toksikologi 2/2012 - Suomen toksikologiyhdistys

TOKSIKOLOGI
Suomen Toksikologiyhdistyksen virallinen jäsenlehti
2/201
/2012
Cancer cell illustration courtesy of iStockphoto/Eraxion
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Sisällysluettelo
Lehden päätoimittajalta ............................................................................................................. 3
Suomen Toksikologiyhdistyksen hallitus vuonna 2012 ............................................................. 4
Uudet toksikologiyhdistyksen jäsenet ....................................................................................... 4
Orion's Experence from SafeSciMET Training Courses ........................................................... 5
33rd annual symposium of Finnish Society of Toxiclogy and abstracts .................................... 8
13 th International Congress of Toxicology (ICTXIII) .............................................................. 19
What are cancer stem cells..................................................................................................... 19
Greetings from Bethesda III .................................................................................................... 22
Tapaa toksikologi - haastattelussa Kirsi Myohanen ................................................................ 24
STY:n 34-vuotissymposium 2013 ........................................................................................... 25
Jäsenmaksu 2012 ................................................................................................................... 26
Jäsenanomus ja osoitteen- ja nimenmuutosilmoitus ............................................................... 27
Kustantaja ja toimitus: Suomen Toksikologiyhdistys r.y.
Päätoimittaja:
Kirsi Vähäkangas, Itä-Suomen yliopisto, Terveystieteiden tiedekunta, PL1627,
70211 Kuopio, [email protected], puh 040-7455254
Toimitussihteeri: Kirsi Myöhänen, [email protected]
Jäsenet:
Arja Rautio ([email protected])
Kai Savolainen ([email protected])
Hanna Tähti ([email protected])
The Finnish Society of Toxicology http://www.toksikologit.fi
EUROTOX http://www.eurotox.com
Society of Toxicology http://www.toxicology.org
www.reachneuvonta.fi
www.ec.europa.eu/enterprise/reach/index_en.htm (mm työpaikat)
IUTOX http://www.iutox.org
www.reachinfo.fi
http://ecb.jrc.it/reach/ (RIP Guidance & Tools)
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Päätoimittajalta
Erään ystäväni minulle tuntematon ystävä sairastaa keuhkosyöpää. Olemme vaihtaneet
sähköposteja asiasta ja olen kertonut, minkä tiedän. He eivät ole terveystieteiden edustajia,
joten monet tupakointiin ja keuhkosyöpään liittyvät tosiasiat ovat heille ilmeisen uusia, mm. se,
että tupakoinnin lopettaminen jopa vasta syöpädiagnoosin jälkeen on potilaalle hyödyllistä.
Hoidot tehoavat paremmin ja potilaat elävät kauemmin, jos tupakointi loppuu. Tähän liittyen
olen myös vilkaissut, mitä uutta on julkaistu tupakasta ja silmiini sattui juttu Phillips Morrisin
aikaisemmin salaisista dokumenteista jotka liittyvät heidän 2000-luvun alkupuolella
julkaisemiinsa tutkimuksiin tupakkaan lisättävistä maku- ym. aineista. Dokumentit tulivat
julkisiksi oikeudenkäyntiin liittyen.
Wertz ja kumppanit (2011, The Toxic Effects of Cigarette Additives. Philip Morris’ Project Mix
Reconsidered: An Analysis of Documents Released through Litigation. PLoS Med 8(12):
e1001145) analysoivat vertaisarviointi-lehdissä julkaistujen artikkeleiden alkuperäisdataa
uudestaan ja havaitsivat, etteivät julkaisut vastanneet todellisuutta. Julkaistut artikkelit
kehuivat ettei lisäaineiden toksisuudesta ole mitään näyttöä. Tosiasiassa, kun tulokset olivat
osoittautuneet positiivisiksi, ne analysoitiin uudelleen ja tällä kertaa normalisoiden
totaalipartikkeleiden määrän suhteen. Näin jäi pimentoon se, että juuri partikkeleiden määrä
lisääntyi lisäaineiden vaikutuksesta. Eläintutkimuksissa oli taas sen verran pieni n, että epäily
heräsi tilastollisen käsittelyn arvosta. Tulosten vääristelyä siis. Savukkeissa on satoja
lisäaineita, jotka tekevät tupakoinnista miellyttävämpää. Jo se on sinänsä huono asia, koska
tupakointi on terveydelle niin haitallista. Wertz ja kumppanit loogisesti ehdottavat näiden
lisäaineiden kieltämistä terveydelle haitallisena. Se auttaisi varmaan tupakoinnin edelleen
vähentämisessä.
Olen viime aikoina lueskellut myös tutkimusetiikkaan liittyviä asioita.
Valitettavasti
tupakkateollisuus ei ole ainoa tutkimustulosten vääristelijä. Kirjallisuudessa väitetään että
tutkimusväärennösten määrä on lisääntymässä kovan kilpailun painostuksessa ja
monimutkaisten nykyaikaisten menetelmien mahdollistamana. Toksikologiassa on kysymys
ihmisten hengestä ja terveydestä. Meillä ei ole varaa antaa tieteenalamme tuolla tavalla
korruptoitua, vaan epäterveet tavat pitää karsia jo opiskeluaikana ja jokainen meistä
senioreista on oman tutkimusryhmänsä tutkimusetiikan opettaja.
Kirsi Vähäkangas
P.S. Wagner katsoo hämmentyneenä pöytää: “Illalliseni pitäisi olla tässä, mutta mitään ei
näy...” – ja kumartuu sitten vilkaisemaan: “Ei pöydän allakaan!” Viivi hetken kuluttua pöydällä
makaavalle Wagnerille: “Mitäs siinä makaat suu auki?” Johon Wagner: “Yritän laukaista
ruokkimisrefleksin”.
Yhtä
epätoivoisena
minä
yritän
laukaista
jäsenmaksun
maksamisrefleksin… Tilihän on seuraava: 800012-1716678 ja jäsenmaksun suuruus 30
euroa.
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TOKSIKOLOGI
Suomen Toksikologiyhdistyksen hallitus vuonna 2012
Vähäkangas Kirsi, puheenjohtaja
Itä-Suomen yliopisto,
Terveystieteiden tiedekunta,
PL 1627, 70211 Kuopio
[email protected]
Myöhänen Kirsi, taloudenhoitaja
Euroopan kemikaalivirasto ECHA
PL 400, 00121 Helsinki
[email protected]
Laakso Juha, sihteeri
Turvallisuus- ja kemikaalivirasto
TUKES
PL 66, 00521 Helsinki
[email protected]
Akkanen Jarkko, jäsen
Itä-Suomen yliopisto
Biologian laitos
PL 111, 80101 Joensuu
[email protected]
Kai Savolainen, jäsen
Työterveyslaitos
Topeliuksenkatu 41 aA
00250 Helsinki
[email protected]
Kohila Tarja, jäsen
Viikki Lab. Animal Centre
PL 56
00014 Helsingin yliopisto
[email protected]
Katri Talvioja, jäsen
Orion Corporation Orion Pharma
PL 65
02101 Espoo
[email protected]
Rautio Arja, jäsen
Centre for Arctic Medicine
PL 7300
90014 Oulun yliopisto
[email protected]
Uudet toksikologiyhdistyksen jäsenet
Uusiksi jäseniksi hyväksyttiin:
Mirja Salkinoja-Salonen, University of Helsinki
Atso Raasmaja, University of Helsinki
Greta Catherine Waissi-Leinonen
Mahsan Rasaei, University of Eastern Finland
Virve Sihvola, HUSLAB/Myrkytystietokeskus
Anne Puustinen, TTL
Erik Peltomaa, FIMEA
Tervetuloa mukaan yhdistyksen toimintaan!
2/2012
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Orion’s Experiences from SafeSciMET Training Courses
The Innovative Medicines Initiative (IMI) is Europe's largest public-private partnership aiming
to improve the drug development process by supporting a more efficient discovery and
development of better and safer medicines for patients. IMI SafeSciMET is a new and unique
pan-European Education and Training programme, jointly supported by European Union and
EFPIA (European Federation of Pharmaceutical Industries and Associations). The program
covers all aspects of safety in drug development and targets safety scientists in the
pharmaceutical industry, regulatory authorities and academia. The aim of the program is to
bridge crucial gaps in the education and training of scientists evaluating the safety of drug
candidates and new medicines and to ensure that European drug safety scientists are at the
forefront of their field. Orion is one of the EFPIA Partners in the SafeSciMET Consortium.
A set of 20 core modules has been set together. All courses have a common format (set at 3
European Credit Transfer System ECTS). The courses consist of one week of on-site face-toface training concluded by an exam. Immediately subsequent to the week of on-site training,
students receive an individual home assignment and a case study, which have to be
completed within six weeks after the course. Modules can be taken as part of continuous
professional development (CPD) or participants can register for the full Master of Advanced
Safety Sciences (MASS) program.
More information can be obtained from website: www.safescimet.eu
SafeSciMET courses are open to all scientists from industry, academia and regulatory
authorities. The applicant normally possesses an MSc degree in a Life Science discipline and
are expected to have at least one year’s working experience in related discipline. Course fees
and discounts are dependent on employment; it is made especially attractive for scientists
from academia. A number of safety scientists from Orion have already participated on the
SafeSciMET courses. Below are comments from some attendees on the courses. In addition,
Stefan Karlsson shares his experiences as a course leader and teacher.
Marja-Leena Toivonen, Head of Nonclinical Safety Evaluation, SafeSciMET Steering
committee member
Teacher experiences
Stefan Karlsson, Nonclinical Safety Evaluation
SafeSciMET 3.3: Organ/Systems Toxicology, University of Constance
The previous knowledge and experiences in the field of safety assessment may vary a great
deal among the course participants and the fields of expertise are also very diverse. This puts
some challenges to the teachers. On the other hand the attendees are very committed and the
lecture environment is very interactive and open. Each course has several teachers and
teachers are encouraged to actively attend lectures and case studies given by other teachers.
When possible, teachers may stay for the whole course and by this concept each course
develops to a close discussion group around a specific scientific field. For a teacher the
course is therefore not solely about teaching but also an opportunity to discuss with and learn
from the course participants and co-teachers, both from universities and industries. The
lectures are of two types, firstly lectures of a specific topic and secondly case studies related
to the same topic. The case studies are either taken from the literature or real-life examples of
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safety problems. This means that the material produced by each teacher is quite
comprehensive and the teacher has to reserve time and efforts to collect the material. In each
course the teachers and the course leaders keep a number of teleconferences in good time
before the course to set up a logic entirety. The SafeSciMET uses an online platform
(Blackboard) located at the University of Utrecht where the teachers collect the course
material. This enables the teachers to see and comment each other´s material and to avoid
overlapping material. A few weeks before the course this platform is open for the registered
participants.
