal - Association of Official Analytical Chemists.

[9]  J. Stegeman,et al.  Sex differences in cytochrome P-450 and mixed-function oxygenase activity in gonadally mature trout. , 1980, Biochemical pharmacology.

[10]  G. Blomkvist,et al.  Polybrominated aromatic pollutants found in fish in Sweden , 1981 .

[11]  Variation of Hepatic Ethoxycoumarin O-de-ethylase Activity with Body Weight and Other Factors in Brook Trout (Salvelinus fontinalis) , 1982 .

[12]  S. Safe,et al.  Binding of polychlorinated biphenyls classified as either phenobarbitone-, 3-methylcholanthrene- or mixed-type inducers to cytosolic Ah receptor. , 1982, Chemico-biological interactions.

[13]  A Poland,et al.  2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. , 1982, Annual review of pharmacology and toxicology.

[14]  S. Safe,et al.  PCB isomers and congeners: induction of aryl hydrocarbon hydroxylase and ethoxyresorufin O-deethylase enzyme activities in rat hepatoma cells. , 1982, Toxicology letters.

[15]  R. L. Binder,et al.  Basal levels and induction of hepatic aryl hydrocarbon hydroxylase activity during the embryonic period of development in brook trout. , 1983, Biochemical pharmacology.

[16]  J. Gierthy,et al.  Application of an in vitro keratinization assay to extracts of soot from a fire in a polychlorinated biphenyl-containing transformer. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[17]  Y. Masuda,et al.  High accumulation of 2,3,4,7,8-pentachlorodibenzofuran to hepatic microsomes of rats. , 1984, Journal of pharmacobio-dynamics.

[18]  A. Brouwer,et al.  Early and differential decrease in natural retinoid levels in C57BL/Rij and DBA/2 mice by 3,4,3',4'-tetrachlorobiphenyl. , 1984, Toxicology and applied pharmacology.

[19]  T. Fujita,et al.  PCBs: structure–function relationships and mechanism of action , 1985, Environmental health perspectives.

[20]  J. Gustafsson,et al.  Interactions of indoles with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver. , 1985, Molecular pharmacology.

[21]  L. Birnbaum The role of structure in the disposition of halogenated aromatic xenobiotics. , 1985, Environmental health perspectives.

[22]  S. Safe,et al.  Polychlorinated biphenyls: correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs). , 1985, Journal of toxicology and environmental health.

[23]  M. Pesonen,et al.  Differential induction of cytochrome P-450-dependent monooxygenase, epoxide hydrolase, glutathione transferase and UDP glucuronosyl transferase activities in the liver of the rainbow trout by beta-naphthoflavone or Clophen A50. , 1985, Biochemical pharmacology.

[24]  George Eadon,et al.  Calculation of 2,3,7,8-TCDD equivalent concentrations of complex environmental contaminant mixtures , 1986, Environmental health perspectives.

[25]  R. Peterson,et al.  Interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with immune responses of rainbow trout. , 1986, Veterinary immunology and immunopathology.

[26]  M. Pesonen,et al.  Biotransformation enzymes in fish as tools for biomonitoring aquatic environment. , 1986, Acta biologica Hungarica.

[27]  D. Williams,et al.  Sex differences in cytochrome P-450 isozyme composition and activity in kidney microsomes of mature rainbow trout. , 1986, Biochemical pharmacology.

[28]  C. Blake,et al.  Structurally specific binding of halogenated biphenyls to thyroxine transport protein. , 1986, Journal of medicinal chemistry.

[29]  S. Safe,et al.  Comparative toxicology and mechanism of action of polychlorinated dibenzo-p-dioxins and dibenzofurans. , 1986, Annual review of pharmacology and toxicology.

[30]  S. Safe,et al.  Synergistic interactions of 2,3,7,8-TCDD and 2,2',4,4',5,5'-hexachlorobiphenyl in C57BL/6J and DBA/2J mice: role of the Ah receptor. , 1987, Toxicology.

[31]  S. Safe,et al.  Aroclor 1254 as an antagonist of the teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1987, Toxicology letters.

[32]  G. Ankley,et al.  Metabolism of alkoxyphenoxazones by channel catfish liver microsomes: effects of phenobarbital, Aroclor 1254 and 3-methylcholanthrene. , 1987, Biochemical pharmacology.

[33]  S. Safe,et al.  Mammalian Biologic and Toxic Effects of PCBs , 1987 .

[34]  C. Miranda,et al.  Effects of polychlorinated biphenyls on porphyrin synthesis and cytochrome P-450-dependent monooxygenases in small intestine and liver of Japanese quail. , 1987, Journal of toxicology and environmental health.

