Workshop Report 04 – Influence of Maternal Toxicity in Studies on Developmental Toxicity

WR 04 : Influence of Maternal Toxicity in Studies on Developmental Toxicity | October 2004

The Workshop was convened to explore whether the criteria to assess the influence of toxic effects induced in the maternal organism on the development of the embryo/foetus could be improved for classification purposes.  Several conclusions and recommendations were made:

1. Regulatory classification of chemicals that have caused signs of developmental toxicity relies on a hazard-based approach.  It does not take full account of exposure conditions during normal handling and use.
2. The currently practiced European classification of chemicals that have shown evidence of developmental toxicity does not provide a clear distinction between developmental effects that occur directly on the embryo/foetus (primary effect) and those that are associated with chemically-induced perturbations of maternal homeostasis (secondary effect). The appropriate consideration of such effects has profound ramifications for the classification of chemicals.
3. Relevance of route and mode of administration of test chemicals, dose-response data as well as toxicokinetics and toxicodynamics were recognised as important criteria that should be considered in the study design.  The existing data are compelling, and one can no longer ignore the scientific evidence that the biological and toxicological effects differ profoundly depending on how the chemical enters into the body.
4. The use of expanded end points that are more sensitive to detect chemically induced maternal toxicity than those specified in the OECD 414 test guideline received endorsement from a majority of the participants.  However, reservations from representatives of regulatory agencies meant that no true consensus could be reached.  An experimental way forward to better define maternal and developmental toxicity in OECD 414 studies received broad support. New data with refined end points to detect the onset of maternal toxicity might improve the interpretation of the results of such studies and might provide a scientific basis for industry and regulators when making decisions leading to classification.
5. The majority of participants agreed with the recommendation to make the regulatory process reflect anticipated human exposure. This would mean that risk characterisation, as well as hazard identification, would become an important component in the classification of chemicals.