Pekka Heikkinen, Research scientist, In vitro biology
SafeSciMet 4.5 Mutagenesis and carcinogenesis, University of Vienna
The course covered mutagenicity and carcinogenicity mechanisms and different tests in great
detail. Experienced specialists guided the participants through the course. The topics started
from the basics of the mutagenicity in bacterial testing moving on to the in vitro mammalian
testing and covering error sources in the different tests. In vitro to In vivo extrapolation and
modelling, in silico and statistical methods were also discussed. The lectures also gave a view
to the predictive power of current in vitro tests. The different genotoxicity and carcinogenity in
vivo models, including transgenic animals, were discussed. Also new emerging techniques
such as Pig-A were covered.
The course material was very extensive, which meant long study days. The best part was the
discussion between regulators and industry representatives after each session. Even though
the material was excellent and the teachers had prepared the lectures very well, there was a
bit too much to digest in one week.
Katri Talvioja, Research scientist, Nonclinical Safety Evaluation
Course 1.1 Drug discovery and development, University of Copenhagen
The course covered all aspects of drug research from target validation up to the postmarketing phase and life-cycle management. Teachers were mainly from Danish pharmas
(Lundbeck, Leo pharma, Novo Nordisk) and had a practical approach on the topics with many
examples. I was already familiar with certain topics but for instance it was very interesting and
useful to hear about the business aspects and marketing points of view that are essential from
the very early phases on. This course stressed out the multidisciplinary nature of drug
discovery, development , manufacturing and marketing. The home assignment consisted of
comparing strategies of two pharmaceutical companies and how they prepare to face future
challenges.
SafeSciMeET 2.2 Regulatory requirements and guidelines, University of Lisbon,
This course was about the contents of various safety guidelines and the way the regulatory
bodies interpret them and look at the data submitted to them. The most important take home
message was: Discuss with your Regulator as early and as much as possible!
The faculty consisted of senior officers from the regulatory bodies and experienced fellows
from pharmaceutical industry (Novartis, Roche, Boehringer Ingelheim). The most interesting
part of the lectures was the faculty members challenging and questioning each other at the
end of the lectures. The home assignment was an imaginary case with a positive
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carcinogenicity finding for which we needed to put together the regulatory and scientific basis
for a company decision and the communication plan towards the authorities.
Chira Malmström, Research scientist, DMPK
SafeSci Met 2.3 Pharmaco/toxicokinetics and pharmaco/toxicodynamics, Uppsala University
This course was an intense course starting from basic PK/TK theory, very quickly moving to
more extensive in depth in vitro and in vivo DMPK integrating Pharmacodynamic and Safety
issues finally ending up with up-to-date thinking in pharma industry based on EFPIA partner’s
real cases for further processing. The lecturers were a good mixture from both academia and
industry and was pedagogically very well built, as each day/theme started with theory and
ended with implication of theory to practical real life cases.
The home assignment was to investigate the PK/PD (TK/TD) and the role of rather newly
identified particular DMPK mechanism in drug induced adverse event of a drug on market.
The course was excellently designed and inspiring, the home assignment was however on the
limit of being too extensive/time consuming and not so useful since eventually no feedback
was received.
SafeSci Met Course 6.1 Clinical Safety-Pre-Approval, Roche, Basel
This important course focused on the bridging between non-clinical and clinical safety data,
discussing/analyzing possible preclinical safety signals and the implications for clinical safety,
pin pointing out that patient safety is the most important issue at this stage. These case
studies were of particular interest since they were real pharma projects the nonclinical safety
data of which was analysed during the course first in small groups, then together with
lecturers to produce a syntax on recommendation (go/no go or how could proceed )
without risking patent safety. Likewise, possible clinical safety signals should be back
translated to nonclinical for “lessons learned” type cases. This course was an excellent
introduction into clinical safety thinking for a non clinical scientist. Some last minute
rearrangements had occurred for the organizer which unfortunately was reflected in the
uneven course material provided.
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33rd annual symposium of Finnish Society of Toxicology and abstracts
Environmental and ecotoxicology of pharmaceuticals and nanoparticles
16.-17.4.2012
Huhtikuussa 2012 pidettiin yhdistyksen 33. vuosittainen symposium, jonka teemaksi oli valittu
lääkeaineiden ja nanopartikkelien ympäristö- ja ekotoksikologia. Symposium järjestettiin
yhdessä Ympäristöterveyden tohtoriohjelman (SYTYKE), Suomen lääketutkimuksen
tohtoriohjelman (FinPharma) toksikologian jaoksen, Valuma-alueen ja vesistöjen tohtorikoulun
(Value) sekä Ympäristötieteen ja tekniikan (EnSTe) tohtoriohjelman kanssa. Yli 60 aiheesta
kiinnostunutta saivat nauttia korkeatasoisista tieteellisistä esitelmistä sekä posteriesityksistä.
Yhteensä tieteellisiä esityksiä oli n. 20. Symposium oli jaettu painotukseltaan kahteen
teemaan. Ensimmäisenä päivänä esitykset keskittyivät lääkeaineisiin sekä ilmansaasteisiin ja
toisena päivänä painotus oli nanopartikkeleissa. Kumpanakin päivänä aihepiirit alkoivat
perustutkimuksen parista ja kulkivat siitä testaamiseen, riskinarviointiin sekä osittain myös
hallinnollisiin kysymyksiin. Samalla saimme päivitettyä tietoa haitta-aineiden lähteistä ja
pitoisuuksista ympäristössä. Symposiumin kruunasi maittava ja lämminhenkinen
kokousillallinen, jossa jatkuivat jo tieteellisen ohjelman aikana alkaneet tieteelliset keskustelut.
Kiitokset kaikille symposiumin osallistuneille ja erityiskiitos järjestelyissä mukana olleille.
Kokouksen abstaktit:
Regulatory testing and assessment of nanomaterials
Jukka Ahtiainen
The safety assessment of nanomaterials (NMs), as well as any substance, is relaying on the testing of the
intrinsic properties, fate and biological effects of the substance. Hence the basic tools, the test guidelines and
methods for testing chemicals are of fundamental importance. Another important step is the interpretation of the
testing results, and whether they properly address the information requirements set down in regulations and also
checking the data quality. It is clear that NMs have features and intrinsic properties which require additional
guidance both for the testing and the safety assessment.
OECD Test Guidelines and EU test methods
The "traditional" test guidelines have been developed and validated to be used for the hazard identification and
risk assessment of several kinds of chemicals e.g. industrial chemicals, pesticides, biocides and veterinary drugs.
But are any of these existing test guidelines applicable to the regulatory testing of nanomaterials? The OECD
guidelines for the testing of chemicals (TGs) have been widely used for regulatory purposes all over the world
since the establishment of the Mutual Acceptance of Data (MAD) principle in 1981. This principle ensures that, if
a chemical or substance is tested accordingly to an OECD test guideline under GLP (Good Laboratory Practice),
the data should be accepted in all OECD countries. The rationale behind this agreement has been to save
resources and to avoid unnecessary duplication of vertebrate testing. These TGs are then adopted to the EU
Test Method Regulation (EU 440/2008) if there is a regulatory need for them in EU legislation. The current test
methods for testing chemicals mainly cover the assessment of phys-chem properties, environmental fate (e.g.
degradation and bioaccumulation) and biotic effects (ecotoxicity and toxicity).
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General applicability of current tests protocols
There have been surveys on the availability and applicability of existing test methods for ecotoxicological
assessment of nanomaterials [1]. It can be generally concluded that the general biological "endpoints" measured
in many test guidelines e.g. reproduction are relevant for nanomaterials. However, it has been reported that
different techniques of dosing the nanomaterial to the test system (e.g. use of solvents, sonication, stirring) will
affect the response and that current guidelines do not provide sufficient direction on this. The published studies
on the ecotoxicity of nanomaterials have also been critically reviewed [2], which revealed that the test conditions
during the exposure e.g. pH and organic matter content have effects on the aggregation of the nanomaterial and
hence on its bioavailability [3]. In addition, test media composition and physicochemistry is also likely to affect the
functionalization of particular types of nanomaterials, which could affect their subsequent behaviour and toxicity
[4]. In principle, most of the global "endpoints", or more precisely measurement variables, are applicable to
nanomaterials effects assessment. However, both the dosage of the test material and the verification of the
exposure by detection and characterization (mass, particle size distribution, surface area, zeta potential) of the
material in the test media and, potentially, in the test organism need specific guidance, in order to gain regulatory
relevant data. In addition, as test protocols may have to be adapted for testing individual nanomaterials, will this
test the principle of mutual acceptance of data? The test conditions e.g. organic matter content during the test,
will affect the form and bioavailability of the nanomaterial, and detailed guidance is needed on the test conditions,
or at least the conditions during the test should be documented very carefully in order to receive comparable and
understandable results. This would enable the proper use of test guidelines under the MAD principle for the
regulatory purposes.
OECD review of existing test guidelines and guidance development
The existing OECD test guidelines have been reviewed in the light of their applicability for testing the
nanomaterials under the OECD Working Party of Manufactured Nanomaterials (WPMN) [5]. For this review four
subgroups evaluated the guidelines for: physico-chemical characterization, effects on environmental biota,
environmental fate and health effects. The tasks of the subgroups also included a search for a possible guidance
for nanomaterial testing, to propose possible modifications to the existing test guidelines and to identify needs for
new methods.The applicability of these methods to the testing of nanomaterials was evaluated in the light of
published literature. The limited number of studies published to date do not yet provide enough knowledge to
develop fixed guidance on how to approach the dosimetry of nanomaterials or modify existing test methods when
testing nanomaterials. However, these previous studies did indicate the directions: What could be done and what
should not be done. A preliminary conclusion possible from the work undertaken to date is that any guidance on
the dosimetry and exposure of nanomaterials for testing in ecotoxicology could and maybe should be the same
for both effects and bioaccumulation studies. At the same time of the test method reviews the OECD WPMN has
prepared a strategy for testing a representative set of nanomaterials, including 13 materials. The purpose of this
testing exercise is primarily to gain explorative data on the possible hazards of the selected nanomaterials, but
also to evaluate the applicability of the existing OECD test guidelines for nanomaterial testing. After finalizing this
explorative phase 2012, it is hoped that better guidance on dosimetry and test designs can be established. It
should also be possible to understand how the testing of nanomaterial versus corresponding bulk material differs.
OECD has also developed and published the Preliminary Guidance Notes on Sample Preparation and Dosimetry
[11] in order to guide the practical testing of above mentioned testing groups. This guidance has been currently
(2012) updated. Some of the practical considerations for conducting ecotoxicity testing with nanomaterials are
compiled also in Handy et al. 2012 [12]. Eventually, more specific technical guidance (e.g. OECD Guidance
documents) is needed for toxicity testing in various environmental compartments or for different routes of
exposure in toxicology (e.g. inhalation toxicity).
