The report of the afternoon symposium about skin exposures, which was organised on 10th March 2016 by section Occupational Toxicology and Contactgroep Gezondheid en Chemie, can be read here.
Powerpoint presentations can be found here:
Board of Occupational Toxicology section
Dr. F.J. (Frans) Jongeneelen
Dr. T.M. (Teake) Pal
Dr. N.G.M. (Nicole) Palmen, secretary
Drs. J. (Jeroen) Terwoert
Objectives of the Occupational Toxicology section
The objectives and related activities of the Occupational Toxicology Section are as follows:
1. To promote and coordinate scientific activities in the field of occupational toxicology, for example:
• organizing and promoting scientific meetings;
• liaising with scientists working in related fields and to stimulate interdisciplinary cooperation, in particular promoting cooperation in occupational health services and academic institutions;
• the promotion of international contacts in the field of occupational toxicology;
• identifying gaps in knowledge regarding risk assessments.
On the 24th of March 2016, the sections on Reproductive Toxicology and Pharmaceutical Toxicology organized a spring symposium entitled: ‘Pediatric drug development: a fi eld in maturation’.
The invited speakers shared an overview of the latest insights on risk assessment of pediatric drugs from various perspectives. After a word of welcome, Saskia de Wildt kicked off the program with her presentation ‘Developmental Pharmacology: setting the stage’. Of the existing drugs on the market, there are still few drugs that are investigated for children. This has resulted in a diversity of dose recommendations for children through the years. In the Dutch Pediatric Formulary, the diverse dose recommendations have been combined in a single uniform dosing guideline. In the past, fatalities have occurred with ‘adult’ drugs in the pediatric patient population. Exposure might be diff erent in children, e.g. due to the ontogeny of the metabolizing enzymes and transporters, distribution volume, organ development. In clinical practice, a way to determine clinical doses for children without the supporting juvenile toxicity data has been established, assuming that when similar exposures are reached in children this will result in similar clinical effi cacy. To address some of these concerns, juvenile animal studies are conducted, as the second speaker Jan Willem van der Laan explained. The studies are conducted according to regional guidelines. In the form of the ICH S11 Guideline, an international harmonisation is on its way. The impact of the juvenile animal studies and need for harmonisation is illustrated by an overview of anti-cancer drug development for children. In half of the studies new target organ toxicities were observed in juvenile animals. The exposure levels in the juvenile animals were often higher than in the adults, which may result in toxicities at lower dose levels. Species selection, dose regimen, dose-range fi nding studies, dose adaptation and age at start of dosing as well as dose duration are important aspects to consider. Illustrative of the need to understand the pediatric-specifi c pharmacodynamic (PD) and pharmacokinetic (PK) properties of a specifi c pharmaceutical compound was the presentation provided by Catherijne Knibbe. In clinical practice, drugs are often dosed on a mg/kg basis. As pediatric patients can have a higher clearance of the drug/kg body weight, higher dose levels might be required in the pediatric age category for the desired PD eff ect. Population PK-PD modelling can help to predict the dose levels required in the pediatric population, needed to achieve the desired PD eff ect. This method allows for few samples per individual, while more individuals are needed. Individualized dosing guidelines for specifi c drugs can be established, while for compounds metabolized through the same pathways a ‘system’ approach could be envisioned. The meeting continued (after a lunch break) with real-life examples presented by Graham Bailey. As the title of his presentation mentioned: expect the unexpected when conducting non-clinical juvenile animal studies. To list just some of the discussion points when designing a juvenile animal study: the age of the animals at the start of dosing should be representative of the relative developmental stage of the intended pediatric clinical population. Making a study more complicated rarely makes interpretation easier. As mentioned by previous speakers, the ontogeny of the drug metabolizing enzymes and transporters should be taken into account, including species diff erences. Don’t forget that guidelines should be considered as just one way of achieving an objective, they should never be followed rigidly if there is a good scientifi c justifi cation not to. But how to we deal with pharmaceuticals for the pediatric population from a quality perspective? Diana van Riet explained how adequate product quality relates to chemical quality, pharmaceutical quality, usability including patient acceptability, and user instruction. Assessment of child and parent preference and acceptability of diff erent formulations (from tablet to liquid) has revealed that historical assumptions are not always accurate. Further, the excipients used in the adult formulation are not always appropriate for use in the pediatric population due to safety concerns. The European Paediatric Formulation Initiative (EuPFI) Safety & Toxicity of Excipients for Paediatric (STEP) initiative is useful source for information on safety of specifi c excipients. (www.eupfi .org) Once on the market, pharmaceuticals are carefully monitored for potential side eff ects. This pharmacovigilance, e.g. the monitoring of safety of pharmaceuticals after authorisation, was further detailed by Boukje Raemaekers. Information provided to the Netherlands Pharmacovigilance Centre (Lareb; www.lareb.nl) can be in the form of spontaneous reports of suspected adverse drug reactions from either healthcare professionals or consumers. On the label of medicines, it is mentioned that side eff ects can be reported at Lareb. After careful assessment, signals of adverse drug reactions might result in regulatory actions, Dear Healthcare Professional (DHCP) letters, product information updates and/or educational materials. Overall, the day as organised by the sections on Reproductive Toxicology and Pharmaceutical Toxicology provided an overview of pediatric medicines, from the view of the health care professional, researcher, up to the regulator. Furthermore, they provided food for thought, like what should be the focus of the juvenile toxicity testing: the changing pharmacodynamic target during development, or the diff erences in exposure between children and adults; PD versus PK. This was clearly visible from the lively discussions between the participants during the drinks at the end of the day. We sincerely hope that the overview provided was appreciated by the participants. We in our turn would like to thank all the presenters and participants, as these meetings cannot be organized without them!
The board consists of:
The Pharmaceutical toxicology section was founded on the anniversary annual meeting of the Dutch Society of Toxicology of June 18th, 2009. Currently contemplated affiliation with the Federation of Innovative Drug Research Netherlands (FIGON).
Objectives of the Pharmaceutical toxicology section:
1. To promote and coordinate scientific activities in the field of drug toxicology in the broadest sense, to include other cellular and systemic mechanisms of toxicity, pharmaco / toxicokinetics, biotransformation, risk extrapolation to human / animal and pharmacovigilance.
Board of the Environmental Toxicology section
The Environmental Toxicology Section was established in 1982. The section's objective is to promote scientific research and education in environmental toxicology. In addition, it is committed to promoting the application of environmental toxicology research for the preservation and improvement of the quality of the environment. Together with its members symposia and workshops are organized in order to achieve this objective. The section follows activities of international organizations such as SETAC and SECOTOX closely, and contributes as necessary to these (sub) activities. Since 2006 the board meets operates with the board of the Environmental Chemistry Section of the Royal Dutch Chemical Society (KNCV). This cooperation suits extremely well and will therefore be continued. These two boards can thus be seen as a single board. The board is always open to suggestions from its members for topics for workshops, excursions, seminars, symposia.
Work area of the Environmental Toxicology Section
The cycle of toxic substances in the environment and the potential effects of these substances on wildlife fall within the area of interest of environmental toxicology. In addition, it focuses not only on individual organisms, but they try to understand the survival of ecosystems, communities of different species of plants and animals in relation to their surroundings. Ecotoxicology studies how materials are distributed in water, soil and air, their possible conversion into other substances, how substances enter a community and leave, how they are transmitted through food, and what the consequences are for the survival of communities. The ultimate goal is making predictions about the risks posed by certain substances to the environment.