Background
Definitive risk assessment of endocrine disruption relies on the 2-Generation Study, which is resource intensive in terms of animal use, cost and time (approx. 2 years until reporting). Whilst the scientific rationale for an increase in trans-generational sensitivity is unclear, there are some indications that certain effects might either only be detected or may increase in severity in the second generation. Nevertheless, the question has been raised whether a 1-Generation Study with appropriate enhancements could also allow for a reliable risk assessment.
Scope
A project is proposed to review public (and potentially industry) data with the following terms of reference:
- Collect all studies since 1985 from the open literature in rats and mice covering at least a time span of the present multi-generation study (OECD TG416) including those with a longer duration and/or other parameters.
- Similarly, multi-generation studies on ecologically relevant species, especially fish or birds, should be included.
- These studies shall be evaluated as follows:
(i)Separate two sets of studies, namely those without an increase in severity or quality of effects from the first to the following generations from those where such an increase was reported.
(ii)For these latter studies compile the effects with such a trans-generational increase and evaluate whether a consistent pattern emerges.
(iii)In collaboration with a statistician, the data base identified under (ii) has to be critically evaluated to establish whether an increase in trans-generational effects is real or has occurred by chance as a result of the multitude of parameters investigated in multi-generation studies. In this context, the evaluation of effects with a decreased trans-generational sensitivity could also be helpful.
(iv) Compare the toxicological profile of the substances with studies identified under (ii) with the effects shown in generation studies with special emphasis on dose-response relationship, lowest effect level, No Adverse Effect Level and most sensitive effect. - Parallel to the evaluation of the open literature, the contractor should work with Cefic to approach member companies (especially those in the agrochemical business) to establish whether and under what conditions they are willing to include their internal data in such a data base. A decision should be made whether the internal data from industry should be included in this evaluation.
If there is a clear indication that trans-generational effects are either missing or occurring by chance this information will provide a solid base to develop a resource effective 1-Generation test protocol for the risk assessment of endocrine active chemicals.
