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Identifying trans-generic biotransformation potential

Background

It is widely held that some chemicals are easily metabolised (almost universally)
while others may either be selectively (i.e. species specific) or non-metabolisable.
The main aim of this work is to see if there is validity in this concept - and if there are
structural or sub-groups that can be extracted. This project will start the process of
building an approach that will enable those chemicals that are poorly or nonmetabolisable
to be quickly and easily separated from those that are metabolized and
to establish the boundaries/limits. This will then enable environmental testing to be
appropriately targeted, depending upon other properties and possible effects. Data
relating to the ability of different systems, e.g. microbes, fish, mammals to transform
chemicals should be collected and reviewed. Trends that may help identify certain
groups of chemicals as being universally or partly degradable should be identified.
This information could, for example, help refine bioconcentration testing strategies or
exclude chemicals that are metabolised from any such testing. It may also help in the
assessment of the environmental degradation of that chemical.

Objectives

Review biodegradation and biotransformation in organisms from different taxa and
trophic levels (including for example fish, higher plants and mammals). Include
existing data from BCF, biodegradation databases, and company data (or databases).
Highlight key groupings, chemical structures associated with universal lability,
limited or specific lability and no lability (or practically none). Develop an approach
that would use the data within a testing scheme to reduce the numbers of animals used
should an OECD 305 study be necessary. Recommend a validation study addressing
cross-species biotransformation potential.

Scope

Proposals submitted for consideration should address the following areas under
individual sub-headings:

  • The title of the research proposal;
  • The name and affiliation of the principal investigator and the laboratory or laboratories in which the research will be conducted;
  • Evidence of the principal investigator's knowledge of, and contribution to, current understandings of persistence and how it may be measured;
  • A clear definition of the research objectives, including a description of the mechanistic basis for the proposed research;
  • A clear plan of investigation, including a clearly defined milestone plan which identifies all critical decision points in the research programme;
  • A detailed breakdown of costs.

Monitoring
The successful applicant(s) will be required to submit a progress report six months into the programme. A detailed review of the project and the achievements will be provided by the principal investigator at the end of the project. The successful applicant or applicants will also be required to prepare for publication a manuscript describing the work undertaken and the results achieved.To start in 2005, duration approximately 12 months.

 

Timing: To start in 2005, duration approximately 12 months.

Cost: Budget: 100,000 EUROS

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