Search tips
Search criteria 


Logo of envhperEnvironmental Health PerspectivesBrowse ArticlesAbout EHPGeneral InformationAuthorsMediaProgramsPartnerships
Environ Health Perspect. 1998 December; 106(12): 775–792.
PMCID: PMC1533232
Research Article

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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (5.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Shain W, Bush B, Seegal R. Neurotoxicity of polychlorinated biphenyls: structure-activity relationship of individual congeners. Toxicol Appl Pharmacol. 1991 Oct;111(1):33–42. [PubMed]
  • Seegal RF, Bush B, Shain W. Lightly chlorinated ortho-substituted PCB congeners decrease dopamine in nonhuman primate brain and in tissue culture. Toxicol Appl Pharmacol. 1990 Oct;106(1):136–144. [PubMed]
  • Brouwer A, van den Berg KJ. Early and differential decrease in natural retinoid levels in C57BL/Rij and DBA/2 mice by 3,4,3',4'-tetrachlorobiphenyl. Toxicol Appl Pharmacol. 1984 Apr;73(2):204–209. [PubMed]
  • Brouwer A. Role of biotransformation in PCB-induced alterations in vitamin A and thyroid hormone metabolism in laboratory and wildlife species. Biochem Soc Trans. 1991 Aug;19(3):731–737. [PubMed]
  • Waller CL, Minor DL, McKinney JD. Using three-dimensional quantitative structure-activity relationships to examine estrogen receptor binding affinities of polychlorinated hydroxybiphenyls. Environ Health Perspect. 1995 Jul-Aug;103(7-8):702–707. [PMC free article] [PubMed]
  • Safe S. 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). Crit Rev Toxicol. 1990;21(1):51–88. [PubMed]
  • Birnbaum LS, Morrissey RE, Harris MW. Teratogenic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin and three polybrominated dibenzofurans in C57BL/6N mice. Toxicol Appl Pharmacol. 1991 Jan;107(1):141–152. [PubMed]
  • Hornung MW, Zabel EW, Peterson RE. Additive interactions between pairs of polybrominated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners in a rainbow trout early life stage mortality bioassay. Toxicol Appl Pharmacol. 1996 Oct;140(2):345–355. [PubMed]
  • Hornung MW, Zabel EW, Peterson RE. Toxic equivalency factors of polybrominated dibenzo-p-dioxin, dibenzofuran, biphenyl, and polyhalogenated diphenyl ether congeners based on rainbow trout early life stage mortality. Toxicol Appl Pharmacol. 1996 Oct;140(2):227–234. [PubMed]
  • Aulerich RJ, Bursian SJ, Napolitano AC. Biological effects of epidermal growth factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin on developmental parameters of neonatal mink. Arch Environ Contam Toxicol. 1988 Jan;17(1):27–31. [PubMed]
  • Aulerich RJ, Bursian SJ, Evans MG, Hochstein JR, Koudele KA, Olson BA, Napolitano AC. Toxicity of 3,4,5,3',4',5'-hexachlorobiphenyl to mink. Arch Environ Contam Toxicol. 1987 Jan;16(1):53–60. [PubMed]
  • Ahlborg UG, Brouwer A, Fingerhut MA, Jacobson JL, Jacobson SW, Kennedy SW, Kettrup AA, Koeman JH, Poiger H, Rappe C, 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. Eur J Pharmacol. 1992 Dec 1;228(4):179–199. [PubMed]
  • Tanabe S, Kannan N, Subramanian A, Watanabe S, Tatsukawa R. Highly toxic coplanar PCBs: occurrence, source, persistency and toxic implications to wildlife and humans. Environ Pollut. 1987;47(2):147–163. [PubMed]
  • van Scheppingen WB, Verhoeven AJIM, Mulder P, Addink MJ, Smeenk C. Polychlorinated Biphenyls, Dibenzo-p-dioxins, and Dibenzofurans in Harbor Porpoises (Phocoena phocoena) Stranded on the Dutch Coast Between 1990 and 1993. Arch Environ Contam Toxicol. 1996 May;30(4):492–502. [PubMed]
