Exchanging Knowledge, Identifying Challenges, Building Synergies - 17-18 December 2020 - European ...
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Exchanging Knowledge, Identifying Challenges, Building Synergies
17-18 December 2020 FORUM REPORT
Environment
GETTING IN TOUCH WITH THE EU In person All over the European Union there are hundreds of Europe Direct information centres. You can find the address of the centre nearest you at: https://europa.eu/european-union/ contact_en On the phone or by email Europe Direct is a service that answers your questions about the European Union. You can contact this service: – by freephone: 00 800 6 7 8 9 10 11 (certain operators may charge for these calls), – at the following standard number: +32 22999696 or – by email via: https://europa.eu/european-union/contact_en FINDING INFORMATION ABOUT THE EU Online Information about the European Union in all the official languages of the EU is available on the Europa website at: https://europa.eu/european-union/index_en EU publications You can download or order free and priced EU publications at: https://op.europa.eu/en/publications. Multiple copies of free publications may be obtained by contacting Europe Di- rect or your local information centre (see https://europa.eu/ european-union/contact_en). DISCLAIMER: The content of this document does not reflect the official opinion of the organisers. Neither the European Union institutions and bodies, nor any person acting on their behalf may be held responsible for the use which may be made of the information contained therein. Manuscript completed in March 2021 The European Commission is not liable for any consequence stemming from the reuse of this publication. Luxembourg: Publications Office of the European Union, 2021 © European Union, 2021 The reuse policy of European Commission documents is implemented based on Commission Decision 2011/833/EU of 12 December 2011 on the reuse of Commission documents (OJ L 330, 14.12.2011, p. 39). Except otherwise noted, the reuse of this document is authorised under a Creative Commons Attribution 4.0 International (CC-BY 4.0) licence (https://creative- commons.org/licenses/by/4.0/). This means that reuse is allowed provided appropriate credit is given and any changes are indicated. For any use or reproduction of elements that are not owned by the European Union, permission may need to be sought directly from the respective rightholders. PDF ISBN 978-92-76-31365-6 doi: 10.2779/32496 KH-02-21-294-EN-N
Opening session 2
The definition of endocrine disruptors in the Classification, 3
Labelling and Packaging of Chemicals Regulation
Work in progress on endocrine disruptors 5
Advances in test methods 11
EURION Cluster: testing and screening methods 14
to identify endocrine disruptors
The “integrated Fish Endocrine Disruptor Test” (iFEDT) 19
Human Biomonitoring for Europe (HBM4EU) 21
The PEPPER platform: a French initiative for the 23
pre-validation of test methods for endocrine disruptors
The Fitness Check on Endocrine Disruptors 25
Chemicals Strategy for Sustainability: High Level Segment 32
Panel Discussion with stakeholders on endocrine disruptors 40
Conclusions and next steps 46
1
Opening
session
ion
is s
mm
Co
an
op e
E ur
:©
P ho to
Virginijus Sinkevičius
European Commissioner for the Environment,
Oceans and Fisheries
“Good morning, Ladies and Gentlemen and a very warm welcome We will also be looking further into the future, with some news
to this Second Annual Forum on Endocrine Disruptors. It has been about next year. Our plan is to include endocrine disruptors as a
something of a challenge to organise, for obvious reasons, but hazard classification in the Classification, Labelling and Packaging
here we are at last. I am very glad we have still managed to do it Regulation. We will be making that proposal in early 2021, but we
in 2020, and so soon after the adoption of the Chemicals Strategy will not stop there because the scope for action to address endo-
for Sustainability. We promised to deliver the Chemicals Strate- crine disruptors for sustainability is much broader. We will discuss
gy in the European Green Deal, but also said that the regulatory that tomorrow with ministers from some Member States.
framework should rapidly reflect scientific evidence on the risk
posed by endocrine disruptors. One thing I would like to stress is the need for speed. We are de-
termined to step up the pace. Our goal is to ensure that endocrine
Here in this Forum, we understand the urgent need to act. We disruptors are banned in consumer products as soon as they are
know that endocrine disrupting chemicals are of special concern. identified, unless their use in these articles is essential for society.
They affect people and animals at moments when the body is As you know, over the past two years, the Joint Research Centre
particularly vulnerable, at critical moments such as conception, has been carrying out a Fitness Check to see how well our current
embryo development, early childhood and puberty. The effects legislation protects us from exposure to endocrine disruptors. The
are permanent and sometimes are even carried over to the next outcome showed a need to step up the protection, and we are
generation. determined to apply this as widely as we can. Our colleagues in
the JRC will be sharing how they reached those conclusions in a
The Commission has always been committed to ensuring a high session tomorrow.
level of protection of EU citizens and the environment. It is an
obligation in our founding treaties and a principle that governs It is a full programme and I am sure it will make for some very
our daily work. Under this Commission, with President von der constructive debates. I wish you the best for these days. At the
Leyen, the European Green Deal makes that commitment more Commission we will be listening and taking part, and we will be
explicit than ever before. It starts with the zero pollution am- determined to act on the conclusions. Thank you.”
bition for a toxic-free environment by 2030, and it continues
through the Chemicals Strategy for Sustainability.
And now it is time to extend that thinking to endocrine disruptors.
As you know, we have been looking to improve protection against
endocrine disruptors for quite some time. This year we have con-
centrated our energies into two specific areas. The first of those is
updating data requirements for endocrine disruptors in the REACH
Regulation. Under the future arrangement, companies will need
to submit specific information if the substances they put on the
market have been identified as endocrine disruptors. The second
area is definitions, more specifically drawing up a definition of en-
docrine disruptors which can apply to all chemicals legislation. You
will be hearing about these actions in much more detail later.
2
The definition of endocrine
disruptors in the Classification,
Labelling and Packaging of
Chemicals Regulation
a
vil
The EU Chemicals Strategy for
A
de
na
sti
Sustainability was adopted by
C ri
©
t o:
Ph o
the European Commission on 14
October 2020, as the first step
towards a toxic-free environment
under the European Green Deal.
The Chemicals Strategy proposes
to establish endocrine disruptors
as a hazard category in the
Classification, Labelling and
Cristina de Avila Packaging (CLP) Regulation.
Head of the Sustainable Chemicals Unit in
DG ENV, European Commission
Cristina de Avila said the new definition which works with competent authorities
of endocrine disruptors in the CLP Regu- for REACH and CLP, explained Ms de Avi-
lation was first called for in the Commu- la. This group met three times in 2020, The WHO definition:
nication ‘Towards a comprehensive Euro- with Member States and stakeholders, to
pean framework for endocrine disruptors’, discuss options for implementing endo-
adopted in November 2018. In that Com- crine disruptor criteria in the CLP Regu- “An endocrine disruptor
munication, the Commission committed lation. This fed into the development of
to establishing a horizontal identification the Chemicals Strategy for Sustainability.
is an exogenous substance
across EU legislation, broadly based on or mixture that alters
the accepted WHO definition. The Chemicals Strategy is based on a
lengthy and thorough evaluation of exist- the function(s) of the
Other Chemicals Strategy actions include ing legislation, she said. We have in the
an update of the REACH (Registration, EU the most advanced knowledge–base
endocrine system and
Evaluation, Authorisation and Restric- on chemicals, and extensive European ac- consequently causes
tion of Chemicals) Regulation, through a tivity to regulate chemicals.
review of information requirements for adverse effects in an intact
endocrine disruptors. This involves having Over the past five years the efficiency
the criteria to identify them, and also the of chemicals legislation has been thor-
organism, or its progeny,
necessary information. It follows a revi- oughly evaluated. This has enabled an or (sub)populations.”
sion of such information requirements in overview of how endocrine disruptors are
the Plant Protection Products Regulation. addressed in every piece of relevant EU
Source: World Health Organisation /
legislation. The findings were published
International Programme on Chemical
We established an expert Working Group alongside the Chemicals Strategy, as a Safety (WHO/IPCS) 2002.
of CARACAL to advise the Commission Staff Working Document.
and ECHA (European Chemicals Agency),
3
The Chemicals Strategy is aiming to give Ms de Avila, so we do not want to have a developed for pesticides and biocides; and
a response to alerts coming from science, revolution we want to have an evolution. be applied across all legislation. We also
stated Ms de Avila. This supports our good In particular, we want to strengthen the concluded that it was best to separate the
regulatory system in reducing citizens’ REACH and CLP Regulations, as the corner- classes between human health and the
exposure to harmful chemicals. We know stones of the chemicals regulatory system. environment, she said, because legislation
endocrine disrupting chemicals can cause She highlighted flagship actions on endo- covering these areas has different scopes,
chronic diseases, and affect hormonal, im- crine disruptors in the Chemicals Strategy, for example, the Cosmetics Regulation
mune and vascular systems. in addition to the commitment to establish only covers health.
horizontal hazard identification under the
In the Chemicals Strategy we set out a vi- CLP Regulation. Endocrine disruptors will Regarding the possibility of sub-categories
sion to ensure that by 2030 we achieve a be banned from consumer products, by in- for hazard classes, Ms de Avila said this
toxic-free environment, where chemicals troducing or extending the existing generic will be discussed as part of the proposed
are produced and used in a way that max- risk approaches for carcinogens, mutagens criteria under CLP. Sub-classes exist for
imises their contribution to society, while and reproductive toxins. Such approaches carcinogens, mutagens and reproductive
minimising harm to the planet and current will also be introduced in areas where they toxins. A category of ‘suspected endocrine
and future generations. do not exist today. The concept of essen- disruptors’ (in addition to the category for
tial uses will be applied, to ensure that the known ones), she said, based on the ex-
This well be achieved through overarching most harmful endocrine disruptors are perience with carcinogens, would better
and mutually-supporting objectives, she only used where essential for health, safe- reflect the science and enable a more nu-
said. We have identified three key enablers ty or the functioning of society, or if there anced response to risk management.
to achieve the objectives: simplification are no acceptable alternatives.
and coherence of the chemical legislation In addition, a targeted impact assessment
framework; an improved knowledge-base Other Chemicals Strategy initiatives on is planned to estimate the number of sub-
that is able to respond faster to science; endocrine disruptors include the commit- stances that will fall under each hazard
and the global dimension. ment to amend Article 57 of REACH, where category, to be used during the review pro-
we identify Substances of Very High Con- cess for each downstream piece of legisla-
Legislation can be strengthened, for in- cern (SVHC), which means that endocrine tion, and when amending legislation. New
stance, by ensuring all chemicals on the disruptors will have their own entry. Then, label elements are also being developed,
market are used safely and sustainably; she said, we are committed to accelerat- namely, the H-(hazard) and P-(precaution-
by promoting and rewarding the substi- ing the development of methods used to ary) statements.
tution of chemicals that pose long-term generate information on endocrine disrup-
risks to humans and the environment; and tors through the screening and testing of In terms of the next steps, after the adop-
by avoiding the most harmful chemicals substances. tion of the criteria under CLP, we will pro-
in consumer products or those that affect pose the adoption of the new endocrine
vulnerable groups. Ms de Avila clarified that the introduction disruptor classification under the GHS
of hazard classes for endocrine disruptors (Globally Harmonized System of Classi-
We want to build on the impressive ex- in the CLP Regulation will be based on the fication and Labelling of Chemicals), as a
isting legislation we have in the EU, said WHO definition; build on criteria already new building block, said Ms de Avila.
Q&A Teri Schultz, the moderator on the first day, asked the questions
from the live chat at this virtual conference.
Blanca Serrano (European Chemical in place under REACH to review and endocrine disruptor identification, Ms
Industry Council - Cefic) expressed sur- evaluate endocrine disruptors. However, de Avila pointed out that the Chemicals
prise that the new hazard classes under she said, there is an established system in Strategy promoted the ‘one substance - one
the CLP Regulation had been agreed, as CLP, used for other hazard classes, such as assessment’ process, and will ensure data
they were under the impression that the carcinogens, and the treatment of endo- is available to all relevant authorities. The
discussion was still ongoing. She asked crine disruptors should not be different. issue of coherence is very important in the
if this could be clarified, and if the legal The Commission regards the CLP as a Chemicals Strategy, she said.
advice is being made available? cornerstone in EU legislation to identify
hazardous substances. Another comment concerned the large
Natacha Cingotti (Health and Environ- number of animals still being used for
mental Alliance - HEAL) asked if there Ms de Avila reiterated that classification is endocrine disruption testing. Ms de Avila
was a need for an impact assessment in exclusively hazard-based; based on the in- agreed that more work is needed to find
order to proceed, given the work done trinsic properties of a substance. It is what alternatives to animal testing, for all hazard
through various chemicals evaluations. you do with that substance that determines classes of chemicals. The Commission is
risk. Therefore, risk-based measures con- committed to reducing animal testing,
Cristina de Avila stressed the clear polit- cern specific uses in pesticides, toys, food she said, but the ultimate aim is to protect
ical commitment of the Commission, as contact materials, cosmetics and other human health and the environment.
established in the Chemicals Strategy. products. We cannot control their use, she
said, so a generic approach is necessary for To this end, a Commission Scientific Con-
She noted that the new hazard category in classification. ference on 2-3 February 2021 ‘Towards
the CLP Regulation has become a sensitive replacement of animals for scientific pur-
issue for the chemical industry, who Responding to a comment on the poses’ will highlight the new technologies
believe that adequate provisions are already importance of data sharing to speed up enabling a move away from animal testing.