EU guidance for the safety assessment under the REACH
We have the basic tools (test methods) as stated above, and they seem to be mostly adequate to address most
of the data requirements set down in REACH. More harmonised guidance should be developed how to use the
test guidelines and how to verify the exposure to the substance during the tests. Some of these "nanorelevant"
issues should be also included also in the guidance for the safety assessment in the substance registration
guidance. It seems that at least for the ecotoxicity and environmental fate assessment the endpoints or
measurement variables are adequate. The science has indicated some "nano-relevant" endpoints e.g. heart rate
in Daphnia, mucus excretion in fish gills, effects seen in bronchious alveoli lavage analysis (BAL) in inhalation
studies or ROS reactions in tissues, but these are hardly "nano-specific" as also other substances can cause
them. However, it is clear that totally new internationally harmonised methods are needed for the physicalchemical characterization of the nanomaterials. There has been a lot of debate on the substance identification
regards to nanomaterials and their registration. Whatever the decision would be on the registration (separate or
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together with the bulk substance), it is clear that the nanoform safety should be addressed separately and
adequately.
References
[1] Crane, M., Handy, RD, Garrod, J and Owen R. 2008. Ecotoxicity test methods and environmental hazard
assessment of engineered nanoparticles. Ecotoxicology 17: 421-437.
[2] Klaine, SJ, Avarez, PJJ, Batley, GE, Fernandes, TF, Handy, RD, Lyon, DY, Mahendra, S, McLaughlin, MJ,
and Lead, JR, 2008. Nanomaterials in the environment: behaviour, fate, bioavailability, and effects.
Environmental Toxicology and Chemistry, 27:1825-1851.
[3] Baalousha, M., Manciulea, A., Cumberland S., Kendall, K. and Lead, J.R. 2008. Aggregation and surface
properties of iron nanoparticles: influence of pH and natural organic matter. Environmental Toxicology and
Chemistry, 27:1875-1882.
[4] Canas, JE, Long, M, Nations, S, Vadan, R and Dai, L. 2008. Effects of functionalized and nonfunctionalized
singlewalled carbon nanotubes on root elongation of select crop species. Environmental Toxicology and
Chemistry, 27:1922-1931.
[5] OECD 2009. Preliminary Review of OECD Test Guidelines for their Applicability to Manufactured
Nanomaterials. Organization for Economic Coordination and Development Paris, France.
[6] OECD 2008. OECD Test Guideline 225. Sediment-water Lumbriculus toxicity test using spiked sediment.
Organization for Economic Coordination and Development Paris, France.
[7] OECD 1996. OECD Test Guideline 305. Bioconcentration: Flow-through Fish Test. Organization for Economic
Coordination and Development Paris, France.
[8] Fisk AT, Norstrom RJ, Cymbalisty CD, Muir DCG. 1998. Dietary accumulation and depuration of hydrophobic
organochlorines: Bioaccumulation parameters and their relationship with the octanol/water partition coefficient.
Environ Toxicol Chem 17:951-961.
[9] Stapleton HM, Letcher RJ, Li J, Baker JE. 2004. Dietary accumulation and metabolism of polybrominated
diphenyl ethers by juvenile carp (Cyprinus carpio). Environ Toxicol Chem 23:1939-1946.
[10] OECD 2010. OECD Test Guideline 317. Bioaccumulation in terrestrial oligochaetes. Organization for
Economic Coordination and Development Paris, France.
[11] OECD 2010. Preliminary Guidance Notes on Sample Preparation and Dosimetry for the Safety Testing of
Manufactured Nanomaterials. Organization for Economic Coordination and Development Paris, France.
[12] Handy, R.D., van der Brink, N., Chappel, M., Mühling, M., Behra, R., Dusinska, M., Simpson, P., Ahtiainen,
J., Jha, A.N., Seiter, J., Bednar, A., Kennedy, A., Fernandes, T.F. and Riediker, M. 2012. Practical considerations
for conducting ecotoxocity test methods with manufactured nanomaterials: what have we learnt so far?
Ecotoxicology DOI 10.1007/s 10646-012-0862-y, http://www.springerlink.com/content/46323q13m57gr61r/
Eco in ecotoxicology?
Jarkko Akkanen
University of Eastern Finland, Department of Biology, Joensuu campus, P.O.Box 111, Joensuu, Finland,
[email protected]
The term ecotoxicology was first introduced by Truhaut 1969, from where started the development of the field.
Obviously eco stands for ecology and ecotoxicology has been defined as the study of effects of chemicals on
populations, communities and ecosystems. This extends toxicology and environmental toxicology, which are
many times defined to focus on individual level and below, to higher levels of biological hierarchy. Ecotoxicology
has strong toxicological background and thus it is still very much driven by environmental toxicologists and
chemists. It is also quite much laboratory oriented. LC50 and EC50 values are used to protect ecosystems in real
life situations, which mean quite brave extrapolations across species, environmental conditions and biological
interactions. Lethality and acute effects dominate in testing, which is seldom the case in real field situations.
Exposure route is not necessarily water as mostly expected in testing. Tests are conducted with single species
neglecting possible changes in trophic interactions. Therefore, true evaluation of community and ecosystem level
effects is extremely difficult. These challenges would need also input by ecologists. Yet, in many cases ecologists
and ecotoxicologists are quite far from each other. More ecology is needed in ecotoxicology to truly live up to the
expectations about protecting natural ecosystems and also avoid overprotection. However, ecology alone cannot
provide all the answers. In order to relate effects in ecosystem level to a certain chemical or chemical group we
need toxicological knowledge.
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Triclosan, contained in personal hygiene products, is spermtoxic and impairs mitochondrial functions in
somatic cells.
1
1,5
2
4
3
Maria A. Andersson , Vera V. Teplova , Carl G. Gahmberg , Merja Roivainen , Leif C. Andersson , Christine
6
1
Ek-Kommonen and Mirja Salkinoja-Salonen
1
Department of Food and Environmental Sciences, Biocenter I, Viikinkaari 9,
2
Dept of Biosciences (Biochemistry), Biocenter 2, POB 56 and the
3
Haartman Institute (Pathology), Haartmannink 3, POB21, Helsinki University, FI 00014, Finland
4
The National Institute of Health and Welfare, Laboratory for Virology, Mannerheimintie 166, FI00300 Helsinki,
Finland
5
Institute of Theoretical and Experimental Biophysics, RAS, Pushchino, Moscow Region, RU-142290, Russia
6
Dept of Virology, Finnish Food Safety Authority, Mustialankatu 3, FI 00079 Helsinki, Finland
The antibacterial preservative 2,3,3’-trichloro-2’-hydroxydiphenyl ether (mol. wt. 289.5), trivial names triclosan
and irgasan, introduced in health care industry in 1972 and since then in wide spread use in personal care
products, textiles, food contact materials. Triclosan was approved in 1986 by the European Community Cosmetic
Directive in cosmetic products at concentrations up to 0.3% w/w. Its usage in Europe is estimated as ca. 450 000
kg per year. It is poorly biodegradable, lipophilic (log Kow 4.76), bioaccumulates in biota (BCF = 2.5) and is
rapidly taken up by the skin. Triclosan is presently found almost everywhere in the environment and also in
humans, including breast milk. Its effects on metabolic functions of mammalian cells have not been studied at
any systematic level. We report here adverse effects of triclosan on mitochondrial and non-mitochondrial
functions of human peripheral blood mononuclear cells (PBMNC, from healthy donor blood), porcine
spermatozoa and porcine kidney epithelial cells (PK-15), human keratinocytes (HaCaT) , murine insulinoma
(MIN-6) and neuroblastoma cells (MNA). Spermatozoan motility was inhibited and the mitochondria depolarized
by exposure to 1 µg ml-1 of triclosan. 12 – 24 h exposure to 4 – 8 µg ml-1 of triclosan caused depolarization of
mitochondria in PBMNC, PK-15 cells, HaCaT cells and MIN-6 cells and extension to 48 h caused excessive
glucose consumption and metabolic acidosis . Plasma membrane permeability barrier function remained intact
up to exposures of 30 µg ml-1. The spermatozoa and insulin-producing cells (MIN-6) lost the mitochondrial
membrane potential and underwent necrotic cell death at exposure concentrations 4 times lower than
keratinocytes, kidney epithelial or the human blood mononuclear cells (PBMNC) . The results show that exposure
concentrations likely to result from use of triclosan containing consumer products, have potential of causing toxic
damage mammalian cells and that spermatozoa and insulin producing cells were particularly sensitive.
EU fish II ; Environmental pollutants in Baltic fish and other domestic fish: PCDD/F, PCB, PBDE, PFC and
OT compounds
Anja Hallikainen, Riikka Airaksinen, Panu Rantakokko, Jani Koponen, Jaakko Mannio, Pekka J.Vuorinen, Timo
Jääskeläinen, Hannu Kiviranta
The EU FISH II project was launched to obtain information on current levels of polychlorinated dibenzo-p-dioxins
(PCDD/F) and polychlorinated biphenyls (PCB) as well as polybrominated diphenylethers (PBDE) in Baltic fish,
domestic freshwater fish and farmed fish. The EU fish II project was coordinated by the Finnish Food Safety
Authority Evira. Variations in the levels were studied by age and size of the fish as well as by species and areas.
Analyses of the presence of perfluorinated compounds (PFC) and organotin compounds (OT) in muscles and
liver were also carried out within the scope of the project. The 2009 results were compared with the results of the
previous project conducted in 2002-2003. Analyses of PCDD/F and PCB levels in fish highlight the same species
that have also previously been found to be susceptible to accumulation of these environmental toxins. Baltic
herring, salmon and sea trout as well as river lamprey and now in this study also European flounder and old
bream in Kotka area show levels of PCDD/F and PCB compounds exceeding the maximum stipulated limits. In
Baltic fish, the median levels of dioxin equivalents in sprat, vendace, perch, pike, pikeperch, burbot and cod are
not even half of the permitted maximum level, which is 3.5 pg/g of fresh weight. The comparison of the levels
measured in 2002-2003 with the 2009 levels of PCDD/F and PCB as well as PBDE compounds shows that the
mean levels have decreased in salmon and herring. Dioxins and dioxin-like PCB compounds are still the worst
contaminants in the Baltic Sea. The OT levels measured in the muscles of open sea fish were about one third
lower than in the fish samples caught in 2005–2007. The levels of PBDE, PFOS and OT were low, with a few
exceptions. The Bothnian Sea and the fishing areas of Pori, Turku and Kotka took the lead in the contamination
ranking, but the worst area was Vanhankaupunginlahti Bay of Helsinki, where both OT and PFOS levels give
cause to recommend consumption restrictions, at least as far as large perch are concerned. New data on the
content of hazardous substances in fish were obtained for use in risk management and exposure assessment.
Finally, the project will provide data for dietary advice regarding the potential risks associated with the
consumption of contaminated fish among the most sensitive groups of the Finnish population.
