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NUMMER 3OKTOBER 2017

TCDDT O X I C O L O G I E

Eitje erbij? De fipronil affaire

Toxicologen zijn nodig!

The NVT Annual Meeting 2017 Prize Winners

é

NVT annual meeting 2017

TCDD 2

Beste lezers,Toxicologische Communicatie, Data en Documentatie

Bestuur

Henk van Loveren, Maastricht University

F.R. (Flemming) Cassee, Rijksinstituut voor

Volksgezondheid en Milieu

Minne Heringa, Rijksinstituut voor

Volksgezondheid en Milieu

Milou Dingemans, Universiteit Utrecht, Utrecht

Peter Theunissen, CBG-MEB

S. (Suzanne) Heemskerk, UMC St Radboud

Rob Stierum, TNO Kwaliteit van Leven

SecretariaatMinne Heringa, Rijksinstituut voor

Volksgezondheid en Milieu

Postvak 1, Postbus 1, 3720 BA Bilthoven

E-mail: secretaris@toxicologie.nl

RedactieCarolien Schophuizen, Royal HaskoningDHV, Nijmegen

Folke Dorgelo, Toxicoloog

Jacqueline Biesterbos, Nederlandse Voedsel en Warenautoriteit

(NVWA), Utrecht

Martje de Groot, Universiteit Utrecht, Utrecht

Harm Heusinkveld, Institute for Risk Assessment Sciences (IRAS),

Universiteit Utrecht, Utrecht

Hedwig Braakhuis, Rijksinstituut voor Volksgezondheid en Milieu,

Bilthoven

Maaike Steenhof, Janssen Pharmaceutica N.V., Beerse, België

Barae Jomaa, AkzoNobel, Deventer

WebredactieSamantha Guichelaar, Rijksinstituut voor Volksgezondheid en Milieu,

Bilthoven

Floris Groothuis, Institute for Risk Assessment Sciences (IRAS),

Universiteit Utrecht, Utrecht

Bestuursvergaderingen 201723 januari, 20 maart, 15 mei, 25 september, 20 november

Lidmaatschap en AdreswijzigingenMarjan Sewradj-Mulder

Ledenadministratie NVT, p/a KNCV

Postadres: Postbus 249, 2260 AE Leidschendam

tel. 070 - 337 87 97

Via NVT website na inloggen http://www.toxicologie.nl

E-mail: ledenadministratie@kncv.nl

Het lidmaatschap wordt automatisch verlengd tenzij de NVT-

ledenadministratie vóór 1 december van het lopende jaar schriftelijk

of per e-mail een opzegging heeft ontvangen. Hiervan ontvangt u een

bevestiging.

Contributie NVTIncl. abonnement TCDD 53,= euro

(extra kosten EEMS: 10,= euro)

Sluitingsdata kopij 201724 November

Kopijbusredactie@toxicologie.nl

Website NVThttp://www.toxicologie.nl

VormgevingMarleen Mulder

Green Bean Design, Nunspeet

www.greenbeandesign.nl

2 Redactioneel

4 Nieuws van het bestuur

5 Eitje erbij?

6 Toxicologen zijn nodig

Alles om ons heen in de moderne maatschappij is

gebaseerd op wetenschap. Er loopt vrijwel niets zonder.

En zo is dat ook voor veiligheid. Voor chemische

veiligheid heeft de toxicologische wetenschap gezorgd.

De wetenschap maakt stormachtige ontwikkelingen door.

Die bieden veel kansen maar evenveel uitdagingen.

7 GUIDEnano: a web-based guidance tool for risk

assessment and mitigation of nano-enabled products

8 2017 joint meeting of the Neurotoxicity Society and

International Neurotoxicology Association

9 De nieuwe website is gelanceerd

10 Call for Proposals for the EUROTOX 2019 Congress

Scientific Programme

12 Invitation to submit proposals for the 15th IUTOX

Congress, Hawaii

The Society of Toxicology (SOT), is proud to co-host the

next triennial IUTOX International Congress of Toxicology

(ICT) to be held July 15–18, 2019, at the Hawaii

Convention Center in Honolulu, Hawaii, USA.

13 Special coverage: 2017 Annual Meeting of the

Netherlands Society of Toxicology

16 Blood analysis local residents confirms longtime

exposure to PFOA

18 Toxafette

By Baptiste Poursat

19 Proefschrift promopraatje

By Rozaini Abdullah

19 Registratie Cie

REDACTIONEEL

TCDDT O X I C O L O G I E

Graag willen we jullie in dit redactioneel laten kennismaken met twee

nieuwe redactieleden die het TCDD team komen versterken; Folke Dorgelo

en Carolien Schophuizen.

Mag ik mij even voorstellen: ik ben Folke Dorgelo, gestart in de

jaren ‘80 als toxicoloog bij de toenmalige Landbouwhogeschool te

Wageningen. Na diverse functies bij Het Rikilt in Wageningen en het

(toenmalige) ministerie van VROM heb ik vanaf 2002 gewerkt bij het

Ctgb in Wageningen. In 2014 ben ik met pensioen gegaan. Na een paar

jaar rustig aan gedaan te hebben wil ik mij nu weer graag inzetten voor

de toxicologie in Nederland. Mijn interesse gaat in het bijzonder uit naar de wisselwerking

met de media, waar het gaat om nuancering van berichtgeving en risicocommunicatie. Als

deelnemer van de redactie van TCDD hoop ik daaraan te kunnen bijdragen. Ik hoop op een

goede samenwerking met iedereen.

Ook ik stel me graag aan jullie voor. Mijn naam is Carolien Schophuizen.

Na de studie Biomedische Wetenschappen aan de Radboud Universiteit

Nijmegen, heb ik mijn promotieonderzoek afgerond waarin ik het

transport van uremische toxines door niercellen onderzocht. Begin

2016 verruilde ik het lab voor een positie als regulatory affairs manager

bij Synthon BV en sinds maart 2017 ben ik werkzaam als toxicoloog bij

de afdeling Chemicals Management van Royal HaskoningDHV. Ik werk graag samen met

verschillende partijen, het liefst op het snijvlak tussen uiteenlopende disciplines en vind het

daarom ook erg leuk om als redactielid een bijdrage te mogen leveren aan de komende

TCDDs.

Verder brengt deze TCDD u onder andere het nieuws van het bestuur en een bijdrage van

onze kersverse voorzitter Henk van Loveren. Ook een korte uiteenzetting over de fipronil

affaire, de zomerhit van 2017 mocht niet ontbreken. Daarnaast schreef Anke Tukker een

inspirerend reisbeursverslag over haar deelname aan de INA-NTS meeting in Brazilië, en

wordt u meegenomen in de wereld van GUIDEnano. Het proefscrhift promopraatje komt

deze keer van Rozaini Abdullah en ook de AIO toxafette zet zich weer voort. In deze TCDD

vindt u tevens informatie over het 15e IUTOX Congres in Hawaii en een uitnodiging

voor het 1e internationale koningscobra symposium.

