Abstract
The potency of 2,3,4,7,8-pentachlorodibenzofuran (P5CDF) and of three defined 2,3,7,8-TCDD-free mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs) to induce cleft palates in NMRI mice was studied. The data were compared with a dose-response curve for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The slope of the dose-response curve for P5CDF was the same as for TCDD. However, application of the International-TCDD-Toxic-Equivalency (I-TE) factor (NATO/CCMS 1988) of 0.5 overestimated the potency of the pentachlorinated congener about 2.5-fold under these experimental conditions, suggesting 0.2 as a TE factor. When assessing the cleft palate frequency on the basis of I-TEs and the weight of the substances, the potencies of the two PCDF mixtures studied were also clearly overestimated. This result was not substantially changed when using the TE factor of 0.2 for P5CDF. For the PCDD mixture studied, the cleft palate-inducing potency found largely agreed with the prediction when applying the I-TE factors. According to our data, the use of TE factors as calculated by the UBA/BGA (1985) or the NATO/CCMS (1988) are both conservative when attempting to assess the cleft palate incidence induced by PCDF mixtures in mice.
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Abraham K, Krowke R, Neubert D (1988) Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: 1. Dose-dependent tissue distribution and induction of hepatic ethoxyresorufin O-deethylase in rats following a single injection. Arch Toxicol 62: 359–368
Beck H, Eckart K, Mathar W, Wittkowski R (1989) Dependence of PCDD and PCDF levels in human milk on various parameters in the Federal Republic of Germany. Chemosphere 18: 1063–1066
Beck H, Droß A, Ende M, Fürst C, Fürst P, Hille A, Mathar W, Wilmers K (1991) Polychlorierte Dibenzofurane und -dioxine in Frauenmilch. Bundesgesundheitsblatt 34: 564–568
Birnbaum LS (1991) Developmental toxicity of TCDD and related compounds: species sensitivities and differences. In: Gallo M, Scheuplein RJ, van Heijden KA (eds) Banbury Report 35, Biological basis for risk assessment of dioxins and related compounds. Cold Spring Harbor Laboratory Press, pp 51–64
Birnbaum LS, Harris MW, Barnhart ER, Morrissey RE (1987) Teratogenicity of three polychlorinated dibenzofurans in C57BL/6N mice. Toxicol Appl Pharmacol 90: 206–216
Chahoud I, Kwasigroch TE (1977) Controlled breeding of laboratory animals. In: Neubert D, Merker H-J, Kwasigroch TE (eds) Methods in prenatal toxicology. Georg Thieme, Stuttgart, pp 78–91
Czuczwa JM, McVeety BD, Hites RA (1984) Polychlorinated dibenzo-p-dioxins and dibenzofurans in sediments from Siskiwit lake, Isle Royale. Science 226: 568–569
Flodström S, Ahlborg UG (1991 a) Liver tumour promoting activity of some polychlorinated dibenzo-p-dioxin-, dibenzofuran- and biphenyl-congeners in female rats. Dioxin '91 [Abstract]: S59
Flodström S, Ahlborg UG (1991 b) Promotion of hepatocarcinogenesis in rats by PCDDs and PCDFs. In: Gallo M, Scheuplein RJ, van Heijden KA (eds) Banbury Report 35, Biological basis for risk assessment of dioxins and related compounds. Cold Spring Harbor Laboratory Press, pp 405–412
Fürst P, Meemken H-A, Groebel W (1986) Determination of polychlorinated dibenzodioxins and dibenzofurans in human milk. Chemosphere 15: 1977–1980
Goldstein JA (1980) Structure-activity relationship for the biochemical effects and the relationships to toxicity. In: Kimbrough RD (ed) Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins and related products. Elsevier/North Holland, Amsterdam, pp 151–190
Golor G, Koch E, Schulz-Schalge T, Yamashita K, Wiesmüller T, Körner W, Hagenmaier H, Neubert D (1992) Concentration-effect analysis with TCDD, H7CDD and OCDD in female Wistar rats. Chemosphere 25: 923–930
Hagenmaier H, Brunner H, Haag R, Kraft M (1986) Selective determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the presence of a large excess of other polychlorinated dibenzodioxins and polychlorinated dibenzofurans. Fresenius Z Anal Chem 323: 24–28