[35]  S. Aust,et al.  Specific binding of polyhalogenated aromatic hydrocarbon inducers of cytochrome P-450d to the cytochrome and inhibition of its estradiol 2-hydroxylase activity. , 1987, Toxicology and applied pharmacology.

[36]  H. Buser Brominated and brominated/chlorinated dibenzodioxins and dibenzofurans: potential environmental contaminants , 1987 .

[37]  Disposition and excretion of 2,3,4,7,8-pentachlorodibenzofuran in the rat. , 1987, Toxicology and applied pharmacology.

[38]  S. Safe,et al.  Nonadditive interactive effects of polychlorinated biphenyl congeners in rats: role of the 2,3,7,8-tetrachlorodibenzo-p-dioxin receptor. , 1987, Canadian journal of physiology and pharmacology.

[39]  L. Birnbaum,et al.  Teratogenicity of three polychlorinated dibenzofurans in C57BL/6N mice. , 1987, Toxicology and applied pharmacology.

[40]  S. Tanabe,et al.  Highly toxic coplanar PCBs: occurrence, source, persistency and toxic implications to wildlife and humans. , 1987, Environmental pollution.

[41]  S. Bursian,et al.  Toxicity of 3,4,5,3′,4′,5′-hexachlorobiphenyl to mink , 1987, Archives of environmental contamination and toxicology.

[42]  The effects of receptor antagonists on the AHH induction activity of 2,3,7,8-TCDD in C57BL/6 and DBA/2 mice: 1,3,6,8-tetrachlorodibenzofuran , 1987 .

[43]  L. Birnbaum,et al.  Dioxin-like effects observed in male rats following exposure to octachlorodibenzo-p-dioxin (OCDD) during a 13-week study. , 1988, Toxicology and applied pharmacology.

[44]  M. P. Arlotto,et al.  6-Methyl-1,3,8-trichlorodibenzofuran as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist: inhibition of the induction of rat cytochrome P-450 isozymes and related monooxygenase activities. , 1988, Molecular pharmacology.

[45]  C. Schlatter,et al.  Subchronic toxicity of some chlorinated dibenzofurans (PCDFs) and a mixture of PCDFs and chlorinated dibenzodioxins (PCDDs) in rats , 1988 .

[46]  L. Birnbaum,et al.  Disposition of octachlorodibenzo-p-dioxin (OCDD) in male rats. , 1988, Toxicology and applied pharmacology.

[47]  B. Brunström,et al.  Effects of TCDD and its congeners 3,3',4,4'-tetrachloroazoxybenzene and 3,3',4,4'-tetrachlorobiphenyl on lymphoid development in the thymus of avian embryos. , 1988, Pharmacology & toxicology.

[48]  S. Tanabe,et al.  Toxic potential of non-ortho and mono-ortho coplanar PCBs in commercial PCB preparations: “2,3,7,8-T4 CDD toxicity equivalence factors approach” , 1988, Bulletin of environmental contamination and toxicology.

[49]  K. Chae,et al.  Estrogen receptor-binding activity of polychlorinated hydroxybiphenyls: conformationally restricted structural probes. , 1988, Molecular pharmacology.

[50]  S. Safe,et al.  Applications of the in vitro aryl hydrocarbon hydroxylase induction assay for determining "2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents": pyrolyzed brominated flame retardants. , 1988, Toxicology.

[51]  S. Bursian,et al.  Acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to Mink , 1988, Archives of environmental contamination and toxicology.

[52]  David E. Williams,et al.  The role of biotransformation in the toxicity of chemicals , 1988 .

[53]  B. Brunström,et al.  Effects of the TCDD congeners 3,3',4,4'-tetrachlorobiphenyl and 3,3',4,4'-tetrachloroazoxybenzene on lymphoid development in the bursa of Fabricius of the chick embryo. , 1988, Toxicology and applied pharmacology.

[54]  J. Boer Organochlorine compounds and bromodiphenylethers in livers of Atlantic cod (Gadus morhua) from the North Sea, 1977-1987 , 1989 .

[55]  M. E. Hahn,et al.  Effects of ortho- and non-ortho-substituted polychlorinated biphenyl congeners on the hepatic monooxygenase system in scup (Stenotomus chrysops). , 1989, Toxicology and applied pharmacology.

[56]  S. Safe,et al.  Aroclor 1254 as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in mice , 1989 .

[57]  J. Clarke,et al.  Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener-specific analysis. , 1989, Environmental health perspectives.

[58]  S. Safe,et al.  2,2′,4,4′,5,5′-Hexachlorobiphenyl as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in C57BL6J mice , 1989 .

[59]  W. Seinen,et al.  Interactive effects of PCDD's, PCDF's and PCB's as assessed by the E.L.S.-bioassay , 1989 .

