Skip to main content

Novel approaches for testing metabolism disrupting chemicals

GOLIATH - Generation Of Novel, Integrated and Internationally Harmonised Approaches for Testing Metabolism Disrupting Chemicals

GOLIATH focusses on one of the most urgent regulatory needs in the field of endocrine disrupting chemicals, namely the lack of methods for testing EDCs that disrupt metabolism – chemicals collectively referred to as ‘metabolism disrupting chemicals’ (MDCs). MDCs are natural and anthropogenic chemicals that have the ability to promote metabolic changes that can ultimately result in obesity, diabetes and/or fatty liver in humans. GOLIATH will generate the world’s first integrated approach to testing and assessment (IATA) specifically tailored to MDCs.

With a focus on the main cellular targets of metabolic disruption – hepatocytes, pancreatic endocrine cells, myocytes and adipocytes – GOLIATH will develop new methods and optimise existing methods that span the entire adverse outcome pathway (AOP) spectrum, using in silico predictive modelling and high throughput screening, (pre-)validated ready-to use in vitro assays and optimised in vivo toxicity testing guidelines.

GOLIATH will provide key information on the endocrine mode of action by which MDCs disrupt metabolic pathways and induce adverse effects on human health by incorporating multi-omics technologies, and translating results from in vitro and in vivo assays to adverse metabolic health outcomes in humans at real life exposures.

Meet the Principal Investigator(s) for the project

Dr Luigi Margiotta-Casaluci
Professor Andreas Kortenkamp
Professor Andreas Kortenkamp - Traditional chemicals risk assessment has a quite artificial orientation: It treats chemicals as if they act in isolation, when in reality there is exposure to multiple substances. For more than 15 years, our team have been engaged in efforts to find ways of improving risk assessment by taking “cocktail effects” into account. This work has proceeded in stages: Firstly, when we have information about the toxicity of individual mixture components, is it possible to predict the effects of the combination? Working with mixtures of endocrine disrupting chemicals we have shown that this is achievable. Secondly, what is the composition of mixtures of environmental relevance, and what effects do they produce? Work on this aspect of the mixtures issue is currently proceeding in our group. We are also interested in making an impact on chemical regulation by addressing the questions: Which chemicals should be grouped together for mixtures risk assessment? What are scientifically sound grouping criteria? We have prepared scientific reports for the European Commission, including the State of the Art Report on Mixture Toxicology. Currently we are writing a State of the Art Assessment for Endocrine Disrupters, a project also commissioned by the European Commission. Another research interest is in unravelling the details of estrogen signalling and estrogen-mediated effects with a view to understanding hormonal cancers, especially breast cancer. Here, I closely collaborate with Dr Elisabete Silva. Qualifications1983: Degree in Chemistry, Philosophy and Educational Sciences from University of Muenster, Germany 1989: PhD (with distinction) from Bremen University, Bremen, Germany Career 1990-1991: Post-doctoral Fellow at Queen Mary London, University of London. 1991-2000: Lecturer in Environmental Toxicology, School of Pharmacy, University of London, London. 2000-2005: Senior Lecturer, School of Pharmacy, University of London, London. 2005-2007: Reader and Head of Centre for Toxicology, School of Pharmacy, University of London, London. 2007-2011: Professor for Molecular Toxicology, Head of Centre for Toxicology, School of Pharmacy, University of London, London. 2011-present: Professor in the Institute for the Environment, Brunel University.

Related Research Group(s)

human body

Inflammation Research and Translational Medicine - Driving scientific innovation and discovery for diagnosis, treatment, and management of cardiovascular disease, inflammatory and immune disorders, microbial resistance, and cancer.

Partnering with confidence

Organisations interested in our research can partner with us with confidence backed by an external and independent benchmark: The Knowledge Exchange Framework. Read more.

Project last modified 21/11/2023