Octanol/Air Partition Coefficient─A General-Purpose Fragment Model to Predict Log Koa from Molecular Structure.

The octanol/air partition coefficient Koa is important for assessing the bioconcentration of airborne xenobiotics in foliage and in air-breathing organisms. Moreover, Koa informs about compound partitioning to aerosols and indoor dust, and complements the octanol/water partition coefficient Kow and the air/water partition coefficient Kaw for multimedia fate modeling. Experimental log Koa at 25 °C has been collected from literature for 2161 compounds with molecular weights from 16 to 959 Da. The curated data set covers 18.2 log units (from -1.0 to 17.2). A newly developed fragment model for predicting log Koa from molecular structure outperforms COSMOtherm, EPI-Suite KOAWIN, OPERA, and linear solvation energy relationships (LSERs) regarding the root-mean-squared error (rms) and the maximum negative and positive errors (mne and mpe) (rms: 0.57 vs 0.86 vs 1.09 vs 1.19 vs 1.05-1.53, mne: -2.55 vs -3.95 vs -7.51 vs -7.54 vs (-5.63) - (-7.34), mpe: 2.91 vs 5.97 vs 7.54 vs 4.24 vs 6.89-10.2 log units). The prediction capability, statistical robustness, and sound mechanistic basis are demonstrated through initial separation into a training and prediction set (80:20%), mutual leave-50%-out validation, and target value scrambling in terms of temporarily wrong compound-Koa allocations. The new general-purpose model is implemented in a fully automatized form in the ChemProp software available to the public. Regarding Koa indirectly determined through Kow and Kaw, a new approach is developed to convert from wet to dry octanol, enabling higher consistency in experimental (and thus also predicted) Koa.

Henry's Law Constant─A General-Purpose Fragment Model to Predict Log Kaw from Molecular Structure.

Henry's law constant is important for assessing the environmental fate of organic compounds, including polar accumulation, indoor contamination, and the impact of airborne predominance on persistence. Moreover, it can be used in the context of alternative 3R bioassays to inform about the compound loss through volatilization as a confounding factor. For 2636 compounds, curated experimental log Kaw (air/water partition coefficient) data at 25° covering 23.6 orders of magnitude (from -18.6 to 5.0) have been collected from the literature. Subsequently, a new fragment model for predicting log Kaw from molecular structures has been developed. According to the root-mean-squared error (rms) and the maximum negative and positive errors (mne and mpe), this general-purpose model outperforms COSMOtherm, EPISuite HENRYWIN, OPERA, and LSER with calculated input parameters significantly (rms 0.50 vs 0.92 vs 1.25 vs 1.28 vs 1.38, mne -2.74 vs -6.78 vs -9.11 vs -6.24 vs -6.27, mpe 2.25 vs 6.22 vs 8.27 vs 11.5 vs 7.69 log units). Initial separation into a training and prediction set (80%:20%), mutual leave-50%-out validation, and target value scrambling (temporarily wrong compound-Kaw allocations) demonstrate the prediction capability, statistical robustness, and mechanistically sound basis of the fragment scheme. The new model is available to the public in fully computerized form through the ChemProp software, and can be combined with a separate existing model to extend the log Kaw prediction to temperatures different from 25 °C.

Computational material flow analysis for thousands of chemicals of emerging concern in European waters.

Knowledge of exposure to a wide range of chemicals, and the spatio-temporal variability thereof, is urgently needed in the context of protecting and restoring aquatic ecosystems. This paper discusses a computational material flow analysis to predict the occurrence of thousands of man-made organic chemicals on a European scale, based on a novel temporally and spatially resolved modelling framework. The goal was to increase understanding of pressures by emerging chemicals and to complement surface water monitoring data. The ambition was to provide a first step towards a "real-life" mixture exposure situation accounting for as many chemicals as possible. Comparison of simulated concentrations and chemical monitoring data for 226 substance/basin combinations showed that the simulated concentrations were accurate on average. For 65% and 90% of substance/basin combinations the error was within one and two orders of magnitude respectively. An analysis of the relative importance of uncertainties revealed that inaccuracies in use volume or use type information contributed most to the error for individual substances. To resolve this, we suggest better registration of use types of industrial chemicals, investigation of presence/absence of industrial chemicals in wastewater and runoff samples and more scientific information exchange.

