Background
Currently, the LRI-sponsored project ECO6 is addressing aquatic biotransformation and establishing a database containing relevant information to reduce the need for fish testing in OECD 305. The two areas in chemical assessment where information on degradability and biotransformation would be helpful are;
- PBT assessments, where a weight of evidence approach can be used to support decisions made on the potential for chemicals to bioaccumulate or to degrade in the environment. Understanding relationships between degradation in microbial systems and biotransformation and bioconcentration in higher trophic levels (e.g., invertebrates, vertebrates) will help in such a weight of evidence approach.
- Aquatic, terrestrial and marine assessments, where a technical basis is needed for the extrapolation of biotransformation rates of chemicals between vertebrate species (e.g., fish, rats, humans) which can thus be incorporated into food-chain models.
Scope
Based on a critical review of available literature, analyse and develop quantitative relationships relating to biodegradation, biotransformation and bioaccumulation in organisms from different taxa and trophic levels, particularly with respect to parent compound biotransformation rates. Of particular interest is the development of relationships between microbial system, invertebrates and vertebrate species (e.g., fish, mammals, humans). Fish and higher vertebrate degradation and biotransformation rates are currently stored in databases regarding BCF and bioaccumulation from the LRI-sponsored projects ECO6 and ECO7. In the present proposal, we recommend a multi-disciplinary team adopt the following strategies:
- Highlight chemical structures associated with universal lability, limited or specific lability, and no lability (or practically none).
- Develop links and liaise with research to support the development and validation of in silico and in vitro biotransformation models and/or assays.
- By providing critical reviews of data, collaborate with other groups (e.g. ILSI-HESI) to support the development of in vitro assays for estimating biotransformation rates in key species for the regulatory assessment of chemicals, including fish and mammals.
- Provide information to support the validation of promising in vitro systems, e.g. trout and carp S9 and hepatocytes, that measure biotransformation in collaboration with other parties (e.g. ECVAM).
It is expected that the findings will developed into a peer reviewed publication, following presentation at a suitable scientific conference. Short interim reports on progress are required at 3 to 6-monthly intervals.