  • Binder RL, Stegeman JJ. Basal levels and induction of hepatic aryl hydrocarbon hydroxylase activity during the embryonic period of development in brook trout. Biochem Pharmacol. 1983 Apr 1;32(7):1324–1327. [PubMed]
  • Andersson T, Pesonen M, Johansson C. 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. Biochem Pharmacol. 1985 Sep 15;34(18):3309–3314. [PubMed]
  • Lindström-Seppä P, Pesonen M. Biotransformation enzymes in fish as tools for biomonitoring aquatic environment. Acta Biol Hung. 1986;37(1):85–92. [PubMed]
  • Miranda CL, Wang JL, Chang HS, Buhler DR. 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. Biochem Pharmacol. 1990 Jul 15;40(2):387–390. [PubMed]
  • Pesonen M, Goksøyr A, Andersson T. Expression of P4501A1 in a primary culture of rainbow trout hepatocytes exposed to beta-naphthoflavone or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch Biochem Biophys. 1992 Jan;292(1):228–233. [PubMed]
  • Mably TA, Bjerke DL, Moore RW, Gendron-Fitzpatrick A, Peterson RE. In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3. Effects on spermatogenesis and reproductive capability. Toxicol Appl Pharmacol. 1992 May;114(1):118–126. [PubMed]
  • Williams DE, Masters BS, Lech JJ, Buhler DR. Sex differences in cytochrome P-450 isozyme composition and activity in kidney microsomes of mature rainbow trout. Biochem Pharmacol. 1986 Jun 15;35(12):2017–2023. [PubMed]
  • Stegeman JJ, Chevion M. Sex differences in cytochrome P-450 and mixed-function oxygenase activity in gonadally mature trout. Biochem Pharmacol. 1980 Feb 15;29(4):553–558. [PubMed]
  • Ankley GT, Reinert RE, Mayer RT, Burke MD, Agosin M. Metabolism of alkoxyphenoxazones by channel catfish liver microsomes: effects of phenobarbital, Aroclor 1254 and 3-methylcholanthrene. Biochem Pharmacol. 1987 Apr 15;36(8):1379–1381. [PubMed]
  • Gooch JW, Elskus AA, Kloepper-Sams PJ, Hahn ME, Stegeman JJ. Effects of ortho- and non-ortho-substituted polychlorinated biphenyl congeners on the hepatic monooxygenase system in scup (Stenotomus chrysops). Toxicol Appl Pharmacol. 1989 May;98(3):422–433. [PubMed]
  • McKinney JD, Chae K, Gupta BN, Moore JA, Goldstein HA. Toxicological assessment of hexachlorobiphenyl isomers and 2,3,7,8 tetrachlorodibenzofuran in chicks. I. Relationship of chemical parameters. Toxicol Appl Pharmacol. 1976 Apr;36(1):65–80. [PubMed]
  • Goldstein JA, McKinney JD, Lucier GW, Hickman P, Bergman H, Moore JA. Toxicological assessment of hexachlorobiphenyl isomers and 2,3,7,8,-tetrachlorodibenzofuran in chicks. II. Effects on drug metabolism and porphyrin accumulation. Toxicol Appl Pharmacol. 1976 Apr;36(1):81–92. [PubMed]
  • Miranda CL, Henderson MC, Wang JL, Nakaue HS, Buhler DR. Effects of polychlorinated biphenyls on porphyrin synthesis and cytochrome P-450-dependent monooxygenases in small intestine and liver of Japanese quail. J Toxicol Environ Health. 1987;20(1-2):27–35. [PubMed]
  • Nosek JA, Craven SR, Sullivan JR, Hurley SS, Peterson RE. Toxicity and reproductive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in ring-necked pheasant hens. J Toxicol Environ Health. 1992 Mar;35(3):187–198. [PubMed]
  • Hoffman DJ, Melancon MJ, Klein PN, Rice CP, Eisemann JD, Hines RK, Spann JW, Pendleton GW. Developmental toxicity of PCB 126 (3,3',4,4',5-pentachlorobiphenyl) in nestling American kestrels (Falco sparverius). Fundam Appl Toxicol. 1996 Dec;34(2):188–200. [PubMed]