4
Work
in progress
on endocrine
disruptors
In this session, the European Commission and European agencies
summarised their work on endocrine disruptors.
The speakers were: Arimatti Jutila, European Chemicals Agency (ECHA);
Maristella Rubbiani, DG SANTE; Maria Arena, European Food Safety
Authority (EFSA); Petra Leroy Čadová, DG Internal Market, Industry,
Entrepreneurship and SMEs, European Commission; and Vera Rogiers,
Scientific Committee on Consumer Safety (SCCS).
5
The European Chemicals
P ho
to:
©
JU
TIL
A
Ar
im
Agency (ECHA)
at
ti
Arimatti Jutila
Hazard Assessment Directorate, ECHA, Helsinki
Arimatti Jutila is the co-chair of ECHA’s Endocrine
Disruptor Expert Group (ED EG), which provides
scientific advice regarding the identification of
endocrine disrupting properties of chemicals under
REACH and the Biocidal Products Regulation (BPR).
He gave a progress report on their activities.
There is a wide range of legislation in We have already received two SVHC inten- Of those, 15 substances were considered
ECHA’s portfolio, of which REACH and BPR tions for substances with endocrine dis- as endocrine disruptors and 4 not, but for
specifically address endocrine disruptors. ruptor properties to look at in 2021, and I many the assessment is ongoing.
The Classification, Labelling and Packaging think we can expect more, he said.
(CLP) Regulation is foreseen as directly ad- The assessment of biocides for endocrine
dressing them from 2021. Further information can be requested from disruptor properties under the BPR is also
industry to clarify endocrine disruptor con- supported by the ED EG. Scientific crite-
ECHA’s regulatory strategy address- cern. There are 105 substances of endo- ria for endocrine disruptors, based on the
ing chemical substances of concern un- crine disruptor concern on ECHA’s CoRAP WHO definition, has been applied under
der REACH and CLP, involves the use of (Community Rolling Action Plan) list for BPR since June 2018. ECHA, together with
registration dossiers for regulatory risk substance evaluation. In the draft CoRAP EFSA (European Food Safety Authority)
management. ECHA screens the data list (2021 to 2023) there are 17 potential and the Commission’s JRC (Joint Research
in these dossiers regularly to identify endocrine disruptors. The Member States Centre), developed guidance for the imple-
chemicals of concern (candidates) for doing this substance evaluation work are mentation of the criteria.
Member States, competent authorities encouraged to consult ECHA’s Endocrine
and ECHA itself, he said. Disruptor Expert Group (ED EG). So far, the ED EG has discussed 22 biocidal
active substances, 2 of which were consid-
The focus is on fully registered substanc- The ED EG was established in 2013 to ered endocrine disruptors, while for 20 more
es and those structurally similar to them. contribute to the efficient assessment of information is needed. The Biocidal Products
There is an increasing focus on groups substances with endocrine disruptor prop- Committee has discussed 21 biocidal active
of substances, for example, bisphenols erties. Currently the group has 50 external substances and produced 17 opinions, of
and phthalates in the case of endocrine members, from 19 EU Member States and these 3 were endocrine disruptors, 3 not,
disruptors. If further information about a EEA countries, the Commission (DG GROW, and for 11 no conclusion was possible. The
chemical is required, this can be request- DG ENV, DG JRC, DG SANTE), stakeholder Biocidal Products Working Groups discussed
ed (dossier and substance evaluation). organisations (2 industry and 5 public in- 12 active substances, with 4 not considered
The wealth of information sent to ECHA terest), as well as EFSA, OECD and Swit- endocrine disruptors, but more data is re-
is unique in the world. Companies are re- zerland. quired for most substances.
quired to collect or generate information
on the properties and uses of their chem- To date ECHA has hosted 18 ED EG meet- Dr Jutila concluded by mentioning some
icals, assess the risks and recommend ings, with 3 scheduled for 2021. The Expert further endocrine disruptor-related activi-
safety measures. Group provides informal and non-binding ties where ECHA is involved. They are sup-
scientific advice for assessing endocrine porting the development of information
Dr Jutila summarised the progress made disrupting properties of chemicals. Our ex- requirements for endocrine disruptors un-
on regulatory risk management of endo- perience is that in the vast majority of cas- der both REACH and BPR, for example, and
crine disruptors. Currently, there are 17 es, the subsequent regulatory follow-up the development of criteria under the CLP
substances or groups of substances iden- has been in line with the ED EG’s advice, Regulation. In addition, ECHA are current-
tified as SVHCs (Substances of Very High noted Dr Jutila. ly updating the guidance for safety data
Concern) that are included in the Candi- sheets to cover requirements for endocrine
date List due to their endocrine disruptor Since 2013, the ED EG has provided scien- disruptor properties, and are contributing
properties. Butylparaben was added to the tific advice on 99 substance cases, roughly to EURION Cluster projects on endocrine
Candidate List in 2020. 80% under REACH and 20% under BPR. disruptor identification.
6
Q&A Q&A Q&A
The moderator Teri Schultz asked the Pia Juul Nielsen (EDC-Free Europe Anne-Laure Demierre (Federal
questions from the live chat, starting / CHEM Trust) added that when Office of Public Health, Switzerland)
with a query about ECHA’s interac- concluding a substance is not an asked, can you certify that substances
tion with EFSA. endocrine disruptor, does it mean are not assessed many times by differ-
not fulfilling the criteria or it is ent agencies or authorities that reach
Arimatti Jutila replied that EFSA is a scientifically justifiable that it is not different conclusions?
member in the ED EG. A good exam- an endocrine disruptor?
ple of their work with EFSA and the Arimatti Jutila replied, concerning the
JRC is the development of guidance Arimatti Jutila said that for categories harmonisation of approaches, the aim
for endocrine disruptor criteria, for and CLP the discussion is ongoing. is that there should be only one hazard
which there is close collaboration. At the moment, there is no category assessment for each substance. He is
for suspected endocrine disruptors, aware that there are cases where more
and that is how we are working at the than one agency is working on the
moment. When a substance is shown same substance, so it is very important
to not be an endocrine disruptor there to harmonise the approaches.
