title: International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.
abstract: A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.
authors.affiliation: Systems Toxicology Unit, EURL-ECVAM, Institute for Health and Consumer Protection, European Commission, Joint Research Centre, TP 580, Via Fermi 1, 21026, Ispra, VA, Italy, anna.price@jrc.ec.europa.eu.
authors.forename: Anna
authors.initials: A
authors.lastname: Bal-Price
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Crofton
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.forename: Sandra
authors.initials: S
authors.lastname: Allen
authors.forename: Michael
authors.initials: M
authors.lastname: Arand
authors.forename: Timo
authors.initials: T
authors.lastname: Buetler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Delrue
authors.forename: Rex E
authors.initials: RE
authors.lastname: FitzGerald
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Tuula
authors.initials: T
authors.lastname: Heinonen
authors.forename: Helena
authors.initials: H
authors.lastname: Hogberg
authors.forename: Susanne Hougaard
authors.initials: SH
authors.lastname: Bennekou
authors.forename: Walter
authors.initials: W
authors.lastname: Lichtensteiger
authors.forename: Daniela
authors.initials: D
authors.lastname: Oggier
authors.forename: Martin
authors.initials: M
authors.lastname: Paparella
authors.forename: Marta
authors.initials: M
authors.lastname: Axelstad
authors.forename: Aldert
authors.initials: A
authors.lastname: Piersma
authors.forename: Eva
authors.initials: E
authors.lastname: Rached
authors.forename: Benoît
authors.initials: B
authors.lastname: Schilter
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schmuck
authors.forename: Luc
authors.initials: L
authors.lastname: Stoppini
authors.forename: Enrico
authors.initials: E
authors.lastname: Tongiorgi
authors.forename: Manuela
authors.initials: M
authors.lastname: Tiramani
authors.forename: Florianne
authors.initials: F
authors.lastname: Monnet-Tschudi
authors.forename: Martin F
authors.initials: MF
authors.lastname: Wilks
authors.forename: Timo
authors.initials: T
authors.lastname: Ylikomi
authors.forename: Ellen
authors.initials: E
authors.lastname: Fritsche
mesh_terms: D001921:Brain / Q000187:drug effects*; D005333:Fetus / Q000187:drug effects*; D017408:Guidelines as Topic; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods*