European union system for the evaluation of substances: the second version

This publication presents major changes in the assessment of the risks of chemicals to human health and the environment as implemented in the second version of the European Union System for the Evaluation of Substances, EUSES 2.0. EUSES is a harmonised quantitative risk assessment tool for chemicals. It is the PC-implementation of the technical guidelines developed within the framework of EU chemical legislation for industrial chemicals and biocides. As such, it is designed to support decision making by risk managers in government and industry and to assist scientific institutions in the risk assessment for these substances. The development of EUSES 2.0 is a co-ordinated project of the European Chemicals Bureau, EU Member States and the European chemical industry. Several model concepts, the technical background and the user interface of EUSES have been improved considerably. Major changes in the environmental assessment such as the implementation of emission scenario documents for industrial chemicals and biocides, the addition of the marine risk assessment, the enhancement of the regional model to include global scales, and improvements in the secondary poisoning and environmental effects modelling will be discussed. The update of the human risk assessment module in EUSES focuses on the risk characterisation for both threshold and non-threshold substances with, among others, the introduction of assessment factors. The performance of EUSES is illustrated in an example showing the human and environmental risk assessment of a sanitation disinfectant for private use.     

Visualisation of the complexity of EUSES

The interdependencies of parameters applied in the models of EUSES are visualised in a directed connectivity graph. The parameters (inputs, defaults, state variables, outputs) are represented by boxes (nodes) and their relations by lines (edges). The visualisation, on the one hand, clarifies the complexity of the models in EUSES and, on the other hand, creates an overview and transparency. The parameters’ relations to each other can be recognised faster, and the models can be better understood. The complexity was quantified by the number (variety), kind (substance parameter, physico-chemical parameter, concentration, other parameters), and depth (dimension) of the parameter and the number of relations (connectivity). The variety of EUSES (without the modelsSimple Treat andSimple Box whose interior structure is not documented and without the effect and risk characterisation) amounts to 466, the connectivity to 961, and the maximal dimension is 21.     

An intelligent data collection tool for chemical safety/risk assessment

REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) is the new European chemical legislation which aims to assess risk or safety of tens of thousands of chemicals to improve the protection of human health and the environment. The chemical safety assessment process is of an iterative nature. First, an initial, worst-case assessment is conducted after which refinements are made until no risk has been estimated or the risk is adequately controlled. Wasting time and resources on additional testing and implementing risk management measures with low effect on risk conclusions should be avoided as much as possible. This paper demonstrates the usefulness of an intelligent data collection strategy based on a sensitivity (and uncertainty) analysis on the risk assessment model EUSES to identify and order the most important "within-EU-TGD-reducible" input parameters influencing the local and regional risk characterisation ratios. The ordering can be adjusted for the costs involved in additional testing (e.g. ecotoxicity, physico-chemical properties, emission estimates, etc.). The risk refinement tool therefore reduces the resources needed to obtain a realistic risk estimate (both less conservative and less uncertain) as efficient as possible.     

Methyl tertiary hexyl ether and methyl tertiary octyl ether as gasoline oxygenates: assessing risks from atmospheric dispersion and deposition

Methyl tertiary hexyl ether (MtHxE) and methyl tertiary octyl ether (MtOcE) are currently being developed as replacement oxygenates for methyl tertiary butyl ether (MtBE) in gasoline. As was the case with MtBE, the introduction of these ethers into fuel supplies guarantees their introduction into the environment as well. In this study, a screening-level risk assessment was performed by comparing predicted environmental concentrations (PEC) of these ethers to concentrations that might cause adverse effects to humans or ecosystems. A simple box model that has successfully estimated urban air concentrations of MtBE was adapted to predict atmospheric concentrations of MtHxE and MtOcE. Expected atmospheric concentrations of these ethers were also estimated using the European Union System for the Evaluation of Substances (EUSES) multimedia fate model, which simultaneously calculates PECs in the various environmental compartments of air, water, soil, and sediment. Because little or no data are available on the physicochemical, environmental, and toxicological properties of MtHxE and MtOcE, estimation methods were used in conjunction with EUSES to predict both the PECs and the concentrations at which these ethers might pose a threat. The results suggest that these ethers would contaminate the air of a moderately sized U.S. city (Boston, MA) at levels similar to those found previously for MtBE. The risk assessment module in EUSES predicted risk characterization ratios of 10(-3) and 10(-2) for MtHxE and MtOcE, respectively, in Boston, and 10(-2) and 10(-1) in very large urban centers, suggesting that these ethers pose only a minimal threat to ecosystems at the anticipated environmental concentrations. The assessment also indicates that these compounds are possible human carcinogens and that they may be present in urban air at concentrations that pose an unacceptable cancer risk. Therefore, testing of the toxicological properties of these compounds is recommended before they replace MtBE in gasoline.     