  • Bosveld AT, Kennedy SW, Seinen W, van den Berg M. Ethoxyresorufin-O-deethylase (EROD) inducing potencies of planar chlorinated aromatic hydrocarbons in primary cultures of hepatocytes from different developmental stages of the chicken. Arch Toxicol. 1997;71(12):746–750. [PubMed]
  • Kennedy SW, Lorenzen A, Jones SP, Hahn ME, Stegeman JJ. Cytochrome P4501A induction in avian hepatocyte cultures: a promising approach for predicting the sensitivity of avian species to toxic effects of halogenated aromatic hydrocarbons. Toxicol Appl Pharmacol. 1996 Nov;141(1):214–230. [PubMed]
  • Sanderson JT, Bellward GD. 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. Toxicol Appl Pharmacol. 1995 May;132(1):131–145. [PubMed]
  • Nikolaidis E, Brunström B, Dencker L. 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. Toxicol Appl Pharmacol. 1988 Feb;92(2):315–323. [PubMed]
  • Nikolaidis E, Brunström B, Dencker L. 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. Pharmacol Toxicol. 1988 Nov;63(5):333–336. [PubMed]
  • Lorenzen A, Kennedy SW, Bastien LJ, Hahn ME. Halogenated aromatic hydrocarbon-mediated porphyrin accumulation and induction of cytochrome P4501A in chicken embryo hepatocytes. Biochem Pharmacol. 1997 Feb 7;53(3):373–384. [PubMed]
  • Lorenzen A, Shutt JL, Kennedy SW. Sensitivity of common tern (Sterna hirundo) embryo HepatocyteCultures to CYP1A induction and porphyrin accumulation by halogenated aromatic hydrocarbons and common tern egg extracts. Arch Environ Contam Toxicol. 1997 Feb;32(2):126–134. [PubMed]
  • Safe SH. Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment. Crit Rev Toxicol. 1994;24(2):87–149. [PubMed]
  • Birnbaum LS, DeVito MJ. Use of toxic equivalency factors for risk assessment for dioxins and related compounds. Toxicology. 1995 Dec 28;105(2-3):391–401. [PubMed]
  • Waern F, Flodström S, Busk L, Kronevi T, Nordgren I, Ahlborg UG. Relative liver tumour promoting activity and toxicity of some polychlorinated dibenzo-p-dioxin- and dibenzofuran-congeners in female Sprague-Dawley rats. Pharmacol Toxicol. 1991 Dec;69(6):450–458. [PubMed]
  • DeVito MJ, Diliberto JJ, Ross DG, Menache MG, Birnbaum LS. Dose-response relationships for polyhalogenated dioxins and dibenzofurans following subchronic treatment in mice. I. CYP1A1 and CYP1A2 enzyme activity in liver, lung, and skin. Toxicol Appl Pharmacol. 1997 Dec;147(2):267–280. [PubMed]
  • Pohjanvirta R, Unkila M, Lindén J, Tuomisto JT, Tuomisto J. Toxic equivalency factors do not predict the acute toxicities of dioxins in rats. Eur J Pharmacol. 1995 Dec 7;293(4):341–353. [PubMed]
  • Stahl BU, Kettrup A, Rozman K. Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Part I: Acute toxicity and toxic equivalency factors (TEFs). Arch Toxicol. 1992;66(7):471–477. [PubMed]
  • Schrenk D, Lipp HP, Wiesmüller T, Hagenmaier H, Bock KW. Assessment of biological activities of mixtures of polychlorinated dibenzo-p-dioxins: comparison between defined mixtures and their constituents. Arch Toxicol. 1991;65(2):114–118. [PubMed]
  • Schrenk D, Buchmann A, Dietz K, Lipp HP, Brunner H, Sirma H, Münzel P, Hagenmaier H, Gebhardt R, Bock KW. 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. Carcinogenesis. 1994 Mar;15(3):509–515. [PubMed]
  • Couture LA, Elwell MR, Birnbaum LS. Dioxin-like effects observed in male rats following exposure to octachlorodibenzo-p-dioxin (OCDD) during a 13-week study. Toxicol Appl Pharmacol. 1988 Mar 30;93(1):31–46. [PubMed]