Namens de voltallige TCDD redactie wensen wij u weer veel leesplezier!

Folke Dorgelo en Carolien Schophuizen

TCDD 3

TCDD 5

NIEUWS VAN HET BESTUUR

Door: Henk van Loveren

Op alle mogelijke niveaus, van het zeer fundamentele

onderzoek tot aan de TV interviews toe, zijn Nederlandse

toxicologen stevig vertegenwoordigd. De Nederlandse

toxicologie is van oudsher vooraanstaand in de wereld.

Tal van studenten genieten toxicologie training in

Nederland. Tal van Nederlandse toxicologen doen

ervaring op in het buitenland. Eind 2016 waren 78

toxicologen in opleiding en dit aantal is stabiel. We

draaien goed mee in internationale onderzoeksprojecten

en in advies gremia van bijvoorbeeld de Europese Unie,

de Wereld Gezondheids Organisatie, of de Organisatie

voor Economische Samenwerking en Ontwikkeling.

Het toewijzen van Maastricht als de locatie voor de

gezamenlijke meeting van de International Union of

Toxicology en de EUROTOX in 2022 illustreert dit ook.

Om waar mogelijk al die activiteiten te verbinden en

wellicht de kwaliteit van al die activiteiten mee te helpen

waarborgen of te verhogen is een levendige vereniging

als de NVT van evident belang. En we hebben een

levendige vereniging. Dat moge blijken uit de algemene

ledenvergadering en de AIO dag die op 20 en 21 Juni

plaats vonden in Doorn. Het programma was zeer

aantrekkelijk met goede en interessante sessies. Peter van

den Boogaard en Yvonne Rietjens openden beide dagen

met een key note presentatie. Zeer stimulerende, wellicht

zelfs provocerende, voordrachten die enthousiast werden

ontvangen. De beide dagen werden goed bezocht.

Een aantal prijzen werd uitgereikt die de toets der

wetenschappelijke kritiek meer dan konden doorstaan.

Behalve wetenschap

waren er ook

organisatorische zaken

aan de orde. Zo werd

een update van het

Huishoudelijk Reglement

van de NVT aangenomen,

evenals een voorstel van

de Registratie Commissie

voor een nieuw systeem

voor her-registratie. Ook

dergelijke ontwikkelingen

houden de vereniging op

het goede spoor.

Vanaf 22 juni van dit jaar ben ik de nieuwe voorzitter

van de NVT. Dat is een eer en ik dank jullie voor het

vertrouwen. Ik zal mijn best doen om waar mogelijk

de invloed die de vereniging behoort te hebben verder

gestalte te geven. Maar ik realiseer me dat ik voortbouw

op het werk van velen. Met name wil ik de vorige

voorzitter Flemming Cassee daarbij noemen, maar in

feite bouw ik slechts op het werk van jullie allemaal.

Voorzitter NVT

Schadelijke effecten van stoffen waaraan we bloot worden gesteld staan in het publieke

domein hoog op de agenda. Kijk naar de recente fipronil affaire en kijk iets langer

geleden de rubber bolletjes. Perfluorkoolwaterstoffen is een ander voorbeeld. Daarmee

zijn ze ook blijvend een issue in wetenschappelijke zin. De rol van de toxicologie bij

de uiteindelijke beoordeling van het gezondheidsrisico is evident. Wetenschappelijke

ontwikkelingen gaan snel. Die hebben allen een invloed op de uitoefening van het vak.

Het gaat daarbij niet alleen om ontwikkelingen voor het onderzoek naar mechanismen

van toxiciteit, of hoe gegevens uit in vitro onderzoek, proefdieronderzoek, of humaan

onderzoek te vertalen naar risico’s voor de volksgezondheid of werknemers op de

werkplek, maar ook om ontwikkelingen over wetenschappelijk inzicht in risicoperceptie

en risicocommunicatie. Meer en meer wordt van wetenschappers gevraagd uit de

wetenschappelijke ivoren toren neer te dalen en de kennis uit te dragen op een

evenwichtige manier. Facts maar ook fiction benoemen.

NEWS

Minister Schippers geeft in haar eerste brief van

3 augustus aan de Tweede Kamer een helder

overzicht van de situatie. Hieronder is die brief

beknopt weergegeven. De volledige brief en daarop

volgende brieven zijn terug te vinden via https://www.

rijksoverheid.nl/documenten.

Fipronil is een insecticide dat onder meer in

diergeneeskundige producten tegen vlooien, mijten en

teken gebruikt wordt. Fipronil mag niet worden gebruikt

bij dieren die bestemd zijn voor de voedselketen, zoals

kippen.

Begin juni 2017 heeft de NVWA van het Belgische

Federale Agentschap voor de veiligheid van de

voedselketen (FAVV) een verzoek gekregen om

onderzoek te doen naar een servicebedrijf dat

behandeling van bloedluis bij leghennen aanbiedt. De

NVWA heeft de administratie van het servicebedrijf in

beslag genomen en aan de hand van de administratie

bij 8 leghenbedrijven waar behandeling na 1 juli had

plaats gevonden monsters genomen. In deze eieren is

fipronil boven het maximumresiduegehalte (MRL) van

0,005 mg/kg aangetroffen. Deze Europese norm is het

hoogste wettelijk toegestane concentratieniveau van

een bestrijdingsmiddelenresidu in een levensmiddel

of diervoeder. De MRL is gebaseerd op goede

landbouwpraktijken en met het oog op de bescherming

van kwetsbare consumenten.

Op zondag 30 juli is bij een leghenbedrijf een

waarde ver boven de MRL gevonden die leidt tot een

overschrijding van de Acute Referentie Dosis (ARfD).

Deze toxicologische grenswaarde geeft aan hoeveel een

persoon binnen 24 uur binnen mag krijgen zonder dat

er gezondheidsrisico’s optreden. Een overschrijding van

deze grenswaarde betekent dat op basis van de huidige

wetenschappelijke kennis een risico voor de consument

niet uit te sluiten is. Op basis hiervan heeft de NVWA op

maandag 31 juli een publiekswaarschuwing gegeven.

Daarnaast is op de website van de NVWA een lijst van

ei-codes gepubliceerd waar de Acceptabele Dagelijkse

Hoeveelheid (ADI) voor kinderen is overschreden. De

gevonden waardes leveren geen acuut

gevaar op, maar kunnen bij langdurige

consumptie niet als veilig voor kinderen

worden beschouwd.

De groep van bedrijven die besmet

is met fipronil heeft direct een recall

ingezet om deze eieren tot en met de

supermarktketen en de verwerkende

industrie terug te halen. n

Eitje erbij?