Methyl Tertiary Hexyl Ether and Methyl Tertiary Octyl Ether as Gasoline Oxygenates: Assessing Risks from Atmospheric Dispersion and Deposition

Abstract

Methyl tertiary hexyl ether (MtHxE) and methyl tertiary octyl ether (MtOcE) are currently being developed as replacement oxygenates for methyl tertiary butyl ether (MtBE) in gasoline. As was the case with MtBE, the introduction of these ethers into fuel supplies guarantees their introduction into the environment as well. In this study, a screening-level risk assessment was performed by comparing predicted environmental concentrations (PEC) of these ethers to concentrations that might cause adverse effects to humans or ecosystems. A simple box model that has successfully estimated urban air concentrations of MtBE was adapted to predict atmospheric concentrations of MtHxE and MtOcE. Expected atmospheric concentrations of these ethers were also estimated using the European Union System for the Evaluation of Substances (EUSES) multimedia fate model, which simultaneously calculates PECs in the various environmental compartments of air, water, soil, and sediment. Because little or no data are available on the physicochemical, environmental, and toxicological properties of MtHxE and MtOcE, estimation methods were used in conjunction with EUSES to predict both the PECs and the concentrations at which these ethers might pose a threat. The results suggest that these ethers would contaminate the air of a moderately sized U.S. city (Boston, MA) at levels similar to those found previously for MtBE. The risk assessment module in EUSES predicted risk characterization ratios of 10^?3 and 10^?2 for MtHxE and MtOcE, respectively, in Boston, and 10^?2 and 10^?1 in very large urban centers, suggesting that these ethers pose only a minimal threat to ecosystems at the anticipated environmental concentrations. The assessment also indicates that these compounds are possible human carcinogens and that they may be present in urban air at concentrations that pose an unacceptable cancer risk. Therefore, testing of the toxicological properties of these compounds is recommended before they replace MtBE in gasoline.     

Evaluation and comparison of multimedia mass balance models of chemical fate: application of EUSES and ChemCAN to 68 chemicals in Japan

The European Union System for Evaluation of Substances (EUSES) and the ChemCAN chemical fate model are applied to describe the fate of 68 chemicals on two spatial scales in Japan. Emission information on the chemicals has been obtained from Japan's Pollutant Release and Transfer Registry and available monitoring data gathered from government reports. Environmental concentrations calculated by the two models for the four primary environmental media of air, water, soil and sediment agree within a factor of 3 for over 70% of the data, and within a factor of 10 for over 87% of the data. Reasons for certain large discrepancies are discussed. Concentrations calculated by the models are generally consistent with the lower range of concentrations that are observed in the environment. Agreement between modeled and observed concentrations is considerably improved by including an estimate of the advective input of chemicals in air from outside Japan. The agreement between the EUSES and ChemCAN models suggests that results of individual chemical assessments are not likely to be significantly affected by the choice of chemical fate model. Primary sources of discrepancy between modeled and observed concentrations are believed to be uncertainties in emission rates, degradation half-lives, and the lack of data on advective inflow of contaminants in air.     