  • DeVito MJ, Birnbaum LS. The importance of pharmacokinetics in determining the relative potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran. Fundam Appl Toxicol. 1995 Jan;24(1):145–148. [PubMed]
  • van Birgelen AP, DeVito MJ, Akins JM, Ross DG, Diliberto JJ, Birnbaum LS. Relative potencies of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls derived from hepatic porphyrin accumulation in mice. Toxicol Appl Pharmacol. 1996 May;138(1):98–109. [PubMed]
  • Harris M, Zacharewski T, Piskorska-Pliszczynska J, Rosengren R, Safe S. 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. Toxicol Appl Pharmacol. 1990 Sep 1;105(2):243–253. [PubMed]
  • Harper N, Connor K, Steinberg M, Safe S. Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners: nonadditive (antagonistic) interactions. Fundam Appl Toxicol. 1995 Aug;27(1):131–139. [PubMed]
  • Hébert CD, Harris MW, Elwell MR, Birnbaum LS. 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. Toxicol Appl Pharmacol. 1990 Feb;102(2):362–377. [PubMed]
  • Tysklind M, Tillitt D, Eriksson L, Lundgren K, Rappe C. A toxic equivalency factor scale for polychlorinated dibenzofurans. Fundam Appl Toxicol. 1994 Feb;22(2):277–285. [PubMed]
  • Dickerson R, Howie L, Davis D, Safe S. The structure-dependent effects of heptachlorodibenzofuran isomers in male C57BL/6 mice: immunotoxicity and monooxygenase enzyme induction. Fundam Appl Toxicol. 1990 Aug;15(2):298–307. [PubMed]
  • Van den Berg M, De Jongh J, Poiger H, Olson JR. The toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and their relevance for toxicity. Crit Rev Toxicol. 1994;24(1):1–74. [PubMed]
  • Håkansson H, Manzoor E, Trossvik C, Ahlborg UG, Chu I, Villenueve D. Effect on tissue vitamin A levels in the rat following subchronic exposure to four individual PCB congeners (IUPAC 77, 118, 126, and 153). Chemosphere. 1994 Nov-Dec;29(9-11):2309–2313. [PubMed]
  • Chu I, Villeneuve DC, Yagminas A, Lecavalier P, Håkansson H, Ahlborg UG, Valli VE, Kennedy SW, Bergman A, Seegal RF, 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. Fundam Appl Toxicol. 1995 Jul;26(2):282–292. [PubMed]
  • Sargent L, Dragan YP, Erickson C, Laufer CJ, Pitot HC. 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. Carcinogenesis. 1991 May;12(5):793–800. [PubMed]
  • Sawyer T, Safe S. PCB isomers and congeners: induction of aryl hydrocarbon hydroxylase and ethoxyresorufin O-deethylase enzyme activities in rat hepatoma cells. Toxicol Lett. 1982 Sep;13(1-2):87–93. [PubMed]
  • Van Birgelen AP, Van der Kolk J, Fase KM, Bol I, Poiger H, Brouwer A, Van den Berg M. 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. Toxicol Appl Pharmacol. 1994 Aug;127(2):209–221. [PubMed]
  • Hemming H, Bager Y, Flodström S, Nordgren I, Kronevi T, Ahlborg UG, Wärngård L. Liver tumour promoting activity of 3,4,5,3',4'-pentachlorobiphenyl and its interaction with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Eur J Pharmacol. 1995 Mar 16;292(3-4):241–249. [PubMed]
  • Mayura K, Spainhour CB, Howie L, Safe S, Phillips TD. Teratogenicity and immunotoxicity of 3,3',4,4',5-pentachlorobiphenyl in C57BL/6 mice. Toxicology. 1993 Jan 29;77(1-2):123–131. [PubMed]
  • Hemming H, Flodström S, Wärngård L, Bergman A, Kronevi T, Nordgren I, Ahlborg UG. Relative tumour promoting activity of three polychlorinated biphenyls in rat liver. Eur J Pharmacol. 1993 Aug 2;248(2):163–174. [PubMed]
  • Leece B, Denomme MA, Towner R, Li SM, Safe S. Polychlorinated biphenyls: correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs). J Toxicol Environ Health. 1985;16(3-4):379–388. [PubMed]