Q&A
is no follow-up regulatory action, at
least concerning endocrine disruptor
properties, though it may have other
hazardous properties.
Teresa Bernheim (Lanxess
Deutschland) asked how will ECHA’s
Risk Assessment Committee (RAC)
Q&A
and the ED EG work together for
harmonised classification.
Q&A Angel Nadal (Universidad Miguel
Hernández de Elche, Spain) asked
what the consequences are once
Arimatti Jutila said that this is for
classification that is yet to come, so it a substance, such as bisphenol A
may be too early to say. However, for Emma Grange (Cruelty Free Europe) (BPA), has been classified as a SVHC
the part the ED EG plays, she said asked, from the observations of because of its endocrine disruptor
that we are discussing the hazards of ECHA’s handling of SVHC it seems properties.
the substances and then risks will be that even for relatively data-rich
covered elsewhere. substances, deciding on endocrine Arimatti Jutila replied that only when
disruptor status on the basis of an- a substance has been moved from the
Cécile Michel (ANSES, France) imal test data is very difficult, with Candidate List as a SVHC to the Au-
commented that experts are often left a high degree of uncertainty. Would thorisation List do users have to apply
in a position were data does not allow you agree? for an authorisation to use it. How-
conclusions, showing why a suspected ever, there are certain obligations that
class is important. Arimatti Jutila thought that here the apply in relation to the Candidate List
ED EG guidance is very valuable, as also, such as notification of substances
it describes how criteria should be in articles and communication in the
implemented to decide if a substance supply chain. BPA is in the Candi-
is an endocrine disruptor or not. Of date List. BPS and BPF are different
Q&A
course, it requires expert judgement, bisphenols, and this is where screening
and in some cases that can be tricky as and grouping becomes important.
the science of endocrine disruption is
not the easiest one. He agreed that substances already dis-
Natacha Cingotti (HEAL) asked if, cussed by EFSA could also potentially
considering the work ahead and the be discussed by ECHA. Different piec-
lack of data for many substances, the es of legislation can have different in-
ED EG has enough resources to do formation requirements and regulatory
its job? environments, so substances may be
discussed under pesticides regulations
Arimatti Jutila said that the ED EG and also under REACH and PBR.
is a really useful resource for what we
are doing and having 50 experts in the
same room/remote meeting is very val-
uable, but there is only so much they
can do. Initiatives come from Member
States, and so far we have managed
to discuss all the substances they have
brought into the meetings.
7
Pesticides, biocides and food safety
Two speakers contributed to this section on the work in progress on endocrine disruptors:
Maristella Rubbiani, Policy Officer from Unit E4 Pesticides and Biocides, DG for Health and
Food Safety (DG SANTE), European Commission; and Maria Arena, Senior
Scientific Officer at the European Food Safety Authority (EFSA).
Pho
to:
©
Ma
ris
te
lla
Ru
bb
ia n
Maristella Rubbiani (DG SANTE)
i
gave an overview of the application
of endocrine disruptor criteria for plant
protection products and biocides.
A joint ECHA/EFSA Guidance Document When there is a substance that is going There have also been discussions on
was published in June 2018 to help im- to be renewed, or a new substance to be non-active substances contained in bi-
plement the new endocrine disruptor cri- evaluated, we need to consider the new ocidal products having indications of
teria, followed by a review to align plant endocrine disruptor criteria, explained endocrine disruptor properties, said Dr
protection products (PPP) and biocidal Dr Rubbiani. Under DG SANTE, decisions Rubbiani, including at what strength of
products (BP) with the Guidance. Amend- made since November 2018 by the Stand- indication to make public the names of
ments of regulations and procedures for ing Committee on Plants, Animals, Food substances that are under confidentiality.
PPP and BP have been made to specifical- and Feed (PAFF Committee) have taken Other discussions related to the presence
ly foresee implementation of criteria for into account the criteria. The reporting of impurities identified as endocrine dis-
ongoing and future applications. Member States have also applied the new ruptors, and biocidal products generat-
criteria, when dossiers are at their level. ing disinfection by-products identified as
For PPP and BP, endocrine disruptor crite- having endocrine disruptor properties are
ria are already applicable, and in force for Under the new criteria, cases have been ongoing.
ongoing and future evaluations, said Dr initiated for three biocidal substances due
Rubbiani. This meant ‘stopping the clock’ to significant indications of endocrine dis- For both PPP and BP, training has been
at EFSA and Commission level, to give ruptor activity (iodine, PV/iodine, and the conducted on applying the new guidance
assessors enough time to evaluate and fungicide zineb); and for three biocidal and criteria, under the Better Training for
conclude on endocrine disruptor criteria. active ingredients (cholecalciferol or vita- Safer Food (BTSF) umbrella, for asses-
A review of test methods for fulfilling re- min D3, cyanamide, and DBNPA (2,2-Di- sors in Member States. This training was
quirements for PPP is ongoing, in light of bromo-2-cyanoacetamide)). In addition, prepared jointly by the Commission, EFSA
the ECHA/EFSA Guidance Document. 16 biocidal active substances have been and ECHA.
discussed in the ED EG at ECHA.
Ph o
to:
©
Ma
ria
Ar
en
a
Maria Arena (EFSA) then gave a
summary of the endocrine disruptor
assessments for pesticides.
For 23% of substances assessed for hu- crine disruptor properties. For the remaining pared to 3% for the T-modality . This was
mans and ED assessment in line with the substances, additional data were requested. because the dataset for assessing the en-
ECHA/EFSA ED Guidance was waived as docrine disruptors through the T-modality is
not considered scientifically justified, 12% For EAS-modalities (estrogen, androgen often complete, as a number of studies are
were classified as endocrine disruptor, and and steroidogenic), for humans additional available and have generated the data to
29% were considered as not having endo- data was requested in 41% of cases com- comply with other data requirements.
