- to perform a review and critically assess data on the in-vivo and in-vitro biotransformation and bioaccumulation of chemicals in microbes, invertebrates and vertebrates (e.g. fish, mammals and humans). This Phase of the project will build upon previous work performed in ECO6 and ECO7;
- liase with other research groups involved in the development of in silico and in vitro methods for determining biotransformation potential;
- to use the data from 1 to construct a quality assessed relational database on the biotransformation, bioaccumulation, properties, structure and functionality of chemicals so that these data can be used to develop and support the development of in-silico and in-vitro models and/or assays;
- to use 2D substructure searching to investigate those structural moieties that are associated with universal lability, limited lability, specific lability or limited/non lability;
- to explore the relationships that exist between the metabolic/ biotransformation rate of chemicals in microbes, invertebrates and vertebrates and their characteristics (i.e. chemical class, functionality, physico-chemical properties and/or structure) and develop QSARs for estimating biotransformation and bioaccumulation potential in different organisms;
- to investigate relationships that exist between in-vivo metabolic data for different taxonomic groups and in vitro and in-vivo data;
- to provide recommendations on the validation of the developed quantitative approaches and how these approaches can be used in the assessment of a chemicals biotransformation potential as part of the chemical assessment process.
The methods developed in the project will be invaluable in: 1) PBT assessments, where a weight of evidence approach can be used to support decisions on the potential for chemicals to bioaccumulate or degrade in the environment; and 2) Aquatic and terrestrial risk assessments where a technical basis is needed for extrapolation of biotransformation rates between vertebrate species which can then be incorporated into food chain models.
Establishing Relationships of Biotransformation Across Organisms by Karen Tiede, Chris Sinclair, Karen Tiede, Robert Stones, Stewart Owen, Maaike Bilau, Federica Iaccino, Alistair Boxall and Phil Howard