Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Effects of In Utero Exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) on Developmental Landmarks, Steroid Hormone Levels, and Female Estrous Cyclicity in Rats
    Meerts, I.A.T.M. ; Hoving, S. ; Berg, J.H.J. van den; Weijers, B.M. ; Swarts, J.J.M. ; Beek, E.M. van der; Bergman, A. ; Koeman, J.H. - \ 2004
    Toxicological sciences 82 (2004)1. - ISSN 1096-6080 - p. 259 - 267.
    polychlorinated-biphenyls aroclor-1254 - hydroxylated pcb metabolites - reproductive decline - mouse - hypothyroidism - dioxins - dibenzofurans - inhibition - induction - estradiol
    Previous studies have revealed that one of the major metabolites of PCBs detected in human blood, 4-OH-2,3,3',4',5-pentaCB (4-OH-CB107), accumulated in fetal liver, brain, and plasma and reduced maternal and fetal thyroid hormone levels after prenatal exposure to pregnant rats from gestational days (GD) 10¿16. In the present study, the effects of 4-OH-CB-107 on developmental landmarks, steroid hormone levels, and estrous cyclicity of rat offspring after in utero exposure to 4-OH-CB107 was investigated. Pregnant rats were exposed to 0, 0.5, and 5.0 mg 4-OH-CB107 per kg bw from GD 10 to GD 16. Another group of rats was exposed to Aroclor 1254 (25 mg/kg bw) to study the differences between effects caused by parent PCB congeners and the 4-OH-CB107 alone. A significant, dose-dependent prolongation of the estrous cycle was observed in 75% and 82% of female offspring exposed to 0.5 and 5.0 mg 4-OH-PCB107, respectively, compared to 64% of Aroclor 1254 (25 mg/kg) exposed offspring. The diestrous stage of the estrous cycle was prolonged, resembling a state of pseudopregnancy, which might reflect early signs of reproductive senescence. Plasma estradiol concentrations in female rat offspring were significantly increased (50%) in the proestrous stage after exposure to 5 mg 4-OH-CB107 per kg bw. No effects on estradiol levels were observed in Aroclor 1254 treated animals. These results indicate that in utero exposure to 4-OH-CB107 leads to endocrine-disrupting effects, especially in female offspring. The possible impact on neurobehavior following exposure to 4-OH-CB107 will be reported elsewhere
    Carry-over of dioxins and PCBs from feed and soil to eggs at low contamination levels
    Traag, W.A. ; Kan, C.A. ; Zeilmaker, M. ; Hoogerbrugge, R. ; Eijkeren, J. van; Hoogenboom, L.A.P. - \ 2004
    onbekend : Rikilt - Institute of Food Safety (Report / RIKILT 2004.016) - 77
    pluimveehouderij - dioxinen - polychloorbifenylen - voedselbesmetting - bodemverontreiniging - bioaccumulatie - poultry farming - dioxins - polychlorinated biphenyls - food contamination - soil pollution - bioaccumulation
    In order to study the relationship between dioxin and PCB levels in feed and eggs, laying hens were fed with compound feed containing six different levels of dioxins, dioxin-like PCBs and indicator PCBs for a period of 56 days. This was followed by a period of another 56 days on clean feed.Data were successfully modelled in order to predict the levels after different exposure scenario’s. Overall, these data show that exposure to dioxins and dioxin-like PCBs rapidly results in increased levels in eggs and that the current EU limit for feed cannot guarantee egg levels below the EU-limit. Therefore, dioxin levels in chicken feed should be as low as possible and the current limit for dioxins in feed should be further reduced, at least in the case of chicken feeds. More in general, it is important to further harmonize the tolerance limits for feed and edible products like meat, eggs and milk. Information about the carry-over of contaminants in farm animals is essential for this purpose.
    Is saneren wel altijd nodig?
    Jonker, M.T.O. ; Koelmans, A.A. ; Sinke, A. ; Brils, A. - \ 2004
    H2O : tijdschrift voor watervoorziening en afvalwaterbehandeling 37 (2004). - ISSN 0166-8439 - p. 28 - 30.
    verontreinigingsbeheersing - polychloorbifenylen - polycyclische koolwaterstoffen - dioxinen - besluitvorming - schoonmaken - waterorganismen - waterbodems - pollution control - polychlorinated biphenyls - polycyclic hydrocarbons - dioxins - decision making - cleaning - aquatic organisms - water bottoms
    Recent onderzoek heeft aangetoond dat zowel roet- en kooldeeltjes als verweerde olieresiduen giftige organische verontreinigingen,zoals PAK, extreem sterk kunnen binden. Deze materialen zijn wijd verspreid in waterbodems en kunnen ervoor zorgen dat de giftige stoffen vele malen minder worden opgenomen door organismen dan tot nu toe werd aangenomen. De huidige risico-evaluatieprocedure voor waterbodems gaat volledig voorbij aan dit feit, waardoor risico's kunnen worden overschat. Het is daardoor mogelijk dat saneringen plaatsvinden die in feite niet noodzakelijk zijn. De in dit onderzoek ontwikkelde methode kan helpen om hierover uitsluitsel te geven
    Intra- and interlaboratory calibration of the DR Calux bioassay for the analysis of dioxins and dioxin-like chemicals in sediments
    Besselink, H.T. ; Schipper, C.A. ; Klamer, H. ; Leonards, P.E.G. ; Verhaar, H. ; Felzel, E. ; Murk, A.J. ; Thain, J. ; Hosoe, K. ; Schoeters, G. ; Legler, J. ; Brouwer, A. - \ 2004
    Environmental Toxicology and Chemistry 23 (2004)12. - ISSN 0730-7268 - p. 2781 - 2789.
    dioxinen - toxiciteit - biotesten - waterbodems - ecotoxicologie - dioxins - toxicity - bioassays - water bottoms - ecotoxicology - equivalency factors tefs - in-vitro bioassay - round-robin - pcbs - pcdds - pcdfs - support - water - assay
    In the Fourth National Policy Document on Water Management in the Netherlands, it is defined that in 2003, in addition to the assessment of chemical substances, special guidelines for the assessment of dredged material should be recorded. The assessment of dredged material is based on integrated chemical and biological effect measurements. Among others, the DR CALUX® (dioxin responsive–chemically activated luciferase expression) bioassay has tentatively been recommended for inclusion in the dredged material assessment. To ensure the reliability of this bioassay, an intra- and interlaboratory validation study, or ring test, was performed, organized by the Dutch National Institute for Coastal and Marine Management (RIKZ) in cooperation with BioDetection Systems BV (BDS)
    In the Fourth National Policy Document on Water Management in the Netherlands [1], it is defined that in 2003, in addition to the assessment of chemical substances, special guidelines for the assessment of dredged material should be recorded. The assessment of dredged material is based on integrated chemical and biological effect measurements. Among others, the DR CALUX(R) (dioxin responsive-chemically activated luciferase expression) bioassay has tentatively been recommended for inclusion in the dredged material assessment. To ensure the reliability of this bioassay, an intra- and interlaboratory validation study, or ring test, was performed, organized by the Dutch National Institute for Coastal and Marine Management (RIKZ) in cooperation with BioDetection Systems BV (BDS). The intralaboratory repeatability and reproducibility and the limit of detection (LOD) and quantification (LOQ) of the DR CALUX bioassay were determined by analyzing sediment extracts and dimethyl sulfoxide (DMSO) blanks. The highest observed repeatability was found to be 24.1%, whereas the highest observed reproducibility was calculated to be 19.9%. Based on the obtained results, the LOD and LOQ to be applied for the bioassay are 0.3 and 1.0 pM, respectively. The interlaboratory calibration study was divided into three phases, starting with analyzing pure chemicals. During the second phase, sediment extracts were analyzed, whereas in the third phase, whole sediments had to be extracted, cleaned, and analyzed. The average interlaboratory repeatability increased from 14.6% for the analysis of pure compound to 26.1% for the analysis of whole matrix. A similar increase in reproducibility with increasing complexity of handlings was observed with the interlaboratory reproducibility of 6.5% for pure compound and 27.9% for whole matrix. The results of this study are intended as a starting point for implementing the integrated chemical-biological assessment strategy and for systematic monitoring of dredged materials and related materials in the coming years.
    TIE-studie van dioxine-achtige stoffen in zwevend stof en sediment met behulp van de DR-CALUX assay en gas chromatografie met time-of-flight massaspectrometrie
    Leonards, P.E.G. ; Veen, I. van der; Hesselingen, J.M. van - \ 2004
    onbekend : RIVO Milieu en Voedselveiligheid (RIVO rapport C076/04) - 12
    dioxinen - gaschromatografie - massaspectrometrie - dioxins - gas chromatography - mass spectrometry
    In dit onderzoek werd de toxiciteit van dioxine-achtige stoffen met behulp van de DR-CALUX assay van zwevend stof en sediment monsters bepaald.
    Analyse van baggerslib met de DR-CALUX assay en een screening met gaschromatografie met time-of-flight massaspectrometrie
    Leonards, P.E.G. ; Hoek-van Nieuwenhuizen, M. van; Hesselingen, J.M. van - \ 2004
    onbekend : RIVO Milieu en Voedselveiligheid (RIVO rapport C066/04) - 17
    toxiciteit - dioxinen - mariene sedimenten - sediment - havens - anaërobe afbraak - verontreinigde sedimenten - toxicity - dioxins - marine sediments - sediment - harbours - anaerobic digestion - contaminated sediments
    In dit onderzoek werd de toxiciteit van dioxine-achtige stoffen met behulp van de DR-CALUX assay van sediment uit het Zeehavenkanaal van Delfzijl bepaald. De toxiciteit was vergelijkbaar met de resultaten uit het onderzoek van 2002. De activiteit van het sediment bewerkt met een niet-destructieve methode (GPC) was 100 maal hoger dan wanneer het sediment werd bewerkt met het standaard protocol (SPECIE-01) waarbij een chemisch agressieve methode wordt toegepast. Dit bevestigt de resultaten uit eerder onderzoek. Na 18 maanden van anaërobe degradatie van het sediment was de DR-CALUX activiteit van de totale hoeveelheid extraheerbare stoffen met een DR-CALUX activiteit onveranderd, maar een verhoging werd waargenomen voor de fractie waarin zich dioxinen, furanen en PCB’s bevonden. Onduidelijk is waardoor deze verhoging werd veroorzaakt. Echter een sterke afname in DRCALUX activiteit werd gevonden voor stoffen die biologisch beschikbaar zijn. In sediment werd een drietal stoffen (dichloroanthraceen, dichloro-lichexanthone, dichloorbenzidine) met gaschromatografie met time-of-flight massaspectrometrie geïdentificeerd. Deze stoffen bezitten mogelijk een DR-CALUX activiteit en kunnen daarom bijdragen in de dioxine-achtige toxiciteit. Uitgezocht zou moeten worden of deze stoffen inderdaad een activiteit bezitten en hoeveel van de toxiciteit verklaard kan worden.
    Overzicht dioxine proeven uitgevoerd in Nederland met koeien en schapen
    Kan, C.A. ; Meijer, G.A.L. - \ 2003
    Lelystad : ID-Lelystad (Rapport / ID-Lelystad 03/0000744)
    dioxinen - dierlijke producten - koeien - schapen - besmetting - toxische stoffen - dioxins - animal products - cows - sheep - contamination - toxic substances
    De problemen met dioxinen en dibenzofuranen in koeien en schapen in de omgeving van de Afvalverwerking Rijnmond (Lickebaert gebied 1985-1990) en de contaminatie van citruspulp (1998-1999) hebben aanleiding gegeven tot een aantal proeven. In deze notitie worden de belangrijkste gegevens van deze proeven samengevat. Doel van dit overzicht is om de huidige kennis en kennishiaten met betrekking tot risico's van overdracht van dioxine-achtige verbindingen naar het dierlijk product melk (en vlees) in kaart te brengen
    Steeds minder dioxinen, furanen en dioxineachtige PCB's in de voeding
    Boon, P.E. ; Klaveren, J.D. van; Bakker, M. ; Baumann, B. ; Hoogerbrugge, R. - \ 2003
    Voeding Nu 5 (2003)9. - ISSN 1389-7608 - p. 17 - 19.
    vissen - dioxinen - heterocyclische zuurstofverbindingen - herbicidenverontreinigingen - polychloorbifenylen - gechloreerde koolwaterstoffen - voedselveiligheid - voedselconsumptie - blootstelling - nederland - europa - fishes - dioxins - heterocyclic oxygen compounds - herbicide impurities - polychlorinated biphenyls - chlorinated hydrocarbons - food safety - food consumption - exposure - netherlands - europe
    Ondanks de steeds verder dalende dioxine- en PCB-gehalten in voedingsmiddelen verdienen deze stoffen ook in de toekomst blijvende aandacht. Dit geldt zeker voor PCB-gehalten in vis
    Voeding en gezondheid - toxische stoffen in de voeding
    Rietjens, I.M.C.M. ; Alink, G.M. - \ 2003
    Nederlands Tijdschrift voor Geneeskunde 147 (2003)48. - ISSN 0028-2162 - p. 2365 - 2370.
    voeding - toxinen - voedselbesmetting - verontreiniging - zware metalen - dioxinen - polychloorbifenylen - aromatische koolwaterstoffen - polycyclische koolwaterstoffen - aminen - acrylamiden - nutrition - toxins - food contamination - pollution - heavy metals - dioxins - polychlorinated biphenyls - aromatic hydrocarbons - polycyclic hydrocarbons - amines - acrylamides
    With respect to food, the most important factors causing adverse health effects are: an unbalanced diet, overconsumption of alcohol or fat, the presence of microbial contamination and the presence of natural toxines. Two additional factors, the presence of environmental contaminants and products formed on heating food, may also be of importance. It is generally assumed that, when combined, food-related factors contribute to around 35% of overall cancer incidence
    Effecten van hormoonverstorende stoffen op kikkers
    Lee-de Groot, M.B.E. ; Brink, N.W. van den; Hout, A. van der; Bie, P.A.F. de; Stumpel, A.H.P. ; Bosveld, A.T.C. - \ 2003
    Wageningen : Alterra (Alterra-rapport ) - 77
    amphibia - estradiol - dioxinen - toxicologie - voortplantingsorganen - mortaliteit - hormonen - biotesten - ecotoxicologie - hormoonverstoorders - amphibia - estradiol - dioxins - toxicology - reproductive organs - mortality - hormones - bioassays - ecotoxicology - endocrine disruptors
    Omdat de ontwikkeling van amfibieën sterk hormoon-gereguleerd is, is onderzocht in hoeverre de kikker een geschikte indicator is voor hormoonverstorende stoffen in het milieu. Hiertoe zijn in het laboratorium blootstellingstudies uitgevoerd met kikkerlarven en volwassen Rana kikkers, welke algemeen in Nederland voorkomen. Onderzocht is in hoeverre oestradiol (E2) en tetrachloordibenzo-p-dioxine (TCDD) de ontwikkeling, overleving, lichaams- en orgaangewichten, geslachtsorganen en -hormonen, en specifieke cytochroom P450 enzymen beïnvloeden. Ook is de onderlinge samenhang van deze ettectparameters bestudeerd. In een in-situ veldstudie zijn de overleving en ontwikkeling van larven van Rana Kikkers, die zijn uitgezet in de sterk verontreinigde Volgermeerpolder en een niet-verontreinigde referentielocatie, beschouwd. Naast dit alles zijn juveniele Rana kikkers gevangen uit beide locaties, waarin interne concentraties dioxine-achtige stoffen en activiteiten van specifieke cytochroom P450 enzymen zijn bepaald.
    Validatie en toepassing van de CALUX-bioassay voor diervoeders
    Traag, W.A. ; Hoogenboom, L.A.P. - \ 2001
    Wageningen : RIKILT (Rapport / Rijks-Kwaliteitsinstituut voor land- en tuinbouwprodukten RIKILT 2001.004) - 12
    biotesten - dioxinen - voer - citruspulp - screenen - bioassays - dioxins - feeds - citrus pulp - screening
    Dioxins and dioxin-like PCBs in foodstuffs : occurrence and dietary intake in the Netherlands at the end of the 20th century
    Freijer, J.I. - \ 2001
    Bilthoven etc. : RIVM [etc.] (RIVM report 639102022)
    dioxinen - polychloorbifenylen - voedingsmiddelen - voedselproducten - landbouwproducten - voedselconsumptie - voedselopname - nederland - dioxins - polychlorinated biphenyls - foods - food products - agricultural products - food consumption - food intake - netherlands
    Information on the occurrence of dioxins and dioxin-like PCBs in foodstuffs in the Netherlands. The data collected during measurement programmes on occurrence were combined with food consumption data to assess the dietary intake of dioxins and dioxin-like PCBs in the general population.
    Validatie van biomarkers voor de bepaling van effecten van doorvergiftiging in terrestrische fauna : effecten van TCDD en PAK in de huisspitsmuis (Crocidura russula)
    Bosveld, A.T.C. ; Bie, P.A.F. de - \ 2001
    Wageningen : Alterra (Alterra-rapport 154) - 75
    crocidura russula - benzopyreen - aromatische koolwaterstoffen - toxische stoffen - dioxinen - toxicologie - verontreiniging - biochemische merkers - biologische indicatoren - ecotoxicologie - crocidura russula - benzopyrene - aromatic hydrocarbons - toxic substances - dioxins - toxicology - pollution - biochemical markers - biological indicators - ecotoxicology
