Effects of marine pharmaceuticals in zebrafish and ZFL cell line - emphasis

Abstract

Pharmaceuticals are considered emerging organic contaminants and concerns on their environmental impact have been raised in the last decades as they have been detected in the environment. Pharmaceuticals enter the aquatic environment mainly due to WWTP effluent discharges or after direct application for veterinary purposes, such as in aquaculture and animal-infection preventing. A commonly found group of pharmaceuticals in the aquatic environment is antineoplastics. Antineoplastics is one of the least studied groups concerning environmental impact and have been considered to represent specific risks to non-target aquatic species due to their mode of action (MoA). They are biologically active compounds that interact with a target molecule and though encountered at low concentrations in the environment (ng/L to ¼g/L), may promote toxicity through different mechanisms or affect organisms with the same target molecule. Such distinct characteristics that antineoplastics possess make them unpredictable in terms of environmental effects. Therefore, the need of an in-depth assessment of such effects is necessary for an environmental risk assessment to promote and develop a risk-based regulation and develop standardized testing procedures for antineoplastics. There are 4 main questions that will be addressed in the EMPHASIS project proposed in this application.Q.1: Do marine pharmaceuticals (MPs) cause eco-, geno- and cytotoxicity to ZF and ZFL cell line?Q.2: What is the bioconcentration potential of MPs to ZF and ZFL cell line?Q.3: How do MPs affect the microbiota (bacterial and fungal communities? composition and number) in ZF?Q.4: How the MPs are metabolized by ZF and ZFL cell line?To address those questions, the EMPHASIS project aims at evaluating i) the effects of clinic antineoplastics (two marine-derived ones, trabectedin and eribulin mesylate) and novel compounds with anticancer properties using in vivo and in vitro models, ii) the potential of cell lines to serve as alternative eco-toxicological models by validating them with the use of in vivo animal models and iii) to evaluate and validate the ecotoxicological effects of new potential MPs when compared to clinic MPs. Finally, with the use of the Adverse Outcome Pathway (AOP) approach, the link between several key events and the effects at different organizational levels will provide robust information for use in regulatory risk assessment. (AU)