8For NTOs (non-target organisms), addition- full ED assessment was waived for human
al information was requested for 73% of health, and in 9 cases for NTOs.
cases (46 substances). When the substance
was considered to meet the endocrine
disruptor criteria in NTOs, this was mainly
For 15 substances, an EFSA conclusion is
publicly available on endocrine disruptor
Q&A
based on adversity for mammals which was properties, though for most active sub-
considered relevant at population level. stances additional data have been request- Claire Beausoleil (ANSES - French
ed. There are differences in the assessment Agency for Food, Environmental
From the substances assessed from No- of human health and NTOs (e.g. availability and Occupational Health & Safety):
vember 2018, until 2 days before this Fo- of data, conditions for waiving), though the What is planned in order to include
rum, 8 of the 66 were identified as endo- ECHA/EFSA Guidance Document was al- non-EATS modalities in the guidance
crine disruptors. Of these, 5 were identified ways followed. (e.g. for metabolic disruptors)?
as endocrine disruptors through the T-mo-
dality, with 1 each for E, A, and S modalities, EFSA has built a database containing all Maria Arena answered that for non-
said Dr Arena. Out of the 8, 4 were consid- the assessments done so far, along with EATS modalities, this depends on the
ered to meet endocrine disruptor criteria for rationale for the decisions, which is shared available knowledge and test methods.
both human health and NTOs. with Member States and ECHA. The next Once new test methodology becomes
steps, concluded Dr Arena, will be an Annex available that capture other modalities,
Dr Arena explained that according to the on how to consider XETA (OECD TG 248), in it will be discussed with the European
ECHA/EFSA guidance, an endocrine disrup- the assessment strategy of the ECHA/EFSA Commission how and when a revision
tor assessment can be waived when not ED Guidance which will be published early of the Guidance Document may be
scientifically justified due to a substance’s next year after a webinar with stakeholders; needed.
physio-chemical properties or (eco)toxi- and the establishment of an EFSA Working
cological profile, or because testing is not Group on endocrine disruptors in 2021.
technically feasible. For 15 substances, a
Cosmetics and consumer safety
Two speakers contributed to this section concerning work in progress on
Phot
endocrine disruptors: Petra Leroy Čadová, Policy Officer in Unit D4 ‘
o: ©
Eu
rop
ea
Consumer Industry’ of DG Internal Market, Industry, Entrepreneurship
n
C
and SMEs (DG GROW); and Vera Rogiers, Co-chair of the
om
m
Scientific Committee on Consumer Safety (SCCS).
iss
ion
Petra Leroy Čadová (DG GROW)
reported on the European Commission’s
review of the Cosmetics Regulation
with regard to substances with
endocrine-disrupting properties.
Published in November 2018, the review disruptors, launched just after its publica- Following the call for data, the Commis-
concluded that (i) the cornerstone of the tion, and the Commission’s commitment to sion submitted five mandates to the SCCS
Cosmetics Regulation is the scientific risk establish a priority list of substances with for risk assessment regarding three UV-fil-
assessment of ingredients carried out by potential endocrine disrupting-properties ters (octocrylene, benzophenone-3 and
the SCCS; (ii) scientific concerns with regard used in cosmetics by 2019. homosalate), one preservative (propylpar-
to endocrine-properties can be addressed in aben) and one hair dye (resorcinol). Three
this safety assessment; and (iii) the Regula- Ms Leroy Čadová informed that a consul- preliminary SCCS opinions (homosalate,
tion provides adequate tools to regulate the tation of the Working Group on Cosmetics propylparaben and resorcinol) have already
use of cosmetic substances that present a Products (comprising Member States, in- been published for a commenting period.
potential risk for human health and enables dustry, SMEs, and NGOs) had taken place
the Commission to take appropriate regula- leading to the consolidation of a list of 28 An ongoing call for data on the remaining
tory measures. potential endocrine disrupting substances, nine Group A substances is running until 15
14 in Group A1 with higher priority, and 14 January 2021. The Commission is planning
The report also made reference to the in Group B2. A call for data on the Group A to launch another call for data in early 2021
cross-sectoral fitness check on endocrine substances was organised in 2019. on the Group B substances.
1. Benzophenone-3 (BP-3); kojic acid; 4-methylbenzylidene camphor (4-BC); propylparaben; triclosan; resorcinol; octocrylene; triclocarban; butylated hydroxytoluene (BHT);
benzophenone; homosalate; benzyl salicylate; genistein; daidzein.
2. Butylparaben; methylparaben; tert-butylhydroxyanisole / butylated hydroxyanisole (BHA); cyclopentasiloxane / decamethylcyclopentasiloxane / D5; ethylhexyl ethoxycin-
namate (EHMC) / octylmethoxycinnamate (OMC) / octinoxate; cyclomethicone; benzophenone-1 (BP-1); salicylic acid; benzophenone-2 (BP-2); butylphenyl methylpropianol /
BMHCA; benzophenone-4 (BP-4); triphenyl phosphate; benzophenone-5 (BP-5); deltamethrin.
9Pho
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Ve
r a
R
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Vera Rogiers talked in more
detail about the activities of the
Scientific Committee on Consumer
Safety (SCCS) concerning potential
endocrine disruptors.
The SCCS is an independent group of sci- Prof Rogiers stressed three points that • For new ingredients, animal studies
entists who provide advice to the European characterise the risk of any substance of (after 2013) are not allowed for the
Commission. Usually, the SCCS responds concern. Firstly, a hazard identification giv- purpose of cosmetics (only Level 1
to given mandates from DG GROW, and ing the intrinsic properties of a chemical, and 2 test methods);
conducts a risk assessment based on sci- then a dose-response assessment in which
entific criteria. Endocrine disruptors are different doses are used to observe which • For environmental reasons and
approached like any other chemicals of po- dose cause adversity, and thirdly an expo- workplace safety, animal data may
tential risk to human health, on a case-by- sure assessment giving the time, frequency be requested by agencies, and SCCS
case basis. To be clear, she said, we are not and amount to which one is exposed. has to consider this;
classifying substances, we do risk assess-
ment. This is done according to the publicly Since we want safe cosmetics, SCCS calcu- • Animal-free test methods are not
available SCCS Notes of Guidance for the lates a very conservative margin of safety yet available to derive a systemic
testing of cosmetic ingredients. based on the highest dose that humans can PoD for human safety assessment.
be exposed to without any adversity. This
We follow the WHO definition of endocrine approach was used in the three public-
disruptors (see page 3), explained Prof Ro-
giers, in which three important points must
be fulfilled: i) an adverse effect must be
ly-available SCCS opinions to date.