    Om eventuele effecten van PAK's bij kleine zoogdieren uit de wilde fauna te kunnen herkennen is in een viertal blootstellingstudies onderzocht wat de effecten zijn van benzo[a]pyreen (BaP) of een mengsel van negen verschillende polycyclische aromatische koolwaterstoffen (PAK). Daarnaast is het effect onderzocht van tetrachloordibenzo-p-dioxine (TCDD), als modelstof voor de veroorzakers van Ah receptor gemedieerde effecten. Het onderzoek is verricht aan de huisspitsmuis (Crocidura russula), een algemeen in het wild voorkomend klein zoogdier. In de verschillende studies zijn het verloop van het lichaamsgewicht en verschillen in orgaangewichten beschouwd naast de effecten op cytochroom P450 enzymen (EROD, MROD, PROD, BROD en specifieke testosteronhydroxylases) en de histopathologie van de geslachtsorganen.
    Scenario studies on maximum levels for dioxins, dibenzofurans and dioxin-like PCBs in fish
    Hoogenboom, L.A.P. ; Klaveren, J.D. van; Baars, A.L. ; Leeuwen, F.X.R. van; Hoogerbrugge, R. ; Leeuwen, S.P.J. van; Boer, J. de - \ 2001
    Unknown Publisher - 29
    dioxinen - polychloorbifenylen - besmetters - voedselbesmetting - vis - visproducten - voeding en gezondheid - voedselveiligheid - dioxins - polychlorinated biphenyls - contaminants - food contamination - fish - fish products - nutrition and health - food safety
    Dioxins, dibenzofurans and dioxin-like polychlorinated biphenyls (together called 'dioxins') are persistent environmental contaminants with a comparable chemical structure and similar toxicological characteristics. Since fish is one of the food items containing variable and sometimes high amounts of dioxins, the authorities asked RIVM, RIKILT and RIVO to investigate the possibility of setting maximum levels for dioxins in fish in order to protect fish consumers from high intake of these contaminants. To this, scenario studies were performed estimating the effect of several hypothetical maximum levels for dioxins in fish on the intake of these compounds by fish consumers and the percentage of various fish species that can be expected not to comply with these maximum levels. The studies show that in general the intake reduction will be limited to about 2-8%, while the percentage of non-compliance varies between 0.1 and 10. The available datasets on which these estimations had to be based are very limited. Moreover, the regular consumption of fish has positive health effects too due to the amounts of -3 unsaturated fatty acids.
    Verontreinigingen in visserijproducten consequenties van nationale en europese normstelling
    Boer, J. de - \ 2001
    Aquacultuur 16 (2001)2. - ISSN 1382-2764 - p. 23 - 26.
    vis - visproducten - visconsumptie - voedselveiligheid - wetgeving - voedingsmiddelenwetgeving - voedselinspectie - normen - kwaliteitsnormen - verontreiniging - verontreinigende stoffen - toxische stoffen - polychloorbifenylen - dioxinen - palingen - voedselbesmetting - Nederland - fish - fish products - fish consumption - food safety - legislation - food legislation - food inspection - standards - quality standards - pollution - pollutants - toxic substances - polychlorinated biphenyls - dioxins - eels - food contamination - Netherlands
    Vissen vormen vaak een vergaarbak van allerlei verontreinigingen in het milieu. Uitleg over de belangrijkste groepen verontreiniging, de normstelling voor visserijproducten m.b.t. deze stoffen (WHO-richtwaarden voor de aanvaardbare dagelijkse inname; Warenwet), en resultaten van onderzoek van het RIVO naar gehalten aan PCBs en dioxine in visserijproducten, met name paling van diverse locaties. Een te verwachten verdere verscherping van de normen zal vermoedelijk consequenties hebben voor de aalvisseij op de grote rivieren; het gebruik van sterk met dioxine verontreinigde visolie en vismeel bij het kweken van vis zou zoveel mogelijk beperkt moeten worden
    ANI - voedselfrequentievragenlijst 97/98 : 1. blootstelling aan dioxinen via de voeding : 2. rapportage consumptiegegevens
    Dooren-Flipsen, M.M.H. van; Donkersgoed, G. van; Klaveren, J.D. van - \ 1999
    Wageningen : RIKILT-DLO (Rapport / RIKILT-DLO 99.004) - 148
    voedselconsumptie - dioxinen - voedselsamenstelling - consumptiepatronen - consumenteninformatie - consumenten - nederland - food consumption - dioxins - food composition - consumption patterns - consumer information - consumers - netherlands
    Dioxinetest RIKILT heeft zijn waarde bewezen
    Mengelers, M.J.B. ; Hoogenboom, L.A.P. ; Traag, W.A. - \ 1999
    Voedingsmiddelentechnologie 4 (1999)23. - ISSN 0042-7934 - p. 13 - 16.
    dioxinen - heterocyclische zuurstofverbindingen - analytische methoden - testen - controle - kwalitatieve analyse - toxische stoffen - chemische samenstelling - chemische eigenschappen - voedselbesmetting - voedingsmiddelen - voedselindustrie - voedseltechnologie - analytische scheikunde - dioxins - heterocyclic oxygen compounds - analytical methods - testing - control - qualitative analysis - toxic substances - chemical composition - chemical properties - food contamination - foods - food industry - food technology - analytical chemistry
    Sinds 1992 werkt het Rikilt in samenwerking met de Wageningen Universiteit aan een biologische methode voor het screenen van agrarische producten op dioxinen en dioxineachtige PCB's. De methode is gevalideerd voor het aantonen van dioxinen in melk en in citruspulp uit Brazilie
    Vergelijking extractiemethoden voor de bepaling van bestrijdingsmiddelen, polychloorbiphenylen en polygechloreerde dibenzo-p-dioxinen, dibenzofuranen in grond
    Zuidema, T. ; Traag, W.A. - \ 1998
    Wageningen : RIKILT-DLO (Rapport / RIKILT-DLO 98.001) - 17
    pesticiden - grondanalyse - polychloorbifenylen - polychloordibenzofuranen - dioxinen - bodemverontreiniging - pesticides - soil analysis - polychlorinated biphenyls - polychlorinated dibenzofurans - dioxins - soil pollution
    Biodegradatie van micro-verontreinigingen met behulp van schimmeltechnologie: PCB's, HCH, DDT en dioxinen
    Traag, W.A. ; Zuidema, T. ; Camp, H.J.M. Op den; Pol, A. ; Griensven, L.J.L.D. Van - \ 1998
    Wageningen : RIKILT-DLO (Rapport / DLO-Rijks-Kwaliteitsinstituut voor Land- en Tuinbouwprodukten 98.017) - 2
    bioremediëring - biodegradatie - polychloorbifenylen - hch - ddt - dioxinen - paddestoelen - bodemverontreiniging - bioremediation - biodegradation - polychlorinated biphenyls - hch - ddt - dioxins - mushrooms - soil pollution
    Literatuurstudie naar methoden voor de bepaling van bestrijdingsmiddelen, polychloorbifenylen en polygechloreerde dibenzo-p-dioxinen, dibenzofuranen in grond
    Traag, W.A. ; Zuidema, T. - \ 1997
    Wageningen : RIKILT-DLO (Rapport / DLO-Rijks-Kwaliteitsinstituut voor Land- en Tuinbouwprodukten 97.25) - 17
    polychloorbifenylen - dioxinen - polychloordibenzofuranen - gaschromatografie - nederland - literatuuroverzichten - bodemverontreiniging - polychlorinated biphenyls - dioxins - polychlorinated dibenzofurans - gas chromatography - netherlands - literature reviews - soil pollution
    Human dietary intake of dioxins and planar PCBs in The Netherlands - average, population groups and time trends
    Dooren-Flipsen, M.M.H. van; Klaveren, J.D. van; Liem, A.K.D. - \ 1997
    Wageningen : RIKILT-DLO (Report / DLO-State Institute for Quality Control of Agricultural Products (RIKILT-DLO) 97.36) - 35
    voedselhygiëne - consumptiepatronen - dioxinen - polychloorbifenylen - nederland - food hygiene - consumption patterns - dioxins - polychlorinated biphenyls - netherlands
    De bodemgesteldheid van het saneringsgebied Lickebaert : resultaten van een bodemgeografisch onderzoek
    Scholten, A. ; Brouwer, F. - \ 1995
    Wageningen : DLO-Staring Centrum (Rapport / DLO-Staring Centrum 162) - 68
    bodemkarteringen - kaarten - dioxinen - bodemverontreiniging - nederland - zuid-holland - bodemsanering - soil surveys - maps - dioxins - soil pollution - netherlands - zuid-holland - soil remediation
    Thyroid hormone binding proteins as novel targets for hydroxylated polyhalogenated aromatic hydrocarbons (PHAHs) : possible implications for toxicity
    Lans, M.C. - \ 1995
    Agricultural University. Promotor(en): J.H. Koeman; A. Brouwer. - S.l. : Lans - ISBN 9789054854302 - 152
    polychloorbifenylen - dioxinen - pentachloorfenol - organische halogeenverbindingen - gehalogeneerde koolwaterstoffen - schildklierhormonen - polychlorinated biphenyls - dioxins - pentachlorophenol - organic halogen compounds - halogenated hydrocarbons - thyroid hormones