Environmental risk assessment for trisodium [S,S]-ethylene diamine disuccinate, a biodegradable chelator used in detergent applications

Environmental safety data are presented for [S,S]-Ethylene Diamine Disuccinate ([S,S]EDDS), a new, biodegradable, strong transition metal chelator. An environmental risk assessment for its use in detergent applications, which takes into account the chelating properties of [S,S]-EDDS, is proposed.

A property of [S,S]-EDDS that distinguishes it from other strong transition metal chelators is its, “ready” and transparent (no recalcitrant metabolites) biodegradation profile. Because its sorption to activated sludge solids is low ( Kp of 40 1/kg), removal of [S,S]EDDS during sewage treatment, which is greater than 96% as determined by the Continuous Activated Sludge test , is mainly ascribed to biodegradation. At projected use volumes in detergent applications [S,S] - EDDS predicted steady-state concentration in rivers leaving the mixing zone will be below 5 pg/I due to rapid biodegradation. [S,S]-EDDS exhibits low toxicity to fish and Daphnia ( both EC₅₀s> 1000 mg/l). By contrast, due to limitation of the algal test for chelators apparent toxicity was observed (EC₅₀ = 0.290 mg/l, NOEC - No observable Effect Concentration = 0.125 mg/l). Schowanek et al. [1] demonstrated that this is not toxicity sensu stricto but a chelation effect of trace metals in the test medium and of resulting essential nutrients limitation. This requires specific attention when the results of algal toxicity are to be extrapolated to a field situation to perform realistic risk assessment. Metal speciation calculations, using MINEQL+, show that at the predicted environmental concentrations of [S,S] - EDDS (1–5 μg/l), such a chelation effect would be insignificant. These calculations allow to estimate the NOEC for chelation effects in the field to be in the range of 0.250-0.500 mg/l, depending on the background water chemistry. These values are well above the laboratory NOEC.

An environmental risk assessment was performed using the EUSES (1.0) program. EUSES is currently the EU recommended tool for conducting risk assessments (TGD 1995). It was applied to estimate the river water and soil concentrations from production, formulation and private use life stages. The estimated PEC/PNEC ratio in all relevant environmental compartments is smaller than 1, indicating “no immediate concern” at the anticipated usage level.     

European scenarios for EUSES regional distribution model

The regional multimedia distribution model incorporated into EUSES 1.0 is used for the estimation of regionally predicted environmental concentrations in different European scenarios: a scenario representing a typical region in the north of Europe (high fraction connected to sewer systems, lower environmental temperature, high fractions of surface water and natural soil and a low fraction for agricultural soil) and another scenario representing a typical region in the south of Europe (low fraction connected to sewer systems, higher environmental temperature, low fractions for surface water and natural soil, and a high fraction for agricultural soil). The two scenarios are based on average data of countries in Northern and Southern Europe, but are not realistic for any specific country located in these regions. Scenario calculations were carried out using these two scenarios in addition to the generic standard region, given in EUSES 1.0 as a default scenario, and the North-Rhine Westphalian region. The substance properties, including emissions, were left unchanged for all scenarios. For a number of substances, the calculated concentrations in both the North and the South of Europe turned out to be higher than those calculated with the standard generic scenario. Thus, the standard scenario cannot be considered as a 'worst case' scenario per se. Uncertainties due to the regional heterogeneity within Europe are high. It is recommended to use these two additional scenarios for an improved estimation of possible concentration ranges in Europe.     

Prognosis of environmental concentrations by geo-referenced and generic models: a comparison of GREAT-ER and EUSES exposure simulations for some consumer-product ingredients in the Itter