Normaal gesproken is de zomerperiode een

periode van rust waarin genoten kan worden

van het mooie weer en waar “achterstallig”

werk ingehaald kan worden. Alle collega’s

zijn op vakantie, dus via de email word je

niet lastig gevallen. Dat gold deze zomer niet

voor mij en mijn collega’s bij de Nederlandse

Voedsel- en Warenautoriteit (NVWA). U kon

er waarschijnlijk niet omheen. De media

stonden er namelijk vol van: “Giftig fipronil

aangetroffen in eieren”. Wat begon als iets

kleins werd als snel iets veel groters waar

meerdere landen in Europa bij betrokken

zijn. Iedereen, toxicoloog of niet toxicoloog,

deskundig of niet deskundig heeft een

mening over de fipronil affaire.

Door: JacquelineBiesterbos

Mocht u nieuwsgierig

zijn geworden en

meer informatie over

de fipronil affaire

willen hebben kan ik

u verwijzen naar de

website van de NVWA.

TCDD 4

Nieuws van de voorzitter

Henk van Loveren

TCDD 7TCDD 6

NVWA

Door: Henk van Loveren

De wetenschap maakt stormachtige ontwikkelingen

door. Die bieden veel kansen maar evenveel

uitdagingen. Nieuwe chemische verbindingen, nieuwe

geneesmiddelen, nieuwe voedingsmiddelen hebben

potentie om toegelaten te worden op de markt. De

toxicologie maakt, gedreven door technologische

ontwikkelingen, eveneens enorme ontwikkelingsslagen.

Meer dan ooit zijn we in staat blootstelling te analyseren

tot op de laagste concentraties. Meer dan ooit zijn we

in staat effecten vast te stellen tot op het genomisch

niveau. Meer dan ooit zijn we in staat om met de

computer te voorspellen wat er gebeurt. Maar ook

maatschappelijk zijn er tal van ontwikkelingen die de

toxicologie uitdagen. De klassieke benadering, stop

de verbinding in een proefdier en kijk wat er gebeurt,

voldoet niet meer. Daarnaast is door sociale media de

mondigheid en expertise van burgers toegenomen, vaak

goed, maar soms richting acceptatie van chemische

stoffen ook onnodig bang makend en niet op

(wetenschappelijke) feiten berustend.

Daarmee blijft toxicologie als vakgebied van evident

belang om chemische veiligheid, in het milieu, in de

voeding, van geneesmiddelen en op de werkplek,

blijvend te waarborgen. Om dit op de lange termijn

te kunnen blijven doen zijn toxicologen nodig.

Wetenschappers die meer dan vroeger ook uitstapjes

maken naar de celbiologie, naar de epidemiologie,

naar “computational” hulpmiddelen. Maar die ook de

aansluiting kunnen blijven houden met wat uiteindelijk

op het bord van de regelgever terecht komt, of

uiteindelijk zelfs daar actief zullen zijn.

De Nederlandse Vereniging voor Toxicologie

probeert een sterke beroepsvereniging te zijn die

een platform biedt aan de toxicologen in Nederland,

ontwikkelingen in het eigen en andere vakgebieden

signaleert, ontwikkelingen in het buitenland signaleert

en verbindingen legt. (Bij)scholing stimuleert. Een

vereniging vóór maar ook dóór toxicologen.

Zonder (bij)scholing geen adequate kennis. Er blijft een

goede en zich steeds vernieuwende, opleiding van

toxicologen nodig. Die krijgt voor een deel gestalte

in verschillende curricula aan onze universiteiten.

Daarnaast zal de postdoctorale scholing van

toxicologen belangrijk blijven, zo niet steeds belangrijker

worden. Dat is van belang voor het vakgebied zelf, maar

tevens voor organisaties zoals de voedingsindustrie, de

chemische industrie en de geneesmiddelenindustrie,

naast wetenschappelijke instellingen waar

beoordelingen van schadelijkheid worden uitgevoerd,

zoals de NVWA, CBG, GR, RIKILT, NIZO, Alterra, RIVM, of

de ministeries VWS, SZW, I&M, EZ.

Wij roepen deze organisaties op om hun medewerkers

die actief zijn op het gebied van de toxicologie

ruimte te geven voor het volgen van opleidingen en

(bij)scholingscursussen. Zonder die ruimte kan het

kennisniveau niet op het peil blijven waarop het behoort

te zijn. Ook roepen wij deze organisaties op hun

medewerkers die ambitie hebben deel te nemen aan

bestuursactiviteiten van de Vereniging voor Toxicologie

daarvoor ruimte te geven. Het betreft een investering

in tijd, maar betaalt zich terug in kwaliteit en is van

maatschappelijk belang. n

Alles om ons heen in de moderne maatschappij is gebaseerd op wetenschap.

Er loopt vrijwel niets zonder. En zo is dat ook voor veiligheid. Voor chemische

veiligheid heeft de toxicologische wetenschap gezorgd.

Toxicologen zijn nodig

NIEUWS

Door: Margriet Park,

Susan Wijnhoven

The recently finalized EU FP7 project GUIDEnano aimed

to develop a methodology to address the human and

environmental health risks of nano-enabled products,

considering the whole product life cycle, i.e. synthesis

of nanomaterials (NM), manufacturing of NM-enabled

products, use, and end-of-life phase. The project

consortium consisted of 40 international partners,

including universities, research institutes and industrial

partners developing NM-enabled products. RIVM was

in charge of leading the work packages related to risk

assessment and human hazard

assessment.

Over the course of three and a half

years, an interactive web-based

guidance tool was developed

that provides a quantitative

human and environmental risk

evaluation, provides insight into the

uncertainties of the evaluation and,

where needed, proposes measures

for risk management such as

methods for exposure reduction

or for producing materials that are

inherently safe(r) by design.

The correct implementation of this

guidance ensures that the risks

associated with a NM-enabled

product, throughout its whole life

cycle, have been appropriately

evaluated and mitigated to an acceptable level,

according to the most recent knowledge at the time

of implementation. The evaluation of a NM-enabled

product using this Tool will also be useful for risk

communication to regulators, insurance companies,

and society. More information is available at

www.guidenano.eu. n

Nanotechnology is one of the key emerging technologies identified by the

European Union in its 2020 Strategy. Its enormous potential is fostering large

investments on the development of new industrial applications, reflected

in the increasing number of nano-enabled products that reach the market.

However, despite these large investments, uncertainties still exist on the safety

for workers, downstream users and consumers, the ecosystems, and the

general population that may be exposed through the environment.

GUIDEnano: a web-based guidance tool for risk assessment and mitigation of nano-enabled products

TCDD 8

WEBSITEREISBEURSVERSLAG

By: Anke Tukker

So finally May arrived and, from May 20 till May 23, I

participated in the 16th meeting of the International

Neurotoxicology Association (INA) in Florianopolis,

Brazil. This association organises biannual meetings and

this year it was a joint meeting with the Neurotoxicity

Society (NTS).