    Some toxic effects caused by polyhalogenated aromatic hydrocarbons (PHAHs) develop through alterations in the reproductive and thyroid hormone regulatory systems, thereby affecting (brain) development, reproduction and behaviour of several species (Stone, 1995, Birnbaum, 1994, for review: Brouwer et al. , 1995, Peterson et al. , 1993). In this thesis we have focused on the effects of different classes of PHAHs, eg. polychlorinated biphenyls (PCBs), dibenzofurans (PCDFs) and dibenzo- p -dioxins (PCDDs) and their hydroxylated metabolites on thyroid hormone homeostasis. These changes seem to be partly caused by Ah-receptor mediated changes in thyroid hormone glucuronidation, and effects on the thyroid gland affecting hormone production and secretion. However, hydroxylated metabolites of PCBs, PCDFs and PCDDs may have an additional effect on thyroid hormone transport. Previous studies (Brouwer, 1987) have shown that exposure to 3,3',4,4'- tetrachlorobiphenyl (TCB) can disturb the plasma transport of thyroxine (T 4 ) and retinol in rats through specific competition of a hydroxylated metabolite, 4-OH-3,3',4',5-tetraCB, with T 4 for the thyroid hormone binding site of transthyretin (TTR), the major thyroid hormone transport protein in rodents. This observation raised the question if structurally related hydroxylated PHAH- metabolites could interact with TTR in the same way, as well as with other thyroxine binding proteins, like thyroxine binding globulin (TBG) and type-1-deiodinase (ID-1), subsequently disturbing thyroid hormone transport and metabolism. Special attention was also paid on the structure-activity relationships of hydroxylated PHAH metabolites for binding to TTR by using in vitro and in vivo studies and X-ray crystallographic structure analysis,

