Advance on risk assessment methods of multiple chemicals combined exposure and its enlightenment to the construction of relevant systems in China

People in the real world are exposed to multiple chemicals via multiple routes and co-exposure to multiple agents may induce joint effects, which draws extensive attention from the international community. Regulations of many countries oblige risk assessors to conduct cumulative risk assessments based on their own guidelines, findings of which provide the basis for scientific decision-making. By analyzing the method and frameworks of international risk assessment models of multiple chemicals, this paper explores the establishment of a risk assessment framework of multiple chemicals combined exposure to in food in China

Future water quality monitoring - Adapting tools to deal with mixtures of pollutants in water resource management

Environmental quality monitoring of water resources is challenged with providing the basis for safeguarding the environment against adverse biological effects of anthropogenic chemical contamination from diffuse and point sources. While current regulatory efforts focus on monitoring and assessing a few legacy chemicals, many more anthropogenic chemicals can be detected simultaneously in our aquatic resources. However, exposure to chemical mixtures does not necessarily translate into adverse biological effects nor clearly shows whether mitigation measures are needed. Thus, the question which mixtures are present and which have associated combined effects becomes central for defining adequate monitoring and assessment strategies. Here we describe the vision of the international, EU-funded project SOLUTIONS, where three routes are explored to link the occurrence of chemical mixtures at specific sites to the assessment of adverse biological combination effects. First of all, multi-residue target and non-target screening techniques covering a broader range of anticipated chemicals co-occurring in the environment are being developed. By improving sensitivity and detection limits for known bioactive compounds of concern, new analytical chemistry data for multiple components can be obtained and used to characterise priority mixtures. This information on chemical occurrence will be used to predict mixture toxicity and to derive combined effect estimates suitable for advancing environmental quality standards. Secondly, bioanalytical tools will be explored to provide aggregate bioactivity measures integrating all components that produce common (adverse) outcomes even for mixtures of varying compositions. The ambition is to provide comprehensive arrays of effect-based tools and trait-based field observations that link multiple chemical exposures to various environmental protection goals more directly and to provide improved in situ observations for impact assessment of mixtures. Thirdly, effect-directed analysis (EDA) will be applied to identify major drivers of mixture toxicity. Refinements of EDA include the use of statistical approaches with monitoring information for guidance of experimental EDA studies. These three approaches will be explored using case studies at the Danube and Rhine river basins as well as rivers of the Iberian Peninsula. The synthesis of findings will be organised to provide guidance for future solution-oriented environmental monitoring and explore more systematic ways to assess mixture exposures and combination effects in future water quality monitoring.Seventh Framework Programme (E.U

International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals (“chemical mixtures”) is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation) to tier 3 (full probabilistic models). This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area

The challenges of consulting the public on science policy: examining the development of European risk assessment policy for genetically modified animals

With the growing importance of public engagement in science policy-making and declining levels of public trust in food production, the European Food Safety Authority (EFSA) has attempted to embed ‘good governance’ approaches to strengthen scientific independence and open-up risk decision-making, which include the use of public consultations. However ‘opening-up’ of risk assessment policies reveals some tensions, namely: balancing the goals of scientific excellence and transparency; protecting science from interests; addressing value judgments; limited opportunities to debate ethical and social issues. EFSA’s development of risk assessment policy for genetically modified animals is used as a case study to analyse these tensions. This analysis suggests that in order to fulfil good governance commitments and maintain trust in risk governance closer cooperation between EFSA and the European Commission is required to provide ‘space’ for debating the broader risk management issues. This publically-accessible space may be needed alongside rather than instead of EFSA’s consultation

Towards a non-animal risk assessment for anti-androgenic effects in humans

In recent years, concern has been raised over the possibility that substances in foods, consumer products and the environment are causing health effects in humans and the environment due to their ability to perturb endocrine signalling. Toxicological risk assessments therefore need to be protective for these modes of action. The accepted approach for assessing potential ‘endocrine disrupting chemicals’ (EDCs) involves the generation of laboratory animal data. The growing dissatisfaction of many scientists with the relevance of animal studies to the assessment of human risk and increasing societal demand for an end to animal testing presents challenges and opportunities in the safety evaluation of these substances. This thesis examines the opportunities to apply non-animal approaches to the risk assessment of anti-androgenic substances in consumer products. Gaps were identified that are currently preventing the adoption of such an approach, which broadly cover three areas. Firstly, under the current paradigm, in vitro alerts for anti-androgenicity invariably trigger animal testing, so an approach to allow risk-based decision making using only in vitro and exposure data is needed. Secondly, there is a lack of in vitro tools able to characterise the effects of substances affecting the hypothalamic and pituitary control of gonadotropin secretion; a search was conducted for cells that could address this. Thirdly, there are currently no in vitro models capable of distinguishing between exposures that cause adaptive changes to endocrine signalling and those that cause adverse health effects. The use of 3D prostate microtissues was therefore investigated to assess whether these would provide biomarkers to identify tipping points between adaptive and adverse responses. A tiered, exposure-led, and human-relevant risk assessment approach was developed that can be applied to safety decision making and prevent unnecessary animal use. Further developments in some of the higher-tier tools investigated will further reduce and ultimately replace the use of animals in risk assessment of anti-androgens

Plan for development of case studies - Deliverable Report AD 15.1 WP 15 - Mixtures, HBM and human health risk

This deliverable describes the activities in task 15.3 leading up to the development of cases studies for mixture health effects and outlines the proposed case studies. The proposed case studies are: · Developmental neurotoxicity beyond polybrominated diphenylethers · Heavy metals and nephrotoxicity · Anti-androgenic chemicals and male reproductive health · Chromium (VI), nickel and polycyclic aromatic hydrocarbons and lung cancer · Addressing exposure misclassification in mixture studies The Addendum provides further details about multi-year perspective and timing, as well as detailed budgetary aspects per case study.HBM4EU- Grant agreement 733032 HORIZON2020 Programmeinfo:eu-repo/semantics/publishedVersio

Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution

This article reviews the current legislative requirements for risk assessment of combined exposure to multiple chemicals via multiple exposure routes, focusing on human health and particularly on food-related chemicals. The aim is to identify regulatory needs and current approaches for this type of risk assessment as well as challenges of the implementation of appropriate and harmonized guidance at international level. It provides an overview of the current legal requirements in the European Union (EU), the United States and Canada. Substantial differences were identified in the legal requirements for risk assessment of combined exposure to multiple chemicals and its implementation between EU and non-EU countries and across several regulatory sectors. Frameworks currently proposed and in use for assessing risks from combined exposure to multiple chemicals via multiple routes and different durations of exposure are summarized. In order to avoid significant discrepancies between regulatory sectors or countries, the approach for assessing risks of combined exposure should be based on similar principles for all types of chemicals. OECD and EFSA identified the development of harmonized methodologies for combined exposure to multiple chemicals as a key priority area. The Horizon 2020 project “EuroMix” aims to contribute to the further development of internationally harmonized approaches for such risk assessments by the development of an integrated test strategy using in vitro and in silico tests verified for chemical mixtures based on more appropriate data on potential combined effects. These approaches and testing strategies should be integrated in a scientifically based weight of evidence approach to account for complexity and uncertainty, to improve risk assessment