For homosalate, the maximum allowed con-
Q&A
seen in an intact organisms, ii) which is centrate was 10%. SCCS found no robust
shown to be due to endocrine activity, and data for possible endocrine disruptor activ- Ann Gils (KU Leuven, Belgium)
iii) there must be correlation or causality ity or a PoD study on endocrine activity, so asked when the SCCS looks for a safe
between mode of action and adversity. they calculated the lowest Margin of Safety dose for an individual substance, do
by dividing the PoD through the highest ex- they also study the cocktail effect of
We take the conceptual framework of the posure value for which no adversity could the substances? Other participants
OECD (see p. 12) into consideration, she be observed (30mg/kgbw/day taken from a asked about vulnerable people, such
said. Levels 1 and 2 can be done by us as repeated dose toxicity study). The outcome as pregnant women.
assessors. Level 1 consists of historical was that the SCCS recommended the al-
animal data and existing physico-chemical lowable concentration for this UV filter be Vera Rogiers said that vulnerable
information, in silico data, databases with lowered to 1.4%. groups are considered in particular in
endocrine disruptor properties of chemicals, the finished product dossier, which
and new technologies, while Level 2 covers Propylparaben is allowed in a maximum is the responsibility of the cosmetic
in vitro assays for EAS modalities. Levels 3 concentration of 0.14% as a preservative. industry. When the SCCS looks to dif-
to 5 are based on in vivo testing (mamma- It is also used in cosmetics, food and med- ferent endpoints, maternal toxicity and
lian species and non-mammalian species, ications. Using the same approach as for teratogenicity are included. Aggregate
e.g. amphibians, fish, daphnia). These are homosalate, the SSC concluded that the exposures take into account multiple
not done by the cosmetics industry because concentration of 0.14% may be kept for ingredients. We do risk assessment of
of the animal testing and marketing bans. cosmetic products. Similarly, the maximum single ingredients, and that is deter-
concentration of resorcinol allowed in hair mining ‘what is a safe dose’ of that
From our work on Levels 1 and 2, we de- dyes of 1.25% was also considered safe ingredient when present in a cosmetic
rive a PoD (Point of Departure) - a dose and may be kept. product; the finished product is the
that does not give adversity. We use for responsibility of the cosmetic industry.
existing compounds historical information, Prof Rogiers concluded:
their physico-chemical properties, in silico In Europe we have a dual system. The
(computer) data and models (e.g. QSAR, • Risk assessment carried out by Commission looks for substances of
and ‘read across’ to see if information from SCCS is driven not only by toxicity, concern for human health and Member
similar substances can be used), toxicity da- but also by exposure on the basis of States give information on ingredients,
tabases, and new technologies (‘omics, e.g. solid scientific evidence; and then industry has the responsibility
proteomics, genomics). For Level 2, in vitro to create a dossier for each cosmetic
assays focus on estrogen, androgen and • When adverse effects are shown product on the market. As co-chair of
steroidal modalities (EAS). Together, this in reliable historical animal data, the SCCS, I can say that, because of
all provides a Weight-of-Evidence (WoE) a systemic PoD can be derived for that dual system, Europe has the safest
that can be used to assess the likelihood of toxicological endpoints, covering cosmetics in the world, and I really
causing adverse effects. endocrine disruptor effects; mean it!
10Advances
in test methods
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An
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Advances in
Go
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test methods
Anne Gourmelon
OECD, Paris
Anne Gourmelon, of the Organisation for
The OECD Conceptual Economic Cooperation and Development (OECD),
Framework for testing
endocrine disruptors: started her presentation by providing an overview
of existing OECD Test Guidelines (TGs), collected
Level 1: in the Revised Guidance Document 150 on
Existing (historical) data and Standardised Test Guidelines for Evaluating
non-test Information;
Chemicals for Endocrine Disruption.
Level 2:
In vitro assays providing data These include a diverse range of bioassays, odologies for testing endocrine disruptors.
toxicity studies and other tests, within Lev- We started to observe that new methodolo-
about endocrine mechanisms/ els 2 to 5 of OECD’s Conceptual Frame- gies require our Test Guideline Programme
pathways; work, covering EATS (estrogen, androgen, to evolve to accommodate the diversity
thyroid, and steroidogenic) modalities. of technologies, said Ms Gourmelon. We
are proposing solutions to regroup similar
Level 3: Ms Gourmelon then gave examples of the methodologies addressing the same ques-
large number of ongoing projects to de- tion, while maintaining clarity for users.
In vivo assays providing data velop new TGs and update existing ones,
about endocrine mechanisms/ such as ‘TG 458: in vitro androgen receptor Therefore, she continued, we are evolving
transactivation’. Most ongoing projects are from single method Test Guidelines to Test
pathways; led by OECD member countries, but benefit Guidelines containing several methods
from international cooperation. The major- evaluating the same biological target and
ity of current projects are in the field of using the same technique (PBTG) or differ-
Level 4: ecotoxicology, or are looking at new endo- ent technologies (KETG). We are now de-
In vivo assays providing crine pathways (beyond EATS), such as the veloping a proof-of-concept for combining
retinoid signalling pathway. TG methods that are technologically and
data on adverse effects on functionally diverse to predict the same
endocrine-relevant endpoints; The retinoid signalling pathway is critical adverse effect, through a Defined Ap-
for neural tube development, axial pat- proach (DA-TG).
terning and other developmental process-
Level 5: es in organisms. OECD member countries This evolution of testing methods reflects
have prioritised the development of new in an increased understanding of the under-
In vivo assays providing vivo and in vitro methods for this pathway, lying biology. Defined Approaches, agreed
more comprehensive data on along with additional endpoints in existing across countries, will also extend the ben-
in vivo assays. A detailed review paper will efits of mutual acceptance of data beyond
adverse effects on endocrine be published on this in 2021. single TG methods. They can, for instance,
relevant endpoints over more reduce duplication of testing across coun-
Development of new or modified TGs fol- tries, and through consensus-building and
extensive parts of the life cycle
lows a well-established process, with ex- a rule-based approach reduce the need for
of the organism. perts from member countries playing a subjective expert judgements when inter-
central role alongside Expert Groups. The preting data.
R&D stages are key for robust new meth-
12Q&A Q&A
Anthony Tweedale (R.I.S.K. Consul- Suzanne Butt (Glaxo Group Re-
tancy) noted that under the proposed search, UK) noted that it is critical to
amendments to the REACH data know and understand the limitations
requirement Annexes, animal test of the (in vitro) methods; what they
doses are to be ‘sufficient to generate do not cover can be more important
adequate data to assess hazard’. than what they do. How do they
Given these high doses, how can endo- cover the unexpected effect that an in
crine disruptors active at low doses be vivo study would catch?
detected? Are the OECD test methods
sensitive enough? Anne Gourmelon replied that when
a method does not cover a particular
Anne Gourmelon replied that endo- endocrine pathway, it does not mean
crine disruptors have to be evaluated there will never be an issue with
in terms of adverse outcomes observed endocrine activity of this substance for
in animal studies, but also with Mode other endocrine modalities. As we gain
of Action that can be tested in vitro more tools for newer pathways, we
or by screening in vivo assays. All of may better understand the behav-
the available evidence is integrated for iour and potency of chemicals and
evaluation, not just long-term studies their action on the endocrine system
conducted at high doses. and effects at the organism level. A
negatively tested chemical may be con-
A lot of effort is put into the devel- sidered a temporary negative until it is
opment and validation of OECD tested positive for another endocrine
TGs, she said. Some people may think modality.
they are insensitive, others may think
they are too sensitive or burdensome.