[60]  Comparative analysis of polychlorinated dibenzo-'p'-dioxin and dibenzofuran congeners in Great Lakes fish extracts by gas chromatography-mass spectrometry and in-vitro enzyme induction activities , 1989 .

[61]  C. Miranda,et al.  Multiple effects of 3,4,5,3',4',5'-hexachlorobiphenyl administration on hepatic cytochrome P450 isozymes and associated mixed-function oxidase activities in rainbow trout. , 1990, Biochemical pharmacology.

[62]  The structure-dependent effects of heptachlorodibenzofuran isomers in male C57BL/6 mice: immunotoxicity and monooxygenase enzyme induction. , 1990, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[63]  L. Birnbaum,et al.  Relative toxicity and tumor-promoting ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PCDF), and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) in hairless mice. , 1990, Toxicology and applied pharmacology.

[64]  S. Safe,et al.  The structure-dependent effects of heptachlorodibenzofuran isomers in male C57BL/6 mice: immunotoxicity and monooxygenase enzyme induction. , 1990, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[65]  S. Kennedy,et al.  Polychlorinated biphenyl (PCB) effects on hepatic mixed function oxidases and porphyria in birds. I. Japanese quail , 1990 .

[66]  B. Brunström,et al.  Non-ortho- and mono-ortho-chlorine-substituted polychlorinated biphenyls-embryotoxicity and inhibition of lymphoid development , 1990 .

[67]  W. Shain,et al.  Lightly chlorinated ortho-substituted PCB congeners decrease dopamine in nonhuman primate brain and in tissue culture. , 1990, Toxicology and applied pharmacology.

[68]  J. Piskorska-Pliszczynska,et al.  Structure-dependent induction of aryl hydrocarbon hydroxylase activity in C57BL/6 mice by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related congeners: mechanistic studies. , 1990, Toxicology and applied pharmacology.

[69]  Bromo- and bromochloro-dibenzo-p-dioxins and dibenzofurans in the environment , 1990 .

[70]  S. Safe,et al.  Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs). , 1990, Critical reviews in toxicology.

[71]  C. Walker,et al.  Polychlorinated biphenyls (PCBs) in fish-eating sea birds—II. Molecular features of PCB isomers and congeners in adipose tissue of male and female puffins (Fratercula arctica), guillemots (Uria aalga), shags (Phalacrocorax aristotelis) and cormorants (Phalacrocorax carbo) of British and Irish coasta , 1990 .

[72]  A. Opperhuizen,et al.  Bioaccumulation and biotransformation of polychlorinated dibenzo‐p‐dioxins and dibenzofurans in fish , 1990 .

[73]  C. Metcalfe,et al.  Nonadditive interactions of mixtures of 2,3,7,8-TCDD and 3,3′,4,4′-tetrachlorobiphenyl on aryl hydrocarbon hydroxylase induction in rainbow trout (Oncorhynchus mykiss) , 1991 .

[74]  J. Landers,et al.  The Ah receptor and the mechanism of dioxin toxicity. , 1991, The Biochemical journal.

[75]  A. Hanberg,et al.  Swedish dioxin survey: evaluation of the H-4-II E bioassay for screening environmental samples for dioxin-like enzyme induction. , 1991, Pharmacology & toxicology.

[76]  J. Giesy,et al.  H4IIE rat hepatoma cell bioassay-derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents in colonial fish-eating waterbird eggs from the Great Lakes , 1991, Archives of environmental contamination and toxicology.

[77]  B. Brunström Toxicity and erod-inducing potency of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in avian embryos , 1991 .

[78]  Effects of Environmental pH on the Hepatic Mixed Function Oxidases in Atlantic Salmon (Salmo salar) , 1991 .

[79]  R. Peterson,et al.  Potencies of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners, relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin, for producing early life stage mortality in rainbow trout (Oncorhynchus mykiss) , 1991 .

[80]  Study of the separate and combined effects of the non-planar 2,5,2',5'- and the planar 3,4,3',4'-tetrachlorobiphenyl in liver and lymphocytes in vivo. , 1991, Carcinogenesis.

[81]  W. Shain,et al.  Neurotoxicity of polychlorinated biphenyls: structure-activity relationship of individual congeners. , 1991, Toxicology and applied pharmacology.

[82]  A. Brouwer Role of biotransformation in PCB-induced alterations in vitamin A and thyroid hormone metabolism in laboratory and wildlife species. , 1991, Biochemical Society transactions.

[83]  L. Birnbaum,et al.  Teratogenic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin and three polybrominated dibenzofurans in C57BL/6N mice. , 1991, Toxicology and applied pharmacology.

[84]  F. Waern,et al.  Relative liver tumour promoting activity and toxicity of some polychlorinated dibenzo-p-dioxin- and dibenzofuran-congeners in female Sprague-Dawley rats. , 1991, Pharmacology & toxicology.