  • Haag-Grönlund M, Wärngård L, Flodström S, Scheu G, Kronevi T, Ahlborg UG, Fransson-Steen R. Promotion of altered hepatic foci by 2,3',4,4',5-pentachlorobiphenyl in Sprague-Dawley female rats. Fundam Appl Toxicol. 1997 Jan;35(1):120–130. [PubMed]
  • Van Birgelen AP, Van der Kolk J, Fase KM, Bol I, Poiger H, Van den Berg M, Brouwer A. 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. Toxicol Appl Pharmacol. 1994 Jun;126(2):202–213. [PubMed]
  • Morrissey RE, Harris MW, Diliberto JJ, Birnbaum LS. Limited PCB antagonism of TCDD-induced malformations in mice. Toxicol Lett. 1992 Jan;60(1):19–25. [PubMed]
  • Poland A, Greenlee WF, Kende AS. Studies on the mechanism of action of the chlorinated dibenzo-p-dioxins and related compounds. Ann N Y Acad Sci. 1979 May 31;320:214–230. [PubMed]
  • Poland A, Glover E. Chlorinated biphenyl induction of aryl hydrocarbon hydroxylase activity: a study of the structure-activity relationship. Mol Pharmacol. 1977 Sep;13(5):924–938. [PubMed]
  • Brunström B, Andersson L. Toxicity and 7-ethoxyresorufin O-deethylase-inducing potency of coplanar polychlorinated biphenyls (PCBs) in chick embryos. Arch Toxicol. 1988;62(4):263–266. [PubMed]
  • Powell DC, Aulerich RJ, Stromborg KL, Bursian SJ. 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. J Toxicol Environ Health. 1996 Oct 25;49(3):319–338. [PubMed]
  • Powell DC, Aulerich RJ, Meadows JC, Tillitt DE, Giesy JP, Stromberg KL, Bursian SJ. 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. Arch Environ Contam Toxicol. 1996 Oct;31(3):404–409. [PubMed]
  • Poland A, Knutson JC. 2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Annu Rev Pharmacol Toxicol. 1982;22:517–554. [PubMed]
  • Safe SH. Comparative toxicology and mechanism of action of polychlorinated dibenzo-p-dioxins and dibenzofurans. Annu Rev Pharmacol Toxicol. 1986;26:371–399. [PubMed]
  • Peterson RE, Theobald HM, Kimmel GL. Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. Crit Rev Toxicol. 1993;23(3):283–335. [PubMed]
  • DeVito MJ, Birnbaum LS, Farland WH, Gasiewicz TA. Comparisons of estimated human body burdens of dioxinlike chemicals and TCDD body burdens in experimentally exposed animals. Environ Health Perspect. 1995 Sep;103(9):820–831. [PMC free article] [PubMed]
  • Poellinger L, Göttlicher M, Gustafsson JA. The dioxin and peroxisome proliferator-activated receptors: nuclear receptors in search of endogenous ligands. Trends Pharmacol Sci. 1992 Jun;13(6):241–245. [PubMed]
  • Whitlock JP., Jr Mechanistic aspects of dioxin action. Chem Res Toxicol. 1993 Nov-Dec;6(6):754–763. [PubMed]
  • Hankinson O. The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol. 1995;35:307–340. [PubMed]
  • Ema M, Ohe N, Suzuki M, Mimura J, Sogawa K, Ikawa S, Fujii-Kuriyama Y. Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors. J Biol Chem. 1994 Nov 4;269(44):27337–27343. [PubMed]
  • Poland A, Palen D, Glover E. Analysis of the four alleles of the murine aryl hydrocarbon receptor. Mol Pharmacol. 1994 Nov;46(5):915–921. [PubMed]
  • Okey AB, Riddick DS, Harper PA. Molecular biology of the aromatic hydrocarbon (dioxin) receptor. Trends Pharmacol Sci. 1994 Jul;15(7):226–232. [PubMed]
  • Hahn ME, Poland A, Glover E, Stegeman JJ. Photoaffinity labeling of the Ah receptor: phylogenetic survey of diverse vertebrate and invertebrate species. Arch Biochem Biophys. 1994 Apr;310(1):218–228. [PubMed]