The aim of this study was the comparison between predicted environmental concentrations (PEC) derived using a generic aspacial model, European Union System for the Evaluation of Substances (EUSES), and a geo-referenced model, the Geo-referenced Regional Environmental Assessment Tool for European Rivers (GREAT-ER). The PECs of some consumer-product ingredients (boron, LAS) and professional uses (EDTA, NTA and Triclosan) were calculated for the river catchment of the Itter, a small tributary to the river Rhine. The PEClocal and PECregional for the water compartment generated by EUSES (default scenario) were subsequently refined with data that realistically reflects the region of North Rhine-Westphalia (NRW scenario) and the Itter catchment (Itter scenario). The results of the three scenarios were then compared with the PECinitial and PECcatchment calculated by GREAT-ER, that was designed as a higher-tiered exposure assessment tool, and with concrete concentrations in the Itter, measured as 24-h composite samples. While the PECregional of all scenarios was close to the lower end of the measured concentrations, the geo-referenced PECs described equally well the real spacial situation. The measured environmental concentrations confirmed the built-in conservatism of the PEClocal calculations by EUSES showing for all investigated chemicals an unrealistically high PEClocal (default). The refinement in the more realistic scenarios could not provide a straight forward general improvement of the PEClocal. In conclusion, when the EUSES prognosis is refined using more detailed substance and regional specific data, it may provide a fairly accurate modelling especially of substances that are not eliminated in the environment. However, in the case of eliminable substances, it does not match the accuracy of higher-tiered geo-referenced exposure models like GREAT-ER.     

Calculation of environmental concentration and comparison of output for existing chemicals using regional multimedia modeling

The environmental fate of 40 existing chemicals is discussed using the EUSES multimedia distribution and risk assessment model with site-specific parameter setting in an urban area of Japan including a highly industrial region. There has been a strong need to assess the environmental fate of a huge number of existing chemicals. Data on the emission amounts of chemicals are essential for such prediction, and PRTR surveys may yield this data. The study delivered the following results: (1) Volatile compounds with large amounts of emission showed higher predicted concentrations in air, and the concentrations of several compounds agreed well with averaged monitoring data within an order of magnitude. (2) A close relationship was found between the concentration of water and that of sediment, suggesting that the fate of chemicals in sediment essentially depended on the water environment. (3) A group of volatile solvents had high mass distribution ratio to air. Some compounds having high solubility in water were also included in that group due to the high ratio of air emission. Highly hydrophobic compounds with logK(OW) larger than 6.0 showed a high distribution ratio to soil and sediment. (4) Volatile compounds were mostly taken through air. The exposure through fish is a dominant pathway for highly hydrophobic compounds. (5) Exposure ratio could be gathered from physicochemical properties. The exposure from fish intake was roughly estimated by logK(OW), whereas exposure from air and water intake was difficult to estimate simply by vapor pressure and solubility in water, respectively.     

EU risk assessment guidelines

Regional PECs (Potential Environmental Concentrations) calculated with the software EUSES were compared with measured values using different emission and environmental distribution scenarios. The environmental data set recommended in EUSES (default data set) represents a generic standard region. In different scenarios the parameters of the generic region are replaced by concrete values, and estimated parameters (emissions, degradation rates and partition coefficients) are substituted by measured or investigated values. Deviations with regard to the measured values can be up to three orders of magnitude. Despite the basically conservative approximations, underestimations can occur. However, these are usually due to poor monitoring data or inappropriate input values. The use of regional data instead of default parameters only slightly ameliorates the results. The use of real emission and degradation rates alone can improve the results significantly.     

Aquatic fate assessment of the polycyclic musk fragrance HHCB. Scenario and variability analysis in accordance with the EU risk assessment guidelines

By means of the environmental fate and distribution models laid down in the Technical Guidance Documents (TGD) and implemented in the European Union System for the Evaluation of Substances (EUSES) environmental concentrations of the polycyclic musk fragrance HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-[g]-2- benzopyrane; trade name: e.g. Galaxolide) were calculated for the aquatic environment under consideration of various scenarios. The results were then compared to monitoring data from the region of North Rhine-Westphalia (River Ruhr). An uncertainty analysis was carried out to determine sensitive parameters, to integrate environmental variability and to confirm the model's calculations. The standard scenario of EUSES overestimates the measured concentrations, which confirms the conservative nature of the calculations. The regional-specific scenarios lead to lower deviations from the measured values than the standard scenario. Deviations range from one to two orders of magnitude in the effluent of sewage treatment plants; they amount to one order of magnitude for surface water concentrations on a local scale and conform to monitoring data on a regional scale. The use of measured bioconcentration factors for fish instead of estimated ones reduces deviations remarkably. The investigation reveals that unrealistic worst-case calculations of HHCB can at best be ameliorated by the application of more realistic emission rates and measured bioconcentration factors. The use of regional-specific parameters also diminishes the deviations of the calculations from the measured concentrations.     