Applicability of the fish embryo acute toxicity (FET) test (OECD 236) in the regulatory context of Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH).

In 2013 the Organisation for Economic Co-operation and Development (OECD) test guideline (236) for fish embryo acute toxicity (FET) was adopted. It determines the acute toxicity of chemicals to embryonic fish. Previous studies show a good correlation of FET with the standard acute fish toxicity (AFT) test; however, the potential of the FET test to predict AFT, which is required by the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) regulation (EC 1907/2006) and the Classification, Labelling and Packaging (CLP) Regulation (EC 1272/2008), has not yet been fully clarified. In 2015 the European Chemicals Agency (ECHA) requested that a consultant perform a scientific analysis of the applicability of FET to predict AFT. The purpose was to compare the toxicity of substances to fish embryos and to adult fish, and to investigate whether certain factors (e.g., physicochemical properties, modes of action, or chemical structures) could be used to define the applicability boundaries of the FET test. Given the limited data availability, the analysis focused on organic substances. The present critical review summarizes the main findings and discusses regulatory application of the FET test under REACH. Given some limitations (e.g., neurotoxic mode of action) and/or remaining uncertainties (e.g., deviation of some narcotic substances), it has been found that the FET test alone is currently not sufficient to meet the essential information on AFT as required by the REACH regulation. However, the test may be used within weight-of-evidence approaches together with other independent, relevant, and reliable sources of information. The present review also discusses further research needs that may overcome the remaining uncertainties and help to increase acceptance of FET as a replacement for AFT in the future. For example, an increase in the availability of data generated according to OECD test guideline 236 may provide evidence of a higher predictive power of the test. Environ Toxicol Chem 2018;37:657-670. © 2017 SETAC.

PBT assessment under REACH: Screening for low aquatic bioaccumulation with QSAR classifications based on physicochemical properties to replace BCF in vivo testing on fish.

Aquatic bioconcentration factors (BCFs) are critical in PBT (persistent, bioaccumulative, toxic) and risk assessment of chemicals. High costs and use of more than 100 fish per standard BCF study (OECD 305) call for alternative methods to replace as much in vivo testing as possible. The BCF waiving scheme is a screening tool combining QSAR classifications based on physicochemical properties related to the distribution (hydrophobicity, ionisation), persistence (biodegradability, hydrolysis), solubility and volatility (Henry's law constant) of substances in water bodies and aquatic biota to predict substances with low aquatic bioaccumulation (nonB, BCF<2000). The BCF waiving scheme was developed with a dataset of reliable BCFs for 998 compounds and externally validated with another 181 substances. It performs with 100% sensitivity (no false negatives), >50% efficacy (waiving potential), and complies with the OECD principles for valid QSARs. The chemical applicability domain of the BCF waiving scheme is given by the structures of the training set, with some compound classes explicitly excluded like organometallics, poly- and perfluorinated compounds, aromatic triphenylphosphates, surfactants. The prediction confidence of the BCF waiving scheme is based on applicability domain compliance, consensus modelling, and the structural similarity with known nonB and B/vB substances. Compounds classified as nonB by the BCF waiving scheme are candidates for waiving of BCF in vivo testing on fish due to low concern with regard to the B criterion. The BCF waiving scheme supports the 3Rs with a possible reduction of >50% of BCF in vivo testing on fish. If the target chemical is outside the applicability domain of the BCF waiving scheme or not classified as nonB, further assessments with in silico, in vitro or in vivo methods are necessary to either confirm or reject bioaccumulative behaviour.

Contribution of waste water treatment plants to pesticide toxicity in agriculture catchments.

