Deliverable 9.1 - Report on mixtures and implementation strategy in Europe – Assessment of chemical mixtures under consideration of current and future regulatory requirements and scientific approaches

This report gives an overview on the regulatory processes and requirements for risk assessment of chemical mixtures, identifies gaps in the European legislation and summarises potential approaches for the health risk assessment of chemical mixtures

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

FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.Most co-authors were financialy supported with their respective inistitution. Some of the co-authors were financialy supportrd by the Safe and Efficient Chemistry by Design (SafeChem) project (grant no. DIA 2018/11) funded by the Swedish Foundation for Strategic Environmental Research, and by the PARC project (grant no. 101057014) funded under the European Union's Horizon Europe Research and Innovation program

Determination of dimethoate and omethoate in human serum samples. Risk assessment for the operator

A simple and effective analytical procedure has been developed for the determination of dimethoate (DIM) residues and its metabolite, omethoate, in serum samples of pesticide operators. For the selection of the most appropriate method for sample treatment, techniques such as headspace solid phase micro extraction and solid phase extraction and liquid-liquid extraction were applied. The applied method was based on toluene (2 mL) extraction of a 0.5mL serum sample. In this report, it was observed that DIM concentration level affected the ratio of the area response of DIM and one of its oxygenated metabolite, omethoate. In this context, higher concentrations favoured the predominance of DIM while lower concentrations lead to the formation of omethoate. The method was validated using human serum samples spiked with DIM. Good linearity was obtained in the range of 1-10 ng/mL co-calculating DIM and omethoate. Various concentrations of DIM were mixed with serum and stored up to five days at -20°C. Recoveries ranged from 72% to 88% at two spiking levels for six replicates. The detection and quantification limit were calculated at 0.12 and 0.36 ng/mL of serum, respectively. Finally the comparison with the Acceptable Operator Exposure Level (AOEL) of DIM revealed that the maximum exposure of the operators reached the 30% of the AOEL for only two cases. © 2011 Taylor & Francis

The spatial and temporal distribution/variation of pesticide residues in Viotikos Kifissos basin before and after the application of a low input crop management system. A three-year study

A three-year study of the spatial and temporal variation of pesticide residues in Viotikos Kifissos basin (VKB), in central Greece, before and after the application of Low-Input Crop Management systems (LCM), was carried out between May 2009 and November 2011. A total of 253 water samples from 34 sampling points (boreholes, rivers, wells, vadose zone) were analysed for the presence of more than 200 pesticides and degradation products, using liquid and gas chromatography coupled to tandem mass spectrometry. Samples were prepared by solid-phase extraction (SPE) using Oasis HLB cartridges. Almost 70% of the samples were found positive for the presence of pesticides in amounts greater than the limit of detection. The most frequently detected pesticide was fluometuron, followed by s-metolachlor, metalaxyl-M, imidacloprid and ethalfluralin. The highest concentration was recorded for fluometuron (322 μg L−1), ethalfluralin (123 μg L−1) and s-Metolachlor (36.4 μg L−1). Results showed a reduction of the pesticides detected and quantified in water samples during 2011 compared to those measured in 2009 and 2010. © 2015 Taylor & Francis

Optimal designs for estimating linear and quadratic contrasts with three level factors, the case N ≡ 0 mod 3

The purpose of this paper is to find and construct optimal designs for estimating the standardized linear and quadratic contrasts in fractional factorials with k factors, each at 3 levels, when the number of runs or assemblies is N. The case N=3m is examined, the notion of Balanced Arrays BA(N, k, 3, 2) or BA(N, k) for short, is introduced and the optimal BA(N, k) is specified. It is shown that for N=9m the orthogonal array OA(N, k, 3, 2) or OA(N, k) for short, is the φ-optimal design. If N=9m+3 and N=9m+6 the optimal designs are BA(N, k) which are specified for every value of N and k. In the case N=9m+3 and k=3 the optimal BA(N, k) are constructed by augmenting OA(N, k, 3, 2) by three rows which are specified. If the OA(N, k, 3, 2) does not exist, algorithms are developed to construct the optimal BA(N, k). For N=9m+6 and k=3 the optimal BA(N, k) are constructed by augmenting OA(N, k) by six rows, which are specified, otherwise algorithms are developed. Under optimal BA(N, k), the estimators of linear and quadratic contrasts are uncorrelated. The cases N=12,15,21,24,30,33 are examined in detail and optimal BA(N, k) are presented for different values of the number k of factors. © 2017 Informa UK Limited, trading as Taylor & Francis Group