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Effects of deltamethrin on excitability and contractility of the rainbow trout (Oncorhynchus mykiss) heart
Haverinen, J. and Vornanen, M.
University of Eastern Finland, Department of Biology, Joensuu, Finland
Email: [email protected]
Pyrethroids are extensively used for the control of insect pests and disease vectors. Usefulness of pyrethroids is
based on their selective toxicity: they are very effective against insects but relatively harmless to mammals and
birds. Unfortunately, pyrethroids are very toxic to fishes. The high toxicity of pyrethroids to fishes is only partly
explained by slow detoxification rate, suggesting that affinity of pyrethroids to their molecular targets, the Na+
channels, contributes to toxicity. This study tests the hypothesis that the piscine Na+ channels are more sensitive
to a type II pyrethroid, deltamethrin (DM), than are the mammalian Na+ channels. In ventricular myocytes of the
rainbow trout (Oncorhynchus mykiss) heart DM (10- 7-10-5 M) modified Na+ current by slowing inactivation and
shifting the reversal potential of the current to the left. Maximally 27 ± 4% of the cardiac Na+ channels were
modified by DM and the half-maximal effect occurred at the concentration of 1.1 µM. The effect of DM on trout
cardiac Na+ channels is stronger and occurs about an order of magnitude lower concentration in comparison to
the orthologous mammalian Na+ channels. In sinoatrial preparations in vitro DM (10 µM) caused irregularities in
rate, rhythm and force of atrial beating suggesting that DM is arrhythmogenic in the trout heart. Consistent with
this, DM (>0.1 µM) induced spontaneous action potentials in otherwise quiescent ventricular myocytes. DM (10
µM) did not affect calcium current or inward rectifier and delayed rectifier potassium currents. Collectively, these
findings indicate that DM exerts toxic effects on trout heart, and suggest that the higher sensitivity of fishes to
pyrethroid insecticides in comparison to mammals and birds is partially due to the higher affinity of their Na+
channels to pyrethroids.
Keywords: pyrethroids, deltamethrin, rainbow trout, heart, sodium current, excitationcontraction coupling, cardiac
arrhythmias
Mapping the Dawn of Nanoecotoxicology
Anne Kahru
National Institute of Chemical Physics and Biophysics, Lab. Molecular Genetics, Tallinn 12618, Akadeemia tee
23, Estonia, E-mail: [email protected]
Currently, in the conditions of the worldwide global economic recession, exponential growth of population,
shortage of food, feed, fuel and raw materials and increasing environmental and societal problems,
nanotechnologies have big expectations in almost every domain, from energy production to medicine. Moreover,
nanotechnology has been referred to as the next industrial revolution. Currently, the scientific information on
nanoparticles doubles every 2.5 years while information on nanomaterial safety is slower to evolve. Due to the
fast development of nanotechnologies, the likelihood of occupational and environmental contact increases.
Despite being a relatively new discipline, less than 10-years old, nanoecotoxicology faces important and
challenging problems – analysis of the safety of nanotechnologies to the natural environment. The
ecotoxicological research on nanomaterials lags more than 20-years behind the research of nanomaterial
technological applications. Thomson Reuters ISI Web of Science demonstrates that there is currently more than
160,000 papers on nanoparticles. However, for every 1,000 papers on nanoparticles, there is about 10 papers on
their toxicological and 1 paper on ecotoxicological aspects. Since its emergence at 2005, the importance of
nanotechnology environmental and health research has gradually increased, to the extent that the top-cited
papers in the environmental disciplines now frequently focus on nanoparticles. The challenges of
nanoecotoxicology due to the diverse nature of this area of research - hazard of chemicals to ecosystems - and
inherent complex nature of nanomaterials compared with ’regular’ soluble chemicals will be also discussed.
This work has been supported by SF0690063s08 and ETF8561
References:
Kahru, A., Dubourguier, H.-C., 2010. From ecotoxicology to nanoecotoxicology. Toxicology 269, 105-119.
Kahru, A., Ivask, A., Kasemets, K., Blinova, I., 2011. Nanotoxicology: science at the interfaces. Estonian
perspective. In: Research in Estonia. Present and future; J. Engelbrecht, G. Varlamova, Eds.; Estonian Academy
of Sciences, Tallinn, Estonia, 346-367. Online available at:
http://www.akadeemia.ee/_repository/file/PUBLIKATSIOONID/2011/Recearch_in_Estonia.pdf
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Emerging environmental contaminants in wastewater effluents – pharmaceutical’s residues and
engineered nanoparticles: effect on the wastewater treatment and antibiotic resistance gene transfer in
the environment
1
1
2
2
Kaja Kasemets , Anne Kahru , Marika Truu and Jaak Truu
1
National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn Estonia
2
University of Tartu
Introducing of the European Union European Regional Development Fund Project (2012–2015)
“Pharmaceutical’s residues and engineered nanoparticles: effect on the wastewater treatment and antibiotic
resistance gene transfer in the environment”. Partners: University of Tartu; National Institute of Chemical Physics
and Biophysics; Estonian University of Life Sciences.
Introduction: Nanotechnologies and health care are two rapidly developing areas of the society. This developing
in paralleled by the increased use of (i) pharmaceuticals and antibiotics and (ii) synthetic nanoparticles. Indeed,
several manufactured nanoparticles (NPs) (e.g. metallic NPs as nAg, nZnO and TiO2) are increasingly used in
different consumer products. As a result, the risk of end-up of antibiotics and nanomaterials in the wastewater
effluents and treatment plants increases. Both, pharmaceuticals and NPs, separately or in tandem may pose
threats on the wastewater treatment effectiveness as well as to spread of antibiotic resistance genes into the
environment. Moreover, the dispersal of contaminated sewage sludge into the soil may spread these toxic
substances into groundwater and sub-surface water systems and create possibility for their bioaccumulation in
organisms. The long term goal of the current project is to investigate how the antibiotic residues and
nanomaterials may act separately or in tandem on the microbial community of wastewater treatment system
and the wastewater treatment effectiveness both in the laboratory and pilot scale conditions.
The main objectives of this project are to: (1) evaluate the separate and tandem effect of antibiotics residues
and nanoparticles on the wastewater treatment effectiveness and microbial community of treatment system, (2)
evaluate the separate and tandem effect of antibiotics residues and nanoparticles on the composting
effectiveness of contaminated (spiked) sewage sludge, (3) study the development of antibiotic-resistant bacteria
in wastewater treatment system, (4) profile the antibiotic resistance gene transfer in the effluents of different
Estonian wastewater treatment plants.
Methods: Two metallic NPs will be studied: nano-ZnO and nano-Ag as the both NPs growingly used in
consumer and medical products. To differentiate the toxic effect of nanoparticles and soluble metal ions, the
bioavailable fraction of the metals will be quantified by recombinant metal-specific microbial sensors. For toxicity
testing of composted contaminated (spiked) sewage sludge, the photobacterial Vibrio fischeri Solid-Phase FlashAssay and seed germination and growth inhibition test with higher plants sorghum Sorghum saccharatum and
mustard Sinapis alba will be used. Laboratory and pilot-scale biofilm based wastewater treatment systems will be
used for studying the impact of antibiotic residues and nanoparticles on microbial community structure, treatment
efficiency and formation of antibiotic resistance pattern in the system. Pilot-scale wastewater treatment systems
allow running up to 27 parallel mesocosms simultaneously. Changes in microbial community structure will be
assessed using next-generation sequencing approach and antibiotic resistance genes will be quantified using
real-time PCR.
Experiments: We have conducted preliminary experiments in pilot-scale wastewater treatment system fed with
municipal wastewater in order to assess the temporal dynamics of microbial community structure and antibiotic
resistance gene abundances in the biofilm.
This work has been supported by the European Union European Regional Development Fund Project,
SF0690063s08, SF0180127s08, ETF8561, ETF8066 and ETF9001.
Risk assessment of non-dioxin-like PCB 180 and PCB 52 present in food
1
2
1
Merja Korkalainen , Helen Håkansson , Matti Viluksela
1
National Institute of Health and Welfare, Department of Environmental Health, Kuopio, Finland;
2
Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden
PCBs 180 and 52 are abundant non-dioxin-like (NDL) PCB congeners that accumulate in the food chain, and
represent a large portion in technical PCB mixtures, human adipose tissue and mother’s milk. This study
evaluated the endocrine system characteristics of PCBs 180 and 52 following 28-day and in utero/lactational
exposure in rats. The corresponding risks were characterized by comparing maternal adipose tissue
concentrations with human tissue levels. The risk characterization was performed using the margin of exposure
(MoE) concept and utilized uncertainty factors in calculations of tolerable concentrations in human milk and
adipose tissues. The most sensitive effects identified by benchmark dose modelling were retinoid system
modulations in addition to effects on thyroid and steroid hormones. The MoEs for PCB 180 were 120-640 in
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general population and breastfed infants. The MoEs in Baltic Sea fishermen consuming large amounts of
PCBcontaminated fish were 24-63. The limit of tolerable concentration was exceeded among the most exposed
fishermen, while the median exposure levels of both PCB 180 and 52 were acceptable in general population and
breastfed infants. Thus, with the exception of fishermen with the highest tissue concentrations, the existing
exposure levels of PCB 180 or PCB 52, individually, should not raise concern, based on the analysed end-points.
Acknowledgements. This TRISK applied training project was based on data from the European Commission
funded ATHON project (FOOD-CT-2005-022923). The original data will be or have been published separately.
All data providers are gratefully acknowledged.
Significance of pharmaceuticals in the aquatic environmental:Stability and bioavailability
Leif Kronberg, Åbo Akademi University, Finland
Pharmaceuticals are excreted by humans mainly through the urine, which will subsequently be collected in the
waste water. The waste water is passed to municipal waste water treatment plants (WWTPs) where the
pharmaceuticals are subjected to biotransformation/biodegradation reactions and to adsorption to the sludge.
The extent of the bioreactions and adsorption is dependent on the physic-chemical properties of the individual
compounds. Some pharmaceuticals, like diclofenac (DCF) and carbamazepine (CBZ) are reluctant to
biotransformation and are also too polar to be adsorbed and hence found in the effluent and recipient water.