Pesticide residues are frequently found in water bodies and may threaten freshwater ecosystems and biodiversity. In addition to runoff or leaching from treated agricultural fields, pesticides may enter streams via effluents from wastewater treatment plants (WWTPs). We compared the pesticide toxicity in terms of log maximum Toxic Unit (log mTU) of sampling sites in small agricultural streams of Germany with and without WWTPs in the upstream catchments. We found an approximately half log unit higher pesticide toxicity for sampling sites with WWTPs (p < 0.001). Compared to fungicides and insecticides, herbicides contributed most to the total pesticide toxicity in streams with WWTPs. A few compounds (diuron, terbuthylazin, isoproturon, terbutryn and Metazachlor) dominated the herbicide toxicity. Pesticide toxicity was not correlated with upstream distance to WWTP (Spearman's rank correlation, rho = - 0.11, p > 0.05) suggesting that other context variables are more important to explain WWTP-driven pesticide toxicity. Our results suggest that WWTPs contribute to pesticide toxicity in German streams.

An Integrated Data-Driven Strategy for Safe-by-Design Nanoparticles: The FP7 MODERN Project.

The development and implementation of safe-by-design strategies is key for the safe development of future generations of nanotechnology enabled products. The safety testing of the huge variety of nanomaterials that can be synthetized is unfeasible due to time and cost constraints. Computational modeling facilitates the implementation of alternative testing strategies in a time and cost effective way. The development of predictive nanotoxicology models requires the use of high quality experimental data on the structure, physicochemical properties and bioactivity of nanomaterials. The FP7 Project MODERN has developed and evaluated the main components of a computational framework for the evaluation of the environmental and health impacts of nanoparticles. This chapter describes each of the elements of the framework including aspects related to data generation, management and integration; development of nanodescriptors; establishment of nanostructure-activity relationships; identification of nanoparticle categories; hazard ranking and risk assessment.

Nontargeted detection and identification of (aromatic) amines in environmental samples based on diagnostic derivatization and LC-high resolution mass spectrometry.

The presence of aromatic amines in the environment has been in the focus of research, as many of these compounds are known or suspected mutagens and carcinogens. To facilitate the detection of aromatic amines in complex environmental samples by LC-high resolution mass spectrometry, an on-line-post-column and a pre-column derivatization method to label (in an ideal case) all aromatic amines was evaluated by applying different derivatization reagents. 4-Fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) was found to be the most promising labeling reagent due to its high reactivity with both primary and secondary amines and its low signal in positive mode electrospray ionization (ESI+). Post-column on-line derivatization did not result in sufficient signal intensities of derivatives. With pre-column derivatization most of the selected aromatic amines resulted in a derivative that shows common fragments of diagnostic value. The selectivity of NBD-F was studied in depth with a data set of 220 compounds with different functional groups showing that also aliphatic amines and some thiols yield a derivative. The developed method was successfully applied to wastewater effluent samples and several derivatives were confirmed by diagnostic neutral losses.

Micropollutants in European rivers: A mode of action survey to support the development of effect-based tools for water monitoring.

Environmental quality monitoring of water resources is challenged with providing the basis for safeguarding the environment against adverse biological effects from exposure to anthropogenic chemicals originating from diffuse and point sources. Although current regulatory efforts focus on monitoring and assessing a few legacy chemicals, many more anthropogenic chemicals are and will become detected in aquatic resources as a result of progress in analytical techniques. Assessing this type of exposure information based on available standard approaches from prospective risk assessment for single chemicals inevitably leads to indication of risk in most surface water bodies. As an alternative to generic assessment approaches, effect-based monitoring approaches are suggested. This offers the advantage of reducing uncertainties of effect extrapolation and additionally accounts for mixture effects. To become a credible complement to chemical monitoring information, however, a better understanding of the capabilities and gaps of available effect-based tools is needed. The authors therefore undertook to 1) compile organic contaminants detected in freshwater monitoring studies, 2) provide a synopsis of the mode of action knowledge available for the detected compounds, 3) perform a hazard ranking to identify priority mixtures, and 4) reflect on the challenges to make bioassays fit for effect-based monitoring. The present Focus article shows that chemical occurrence in European freshwaters seems to be highly variable in composition and relative abundancies. Further, although the present mode of action knowledge remains limited, the authors already see the need for batteries of effect-based tools if a more comprehensive coverage of prevailing effect qualities for mixtures is to be targeted. Finally, they suggest a list of organic compounds that could serve as a reference list for effect-based tool validation studies. Environ Toxicol Chem 2016;35:1887-1899. © 2016 SETAC.

