Toxicology for the future research, development and education for chemical safety Welcome!

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1 Toxicology for the future research, development and education for chemical safety Welcome! Ulla Stenius, Professor, Head of IMM, Professor, ERT, Programme Director Institute of Environmental Medicine, Karolinska Institutet

2 Ulla Stenius Toxicology student National Institute of Occupational Health Carcinogenesis, risk assessment PhD in 1991 To IMM 1997 Professor 2010 Head of IMM 2014

3 Toxicology student At IMM since then Risk assessment of dioxins/pops, EDCs, pesticides, bisphenol A, contaminated sites PhD in 1996 Professor 2010 Programme director ToxMaster since 2006

4 Toxutbildningen 1985 Anders Bergendorff

5 Tox group of 1985

6 Examination lab course

7 IMM Research Chemical and physical environmental factors Lifestyle factors Genetic interaction Common diseases

8 IMM Education programmes Global master s programme in toxicology Master programme in working life and health Postgraduate training programs in Epidemiology and Environmental factors & Health Health risk assessment training

9 Environmental health risk assessment IMM provides authorities in Sweden and EC with expertise, support and advice regarding environmental health risk assessments.

10 Toxicology for the future! Welcome!

11 Toxicology health effects from exposure to chemicals! Medicines/drugs Food additives Pesticides Cosmetics Consumer products Industrial chemicals Environmental contaminants Consumers - workers

12 Toxicology in Sweden Chemical safety a priority since many years Environmental research dioxins, PCBs, mercury, lead, cadmium EU: Contributed to European legislations REACH, industry responsible for product safety Globally: Stockholm convention persistent organic pollutants (dioxins, PCBs etc) Master s programme in toxicology 40 years in 2016! BPA

13 Toxicology Unwanted health effects of chemicals Increasing demand for qualified toxicologists internationally Master s programme in Toxicology Research - mechanisms and methods Regulatory toxicity testing Health risk/safety assessment Contribute to a future with safe and sustainable use of chemicals - pesticides, food additives, medicines, cosmetics, chemicals in clothes, toys etc

14 Master s programme in Toxicology One of the first toxicology programmes world-wide (started in 1976) Unique in its cohesive focus on toxicology and human health Prepares for either a Research or Professional career Close connection with high-quality research and risk assessment work at IMM, and collaborates with national authorities and AstraZeneca/Swetox Since 2010 a global master s programme, 20 places Now students from Sweden, Denmark, Poland, Holland, England, Austria, Germany, Greece, Spain, Portugal, Romania, Moldavia, India, Bangladesh, Nepal, China, Iran, Turkey, Ethiopia, Sudan, South Africa, Colombia, USA

15 Semester 1 Principles of toxicology Toxicokinetics Target organ toxicology Histopathology and clinical pathology Semester 2 Laboratory animal science Applications of methods in toxicological research (laboratory course) Health risk assessment Semesters 3 and 4 Global toxicology in a sustainable society Regulatory toxicity testing Elective courses: Molecular and cellular toxicology Risk assessment and in silico toxicology Master project Study visit European Commission Joint Research Centre

16 Toxicology in 1976 (or 1985) No Good Laboratory Practice (GLP) LD50 study Ames test only non-animal study No molecular biology omics Cytochrome P450/P448 was new No transparency in Risk Assessment Swedish legislations and decision-making (no EU) No computers

17 Toxicity testing Animal toxicity tests LD50! Animal-welfare groups. campaigned against LD50 testing on animals.. Several countries took steps to ban the oral LD50 - the OECD abolished the requirement for the oral test in 2001 Ames test - the only non-animal test Ames test is a biological assay to assess the mutagenic potential of chemical compounds. The test serves as a quick and convenient assay to estimate the carcinogenic potential of a compound. However, false-positives and false-negatives are known. Published in early 1970s by Bruce Ames and coworkers extracted from Wikipedia

18 Toxicity testing No international harmonisation No standardized test guidelines No Good Laboratory Practice fraud in testing! GLP was introduced in the US following cases of fraud generated by toxicology labs in data submitted to the FDA by pharmaceutical companies. Industrial BioTest Labs (IBT) was the most notable case, where thousands of safety tests for chemical manufacturers were falsely claimed to have been performed or were so poor that police investigators could not piece together what work had been done... Wikipedia

19 Cytochrome P450

20 Risk assessment Toxicity data Uncertainty = factor 100! Expert judgment! No transparency! Health-based guidance value (Tolerable Daily Intake) EFSA Stakeholder conference - October 2013 people want to know not only the conclusions but also how conclusions were reached

21 National risk assessments Sweden outside European Union! Many risk assessments (useful training) Sweden could make the decisions!

22 No computers literature search

23 Toxicology today More strict chemical regulations Responsibility on the producer Strive towards non-animal testing and the 3Rs refine, reduce, replace Advanced laboratory and computational methods Focus on weight of evidence all available data! Increased public interest also students

24 Next-generation toxicologists need to combine: The new toxicology 3R AOP Omics In silico New regulations Weight of evidence The traditional toxicology Still need animal testing/validation Most concepts still valid

25 ToxMaster today recent developments Long tradition in collaboration with AstraZeneca AZ closed down Safety Assessment in 2012 Annika was called to the KI Dean for higher education What implications for the quality of the programme? Participated in planning for Swetox aiming at keeping the quality

26 Regulatory toxicity testing unique course real study

27 Safety Assessment in Drug Discovery and Development Collaboration ToxMaster Swetox VINNOVA-funded National research school KI Environmental Factors and Health KI/IMM International Training in Health Risk Assessment

28 Study visit to EC Joint Research Center since 2004

29 Tox students international since 2010

30 Kick-off at Finnhamn, Stockholm archipelago

31 ToxCast, QSAR, read-across - lecture from US EPA

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33 Statistics (533 in total) International Short Long

34 After graduation chemical safety PhD students at KI, other universities in Sweden, Europe, North America Swedish/European Chemical Agencies, Food Safety Authorities etc Pharmaceutical, Chemical industry Consultants

35 Thanks to ToxMaster IMM Gold sponsor: SOBI Silver sponsors: Toxintelligence IKEM

36 Programme Welcome - Ulla Stenius, head and director of IMM ToxMaster today and recent developments -, programme director AOPs in toxicology and risk assessment - Brigitte Landesmann, EC JRC The air-liquid interface cell model as an alternative method - Lena Palmberg, IMM Big data (omics) in toxicology - Roland Grafström, IMM Fika and mingle students at the roll-up, art exhibition The challenge of identifying endocrine disrupters - Anna Beronius, IMM Assessment of chemical mixtures - Johanna Zilliacus, IMM In silico methods in toxicology and risk assessment - Scott Boyer, Swetox Text mining - Ilona Silins, IMM The role of the microbiome in toxicity - Harri Alenius, IMM Nanotoxicology: challenges and future perspectives - Bengt Fadeel, IMM

37 Ina Schuppe Koistinen - Art meets Science