Upon arrival on the island of Florianopolis along the

Brazilian coast it was raining and this appeared to

be the weather theme of this meeting. This was very

unfortunate and disappointing, since the hotel was

located on the beach. However, it did make it easier to

stay indoors and attend the sessions. Beaches look less

tempting under a grey sky.

The four day programme was full of informative parallel

sessions with topics ranging from neurodegeneration

and inflammation to neurotoxicity test strategies

and the presented work focused both on in vivo and

in vitro studies. The conference was opened by the

Jacob Hooisma keynote lecture with the topic: “The

intersection of genes and environment in relation

to Parkinson’s disease”. The second day of the

conference had sessions on neuroinflammation and

mechanistic understanding of neurotoxicity whereas the

parallel sessions were about drugs of abuse and new

psychoactive substances. On the third day, Parkinson’s

disease returned as a topic, whereas the parallel session

had a focus on data analysis and high-throughput

test methods. During the last day, the focus was on

metabolic derangements predisposing neurotoxicity

and in the parallel sessions on the neurodevelopmental

effects of chemical exposure. The sessions did not

only consist of talks, but there were also many posters.

Not all presented topics were interesting for me.

However, the whole conference provided me with many

opportunities to meet people and discuss my project,

which I found very motivating.

My session was scheduled in the morning of the third

day and was entitled: “Developing an integrated testing

strategy using in vitro data to screen and prioritize

compounds with high throughput/ high content

methods”. The session was nicely organised. It started

with the big picture on data analysis of high-throughput

screening methods. The first talk was about analytical

methods for distilling information from high-throughput

screening methods, but focused mainly on how to

analyse changes in swimming patterns of zebra fish

following chemical exposure. From here the session

moved on to generating data and was on high-

throughput testing of environmental chemicals on

primary rat cortical cultures. In our group, we use the

same test method and therefore it was interesting to

learn and see how other people perform this test and in

which graphical way they present their data. Following

this, the session moved on from rat cell models to

discussing the use of human cells for neurotoxicity

testing. Then it was my turn to present my work. I was

really looking forward to give my presentation and

when the moment finally came I enjoyed it a lot. Before

leaving for Brazil, I heard that based on my abstract

and CV I was selected as a candidate for the David

Ray Award. This meant that my presentation would be

judged by a jury and that I could win a prestigious prize

adding an extra layer of excitement. My talk focussed

on the differences in neuronal activity between different

hIPSC-derived neuronal cell cultures and how they

From the moment that I started as a PhD candidate in the Neurotoxicology research

group at IRAS, Utrecht University, I was hoping to be invited to give a presentation

about my work at an international conference. Sometime last year, I received the

question if I would like to present my work in a platform session during an international

neurotoxicology conference. Of course I said yes to this opportunity and from that

moment onwards I was hoping that this session would be accepted. In November last

year, it became clear that this was the case and that I was going to Brazil to present my

work! I could not wait.

2017 joint meeting of the Neurotoxicity Society and International Neurotoxicology Association

compared to rat primary cortical cultures. The next

speaker also talked about hIPSC-derived neuronal

cultures. However, the speaker presented data in which

the cells were grown in 3D. This topic was very useful

for my project, since one of the goals of my project is

to develop a 3D cell model. The last speaker centred

her talk on AOPs and regulatory frameworks for

developmental neurotoxicity testing.

Besides all the informative and serious activities, social

activities were organised such as a visit to an oyster

farm, the traditional soccer game and an awards dinner

on the last evening. During the awards dinner I heard

that I won the David Ray Award! I felt and still feel really

honoured with this prize.

To conclude, the joint INA-NTS meeting covered

a wide range of neurotoxicological topics thereby

providing the participants the opportunity to broaden

their knowledge. I met many people and had useful

discussions about my work, providing me with many

new insights. All in all, attending this meeting was a

great experience. n

De vorige website zat technisch lastig in elkaar

waardoor we die met ons vrijwilligers team niet goed

functionerend konden houden. Hij was bovendien

gebouwd op een vrij complete template waardoor we

eigenlijk niet zo goed wisten hoe de onderliggende

structuur in elkaar zat. Na een tijd gemopper van

vooral mijzelf, maar vast ook u, de gebruiker, heb ik

besloten een nieuwe website te maken. Dat was nu

eenmaal de beste oplossing voor de lange termijn.

De tijdsinvestering was zeker een voltijd maand, al

heb ik dan de discussies en “nadenk momenten” niet

meegerekend. Gelukkig was er tussen het einde van

mijn promotieproject en nieuw werk wat tijd om de

klus te klaren. Na het ontwikkelen en bouwen is er nog

de nodige tijd overheen gegaan waarin verschillende

mensen de website konden bekijken en testen.

De nieuwe website is gemaakt in een

gebruiksvriendelijker systeem (Wordpress). Omdat hij

van de grond af aan is opgebouwd, ken ik alle ins en

outs waardoor problemen veel gemakkelijker en sneller

zijn op te lossen. Content aanpassen of toevoegen

(door redacteurs) gaat ook een stuk makkelijker en

de mogelijkheden zijn voor hen groter. Een deel

van de content is nu, zoals altijd de bedoeling was,

afgeschermd voor niet-leden (denk bijvoorbeeld aan de

TCDD). Ik zou u willen aanmoedigen om eens een kijkje

te nemen. Een van de nieuwe handigheden is dat u zich

kunt abonneren op de agenda via de “ical feed”, die de

evenementen direct in uw eigen agenda kan zetten.

Als alternatief kunt u gebruik maken van de RSS-feed

of aanmelden voor emailupdates zodat u een bericht

krijgt zodra er een nieuw evenement op de website

wordt aangekondigd. Lees voor alle ins en outs even het

bericht door over de nieuwe website op de website zelf.

De website heeft mogelijk nog wat kinderziektes. Mocht

u er een tegen komen, laat het ons vooral weten via

webmaster@toxicologie.nl. Het is grotendeels mijn

product, waardoor ik er persoonlijk op wil toezien dat

de website optimaal blijft functioneren. Wat de inhoud

betreft zijn er meerdere mensen betrokken om die up-

to-date te houden. Het NVT-secretariaat en de sectie-

auteurs houden hun eigen stukken bij. Website breed

helpen Samantha Kloet en Barae Jomaa ook nog met

de inhoud. Waarschijnlijk krijgen we de komende tijd

wel wat feedback. Het kan dan ook zijn dat er nog wat

dingen aangepast worden. De website zal sowieso af en

toe aanpassingen krijgen aangezien er de wens is om

de zaak zo modern mogelijk en up-to date te houden.

Hopelijk houdt deze website het daarmee een stuk

langer vol dan de vorige.

De nieuwe website is gelanceerd!