  • Hahn ME, Karchner SI. Evolutionary conservation of the vertebrate Ah (dioxin) receptor: amplification and sequencing of the PAS domain of a teleost Ah receptor cDNA. Biochem J. 1995 Sep 1;310(Pt 2):383–387. [PubMed]
  • Hahn ME, Karchner SI, Shapiro MA, Perera SA. Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13743–13748. [PubMed]
  • Garrison PM, Tullis K, Aarts JM, Brouwer A, Giesy JP, Denison MS. Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals. Fundam Appl Toxicol. 1996 Apr;30(2):194–203. [PubMed]
  • Brewster DW, Elwell MR, Birnbaum LS. Toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) in the rhesus monkey (Macaca mulatta). Toxicol Appl Pharmacol. 1988 Apr;93(2):231–246. [PubMed]
  • Voorman R, Aust SD. Specific binding of polyhalogenated aromatic hydrocarbon inducers of cytochrome P-450d to the cytochrome and inhibition of its estradiol 2-hydroxylase activity. Toxicol Appl Pharmacol. 1987 Aug;90(1):69–78. [PubMed]
  • Yoshimura H, Kuroki J, Koga N, Kuroki H, Masuda Y, Fukasaku N, Hasegawa M. High accumulation of 2,3,4,7,8-pentachlorodibenzofuran to hepatic microsomes of rats. J Pharmacobiodyn. 1984 Jun;7(6):414–419. [PubMed]
  • Brewster DW, Birnbaum LS. Disposition and excretion of 2,3,4,7,8-pentachlorodibenzofuran in the rat. Toxicol Appl Pharmacol. 1987 Sep 15;90(2):243–252. [PubMed]
  • Diliberto JJ, Burgin D, Birnbaum LS. Role of CYP1A2 in hepatic sequestration of dioxin: studies using CYP1A2 knock-out mice. Biochem Biophys Res Commun. 1997 Jul 18;236(2):431–433. [PubMed]
  • Mühlebach S, Wyss PA, Bickel MH. The use of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) as an unmetabolizable lipophilic model compound. Pharmacol Toxicol. 1991 Dec;69(6):410–415. [PubMed]
  • de Jongh J, Wondergem F, Seinen W, Van den Berg M. Toxicokinetic interactions between chlorinated aromatic hydrocarbons in the liver of the C57BL/6J mouse: I. Polychlorinated biphenyls (PCBs). Arch Toxicol. 1993;67(7):453–460. [PubMed]
  • De Jongh J, Nieboer R, Schröders I, Seinen W, Van den Berg M. Toxicokinetic mixture interactions between chlorinated aromatic hydrocarbons in the liver of the C57BL/6J mouse: 2. Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs). Arch Toxicol. 1993;67(9):598–604. [PubMed]
  • De Jongh J, DeVito M, Nieboer R, Birnbaum L, Van den Berg M. 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. Fundam Appl Toxicol. 1995 May;25(2):264–270. [PubMed]
  • Murk A, Morse D, Boon J, Brouwer A. 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. Eur J Pharmacol. 1994 Apr 4;270(2-3):253–261. [PubMed]
  • Connor K, Safe S, Jefcoate CR, Larsen M. Structure-dependent induction of CYP2B by polychlorinated biphenyl congeners in female Sprague-Dawley rats. Biochem Pharmacol. 1995 Nov 27;50(11):1913–1920. [PubMed]
  • Boon JP, Oostingh I, van der Meer J, Hillebrand MT. A model for the bioaccumulation of chlorobiphenyl congeners in marine mammals. Eur J Pharmacol. 1994 Apr 4;270(2-3):237–251. [PubMed]
  • Letcher RJ, Norstrom RJ, Lin S, Ramsay MA, Bandiera SM. Immunoquantitation and microsomal monooxygenase activities of hepatic cytochromes P4501A and P4502B and chlorinated hydrocarbon contaminant levels in polar bear (Ursus maritimus). Toxicol Appl Pharmacol. 1996 Apr;137(2):127–140. [PubMed]
  • Birnbaum LS, Harris MW, Barnhart ER, Morrissey RE. Teratogenicity of three polychlorinated dibenzofurans in C57BL/6N mice. Toxicol Appl Pharmacol. 1987 Sep 15;90(2):206–216. [PubMed]