Prioritisation of organic contaminants in a river basin using chemical analyses and bioassays

Region-specific contaminant prioritisation is an important prerequisite for sustainable and cost-effective monitoring due to the high number of different contaminants that may be present. Surface water and sediment samples from the Sava River, Croatia, were collected at four locations covering a 150-km-long river section characterised by well-defined pollution gradients. Analysis of contaminant profiles along the pollution gradients was performed by combining toxicity screening using a battery of small-scale or in vitro bioassays, which covered different modes of action, with detailed chemical characterisation based on gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). A large number of contaminants, belonging to different toxicant classes, were identified in both analysed matrices. Analyses of water samples showed that contaminants having polar character occurred in the highest concentrations, while in sediments, contributions from both non-polar and amphiphilic contaminants should be taken into account. Estimated contributions of individual contaminant classes to the overall toxicity indicated that, besides the classical pollutants, a number of emerging contaminants, including surfactants, pharmaceuticals, personal care products and plasticizers, should be taken into consideration in future monitoring activities. This work demonstrates the importance of the integrated chemical and bioanalytical approach for a systematic region-specific pollutant prioritisation. Finally, the results presented in this study confirm that hazard assessment in complex environmental matrices should be directed towards identification of key pollutants, rather than focusing on a priori selected contaminants alone.     

Coupled mother-child model for bioaccumulation of POPs in nursing infants

Bioaccumulation of persistent organic pollutants (POPs) leads to high levels in human milk and high doses of POPs for nursing infants. This is currently not considered in chemical risk assessment. A coupled model for bioaccumulation of organic chemicals in breast-feeding mother and nursing infant was developed and tested for a series of organic compounds. The bioaccumulation factors (BAFs) in mother, breast milk and child were predicted to vary with log K_OW and, for volatile compounds, with K_AW and concentration in air. The concentrations of POPs in the infant body increase the first half year to about factor 3 above mother and decline thereafter to lower levels. The predicted results are close to empirical data and to an empirical regression. The new mother–child model is compact due to its easy structure and the analytical matrix solution. It could be added to existing exposure and risk assessment systems, such as EUSES.     

Human health and environmental risk assessment: the need for a more harmonised and integrated approach

Historically the procedures for human risk assessment and for risk assessment have developed separately with different terminologies and separate data bases. The identification that there are many common features and that sharing of certain types of data for risk assessment purposes would be beneficial is a driver towards a better integration of their procedures. Risk assessors are facing increasing challenges from governments, stimulated by public pressure for (i) human and environmental risk assessments of an ever growing number of products and processes, (ii) further restrictions of the use of animal tests and human studies on ethical grounds, (iii) the requirement to demonstrate that the assessments are independent, transparent and of high quality, (iv) reducing resources in particular a diminishing number of individuals with the scientific depth, breadth and independence act as risk assessors, (v) the need to incorporate new sciences continually and new discoveries into the risk assessment process. It is important for society that these challenges are met successfully. This requires changes in both risk assessment procedures and in the infrastructure needed to support them. Risk assessment is a science based process for establishing the likelihood of adverse effects to human health and to the environment from specific chemical, biological and physical agents. In the last few years there has been a renewed effort, by international bodies such as WHO, OECD and the EU, to achieve a more integrated and harmonised approach to risk assessment. Before examining the potential for a more integrated approach to risk assessment it is timely to consider the key factors which have led to the current position.     