Inhalation threshold of toxicological concern (TTC) - Structural alerts discriminate high from low repeated-dose inhalation toxicity.

The threshold of toxicological concern (TTC) of a compound represents an exposure value below which the associated human health risk is considered negligible. As such, this approach offers assessing the risk of potential toxicants when little or no toxicological information is available. For the inhalation repeated-dose TTC, the goal was to derive structural alerts that discriminate between high- and low-toxic compounds. A further aim was to identify physicochemical parameters related to the inhalation-specific bioavailability of the compounds, and to explore their use as predictors of high vs low toxicity. 296 compounds with subacute, subchronic and chronic inhalation toxicity NOEC (no-observed effect concentration) values were subdivided into three almost equal-sized high-, medium- and low-toxic (HTox, MTox, LTox) potency classes. Whereas the derived 14 HTox and 7 LTox structural alerts yield an only moderate discrimination between these three groups, the high-toxic vs low-toxic mis-classification is very low: LTox-predicted compounds are not HTox to 97.5%, and HTox-predicted compounds not LTox to 88.6%. The probability of a compound being HTox vs LTox is triggered further by physicochemical properties encoding the tendency to evaporate from blood. The new structural alerts may aid in the predictive inhalation toxicity assessment of compounds as well as in designing low-toxicity chemicals, and provide a rationale for the chemistry underlying the toxicological outcome that can also be used for scoping targeted experimental studies.

Fish embryo toxicity test: identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds.

The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compounds with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided the first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may not yet be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish acute toxicity test or application of assessment factors while considering the very good fish embryo-acute fish toxicity correlation for other compounds.

A Branch-and-Bound Approach for Tautomer Enumeration.

Knowledge about tautomer forms of a structure is important since, e.g., a property prediction for a molecule can yield to different results which depend on the individual tautomer. Tautomers are isomers that can be transformed to each other through chemical equilibrium reactions. In this paper the first exact Branch-and-Bound (B&B) algorithm to calculate tautomer structures is proposed. The algorithm is complete in the sense of tautomerism and generates all possible tautomers of a structure according to the tautomer definition, it is initialized with. To be efficient, the algorithm takes advantage of symmetric and formation properties. Some restrictions are used to enable an early pruning of some branches of the B&B tree. This is important, since a simple enumeration strategy would lead to number of candidate tautomers that is exponentially increasing with the number of hydrogen atoms and their attachment sites. The proposed implementation of the B&B algorithm covers the majority of the prototropic tautomer cases, but can be adapted to other kinds of tautomerism too. Furthermore, a computer processable definition of tautomerism is given in the form of the moving hydrogen atom problem.

Organic chemicals jeopardize the health of freshwater ecosystems on the continental scale.

Organic chemicals can contribute to local and regional losses of freshwater biodiversity and ecosystem services. However, their overall relevance regarding larger spatial scales remains unknown. Here, we present, to our knowledge, the first risk assessment of organic chemicals on the continental scale comprising 4,000 European monitoring sites. Organic chemicals were likely to exert acute lethal and chronic long-term effects on sensitive fish, invertebrate, or algae species in 14% and 42% of the sites, respectively. Of the 223 chemicals monitored, pesticides, tributyltin, polycyclic aromatic hydrocarbons, and brominated flame retardants were the major contributors to the chemical risk. Their presence was related to agricultural and urban areas in the upstream catchment. The risk of potential acute lethal and chronic long-term effects increased with the number of ecotoxicologically relevant chemicals analyzed at each site. As most monitoring programs considered in this study only included a subset of these chemicals, our assessment likely underestimates the actual risk. Increasing chemical risk was associated with deterioration in the quality status of fish and invertebrate communities. Our results clearly indicate that chemical pollution is a large-scale environmental problem and requires far-reaching, holistic mitigation measures to preserve and restore ecosystem health.

Integrated testing strategy (ITS) for bioaccumulation assessment under REACH.