[85]  P. Wyss,et al.  The use of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) as an unmetabolizable lipophilic model compound. , 1991, Pharmacology & toxicology.

[86]  J. Giesy,et al.  Characterization of the H4IIE rat hepatoma cell bioassay as a tool for assessing toxic potency of planar halogenated hydrocarbons in environmental samples , 1991 .

[87]  S. Kennedy,et al.  Polychlorinated biphenyl (PCB) effects on hepatic mixed function oxidases and porphyria in birds—II. American kestrel , 1991 .

[88]  L. Poellinger,et al.  The dioxin and peroxisome proliferator-activated receptors: nuclear receptors in search of endogenous ligands. , 1992, Trends in pharmacological sciences.

[89]  R. Peterson,et al.  Toxicity and reproductive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in ring-necked pheasant hens. , 1992, Journal of toxicology and environmental health.

[90]  C. Schlatter,et al.  Interactions of 2,2′,4,4′,5,5′-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat☆ , 1992 .

[91]  Robert W. Moore,et al.  In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1. Effects on androgenic status. , 1992, Toxicology and applied pharmacology.

[92]  M. Pesonen,et al.  Expression of P4501A1 in a primary culture of rainbow trout hepatocytes exposed to beta-naphthoflavone or 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1992, Archives of biochemistry and biophysics.

[93]  Robert W. Moore,et al.  In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3. Effects on spermatogenesis and reproductive capability. , 1992, Toxicology and applied pharmacology.

[94]  L. Birnbaum,et al.  Limited PCB antagonism of TCDD-induced malformations in mice. , 1992, Toxicology letters.

[95]  J. Jacobson,et al.  Impact of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls on human and environmental health, with special emphasis on application of the toxic equivalency factor concept. , 1992, European journal of pharmacology.

[96]  M. Olsson,et al.  Concentrations of PCDDs and PCDFs in seals from Swedish waters , 1992 .

[97]  M. Berg,et al.  Assessment of the EROD inducing potency of eleven 2,3,7,8- substituted PCDD/Fs and three coplanar PCBs in the chick embryo , 1992 .

[98]  Interactive effects of 2,2'-4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on thyroid hormone, vitamin A, and vitamin K metabolism in the rat. , 1992 .

[99]  R. Tukey,et al.  Response of human CYP1-luciferase plasmids to 2,3,7,8-tetrachlorodibenzo-p-dioxin and polycyclic aromatic hydrocarbons. , 1993, Toxicology and applied pharmacology.

[100]  G L Kimmel,et al.  Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. , 1993, Critical reviews in toxicology.

[101]  J. Gustafsson,et al.  Interactions of indolo[3,2-b]carbazoles and related polycyclic aromatic hydrocarbons with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver. , 1993, Molecular pharmacology.

[102]  Interactive effects of 2,2',4,4',5,5'-hexachlorodibenzo-p-dioxin on thyroid hormone, vitamin A and vitamin K metabolism in the rat. , 1993 .

[103]  Teratogenicity and immunotoxicity of 3,3',4,4',5-pentachlorobiphenyl in C57BL/6 mice. , 1993, Toxicology.

[104]  S. Safe,et al.  Structure-dependent, competitive interaction of hydroxy-polychlorobiphenyls, -dibenzo-p-dioxins and -dibenzofurans with human transthyretin. , 1993, Chemico-biological interactions.

[105]  Potentiation and antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin effects in a complex environmental mixture. , 1993, Toxicology and applied pharmacology.

[106]  U. Ahlborg,et al.  Relative tumour promoting activity of three polychlorinated biphenyls in rat liver. , 1993, European journal of pharmacology.

[107]  Michael Sjöström,et al.  Identifying training sets of PCDDs and PCDFs for use in chemical and biological monitoring , 1993 .

[108]  J. Whitlock,et al.  Mechanistic aspects of dioxin action. , 1993, Chemical research in toxicology.

[109]  Linda S. Birnbaum,et al.  Toxic equivalency factors for dioxin-like PCBs , 1994 .

[110]  B. Hattum,et al.  Occurrence of non-ortho-, mono-ortho- and di-ortho-substituted PCB congeners in different organs and tissues of polecats (Mustela putorius L.) from the Netherlands , 1994 .

[111]  M. van den Berg,et al.  Toxic potency of 3,3',4,4',5-pentachlorobiphenyl relative to and in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat. , 1994, Toxicology and applied pharmacology.

[112]  J. Stegeman,et al.  Comparison of toxic equivalent factors for selected dioxin and furan congeners derived using fish and mammalian liver cell lines , 1994 .

[113]  Y Fujii-Kuriyama,et al.  Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors. , 1994, The Journal of biological chemistry.