Others, like ibuprofen (IBF) are eliminated to over 90% in the treatment plants and should be not occur in the
effluent water. But in the case of IBF, the rate of elimination is not high enough to counteract the elevated
concentration of the compound in the influent water and the consequently the compound is found in recipient
waters. As said, DCF is not undergoing biotransformation, but in the aquatic environment, the compound is
readily subjected to photochemical transformation reactions initiated by the UVlight of the sun. The consequence
is that DCF undergoes intramolecular reactions, rearrangements, and new entities are produced, whose
environmental significance is unknown. Many other pharmaceuticals are “eliminated” through photo
transformation reactions. An issue of great importance is the bioavailability of pharmaceuticals in the aquatic
environment. There is one study showing that traces of anti-depressive pharmaceuticals can be found in the
muscle and the brain of wild fish living in a river containing waste water. We have carried out search for
pharmaceuticals in the bile of fish exposed to pharmaceuticals in aquaria, in cages downstream the discharge
point of WWTPs, and in wild fish caught in a lake where part of the water is waste water. The aquaria study
showed that a large number of metabolites of DCF, naproxen (NPX) and IBF are collected in the fish bile, the
“cage study” showed that fish kept downstream WWTPs take-up pharmaceuticals and finally, the work with wild
fish proved that also these are accumulating pharmaceuticals (DCF, NPX, and IBU) in the bile. This is the first
study showing that anti-inflammatory drugs are bioavailable to wild fish.
Aquatic effects and fate of nanomaterials in the Nordic environment
Jussi Kukkonen
Department of Biological and Environmental Science University of Jyväskylä and Department of Biology
University of Eastern Finland
Examples of effects of fullerene and nanosilver in water or sediment tests on Daphnia magna and two benthic
organism, Lumbriculus variegatus (Oligochaeta) and Chironomus riparius larvae, are presented and discussed.
Fullerene agglomerates were prepared using a water stirring method. Fullerene accumulation into D. magna was
rapid during the first few hours, and based on accumulation modeling, 90% of the steady-state concentration was
reached in 21 h. After exposure for 24 h to a 2 mg/L fullerene solution, the daphnia accumulated 4.5 g/kg wet
weight. Daphnids exposed to 2 mg/L fullerenes for 24 h eliminated 46 and 74% of the accumulated fullerenes
after depuration in clean water for 24 and 48 h, respectively. Transmission electron microscopy revealed that the
majority of the fullerenes present in the gut of daphnids were large agglomerates. L. variegatus were exposed to
10 and 50 mg fullerenes/kg sediment dry mass for 28 d. These concentrations did not impact worm survival or
reproduction compared to the control. However, feeding rates were slightly decreased for both concentrations
indicating fullerenes’ disruptive effect on feeding. C. riparius were exposed after allowing suspended fullerenes to
settle down creating a layer of nC60 on top of the sediment, another environmentally realistic exposure method.
Two different feeding levels were used. In the 0.5 % food level treatment, there were significant differences in all
growth-related endpoints for fullerene exposed organisms compared to controls. Fewer effects were observed for
the higher food treatment. Fullerene agglomerates were observed by electron microscopy in the gut but no
absorption into the gut epithelial cells was detected in either organism. Electron micrographs of L. variegatus also
indicated that 16 % of the epidermal cuticle fibers of the worms were destroyed in the 50 mg/kg exposures, which
may make worms susceptible to other contaminants. For C. riparius, microvilli were damaged and significantly
shorter.
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Antibiotic contamination and antibiotic-resistant bacteria in Baltic Sea aquaculture
Windi Muziasari, Antti Karkman, Manu Tamminen, Ogo Mitsuko, Satoru Suzuki, and Marko Virta
Dept. of Food and Environmental Science, University of Helsinki, Helsinki, Finland
Center for Marine Environmental Studies, Ehime University, Matsuyama, Japan
e-mail: [email protected]
Aquaculture environment has been suggested to be a reservoir of antibiotic resistance genes due to prophylactic
and therapeutic use of antibiotics. It has been observed that antibiotic resistance genes are
persistent
in
the sediment below aquaculture even in the absence of selection pressure. Here, HPLC analyses were
conducted to monitor the selection pressure in the sediment aquaculture farms and amount of tetracycline
resistance genes was measured by quantitative PCR. Sediment samples were collected from two medium sizes
of marine fish farms and pristine areas in the northern Baltic Sea during summer time for six successive years.
HPLC measurements revealed a high concentration of oxytetracycline in the sediment samples of 2011 which
suggests the presence of a selection pressure in the aquaculture farm sediment for tetracycline resistance.
Teracycline and oxytetracycline concentration were low in all other sampling times. The number of tetracycline
resistance genes was elevated in all farm samples but not in pristine samples taken from similar area. In future
studies, resistant bacteria from sediment, fish feeds, and fish guts will be isolated by using dependent-bacterial
culture methods to further clarify the relation between resistant bacteria and fish pathogens.
Different waters – different fates of fullerene: Fullerene’s agglomeration in four natural freshwaters
1
2
1
1, 3
K. Pakarinen , E. Petersen , J. Akkanen , J.V.K. Kukkonen
1
University of Eastern Finland, Department of Biology, PO box 111, 80101 Joensuu, Finland
2
Biochemical Science Division, National Institute of Standards and Technology (NIST), Gaithersburg, USA
3
University of Jyväskylä, Department of Biological and Environmental Sciences
Fullerene’s ability to form stabile water suspension by agglomeration allows fullerene to remain in water phase
for weeks or months. This may increase the exposure of aquatic organisms as well as enhance the transport in
aquatic systems. In the presence of dissolved natural organic matter (DNOM) the situation will become more
complicated. Enhanced stability of fullerene in water with DNOM has shown in several studies. On the other
hand, there is also evidence that the presence of DNOM may cause more fullerenes settling to the bottom.
Different target organisms are achieved by these opposed behaviors: fullerene may be available either to pelagic
or benthic organisms. Fullerene’s agglomeration behavior in four kinds of natural waters with differing quality and
quantity of DNOM and artificial freshwater (AFW) without DNOM was under investigation. Fullerene’s stability in
water phase varied between tested waters: in one of the examined natural waters fullerene was found in water
phase in remarkable concentrations after one year, whereas in one other water fullerene concentration was
plunged to few per cent compared to initial concentration in days. According to these findings it is critical to
understand fullerene’s behavior in real environment when assessing the targets of risks, which fullerenes may
cause if they are released into environment.
How to regulate and assess the environmental risk of pharmaceuticals
Markku Pasanen. University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy, POBox 1627,
70211 Kuopio, Finland
According to the European Directives and National legislation, prior to marketing, an environmental risk
assessment (ERA) has to be carried out for all new medicinal products – both human or veterinary drugs, via
centralised, decentralised, mutual recognition or national procedures (Article 8(3) of Directive 2001/83/EC;
Directive 92/18/EC). In addition, variations for old products - such as indication widening - will require an up-date
of environmental risk assessment. The directive does not include manufacturing processes of pharmaceuticals
which are under different legislation. Based on the directives, the European competent authority, EMA, has
provided guidelines on how to approach ERA from the regulatory point of view. However, for human medicines,
the ERA assessment can never prohibit the marketing authorisation of a new medicinal product on the ERA
alone; the overall benefit/risk ratio is the determining factor for marketing approvals. For veterinary medicinal
products, the ERA is much more demanding than for human pharmaceuticals. For instance, the equations used
in ERA calculations are much more complicated, with several variables (targeted animal species, geographical
location, food chains etc.) not needing to be considered for human pharmaceuticals. Moreover, for veterinary
products, the ERA guidance has been realised up to the global level via the International Congress for
Harmonization document.
References
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CHMP Guideline on the environmental risk assessment of medicinal products for human use CVMP Revised
guideline on environmental impact assessment for veterinary medicinal products in support of the vich guidelines
gl6 and gl 38 CVMP/VICH Topic GL6 (Ecotoxicity Phase I). Guideline on Environmental Impact Assessment
(EIAs) for Veterinary Medicinal Products - Phase I, CVMP/VICH/592/98-FINAL, London, June 30 2000
CVMP/VICH Topic GL38. Guideline on Environmental Impact Assessment for Veterinary Medicinal Products Phase II, CVMP/VICH/790/03-FINAL, London, October 2005
Environmental Impact of Micropollutants Present in Urine – Developing Countries Perspective
M.Sc. Sanna Pynnönen*, Prof. Tuula Tuhkanen, Tampere
University of Technology *Department of Chemistry and Bioengineering, P.O. Box 541, 33101
Tampere, Finland, E-mail address: [email protected], Telephone: +358 401 981 144
Urine comprises only about 1 % of the wastewater each person produces in a day. Yet, it contains most of the
nutrients and micropollutants which arrive as diluted wastewater stream from households to the wastewater
treatment plant. Micropollutants are defined as compounds with molecular weight of 200 to 500/1000 Da and
being present in the aquatic environment at µg or ngL-1 range. Pharmaceutical compounds are knowingly
designed to affect biochemical and physiological functions of biological systems in humans. Nonetheless, they
can also elicit biochemical and physiological changes in soil, plants and aquatic organisms. Most of the
pharmaceuticals humans consume are excreted via urine (partly via faeces) as unchanged parent compound or
as metabolites. Urine diverting toilets (NoMix-technology) enable the use of human urine as an effective fertilizer.
However, urine is not legally recognized as fertilizer e.g. by EU legislation. One obstacle is that there is not
enough knowledge about the disadvantageous actions these compounds may elicit in crop plants. The problem
is even bigger in developing countries, where no adequate sanitation system is available. Yet, people consume
large amounts of antiamoebiasis and antiprotozoal pharmaceuticals as well as drugs designed to treat HIVinfections. Based on studies, many micropollutants have been detected in aquatic environment, and some
analyses have reported their accumulation in soils that have been irrigated with wastewater. There are no data
available on how these compounds used widely in developing countries will behave in soils and plants or do they
inflict negative effects in humans or other organisms when released into the environment. More knowledge is
needed on the (i) negative effects of pharmaceutically active ingredients, the (ii) possible risk caused by leaching
and infiltration of them into the groundwater and (iii) ways to remove them prior to utilizing source separated urine
as a fertilizer.
Organic pollutants and pharmaceuticals in digestates from three biogas plants in Finland
Suominen K., Torniainen M., Maunuksela L., Jalava T., Salo T., Paavola T., Sagizbaeva O., Ranta J., Lehto M.
Biogas technology is a competitive process for managing biodegradable waste and by-products from
communities, industry and agriculture. Use of biogas plant digestates as fertilizer is in prior importance in
recycling depleting nutrients such as phosphorus and supporting organic material for maintaining growth
capability of agricultural soils. However, biogas plants digestates may contain organic pollutants originating from
their raw materials. In this study, concentrations of polyaromatic hydrocarbons (PAH), polychlorinated dibenzopdioxins and furans (PCDD/F), polychlorinated biphenyls (PCB), linear alkylbenzene sulphonates (LAS),
nonylphenols and nonylphenol ethoxylates (NP, NPEO), bis(2-ethylhexyl)phthalate (DEHP), brominated flame
retardants (polybrominated diphenyl ethers [PBDE], tetrabromobisphenol A [TBBP-A], decabromobiphenyl
[DeBB], hexabromocyclododecane [HBCD]) and adsorbable organic halogen (AOX) were determined in the
digestates from three biogas plants in Finland during 2010–2011. Concentrations of PCB, DeBB and TBBP-A
were below limit of quantification (LOQ) in all the studied samples but other compounds or compound groups
were detectable. Concentrations PCDD/F and PBDE were highest in digestates from the plant that processed
only sludges from municipal waste water treatment plant (MWTP). Their concentrations were close or below limit
of quantification in digestates from the plant that processed pig manure and by-products from food industry.
