7th ECETOC Symposium at EEMS Annual Meeting looks at thresholds for genotoxins and their application in risk assessment

For the 7th occasion since 1998, ECETOC supported EEMS, the European Environmental Mutagen Society with the organisation of a symposium on 25 September, the last day of its 2008 annual general meeting, held in Cavat, Croatia. Cefic’s Long-range Research Initiative (LRI) kindly sponsored the event.

Although the subject matter is one which can elicit doubt, the tone of the symposium was very positive. However, the involvement of speakers from a regulatory background, along with the sound defensible science presented by all speakers, resulted in a very successful consideration of the subject. This was also reflected in the nature of the questions posed to speakers and responses given.

The presentations clearly demonstrated the existence of thresholds for DNA damaging mutagens as well as aneugens, thus changing the paradigm that “one molecule is sufficient to cause cancer’ even for classes of genotoxins (such as alkylating agents) for which linear dose response relations have been considered to be the norm. Yet, for some compounds there appears to be no clear threshold, or none which will be relevant for risk assessment. If the underlying biological mechanism can be explained satisfactorily, the genotoxic threshold may be extrapolated with confidence to estimate a safe dose for man.

However, this may not be possible for all compounds. Expert judgement on a case-by-case basis is necessary at this stage of knowledge of the biological basis of genotoxicity thresholds. Although the symposium showed that there is clear progress in using thresholds in risk assessment, and growing acceptance of the principle by regulatory authorities, more research is needed to develop a better understanding of the underlying mechanisms.The ECETOC symposium was well attended by over 300 (out of a total of 400) registered EEMS conference participants, mostly from academia, government, contract research organisations and the pharmaceutical/chemical industry. Participants of a subsequent ECETOC workshop on DNA adducts (Cavtat, 25-26 September) were also in attendance. The audience, including many key and young scientists, showed a high interest in the practical application of genotoxic thresholds in chemical risk assessment.

All speakers at the symposium have been committed to writing a manuscript for publication as a special issue of Mutation Research, together with papers from the DNA adduct workshop. The issue will count as ECETOC Monograph.