S2 Abstracts / Toxicology Letters 229S (2014) S2–S3

Keynote lecture

Keynote 1Toxicology: Past successes, present realities andfuture challenges

Allister Vale 1,2

1 National Poisons Information Service and West Midlands PoisonsUnit, City Hospital, Birmingham, UK, 2 School of Biosciences,University of Birmingham, UK

Toxicologists based in Edinburgh, the location of the 50thCongress, have made important contributions to science over thepast 200 years, which will be described to illustrate these pastsuccesses. Toxicology remains an area of scientific excitement andof social and economic relevance. In the main, toxicologists haverisen to the challenges presented to them over the last 50 yearsand now the worth of these endeavours is recognized by others.Toxicology has been placed on the political agenda, both nationallyand internationally. This means that there are now new opportuni-ties which must be addressed if the specialty is to remain credible,particularly within the fields of human and environmental health,the theme of this Congress (Advance Science for Human andEnvironmental Health). Although toxicologists have contributedto reducing the harm caused to man as a result of exposure todrugs and other chemicals, the challenge for toxicologists in thefuture will be for them to take an even more active role in opposingmore effectively poor science, including inadequate interpretationof data (such as those about supposed risk that are not basedon an objective evaluation of the available data), and regulatorydecisions that defy common sense. As Lewis Smith has said, “If wedo not address these challenges, in another 100 years someonewill be writing about the challenge facing toxicologists in the nextcentury, still marvelling at our failure to tackle those of the past.”

http://dx.doi.org/10.1016/j.toxlet.2014.07.007

Keynote lecture

Keynote 2The application of transgenic animal models toelucidate human pathways of drug metabolismand chemical toxicity

Roland Wolf 1,∗, Nico Scheer 2, Colin Henderson 1

1 University of Dundee, Dundee, UK, 2 TaconicArtemis, Cologne,Germany

Our research programme has applied molecular geneticapproaches to define pathways of drug metabolism and chemi-cal toxicity. These studies have involved both in vitro and in vivostrategies with a particular emphasis on the use of transgenicanimal models. A number of experimental approaches have beentaken including gene deletion by homologus recombination, theintroduction of allelic variants onto a mouse null background, thehumanisation of mice for both the transcription factors whichcontrol the expression of drug metabolising enzymes as well asmodels where murine genes such as cytochrome P450s have beenexchanged for their human counterparts. In addition, we havedeveloped a number of reporter mouse lines which measure in vivoresponses to chemical and oxidative stress, DNA damage andapoptosis. These latter models facilitate mechanistic studies toestablish pathways of chemical toxicity in vivo. They can also be

applied to study degenerative disease and evaluate novel thera-peutic interventions. In this presentation the applications of thesemodels applied to drug development and understanding the risk ofenvironmental chemicals to man will be described.

http://dx.doi.org/10.1016/j.toxlet.2014.07.009

HESI CITE Seminar Series

Keynote 3Advancing scientific innovation towardsimproved public health

Timothy W. Gant

Centre for Radiation, Chemical and Environmental Hazards, PHE,United Kingdom

Health and wellbeing is concerned as much with living well(life quality) as with a longer life. Recognition and protection fromenvironmental hazards, such as chemicals, is an important com-ponent of public health practice to improve health and wellbeing.Chemical usage contributes in many positive ways to health andwellbeing but there is a balance to be achieved to ensure max-imum benefit with minimum risk. Nothing new to toxicologists,but achievement of the balance is continually evolving due ina substantial part to the impact of new technology in biologi-cal science. Over the last 20 years the collectively termed ‘omictechnologies, have given broader and more rapid insight intoexposure, biomarkers of response (hazard metrics), mechanisms,adverse outcomes and more recently susceptibilities. Bioinformat-ics is the glue for all of these technologies; essential for data storage,processing, and analysis. Using these technologies more data isacquired more rapidly for all components of the toxicity path. Thesedata can improve understanding, but also raise many more ques-tions. The ‘omic technologies have not been, and never will be, thepanacea for all the challenges in toxicology for precisely this rea-son. For this same reason reason ‘omic technologies have yet tofind their way into regulatory acceptance. In this lecture we willexplore the current and likely future application of ‘omic technolo-gies in public health and their positive impact on our health andwellbeing.

http://dx.doi.org/10.1016/j.toxlet.2014.07.011

Bo Holmstedt Memorial Foundation (BHMF) Lecture

Keynote 4Adverse drug reactions: From man to moleculeand back again

B. Kevin Park

University of Liverpool, UK

The use of drugs as medicines has made an enormous contri-bution to human health and the drug discovery process has beendirected at most aspects of human disease. However, all drugs areassociated with adverse drug reactions (ADRs) which vary in fre-quency and severity dependent on drug and patient population, andthe overall burden to both the NHS and to industry is large. ADRs canoccur with any drug, may affect any organ system, and vary widelyin severity. We divide ADRs into on-target (or type A) reactionsand off-target (or type B) reactions. Type B or idiosyncratic reac-tions, although less common, are nevertheless extremely importantbecause of their relative severity, and because they account for