  • Lipp HP, Schrenk D, Wiesmüller T, Hagenmaier H, Bock KW. Assessment of biological activities of mixtures of polychlorinated dibenzo-p-dioxins (PCDDs) and their constituents in human HepG2 cells. Arch Toxicol. 1992;66(3):220–223. [PubMed]
  • Sanderson JT, Aarts JM, Brouwer A, Froese KL, Denison MS, Giesy JP. 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. Toxicol Appl Pharmacol. 1996 Apr;137(2):316–325. [PubMed]
  • Hanberg A, Ståhlberg M, Georgellis A, de Wit C, Ahlborg UG. Swedish dioxin survey: evaluation of the H-4-II E bioassay for screening environmental samples for dioxin-like enzyme induction. Pharmacol Toxicol. 1991 Dec;69(6):442–449. [PubMed]
  • Tillitt DE, Ankley GT, Verbrugge DA, Giesy JP, Ludwig JP, Kubiak TJ. H4IIE rat hepatoma cell bioassay-derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents in colonial fish-eating waterbird eggs from the Great Lakes. Arch Environ Contam Toxicol. 1991 Jul;21(1):91–101. [PubMed]
  • Zacharewski T, Harris M, Safe S, Thoma H, Hutzinger O. Applications of the in vitro aryl hydrocarbon hydroxylase induction assay for determining "2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents": pyrolyzed brominated flame retardants. Toxicology. 1988 Oct;51(2-3):177–189. [PubMed]
  • Bannister R, Safe S. 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. Toxicology. 1987 May;44(2):159–169. [PubMed]
  • Safe S, Bandiera S, Sawyer T, Robertson L, Safe L, Parkinson A, Thomas PE, Ryan DE, Reik LM, Levin W, et al. PCBs: structure-function relationships and mechanism of action. Environ Health Perspect. 1985 May;60:47–56. [PMC free article] [PubMed]
  • Rickenbacher U, McKinney JD, Oatley SJ, Blake CC. Structurally specific binding of halogenated biphenyls to thyroxine transport protein. J Med Chem. 1986 May;29(5):641–648. [PubMed]
  • Lans MC, Klasson-Wehler E, Willemsen M, Meussen E, Safe S, Brouwer A. Structure-dependent, competitive interaction of hydroxy-polychlorobiphenyls, -dibenzo-p-dioxins and -dibenzofurans with human transthyretin. Chem Biol Interact. 1993 Jul;88(1):7–21. [PubMed]
  • Korach KS, Sarver P, Chae K, McLachlan JA, McKinney JD. Estrogen receptor-binding activity of polychlorinated hydroxybiphenyls: conformationally restricted structural probes. Mol Pharmacol. 1988 Jan;33(1):120–126. [PubMed]
  • McKinney JD, Waller CL. Polychlorinated biphenyls as hormonally active structural analogues. Environ Health Perspect. 1994 Mar;102(3):290–297. [PMC free article] [PubMed]
  • Gierthy JF, Crane D, Frenkel GD. Application of an in vitro keratinization assay to extracts of soot from a fire in a polychlorinated biphenyl-containing transformer. Fundam Appl Toxicol. 1984 Dec;4(6):1036–1041. [PubMed]
  • Kannan N, Tanabe S, Tatsukawa R. Toxic potential of non-ortho and mono-ortho coplanar PCBs in commercial PCB preparations: "2,3,7,8-T4 CDD toxicity equivalence factors approach. Bull Environ Contam Toxicol. 1988 Aug;41(2):267–276. [PubMed]
  • Safe S. Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds. Teratog Carcinog Mutagen. 1997;17(4-5):285–304. [PubMed]
  • Biegel L, Harris M, Davis D, Rosengren R, Safe L, Safe S. 2,2',4,4',5,5'-hexachlorobiphenyl as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in C57BL/6J mice. Toxicol Appl Pharmacol. 1989 Mar 1;97(3):561–571. [PubMed]
  • Zhao F, Mayura K, Harper N, Safe SH, Phillips TD. 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. Chemosphere. 1997 Mar-Apr;34(5-7):1605–1613. [PubMed]
  • Smialowicz RJ, DeVito MJ, Riddle MM, Williams WC, Birnbaum LS. 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. Fundam Appl Toxicol. 1997 Jun;37(2):141–149. [PubMed]