Among the diversity of testing method-
ologies that have been standardised and
harmonised, there are certainly sensitive
assays that have been developed and
they need to be integrated overall.
Q&A
The IATA (Integrated Approaches to Testing
and Assessment) case study project, which
Paul Fowler (Professor in the
exists outside of the Test Guideline Pro-
Institute of Medical Sciences at the
gramme, reviewed a Defined Approach for
University of Aberdeen), asked if the
estrogen receptor pathway in 2019, paving
Q&A
OECD is considering the IGF (Insu-
the way for future testing strategies that
lin-like Growth Factor) system as a
combine multiple non-animal methods.
target for endocrine disruption.
A problem flagged up by researchers and
Emma Grange (Cruelty Free Europe) Anne Gourmelon said that, for the
regulatory authorities has been the use
queried whether the question of how moment, there is nothing specifically
of different terms to describe the same
well animal testing methods reliably on IGF, but the OECD has a new
biology. This hampers systematic reviews
identify endocrine disruptors has project on the work plan that is a
and data mining. It is being addressed in
been sufficiently addressed? review paper, led by a consortium of
the new OECD Harmonised Templates for
European member countries, to gain
Reporting study summaries for endocrine
Anne Gourmelon responded with two a better knowledge and understanding
disruptor in vitro assays.
points. Firstly, we are exploring new of endocrine disruption of metabolic
pathways, new in vitro methods, and pathways.
One takeaway message from my talk to-
day, concluded Ms Gourmelon, is that there new endpoints to integrate into in vivo
are various ways to engage in projects in methods to make them more sensitive
relation to endocrine disruptor assessment, to endocrine disruptors. Secondly, she
beyond just TG development. In particular, said, for the test methods that exist
Adverse Outcome Pathways (AOPs) devel- there is concern, and work ongoing
opment, as a one-stop-shop in knowledge to make animal tests more sensitive
management for endocrine disruptor path- and more relevant to endocrine
ways, and the IATA case study project that disruptor testing. All the work at the
is enabling countries to share and explore OECD builds on research efforts from
the use of novel methodologies. member countries and industry, who
generate a lot of data, which is inte-
grated in a way that ensures robustness
and reliability.
13EURION Cluster:
testing and screening
methods to identify
endocrine disruptors
Presentations in this session were made by:
Andreas Kortenkamp, Brunel University, UK;
Juliette Legler, Utrecht University, the Netherlands; and
Majorie van Duursen, Vrije Universiteit Amsterdam, the Netherlands.
The EURION Cluster (European Cluster to Improve Identification of Endocrine
Disruptors) comprises eight projects funded through
the European Commission’s Horizon 2020 Research and Innovation
Programme, with a total investment of close to €50 million.
The projects focus on different aspects of testing and screening
methods for endocrine disruptors. Together, they can optimise
synergies to maximise their impact. In particular, they focus on
three areas with significant gaps and challenges: the thyroid
hormone system, metabolic hormones, and female reproduction.
14Thyroid hormone
Phot
o: ©
An
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K
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nk
system
am
p
Andreas Kortenkamp summarising
work published in 2016 by Tim Korevaar
and colleagues in the Netherlands, which
showed that low levels of thyroid hormone
during pregnancy lead to low IQ in infants.
This revealed the sensitivity of the system
and the importance of babies getting the
right amount of thyroid hormone.
The thyroid hormone system is very com- When measuring thyroid hormone serum Three EURION Cluster projects are ad-
plex, he said, with several entry points concentrations the assumption has been dressing this challenge: Athena, ERGO
where it is possible to disturb the system. that decreasing levels equate to disruption and SCREENED. All three are developing
Research is focusing on entry points for of thyroid hormone action in peripheral tis- in vitro assays, including 3D models in the
which there are no assays: the transport sues such as the brain. However, explained SCREENED project. These testing strate-
processes for thyroid hormones from the Prof Kortenkamp, this is not always the gies are based on Adverse Outcome Path-
placenta to the developing foetus, and to case, due to the complexity of thyroid hor- way (AOP) networks and ‘read across’ be-
the brain of the foetus. mone transport from the blood brain bar- tween vertebrate classes.
rier to neurons.
Thyroid hormones are essential for three The idea is to highlight which entry points
major steps in brain development: i) ra- To highlight this, he described two cases of the thyroid hormone system have the
dial cell migration (neurons moving to of severe defects in hormone action that most drastic effects on hormone disrup-
their correct position in the outer cor- occur without substantial changes in se- tion, and develop a testing strategy that
tex); ii) the GABA switch, which plays a rum thyroid hormones. The first is due to starts with these entry points; for exam-
vital regulatory role for the maturation a mutated thyroid receptor unable to re- ple, inhibition of iodide uptake or inhibition
of neurons; and iii) the differentiation of spond to hormones, resulting in neurode- of hormone synthesising enzyme. We are
different types of neurons. velopment deficits and skeletal abnor- also developing downstream markers of
malities. The second is due to a mutated disrupted brain development in the Athena
Prof Kortenkamp then gave an overview thyroid hormone transporter preventing project, he said.
of thyroid-relevant tests necessary in the the brain taking up hormone, leading to
data submitted for placing products on the severe intellectual disability (Allan-Hern- Prof Kortenkamp concluded by focusing on
EU market. These tests concern thyroid don-Dudley Syndrome). In both cases, se- one downstream test being developed by
hormone serum levels and thyroid histo- rum thyroid hormone levels can be in the the Athena project, which he coordinates.
pathology, in line with the Plant Protection normal range. Work in the USA established a disorder
Products Regulation, Biocidal Products involving misplaced brain neurons, when
Regulation, and REACH. The dilemma is therefore this, said Prof animals were treated with a chemical that
Kortenkamp: changes in thyroid hormone disrupts thyroid hormone synthesis. We
None of these data testing requirements levels alone cannot detect the risks to are developing this further to see if it is a
specify the need for in vitro tests or down- neurodevelopment, but at the moment useful biomarker for disrupted brain func-
stream effects on brain function. This is a we have nothing else. In the absence of tion, he said.
problematic situation that we think endan- biomarkers for altered neurodevelop-
gers the correct identification of thyroid ment, thyroid hormone change is seen
hormone system disrupting chemicals, he as an appropriate starting point for risk
said. It also means that regulators have to assessment.
make decisions on the basis of rather in-
complete data sets.