Hagenmaier H, Brunner H, Haag R, Kraft M (1987) Copper-catalyzed dechlorination/hydrogenation of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and other chlorinated aromatic compounds. Environ Sci Technol 21: 1085–1088
McConnell EE (1980) Acute and chronic toxicity, carcinogenesis, reproduction, teratogenesis and mutagenesis in animals. In: Kimbrough RD (ed) Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins and related products. Elsevier/North Holland, Amsterdam, pp 109–150
NATO/CCMS (1988) Pilot study on international information exchange on dioxins and related compounds. International equivalency factors (I-TEF) method of risk assessment for complex mixtures of dioxins and related compounds. NATO Report No. 176: 1–26
Neubert D, Abraham K, Golor G, Krowke R, Krüger N, Nagao T, Neubert R, Schulz-Schalge T, Stahlmann R, Wiesmüller T, Hagenmaier H (1991) Comparison of the effects of PCDDs and PCDFs on different species taking kinetic variables into account. In: Gallo M, Scheuplein RJ, van Heijden KA (eds) Banbury Report 35, Biological basis for risk assessment of dioxins and related compounds. Cold Spring Harbor Laboratory Press, pp 27–44
Neubert D, Golor G, Neubert R (1992) TCDD toxicity-equivalencies for PCDD/PCDF congeners: prerequisites and limitations. Chemosphere 25: 65–70
OME (1984) Ontario Ministry of the Environment, Scientific Criteria Document for Standard Development. No. 4-84, Toronto, Canada
Ono M, Wakimoto T, Tatsukawa R, Masuda Y (1986) Polychlorinated dibenzo-p-dioxins and dibenzofurans in human adipose tissues of Japan. Chemosphere 15: 1629–1634
Poiger H, Pluess N, Schlatter C (1989) Subchronic toxicity of some chlorinated dibenzofurans in rats. Chemosphere 18: 265–275
Poland A, Knutson JC (1982) 2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Annu Rev Pharmacol Toxicol 22: 517–554
Rappe C, Buser HR, Stalling DL, Smith LM, Dougherty RC (1981) Identification of polychlorinated dibenzofurans in environmental samples. Nature 292: 524–526
Rappe C, Anderson R, Bergquist PA, Brohede C, Hansson M, Keller LO, Lindstrom G, Marklund S, Nygren M, Swanson SE, Tysklind M, Wiberr K (1987) Overview on environmental fate of chlorinated dioxins and dibenzofurans. Sources, levels and isomeric pattern in various matrices. Chemosphere 16: 1603–1618
Ryan JJ (1986) Variation of dioxins and furans in human tissues. Chemosphere 15: 1585–1593
Ryan JJ, Lizotte R, Lau BP-Y (1985) Chlorinated dibenzo-p-dioxins and chlorinated dibenzofurans in Canadian human adipose tissue. Chemosphere 14: 697–706
Tarkowski S, Yrjänheikki E (1989) WHO coordinated intercountry studies on levels of PCDDs and PCDFs in human milk. Chemosphere 19: 995–1000
UBA/BGA (1985) Sachstand Dioxine — Nov. 1984, Umweltbundesamt Berichte 5/85, Erich Schmidt Verlag, Berlin (in German), pp 257–266
USEPA (US Environmental Protection Agency) (1985) Health assessment document for polychlorinated dibenzo-p-dioxins. EPA/600/ 8-84/014F
USEPA (US Environmental Protection Agency) (1987) Interum procedures for estimating risks associated with exposures to mixtures of chlorinated dibenzo-p-dioxins and -dibenzofurans (CDDs and CDFs). EPA/625/3-87/012
van der Heijden CA, Knapp AG, Kramers PGN, van Logten MJ (1982) Report DOC/LCM 300/292. State Institute of National Health, Bilthoven, The Netherlands
Wilson JG (1965) Methods for administering agents and detecting malformations in experimental animals. In: Wilson JG, Warkany J (eds) Teratology principles and techniques. University of Chicago Press, Chicago, pp 262–277
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Nagao, T., Golor, G., Hagenmaier, H. et al. Teratogenic potency of 2,3,4,7,8-pentachlorodibenzofuran and of three mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans in mice. Problems with risk assessment using TCDD toxic-equivalency factors. Arch Toxicol 67, 591–597 (1993). https://doi.org/10.1007/BF01974065
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DOI: https://doi.org/10.1007/BF01974065