Door: Floris Groothuis

TCDD 9

INVITATION

TCDD 10

Call for Proposals for the

EUROTOX 2019 Congress Scientific Programme

On behalf of the Scientific Programme Committee (SCP) I invite you to submit your proposal

for the EUROTOX 2019 Congress that will be held in Helsinki, September 8- 11, 2019.

This year’s theme is “Toxicology - Science providing solutions”. It reflects our inclination to tackle topics

dealing with new and emerging technologies, personalized medicine, epidemiology of exposure to

chemicals, as well as environmental issues. Submissions in line with this theme are strongly encouraged.

Make sure to follow the general guidelines below when preparing your proposal.

We urge all Individual Members, Member Societies, Speciality Sections, SubCommittees and Corporate

Members, as well as scientific and industry partners to contribute. Only a common effort will guarantee a

high quality programme and keep our annual congress a reference point for the toxicologists not only in

Europe but also internationally.

Please submit your scientific proposals using the attached form making sure to include the organizer details,

the recommended speakers, and a brief presentation for the proposal. Send your proposals to the EUROTOX

Secretariat (secretariat@eurotox.com) by December 8, 2017.

The EUROTOX 2019 Scientific Programme Committee members are:

• Heather Wallace, Chair

• Aristidis Tsatsakis, EUROTOX Executive Member

• Thomas Weiser, EUROTOX Executive Member

• 2019 LOC Scientific Programme Committee

• Kai Savolainen, 2019 Congress President

• David Bell, Local SPC Chair

• Chairs of the EUROTOX Speciality Sections

• Jan Vondracek, Carcinogenesis

• Georges Kass, ERAS Risk Assessment

• Marc Pallardy, Immunotoxicology & Chemical Allergy

• Hilmi Orhan, Molecular Toxicology

• Eva Bonefeld- Jørgensen, EUROTOX 2020 Copenhagen congress delegate

We also urge you to support and encourage young scientists in your sessions since taking part in symposia

and workshops is still an important activity for help them to develop their scientific and professional skills.

Thank you in advance for your continuous support and contribution, and I look forward to receiving your

proposal.

Yours truly,

Prof. Heather Wallace

Scientific Programme Committee Chair

ROUNDTABLE: A discussion based session of

120 minutes with 4 participants. Only short

presentations should be planned (5- 10 minutes

each presenter) with the majority of time allocated

for open discussion with the panel and the

audience.

CONTINUING EDUCATION COURSE (CEC): An

educational session where 4- 6 experts in the field

present a balanced view of established principles.

Proposers/chairs should ensure they work with

individual speakers to achieve balance and prevent

repetition. Scheduled Sunday from 9:00 am to 4:00

pm, including coffee and lunch breaks.

KEYNOTE LECTURE: 1 speaker, lasting a total of 45

minutes. For international renowned leaders in the

field to present recent hot topics or an authoritative

overview of issues of broad interest.

USE THE SUBMISSION TEMPLATE

Please use the submission template that can be

downloaded from the EUROTOX website.

TCDD 11

The theme for the 2019 congress is “Toxicology - Science providing solutions”. It reflects

our inclination to tackle topics dealing with new and emerging technologies, personalized

medicine, epidemiology of exposure to chemicals, as well as environmental issues.

Submissions in line with this theme are strongly encouraged. Make sure to follow the

general guidelines below when preparing your proposal.

SUBMISSION DEADLINE IS DECEMBER 8, 2017 SEND PROPOSALS VIA EMAIL TO secretariat@eurotox.com

• Proposals will be evaluated based on the following

criteria: scientific quality, relevance, timeliness and

completeness of the information (including details

of all speakers, chairs, title, and short description).

• Geographical distribution (not more than 2 speakers

from the same country, except for CEC’s)

• The Congress Organization strongly encourages

interaction between Academia- Industry-

Regulators and interdisciplinary approaches (basic

research, clinical/epidemiological, regulation)

therefore we ask that you make every effort to

include speakers from all mentioned organizations.

GENERAL GUIDELINES FOR SCIENTIFIC PROPOSALS

SPECIFIC GUIDELINES FOR SCIENTIFIC PROPOSALS

SYMPOSIA: aims to be topical or cutting edge

scientific knowledge exchange with experts in

the area presenting data from their research and

answering questions from the audience.

• Should be 2 hours and have 4 speakers.

• The first speaker should set the scene for the

symposium by explaining briefly the background to

the topic before presenting his/her data.

• The talks should be 25 minutes with 5 minutes for

questions. A total of 30 min per speaker.

• The symposium needs a chair and co- chair.

WORKSHOP: aims to review a specific topic or area,

providing state of the art opinions or presenting a

controversial viewpoint, with a panel discussion as

well as questions and answers being an integral part

of the workshop.

• Selected area of interest can include methods or

technology topics.

• Should last 2 hours and have 4 speakers giving in

depth expertise.

• Presentations should last 25 min.

• There should be 20 min for Q & A in the form of a

panel discussion (all 4 speakers) at the end of the

presentations.

• The Chair should introduce the topic and set the

scene for the talks and discussion.

• The workshop needs a chair and co- chair.

INVITATION

TCDD 13

INVITATION

The Scientific Program Committee is looking forward to

working with the IUTOX and other societies to create an

inclusive and diverse program that highlights excellence

in science and practice of toxicology around the globe.

We will ensure the balance of interests of different

countries and world regions. It is imperative that the

attendees feel that scientific sessions and continuing

education courses are informative, inspiring, and present

strategies that can be implemented to improve human

and environmental health in countries with both robust

and developing research and regulatory enterprises.

We wish to serve as a global forum for the exchange of

ideas that can create impacts at all time scales, create

lasting partnerships, and lead to measurable elevation of

the competency of the toxicologists globally.

The Scientific Program of the ICTXV meeting will

consist of Continuing Education Courses, Keynote

lectures, Symposia, and Platform and Poster sessions.

The scientific symposium proposal submission site will

launch later in June 2017 for your submissions, and we

welcome Symposium proposal submissions before the

December 31, 2017 deadline. Each symposium will be

120 minutes in length and should include four speakers.

All proposals submitted before the deadline will be

reviewed by the Scientific Program Committee, and the

symposia accepted for the Scientific Program of ICTXV

will be announced at the SOT Annual Meeting in San

Antonio, Texas in March 2018.

The following is a list of criteria that the Scientific

Program Committee will use to evaluate proposals for

the symposia. We encourage submitters to carefully

review these criteria and make every attempt to tailor

their proposed sessions accordingly. It is expected that

15 Symposia will comprise the main part of the ICTXV

scientific program and we expect competition to be

formidable.

The Society of Toxicology (SOT), is proud to co-host the next triennial IUTOX

International Congress of Toxicology (ICT) to be held July 15–18, 2019, at

the Hawaii Convention Center in Honolulu, Hawaii, USA. The theme of this

meeting, to ensure relevance and interest to the worldwide community of

toxicologists and environmental health scientists, is “Toxicology Solutions for

Global Public, Environmental, and Personal Health.”

