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Transfer of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) via placenta and through milk in a marmoset monkey

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Abstract

A defined mixture of polychlorinated dibenzop-dioxins and dibenzofurans (PCDDs and PCDFs) was subcutaneously administered to a pregnant marmoset monkey (Callithrix jacchus) 11 weeks prior to delivery. Transfer of PCDDs and PCDFs via placenta and mother's milk was investigated by measurement of concentrations in a newborn 1 day after birth and in an infant of the same litter after a lactation period of 33 days. Furthermore, comparative measurements were performed in different tissues of the mother at the end of the lactation period, and in addition, in two groups of four adult monkeys each 1 and 6 weeks after treatment. Deposition of the PCDDs and PCDFs into fetal liver was very low for most of the 2,3,7,8-substituted congeners. Highest deposition was observed for 2,3,7,8-T4CDD and 1,2,3,7,8-P5CDD. For all other compounds concentrations in the hepatic tissue of newborn shortly after birth were lower than one tenth of corresponding concentrations in adults. Especially for PCDFs, prenatal deposition in fetal liver was extremely low. Fetal liver is apparently largely unable to accumulate PCDDs/PCDFs. In contrast to liver, concentrations of 2,3,7,8-substituted PCDDs/PCDFs in adipose tissue of the newborn were at least one third of the levels in adults. However, concentrations of OCDD and OCDF were about three times higher in the newborn than in adult adipose tissue. Transfer of some of the 2,3,7,8-substituted PCDDs and PCDFs to the off-spring via mother's milk was considerable, leading to hepatic concentrations in the suckled infant at the end of the 33-day nursing period well above corresponding concentrations in the dam. When hepatic concentrations in the infant and dam were compared 2- to 4-fold higher concentrations were found in the infant's liver for 2,3,7,8-T4CDD/F and for 1,2,3,7,8-P5CDD. In the case of the 2,3,7,8-substituted H6CDDs, P5CDFs, and most of the H6CDFs, hepatic concentrations in the infant and dam were in the same range at the end of the suckling period. In contrast to this, less than one tenth the concentration of OCDD was found in the infant's liver when compared with adult liver. A corresponding phenomenon was observed for PCDFs. At the maximum absorption, 1 week after injection, for almost all 2,3,7,8-substituted congeners highest concentrations were measured in hepatic tissue of adult monkeys. This is especially true for those substances with six and more chlorine atoms. Besides adipose tissue, comparatively high levels were found in thymus and also in lung tissue. The limited data available point to a long persistence of some of the 2,3,7,8-substituted congeners in the thymus. Especially low concentrations of all the congeners were measured in the brain and testes.

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Abbreviations

PCDDs and PCDFs:

poly-chlorinated dibenzo-p-dioxins and dibenzofurans

T4CDDs and T4CDFs:

tetra-chlorinated dibenzo-p-dioxins and dibenzofurans

P5CDDs and PSCDFs:

penta-chlorinated dibenzo-p-dioxins and dibenzofurans

H6CDDs and H6CDFs:

hexachlorinated dibenzo-p-dioxins and dibenzofurans

H7CDDs and H7CDFs:

hepta-chlorinated dibenzo-p-dioxins and dibenzofurans

OCDD and OCDF:

octa-chlorinated dibenzo-p-dioxin and dibenzofuran

References

  • 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

    Article  PubMed  Google Scholar 

  • Abraham K, Krowke R, Neubert D (1989a) Absorption of TCDD following parenteral application in rats using various vehicles. Chemosphere 19: 893–898

    Article  Google Scholar 

  • Abraham K, Weberru\ U, Wiesmüller T, Hagenmaier H, Krowke R, Neubert D (1989b) Comparative studies on absorption and distribution in the liver and adipose tissue of PCDDs and PCDFs in rats and marmoset monkeys. Chemosphere 19: 887–892

    Article  Google Scholar 

  • Abraham K, Wiesmüller T, Brunner H, Krowke R, Hagenmaier H, Neubert D (1989c) Absorption and tissue distribution of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in the rat. Arch Toxicol 63: 193–202

    Article  PubMed  Google Scholar 

  • Abraham K, Wiesmüller T, Brunner H, Krowke R, Hagenmaier H, Neubert D (1989d) Elimination of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in rat faeces. Arch Toxicol 63: 75–78

    Article  PubMed  Google Scholar 

  • Beck H, Eckart K, Mathar W, Wittkowski R (1987) Isomerenspezifische Bestimmung von PCDD and PCDF in Human- und Lebensmittelproben VDI-Berichte 634: 359–382

    Google Scholar 

  • Beck H, Eckart K, Mathar W, Wittkowski R (1989a) PCDD and PCDF body burden from food intake in the Federal Republic of Germany. Chemosphere 18: 417–424

    Article  Google Scholar 

  • Beck H, Eckart K, Mathar W, Wittkowski R (1989b) Dependence of PCDD and PCDF levels in human milk on various parameters in the Federal Republic of Germany. Chemosphere 18: 1063–1066

