Last week, we presented work from the TRI project at the Annual Congress of the British Toxicology Society (BTS) in Solihull, UK. We presented a poster describing:
- the challenge of implementing mixture risk assessment (MRA) as part of routine chemical risk assessment
- the approach we are taking in reviewing the relevant legislation and literature, including the generation of a database, CREST, on which there will be more soon on this blog.
- the case studies we are developing to illustrate the problem and to identify pragmatic solutions to the issue.
Here is our abstract:
Towards the routine regulatory implementation of mixture risk assessment
Richard M. Evans, Olwenn V. Martin, Martin Scholze, Michael Faust and Andreas Kortenkamp
Including mixture risk assessment (MRA) in the risk assessment of chemicals is currently a topic of great interest to toxicologists, regulators and the public. A major challenge is how the available science can or should be implemented in practice. There is scientific consensus that the Concentration Addition (CA) model is a suitable default concept for predicting experimental mixture effects, i.e. the expected toxic effect when two or more chemicals that each cause the given effect are applied in combination. However, although it is straightforward to calculate the predicted mixture effect in experimental studies, the path to routine implementation of MRA in risk assessment is less clear. The Hazard Index (HI) approach is the most common practical implementation of CA, and we have analysed whether there are scientific, regulatory or pragmatic obstacles to the routine use of the HI in practice.
We highlights aspects that are particularly relevant to MRA from a review of relevant legislation, the relationships between chemical regulations, typical data availability and empirical evidence for mixture effects; and we discuss technical challenges such as the use of International Chemical Identifiers (InChIs) to link disparate chemical information. We describe a public-access database that will make this information freely available and we present case studies to illustrate the challenges and opportunities of implementing MRA. We hope to generate constructive discussion around options, pragmatic solutions and realistic objectives/aspirations in the pursuit of the regulatory implementation of MRA.
The BTS scientific program for the conference included:
- Fetal Programming and Assessing Toxicity in an Ageing Population
- In Vitro Models and Tools for Renal Toxicology
- Emergency Toxicology – Acute Toxicity Risk Assessment
- Mathematical Toxicology
- Renal Pathology – Integration with Toxicology
- Pharmaceuticals in the Environment
- Oligonucleotides – Application in Health and the Environment
- In Silico Toxicology (Continuing Education Programme:)
- Prokaryotic resistance to antibiotic toxicity; a global health challenge (Hot Topic Lecture). Dr Robert Hill (Public Health England, UK).
- Epidemiology; its contribution to the assessment and management of risks to health from chemicals (Plenary Lecture). Professor David Coggon (University of Southampton, UK).
- Immunotoxicology and beyond (Barnes Prize Lecture). Professor Ian Kimber OBE (University of Manchester, UK).
- Advances in Scientific Understanding of Toxicological Potential – towards improved predictive capability (RCPath Cameron Lecture). Dr Jayne Wright (Jayne Wright Ltd, UK).