Invitation to submit proposals for the

15th IUTOX Congress, Hawaii

TCDD 12

Criteria for evaluation of the Scientific Symposia for ICTXV:

1. Scientific excellence of the proposed individual talks and the

session overall.

2. Relevance of the topic of the Symposium to the overall

theme of ICTXV, “Toxicology Solutions for Global Public,

Environmental, and Personal Health.”

3. Balance of the scientific content with respect to the utility and

relevance of the information presented for improving human

and environmental health in countries with both robust and

developing research and regulatory enterprises.

4. Speaker diversity with respect to the geographical area

represented, gender, and sector (government, industry,

academia, other).

5. Availability of support for speaker travel to ICTXV. [This criterion

is not a requirement, but a strong encouragement.]

Scientific Program Committee for ICTXV

William Slikker (USA) – ICTXV Chair

Ivan Rusyn (USA) – ICTXV Scientific Program Committee Chair

Peter N. Di Marco (Australia) – ICTXV Scientific Program Committee Co-

Chair and IUTOX President-Elect

Peter Goering (USA) – ICT XV Scientific Program Committee Co-Chair and

Chair of the Continuing Education Committee

Silvia Barros (Brazil), A. Nurşen Başaran (Turkey), Emanuela Corsini (Italy)

Claude Emond (Canada), Lijie Fu (China), Mary Gulumian (South Africa)

Keon Wook Kang (Republic of Korea), Yoshito Kumagai (Japan), Ofelia

Olivero (USA), Betzabet Quintanilla Vega (Mexico), M. Wahajuddin (India)

Further details, including Symposium Session Speaker

Reimbursement Policies and Details, are available online.

We are looking forward to developing an exciting program

from the proposals submitted for consideration for the ICTXV

Meeting.

Sincerely,

VERSLAG

The overall rating of the conference by the participants

was good, scale 4 out of 5. This rating was based on

the evaluation form filled by 56 participants: 22% PhD

students, 30% MSc students, and 48% professional. Also,

the program setup and content were very well received

with high evaluation ratings .

The first day of the NVT annual meeting was opened by

the president of the Netherlands Society of Toxicology,

Prof. dr. Flemming Cassee, The NVT-member day

started with a lively and inspiring lecture from Prof. dr.

Peter J. Boogaard, entitled “Translational toxicology of

the 21st century” (Pict. 1), continued by parallel sessions

of 4th year/senior PhD candidate presentations and

“(Eco)toxicology and nanoparticles: from measurement

to regulation”. A lively discussion followed: is

nanotoxicology a hype? After lunch, 2 parallel sessions:

business meeting NVT and career pitching took place.

Several speakers with different working background,

for example academia, industry, and government

institution, were invited to share their experiences to the

audience in the career pitching session.

During the NVT business meeting this year a number

of items were discussed (such as annual report of the

board, Finances 2016, ERT re-registration process,

reports of the different committees) including the switch

of the chair and vice-chair of the board. The NVT-

member day was then continued by another parallel

session of “Panel discussion: translational toxicology

and alternatives” and “Occupational toxicology: It’s the

exposure, stupid”. Then, various sections of the Society

gave a short pitch and the day was completed with the

award ceremony for the Joep van den Bercken prize

This year, the Annual Meeting of the Netherlands Society

of Toxicology was held on the 20th and 21st of June at

the Kaap Doorn Conference Centre, Doorn, with theme

“Translational Toxicology: from Molecule to Regulations”.

The first day was the NVT-member day, which included

the annual NVT business meeting, whereas the second

day was the ‘young scientists’-day.

2017 Annual Meeting of the

Netherlands Society of Toxicology

Date: 20-21 June 2017

Venue: Kaap Doorn Conference Centre, Doorn

Theme: Translational Toxicology –

from Molecule to Regulations

Number of participants:

- day 1 (20 June) = 152;

- day 2 (21 June) = 62;

- (Number of participation for both days) PhD

students = 29; MSc students = 24;

and professional = 114.

Pict. 1

2017, IUTOX 2020 logo competition, the best 4th year/

senior PhD presentation, and the best 3 abstracts of

MSc students. After the reception and dinner, the first

day ended with the evening (social) program, where

participants joined in a pub-quiz with drinks and

enjoyed music by DJ Marcel van Drunen, Mars Music.

The chairman of the 2017 NVT meeting, Prof. dr. Henk

van Loveren, initiated the second day of the meeting,

which was the young scientists-day. It was then

followed by a very intriguing talk by Prof. dr. ir. Ivonne

Rietjens entitled “Using the wealth of toxicological

data for human risk assessment” (Pict. 2). A remarkable

statement was that for nanotoxicology currently we

cannot do without animal experiments. After the coffee

break, 5 PhD students had the opportunity to give a 15

min presentation on their topic and compete for the

Speed Presentation prize. The young scientists-day

was then proceeded by 3 parallel workshops, including

the session of 3 workshops on transferable skills

development (visualizing your story and negotiation)

and the 50 shades of scientific integrity. The participants

really enjoyed the workshop with a lively discussion

during the sessions. This was also mirrored by the

evaluation with the overall rating of the workshops at

4.3 out of 5. The program was then continued by the

speed presentation of 5 selected MSc students. The

young scientists day ended with prize award for the

speed presentations of PhD and MSc students and was

concluded with a reception (Pict. 3).

TCDD 14

Pict. 2

Pict. 3

VERSLAG

Soheil defended his thesis on March 22 2017 ISBN 978-94-6233554-7

The organizing

committee:

Henk van Loveren,

Martijn Rooseboom,

Rob Stierum,

Christina Giannakou,

Carin Lunenburg,

Charlotte Pauwels,

Lenny Kamelia.

Jury:

• Prof. Bas Blaauboer

(IRAS-UU)

• Dr. Suzanne

Heemskerk

(Radboudumc)

• Dr. Martijn

Rooseboom (Shell)

• Dr. Rob Stierum

(TNO)

Thank you for participating and contributing to

the annual meeting of this year, it was a really

successful meeting and we are looking forward

to seeing you again at next year NVT meeting!

n

• 4th year/senior PhD presentation: Rianne Fijten, Department of

Pharmacology & Toxicology, Maastricht University (Pict. 4).

• The best 3 abstracts of MSc students: (Pict. 5)

o Nina Blaimschein: Department of Pharmacology & Toxicology, Radboud

UMC, Nijmegen.

o Renate Groot: Institute for Risk Assessment Sciences, Utrecht University.

o Tijmen van den Berge: Department of Pharmacology & Toxicology,

Radboud UMC, Nijmegen.

They were awarded with a total reimbursement for the NVT days 2017.

