Evaluation of the Use of QSARS for Priority Setting and Risk Assessment

Abstract Impending changes in EEC legislation have accelerated the need to define the principles and practical considerations of the use of QSARs in priority setting and risk assessment. It is important to delineate the limitations of this approach and to review whether and how this information should be used in the risk assessment. The value and limitations of QSARs for use in priority setting and risk assessment will not be discussed in detail since the European Chemical Industry Ecology and Toxicology Centre (ECETOC) has only recently established a Task Force to tackle this issue. The terms of reference of the Task Force are: (1) compare the predictions obtained with QSARs to measured data using ECETOC databases and other sources of data and comment on the validity and applicability of such QSARs; (2) identify and review software packages which are available for accessing and using appropriate QSARs; (3) identify those aspects of environmental distribution, fate and effects where the further development of QSARs is desirable and feasible; and (4) provide a scientific basis for ECETOC's contribution to the activities of the European Chemicals Bureau (ECB) in this area. In this short paper, only an initial and personal evaluation is made of when and where to use QSARs in the priority setting and risk assessment process within the regulatory framework. Some critical remarks and suggestions are provided to guide future developments and integration of QSARs in the risk assessment process.     

Use of Knowledge Bases and QSARS to Estimate the Relative Ecological Risk of Agrichemicals: A Problem Formulation Exercise

Abstract

Ecological risk assessments can be used to establish the likelihood that an adverse effect will result from exposure to one or more chemicals. When evaluating contaminated sites with many chemicals present, risk assessors must grapple with the problem of quickly identifying the chemicals that are most likely to be of concern, based on effect and exposure assessment information. Many times data gaps exist and the risk assessor is left with decisions on which models to use to estimate the parameter of concern. In the present paper, a procedure is presented for ranking agrichemicals, utilizing the ASTER (ASsessment Tools for the Evaluation of Risk) system. The procedure was employed to rank the relative ecological risk of forty-nine pesticides historically used in agricultural sites in the Walnut Creek watershed near Ames, Iowa, USA. Empirical data from the ASTER system were used when available in the associated data-bases, and quantitative structure-activity relationships and expert systems were invoked when data were lacking. Separate rankings were conducted based on major species taxonomic groupings. Resulting toxic effects thresholds were compared to surface water concentrations.     

Evaluation and improvement of QSAR predictions of skin sensitization for pesticides

In vivo skin sensitization assays have to be provided by applicants to the competent authorities in the European Union for the approval of active substances (AS) in pesticides. This study aimed to test the practicability of in silico predictions for AS by freely available (Q)SAR tools to evaluate their use as a time- and cost-effective alternative to animal testing in the context of the 3R concept. Predictions of skin sensitization for 48 selected sensitizing and non-sensitizing AS by the software programs CAESAR, Toxtree, OECD (Q)SAR Toolbox, CASE Ultra, Leadscope and SciQSAR were collected and compared. Different data evaluation methodologies (score definition, mean, weighted mean, threshold score definition) were applied to optimize the predictions. The calculation methods were internally cross-validated and further validated with an additional validation set of 80 AS. Although the presented calculation methodologies are not suitable as a stand-alone method, this study has shown weaknesses and strengths of some prominent (Q)SAR programs and diverse combinatorial options in the prediction of skin sensitization by pesticidal AS. The present study will help to foster discussions on in silico alternatives to animal testing in the pesticide area.     

温州横阳支江地表水健康风险评价

对温州市横阳支江水的监测数据,利用风险评价模型进行了风险评价。结果表明,由非致癌物饮水途径健康危害的总风险值处在10^-8～10^-9水平,风险水平均远低于国际辐射防护委员会（ICRP）推荐的通过饮水途径最大可接受风险水平（5×10^-5a^-1）,因此通过饮水途径所引起的慢性非致癌物暴露不会对暴露人群引起健康危害。砷对暴露人群所导致的致癌风险在10^-5a^-1水平,风险水平均接近于国际辐射防护委员会（ICRP）推荐的通过饮水途径最大可接受风险水平,因此,应优先对砷进行管理。最后探讨了生态风险评价中存在的问题和尚需进一步研究的工作。     

宁波市饮用水中重金属污染物镉健康风险评价

对宁波市区内36个监测点的饮用水中Cd的质量浓度进行了调查研究,并应用目前美国环保局推荐的健康风险评价模型对各区饮用水中Cd所引起的健康风险度作了初步评价。结果表明,宁波市区镉的平均质量浓度范围为0～3.2μg/L;通过饮水途径所引起的致癌健康风险中Cd在邱隘的致癌风险最大(8.7×10-6.a-1),但低于国际辐射防护委员会(ICRP)推荐的通过饮水途径最大可接受风险水平(5×10-5.a-1)。由于邱隘地区饮用水中的镉风险度相对较高,因此应优先对其进行管理。总体来说,Cd的个人年风险在10-6水平,所以宁波市通过饮水所引起的慢性镉暴露不会对暴露人群引起健康危害。     

