Nanotoxicology and metabolomics

Nanotechnology consumer products are now part of our everyday lives with the use of nanoparticles in fuels, cosmetics, food packaging, drug delivery systems, therapeutics and many other applications. Despite the obvious benefit of these nanoparticles there are many unanswered questions on the potential environmental and human health risks associated with the production, use and disposal of these materials, and there is minimal quantitative data to assess the risks.

Omics technologies provide an unbiased approach to assess an organism’s response to the nanoparticles and help to identify adaptive and toxic responses. The data generated in omic studies provides molecular-level information that can in principle link the initial exposure to an adverse outcome at the organism and population level. This approach is termed Adverse outcome pathways and represents a new concept to help to assess the risk and drive regulatory procedures. The sequence of events from the initial exposure or molecular initiating event sparks a chain of key events that manifest at the molecular, cellular, tissue, organ and organism level. To develop the adverse outcome pathway we need to understand, discover and characterise the biological mechanism and the level of perturbation that is required in the biological system before dysregulation and toxicity occurs. This approach provides a mechanism to understand the toxicity (and to infer it, or read it across, to other nanoparticles) rather than simply observing the effects of the toxicant.

Adverse Outcome Pathway

NanoMILE is an important EU funded project to establish a fundamental understanding of the mechanisms of nanomaterial interactions with living systems and the environment across the entire life cycle of nanomaterials in a wide range of target species. The aim of the project is to apply ‘omic technologies to understand the potential impacts of nanoparticles on human health and the environment, provide guidelines on the toxicology of nanoparticles and support the sustainable development of nanotechnology.

At the University of Birmingham we study the model organisms Chlamydomonas reinhardtii (a unicellular green algae) and Daphnia magna (water flea) and apply both transcriptomic and metabolomics technologies to understand the interaction between the organism, nanoparticles and environment.

In a recent study by Taylor et al. 2016 the molecular toxicity of cerium oxide nanoparticles, a nanoparticle commonly used as a fuel catalyst was investigated in the freshwater algae Chlamydomonas reinhardtii. The study focussed on the freshwater environment, as it is an anticipated sink for nanoparticle discharge. Algae were exposed to a range of nanoparticle concentrations from predicted environmental levels to concentrations that are expected to be hazardous and supra-environmental levels. The results indicated that nanoparticles did not influence the growth of the algal cells but were taken up by the cells and internalised into intracellular vesicles. By applying transcriptomics and metabolomics it was found that at the supra-environmental levels of nanoparticles molecular changes were detected. Transcripts and metabolites were down-regulated in the carbon fixation pathway and changes in the transcript and metabolite levels were observed in coenzyme A and fatty acid biosynthesis, amino acid, nucleotide and carbohydrate metabolism. The observations of the study were consistent with a repression of photosynthesis and carbon-fixation.

Bridging the gap from research output to regulatory procedure

The molecular changes identified in this study can direct the construction of the adverse outcome pathway and thereby facilitate the regulatory hazard assessment for the long-term effects of the cerium oxide nanoparticle in the environment. The potential repercussions of the internalisation of the nanoparticles in the algal cells and aquatic food chain should be addressed as part of a rigorous hazard assessment of the nanomaterial.