15Pho
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Ba
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i Metabolism disrupting
em
an
chemicals
s
Juliette Legler introduction the
three EURION Cluster projects
focusing on metabolism disrupting
chemicals (MDCs): EDCMET, Goliath
and OBERON.
The incidence of obesity and metabolic One example of an assay being developed The OBERON project is developing an in-
disorders has increased exponentially over within EDCMET is a new reporter gene as- tegrated strategy to test endocrine dis-
the past few decades, and we know this say for determining the binding of chemi- ruptors for the role they play in metabolic
is not only due to genetic disposition, she cals to human nuclear receptors involved disorders. The project takes a multi-disci-
said. Exposure to the class of endocrine in energy metabolism and metabolic disor- plinary approach, combining human epi-
disruptors called MDCs has been linked ders. This will involve the high-throughput demiological studies, in silico and in vitro
to disorders like obesity, diabetes, and screening of chemicals for their interaction assays, animal studies and computation
non-alcoholic fatty liver disease. with key receptors, including androgen and studies, within an integrated framework,
estrogen receptors that are important in to augment in vivo studies.
MDCs affect energy homeostasis; affect energy homeostasis, as well as another
multiple endocrine mechanisms and cell suite of receptors involved, for example, in One example of an OBERON project assay
types implicated in metabolic control; and fat cell differentiation, insulin regulation in is the zebrafish obesogenic test (ZOT), a
affect gene expression and biosynthesis of liver cells, and uptake in muscle cells. tool to identify MDCs involved in obesity.
key enzymes, hormones and adipokines The test identifies the effects of chemi-
essential for controlling energy homeo- GOLIATH (testing metabolism disrupting cals on the size and function of fat cells
stasis. Many types of tissues are involved: chemicals), which I coordinate, is looking in larval zebrafish. It is being taken to
liver, pancreas, muscle, heart, brain, and to generate novel and harmonised ap- pre-validation by the PEPPER consortium
adipose. proaches for testing MDCs, said Prof Leg- (see p. 24).
ler. The project team are developing in vit-
However, there are no tests currently avail- ro and high-throughput screening assays, Ultimately, we want to develop an interna-
able for MDCs. All three projects there- using human adipose, skeletal muscle tionally harmonised, integrated approach
fore aim to identify the action of these and pancreas tissue. They are focusing on to testing and assessment, with a suite of
chemicals, define key events, and provide regulation and uptake of insulin, working assays for MDCs that are much needed for
stronger evidence for their role in adverse with epidemiologists to identify the most their regulation, concluded Prof Legler.
outcomes. Together, the projects will cre- important outcomes in humans, and also
ate a large battery of in vitro and in silico conducting fish assays to look at effects in
assays, and improved animal studies for vertebrate models.
metabolic disorders, said Prof Legler.
An example of an assay being developed in
The EDCMET (Metabolic effects of Endo- GOLIATH is the CYP Induction Assay, based
crine Disrupting Chemicals: novel testing on one originally developed for pharma-
METhods and adverse outcome pathways) ceuticals. It can quickly detect if chemicals
project is developing in vitro and in silico can be metabolised by CYP (cytochromes
assays within an AOP framework, for key P450) enzymes. We think it is an excellent
molecular initiating events that lead to and sensitive method for detecting me-
adverse outcomes. Key events are being tabolites in human liver cells, and we are
studied in rodents, and adverse outcomes extending its application to include MDCs,
also from human epidemiological studies. explained Prof Legler.
16Female reproductive
Phot
o: ©
Ma
jor
ie
va
n
Du
and endocrine
ur
se
n
disrupting chemicals
Majorie van Duursen introduced the FREIA
(Female Reproductive toxicity of EDCs:
a human evidence-based screening and
Identification Approach) project, the only
EURION Cluster project dealing with
female reproduction.
One in six couples worldwide face fertility The FREIA project focuses on different With a move away from animal-based
problems, and ovulation disorders - such life stages, explained Prof van Duursen. risk assessment towards more mecha-
as irregular menstrual cycles, polycystic For the development of the fetal ova- nism-based risk assessment, there is a
ovary syndrome, and early menopause - ry, ovaries from terminated pregnancies need for clearer descriptions of pathways
account for infertility in one out of four cultured in vitro are exposed to selected leading to adverse health outcomes. Sev-
infertile couples. That is why the FREIA chemicals, to observe effects on number eral putative AOPs for female reproduc-
project focuses on the ovary. of germ cells present and germ cell death. tive toxicity have been postulated by the
FREIA consortium, including one for acti-
There are several studies in humans In adult life, every month one oocyte vation of the androgen receptor leading
showing that effects on the ovary during matures and is released for fertilisation. to reduced ovulation.
early life development can lead to prob- However, results from the FREIA project
lems later in life, she said, this is called show that the fluid surrounding the oo- In a nutshell, FREIA conducts experimen-
Ovarian Dysgenesis Syndrome (ODS). cyte contains many known and suspect- tal studies with EDCsin human tissue
Chemical exposure early in life can affect ed endocrine disruptors; plasticisers and (ovary, adrenal, follicles), in vitro and in
ovarian development, but mechanisms PFAS were measured in Swedish and Es- silico studies, and rat studies, to provide
are mostly unclear. tonian follicular fluids. Within the FREIA human-relevant biomarkers, and mecha-
project the effects of these chemicals on nistic descriptions of AOPs with a focus
Therefore, we need a better understand- oocyte maturation processes and subse- on sensitive life stages for female re-
ing of biology and the processes under- quent fertility outcomes will be assessed. productive toxicity. In the end, we hope
lying ovarian development, in order to to see female reproductive toxicity dealt
develop better testing methods. One aim Prof van Duursen questioned whether the with across regulations, concluded Prof
of the FREIA project is to address this current Test Guideline endpoints for fe- van Duursen.
knowledge gap. male reproduction are sensitive enough.
For example, vaginal opening as a marker
Because biology is different for different of puberty onset in animal studies. The
life stages, it is logical to assume that the pulsatory release of gonadotropin-releas-
effects of endocrine disruptors are differ- ing hormone (GnRH) by the hypothalamus
ent for different life stages. Females are appears to be a more sensitive marker.
born with a pool of follicles and do not Another sensitive endpoint is the mam-
gain more during their life. Depending on mary gland, she said.
life stage, exposure to EDCs may result in
fewer oocytes, changes in onset of puber-
ty, or fertility problems later in life.
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