宁波市饮用水中重金属铁锌铜健康风险度评价

对宁波市区内36个样点的饮用水中Fe,Zn,Cu的质量浓度进行了调查研究,并应用目前美国环保局推荐的健康风险评价模型对各区饮用水中Fe,Zn,Cu所引起的健康风险度作了初步评价。结果表明,宁波市区Fe,Zn,Cu的平均质量浓度范围分别为Fe 35~809μg/L,Zn51~1 147μg/L,Cu 14~98μg/L;通过饮水途径所引起的非致癌健康风险中Zn在邱隘(样点)的致癌年风险最大(1.7×10-5),但低于国际辐射防护委员会(ICRP)推荐的通过饮水途径最大可接受年风险水平(5×10-5),Cu,Fe的年风险水平(10-8~10-9)均远低于ICRP推荐的最大可接受风险水平。因此与Fe,Cu相比,Zn为主要的风险污染物,应进行优先管理。     

瑞安东山垃圾场地下水污染对人体的健康风险评价

以某垃圾场污染调查为依据,采用污染场地健康风险评价方法综合评价了由地下水污染带来的人群健康风险。综合分析表明,场地目标污染物为NO3^-、甲苯、二甲苯和锰,成年人和儿童两类人群通过饮水暴露途径的健康风险均远远大于洗浴带来的健康风险,儿童的洗浴风险大于成年人;无论饮水还是洗浴途径,4种污染物质中,锰的风险贡献最大,其次为硝酸根;从评价的4个污染因子来看,该垃圾场地下水对人体健康的危害已经相当大,须引起重视。     

Molecular Similarity and Risk Assessment: Analog Selection and Property Estimation Using Graph Invariants

Abstract

Four molecular similarity measures have been used to select the nearest neighbor of chemicals in two data sets of 139 hydrocarbons and 15 nitrosamines, respectively. The similarity methods are based on calculated graph invariants which include atom pairs, connectivity indices and information theoretic topological indices. The property of the selected nearest neighbor by each method was taken as the estimate of the property under investigation. The results show that for these data sets, all four methods give reasonable estimates of the properties studied.     

Assessment of QSARS for Predicting Fate and Effects of Chemicals in the Environment: An International European Project

Abstract In 1993, an international project on QSAR has been started with funding from the Commission of the European Union. The first part of the project is focused on preparing an overview of existing models for the prediction of environmental parameters such as bioconcentration, sorption, degradation and ecotoxicity. Emphasis will be given to defining the limitations of the models. Since all models, including QSARs, have their limitations, it is important that these limitations are known in case QSARs are actually used and applied within the risk assessment context. The second part of the project is directed towards experimental research on new developments with emphasis on the use of multivariate techniques and quantum chemical properties. In this short paper, a general outline of the project will be given, as well as some first results. Results of experimental work within this project will be published in the proceedings of the 6th International Workshop on QSAR in Environmental Sciences and will appear in this same journal.     

Evaluation of Critical Body Residue QSARS for Predicting Organic Chemical Toxicity to Aquatic Organisms

Abstract

The critical body residue (CBR) is the concentration of chemical bioaccumulated in an aquatic organism that corresponds to a defined measure of toxicity (e.g., mortality). The CBR can provide an alternative measure of toxicity to traditional waterborne concentration measurements (e.g., concentration in water causing 50% mortality). The CBR has been suggested as a better estimator of dose than the external water concentration and has been postulated to be constant for chemicals with the same mode of action. CBR QSARs have both theoretical and experimental support, developed primarily from studies on the acute toxicity of narcotic chemicals to small fish. CBR QSARs are less well developed for the aquatic toxicity of non-narcotic chemicals. CBRs vary substantially with the mode of action and toxicity endpoint, and may be affected by genetic, hormonal or environmental variation. CBR QSARs may not be applicable to very hydrophobic chemicals, chemicals with specific modes of action, or those with toxicity controlled by kinetic processes such as biotransformation. CBRs models have not been developed or evaluated for sediment and dietary exposure routes. Application of CBR QSARs to contaminated site assessments will require further research and development.     

Comparative QSAR: Radical Toxicity and Scavenging. Two Different Sides of the Same Coin

Abstract

From an analysis of the toxicity of phenols to rat embryos and anilines to embryo fibroblast cells a new type of toxicity is postulated for these classes of compounds. Substituents which increase the electron density on the aromatic ring as estimated by σ⁺ or ε_HOMO increase potency. It is postulated that it is the radical form of the phenols and the anilines that accounts for their toxicity. The results are compared with QSAR for radical scavengers and oxidoreductases acting on phenols, anilines and carbazoles.     

卤代苯和苯酚衍生物的位电荷密度能和1og Kow与-lg LC50的QSAR研究

以简易的量子化学方法计算了二十多种卤代苯和苯酚衍生物的FMO位电荷密度能,并进行定量结构-活性相关(quantiktive struvyitr biodegradability)研究,获得满意的结果.最后从生物酶促反应本质、污染物-生物酶的轨道控制反应角度对QSAR提出新的解释.     

