Climate change effects on POPs' environmental behaviour: a scientific perspective for future regulatory actions

Abstract Since the adoption of the United Nations Framework Convention on Climate Change, international efforts were aimed at limiting global change, and at managing and reducing its inevitable impacts. The growing concern on climate change related issues lead to create international agreements such as the Kyoto Protocol, and to establish the Intergovernmental Panel on Climate Change aimed at studying climate evolution and at defining common actions through the adoption of joint climate change mitigation and adaptation measures. From the time when international Task Forces, projects and programs were shared in order to deal with the reduction of environmental exposure to persistent organic pollutants (POPs), international organisations have also been committed to estimate how climate change may affect POPs' environmental behaviour and distribution. In this review paper, we report the track of POPs' regulation efforts driven towards decreasing POPs' environmental concentrations through reducing or banning POP emissions in the environment. We also report scientific studies on climate change related effects on POPs' environmental behaviour in order to feature how climate change is influencing POPs' fate and transport. Our final aim is to identify how POPs–related regulations may take into account climate change in managing current or future POPs sources. We find in several case studies on this topic that climate change is considered to contribute to enhance POPs' long–range transport and that remote areas are considered likely to be the most impacted by POPs' pollution under a climate change perspective. Our findings also consider that continuous monitoring programs oriented towards the observation of secondary POP sources and the enhancement of inventories reporting primary and secondary POP emissions are useful in dealing with POPs' exposure under climate change scenarios. We also suggest how communication between science and regulation should be driven towards considering climate change effects into chemicals' legislation

Evaluation of the availability and applicability of computational approaches in the safety assessment of nanomaterials: Final report of the Nanocomput project

This is the final report of the Nanocomput project, the main aims of which were to review the current status of computational methods that are potentially useful for predicting the properties of engineered nanomaterials, and to assess their applicability in order to provide advice on the use of these approaches for the purposes of the REACH regulation. Since computational methods cover a broad range of models and tools, emphasis was placed on Quantitative Structure-Property Relationship (QSPR) and Quantitative Structure-Activity Relationship (QSAR) models, and their potential role in predicting NM properties. In addition, the status of a diverse array of compartment-based mathematical models was assessed. These models comprised toxicokinetic (TK), toxicodynamic (TD), in vitro and in vivo dosimetry, and environmental fate models. Finally, based on systematic reviews of the scientific literature, as well as the outputs of the EU-funded research projects, recommendations for further research and development were also made. The Nanocomput project was carried out by the European Commission’s Joint Research Centre (JRC) for the Directorate-General (DG) for Internal Market, Industry, Entrepreneurship and SMEs (DG GROW) under the terms of an Administrative Arrangement between JRC and DG GROW. The project lasted 39 months, from January 2014 to March 2017, and was supported by a steering group with representatives from DG GROW, DG Environment and the European Chemicals Agency (ECHA).JRC.F.3-Chemicals Safety and Alternative Method

A framework for grouping and read-across of nanomaterials- supporting innovation and risk assessment

According to some legislation grouping can streamline data gap filling for the hazard assessment of substances. The GRACIOUS Framework aims to facilitate the application of grouping of nanomaterials or nanoforms (NFs), in a regulatory context and to support innovation. This includes using grouping to enable read-across from (a) source(s), for which data and information exist, to a similar target NF where information is lacking. The Framework provides an initial set of hypotheses for the grouping of NFs which take into account the identity and use(s) of the NFs, as well as the purpose of grouping. Initial collection of basic information allows selection of an appropriate pre-defined grouping hypothesis and a tailored Integrated Approach to Testing and Assessment (IATA), designed to generate new evidence to support acceptance or rejection of the hypothesis. Users needing to develop their own user-defined hypothesis (and IATA) are also supported by the Framework. In addition, the IATA guides acquisition of the information needed to support read-across. This approach gathers information to render risk assessment more efficient, affordable, as well as reducing the use of test animals

Emissions of pharmaceuticals and plant protection products to the lagoon of Venice: development of a new emission inventory

Estimating the emissions of chemical pollutants to water is a fundamental step for the development and application of effective and sustainable management strategies of water resources, but methods applied so far to build chemicals inventories at the European or national scale show several limitations when applied at the local scale. The issue is particularly relevant when considering contaminants of emerging concern (CECs), whose environmental releases and occurrence are still poorly studied and understood. In this work, an approach to estimate water emissions of nine active pharmaceutical ingredients (APIs) and ten most applied plant protection products (PPPs) is presented, considering proxy indicators (e.g., sales data and census information). The application area is the lagoon of Venice (Italy), a complex transitional environment highly influenced by anthropic pressures (e.g., agricultural and industrial activities, animal breeding, and wastewater discharge). The presented approach can be tailored to the information available for any local scale case study. Data on annual regional sales of PPPs and APIs were integrated with georeferenced demographic and economic statistics (such as census and land-use information) to estimate chemicals emissions to surface water and groundwater. A sensitivity and uncertainty analysis identified the main factors affecting emissions estimates, and those contributing more significantly to results uncertainty. Results showed the highest estimated emissions of APIs for antibiotics (i.e., amoxicillin, clarithromycin, azithromycin, and ciprofloxacin) used for humans and animals, while most of hormones’ emission (i.e., 17- α-ethinylestradiol and 17-β-estradiol) derived from animal breeding. Regarding PPPs, glyphosate and imidacloprid emissions were one to two orders of magnitude higher compared to the other chemicals. Uncertainty and sensitivity analysis showed that the variability of each parameter used to estimate emissions depends greatly both on the target chemical and the specific emission source considered. Excretion rates and removal during wastewater treatment were major key parameters for all the target pharmaceutical compounds, while for PPPs the key parameter was their loss into the natural waters after application

