Endokrine Modulatoren

Hinweise aus epidemiologischen Studien bedürfen einer kritischen Überprüfung in Modellsystemen
  • M. Hoffmann
  • S. Gebauer
  • M. Nüchter
  • R. Baber
  • J. Ried
  • M. von Bergen
  • W. Kiess
Leitthema

Zusammenfassung

Endokrin disruptive Chemikalien (EDC) verursachen durch Interaktion mit hormonellen Systemen negative gesundheitliche Effekte. Sie werden nach chemischer Struktur, Wirkung auf bestimmte Hormonsysteme, Bioakkumulation, Persistenz in der Umwelt oder klinisch beobachtbarer Auswirkung klassifiziert. Zur Erforschung der komplexen Wirkungsweise im Menschen stehen bislang nur unzureichende In-vitro-Modellsysteme zur Verfügung, die zudem nicht ausreichend hochdurchsatzfähig sind, wodurch sich die Risikoevaluation ausgesprochen schwierig gestaltet. Hinzu kommt, dass in den Industrienationen lebende Menschen meist gegenüber EDC-Substanzgemischen mit unterschiedlichen Wirkungsweisen exponiert sind. Derzeit unklar ist die klinische Bedeutung der durch EDC in vulnerablen Entwicklungsphasen ausgelösten epigenetischen Veränderungen. Epidemiologische Studien werden aufgrund ihrer nicht immer garantierten Reproduzierbarkeit kritisiert, dennoch bleiben sie zur Entwicklung und Prüfung von Hypothesen zur Wirkungsweise von EDC im klinischen Kontext wegen fehlender geeigneter Modellsysteme die Methode der Wahl. Positive Hinweise auf Assoziationen sind trotz zuweilen widersprüchlicher Ergebnisse der entscheidende Schlüssel zur Selektion von Faktoren, die anschließend in Modellsystemen ergebnisoffen überprüft werden können. Dieser Beitrag stellt hauptsächlich die positive epidemiologische Evidenz der durch EDC ausgelösten Effekte in den Bereichen Wachstum und Metabolismus, neurokognitive Entwicklung sowie Sexualentwicklung und Reproduktion dar. Daraus ergibt sich die Notwendigkeit einer engen Verknüpfung von epidemiologischer und mechanistischer Forschung in Modellsystemen, insbesondere auf den Gebieten des Zusammenwirkens verschiedener EDC und der Auswirkungen pränataler und frühkindlicher Exposition.

Schlüsselwörter

Endokrine Disruptoren Epidemiologie Risikobewertung Rezeptorbindung Modellsysteme 

Abkürzungen

BPA

Bisphenol A

DDT

Dichlorodiphenyltrichloroethan

EDC

Endokrin disruptive Chemikalien

IPCS

International Programme on Chemical Safety

OCP

Chlororganische Pestizide

PAE

Phthalsäureester

PAH

Polyaromatische Kohlenwasserstoffe

PBDE

Polybromierte Diphenylester

PCB

Polychlorierte Biphenyle

PFOA

Perfluoroctansäure

PFAS

Polyfluorierte Alkylsubstanzen

PFOS

Perfluoroctansulfonsäure

POP

Persistente organische Schadstoffe

TCDD

Tetrachlorodibenzodioxin

DOHaD

Entwicklungstechnische Ursprünge von Gesundheit und Krankheit

Endocrine disruptors

Evidence from epidemiological studies necessitates a critical review of model systems

Abstract

Endocrine disruptive chemicals (EDCs) cause adverse health effects through interaction with endocrine systems. They are classified by chemical structure, effects on specific endocrine systems, bioaccumulation, persistence in the environment, or clinically observable effects. For research of the complex mechanisms of action in the human body, only in vitro model systems have so far been available, that have insufficient high-throughput capacity, which makes risk evaluation more difficult. In addition, in industrial nations, living people are often exposed to mixtures of substances, with various effects. The clinical importance of epigenetic changes caused by the action of EDCs during vulnerable phases of development is currently unclear. Epidemiological studies are criticized because reproducibility is not always guaranteed. Nevertheless, they remain the method of choice for the development and analysis of suitable model systems. Positive associations, in spite of sometimes conflicting results, are key in the selection of factors that can then be analysed in model systems in an unbiased way. This article depicts the mainly positive epidemiological findings for EDC-caused effects in the fields of growth and metabolism, neurocognitive development and sexual development and reproduction. As a result, there is a need for closer linkage between epidemiological studies and mechanistic research into model systems, especially focusing on the interaction of different EDCs and the consequences of prenatal and early life exposure.

Keywords

Endocrine disruptors Epidemiology Risk assessment Receptor binding Model systems 

Notes

Förderung

Unsere wissenschaftliche Arbeit wird von der Europäischen Union im Rahmen des MixRisk-Konsortiums finanziell unterstützt.

Einhaltung ethischer Richtlinien

Interessenkonflikt

M. Hoffmann, S. Gebauer, M. Nüchter, R. Baber, J. Ried, M. von Bergen und W. Kiess geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • M. Hoffmann
    • 1
    • 2
  • S. Gebauer
    • 3
    • 4
  • M. Nüchter
    • 2
  • R. Baber
    • 2
  • J. Ried
    • 5
  • M. von Bergen
    • 4
    • 6
    • 7
  • W. Kiess
    • 1
    • 2
  1. 1.Klinik und Poliklinik für Kinder- und Jugendmedizin, Zentrum für pädiatrische ForschungUniversitätsklinikum Leipzig AöRLeipzigDeutschland
  2. 2.LIFE – Leipziger Forschungszentrum für ZivilisationserkrankungenUniversität LeipzigLeipzigDeutschland
  3. 3.Universitätsmedizin Leipzig, IFB AdipositasErkrankungenUniversitätsklinikum Leipzig AöRLeipzigDeutschland
  4. 4.Department Molekulare SystembiologieHelmholtz Zentrum für UmweltforschungLeipzigDeutschland
  5. 5.Lehrstuhl für Systematische Theologie II (Ethik)Friedrich-Alexander-Universität Erlangen-NürnbergErlangenDeutschland
  6. 6.Institut für BiochemieFakultät für Biowissenschaften, Pharmazie und PsychologieLeipzigDeutschland
  7. 7.Department für Chemie und BiowissenschaftenUniversität AalborgAalborgDänemark

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