    In vitro studies on interactions of hydroxylated PHAH metabolites with thyroxine binding proteins

    In in vitro studies the interactions of several hydroxylated PHAH metabolites with 3 different T 4 binding proteins, eg. TTR, thyroxine binding globulin (TBG) and type-1-deiodinase (ID-1), were investigated (Chapter 2, 3 and 4). The inhibition of T 4 binding to TTR by hydroxylated PHAH metabolites was studied using in vitro T 4 -TTR bindingstudies. These studies revealed the structural requirements for competition of T 4 binding to TTR by hydroxylated PHAH metabolites: para- or meta-hydroxylation on one or both phenylrings, with one or more adjacent chlorine substitutions (Chapter 2). PHAH metabolites with these structural characteristics showed a remarkable resemblance to T 4 the natural ligand for TTR, consequently displacing T 4 from the T 4 binding site of TTR. Both non-planar, ortho-chlorinated hydroxylated PCB metabolites and rigid, planar hydroxylated PCDF or PCDD metabolites could inhibit T 4 -TTR binding. However, the ortho-hydroxylated PHAH metabolites and parent PHAH compounds, like TCDD, 2,3,3',4,4'-pentaCB and 3,3',4,4'-tetraCB could not inhibit T 4 -TTR binding in vitro.

    In subsequent in vitro studies, a wide range of hydroxylated PHAH metabolites did not inhibit T 4 binding to TBG, the major plasma thyroid hormone transport protein in man (Chapter 3). This indicates that ligand interactions with TTR or TBG are clearly different. Additional studies with iodothyronine derivatives, showed that tri-iodophenol and to a lesser extent di-iodotyrosine could inhibit T 4 -TTR binding but not T 4 -TBG binding in vitro. Finally, the enzymatic activity of hepatic ID-1, which plays a role in the (in)activation of thyroid hormones, could be competitively inhibited mainly by di-para-hydroxylated, meta-halogenated PHAH metabolites while mono-hydroxylated PHAH metabolites were 10 to 100 times less potent (Chapter 4). The differences between the structural requirements of hydroxylated PHAH metabolites for interactions with TTR, TBG and ID-1, are in line with previous studies in which related hydroxylated PHAH compounds or iodothyronine derivatives were used. In conclusion, specific hydroxylated PHAH metabolites can disturb T4-TTR interactions, or inhibit ID-1 activity in vitro, indicating that hydroxylated PHAH metabolites may play an additional role in the observed disturbances in thyroid hormone transport and metabolism after PHAH exposure in vivo .

    In vivo studies on effects of Aroclor 1254 and TCDD on thyroid hormone transport and metabolism

    Two in vivo experiments were carried out to study role that both disturbances in plasma T 4 transport and hepatic T 4 metabolism caused by hydroxylated PHAH metabolites play in the observed decreases in plasma T 4 levels. Rats were exposed to Aroclor 1254, a commercial mixture containing persistent and metabolisable PCB congeners (Chapter 5) or the persistent 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) (Chapter 6).

    In adult Wistar rats, that were exposed to a high dose of Aroclor 1254, plasma T 4 levels were decreased on day 3 and day 8 (Chapter 5). In addition, high levels of a single hydroxylated PCB metabolite, eg. 4-OH-2,3,3',4',5-pentaCB, were detected in plasma of the rats on day 8, while lower concentrations of this metabolite were present in the blood on day 3. However, the T 4 binding capacity in plasma was decreased only in the high dosed group on day 8 but not on day 3, indicating a threshold level for the hydroxylated PCB metabolite to disturb T 4 -TTR binding. On both day 3 and 8, hepatic cytochrome P450 1A1 levels and activity were induced, which is essential for the formation of hydroxylated metabolites. Hepatic T 4 glucuronidation was induced simultaneously. The decreased plasma T 4 levels found in all exposure groups could therefore be attributed to both disturbed plasma T 4 transport and/or induced T 4 glucuronidation. No significant changes in plasma T 3 levels were found following Aroclor 1254 treatment. In addition, hepatic ID-1 activity was not decreased, suggesting that the in vitro inhibition by hydroxylated PCB metabolites does not occur in vivo. However in an earlier study Adams et al. (1990), in vivo exposure to the easily metabolisable 3,3',4,4'-tetraCB or persistent TCDD could inhibit ID-1 activity. The levels of PCB metabolites with the required structure for inhibition of hepatic ID-1 activity were possibly too low (Chapter 4) liver after Aroclor 1254 exposure in vivo.

    Another remarkable finding was the selective retention of a single specific hydroxylated PCB metabolite, 4-OH-2,3,3',4',5-pentaCB, in plasma of rats exposed to a complex mixture of PCB congeners (Fig. 1). This was the result of the presence of PCB-congeners that strongly induce cytochrome P4501AI activity and PCB-congeners that could easily form hydroxylated PCB metabolites in the Aroclor 1254 mixture, and the strict selectivity of the TTR present in plasma retaining only hydroxylated PCB metabolites that meet the structural requirements as described in Chapter 2. Surprisingly the 4-OH- 2,3,3',4',5-pentaCB metabolite which was formed and selectively retained in plasma, has a hydroxy group on the highest chlorinated ring, in contrast to the expected formation of mainly metabolites with a para - or meta -hydroxy group on the least chlorinated ring. However, the inhibition potencies of T 4 -TTR binding for the 4-OH-2,3,3',4',5-pentaCB metabolite (Chapter 5) and the structurally related 4'-OH-2,3,3',4,5'-pentaCB metabolite (Chapter 2) were almost similar. There is no clear indication yet on the mechanism of selective retention of the 4-OH-2,3,3',4',5-pentaCB in rat plasma, although pharmacokinetics and tissue levels of the presumed parent compounds 2,3,3',4,4'- pentaCB (CB 105) or 2,3',4,4',5-pentaCB (CB 118) may play a role.

    No detectable levels of hydroxylated metabolites were found by GC-MS analysis of plasma extracts of rats at both day 3 and 8 following exposure to the persistent TCDD, although cytochrome P4501A1 levels and activity were markedly induced (Chapter 6). In addition no unequivocal decrease in T 4 -TTR binding in plasma of TCDD-exposed rats was observed. However, hepatic thyroid hormone metabolism was clearly altered: T 4 glucuronidation and brain type-2-deiodinase (ID-2) activity were increased and hepatic ID-1 activity was decreased, which may explain the observed plasma T4 reductions in the TCDD exposed rats. These changes in thyroid hormone homeostasis suggest a hypothyroxinemic state of the TCDD-exposed rats, although no decreased plasma T4 levels were found. The decrease in ID-1 activity after TCDD exposure was not likely to be caused by hydroxylated metabolites, as was described in Chapter 4, but may be caused by direct effects of TCDD on ID-1 activity or by the assumed hypothyroid state of the TCDD exposed rats.

    While Aroclor 1254 exposure disturbed T4 plasma transport and increase T 4 glucuronidation (Chapter 5), TCDD exposure only enhanced the hepatic elimination of T4 (Chapter 6), leading to decreased plasma T 4 levels. Although the in vivo studies described in this thesis indicate two different mechanisms for decreases in plasma T 4 levels after PHAH exposure, we can not exclude a third possible mechanism since several studies described changes on thyroid gland histology and thyroid hormone secretion after exposure to Aroclor 1254, TCDD and related compounds.