[114]  P. Harper,et al.  Molecular biology of the aromatic hydrocarbon (dioxin) receptor. , 1994, Trends in pharmacological sciences.

[115]  M. van den Berg,et al.  Toxic potency of 2,3,3',4,4',5-hexachlorobiphenyl relative to and in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat. , 1994, Toxicology and applied pharmacology.

[116]  M. E. Hahn,et al.  Photoaffinity labeling of the Ah receptor: phylogenetic survey of diverse vertebrate and invertebrate species. , 1994, Archives of biochemistry and biophysics.

[117]  H. Håkansson,et al.  Effect on tissue vitamin A levels in the rat following subchronic exposure to four individual PCB congeners (IUPAC 77, 118, 126, and 153). , 1994, Chemosphere.

[118]  G. Clark,et al.  Dioxin-responsive genes: examination of dose-response relationships using quantitative reverse transcriptase-polymerase chain reaction. , 1994, Cancer research.

[119]  C. Richter,et al.  Production of a novel recombinant cell line for use as a bioassay system for detection of 2,3,7,8‐tetrachlorodibenzo‐P‐dioxin‐like chemicals , 1994 .

[120]  Promotion of preneoplastic foci in rat liver with 2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin and a defined mixture of 49 polychlorinated dibenzo-p-dioxins. , 1994, Carcinogenesis.

[121]  Annika Hanberg,et al.  Toxic equivalency factors for dioxin-like PCBs , 1994, Environmental science and pollution research international.

[122]  M. van den Berg,et al.  The toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and their relevance for toxicity. , 1994, Critical reviews in toxicology.

[123]  C. Waller,et al.  Polychlorinated biphenyls as hormonally active structural analogues. , 1994, Environmental health perspectives.

[124]  R. Norstrom,et al.  Monitoring biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in great blue heron chicks (Ardea herodias) in British Columbia. , 1994, Journal of toxicology and environmental health.

[125]  E. Glover,et al.  Analysis of the four alleles of the murine aryl hydrocarbon receptor. , 1994, Molecular pharmacology.

[126]  C Rappe,et al.  A toxic equivalency factor scale for polychlorinated dibenzofurans. , 1994, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[127]  B. Stahl,et al.  Subchronic (13-week) toxicity of heptachlorodibenzo-p-dioxin in male Sprague-Dawley rats. , 1994, Chemosphere.

[128]  A. Brouwer,et al.  In vitro metabolism of 3,3',4,4'-tetrachlorobiphenyl in relation to ethoxyresorufin-O-deethylase activity in liver microsomes of some wildlife species and rat. , 1994, European journal of pharmacology.

[129]  M. Hillebrand,et al.  A model for the bioaccumulation of chlorobiphenyl congeners in marine mammals. , 1994, European journal of pharmacology.

[130]  R. Norstrom,et al.  Biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in double-crested cormorant chicks (Phalacrocorax auritus). , 1994, Journal of toxicology and environmental health.

[131]  S. Safe,et al.  Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment. , 1994, Critical reviews in toxicology.

[132]  R. Peterson,et al.  Translocation of 2,3,7,8-Tetrachlorodibenzo-p-dioxin from Adult Female Lake Trout (Salvelinus namaycush) to Oocytes: Effects on Early Life Stage Development and Sac Fry Survival , 1994 .

[133]  M. DeVito,et al.  Use of toxic equivalency factors for risk assessment for dioxins and related compounds. , 1995, Toxicology.

[134]  R. Peterson,et al.  Toxic equivalency factors of polychlorinated dibenzo-p-dioxin, dibenzofuran and biphenyl congeners based on early life stage mortality in rainbow trout (Oncorhynchus mykiss) , 1995 .

[135]  R. Pohjanvirta,et al.  Toxic equivalency factors do not predict the acute toxicities of dioxins in rats. , 1995, European journal of pharmacology.

[136]  J. Parrott,et al.  Relative potency of polychlorinated dibenzo‐p‐dioxins and dibenzofurans for inducing mixed‐function oxygenase activity in rainbow trout , 1995 .

[137]  M. Feeley,et al.  Toxicity of PCB 77 (3,3′,4,4′-Tetrachlorobiphenyl) and PCB 118 (2,3′,4,4′,5-Pentachlorobiphenyl) in the Rat Following Subchronic Dietary Exposure , 1995 .

[138]  A. Bosveld,et al.  Effects of PCDDs, PCDFs and PCBs in common tern (sterna hirundo) breeding in estuarine and coastal colonies in the netherlands and belgium , 1995 .

[139]  Paul D. Jones,et al.  Development of toxic equivalency factors for PCB congeners and the assessment of TCDD and PCB mixtures in rainbow trout , 1995 .

