Evaluation of innovative methods to assess neuroactive substances in water

Neurotoxicity screening is a rapidly developing field in which the adverse effects of substances are assessed to identify those chemicals that have the potential to affect the nervous system. Scientific evidence shows that even mild impairments in the nervous system can lead to transient or persistent effects on cognitive and mental health, and each of these can be inflicted via direct or indirect exposure. Based on known modes of action (MoA) of organic contaminants detected in freshwater monitoring studies, neuroactive compounds represent the largest category, comprising pharmaceuticals, pesticides and illicit drugs, i.e., almost 30% of all detected chemicals (Busch et al., 2016, Legradi et al., 2018). This emphasises the need for tools for rapid exposure and effect assessments to prevent possible harm to public health. Exposure to neuroactive compounds occurs via different routes. However, a good
understanding of the links between exposure to these substances and the mechanism by which these affect the nervous system remains largely unknown. Therefore, there is a need for consistent guidance on the development of relevant test methods and the reliable evaluation of data on neuroactive substances for assessing their potential risk. Limited testing capacity has led regulators to encourage the development and use of more informative New Approach Methods, including in vitro, in silico and alternative in vivo approaches to predict the neurotoxicity or developmental neurotoxicity (DNT) of chemicals.

Drinkwaterbronnen kunnen verontreinigd zijn met chemische stoffen die schadelijke effecten kunnen hebben op het zenuwstelsel. Onvoldoende kennis van de toxiciteit en de mechanismen die ten grondslag liggen aan de neurotoxiciteit van deze stoffen maakt het inschatten van de risico’s moeilijk. Om deze kennisleemte op te vullen, is een in silico methode onderzocht gebaseerd op de Quantitative Structure-Activity Relationship (QSAR)-benadering en ongewerveld diermodel (planarian = platworm) om de neurotoxiciteit te voorspellen van chemische stoffen die relevant zijn voor water. Deze combinatie van innovatieve methoden maakt het mogelijk de waterkwaliteit te beoordelen door theoretische voorspellingen effectief te koppelen aan werkelijke neurotoxische effecten die worden waargenomen in een platwormmodel. Verder onderzoek zal bijdragen aan de validatie van deze combinatie die theoretische voorspellingen en empirische bepalingen combineert.