    Structural basis for interactions of hydroxy-PCB metabolites with TTR

    The selective retention of a specific hydroxylated PCB metabolite in vivo (Chapter 5), inspired us to look into the interactions of hydroxylated PCB metabolites with TTR in more detail, and to try to find a structural basis for the structural requirements for TTR binding as described in Chapter 2. X-ray crystallographic analysis of a complex of TTR with a hydroxylated PCB metabolite, eg. 4,4'- (OH) 2 -3,3',5,5'-tetraCB, refined to a 2.7 A resolution, revealed a hydrogen bond formation between a para-hydroxy group of the metabolite with the paired Serine 117 amino acid residues, present in the centre of the TTR binding channel (Chapter 7). The location of this hydroxylated PCB metabolite, deep in the binding channel, and the hydrogen bond formation could explain the stronger TTR binding affinity of this metabolite than the natural ligand T 4 . The chlorine atoms present on the meta-positions of the 4,4'-(OH) 2 -3,3',5,5'-tetraCB, metabolite, fitted easily in the T 4 -iodine binding pockets present in the TTR binding channel. Additional computer-assisted graphics modelling studies on the interactions of several hydroxylated PCB metabolites with TTR, showed that hydroxy groups present on meta-positions could also form hydrogen bonds with the paired Serine 117 residues in the centre of the binding channel (Chapter 7). Furthermore, the modelling studies showed no significant differences between the interactions of hydroxylated PCB metabolites and the structurally related pentachlorophenol (PCP) with TTR, although in vivo studies by others indicated the disruption of the complex of retinol binding protein (RBP) and TTR after binding of a hydroxylated PCB metabolite but not by PCP in rodents. In conclusion, the detailed structural studies described in Chapter 7 confirmed the necessity of para- or meta- hydroxylation and adjacent chlorine substituents as structural elements of hydroxylated metabolites of PCBs and related compounds for interactions with TTR (Chapter 2), leading to selective retention of a specific hydroxylated PCB metabolite in plasma of rats exposed to a complex PCB mixture in vivo (Chapter 5).

    Concluding remarks

    The outcome of the present study clearly reveals the structural requirements that are essential for interactions of PHAH metabolites and other related chemicals for interactions with TTR. Hydroxylated PHAH metabolites can structurally resemble the thyroid hormone T 4 Overall the structural requirements for TTR interaction were hydroxysubstitution on the para - or meta positions of one or both of the phenyl rings, with adjacent chlorine substitutions, herewith confirming some of the suggestions for TTR interactions of related hydroxylated PHAH metabolites by Rickenbacher et al . (1986). Especially the observation by X-ray crystallographic structure analysis that a hydrogen bond could be formed in the TTR binding channel upon binding of a hydroxylated PCB metabolite, provides strong evidence that para - or meta -hydroxylation of the PHAH compound forms an essential prerequisite for binding to the T4 binding site of TTR. No interactions with TTR were found for the tested parent PHAH compounds, contradictory to earlier suggestions of McKinney et al. (1985) which were based mainly on computer modelling and few in vitro binding studies (Rickenbacher et al , 1986). It should be noted that graphics modelling may show that parent PHAH compounds may fit the TTR binding site, but gives little information on binding affinity to TTR. In an affirmative in vitro T 4 -TTR binding assay, several parent PCB congeners (3,3',4,4'-tetraCB, 3,3',4,4',5-pentaCB, 3,3',4,4',5,5'-hexaCB, 2,3,3',4,4'-pentaCB, 2,2',5,5'- tetraCB), TCDD and Aroclor 1254, a commercial PCB mixture, were tested at high concentrations and exhibited no inhibition of T 4 -TTR binding (unpublished data).

    Fig. 1.

    PHAH metabolites that are predicted to have high binding affinities for TTR are indeed detected in plasma of rodents experimentally exposed to PCBs or PCDFs (Morse et al ., 1995b, Koga et al ., 1990, Kuroki et al. , 1993). For instance, exposure to a complex mixture of PCBs, Aroclor 1254, led to the selective retention in blood of a single PCB metabolite, 4-OH-2,3,3',4',5- pentaCB, which met the structural requirements for TTR binding (Bergman et al ., 1994).

    On the basis of the proposed structural requirements we can give an explanation for the interactions of related compounds with TTR as found by others, for instance pentachlorophenol (Van den Berg, 1990, Van Raay et al ., 1994, Den Besten et al ., 1991), natural compounds like flavones and halogenated aurones (Cody, 1989; Ciszak et al ., 1992) and certain drugs like milrinone (Wojtczak et al. , 1993). Moreover, these structural insights make it possible to predict whether other related classes of environmental contaminants can interact with TTR. In addition, due to combined exposure in the environment, one may expect additivity of binding to TTR of hydroxylated PHAH metabolites with other structurally related environmental or natural compounds.

    An important question is whether these experimental data can be extrapolated to other species. Two factors are essential for the TTR mediated selective retention of hydroxylated PHAH metabolites namely the presence of TTR in blood and the formation of relevant PHAH metabolites. It is most likely that hydroxylated. metabolites can be formed in many species other than rodent. Recently hydroxylated PCB metabolites were identified in human and seal plasma, which were environmentally exposed to background PCB levels (Bergman et al. , 1994). The major metabolites were again the 4-OH-2,3,3',4',5-pentaCB metabolite and to a lesser extent 4-OH-2',3,3',4',5-pentaCB in seal and human plasma and 4-OH-2,2',3,4',5,5',6-heptaCB in human plasma. Thus the hydroxylated PCB metabolites detected in vivo completely matched the structural requirements for TTR binding. The PHAH metabolite patterns in plasma of both experimentally and environmentally exposed animals and humans are species specific and depend not only on the structural requirements for binding to TTR, but also on the exposure situation and the capacity of biotransformation of PHAHs of the species.

    The species-specific metabolism of PHAHs decreases in the order: terrestrial mammals>aquatic mammals>birds>fish (Safe, 1989). Several mammalian and avian species, like rats, seals, porpoises and eiderducks could form hydroxylated metabolites in in vitro microsomal incubations with the model substrate 3,3',4,4'-tetraCB (TCB). However fish, like trout and flounder, could not metabolise TCB, although cytochrome P4501A-like activity, responsible for biotransformation of planar PHAHs, can be induced (Murk et al., 1994, Morse et al., 1995c, Ishida et al., 1991).

    The selective retention of specific hydroxylated PHAH metabolites in plasma through binding to TTR is expected in species that both can metabolise PHAHs and posses TTR as a plasma thyroid hormone binding protein. TTR is a evolutionary conservative protein present in plasma of not only rodents but also other placental mammals, birds and to a lesser extent in reptiles. No TTR was detected in the lower species like fish and amphibians. In higher mammals like man, however, not only TTR but also thyroxine binding globulin (TBG), is present in blood as a primary thyroid hormone transport protein. In conclusion, hydroxylated PHAH metabolites can be formed and selectively retained by TTR in blood of a wide variety of species.

    The toxicological consequences of the TTR mediated selective retention of hydroxylated PHAH metabolites in plasma are not yet fully understood. The TTR protein plays a primary role in the transport of thyroid hormones in the blood of many species. Although TTR binds less T 4 than TBG in human serum, TTR may be responsible for much of the immediate delivery of T 4 and T 3 to cells due to the lower binding T 4 affinity. Furthermore TTR is important for the transport of retinol in blood by forming a complex with retinol-binding protein (Robbins, 1991).

    Disturbances in thyroid hormone plasma levels are found in several species experimentally or environmentally exposed to PHAHs, like rodents, seal (Brouwer et al., 1989) and man (Koopman Esseboom et al., 1994), species in which hydroxylated PCB metabolites were also present in plasma. Disruption of thyroid hormone homeostasis after exposure to PHAHs can however be caused by at least two mechanisms, eg. the disturbed plasma T 4 transport through competitive binding of hydroxylated PHAH metabolites to TTR, but also the Ah-receptor mediated induction of T 4 glucuronidation by parent compounds.