REACH (registration, evaluation, authorisation and restriction of chemicals) regulation requires that all the chemicals produced or imported in Europe above 1 tonne/year are registered. To register a chemical, physicochemical, toxicological and ecotoxicological information needs to be reported in a dossier. REACH promotes the use of alternative methods to replace, refine and reduce the use of animal (eco)toxicity testing. Within the EU OSIRIS project, integrated testing strategies (ITSs) have been developed for the rational use of non-animal testing approaches in chemical hazard assessment. Here we present an ITS for evaluating the bioaccumulation potential of organic chemicals. The scheme includes the use of all available data (also the non-optimal ones), waiving schemes, analysis of physicochemical properties related to the end point and alternative methods (both in silico and in vitro). In vivo methods are used only as last resort. Using the ITS, in vivo testing could be waived for about 67% of the examined compounds, but bioaccumulation potential could be estimated on the basis of non-animal methods. The presented ITS is freely available through a web tool.

A comparative survey of chemistry-driven in silico methods to identify hazardous substances under REACH.

This paper presents an inventory of in silico screening tools to identify substance properties of concern under the European chemicals' legislation REACH. The objective is to support the selection and implementation of appropriate tools as building blocks within integrated testing strategies (ITS). The relevant concerns addressed are persistence, bioaccumulation potential, acute and long-term aquatic toxicity, PBT/vPvB properties ((very) persistent, (very) bioaccumulative, toxic), CMR (carcinogenicity, mutagenicity, reproductive toxicity), endocrine disruption and skin sensitisation. The inventory offers a comparative evaluation of methods with respect to the underlying algorithms (how does the method work?) and the applicability domains (when does the method work?) as well as their limitations (when does the method not work?). The inventory explicitly addresses the reliability of predictions of different in silico models for diverse chemicals by applicability domain considerations. The confidence in predictions can be greatly improved by consensus modelling that allows for taking conflicting results into account. The inventory is complemented by a brief discussion of socio-economic tools for assessing the potential efficiency gains of using in silico methods compared to traditional in vivo testing of chemical hazards.

The OSIRIS Weight of Evidence approach: ITS for the endpoints repeated-dose toxicity (RepDose ITS).

In the FP6 European project OSIRIS, Integrated Testing Strategies (ITSs) for relevant toxicological endpoints were developed to avoid new animal testing and thus to reduce time and costs. The present paper describes the development of an ITS for repeated-dose toxicity called RepDose ITS which evaluates the conditions under which in vivo non-guideline studies are reliable. In a tiered approach three aspects of these "non-guideline" studies are assessed: the documentation of the study (reliability), the quality of the study design (adequacy) and the scope of examination (validity). The reliability is addressed by the method "Knock-out criteria", which consists of four essential criteria for repeated-dose toxicity studies. A second tool, termed QUANTOS (Quality Assessment of Non-guideline Toxicity Studies), evaluates and weights the adequacy of the study by using intra-criterion and inter-criteria weighting. Finally, the Coverage approach calculates a probability that the detected Lowest-Observed-Effect-Level (LOEL) is similar to the LOEL of a guideline study dependent on the examined targets and organs of the non-guideline study. If the validity and adequacy of the non-guideline study are insufficient for risk assessment, the ITS proposes to apply category approach or the Threshold of Toxicological Concern (TTC) concept, and only as a last resort new animal-testing.

The OSIRIS Weight of Evidence approach: ITS mutagenicity and ITS carcinogenicity.

Risk assessment of chemicals usually implies data evaluation of in vivo tests in rodents to conclude on their hazards. The FP7 European project OSIRIS has developed integrated testing strategies (ITS) for relevant toxicological endpoints to avoid unnecessary animal testing and thus to reduce time and costs. This paper describes the implementation of ITS mutagenicity and carcinogenicity in the public OSIRIS webtool. The data requirements of REACH formed the basis for these ITS. The main goal was to implement procedures to reach a conclusion on the adequacy and validity of available data. For the mutagenicity ITS a quantitative Weight of Evidence approach based on Bayesian statistics was developed and implemented. The approach allows an overall quality assessment of all available data for the five types of mutagenicity data requirements: in vitro bacterial mutagenicity, in vitro and in vivo chromosome aberration, in vitro and in vivo mammalian mutagenicity. For the carcinogenicity ITS a tool was developed to evaluate the quality of studies not conforming (entirely) to guidelines. In a tiered approach three quality aspects are assessed: documentation (reliability), study design (adequacy) and scope of examination (validity). The quality assessment is based on expert and data driven quantitative Weight of Evidence.

