Adverse Outcome Pathways for Endocrine Disruption in Daphnia magna, a conceptual approach for mechanistically-based Risk assessment (EDRISK).
Computational (predictive) and experimentally derived development of Adverse Outcome Pathways for endocrine disruption in Daphnia magna to establish links between perturbations of key molecular events and adverse outcomes of regulatory relevance.
Endocrine disruptors (ED) have received considerable scientific attention since the documentation of reduction in sperm count in young men and feminization of various aquatic vertebrates in the early 1990s (Ashby et al., 1997). It’s today commonly accepted that a number of exogenous compounds have the potential to interfere with the endocrine system of animals and potentially modulate (perturb) vital endocrine processes to a degree causing an adverse apical effect (outcome) associated with growth, development and reproduction.
Endocrine disrupting (ED) effects have been well characterised in aquatic vertebrates and mammals, but lack of knowledge of ED effects in invertebrates is a major limiting factor to risk assessment of endocrine disrupting chemicals. Crustacean hormone signaling has been shown to be susceptible to endocrine disruption by disturbances in hormone homeostasis and interference with cellular targets. Examples such as masculinization of gastropod snails by tributyltin (Schulte-Oehlmann et al., 2000), and interference with normal moulting and reproduction by several industrial compounds in crustaceans (LeBlanc, 2007) clearly show that ED should be considered a threat to a broad diversity of aquatic life.
Crustaceans rely on peptide hormones as intermediate and terminal signal transducers, but they also utilize ecdysteroids (i.e. 20-hydroxyecdysone) and terpenoids (i.e. methyl farnesoate) as major terminal endocrine signaling molecules. Experimental studies on potential ED effects mediated through these and other crustacean hormone systems will in the EDRISK project be used to develop links between the mode of action (MoA) and adverse effects (outcomes) relevant for risk assessment.
The Norwegian Institute for Water Research (NIVA) is managing a Norwegian Research Council (NRC) funded project “221455-Adverse Outcome Pathways for Endocrine Disruption in Daphnia magna, a conceptual approach for mechanistically-based Risk assessment (EDRISK)" in the period 2013 – 2017.
The objective of the present project is to develop and evaluate Adverse Outcome Pathways (AOP) for EDs in the freshwater crustacean D. magna (Water flea) as a conceptual framework for mechanistically-based risk assessment of single compounds and complex mixtures of these.
Ashby, J., Houthoff, E., Kennedy, S.J., Stevens, J., Bars, R., Jekat, F.W., Campbell, P., Van Miller, J., Carpanini, F.M., Randall, G.L., 1997. The challenge posed by endocrine-disrupting chemicals. Environ Health Perspect 105, 164-169.
LeBlanc, G.A., 2007. Crustacean endocrine toxicology: a review. Ecotoxicol. 16, 61-81.
Schulte-Oehlmann, U., Tillmann, M., Markert, B., Oehlmann, J., Watermann, B., Scherf, S., 2000. Effects of endocrine disruptors on prosobranch snails (Mollusca: Gastropoda) in the laboratory. Part II: Triphenyltin as a xeno-androgen. Ecotoxicol. 9, 399-412.