Table Of ContentHormone-Disruptive Chemical Contaminants in Food
Issues in Toxicology
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2:Male-mediated Developmental Toxicity
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11: Hormone-Disruptive Chemical Contaminants in Food
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Hormone-Disruptive Chemical
Contaminants in Food
Edited by
Ingemar Pongratz and Linda Vikstro¨ m Bergander
Department of Biosciences and Nutrition, Karolinska Institute, Huddinge,
Sweden
IssuesinToxicologyNo.11
ISBN: 978-1-84973-189-8
ISSN: 1757-7179
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Foreword
Even though effects of both endogenous and exogenous endocrine disruptors
were first observed and described a long time ago, it was not obvious that
these effects were related to disturbances in hormone homeostasis. The obser-
vations were not spelled out as disrupters of the endocrine systems. Examples
of such effects are milk production in young boys after consumption of milk
from cows feeding on clover in the spring or the effects observed in birds of
prey and their insufficiency to reproduce successfully. Experimental studies
in the early 1970’s induced a prolongation in the estrous cyclicity of mice.
However, over the last two decades endocrine disrupting chemicals and their
effects have become more obvious and are now a matter of major concern.
Numerous national and international reports were produced to address
this issue in the latter part of the 1990’s, including one from the UNEP/
WHO 2002.*
Thereafter an intense amount of work was devoted to improving our
knowledge and understanding of EDCs and their effects. The present book
‘‘Hormone-disruptive Chemical Contaminants in Food’’ is one of a few such
attempts to summarize the current state-of-the science. Focusing on EDCs in
foodishighlyrelevantsincethisisindeedthemajorsourceofhumanexposure
to these chemicals. Over the last decade the EU legislation on chemicals -
REACH (Registration, Evaluation and Authorization of Chemicals) has been
agreed and now implemented. Even though ED effects are not addressed as
such, the endpoints regarding, e.g. reproductive toxicity, are highly dependent
onhormoneregulations,aswellascancer.Inarecentglobalprojectrelatedto
REACH and EDCs, the EU have adopted a report on the ‘‘State of the Art
*http://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/
IssuesinToxicologyNo.11
Hormone-DisruptiveChemicalContaminantsinFood
EditedbyIngemarPongratzandLindaVikstro¨mBergander
rRoyalSocietyofChemistry2012
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
v
vi Foreword
AssessmentofEndocrineDisrupters;2ndInterimreport’’.wThepresentbookis
timely and addresses natural and anthropogenic EDCs, verity of endocrine
endpoints, hormone systems and novel methodology for studies of EDCs and
their effects.
So far slightly more than 140,000 chemicals in commerce have been regis-
tered under REACH and by adding a number of natural endocrine active
compounds; it is easy to understand the enormous complexity of possible
chemical structures interacting. The phrase herein defines, that metabolism is
furthercontributingtothenumberofpotentialEDCs;ahighlyappropriateand
relevantconclusion.Bylookingintothenumberofendogenousandexogenous
compoundsplustheirmetabolitesitiscleartoseethataverycomplexexposure
scenarioexists.Addingtothisaretwodifferentsituationsnumerouschemicals
possessingbothpersistencyandbioaccumulativitycharacteristicson onehand
and chemicals characterized by their pseudopersistency, e.g. exposure to
polycyclic aromatic hydrocarbons and phthalate esters on the other.
The present book introduces the reader to the extensive complexity of the
hormone systems through selectedin-depth examples. The important issuesof
reproduction,fertility-relatedissues,teratogenicityandcancerinoffspring,are
addressed and it reaches the conclusion that male reproductive function is at
risk. This is very much in agreement with findings of others and supported by
both experimental data and observations in wildlife, a mirror of an endpoint
that is devastating for populations, independent of species.
