MolPoP

Establishing causal relationships between pollutant-induced responses at the molecular level and adverse effects at the individual and population level is instrumental to the integration of scientific and regulatory efforts taken world-wide. NIVA addresses this challenge in the research project MolPoP, funded by the Ministry of Environment through institutional basic funding.

Background

Organisms living in the recipient of various discharges from natural, municipal and industrial sources are exposed to a high number of chemicals where the effects and risk may only be partially known. Current effort within the research community often focus on characterizing the Mode of Action (MoA) of chemicals, whereas parallel regulatory effort tend to focus on assessing adverse (apical) toxicity endpoints relevant for risk assessment. This bias in approaches has led to sub-optimal usage of data from the research community to support regulatory processes and vis versa regulatory decisions endorsed without thorough mechanistical understanding of the cause-effect relationships. Effort to provide causal relationships between MoA and adversity using weight of evidence (WoE) approaches have led to the development of conceptual approaches such as Adverse Outcome Pathways (AOPs) and recently also proposed to guide the scientific identification of chemicals of particular concern. Despite world-wide initiatives to develop such approaches within (eco)toxicology, there is still a need to establish tools and approaches that allow integration of molecular responses with effects occurring at the individual and the population level.

Project

The Norwegian Institute for Water Research (NIVA) has funded the project “Linking pollutant induced molecular responses to adverse effects at the individual and population level in aquatic organisms (MolPoP)” as part of their Strategic institute Initiative (SIS) from 2011 to 2013.

Objectives

Establish relationship between molecular responses, individual and population effects as tools to assess the hazard and risk of single pollutants and mixtures of these. The objectives will be delivered by 1) developing a suite of molecular tools for biomarker and effect assessment in a battery of aquatic species, 2) develop and evaluate predictive tools for assessing population effects, 3) develop predictive tools for assessing mixture toxicity and multiple stressors, and 4) provide a causal linkage between responses occurring at the molecular level to adverse effects at the individual and population level for single chemicals (stressors) and mixtures of these. 

Approaches

Molecular tools
Advanced genomics approaches such as RNA-sequencing, RNA oligonucleotide microarray-analysis and quantitative rtPCR will be developed for a suite of aquatic invertebrates and vertebrates to allow “Genome-wide” characterization of the toxic MoA. Future aspects will focus on proteomics, metabolomics and epigenetic analysis to provide a holistic assessment of molecular responses and support “systems toxicology” approaches.

Predicting population effects
Effects of chemicals (stressors) of individual organisms are often extrapolated to the population-level via estimating effects on demographic rates (growth, fecundity, survival). A set of models will be evaluated and modified (upon need) to extrapolate individual effect data to population level for a selection of aquatic species. 

Combined toxicity assessment
Combined toxicity of multiple chemicals and stressors may be predicted on basis of knowledge of MoA and the assembly of compounds (stressors). Development and evaluation of such predictive models will be performed in a selection of bioassays, relevant endpoints and exposure scenarios.