• IUTOX 2022 logo: Laura van Dijk (Pict. 6)

• Joep van den Bercken prize 2017: Tom Schirris (Pict. 7)

Prizes awarded:

Pict.4

Pict. 5

Pict. 6

Pict. 7

Pict. 8

Pict. 9

Pict. 10

Pict. 11

• PhD Speed presentation: Anne Zwartsen, UMC Utrecht and IRAS (Pict.8)

• MSc Speed presentation: Alizee Desrousseaux, Endocrine Toxicology

Group, IRAS, Utrecht University (Pict. 9)

• PhD poster presentation: Sven Rouschop, Department of Pharmacology &

Toxicology, Maastricht University (Pict. 10)

• MSc poster presentation: Nina Blaimschein, Department of Pharmacology

& Toxicology, Radboud UMC, Nijmegen (Pict. 11)

TCDD 15

VERSLAG

TCDD 16 TCDD 17

RIVM

Local residents who have lived in the vicinity of

the factory for a long period of time have higher

concentrations of PFOA in their blood than residents

who live further away or who have lived in the vicinity of

the factory for shorter periods of time. This is the result

of research by RIVM in cooperation with the the Service

Youth and Health, South Holland South.

PFOA in blood

RIVM has measured PFOA blood values in residents

in two zones around the chemical factory DuPont/

Chemours (DOI 10.21945/RIVM-2017-0077). The results

show that these measured blood values correspond well

with the calculated values in an earlier study in 2016

on the emission of PFOA by DuPont/Chemours. These

findings support the conclusion of the earlier study that

it is likely that residents around Dupont/Chemours have

been chronically exposed to high values of PFOA.

Residents who live for a long time in the vicinity of the

plant have higher blood values than residents who live

further away from the plant or for a shorter period of

time. The latter two groups show serum PFOA values

corresponding to background values such as those

found in European studies (3.5 ng/mL). Some of the

residents (4.7%) have higher blood values than expected

in view of the European studies.

From a sample of residents of the municipalities of

Dordrecht, Sliedrecht and Papendrecht people were

invited to participate. A blood sample was taken from

a total of 382 local residents (response 58%) in the

autumn of 2016. In this blood sample, the content

of PFOA was determined. Participants who wanted

to know their PFOA levels were informed about their

individual PFOA blood value.

This study was conducted by RIVM in collaboration with

the Service Youth and Health, South Holland South. The

study was commissioned by the Province of South-

Holland. At the same time a literature review on effects

of PFOA on humans will be issued.

Analysis of Scientific Literature

An analysis of scientific literature shows that there

are links between undesirable changes in the body

and the PFOA concentration in the blood. However,

scientists are still rather unsure about the exact blood

concentrations at which these undesirable changes

occur in the body.

Associations were found between blood concentrations

of PFOA in humans and possible health effects and

functioning of the body. This is the result of a review of

previously performed reviews of the scientific literature

on studies conducted among humans by the National

Institute for Public Health and the Environment. It is not

certain whether PFOA is the true cause or whether there

are other explanations for the observed associations.

This study (DOI 10.21945/RIVM-2017-0086) was

performed because of questions raised by residents who

live in the vicinity of the Dupont/Chemours factory in

Dordrecht concerning possible health effects due to the

emission of PFOA by the factory. The objective of this

review was to address the question what biological and

physiological parameters and diseases are associated

with blood PFOA concentrations in humans, to

determine in what ranges of blood concentrations the

associations are observed and to provide an indication

of the magnitude of the associations. Concentrations of

PFOA in blood are an indication of the level of exposure

to this chemical.

The strength of evidence for the existence of a possible

association differs between the observed effects. The

clearest evidence has been found for a relationship

The results of blood analysis show that measured blood values correspond well with the

calculated values in an earlier study in 2016 on the emission of perfluorooctanoic acid

(PFOA) by DuPont/Chemours. These findings support the conclusion of the earlier study

that it is likely that residents around Dupont/Chemours have been chronically exposed

to high values of PFOA. Long-term exposure to PFOA may have affected the health of

people living nearby the DuPont/Chemours factory.

Blood analysis local residents confirms longtime exposure to PFOA

TCDD 16 TCDD 17

RIVM

between exposure to PFOA and higher total cholesterol

concentrations in blood, higher concentrations of the

liver enzyme ALT in blood and a lower birth weight.

For all other examined associations, the evidence is

less clear. There are indications of an association with

higher blood concentrations of other liver enzymes,

LDL-cholesterol and uric acid. Indications have also

been found for a higher risk of chronic inflammation

of the bowel (ulcerative colitis), testis and kidney

cancer, as well as pregnancy-induced hypertension

and preeclampsia. Furthermore, associations have been

found between exposure to PFOA and a decreased

vaccination response, changes in concentrations of

thyroid hormones in blood and thyroid disease.

Individual health study of little use

RIVM expects that an (individual) health study

among local residents will produce little to no health

benefits for the people in question. In some cases the

undesirable changes in the body which may occur

as a consequence of exposure to PFOA can already

be detected by routine health surveillance and can

therefore be treated. Possible serious health effects

are kidney cancer, testicular cancer and chronic

inflammation of the mucous membrane of the colon

(ulcerative colitis). These possible effects occur only on

a very limited scale.

As a result, the chance that a screening for these

conditions will lead to the

detection of any new cases

is very small. People who are

concerned about their health

are advised to contact their GP.

RIVM Proposes Water Quality

Standard

RIVM proposes water quality

standards for PFOA (DOI

10.21945/RIVM-2017-0044).

This perfluoro compound

has been used for the production of Teflon and is

found in many surface waters around the world. The

quality standard for chronic exposure accounts for the

accumulation of PFOA in fish. Using this information,

RIVM has calculated a safe concentration in water

of 48 nanograms per liter, which is protective for

lifetime consumption of fish by humans and wildlife.

For this research an extensive overview was made

of the scientific data on effects of PFOA on aquatic

organisms and the accumulation in biota. Based on

the oral risk limit for humans as derived recently by

RIVM, a maximum allowable concentration in fish was

calculated assuming a lifetime daily consumption.

This biota standard is converted to an equivalent safe

concentration in water using information on the uptake

of PFOA from water by fish. Data on bioaccumulation

are needed because the water quality standard

for ecological effects on aquatic organisms is not

sufficiently protective for food chain effects. PFOA has a

relatively low toxicity for water organisms, but may pose

a problem when entering the food chain via fish. The

use of PFOA is restricted by European law, but it can still

reach the environment from PFOA-containing products

that were produced in the past. Because of its high

persistence, emissions will lead to long term presence in

the environment. An initial comparison with monitoring

data indicates that the safe concentration derived in this

research is not exceeded in Dutch surface waters.