[140]  B. Hattum,et al.  Assessment of experimental data on PCB‐induced reproduction inhibition in mink, based on an isomer‐ and congener‐specific approach using 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin toxic equivalency , 1995 .

[141]  C Rappe,et al.  Selection of Polychlorinated Biphenyls for use in Quantitative Structure-Activity Modelling. , 1995, SAR and QSAR in environmental research.

[142]  D. Minor,et al.  Using three-dimensional quantitative structure-activity relationships to examine estrogen receptor binding affinities of polychlorinated hydroxybiphenyls. , 1995, Environmental health perspectives.

[143]  The importance of pharmacokinetics in determining the relative potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran. , 1995, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[144]  L. Poellinger Mechanism of Signal Transduction by the basic Helix-Loop-Helix Dioxin Receptor , 1995 .

[145]  S. Safe,et al.  Structure-dependent induction of CYP2B by polychlorinated biphenyl congeners in female Sprague-Dawley rats. , 1995, Biochemical pharmacology.

[146]  The Importance of Pharmacokinetics in Determining the Relative Potency of 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,3,7,8-Tetrachlorodibenzofuran , 1995 .

[147]  L. Lindqvist,et al.  EROD induction in cultured chick embryo liver: A sensitive bioassay for dioxin‐like environmental pollutants , 1995 .

[148]  S. Kennedy,et al.  Toxicity of PCB 77 (3,3',4,4'-tetrachlorobiphenyl) and PCB 118 (2,3',4,4'5-pentachlorobiphenyl) in the rat following subchronic dietary exposure. , 1995, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[149]  J. T. Sanderson,et al.  Hepatic microsomal ethoxyresorufin O-deethylase-inducing potency in ovo and cytosolic Ah receptor binding affinity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: comparison of four avian species. , 1995, Toxicology and applied pharmacology.

[150]  M. Clayton,et al.  Interactions of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners for producing rainbow trout early life stage mortality. , 1995, Toxicology and applied pharmacology.

[151]  Organohalogen compounds , 1995, Environmental science and pollution research international.

[152]  M. E. Hahn,et al.  Evolutionary conservation of the vertebrate Ah (dioxin) receptor: amplification and sequencing of the PAS domain of a teleost Ah receptor cDNA. , 1995, The Biochemical journal.

[153]  U. Ahlborg,et al.  Liver tumour promoting activity of 3,4,5,3',4'-pentachlorobiphenyl and its interaction with 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1995, European journal of pharmacology.

[154]  S. Safe,et al.  Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners: nonadditive (antagonistic) interactions. , 1995, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[155]  Induction of cytochrome P450 isoenzymes after toxicokinetic interactions between 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,2',4,4',5,5'-hexachlorobiphenyl in the liver of the mouse. , 1995 .

[156]  A toxic equivalency factor scale for polychlorinated biphenyls (PCBs) in chicken hepatocytes , 1995 .

[157]  M. DeVito,et al.  Comparisons of estimated human body burdens of dioxinlike chemicals and TCDD body burdens in experimentally exposed animals. , 1995, Environmental health perspectives.

[158]  O. Hankinson The aryl hydrocarbon receptor complex. , 1995, Annual review of pharmacology and toxicology.

[159]  R. Peterson,et al.  Potency of 3,3′,4,4′,5‐pentachlorobiphenyl (PCB 126), alone and in combination with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), to produce lake trout early life‐stage mortality , 1995 .

[160]  Christoffer Rappe,et al.  Ultraviolet absorption characteristics and calculated semi‐empirical parameters as chemical descriptors in multivariate modelling of polychlorinated biphenyls , 1996 .

[161]  S. Bursian,et al.  Effects of 3,3',4,4'-tetrachlorobiphenyl, 2,3,3',4,4'-pentachlorobiphenyl, and 3,3',4,4',5-pentachlorobiphenyl on the developing chicken embryo when injected prior to incubation. , 1996, Journal of toxicology and environmental health.

[162]  J. L. Zajicek,et al.  Dietary Exposure of Mink to Carp from Saginaw Bay. , 1996 .

[163]  J. Giesy,et al.  Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals. , 1996, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[164]  R. Peterson,et al.  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) , 1996 .

[165]  G. Pendleton,et al.  Developmental toxicity of PCB 126 (3,3',4,4',5-pentachlorobiphenyl) in nestling American kestrels (Falco sparverius). , 1996, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[166]  S. Safe,et al.  Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. , 1996, Biochemical pharmacology.

[167]  L. Johnson,et al.  Effects of developmental exposure to indole-3-carbinol or 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproductive potential of male rat offspring. , 1996, Toxicology and applied pharmacology.

[168]  Effects of Polyhalogenated Aromatic Hydrocarbons on Piscivorous Avian Wildlife , 1996 .

