Regulatory Toxicology (Wilks)

The group conducts research in the fields of evidence-based toxicology, development of pathway-based approaches and improving principles and practice of human health risks related to environmental chemical exposures.

Evidence-based toxicology

Evidence-based toxicology aims to transparently, consistently, and objectively assess available scientific evidence in toxicology. For example, systematic reviews (SRs) are a structured process to assess existing evidence relating to a specific research question. One indispensable part of SRs is to apply pre-defined quality criteria in order to appraise the overall strength of evidence. We have been contributing to efforts trying to apply SR methodology and quality assessment criteria to toxicological and environmental health evidence related to a given health hazard or chemical exposure risk. As part of the WHO Chemical Risk Assessment Network’s initiative on the use of systematic reviews we are contributing to webinars, scientific symposia and a publication to promote evidence-based methods in toxicology.

List of relevant publications:

• Implementing systematic review techniques in chemical risk assessment: Challenges, opportunities and recommendations
• Neurodevelopmental and neurobehavioural effects of polybrominated and perfluorinated chemicals: a systematic review of the epidemiological literature using a quality assessment scheme
• A critical review of frameworks used for evaluating reliability and relevance of (eco)toxicity data: Perspectives for an integrated eco-human decision-making framework
• BPA plan ready for new EFSA assessment in 2018

Adverse Outcome Pathway (AOP) framework

21st century toxicology is moving from empirical animal endpoints to evidence-based toxicity pathways. An AOP is a simplified structured representation of sequential causally-related key events (KE) linking a stressor-induced molecular initiating event (MIE) to an adverse outcome (AO). Shared key events generate AOP networks which can represent conservation and divergence of toxicological responses across taxa, life stages, etc. The AOP KnowledgeBase/AOP Wiki (AOPwiki.org; OECD with US EPA, EU JRC and others) is a data repository, which is critical for sharing and updating KEs and key event relationships (KER) as living documents. The AOP framework has many potential uses, including establishing the relevance of in vitro and in silico data for human and environmental hazard profiling and risk assessment.

List of relevant publications:

• Adverse Outcome Pathway on chronic binding of antagonist to N-methyl-D-aspartate receptors during brain development leading to neurodegeneration with impairment in learning and memory in aging
• Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity
• Bisphenol A- -Why an adverse outcome pathway framework needs to be applied

Improving human health risk assessment

Group members participate in a number of initiatives aimed at improving the ability of risk assessors to predict health impacts of chemicals. For example, the International STakeholder NETwork (ISTNET) is a collaboration of regulators, academic researchers and industry scientists to develop guidance on how alternative (non-animal) test methods can be used in regulatory risk assessments for developmental neurotoxicity. Conclusions from a number of workshops have been published in the peer-reviewed literature (e. g. Bal-Price et al 2015 & 2018). The Health and Environmental Sciences Institute (HESI)’s “Risk assessment in the 21st century” (Risk21) project aims to provide a harmonised approach to evaluating chemicals using risk- rather than hazard-based methods. We have been contributing in particular to the work stream on cumulative assessment, i.e. risk assessment of chemical mixtures (e. g. Solomon et al 2016, Moretto et al 2017).

List of relevant publications:

• International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes
• OECD/EFSA workshop on developmental neurotoxicity (DNT): The use of non-animal test methods for regulatory purposes
• Consensus statement on the need for innovation, transition and implementation of developmental neurotoxicity (DNT) testing for regulatory purposes
• Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity
• Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans
• A framework for cumulative risk assessment in the 21st century

EU-funded projects

We have been consortium members or partners in a number of EU-funded programmes (7th Framework Programme, Horizon 2020 and Marie Skłodowska-Curie Innovative Training Network).

• HEROIC – Health and Environmental Risks: Organisation, Integration and Cross-fertilisation ofScientific Knowledge (2011 – 2014)

We coordinated this project aimed to identify and explore new ways of improvement, harmonisation and integration of tools and methods used in human health risk assessment and environmental risk assessment. We were overall coordinator of the project.

• NanoReg2 – Development and implementation of Grouping and Safe-by-Design approaches within regulatory frameworks (2016 – 2019)

The Regulatory Toxicology group and the research group of Prof. Jörg Huwyler (Pharmaceutical Technology) joined this project in 2016. Work in our group focused mainly on developing grouping strategies for nanomaterials with the aim to assist regulatory bodies in producing a coherent framework for manufactured nanomaterial (MNM) risk assessment and support recommendations for Safe by Design (SbD).

• EUROoC – Interdisciplinary training network for advancing Organ-on-a-chip technology in Europe (2018 – 2020)

We are a partner organization in this MSCA-ITN project which focuses on the interdisciplinary training of young researchers in all aspects of the development and application of organ-on-a-chip systems. Our contribution is mainly focused on training aspects for regulatory applications of these technologies.