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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
Authors:Hanspaul Hagenmaier  Thomas Wiesmüller  Georg Golor  Ralf Krowke  Hans Helge  Diether Neubert
Affiliation:(1) Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, D-7400 Tübingen;(2) Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Garystr. 5, D-1000 Berlin 33;(3) Kaiserin Auguste Victoria Haus, Kinderklinik, Freie Universität Berlin, Heubnerweg 6, D-1000 Berlin 19
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.The term ldquodepositionrdquo 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.).
Keywords:Tissue distribution  Toxicokinetics  Placental transfer  Mother's milk  Polychlorinated dibenzo-p-dioxins (PCDDs)  Polychlorinated dibenzofurans (PCDFs)  Marmoset monkeys (Callithrix jacchus)
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