Endocrine disrupting mechanism of typical environmental pollutants
Dr Ivana Vinković Vrček, Institute for Medical Research and Occupational Health, Zagreb, Croatia
Prof Sijin Liu, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, People’s Republic of China
Considering specific physico-chemical properties and reactivity of materials at the nanoscale, risk assessment should take into account effects, activity and toxicity of complex chemical mixtures that are generated during life cycle of engineered materials like nanomaterials and plastics. However, our understanding of the potential contamination of the human population by micro- or nanoplastics sourced from the environment is in its infancy, leaving many questions unanswered. Proposed EmergeTox project aims to generate a comprehensive knowledge and database on the intrinsic properties, stability and interaction of two types of emergent nano-based pollutants – plastic and metallic nanoparticles – to gain better mechanistic understanding of their impact on human health under various exposure settings. Synergistic toxic effects of these NPs with and without the presence of endocrine disrupting chemicals (PCBs and parabens) will be tested both in vitro and in vivo using mammalian models. Project will implement Adverse Outcome Pathways (AOP) as the main tool to organize information for routine integration of mode of action (MOA) information into risk assessment. Evaluation of AOPs will be focused on cytotoxicity, mutagenic activity, oxidative stress response, androgen receptor activity, agonism and antagonism, estrogen receptor activity, acetylcholinesterase inhibition, CYP2E1 activation and formation of protein adducts, following two main outcomes: cancer and neurodegeneration. Information on health risks from such complex mixtures will be translated into guidelines and recommendations for for early hazard identification, risk assessment and the design of sustainable solutions for safe production, use and disposal of innovative nano-enabled products.
Two main specific scientific and technical project objectives are:
- Evaluation of stability and transformations of selected metallic and plastic NPs in various biological test media with and without the presence of endocrine disrupting compounds.
- Safety evaluation of NPs to evaluate and define key AOPs.