[169]  S. Kennedy,et al.  Biological effects of polychlorinated dibenzo‐p‐dioxins, dibenzofurans, and biphenyls in bald eagle (Haliaeetus leucocephalus) chicks , 1996 .

[170]  R. Peterson,et al.  Additive interactions between pairs of polybrominated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners in a rainbow trout early life stage mortality bioassay. , 1996, Toxicology and applied pharmacology.

[171]  M. DeVito,et al.  Relative potencies of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls derived from hepatic porphyrin accumulation in mice. , 1996, Toxicology and applied pharmacology.

[172]  M W Hornung,et al.  Toxic equivalency factors of polybrominated dibenzo-p-dioxin, dibenzofuran, biphenyl, and polyhalogenated diphenyl ether congeners based on rainbow trout early life stage mortality. , 1996, Toxicology and applied pharmacology.

[173]  S. Kennedy,et al.  Cytochrome P4501A induction in avian hepatocyte cultures: a promising approach for predicting the sensitivity of avian species to toxic effects of halogenated aromatic hydrocarbons. , 1996, Toxicology and applied pharmacology.

[174]  S. Kennedy,et al.  Rapid assessment of induced cytochrome P4501A protein and catalytic activity in fish hepatoma cells grown in multiwell plates : Response to TCDD, TCDF, and two planar PCBs , 1996 .

[175]  J. F. Brown,et al.  Evaluating the impact of exposure to environmental contaminants on human health. , 1996, Clinical chemistry.

[176]  P. Campbell Expression of CYP1A1 in livers and gonads of Pacific salmon: quantitation of mRNA levels by RT-cPCR , 1996 .

[177]  Reproductive effects in F1-generation rats perinatally exposed to PCB126, PCB 118, PCB 153 or 2,3,4,7,8-PnCDF , 1996 .

[178]  R. Letcher,et al.  Immunoquantitation and microsomal monooxygenase activities of hepatic cytochromes P4501A and P4502B and chlorinated hydrocarbon contaminant levels in polar bear (Ursus maritimus). , 1996, Toxicology and applied pharmacology.

[179]  Organochlorine contaminants in double-crested cormorants from Green Bay, WI: I. Large-scale extraction and isolation from eggs using semi-permeable membrane dialysis , 1996, Archives of environmental contamination and toxicology.

[180]  S. Kennedy,et al.  Chicken Embryo Hepatocyte Bioassay for Measuring Cytochrome P4501A-Based 2,3,7,8-Tetrachlorodibenzo- p-dioxin Equivalent Concentrations in Environmental Samples , 1996 .

[181]  Cytochrome P450 induction in weanling and adult rats perinatally exposed to PCB 126, PCB 118, PCB 153 or 2,3,4,7,8-PnCDF , 1996 .

[182]  D. Tillitt,et al.  Effects of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) injected into the yolks of chicken (Gallus domesticus) eggs prior to incubation , 1996, Archives of environmental contamination and toxicology.

[183]  Potency of a complex mixture of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin in causing fish early life stage mortality. , 1996 .

[184]  Polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans in harbor porpoises (Phocoena phocoena) stranded on the Dutch coast between 1990 and 1993 , 1996, Archives of environmental contamination and toxicology.

[185]  J. Giesy,et al.  Comparison of Ah receptor-mediated luciferase and ethoxyresorufin-O-deethylase induction in H4IIE cells: implications for their use as bioanalytical tools for the detection of polyhalogenated aromatic hydrocarbons. , 1996, Toxicology and applied pharmacology.

[186]  M. van den Berg,et al.  Synergistic effect of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic porphyrin levels in the rat. , 1996, Environmental health perspectives.

[187]  Toxic equivalency factors for tetra- through octachlorinated dibenzofurans in PLHC-1 fish hepatoma cell line , 1996 .

[188]  P. Leonards,et al.  Concentration-Dependent Changes of PCB Patterns in Fish-Eating Mammals: Structural Evidence for Induction of Cytochrome P450 , 1997, Archives of environmental contamination and toxicology.

[189]  Organochlorine Contaminants in Double-Crested Cormorants from Green Bay, Wisconsin: II. Effects of an Extract Derived from Cormorant Eggs on the Chicken Embryo , 1997, Archives of environmental contamination and toxicology.

[190]  S. Bursian,et al.  Effects of 3,3′,4,4′,5‐pentachlorobiphenyl (PCB 126), 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), or an extract derived from field‐collected cormorant eggs injected into double‐crested cormorant (Phalacrocorax auritus) eggs , 1997 .

[191]  Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds. , 1997, Teratogenesis, carcinogenesis, and mutagenesis.

