Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment.

The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, "Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment" was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages.

Correction to: Occurrence and risk assessment of trace metals and metalloids in sediments and benthic invertebrates from Dianshan Lake, China.

The article Occurrence and risk assessment of trace metals and metalloids in sediments and benthic invertebrates from Dianshan Lake, China, written by Yan Wu, Yihui Zhou, Yanling Qiu, Da Chen, Zhiliang Zhu, Jianfu Zhao and Åke Bergman.

Phthalate esters on urban airborne particles: Levels in PM10 and PM2.5 from Mexico City and theoretical assessment of lung exposure.

Endocrine disrupting chemicals (EDCs) from the environment are associated with reproductive abnormalities (i.e. decreased sperm concentration; increased endometriosis) and alterations of the cardiovascular system (i.e. increased blood pressure and risk of coronary disease). Some phthalates esters have been identified as EDCs, for which inhalation is considered as one of the routes of exposure. However, only little is known regarding inhalational exposure to EDCs via urban airborne particles. In the present study, we report the monthly concentration of 8 phthalate esters measured in PM10 and PM2.5 collected and recovered during 7 months in a highly populated area of Mexico City. Using the levels of PM10 and PM2.5 reported by the automatized network of environmental monitoring of Mexico City for the sampling site, we estimated exposure levels for people of different ages and gender. Two endocrine disrupting compounds, the phthalate esters DEHP and DnBP, were found on the particles in higher concentrations during the warmer months of the year. The highest concentration was reported for DEHP (229.7µg/g of particles) in PM2.5 collected in May 2013. After calculations of the DEHP concentration in the atmosphere, and using the respiratory flow rate, we determined males were potentially exposed to larger quantities of DEHP, reaching up to 18ng/8h in April 2013. Despite the concentrations of phthalates seem to be rather small, a comprehensive characterization of its presence is necessary in order to evaluate the overall exposure to these compounds, providing a clear view of exposure on children, adolescents and pregnant women.

A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals.

BACKGROUND: The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. METHODS: We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. RESULTS: Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. CONCLUSIONS: When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.

Science and policy on endocrine disrupters must not be mixed: a reply to a "common sense" intervention by toxicology journal editors.

The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.

Assessment of emerging and traditional halogenated contaminants in Guillemot (Uria aalge) egg from North-Western Europe and the Baltic Sea.

Persistent organic pollutants (POPs) are readily detected in biological samples at remote sites in the Arctic and sub-Arctic due to long-range transport from source areas. The aim of this study was to investigate the presence of POPs, polybrominated contaminants and their metabolites in guillemot (Uria aalge) eggs from Iceland, the Faroe Islands, Norway and Sweden to assess spatial trends of these compounds in the Arctic and sub-Arctic areas of Europe. Egg samples were extracted, and cleaned for chemical analysis. Concentrations of PCBs, 4,4'-DDE and beta-HCH were an order of magnitude higher in eggs from the Baltic Proper compared to eggs from the North Atlantic. Concentrations of HCB were of the same magnitude at all sites, ranging from 160 to 520 ng/g fat. Concentration of BCPS was 100 times higher in eggs from the Baltic compared to eggs from the North Atlantic and seems therefore to be special regional problem. Concentrations of PBDEs were lower in eggs from the North Atlantic compared to eggs from the Baltic Proper but the difference was not as large as for PCBs and 4,4'-DDE. HBCDD showed the same spatial trend as PCBs, where the concentrations in eggs from the Baltic Proper were an order of magnitude higher than in eggs from the North Atlantic. OH-PCB and MeSO(2)-PCB metabolites of PCBs, showed the same trend as the parent compounds while spatial trends of MeSO(2)-DDE and OH-PBDEs, metabolites of 4,4'-DDE and PBDEs, respectively, differed from the trend of the parent compounds. This may be due to two factors; firstly, the limited ability of birds to metabolise DDT, and secondly, to natural production of OH-PBDE, respectively. Guillemot is suggested as a monitoring species for circumpolar monitoring.

Exposure assessment of polybrominated diphenyl ethers (PBDEs) in Mexican children.

Flame retardants (FRs) constitute a group of compounds that are added to materials in order to suppress, reduce, or delay fire. At present the most used FRs are the polybrominated diphenyl ethers (PBDEs), and diverse studies have found individuals exposed to them. However, few studies have reported data in children. The objective of this report was to assess PBDEs levels in children of six communities in México. During the year 2006 we analyzed a total of 173 healthy children (aged 6-13 years old). Plasma samples were taken and quantified (gas chromatography/mass spectrometer) for PBDEs. Six PBDEs congeners (BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, and BDE-209) were quantified in blood serum. We detected exposure to PBDEs in all the communities. The total PBDEs levels ranged from no detectable (nd) to 43.4 ng g(-1) lipid, the dominant PBDE congener was BDE-47, followed by BDE-100, BDE-99 and BDE-153, whereas the levels of BDE-209 were below LOD. Children living in an industrial and urban area (Cd. Juarez, Chih) had the highest levels of PBDEs, approximately two times that of children living in El Refugio, S.L.P. (a rural area) or in Milpillas, S.L.P. (municipal landfill) and 4-5 times higher than levels found in children living in San Luis Potosi, S.L.P. (urban area), in Chihuahua, Chih. (urban area), and San Juan Tilapa, Edo. Mex. (municipal landfills). Results cannot be generalized since the communities selected are not representative of the Mexican population. However, they do indicate that Mexican children are exposed to PBDEs.

A standardized method for assessment of oxidative transformations of brominated phenols in water.

The term persistence has been used to confusion since it is used as a conceptual parameter without a uniform definition. Work is therefore being done in order to unite ideas and describe persistence based on the chemical reactivity and chemico-physical properties of compounds via investigation of the main degradation pathways in the environment; photolysis, hydrolysis-substitution-elimination (hse), oxidation, reduction and radical reactions. The present work is focused on developing a method to determine oxidative degradation rates of chemicals and thereby measurement of their susceptibility to undergo oxidation reactions. The method based on potassium permanganate works well for water soluble compounds and is easy, robust, inexpensive and reproducible. By using the method and varying the analysed substances, the degradation rates for brominated phenols, two chlorinated phenols and high volume production compounds such as tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA) and bisphenol A (BPA) have been determined at pH 7.6+/-0.2. The reaction rates of the two halogenated BPA's are particularly fast, giving half-lives in seconds. The other test compounds have slower reaction rates but easily measured under the reaction conditions applied. The reactions are temperature dependent. There is evidence that pK(a) and the substitution pattern of the halogens affects the rate of the reactions. The method is robust and applicable for reaction rate constant measurements of present and potential future environmental contaminants.

An overview of commercially used brominated flame retardants, their applications, their use patterns in different countries/regions and possible modes of release.

Brominated flame retardants (BFRs) are used in a variety of consumer products and several of those are produced in large quantities. These compounds have been detected in environmental samples, which can be attributed to the anthropogenic uses of these compounds. Brominated flame retardants are produced via direct bromination of organic molecules or via addition of bromine to alkenes; hence, an overview of the production and usage of bromine over the past three decades is covered. Production, application, and environmental occurrence of high production brominated flame retardants including Tetrabromobisphenol A, polybrominated biphenyls, Penta-, Octa-, Deca-brominated diphenyl ether (oxide) formulation and hexabromocyclododecane are discussed.