    The possible disruption of the TTR-RBP complex upon binding of a hydroxylated PHAH metabolite can also markedly decrease plasma retinol levels in rodents (Brouwer, 1987). It was suggested that seals exposed to PHAHs in the environment, have an impaired function of the immune system (de Swart, 1995), possibly resulting from disturbed retinoid levels (Brouwer, 1991, Brouwer et al. 1989). Hydroxylated PHAH metabolites may attribute to these effects on thyroid hormone and retinoid homeostasis through interactions with TTR in plasma. It is not known whether similar effects occur in man.

    TTR is the major thyroid hormone binding protein in cerebro-spinal fluid (CSF), suggesting a role in distribution of thyroid hormones in the central nervous system. This TTR is produced in the choroid plexus and is present in high concentrations in CSF of rats and humans, even at a very early stage in development. Moreover, in all species where TTR is present in blood, TTR has also been detected in brain. Because TTR is an important carrier for T 4 to target tissues, for instance brain, one may expect that it may also act as a facilitated transport system for hydroxylated PHAH metabolites. This is in accordance with observations of a strong accumulation of hydroxylated PCB metabolites of maternal origin in the plasma and brain of late gestational fetuses from pregnant rats or mice exposed to PCBs (Morse et al., 1995b,d, Darnerud et al., 1995). In rat fetuses perinatally exposed to Aroclor 1254 the selective accumulation of the 4-OH-2,3,3',4',5-pentaCB metabolite in maternal plasma and fetal plasma and brain led to decreases in brain T 4 levels, while brain T 3 levels were only lightly changed. In addition plasma and hepatic retinoid concentrations were decreased in fetal and neonatal offspring (Morse et al., 1995a). The hydroxylated metabolites accumulated to high levels in fetal rat brain and may themselves attributeto observed neurochemical changes (Morse, 1995).

    Hydroxylated PHAH metabolites have been shown to possess biological activity in vitro (Brouwer, 1994). Hydroxylated PCB metabolites can interfere with mitochondrial structure and function in vivo and in vitro (Lans et al., 1990, Narashimhan et al., 1991). Moreover, they can bind to the Ah-receptor and weakly induce EROD activity. In addition, an in vitro marker of tumor promoting potential, the gap-junctional intercellular communication, could be weakly inhibited. Hydroxylated PCB metabolites can also exert (anti)-estrogenic activities in vivo (Bergeron et al., 1994) and in vitro (Kramer et al., 1994). No clear structure activity relationships for (anti)- estrogenicity could be found for the tested hydroxylated PCB metabolites. However, the hydroxylated PCB metabolites selectively retained in fetal plasma and brain (Morse et al., 1995d) do have a weak (anti)-estrogenic activity. The intrinsic capacity to disrupt endocrine systems, eg. thyroid and estrogen status, and the relatively large accumulating levels of hydroxylated PCB metabolites in late gestational rat fetuses, suggests there is a potential risk for adverse developmental effects by these hydroxylated PHAHs. This possible hydroxy PCBmediated route of developmental toxicity should be investigated in a sound in vivo experimental setup.

    Subtle changes in plasma thyroid hormone levels and parameters for neurological development were described in children exposed to background levels of PHAHs in utero and through lactation (Koopman-Esseboom et al., 1994, Sauer et al., 1994, Pluim et al., 1993). Hydroxylated PHAH metabolites did not interact with TBG, the major T 4 binding protein in human plasma (Lans et al., 1994). However, the hydroxylated PCB metabolites which are recently detected in human plasma (Bergman et al., 1994) are mainly bound to TTR, as was found after selective purification of TTR from human plasma (unpublished results). Therefore TTR-mediated accumulation of hydroxylated PCB metabolites or related compounds in fetal plasma and brain and subsequent decreases in T 4 levels, as found in late gestational rat fetuses, may be of concern for fetal growth and (brain) development in a wide variety of species, including man.