Amounts of pharmaceuticals were highest in the digestates from plants that processed MWTP sludge. The most
abundant pharmaceuticals in these digestates were ibuprofen (painkiller) and erythromycin (antibiotic). Only
concentrations of ketoprofen, ibuprofen and propyphenazone (painkillers) exceeded the LOQ in the samples from
the plant that processed pig manure and byproducts from food industry. The potential routes of accumulation of
organic pollutants into food chain from the raw materials processed in biogas plants and through digestates used
as an organic fertilizer in agricultural soils will be studied. The process of uptake of contaminants into food,
particularly in agricultural plants, can be mathematically modeled. The two independent ways of uptake of
contaminants from the soil are considered: uptake with transpiration water, and diffusion from the soil into root.
The models are based on the contaminant-specific parameters from the literature, concentration data from the
current study, and plant metabolism processes.
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The agglomeration of silver nanoparticles in growth media and their toxicity to green algae
Pseudokirchneriella subcapitata.
Tuominen, M., Schultz, E. and Sillanpää, M
The Finnish Environment Institute, Laboratories, Hakuninmaantie 6, 00430 Helsinki, Finland
In this study the toxicity of two commercial silver nanoparticles (NP) to the green algae Pseudokirchneriella
subcapitata was studied. These silver NPs included a polyvinylpyrrolidone (PVP) capped silver NP
(Nanostructured & Amorpheus Material Inc, nominal size of <15 nm) and a silver NP capped with starch (Strem
Chemicals Inc, nominal size of 5-10nm in solution). The toxicity of the silver NPs was established following the
freshwater algal growth inhibition test with unicellular green algae (ISO 8692). The agglomeration of the silver
NPs was studied by measuring the hydrodynamic diameter (HDD) with a dynamic laser scattering device
(Zetasizer Nano ZS, Malvern Instruments). The initial HDD for the PVP and starch capped silver NP dispersions
were 55.3 ± 1.5 nm and 175.8 ± 3.1, respectively. Prior to the toxicity testing with the silver NPs, experiments
were conducted to determine the effects of the growth medium on the silver dispersions. The high ionic strength
of the growth medium could potentially lead to the agglomeration of the silver NPs, therefore the growth medium
was used at full strength or diluted with a factor of 2, 5 and 10. These preliminary studies showed that while the
dilution factor increases the stability of the silver NPs decreases. These studies concluded that these silver NPs
remained stable in full strength growth media throughout the exposure time and no dilution was necessary. The
toxicities for PVP coated and starch coated silver NPs were found to be 112.1 µg/l and 93.6 µg/l, respectively.
Environmental Risk Assessment of Pharmaceuticals: Two Case Studies from the Pharmaceutical
Industry
Kaisa Unkila, Orion Pharma, Research and Development, Turku, Finland
Environmental risk assessment (ERA) is required for the application of marketing authorization for a new
medicinal product. The ERA of the human medicinal product, based on the European Medicines Agency’s
guideline (Doc. Ref. EMEA/CHMP/SWP/4447/00), is a stepwise procedure consisting of two phases. In Phase I,
the exposure of the environment to the active pharmaceutical ingredient (API) is estimated by using consumption
data and investigating physico-chemical properties of the compound. If the value of calculated predicted
environmental concentration in surface water remains below the action limit (0.01 µg/l), and no other concerns
are expected, the assessment may stop in Phase I. If the value is equal or exceeds the trigger limit, Phase II
environmental fate and effect analysis should be carried out. In the first set of the experimental studies (Tier A),
the toxicology and fate of the API in the aquatic environment are explored. If potential alerts in these screening
studies were recognized, then further extended environmental risk and fate studies (e.g. Tier B studies in the
terrestrial compartment) should be considered. Two pharmaceutical industry case studies of ERA of human
medicinal products will be presented.
Accumulation and depuration potential of fullerene-C60 in the presence of humic substances in Daphnia
magna
1
1
2
1
1,3
Greta Waissi-Leinonen , Kukka Pakarinen , Elijah Petersen , Jarkko Akkanen , Jussi Kukkonen
1
University of Eastern Finland, Department of Biology, Joensuu Campus
2
Biochemical Science Division, National Institute of Standards and Technology (NIST), Gaithersburg, USA
3
University of Jyväskylä, Department of Biological and Environmental Sciences
The properties of carbon nanoscale materials are unusual with how nanotechnology has been developed highly
in research objectives. On the other hand, those properties have led to another concern, their risk to biological
systems. The research of carbon nanomaterials, such as fullerene, is in current interest and importance due to
their possible harmful effects on organisms. This study discusses one carbon nanomaterial, fullerene-C60, and
its characteristics and behavior in two different waters. It has not been known how freshwater conditions, where
humic substances are typical, affect the behaviour of the fullerene particles. In this study the acute toxicity,
bioaccumulation and depuration rate of fullerene-C60 by using Daphnia magna as a test animal were
investigated, on the basis of which results the behaviour of fullerenes can be outlined. Identifying concentrations
and movement of fullerene particles, a spectroscopic method and transmission electron microscopy were used.
In this research some differences between artificial- and humic water suspensions were found. Amount of
accumulated fullerene was lower in humic water. In both artificial and humic waters the kinetics of
bioaccumulation was similar: fast during the first hours, and it received the steady state in 24 hours. Instead
excrete of fullerene occurred more rapidly when humic substances were present. This indicates the importance
of humic susbstances for fullerene behaviour aquatic environments.
Key words: Carbon nanoparticle, fullerene, humic substances, Daphnia magna, accumulation, depuration
18
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Human placental perfusions of anticancer drug doxorubicin and liposomes encapsulated with
doxorubicin
1
2
1
3
2
1
Veid J , Soininen SK , Meftah A , Auriola S , Ruponen M , Vähäkangas K
1
Faculty of Health Sciences, School of Pharmacy / Toxicology, University of Eastern Finland, P.O.BOX 1627, FI70211, Kuopio, Finland
2
Faculty of Health Sciences, School of Pharmacy / Biopharmacy, University of Eastern Finland, P.O.BOX 1627,
FI- 70211, Kuopio, Finland
3
Faculty of Health Sciences, School of Pharmacy / Pharmaceutical Chemistry, University of Eastern Finland,
P.O.BOX 1627, FI-70211, Kuopio, Finland
Purpose: Sometimes the maternal illness, such as cancer, needs radical medication during the pregnancy.
Liposomal doxorubicin (DOX) is as efficient as free DOX in the treatment of metastatic cancer, but it has fewer
side effects, such as heart problems and nausea. However, little is known about the transfer of anticancer drugs
and nanomaterials through human placenta. So far, there are only three experimental studies on the transfer of
nanoparticles in human placenta, and the results are contradictory (Myllynen et al., 2008; Wick et al., 2010;
Menjoge et al., 2011). It seems that both the size and coating have an effect on the transfer.
Methods and Results: We used human placental perfusion (Myllynen et al. 2003, Veid and Karttunen et al. 2011)
to study transfer of free DOX and liposomal DOX. The studied substances (5 µM) were added into the maternal
circulation and the transfer from maternal to fetal side was assessed by using LC-MS/MS. Free DOX was
detected in the fetal circulation already at 30 minutes after the addition of the drug in the maternal side, and
~11% of the dose in maternal side was transferred to fetal side during a 6 hour perfusion. In contrast, liposomes
were not detected from the fetal circulation in a 4 hour perfusion. Although in the maternal sample, we could
clearly demonstrate nanoparticles (ø 64.9 nm±13.6 nm), nanoparticles were not detected in any of the fetal
samples. This indicates that most likely intact liposomes were not able to go through the human placenta.
However, ~6% of free DOX released from the liposomes was detected from the fetal circulation after a 4 hour
perfusion.
Conclusions: More studies are needed to confirm the findings and clarify the mechanisms of transfer of DOX. In
the future, the amount of free DOX will be analyzed from the perfused tissue with LC-MS/MS.
Myllynen et al. Eur J Clin Pharmacol 58: 677−682, 2003;
Myllynen et al. Reprod Toxicol 26: 130−7, 2008;
Wick et al. Environ Health Perspect 118: 432−6, 2010;
Menjoge et al. J Control release 150: 326−38, 2011;
Veid and Karttunen et al. Toxicol Lett 205: 357−64, 2011
Dioxin-induced genomic instability in mouse embryonic fibroblasts
1
1
2
2
2
Matti Viluksela , Merja Korkalainen , Katriina Huumonen , Jonne Naarala , Jukka Juutilainen
1
National Institute of Health and Welfare, Department of Environmental Health, Kuopio, Finland;
2
Department of Environmental Science, University of Eastern Finland, Kuopio, Finland
Genomic instability (GI) is an increased formation rate of alterations in the genome that is observed as delayed
damage (e.g. mutations, chromosomal aberrations, micronuclei, apoptosis) many generations later in the
progeny of exposed cells. Ionizing radiation and some genotoxic chemicals have been shown to induce GI, but
the role of GI in nongenotoxic carcinogenesis is not known. The aim of this study was to investigate the ability the
nongenotoxic carcinogen TCDD to induce GI. Mouse embryonic fibroblasts (C3H10T1/2) were exposed to
TCDD, and GI was monitored over several cell generations using induction of micronuclei (MN), and expression
of cancer-related genes, DNA methyl transferases (DMNTs) and miRNA as well as global DNA methylation as
endpoints. The ability of TCDD pretreatment to modify menadione-induced DNA damage and repair was studied
using Comet assay. Cd was used as a genotoxic carcinogen positive control. TCDD-treatment, opposite to Cd,
did not cause genotoxic damage directly after exposure. In contrast, TCDD (but not Cd) induced a delayed
increase in MN and altered expression of cancer-related genes in the progeny of exposed cells. Similar pattern
was also observed in miRNA expression profiles. TCDD did not affect the expression of DMNTs or global
methylation. Increased sensitivity of TCDD-pretreated cells to menadione in Comet assay indicated that the
genomic stability was compromised already at the end of TCDD exposure. In conclusion, TCDD is able to induce
GI that is associated with impaired response to DNA damage, but not with DNA methylation pattern.
Funded by the Academy of Finland (123439).
