Toxicants for developmental neurotoxicity

Topics to be addressed:

1. Identification of mechanistically defined compounds to map pathways for DNT

2. Classification of established DNT compounds according to expected in-vitro effects and mechanisms.

Background:

New test systems for DNT are a high-priority issue for consumer protection and in environmental toxicology. The current use of in-vivo models is not only economically and ethically costly but also carries the danger of misjudgment because of inter-species differences and subgroup variability. Alternative in-vitro methods would allow higher throughput and provide richer information. This aim is followed by DNT 1-3 conference series, initiated by CAAT and continued by ECVAM.

Currently available in-vitro methods model certain biological aspects and pathways that are thought to be relevant for DNT in man. These comprise migration of neuroblasts, generation and differentiation of neuronal precursors or the establishment of functional cellular networks. In order to judge the relevance of the methods, it is examined whether they react specifically to DNT compounds. In order to determine the specificity, information is required on whether a given compound is expected to affect a specific biological process modeled in the test method (“Is ethanol expected to modulate neurite outgrowth?”; “Is warfarin expected to affect neuroblast migration?”). This information is particularly pertinent in situations, where a set of compounds is used to identify pathways and effect markers of DNT by omics technologies in a given test method.

In a complementary approach, several research projects try to establish a map of pathways relevant for DNT. One approach to obtain such information is the use of compounds specifically interfering with such pathways. Also in this area, the availability of an annotated and qualified list of tool compounds is expected to accelerate the progress of science.

The expert panel of this workshop will be engaged to share their expertise from different disciplines to specify DNT toxicants according to their mechanisms and interference with pathways. This should help to identify relevant pathways in in-vitro models and to accelerate research on in vitro DNT models.