    Onderzoek naar polygechloreerde dibenzo-p-dioxinen, dibenzofuranen en planaire gechloreerde bifenylen in Nederlandse melk
    Traag, W.A. ; Rhijn, J.A. van; Spreng, P.F. van de; Roos, A.H. ; Tuinstra, L.G.M.T. - \ 1993
    Wageningen : DLO-Rijks-Kwaliteitsinstituut voor Land- en Tuinbouwprodukten (Rapport / RIKILT-DLO 93.14) - 13
    melk testen - dioxinen - polychloorbifenylen - polychloordibenzofuranen - nederland - milk testing - dioxins - polychlorinated biphenyls - polychlorinated dibenzofurans - netherlands
    Bereiding van dioxinehoudende extracten ten behoeve van de Werkgroep Dioxine Emissies
    Rhijn, J.A. van - \ 1993
    Wageningen : DLO-Rijks-Kwaliteitsinstituut voor Land- en Tuinbouwprodukten (Rapport / RIKILT-DLO 93.05) - 7
    dioxinen - referentienormen - luchtverontreiniging - dioxins - reference standards - air pollution
    Preparation, homogeneity and stability of milkpowders containing polychlorodibenzo-P-dioxins and polychlorodibenzofuranes
    Roos, A.H. ; Tuinstra, L.G.M.Th. - \ 1992
    Wageningen : DLO-State lnstitute tor Quality Control of Agricultural Products (Report / RIKILT-DLO 92.02) - 15
    melkpoeder - dioxinen - polychloordibenzofuranen - referentienormen - dried milk - dioxins - polychlorinated dibenzofurans - reference standards
    Voor het Community Bureau of Raferenee (BCA) werden een "natuurlijk" gecontamineerd, een laag en een medium niveau gecontamineerd melkpoeder bereid. Van eenzelfde batch boterolie werden drie aparte batches bereid. Aan twee batches werd een verschillende hoeveelheid dioxine toegevoegd. Uitgaande van ondermelk werden met behulp van de drie batches boterolie drie batches melk bereid. Het dioxinengehalte in de drie batches, bepaald met behulp van internationaal geaccepteerde TEF waarden, bedraagt resp. ca. 3, 9 en 14 pg 1-TEQ/g melkvet. Een deel van elke batch melk werd gevriesdroogd en de rest werd verstoven. De aldus bereide gevriesdroogde melkpoeder werd gecontroleerd op homogeniteit en stabiliteit. Voor de homogeniteit werden het vetgehalte, Kjeldahl-N en PCB gehalte bepaald. De stabiliteit werd gecontroleerd in de gevriesdroogde melkpoeders die gedurende ca. één jaar bij -20°C, +20°C en 37°C waren opgeslagen.
    Het ontwikkelen van een methode voor de simultane bepaling van planaire chloorbiphenylen en polychloor dibenzo-P-dioxinen en furanen in melk
    Traag, W.A. ; Rhijn, J.A. van; Kulik, W. ; Spreng, P. van der; Tuinstra, L.G.M.Th. - \ 1992
    Wageningen : DLO-Rijks-Kwaliteitsinstituut voor Land- en Tuinbouwprodukten (Rapport / RIKILT-DLO 92.30) - 15
    melk testen - polychloorbifenylen - polychloordibenzofuranen - dioxinen - analytische methoden - milk testing - polychlorinated biphenyls - polychlorinated dibenzofurans - dioxins - analytical methods
    Ampullering van extracten van luchtmonsters ten behoeve van de analyse van dioxine
    Rhijn, J.A. van; Vries, P.H.U. de - \ 1992
    Wageningen : DLO-Rijks-Kwaliteitsinstituut voor Land- en Tuinbouwprodukten (Rapport / RIKILT-DLO 92.20) - 8
    dioxinen - luchtverontreiniging - bemonsteren - dioxins - air pollution - sampling
    Fate and effects of the insecticide Dursban 4E in indoor Elodea-dominated and macrophyte-free model ecosystems: 1. Fate and primary effects of the active ingredient chloropyrifos.
    Brock, T.C.M. ; Crum, S.J.H. ; Wijngaarden, R. van; Budde, B.J. ; Tijink, J. ; Zuppelli, A. ; Leeuwangh, P. - \ 1992
    Archives of Environmental Contamination and Toxicology 23 (1992)1. - ISSN 0090-4341 - p. 69 - 84.
    gewasbescherming - pesticiden - nadelige gevolgen - selectiviteit - toxiciteit - onbedoelde effecten - niet-doelorganismen - organo-fosforverbindingen - derivaten - chloride - fenolen - fenol - dioxinen - pentachloorfenol - milieu - verontreinigende stoffen - verontreiniging - plant protection - pesticides - adverse effects - selectivity - toxicity - nontarget effects - nontarget organisms - organophosphorus compounds - derivatives - chloride - phenols - phenol - dioxins - pentachlorophenol - environment - pollutants - pollution
    Uitscheiding van polygechloreerde dibenzo-p-dioxinen en -furanen in melk van koeien, die tijdens de droogstand zijn gevoerd met dioxinen besmet voer
    Roos, A.H. ; Berende, P.L.M. ; Traag, W.A. ; Rhijn, J.A. van; Mengelers, M.J.B. ; tUINSTRA, L.G.M.Th. - \ 1991
    Wageningen : RIKILT (Rapport / RIKILT 91-01) - 23
    rauwe melk - vervalsing - besmetting - polychloorbifenylen - polychloordibenzofuranen - dry lot feeding (voeding) - dioxinen - excretie - raw milk - adulteration - contamination - polychlorinated biphenyls - polychlorinated dibenzofurans - dry lot feeding - dioxins - excretion
    In dit verslag worden de resultaten beschreven van het onderzoek met melkgevende koeien die tot het moment van afkalven gevoerd zijn met dioxine-bevattend voer (tot aan het tijdstip van droogzetten in het Lickebaertgebied en na het droogzetten bij het IVVO te Lelystad). Na afkalven kregen de dieren "schoon" voer verstrekt. Bij aanvang van het experiment en vlak na het afkalven werden melkmonsters en vetbiopten genomen, Ook van de geboren kalveren werden direct na de geboorte o.a. subcutaan- en niervet en lever verzameld om de passage van de dioxinen door de uteruswand na te kunnen gaan. Het behulp van de verkregen resultaten kan in de toekomst aangegeven worden hoe lang na het afkalven gewacht moet worden voordat de melk van met dioxinen besmette dieren weer geconsumeerd kan worden. In dit verslag worden de resultaten van de dioxinenanalyses in de melk gerapporteerd.
    Histologische veranderingen bij koeien en schapen die in de praktijk en experimenteel blootgesteld zijn aan polygechloreerde dibenzo-p-dioxinen en -furanen
    Groot, M.J. ; Berende, P.L.M. ; Ossenkoppele, J.S. ; Tuinstra, L.G.M.Th. - \ 1991
    Wageningen : DLO-Rijks-Kwaliteitsinstituut voor Land- en Tuinbouwprodukten (Rapport / RIKILT-DLO 91.25) - 31
    koeien - dioxinen - polychloordibenzofuranen - microscopie - biopsie - schapen - histologie - cows - dioxins - polychlorinated dibenzofurans - microscopy - biopsy - sheep - histology
    Histologisch onderzoek is verricht op organen van koeien en schapen, welke chronisch en experimenteel bloot hebben gestaan aan dioxinen. Alle dieren waren op het moment van slachten klinisch gezond. Bij de meeste dieren werden histologische afwijkingen waargenomen. De waargenomen veranderingen kunnen niet zonder meer aan dioxinen worden toegeschreven aangezien de bodem van het gebied van herkomst van de dieren vervuild was met andere toxische stoffen (o.a. lood , cadmium, fluor, molybdeen), welke ook een bijdrage aan de waargenomen weefselveranderingen zullen hebben geleverd. Daarnaast betrof het oudere dieren waarvan de ziektegeschiedenis weinig bekend was.
    Het dioxinegehalte in Nederlandse visserijprodukten
    Hagel, P. - \ 1990
    IJmuiden : R.I.V.O. (Rapport / Rijksinstituut voor Visserijonderzoek, Afdeling Milieu-onderzoek MO 90-03) - 6
    dioxinen - visproducten - nederland - toxiciteit - ecotoxicologie - dioxins - fish products - netherlands - toxicity - ecotoxicology
    Onderzoek naar dioxinen en dibenzofuranen in Nederlandse melk en melkprodukten
    Roos, A.H. ; Hutzinger, O. ; Tuinstra, L.G.M.T. ; Huf, F.A. - \ 1989
    Wageningen : RIKILT (Rapport / RIKILT 89.41) - 18
    melk - melkproductie - voedselbesmetting - dioxinen - polychloordibenzofuranen - milk - milk production - food contamination - dioxins - polychlorinated dibenzofurans
    In opdracht van de directie Voedings- en Kwaliteitsaangelegenheden van het Ministerie van Landbouw en Visserij is als aanvulling van gegevens met betrekking tot gehalten van polychloordioxinen (PCDD) en polychloordibenzofuranen (PCDF) in melk in de omgeving van vuilverbrandingsinstallaties aanvullend onderzoek gedaan naar melk en melkprodukten uit onverdachte regio's.
    Schatting van de toxiciteit van enkele polychloordibenzo-p-dioxinen, polychloordibenzofuranen en polychloorbifenylen in Nederlandse paling in relatie tot de overige componenten uit deze groepen verbindingen
    Dorgelo, F.O. ; Roos, A.H. ; Kuiper, H.A. - \ 1988
    Wageningen : RIKILT (Rapport / RIKILT 88.49) - 28
    palingen - nederland - polychloorbifenylen - polychloordibenzofuranen - dioxinen - toxiciteit - risicoschatting - eels - netherlands - polychlorinated biphenyls - polychlorinated dibenzofurans - dioxins - toxicity - risk assessment
    Schatting van de toxiciteit van enkele polychloordibenzo-p-dioxinen, polychloordibenzofuranen en polychloorbifenylen in Nederlandse paling in relatie tot de overige componenten uit deze groepen verbindingen.
    Chemical porphyria in man. The diagnosis and occurrence of chronic hepatic porphyria in man caused by halogenated aromatics : Porphyrinogenic action of halogenated aromatics in experimental animals
    Strik, J.J.T.W.A. ; Koeman, J.H. - \ 1979
    Amsterdam : Elsevier - ISBN 9780444801593 - 236
    ziekten van de vrouwelijke geslachtsorganen - ziekten van de mannelijke geslachtsorganen - urinewegziekten - porfyrie - laboratoriumdieren - polybroombifenylen - polychloorbifenylen - dioxinen - female genital diseases - male genital diseases - urinary tract diseases - porphyria - laboratory animals - polybrominated biphenyls - polychlorinated biphenyls - dioxins
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