Environmental risk assessment of existing chemicals

Most of the existing chemicals of high priority have been released into the environment for many years. Risk assessments for existing chemicals are now conducted within the framework of the German Existing Chemicals Program and by the EC Regulation on Existing Substances. The environmental assessment of a chemical involves:

1. exposure assessment leading to the derivation of a predicted environmental concentration (PEC) of a chemical from releases due to its production, processing, use, and disposal. The calculation of a PEC takes into account the dispersion of a chemical into different environmental compartments, elimination and dilution processes, as well as degradation. Monitoring data are also considered.
2. effects assessment. Data obtained from acute or long-term toxicity tests are used for extrapolation on environmental conditions. In order to calculate the concentration with expectedly no adverse effect on organisms (Predicted No Effect Concentration, PNEC) the effect values are divided by an assessment factor. This assessment factor depends on the quantity and quality of toxicity data available.

In the last step of the initial risk assessment, the measured or estimated PEC is compared with the PNEC. This “risk characterization” is conducted for each compartment separately (water, sediment, soil, and atmosphere). In case PEC > PNEC an attempt should be made to revise data of exposure and/or effects to conduct a refined risk characterization. In case PEC is again larger than PNEC risk reduction measures have to be considered.     

Use of geostatistics to evaluate the monitoring well network of a TCE plume

This paper summarises the use of geostatistics to evaluate an existing network of wells in a groundwater monitoring program. The primary objective was to evaluate whether selective well removal would result in a comparable characterisation of a trichloroethylene (TCE) plume. For adequate characterisation, it is important to retain enough wells to evaluate areas with higher concentrations and to show that there is high confidence or low uncertainty in the characterisation. A second objective was to utilise public or commercial software available to consultants in a workplace setting to demonstrate the ease with which this analysis can be performed. A baseline characterisation was generated with the entire well network. Then, subsequent simulations were performed with selected wells removed from the well network. Results indicate that by removing key wells from the network, the TCE plume can be adequately characterised without a significant increase in uncertainty.     

The water-soluble fraction of potentially toxic elements in contaminated soils: relationships between ecotoxicity, solubility and geochemical reactivity

To better understand the impacts posed by soil contamination to aquatic ecosystems it is crucial to characterise the links between ecotoxicity, chemical availability and geochemical reactivity of potentially toxic elements (PTE’s) in soils. We evaluated the adverse effects of water extracts obtained from soils contaminated by chemical industry and mining, using a test battery including organisms from different trophic levels (bacteria, algae and daphnids). These tests provided a quick assessment of the ecotoxicity of soils with respect to possible adverse effects on aquatic organisms although the ecotoxicological responses could be related to the solubility of PTE’s only to a limited extent.The analysis of results of bioassays together with the chemical characterisation of water extracts provided additional relevant insight into the role of conductivity, pH, Al, Fe, and Mn of soil extracts on toxicity to organisms. Furthermore, an important conclusion of this study was that the toxicity of extracts to the aquatic organisms could also be related to the soil properties (pH, Org C and Fe_ox) and to the reactivity of PTE’s in soils which in fact control the soluble fraction of the contaminants.The combined assessment of ecotoxicity in water fractions, solubility and geochemical reactivity of PTE’s in soils provided a more comprehensive understanding of the bioavailability of inorganic contaminants than ecotoxicological or chemical studies alone and can therefore be most useful for environmental risks assessment of contaminated soils.     

Data ranges in aquatic toxicity of chemicals

A significant problem for effect assessment of aquatic ecosystems arises from the large ranges of toxicity data, which can be found in different databases and literature. Here, ranges are given for the aquatic toxicity of 27 high production volume chemicals. Based on these illustrative examples and on the current literature on uncertainty in aquatic effect assessment, toxicity ranges are discussed for their possible causes (variation in experimental condition, species, endpoint, time) and ways to handle them (safety factors). Implications and recommendations on the procedure of risk analysis of chemical substances are drawn. Two main requirements for a comprehensive risk assessment are identified, which often play a minor role in current practice (as they are often neglected) as well as in scientific discussion (as they are meant to be trivial). First, data quality must be checked critically before applying any result of a toxicity test. Secondly, experimental data should take into account different species and acute as well as chronic data. If these aspects are considered in risk analysis, which is common practice in ecotoxicology but not always in the context of practical applications in risk engineering, a more comprehensive picture of the environmental toxicity of a chemical substance can be obtained.