    Article  Google Scholar 

  • Birmingham B, Thorpe B, Frank R, Clement R, Tosine H, Gleming G, Ashman J, Wheeler J, Ripley BD, Ryan JJ (1989) Dietary intake of PCDD and PCDF from food in Ontario, Canada. Chemosphere 19: 507–512

    Article  Google Scholar 

  • Birnbaum LS, Decad GM, Matthews HB, McConnell (1981) Fate of 2,3,7,8-tetrachlorodibenzofuran in the monkey. Toxicol Appl Pharmacol 57: 189–196

    Article  PubMed  Google Scholar 

  • Bowman RE, Schantz SL, Weerasinghe NCA, Gross ML, Barsotti DA (1989a) Chronic dietary intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 5 or 25 parts per trillion in the monkey: TCDD kinetics and dose-effect estimate of reproductive toxicity. Chemosphere 18: 243–252

    Article  Google Scholar 

  • Bowman RE, Schantz SL, Gross ML, Ferguson SA (1989b) Behavioral effects in monkeys exposed to 2,3,7,8-TCDD transmitted maternally during gestation and for four months of nursing. Chemosphere 18: 235–242

    Article  Google Scholar 

  • Brewster DW, Elwell MR, Birnbaum LS (1988) Toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) in the Rhesus monkey (Macaca mulatta). Toxicol Appl Pharmacol 93: 231–246

    Article  PubMed  Google Scholar 

  • Chahoud I, Krowke R, Schimmel A, Merker H-J, Neubert D (1989) Reproductive toxicity and pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1. Effects of high doses on the fertility of male rats. Arch Toxicol 63: 432–439

    Article  PubMed  Google Scholar 

  • Dencker L, Hassoun E, D'Argy R, Alm G (1985) Fetal thymus organ culture as an in vitro model for the toxicity of 2,3,7,8-tet-rachlorodibenzo-p-dioxin and its congeners. Mol Pharmacol 27: 133–140

    PubMed  Google Scholar 

  • Fürst P, Krüger C, Meemken H-A, Groebel W (1989) PCDD and PCDF levels in human milk — dependence on the period of lactation. Chemosphere 18: 439–444

    Article  Google Scholar 

  • Greenlee WF, Dold KM, Irons RD, Osborn R (1985) Evidence for direct action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thymic epithelium. Toxicol Appl Pharmacol 79: 112–120

    Article  PubMed  Google Scholar 

  • Greenlee WF, Dold KM, Osborn R (1987) An in vitro model for studying cellular and molecular mechanisms of thymic atrophy by chlorinated aromatic compounds. In: Berlin A, Deamn J, Draper MH, Smith EMB, Spreafoco F (eds) Immunotoxicology. Martinus Nijhoff Publ, Dordrecht, Boston, Lancester, pp 159–170

    Google Scholar 

  • 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

    Article  Google Scholar 

  • Heger W, Merker HJ, Neubert D (1988) Frequency of prenatal loss in marmoset monkeys (Callithrix jacchus). In: Neubert D, Merker H-J, Hendrickx AG (eds) Non-human primates — developmental biology and toxicology. Ueberreuter Wissenschaftsverlag, Wien, Berlin, pp 129–140

    Google Scholar 

  • Jensen DJ, Hummel RA (1982) Secretion of TCDD in milk and cream following the feeding of TCDD to lactating dairy cows. Bull Environ Contam Toxicol 29: 440–446

    Article  PubMed  Google Scholar 

  • Krowke R, Neubert D (1988) Embryotoxic potency of 2,3,7,8-tet-rachlorodibenzodioxin (TCDD) in marmosets. In: Neubert D, Merker H-J, Hendrickx AG (eds) Non-human primates — developmental biology and toxicology. Ueberreuter Wissenschaftsverlag, Wien, Berlin, pp 499–510

    Google Scholar 

  • Krowke R, Chahoud I, Baumann-Wilschke I, Neubert D (1989a) Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2. Pharmacokinetics in rats using a loading-dose/maintenance-dose regime with high doses. Arch Toxicol 63: 356–360

    Article  PubMed  Google Scholar 

  • Krowke R, Franz G, Neubert D (1989b) Embryotoxicity — is the TCDD-induced embryotoxicity in rats due to maternal toxicity? Chemosphere 18: 291–298

    Article  Google Scholar 

  • Merker H-J, Heger W, Sames K, Stürje H, Neubert D (1988) Embryotoxic effects of thalidomide-derivatives in the non-human primateCallithrix jacchus. I. Effects of 3-(1, 3-dihydro-1 -oxo-2H-isoindol-2-yl)-2,6-dioxopiperidine (EM 12) on skeletal development. Arch Toxicol 61: 165–179

    Article  PubMed  Google Scholar 

  • NATO (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

    Google Scholar 

  • Nau H, Ba\ R, Neubert D (1986) Transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via placenta and milk, and postnatal toxicity in the mouse. Arch Toxicol 59: 36–40