  • van Birgelen AP, Fase KM, van der Kolk J, Poiger H, Brouwer A, Seinen W, van den Berg M. 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. Environ Health Perspect. 1996 May;104(5):550–557. [PMC free article] [PubMed]
  • Safe SH. Development validation and problems with the toxic equivalency factor approach for risk assessment of dioxins and related compounds. J Anim Sci. 1998 Jan;76(1):134–141. [PubMed]
  • Silkworth JB, Brown JF., Jr Evaluating the impact of exposure to environmental contaminants on human health. Clin Chem. 1996 Aug;42(8 Pt 2):1345–1349. [PubMed]
  • Gillner M, Bergman J, Cambillau C, Alexandersson M, Fernström B, Gustafsson JA. 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. Mol Pharmacol. 1993 Aug;44(2):336–345. [PubMed]
  • Wilker C, Johnson L, Safe S. Effects of developmental exposure to indole-3-carbinol or 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproductive potential of male rat offspring. Toxicol Appl Pharmacol. 1996 Nov;141(1):68–75. [PubMed]
  • Chen I, Safe S, Bjeldanes L. Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. Biochem Pharmacol. 1996 Apr 26;51(8):1069–1076. [PubMed]
  • Astroff B, Zacharewski T, Safe S, Arlotto MP, Parkinson A, Thomas P, Levin W. 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. Mol Pharmacol. 1988 Feb;33(2):231–236. [PubMed]
  • Landers JP, Bunce NJ. The Ah receptor and the mechanism of dioxin toxicity. Biochem J. 1991 Jun 1;276(Pt 2):273–287. [PubMed]
  • Silkworth JB, Cutler DS, O'Keefe PW, Lipinskas T. Potentiation and antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin effects in a complex environmental mixture. Toxicol Appl Pharmacol. 1993 Apr;119(2):236–247. [PubMed]
  • De Jongh J, DeVito M, Nieboer R, Birnbaum L, Van den Berg M. 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. Fundam Appl Toxicol. 1995 May;25(2):264–270. [PubMed]
  • Leece B, Denomme MA, Towner R, Li A, Landers J, Safe S. Nonadditive interactive effects of polychlorinated biphenyl congeners in rats: role of the 2,3,7,8-tetrachlorodibenzo-p-dioxin receptor. Can J Physiol Pharmacol. 1987 Sep;65(9):1908–1912. [PubMed]
  • Zabel EW, Walker MK, Hornung MW, Clayton MK, Peterson RE. Interactions of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners for producing rainbow trout early life stage mortality. Toxicol Appl Pharmacol. 1995 Oct;134(2):204–213. [PubMed]
  • Walker MK, Cook PM, Butterworth BC, Zabel EW, Peterson RE. 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. Fundam Appl Toxicol. 1996 Apr;30(2):178–186. [PubMed]
  • Powell DC, Aulerich RJ, Meadows JC, Tillitt DE, Stromborg KL, Kubiak TJ, Giesy JP, Bursian SJ. Organochlorine Contaminants in Double-Crested Cormorants from Green Bay,Wisconsin: II. Effects of an Extract Derived from Cormorant Eggs onthe Chicken Embryo. Arch Environ Contam Toxicol. 1997 Apr;32(3):316–322. [PubMed]
  • Sanderson JT, Elliott JE, Norstrom RJ, Whitehead PE, Hart LE, Cheng KM, Bellward GD. Monitoring biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in great blue heron chicks (Ardea herodias) in British Columbia. J Toxicol Environ Health. 1994 Apr;41(4):435–450. [PubMed]
  • Sanderson JT, Norstrom RJ, Elliott JE, Hart LE, Cheng KM, Bellward GD. Biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in double-crested cormorant chicks (Phalacrocorax auritus). J Toxicol Environ Health. 1994 Feb;41(2):247–265. [PubMed]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Science