[192]  S. Safe,et al.  Inhibition of 3,3',4,4',5-pentachlorobiphenyl-induced chicken embryotoxicity by 2,2',4,4',5,5'-hexachlorobiphenyl. , 1997, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[193]  M. van den Berg,et al.  Interactive effects on the erod‐inducing potency of polyhalogenated aromatic hydrocarbons in the chicken embryo hepatocyte assay , 1997 .

[194]  J. Giesy,et al.  Polychlorinated dibenzo‐p‐dioxins, dibenzofurans, biphenyls and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin equivalents in fishes from Saginaw Bay, Michigan , 1997 .

[195]  John P. Giesy,et al.  An in vitro rainbow trout cell bioassay for aryl hydrocarbon receptor‐mediated toxins , 1997 .

[196]  S. Safe,et al.  Inhibition of 3,3',4,4',5-pentachlorobiphenyl-induced fetal cleft palate and immunotoxicity in C57BL/6 mice by 2,2',4,4',5,5'-hexachlorobiphenyl. , 1997, Chemosphere.

[197]  S. Kennedy,et al.  Sensitivity of Common Tern (Sterna hirundo) Embryo Hepatocyte Cultures to CYP1A Induction and Porphyrin Accumulation by Halogenated Aromatic Hydrocarbons and Common Tern Egg Extracts , 1997, Archives of environmental contamination and toxicology.

[198]  R. Fransson-Steen,et al.  Regular ArticlePromotion of Altered Hepatic Foci by 2,3′,4,4′,5-Pentachlorobiphenyl in Sprague–Dawley Female Rats , 1997 .

[199]  M. E. Hahn,et al.  Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[200]  L. Birnbaum,et al.  Role of CYP1A2 in hepatic sequestration of dioxin: studies using CYP1A2 knock-out mice. , 1997, Biochemical and biophysical research communications.

[201]  R. Smialowicz,et al.  Opposite effects of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on the antibody response to sheep erythrocytes in mice. , 1997, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[202]  M. DeVito,et al.  Dose–Response Relationships for Polyhalogenated Dioxins and Dibenzofurans Following Subchronic Treatment in Mice , 1997 .

[203]  Ethoxyresorufin-O-deethylase (EROD) inducing potencies of planar chlorinated aromatic hydrocarbons in primary cultures of hepatocytes from different developmental stages of the chicken , 1997, Archives of Toxicology.

[204]  D. Dixon,et al.  Derivation of 2,3,7,8-TCDD toxic equivalent factors (TEFs) for selected dioxins, furans and PCBs with rainbow trout and rat liver cell lines and the influence of exposure time. , 1997, Chemosphere.

[205]  M. DeVito,et al.  Dose-response relationships for polyhalogenated dioxins and dibenzofurans following subchronic treatment in mice. I. CYP1A1 and CYP1A2 enzyme activity in liver, lung, and skin. , 1997, Toxicology and applied pharmacology.

[206]  S. Kennedy,et al.  Halogenated aromatic hydrocarbon-mediated porphyrin accumulation and induction of cytochrome P4501A in chicken embryo hepatocytes. , 1997, Biochemical pharmacology.

[207]  M Haag-Grönlund,et al.  Promotion of altered hepatic foci by 2,3',4,4',5-pentachlorobiphenyl in Sprague-Dawley female rats. , 1997, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[208]  Youngchul Kim,et al.  Interactions of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD) and 3,3′4,4′5-pentachlorobihenyl (PCB 126) for producing lethal and sublethal effects in the japanese medaka embryos and larvae. , 1998 .

[209]  Characterization of CYP1A in hepatocytes of cynomolgus monkeys (Macaca fascicularis) and induction by different substituted polychlorinated biphenyls (PCBs) , 1998, Archives of Toxicology.

[210]  Indol(3,2,-bcarbazole (ICZ) is a weaker AH receptor agonist in vivo than in vitro , 1998 .

[211]  M. E. Hahn The aryl hydrocarbon receptor: a comparative perspective. , 1998, Comparative biochemistry and physiology. Part C, Pharmacology, toxicology & endocrinology.

[212]  Dose-response relationships for disposition and hepatic sequestration of polyhalogenated dibenzo-p-dioxins, dibenzofurans, and biphenyls following subchronic treatment in mice. , 1998, Toxicological sciences : an official journal of the Society of Toxicology.

[213]  J. Giesy,et al.  In vitro induction of ethoxyresorufin‐O‐deethylase and porphyrins by halogenated aromatic hydrocarbons in avian primary hepatocytes , 1998 .

[214]  S. Safe Development validation and problems with the toxic equivalency factor approach for risk assessment of dioxins and related compounds. , 1998, Journal of animal science.

[215]  Embryotoxicity of Great Lakes lake trout extracts to developing rainbow trout , 1999 .