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13th International Congress of Toxicology (ICTXIII)
13th International Congress of Toxicology (ICTXIII)
Seoul, Korea
June 30 - July 4, 2013
www.ict2013seoul.org
The ICT 2013 Scientific Program Committee cordially invites you to submit abstracts
<http://www.ict2013seoul.org/abstract.asp> for the Poster Session by the deadline of January
31, 2013. All abstracts will be reviewed by the committee and outstanding abstracts will be
invited to the symposium. Participants are advised to register in
advance<http://www.ict2013seoul.org/regi1.asp> to receive an early registration discount. For
more information on the meeting please visit the website www.ict2013seoul.org
What are cancer stem cells
Kirsi Vähäkangas
Uncontrolled growth, metastasis, and inherent or developing resistance to chemotherapy are
typical features of malignant tumors. Despite tens of years of intensive research on molecular
mechanisms of cancer, universal breakthroughs have not appeared. New medications based
on the found molecular details have not been “magic bullets” and suffer largely from the same
drawbacks as earlier medication: side-effects and resistance. During the past years, the
concept of cancer stem cells has resurfaced with hopes for understanding better the process
of cancer and giving new options for the development of cancer treatment.
Cancer stem cells (CSCs), as normal stem cells, are the cells enabling tissue renewal; in the
case of cancer, renewal and growth of cancer tissue (recent reviews e.g. Pantic 2011,
O’Flaherty et al. 2012). CSCs are a small subpopulation within the cancer tissue and may be
even the origin of some forms of cancer. Although opinions still differ, it is regarded more
probable that cancer stem cells differ from the normal stem cells. The existing literature
reflects current ignorance and confusion about what these cells are. Definitions and
terminology vary, and recently Valent and coworkers (2012) have tried based on the 2011
Working Conference on CSCs, to clarify the situation by proposing a system which
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differentiates between pre-malignant neoplastic stem cells and cancer stem cells (also called
malignant neoplastic stem cells). In addition, they propose operational definitions based on the
experimental model used to identify CSCs, e.g. “neoplasia initiating cells” that can regenerate
neoplastic populations in xenografted immunodeficient mice, and are sustained when further
transplanted into new mice.
Thus. the only conclusive current definition for cancer stem cells is functional: CSCs are tumor
cells that are able to propagate a new tumor when transplanted to immunocompromised mice.
In practice it means a bigger probability to induce a tumor using fewer cancer stem cells than
the other tumor cells. There are other functional in vitro assays related to stemness of cancer
cells: formation of cancer spheroids in culture, ability to invade through an artificial membrane
in so-called invasion assay and asymmetric division to two different daughter cells, one
retaining the ability to self-renew as CSCs and the other to differentiate, however, retaining
capacity to divide. The search for CSC markers has been mainly carried out comparing cell
populations functionally different from each other in these assays. Many markers for CSCs
have been suggested, of which some are tissue specific and many described also in normal
stem cells.
There is a phenomenon called epithelial-mesenchymal transition (EMT) which in epithelial
tumors seems to coexist with CSCs. In this process epithelial cells loose their epithelial
markers, like E-cadherin and upregulate mesenchymal markers, like Vimentin (e.g. Salnikov
2012). In some in vitro studies it has been shown that epithelial cells, indeed, can undergo
such a change in phenotype, which can be induced by hypoxia. On the other hand,
inflammation, known to be associated with carcinogenesis, recruits mesenchymal stem cells
(MSCs) from hematopoietic system into the inflamed tissue (for a review on MSCs, see e.g.
Charbord 2010). They can also transform in the tissue of residence. Lately it has become
evident that mesenchymal stem cells can support the growth of cancer cells and even be
reprogrammed to CSCs (Bao et al. 2012a). This implicates that MSCs may be actively
involved in the carcinogenic process.
To study CSCs one needs markers of stemness and many are listed in CSC reviews (e.g.
Pantic 2011, O’Flaherty et al. 2012). One of the most interesting markers is a CD133 or
Prominin1 (Prom1), a cell surface antigen the function of which is currently unknown. It has
been shown to be associated with chemoresistance of cancer cells and with many other
stemness or pluripotency markers, like Nanog and Oct-4. However, normal stem cells in
some tissues may also express CD133 meaning that either CD133 is not an exclusive CSCmarker, or that CD133 positive cells in tissue represent an origin of a tumor. Another
interesting marker is the activity of a group of enzymes called aldehyde dehydrogenases
(ALDH). The human genome contains 19 ALDH genes and the activity of many of the
encoded proteins is elevated in cancer tissue and in CSCs, but also in normal stem cells
(Muzio et al. 2012). Cancer cells with a high ALDH activity have higher tumorigenicity and
high percentage of ALDH positive cells in a tumor has been associated with lower survival.
Hypoxia regulates CSCs and EMT through many molecular pathways, especially through the
HIF signaling pathway involving such proteins as NF-kappaB, PI3K, Akt, mTOR, Notch, Wnt
and β-catenin (Bao et al. 2012b). Because CSCs are genetically identical to their
differentiated progeny, epigenetic regulation is expected to be paramount. One such emerging
level of regulation is mediated by small non-coding RNAs, especially micro-RNAs (miR), which
downregulate translation of proteins through sequence complementary binding to target
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mRNAs. There is increasing amount of data about the importance of micro-RNAs in cancer
biology, a current hot topic in cancer research (Liu & Tang 2011, Bao et al. 2012b, Yu et al.
2012). Typical of this regulation is that one miR regulates many proteins, and one protein is
regulated by many miRs, so that there is a lot redundancy in the regulation. In breast CSCs
let-7, miR-30, miR-200 family and miR-205 have probably significance (Liu & Tang 2011).
Recently Han and coworkers (2012) demonstrated that miR-21, which is often overexpressed
in solid tumors, regulates EMT and Hif-1α in breast cancer stem-like cells. In other tumor
types other miRs may be more important, e.g. in glioblastoma brain tumor several other miRs
are downregulated (Liu & Tang 2011). This is an emerging very complex field and we have
seen just the very top of an iceberg of the miR-level regulation so far.
All in all, even the vocabulary in the field of cancer stem cells is still developing. Cancer stem
cells, cancer progenitor cells, stem-like cancer cells, cancer cells with stem like characteristics
– one can choose which words to use depending on boldness and trust in the results of
current science. Maybe at the end the definitions are less important than the realization of
their plasticity affected by genetic, epigenetic and (micro)environmental factors. What is
certain, however, is that the concept of cancer stem cells has given a boost to cancer biology
and a lot of fuel for thinking about how cancer process starts and proceeds. What is there for
toxicologists? Toxicity is based on the various biological, biochemical and molecular
mechanisms of the body. In chemical carcinogenesis the above-mentioned mechanisms are
bound to be important. An implication of this is the fact that the toxic chemotherapeutic drugs
seem to affect the stemness of cancer cells creating resistance, and many chemicals have
already been shown to affect micro-RNAs and induce other epigenetic changes (e.g. Singh &
Li 2012). Such changes may be the mechanisms especially of non-genotoxic carcinogens.
Even if a compound is not overtly toxic or mutagenic by current standards, it could affect a
small subpopulation of cells within a tissue and promote the maintenance of cells potential for
CSC-activity. The question is: do we need to develop new standards for testing the
carcinogenicity of compounds.
Acknowledgements
I am indebted to Dr. Ana Robles for interesting discussions on the subject and critical reading of the manuscript
with valuable suggestions for improvement.
References
Bao B, Ahmad A, Li Y, Azmi AS, Ali S, Banerjee S, Kong D, Sarkar FH. Targeting CSCs within the tumor
microenvironment for cancer therapy: a potential role of mesenchymal stem cells. Expert Opin Ther Targets. 16:
1041-1054, 2012a.
Bao B, Azmi AS, Ali S, Ahmad A, Li Y, Banerjee S, Kong D, Sarkar FH. The biological kinship of hypoxia with
CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness. Biochim
Biophys Acta. 1826: 272-296, 2012b
Charbord P. Bone marrow mesenchymal stem cells: historical overview and concepts. Hum Gene Ther. 21:
1045-1056, 2010.
Han M, Wang Y, Liu M, Bi X, Bao J, Zeng N, Zhu Z, Mo Z, Wu C, Chen X.MiR-21 regulates epithelialmesenchymal transition phenotype and hypoxia-inducible factor-1α expression in third-sphere forming breast
cancer stem cell-like cells. Cancer Sci. 103: 1058-1064, 2012.
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Liu C, Tang DG.MicroRNA regulation of cancer stem cells. Cancer Res. 2011 71: 5950-5954, 2011.
Muzio G, Maggiora M, Paiuzzi E, Oraldi M, Canuto RA.Aldehyde dehydrogenases and cell proliferation. Free
Radic Biol Med. 52: 735-746, 2012.
O'Flaherty JD, Barr M, Fennell D, Richard D, Reynolds J, O'Leary J, O'Byrne K.The cancer stem-cell hypothesis:
its emerging role in lung cancer biology and its relevance for future therapy. J Thorac Oncol. 7: 1880-1890, 2012.
Pantic I.Cancer stem cell hypotheses: impact on modern molecular physiology and pharmacology research. J
Biosci. 36: 957-961, 2011.
Salnikov AV, Liu L, Platen M, Gladkich J, Salnikova O, Ryschich E, Mattern J, Moldenhauer G, Werner J,
Schemmer P, Büchler MW, Herr I.Hypoxia Induces EMT in Low and Highly Aggressive Pancreatic Tumor Cells
but Only Cells with Cancer Stem Cell Characteristics Acquire Pronounced Migratory Potential. PLoS One. 2012;
7(9):e46391
Singh S, Li SS.Epigenetic effects of environmental chemicals bisphenol a and phthalates. Int J Mol Sci. 13:
10143-10153, 2012
Valent P, Bonnet D, De Maria R, Lapidot T, Copland M, Melo JV, Chomienne C, Ishikawa F, Schuringa JJ, Stassi
G, Huntly B, Herrmann H, Soulier J, Roesch A, Schuurhuis GJ, Wöhrer S, Arock M, Zuber J, Cerny-Reiterer S,
Johnsen HE, Andreeff M, Eaves C.Cancer stem cell definitions and terminology: the devil is in the details. Nat
Rev Cancer. 12: 767-775, 2012.
Yu Z, Li Y, Fan H, Liu Z, Pestell RG.miRNAs regulate stem cell self-renewal and differentiation. Front Genet.
2012; 3: 191.
Greetings from Bethesda III
It did not work as I hoped – to put these greetings once a month in our webpage. Thus this is
just the third greetings from the other side of Atlantic and not the eleventh! In the meanwhile
we have lived through two really bad storms claiming lives, destroying houses and making
peoples’ lives miserable where ever they hit. During the first storm at the end of June I lost
power for one day, lucky me. Many did not have power for over ten days. After the storm I
could not drive to shop because all the roads were blocked by fallen trees. I also saw
damaged houses. It took weeks to clean everything.