    Article  PubMed  Google Scholar 

  • Neubert D (1988) Significance of pharmacokinetic variables in reproductive and developmental toxicity. Xenobiotica 18 [supp no 1]: 45–58

    PubMed  Google Scholar 

  • Neubert D, Wiesmüller T, Abraham K, Krowke R, Hagenmaier H (1990a) Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys. Arch Toxicol 64: 431–432

    Article  PubMed  Google Scholar 

  • Neubert D, Golor G, Hagenmaier H (1990b) Toxic TCDD-Equivalents, problems and applicability for risk assessment. Toxicol Forum (in press)

  • Neubert R, Jacob-Müller U, Stahlmann R, Helge H, Neubert D (1990c) Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 1. Effects on peripheral lymphocytes of a non-human primate (Callithrix jacchus) after treatment with 2,3,7,8-tet-rachlorodibenzo-p-dioxin. Arch Toxicol: 64: 345–359

    Article  PubMed  Google Scholar 

  • Patterson DG, Hoffman RE, Needham LL, Roberts DW, Bagby JR, Pirkle JL, Falk H, Sampson EJ, Houk VN (1986a) 2,3,7,8-tetrachlorodibenzo-p-dioxin levels in adipose tissue of exposed and control persons in Missouri. An interim report. JAMA 256: 2683–2686

    Article  Google Scholar 

  • Patterson DG, Holler JS, Smith SJ, Liddle JA, Sampson EJ, Needham LL (1986b) Human adipose data for 2,3,7,8-tetrachlorodibenzo-p-dioxin in certain U. S. samples. Chemosphere 15: 2055–2060

    Article  Google Scholar 

  • Patterson DG, Fingerhut MA, Roberts DW, Needham LL, Haring Sweeney M, Marlow DA, Andrews JS, Halperin WE (1989) Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Am J Indust Med 16: 135–146

    Google Scholar 

  • Päpke O, Ball M, Lis ZA, Scheunert K (1989) PCDD/PCDF in whole blood samples of unexposed persons. Chemosphere 19: 941–948

    Article  Google Scholar 

  • Rappe C, Nygren M, Lindström G, Hansson M (1986) Dioxins and dibenzofurans in biological samples of European origin. Chemosphere 15: 1635–1639

    Article  Google Scholar 

  • Hartmann J, Schulz-Schalge T, Golor G, Fischer B, Chahoud I, Neubert D (1990) Comparison of effects of TCDD and a defined PCDD mixture on the number of sperm in rat testes. Dioxin '9, Vol. 1: 181–184

    Google Scholar 

  • Ryan JJ, Schecter A, Lizotte R, Sun WF, Miller L (1985) Tissue distribution of dioxins and furans in humans from the general population. Chemosphere 14: 929–932

    Article  Google Scholar 

  • Schecter A, Fürst P, Ryan JJ, Fürst C, Meemken H-A, Groebel W, Constable J, Vu D (1989a) Polychlorinated dioxin and dibenzofuran levels from human milk from several locations in the United States, Germany and Vietnam. Chemosphere 19: 979–984

    Article  Google Scholar 

  • Schecter A, Fürst P, Krüger C, Meemken H-A, Groebel W, Constable JD (1989b) Levels of polychlorinated dibenzofurans, dibenzodioxins, PCBs, DDT and DDE, hexachlorobenzene, dieldrin, hexachlorocy-clohexanes and oxychlordane in human breast milk from the United States, Thailand, Vietnam, and Germany. Chemosphere 18: 445–454

    Article  Google Scholar 

  • Startin JR, Rose M, Offen C (1989) Analysis of PCDDs and PCDFs in human milk from the UK. Chemosphere 19: 985–988

    Article  Google Scholar 

  • Tarkowski S, Yrjänheikki E (1989) WHO coordinated intercountry studies on levels of PCDDs and PCDFs in human milk. Chemosphere 19: 995–1000

    Article  Google Scholar 

  • Thoma H, Mücke W, Kretschmer E (1989) Concentrations of PCDD and PCDF in human fat and liver samples. Chemosphere 18: 491–498

    Article  Google Scholar 

  • Wiesmiiller T (1990) Untersuchungen zur katalytischen Dechlorierung von Octachlordibenzo-p-dioxin and Octachlordibenzofuran und Anwendung der erhaltenen Gemische in toxikologischen Studien. Inaugural-Dissertation, Fakultät für Chemie und Pharmazie, Eberhard-Karls-Universität, Tübingen

    Google Scholar 

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The term “deposition” is used throughout this paper to designate the presence of PCDDs/PCDFs in a given tissue. This term does not imply any mechanism (storage, active binding, etc.).

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Hagenmaier, H., Wiesmüller, T., Golor, G. et al. Transfer of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) via placenta and through milk in a marmoset monkey. Arch Toxicol 64, 601–615 (1990). https://doi.org/10.1007/BF01974688

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