Role of Physiologically Based Kinetic modelling in addressing environmental chemical mixtures – A review

The role of Physiologically Based Kinetic (PBK) modelling in assessing mixture toxicology has been growing for the last three decades. It has been widely used to investigate and address interactions in mixtures. This review describes the current state-of-the-art of PBK models for chemical mixtures and to evaluate the applications of PBK modelling for mixtures with emphasis on their role in chemical risk assessment. A total of 35 mixture PBK models were included after searching web resources (Scopus, PubMed, Web of Science, and Google Scholar), screening for duplicates, and excluding articles based on eligibility criteria. Binary mixtures and volatile organic compounds accounted for two-thirds of the chemical mixtures identified. The most common exposure route and modelled system were found to be inhalation and rats respectively. Twenty two (22) models were for binary mixtures, 5 for ternary mixtures, 3 for quaternary mixtures, and 5 for complex mixtures. Both bottom-up and top-down PBK modelling approaches are described. Whereas bottom-up approaches are based on a series of binary interactions, top-down approaches are based on the lumping of mixture components. Competitive inhibition is the most common type of interaction among the various types of mixtures, and usually becomes a concern at concentrations higher than environmental exposure levels. It leads to reduced biotransformation that either means a decrease in the amount of toxic metabolite formation or an increase in toxic parent chemical accumulation. The consequence is either lower or higher toxicity compared to that estimated for the mixture based on the additivity principle. Therefore, PBK modelling can play a central role in predicting interactions in chemical mixture risk assessmentJRC.F.3-Chemicals Safety and Alternative Method

Grouping of multi-walled carbon nanotubes to read across genotoxicity: a case study to evaluate the applicability of regulatory guidance

Multi-walled carbon nanotubes (MWCNTs) consist of multiple layers of graphene sheets in a tubular shape. Due to their specific material properties, such as electrical and thermal conductivity, strength, rigidity, and toughness they are useful in a wide variety of applications in electronics, optics and other fields of materials science. Depending on the synthesis and purification method, MWCNTs may differ in size, shape, rigidity and other properties. Previous research has shown that physicochemical properties can influence the translocation and toxicity of MWCNTs. This paper describes a case study following the “Recommendations for nanomaterials applicable to the Guidance on QSARs and Grouping”, developed by the European Chemicals Agency (ECHA). Based on the data availability genotoxicity was selected as the hazard endpoint to explore and illustrate read across. The grouping hypothesis was supported by the use of chemoinformatics techniques such as hierarchical clustering and principal components analysis. The uncertainties of the present case study were evaluated using the Read-Across Assessment Framework (RAAF) developed by ECHA. This study shows the practical application of the ECHA framework for grouping of nanomaterials (NMs) as well as use of the ECHA RAAF for NMs, and how this can be supported by chemoinformatics techniques. Some adaptations to the workflow are suggested for a more practical and straightforward narrative in the reporting.JRC.F.3-Chemicals Safety and Alternative Method

Grouping of multi-walled carbon nanotubes to read-across genotoxicity: A case study to evaluate the applicability of regulatory guidance

Multi-walled carbon nanotubes (MWCNTs) consist of multiple layers of graphene sheets in a tubular shape. Depending on the synthesis and purification method, MWCNTs may differ in size, shape, rigidity and other properties. Previous research has shown that physicochemical properties can influence the translocation and toxicity of MWCNTs. Extensive in vitro and in vivo testing may be required to characterise the hazard of various physical forms of MWCNTs. Grouping of MWCNTs to read-across data for toxicological endpoints could efficiently contribute to reduce and focus MWCNT testing. This paper describes a case study to explore and illustrate read-across of genotoxicity data by following the “Recommendations for nanomaterials applicable to the Guidance on QSARs and Grouping”, developed by the European Chemicals Agency (ECHA). The grouping hypothesis was supported by the use of chemoinformatics techniques such as hierarchical clustering and principal components analysis. The uncertainties of the present case study were evaluated using the Read-Across Assessment Framework (RAAF) developed by ECHA. While the aim of this study was not to conduct a hazard assessment, the study data chosen for illustrative purposes suggest that the MWCNTs analogues selected are not genotoxic. No (major) differences between the analogues were observed which could be attributed to differences in physicochemical properties such as length, diameter or rigidity/straightness. Such properties, however, may have an impact on other hazard endpoints such as carcinogenicity. This study shows the practical application of the ECHA framework for grouping of nanomaterials (NMs) as well as use of the ECHA RAAF for NMs, and how this can be supported by chemoinformatics techniques. Some adaptations to the workflow are suggested for a more practical and straightforward narrative in the reporting