Evaluation of the potential of Potamogeton crispus and Myriophyllum spicatum on phytoremediation of atrazine

Atrazine is one of the most frequently detected pesticides and poses a great risk to humans and the environment. In this study, the effects of two submerged macrophytes, Potamogeton crispus and Myriophyllum spicatum, on phytoremediation of atrazine were evaluated. The results showed that atrazine decayed faster in the pots where these two plants were cultivated than that of the control without the plants during the 60-day course of the experiment. Metabolite analyses of atrazine indicated that atrazine was mainly converted to diaminochlorotriazine and hydroxyatrazine. Dissipation kinetics and risk assessment of atrazine showed that atrazine was degraded rather fast in maize and generally safe for human consumption at the recommended high dosage of atrazine. The maximum permissible intake (MPI) for atrazine was calculated to be 0.23 μg/person/day for a child and 0.72 μg/person/day for an adult. However, due to the large-scale application of atrazine over the years, the atrazine residue still poses a great threat to the environment. By using submerged macrophytes M. spicatum and P. crispus, atrazine could be absorbed from the sediment, hence remediating contaminated sediment and water. This study established a protocol for evaluating submerged plants in absorption or phytoremediation of pesticides.     

EU Approach for Environmental Exposure Assessment: Actual Status and Future Needs

Abstract

To estimate the environmental concentration of a chemical substance, as required by the legislation of the European Union in the context of the risk assessment of chemical substances, several mathematical models are proposed. Representative and reliable analytical monitoring data for the different environmental compartments are indeed only seldom available. The proposed models are simple models as for instance multimedia fugacity models. Although the results of these models only provide an imperfect approximation of the concentration in the different compartments, very high uncertainties can lie upon certain input parameters, like the quantities of the substance released during one of its life-stages, its biodegradation rate in the respective compartments or its partition coefficients between those compartments. The improvement of the risk assessment scheme as proposed by the EU-Member States should focus on these input parameters. This might imply further adapting the test methods or even the requested test battery to the physical-chemical properties or even the structure of a substance.     

北江干流沉积物重金属污染生态风险评价

通过北江干流水体沉积物重金属含量,研究其典型污染物的潜在生态风险。采集了北江干流韶关至清远段7份沉积物样品,经混酸消解后,以电感耦合等离子体质谱仪测定沉积物中重金属含量,并对沉积物重金属分布特征进行了分析。同时利用Hakanson的潜在生态危害指数（RI）评价模式,对北江干流沉积物重金属生态风险进行了评价。评价结果表明,北江干流沉积物中重金属综合生态危害程度均表现为很高级别,其生态危害因子Pb、Cd已成为北江干流突发性水污染事故潜在预警因子。     

Environmental Research for Art Conservation and Assessment of Indoor Conditions Surrounding Cultural Objects

This paper describes the results and conclusions of research directed towards the development and evaluation of a chemical sensor which would provide information on the quality of indoor environments surrounding cultural objects. In our case these objects were paintings housed in major European galleries and the main objective is their preservation through an improved understanding of their microenvironment. The concept was to prepare and expose test tempera paintings which would behave as dosimeters and integrate the environmental response at these locations. Artificial ageing of similar samples was performed to provide a means of calibrating the test paintings. Samples from the test paintings were compared with artificially aged samples and this enabled the sites to be ranked in terms of their suitability for exposure of cultural objects. Additionally, novel methodology involving piezoelectric sensors was designed for monitoring the relative humidity and temperature of the microenvironment of paintings. Dielectric techniques were also used for measuring the effect of relative humidity fluctuations on artists' materials and novel non-invasive dielectric techniques in the microwave region were used for the determination of their moisture content. This revised version was published online in August 2006 with corrections to the Cover Date.     

Assessment of in silico models for acute aquatic toxicity towards fish under REACH regulation

We evaluated the performance of eight QSAR in silico modelling packages (ACD/ToxSuite?, ADMET Predictor?, DEMETRA, ECOSAR, TerraQSAR?, Toxicity Estimation Software Tool, TOPKAT? and VEGA) for acute aquatic toxicity towards two species of fish: Fathead Minnow and Rainbow Trout. For the Fathead Minnow, we compared model predictions for 567 substances with the corresponding experimental values for 96-h median lethal concentrations (LC50). Some models gave good results, with r² up to 0.85. We also classified the predictions of all the models into four toxicity classes defined by CLP. This permitted us to assess other parameters, such as the percentage of correct predictions for each class. Then we used a set of 351 substances with toxicity data towards Rainbow Trout (96-h LC50). In this case the predictability was unacceptable for all the in silico models. The calculated r² gave poor correlations (≤0.53). Another analysis was performed according to chemical classes and for mode of action. In the first case, all the classes show a high percentage of correct predictions, in the second case only narcotics and polar narcotics were predicted with good confidence. The results indicate the possibility of using in silico methods to estimate aquatic toxicity within REACH regulation, after careful evaluation.