It is obvious that food contaminants are linked to sex hormones and their
receptors as well as to the aryl hydrocarbon (Ah) receptor. The authors
visualize the complexity of compounds interacting with these receptors. A
notably high number of anthropogenic chemicals are binding to the Ah
receptor.Examplesofsomeverydifferentresponsesarealsogiven,eventhough
the structural changes in the chemicals exerting these effects are sometimes
minimal. Accordingly, it is important to discuss in silico methodologies for
assessingendocrineeffectsofchemicals.Inviewofallthecomplexresultsfrom
both in vivo and in vitro studies it seems appropriate to conclude as herein
defined, that in silico methodology is a tool that requires interdisciplinary
competence for relevant conclusions.
Eventhoughtheconceptofepigeneticswasgenerallyunderstoodsometime
ago it was not until the last decade that changes in the epigenome were first
discussed in relation to ED and their effects in life. The obvious changes in
molecules due to methylations seem reasonable causes of changes in hormone
system regulations. The examples described indicate a mismatch between
programming and real life which is striking.
To study and promote a better understanding of hormone function and the
vast number of hormone systems, receptor proteins, transport proteins, and
endpoints, it requires the development of new methods for experimental
whttp://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/Authoredby:Richard
Evans, Andreas Kortenkamp, Olwenn Martin, Rebecca McKinlay, Frances Orton, Erika
Rosivatz,2011
Foreword vii
studies. The large number of chemicals, their metabolites and other potential
abiotictransformationproductsrequiresmethodsthatcanbecarriedoutover
a short period of time but still give results from fully integrated organisms.
Hencefinancialaswellastheethicalaspectsneedtobeconsidered.Examplesof
novel developments concerning test systems are given in the present book
showing a positive development in this field of ED research.
ED effects in humans and well-established wildlife are a major threat to
human health and the sustainable development of wildlife populations. It is
therefore urgent to intensify research efforts on EDCs, their effects, mechan-
ismsofactionandtheirsynergieswithnaturalandanthropogenicEDCs,inthe
complexmixturesweareexposedtoviafoodandfeed.Theissuesthatneedto
be solved will require competences from scientists with a deep knowledge in a
variety of disciplines. The issue of EDCs also needs to be communicated to
policymakers, stakeholders and the public, to alert all of us that management
of these chemicals is required. This book ‘‘Hormone-disruptive Chemical
Contaminants in Food’’ serves, in my view, as a base for communicating the
importance of this message of EDCs in food and their in vivo interactions.
A˚ ke Bergman
Professor in Environmental Chemistry
Stockholm University
Preface
Chemicals are an integral part of a modern society and consumers benefit
from different chemicals on a daily basis. However, there are a number of
problems coupled with these products. Because chemicals are present in a
wide range of products and goods, consumers are under constant exposure
to many of them. In this book, we discuss the health problems that are asso-
ciated with the presence of chemical contaminants in food. We highlight
some of the scientific challenges associated with the characterization of bio-
logical effects coupled to exposure to chemical contaminants and some of the
needs for future research efforts in this scientific area.
We go through the scientific challenges associated with, for example, detec-
tionofchemicalcontaminants inacomplex foodmatrix,andwediscusssome
of the problems associated with the current exposure scenarios to chemical
contaminantsinfood,namelythepresenceofrelativelylowdosesofchemicals
with a prolonged exposure time. In this book we have decided to focus our
attention on chemicals that somehow have the potential to interfere with the
endocrine axis, namely the hormonal pathways that are regulated by tran-
scription factors of different families of proteins. In addition, we also discuss
how multidisciplinary scientific approaches are required to develop new
knowledge in this area and how new scientific information needs to be
‘‘translated’’ into legislative action in order to develop relevant safety margins
of exposure to contaminants in food and food items.
In our opinion, future research efforts in this scientific area face several key
challenges, not only of a scientific nature but also other aspects will require
considerableattentionbyallpartiesinthisfield.Onekeyaspectis,forexample,
the need to find new innovative channels of communication between research
providersandresearchusers.Thereisacriticalneedtoshortenthetimeframe
between scientific discovery regarding potential health hazards and legislative
implementation.
IssuesinToxicologyNo.11
Hormone-DisruptiveChemicalContaminantsinFood
EditedbyIngemarPongratzandLindaVikstro¨mBergander
rRoyalSocietyofChemistry2012
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
ix