After about the hottest summer in Bethesda there ever has been (not compatible with my
system) another really bad storm hit in late October. There were warnings about Sandy
beforehand. In TV we could follow the approaching megastorm. In good time the airports and
Metro were shut down and people told to stay at home for that Monday and Tuesday 29th and
30th of October when the storm was expected to land on the upper East coast. I was in bed
with a bad case of bronchitis when my sister and her husband left on the 26th, the last day
there were flights from Dulles airport. I was very happy for them and sorry for myself. Thanks
to skype I did not feel too deserted.
At this end everyone was preparing for the storm and shops were emptying of water and other
resources. This time I was well prepared. I had dragged myself up from the sickbed and
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gone shopping twice in Saturday. I had an extra blanket, bottled water, canned food, several
flashlights and a battery operated radio, and a lot of batteries naturally. Also, we were advised
to pack for potential evacuation and I had done that, too. In Sunday evening my friend Lisa,
who lives a few blocks away, brought me a wonderful chicken meal for dinner. I was dead
tired and very thankful.
I did not sleep close to the windows for those two nights between Sunday and Tuesday. I
have never been afraid of thunderstorms in Finland. After these two storms I am not quite that
confident anymore. And as you probably have seen in TV, the damage was like a war-zone in
those areas in New York and New Jersey, where Sandy hit the hardest. We were spared from
the worst. I did not even lose power this time. The only damage I experienced was some
water through the window rims. In Bethesda, some houses and cars were damaged by falling
trees. One week after Sandy there was a snowstorm in New York. Poor people.
In between the storms, hot summer and some illness, I have worked also in the lab. For the
first time in about 12 years I have done experiments with my own hands. I was quite
astonished when there was a contamination problem during the summer months in cell
culture, but my cells were spared. So I could provide summer students and colleagues cells
from my cultures, which gave me great satisfaction! One of the important reminders by this
work has been the time it takes to get experiments done. Naturally I have not been as swift as
those who have years of fresh routine in their hands. However, it has been fun and will end all
too soon. I just wish that the University will be kind enough to let me carry on science when I
return.
Bethesda was beautiful in spring, during summer and in autumn. Flowers have been
blooming in the gardens non-stop for almost nine months. Amazing. Autumn colors were
impressive: some trees were absolutely bright red and were glowing like flames in the
sunshine. Every morning still I walk to work beside red roses, which now compete with
Christmas decorations. In Montgomery Mall I saw the first Christmas stuff put on show at the
end of September. It seems that Americans substitute the very short Christmas holidays with
a very long Christmas Season! Here the whole holiday is just the first Christmas Day; the
Government may let people go home already midday in Christmas Eve but this is never
announced beforehand.
In Finland we know how to celebrate Christmas long enough and I will be doing just that when
I travel for Finland before Christmas. I wish you all peaceful and relaxing Christmas!
Kirsi Vähäkangas
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TAPAA TOKSIKOLOGI - Haastattelussa Kirsi Myöhänen
1. Kerro nimesi, tittelisi sekä nykyinen työ.
Työskentelen tällä hetkellä Euroopan Kemikaalivirastossa (ECHA) Luokitus ja merkintäyksikössä Junior Scientific
Officerina ja olen hoitovapaalla Turvallisuus- ja Kemikaalivirastosta (Tukes), missä tittelini on Ylitarkastaja
(Senior Advisor).
2. Mikä on pohjakoulutuksesi?
Farmasian tohtori toksikologiassa, proviisori ja Toksikologian maisteri. Lisäksi olen valmistunut 2-vuotisesta
TRISK-koulutuksesta (Accredited Training Programme for highly qualified toxicology experts) ja olen Euroopan
rekisteröity toksikologi (ERT).
3. Missä eri työtehtävissä olet toiminut?
Olen toiminut toksikologian tutkijana Kirsi Vähäkankaan ryhmässä silloisessa Kuopion yliopistossa sekä
vierailevana tutkijana Karolinska Instituutissa Dan Segerbäckin labrassa. Siirryin vuoden 2008 lopulla Helsinkiin
viranomaistehtäviin, aloittaen silloisessa Sosiaali- ja Terveydenhuollon Tuotevalvontakeskuksessa (STTV), josta
kemikaaliyksikkömme siirtyi sittemmin Valviraan ja lopulta Tukesiin. Viime kesän työskentelin vapaaehtoisena
Georgetownin yliopistossa Washington DC:ssa USAssa neurofarmakologian tutkimuksen parissa. Syyskuussa
siirryin takaisin Suomeen ja viranomaistehtäviin ECHAan.
4. Miten ajauduit toksikologian alalle ja miksi kiinnostuit toksikologiasta?
Aloitin vuonna 2003 toksikologian maisteriopinnot, kun olin tovin työskennellyt farmaseuttina apteekissa. Minua
kiinnosti erityisesti ihmisen terveyden suojelu, lähinnä se, että aineet, seokset ja esineet olisivat turvallisia siinä
määrin mitä niille altistumme. Myöhemmin kiinnostuin erityisesti sikiön altistumisesta, koska se oli hyvin
maanläheinen ja huolta aiheuttava aihe, ja onnekseni pääsin mukaan Kirsi Vähäkankaan tutkimusryhmään
tekemään väitöskirjaa ko. aiheesta.
5. Koska liityit STY:hyn?
Uskon, että liityin STY:hyn vuonna 2005. Tunsin heti yhdistyksen omakseni, ja pidän tärkeänä, että Suomen
toksikologeilla on oma yhdistys.
6. Missä tehtävissä olet toiminut STY:ssä?
Olen toiminut STY:n sihteerinä vuosina 2008 ja 2009 ja siitä lähtien taloudenhoitajana, mikä olen edelleen.
Lisäksi olen toiminut vuodesta 2007 Toksikolgi-lehden toimitussihteerinä.
7. Missä luottamustoimissa olet toiminut toksikologian alalla / mitä huomionosoituksia
olet saanut?
Olen työni puolesta toiminut mm. asiantuntijana ECHAn riskinarviointikomiteassa (RAC), OECD testimenetelmien
kansallisena koordinaattorina (terveysvaarat) sekä osallistunut komission hormonihäiriköiden kriteerejä
valmistelevaan työryhmään.
8. Mikä olisi unelma-ammattisi toksikologina?
Unelma-ammattini toksikologina on toimia arvostettuna toksikologina kansainvälisessä työympäristössä, olkoon
se sitten viranomaisena, akateemikkona tai teollisuudessa.
9. Mitä harrastat?
Eniten sydäntäni lähellä on pelastuskoiratoiminta, koulutan pelastuskoiria ja itselläni on viranomaistason
pelastuskoira, jonka kanssa osallistumme ajoittain oikeisiin kadonneiden ihmisten etsintöihin. Lisaksi pidän
matkustelusta ja kaikenlaisesta ulkoliikunnasta.
10. Terveiset toksikologilehden lukijoille?
Olkaa ylpeitä siitä, että olette toksikologeja!
Meitä ei ole paljon, joten pidetään yhtä yhdistyksen
kautta ja verkostoidutaan ympäri maailmaa!
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TOKSIKOLOGI
STY:n 34-vuotissymposium
STY:n 34-vuotissymposiumin aiheena on
Predictive toxicology and drug safety testing
Symposium järjestetään 13.-14.5.2013 Espoossa, varatkaa aika kalenteriinne.
Alustava ohjelma:
Monday 13 May 2013
Opening: Reijo Salonen, Orion Pharma
Session 1: Cardiac safety in vivo and in vitro
• Risto Kerkelä, University of Oulu
• Ari-Pekka Koivisto, Orion Pharma
• Tarja Lehtimäki, Orion Pharma
Session 2: Genetic toxicology and Reactive metabolites
• Risto Juvonen, University of Eastern Finland
• Teija Oinonen, Orion Pharma
Session 3: Case examples
• Leena Sopanen, Orion Pharma
• Pertti Pellinen?; Santen
Wine & snacks + Annual meeting of STY
Dinner in Tapiola Garden Hotel
Tuesday 14 May 2013
Keynote lecture: Marja-Leena Toivonen, Orion Pharma
Session 4: Biomarkers for toxicity
• Markku Pasanen; University of Eastern Finland
• Kristiina Haasio, Orion Pharma
Poster viewing session
Session 5: Toxicological modeling
• Antti Poso, University of Eastern Finland
• Julius Sipilä, Orion Pharma
Session 5: Preclinical safety evaluation for novel therapies
• Tiina Palomäki, FIMEA
• Lotta Vassilev, Oncos Therapeutics
2/2012
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TOKSIKOLOGI
2/2012
Jäsentiedotteet – JÄSENMAKSU 2012 ja osoitteenmuutos
****************************************************************************************
Ilmoitathan meille mikäli sähköpostisi tai postiosoitteesi on muuttunut!
****************************************************************************************
JÄSENTIEDOTE – JÄSENMAKSUN 2012 MAKSAMINEN
Tässä vuoden 2012 jäsenmaksuohjeet, toimi nopeasti.
Saaja: Suomen toksikologiyhdistys ry
Saajan tili: 800012-1716678
Viite: 1009
Summa: 30€, kannattajajäsen 200€
Eräpäivä: 31.5.2012
Viestiin: Jäsenmaksu vuosi 2012. Jos maksaja eri kuin jäsen, jonka maksu maksetaan,
jäsenen nimi ja vuosi.
SUOMEN TOKSIKOLOGIYHDISTYS
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TOKSIKOLOGI
2/2012
SUOMEN TOKSIKOLOGIYHDISTYS
Finnish Society of Toxicology
JÄSENANOMUS
Suku- ja etunimet:
Syntymävuosi:
Arvo tai ammatti:
Kotiosoite ja puhelinnumero:
Työpaikka:
Työpaikan osoite, puhelinnumero
ja telefaxnumero
Sähköpostiosoite:
Opiskelen päätoimisesti ensimmäistä akateemista lopputukintoa varten; yliopisto:
Lyhyt kuvaus aikaisemmasta, erityisesti toksikologiaan liittyvästä toiminnasta
(mm. koulutus, oma erikoisala):
Suosittelijat: (yhdistyksen jäseniä):
_________________________________
Nimen selvennys
____________________________________
Nimen selvennys
Päiväys ja allekirjoitus:
Palautus:
Juha Laakso, [email protected]
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TOKSIKOLOGI
2/2012
SUOMEN TOKSIKOLOGIYHDISTYS
Finnish Society of Toxicology
OSOITTEEN- JA NIMENMUUTOSILMOITUS
Vanha nimi:
Uusi nimi:
Vanha osoite:
Uusi osoite:
Vanha puhelinnumero:
Uusi puhelinnumero:
Vanha faxnumero:
Uusi faxnumero:
Vanha sähköpostiosoite:
Uusi sähköpostiosoite:
Palautus:
Juha Laakso, [email protected]
SUOMEN TOKSIKOLOGIYHDISTYS TOIVOTTAA JÄSENILLEEN
RAUHAISAA JOULUN AIKAA
JA
MENESTYKSEKÄSTÄ UUTTA VUOTTA 2013