Read-Across Prediction of the Acute Toxicity of Organic Compounds toward the Water Flea Daphnia magna.

According to the European REACH Directive, the acute daphnid toxicity needs to be assessed for industrial chemicals with market volumes ≥1 t/a. Employing a data set of 1365 organic compounds with experimental 48-h LC50 data for Daphnia magna, a read-across approach has been developed that makes use of the atom-centered fragment (ACF) method as quantitative measure for structural similarity. Both quantitative log LC50 predictions and a discrimination between narcosis-level and excess toxicity can be obtained, augmented by similarity-triggered information that characterizes a compound as inside or outside the quantitative or qualitative model domain. Reading across proceeds as interpolation of the toxicity enhancement (Te ) over predicted narcosis-level toxicity, taking experimental log Te values from similarity-selected reference compounds as input. The resultant decision tree model yields r(2) =0.85 and rms=0.66 for the subset of 757 compounds (56 %) identified as inside the quantitative model domain, and can handle further 318 compounds (23 %) with the categorical submodel, with 290 compounds (21 %) being outside its domain. The new in silico approach appears useful as ITS (Integrated Testing Strategy) tool for the daphnid toxicity assessment. The discussion includes a comparison of Kow - and LSER-predicted narcosis-level toxicity in the read-across context.

Prediction of the dissociation constant pKa of organic acids from local molecular parameters of their electronic ground state.

A quantum chemical method has been developed to estimate the dissociation constant pK(a) of organic acids from their neutral molecular structures by employing electronic structure properties. The data set covers 219 phenols (including 29 phenols with intramolecular H-bonding), 150 aromatic carboxylic acids, 190 aliphatic carboxylic acids, and 138 alcohols, with pK(a) varying by 16 units (0.38-16.80). Optimized ground-state geometries employing the semiempirical AM1 Hamiltonian have been used to quantify the site-specific molecular readiness to donate or accept electron charge in terms of both charge-associated energies and energy-associated charges, augmented by an ortho substitution indicator for aromatic compounds. The resultant regression models yield squared correlation coefficients (r(2)) from 0.82 to 0.90 and root-mean-square errors (rms) from 0.39 to 0.70 pK(a) units, corresponding to an overall (subset-weighted) r(2) of 0.86. Simulated external validation, leave-10%-out cross-validation and target value scrambling demonstrate the statistical robustness and prediction power of the derived model suite. The low intercorrelation with prediction errors from the commercial ACD package provides opportunity for a consensus model approach, offering a pragmatic way for further increasing the confidence in prediction significantly. Interestingly, inclusion of calculated free energies of aqueous solvation does not improve the prediction performance, probably because of the limited precision provided by available continuum-solvation models.

Occurrence and toxicity of 331 organic pollutants in large rivers of north Germany over a decade (1994 to 2004).

We analyzed the detection frequencies and concentrations for 331 organic compounds measured between 1994 and 2004 in the four largest rivers of north Germany, the Elbe, Weser, Aller, and Ems Rivers, and we assessed the potential risk for aquatic fauna using experimental and predicted acute toxicity data for the green alga Pseudokirchneriella subcapitata, the crustacean Daphnia magna, and the fish Pimephales promelas. The detection frequency for most compounds decreased significantly from 1994 to 2004. Polycyclic aromatic hydrocarbons (PAHs) were most frequently detected, while pesticides were the most important chemical group concerning toxicity for the standard test organisms. The predicted toxicity for D. magna was significantly higher than for the other organisms and reached levels envisaging acute toxic effects on the invertebrate fauna, still in 2004. Most of the compounds responsible for potential acute effects on aquatic organisms are currently not considered as priority substances in the European Union, while only 2 of 25 priority substances that have been measured occurred at levels that may be relevant in terms of toxicity for the selected test organisms. We conclude that attenuation of pesticides and other organic toxicants should play an increased role in river basin management.