RIVM news and summaries of RIVM reports,

for more information please visit www.rivm.nl

De Toxafette

Introduce yourself and tell something about your PhD project.My name is Baptiste. I’m French and I just started

my third year on a PhD project at the University of

Amsterdam. The objective of my project is to study how

microbial adaptation can influence the biodegradation

of new organic pollutants.

What are the major challenges that you have encountered in your project?My project is multidisciplinary, which is of course a

great opportunity to develop skills in different fields,

but also a major challenge. I need to learn and master

advanced techniques in microbiology, analytical

chemistry and molecular biology. In addition, microbial

adaptation is a very challenging and complex topic to

study.

What do you expect from your PhD?I expect my PhD to give me enough competences

and knowledge in order to effectively contribute to

scientific research.

What would you investigate if you have unlimited resources (i.e. time, money, people) in your project?If I had unlimited resources, I would focus my

investigation on microbial adaption at a genomic level

and its implication for the whole community. I would

also extend my research to other organic pollutants,

such as pesticides, and study adaptation mechanisms

on other microorganisms.

How do you combine your PhD with your personal life? Are there choices you have to make?My PhD is part of my life, but I try, as much as possible,

to undertake extra activities after work and not let my

PhD become my only activity. I try to limit late work

and work during the weekend. However, even if I do

something else, my brain doesn’t stop to think about

work. Even sport training can become a brainstorming

session.

What are your future career plans?I don’t have yet a clear plan for my future. I would like

to do a post-doc and to continue in academic research

for a while, but I don’t know where and on what topic.

Are you a member of a society and what do you expect from being a member?I am a member of SETAC. This membership allowed

me to present my work at the annual European

SETAC meeting, and to have the latest news about

environmental toxicology and chemistry.

Answer to the question of the previous AIOQuestion from Thomas: Are there differences in doing

research, either a PhD or a master, in France and the

Netherlands? What French custom would you like to

see incorporated in the Dutch academic world?

There are a few differences in doing research between

France and the Netherlands. For example, in France,

very few master programs are in English and a PhD

project has to be conducted within 3 years. Otherwise,

there is no fundamental difference in research between

those two countries. Also, as I didn’t do my master

thesis and my PhD in France, I don’t have many

experiences with French research as a scientist. I have

more experience in France as a technician and as a

student. So for now, I don’t have a French custom that

I would like to see incorporated in the Dutch academic

world. However, I think French universities could learn

from the Dutch universities, for example, by extending

the PhD program to 4 years.

Do you have a question for the next AIO who will contribute to the Toxafette?Do you develop a network of scientists for your future

career? If yes, how do you proceed? n

Baptiste Poursat By: Baptiste Poursat

AIO TOXAFETTE

TCDD 18 TCDD 19

PROEFSCHRIFT PROMOPRAATJE

Voorletters Achternaam Datum inschrijving Datum afloop

A.G.A. Welten 05-09-2017 05-09-2022

Registratie Cie

Voorletters Achternaam Opleider Datum inschrijving

T. van der Lugt Prof.dr. A. Bast 05-09-2017

J. Kupny Prof.dr. M. van den Berg 05-09-2017

R.B.T Verkooijen Prof.dr. F.G.M. Russel 05-09-2017

L.C.P. Borra Prof.dr. F.G.M. Russel 05-09-2017

M. Shi Prof.dr.ir. I.M.C.M. Rietjens 05-09-2017

C.H.C. Litjens Prof.dr. F.G.M. Russel 05-09-2017

In April 2013, I started my PhD research

at the Sub-department of Toxicology

at Wageningen University under the

supervision of prof. dr. Ivonne Rietjens, dr.

Ans Punt, dr. Jochem Louisse and dr. Sebas

Wesseling. I defended my thesis entitled

‘Integrated strategy for the assessment of

the kidney toxicity: the case of aristolochic

acids’ on March 24, 2017.

Aristolochic acids (AAs) are natural food-borne

nephrotoxic, genotoxic and carcinogenic chemicals.

My study aimed to demonstrate the potential of an

integrated testing strategy using in vitro assays followed

by physiologically-based kinetic (PBK) modeling

and reverse dosimetry in order to predict the in vivo

toxicity of AAs without animal testing. The in vitro

concentration-response curves for cytotoxicity of

aristolochic acid I (AAI) were obtained in kidney cell

lines and translated to in vivo dose-response curves

for kidney toxicity using PBK modeling-based reverse

dosimetry. The points of departure (PODs) obtained

from these predicted in vivo dose-response curves

generally fell within the range of PODs derived from in

vivo literature data on kidney toxicity of AAI. The same

PBK models were subsequently used to translate the

in vitro concentration-response curves for AAI-DNA

adduct formation to in vivo dose-response curves for

kidney AAI-DNA adduct formation. The predicted in vivo

AAI-DNA adduct formation varied within an order of

magnitude compared to the in vivo values reported in

the literature.

Given that the exposure to AAI is often accompanied

by the presence of aristolochic acid II (AAII), the relative

formation of DNA adducts by these two major AA

congeners was investigated. The results revealed that

the predicted AAI-DNA adduct levels were higher than

predicted AAII-DNA adduct levels, indicating that the

difference between the in vitro and in vivo AAI-/AAII-

DNA adduct ratios could only in part be explained by

differences in in vivo kinetics of AAI compared to AAII.

The discrepancy between the difference in DNA adduct

formation of AAI and AAII in the in vitro and the in vivo

situation is an issue that needs further investigation to

also adequately predict the relative differences between

the two AAs.

Furthermore, a risk assessment of plant food

supplements (PFS) and herbal products containing

AAs purchased via online markets was performed and

revealed that, in spite of the ban on AA-containing

products since 2001, consumers can still be exposed

to AAs, which raises concern, especially for people

who frequently use these products. Altogether, this

study presents further support for the use of combined

in vitro-PBK modeling-based alternative tools for risk

assessment and revealed the continued risks posed by

AAs present in PFS and herbal products.

After four years being abroad, I have returned to my

homeland of Malaysia for an academic position at the

Department of Environmental and Occupational Health,

Faculty of Medicine and Health Sciences, Universiti Putra

Malaysia. I am now an active member of the Malaysian

Society of Toxicology and my current research is

focusing on the risk assessment of natural products. n

By: Rozaini Abdullah

Proefschrift promopraatje

TCDD is de nieuwsbrief van de Nederlandse

Vereniging voor Toxicologie (NVT).

De Vereniging beoogt de belangen van

het vakgebied Toxicologie in de ruimste

zin te behartigen; de Vereniging heeft

uitdrukkelijk niet de bedoeling de rechts-

positionele belangen te behartigen van

de individuele leden, tenzij deze belangen

direct gerelateerd zijn aan de beoefening

van het vakgebied. Gehele of gedeeltelijke

overname van de inhoud van TCDD is alleen

mogelijk met schriftelijke toestemming

van de redactie.

ISS

N 15

71-149

8