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 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.     

Acrylamide: considerations for risk management

The presence of acrylamide in many carbohydrate-rich foods is due to its formation during conventional heating and preparation methods. Although acrylamide is established to be a toxic substance, the implications to public health from the amounts found in food are not clear. A better scientific understanding is required to help determine whether, and to what extent, formal risk management action might be necessary. Since acrylamide in food was highlighted in 2002, numerous investigations and initiatives have been developed, including international collaborations across governments, industry, research organizations, and consumer representations. The newly generated information is being used to help the overall understanding of this issue. In particular, new information on health aspects will be important to update the scientific risk assessment. The basis for decisions on possible risk management measures would then be clearer. If future risk assessment concludes that the amounts of acrylamide in food can pose a health threat, then options for risk management will need to be considered, such as limits, guide levels, codes of practice, guidance information, and advice to the food and catering industries and to consumers. In the meantime, it is possible to benefit from progress already made on how acrylamide is formed in food and on ways to lower the amounts present. Raising awareness to the approaches that can reduce the presence of acrylamide in food should be encouraged. Where feasible, such approaches can be assessed for practical use in production, processing, and preparation of the relevant food products.     

TENORM accumulation and management in refineries

A multi-step project has been developed by eni r&m to define a technologically enhanced naturally occurring radioactive material (TENORM) management system in refinery plants, compliant with Italian regulations and international guidelines. The project involves a preliminary survey on refineries to detect, on the basis of the production process, the sections at risk of TENORM accumulation; this analysis is followed by the consequent formation/information to the workers, the dose assessment for workers and the public, the introduction of radiometric characterization before release of potentially contaminated waste.     

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.     

ToxML,a data exchange standard with content controlled vocabulary used to build better (Q)SAR models

Development of accurate quantitative structure–activity relationship (QSAR) models requires the availability of high quality validated data. International regulations such as REACH in Europe will now accept (Q)SAR-based evaluations for risk assessment. The number of toxicity datasets available for those wishing to share knowledge, or to use for data mining and modelling, is continually expanding. The challenge is the current use of a multitude of different data formats. The issues of comparing or combining disparate data apply both to public and proprietary sources. The ToxML project addresses the need for a common data exchange standard that allows the representation and communication of these data in a well-structured electronic format. It is an open standard based on Extensible Markup Language (XML). Supporting information for overall toxicity endpoint data can be included within ToxML files. This makes it possible to assess the quality and detail of the data used in a model. The data file model allows the aggregation of experimental data to the compound level in the detail needed to support (Q)SAR work. The standard is published on a website together with tools to view, edit and download it.     

INAA of coals from the Midwestern USA

The concentrations of 43 elements were determined in coal samples collected from the state of Missouri using INAA at the University of Missouri Research Reactor. The results of the whole coal analysis reveal that the chemical compositions of Missouri coals are highly variable. Enrichment factors were determined for each of the elements determined in this project to provide a measure of the relative enrichment of the element as compared to the average crustal abundance for that element. Most elements are relatively depleted in coals, however the elements As, Br, B, Ca, Cd, Cl, Fe, Mo, Ni, Sb, S, U, Zn and Zr were found to be enriched in Missouri coals. The determination of the relative enrichment of a given element in coal will allow a greater assessment of the environment impact the will be incurred from the use of that coal.     

The estimation of reaction enthalpy for complex molecules using Benson groups</o:p>

Estimation methods developed over years by S. W. Benson and co-workers for calculation the thermodynamic properties of organic compounds in the gas phase are applied to a pharmaceutical real process with all type of non-idealities. The different strategies used to calculate the reaction enthalpy of a chemical process, in the absence of data for complex molecules, using the Benson group additivity method are presented and also compared with the experimental value of reaction enthalpy obtained using reaction calorimetry (Mettler-Toledo, RC1?). We demonstrate that there are some strategies that can be followed to obtain a good estimation of the reaction enthalpy in order to begin the safety assessment of a chemical reaction. This work is part of an industrial project [1] in which the main objective was the risk assessment of chemical real and complex processes using the commonly available tools for the SMEs (with limited resources).     

A practical approach to assessment of sampling uncertainty

The paper reports the approach followed in the SOILSAMP project, funded by the National Environmental Protection Agency (ANPA)of Italy. SOILSAMP is aimed at assessing uncertainties associated with soil sampling in agricultural, semi-natural, urban, and industrial environments. The uncertainty assessment is based on a bottom-up approach, according to the Guide to the Expression of Uncertainty in Measurement published by the International Organization for Standardization (ISO). A designated agricultural area, which has been characterized in terms of elemental spatial distribution, will be used in future as a reference site for soil sampling intercomparison exercises. Received: 19 November 2001 Accepted: 6 January 2002     

Method ruggedness studies incorporating a risk based approach: a tutorial

This tutorial explains how well thought-out application of design and analysis methodology, combined with risk assessment, leads to improved assessment of method ruggedness. The authors define analytical method ruggedness as an experimental evaluation of noise factors such as analyst, instrument or stationary phase batch. Ruggedness testing is usually performed upon transfer of a method to another laboratory, however, it can also be employed during method development when an assessment of the method's inherent variability is required. The use of a ruggedness study provides a more rigorous method for assessing method precision than a simple comparative intermediate precision study which is typically performed as part of method validation. Prior to designing a ruggedness study, factors that are likely to have a significant effect on the performance of the method should be identified (via a risk assessment) and controlled where appropriate. Noise factors that are not controlled are considered for inclusion in the study. The purpose of the study should be to challenge the method and identify whether any noise factors significantly affect the method's precision. The results from the study are firstly used to identify any special cause variability due to specific attributable circumstances. Secondly, common cause variability is apportioned to determine which factors are responsible for most of the variability. The total common cause variability can then be used to assess whether the method's precision requirements are achievable. The approach used to design and analyse method ruggedness studies will be covered in this tutorial using a real example.     

Assessment of heavy metal background values in the soils of inland coastal areas of Venice,Italy

The main aim of this project was to assess background levels of heavy metals in soil in the inland coastal area of Venice, Italy. The pilot study area is located near the industrial area of Porto Marghera, considered of national interest in terms of contaminated soil remediation (Environmental Ministerial Decree n. 471/1999). The Decree under consideration emphasises the importance of the assessment of background values in soil remediation. Results will show cases (As and Sn) in which background values are greater than concentration limit standards given by legislation.     

Trace metal and metalloid species determination: evolution and trends

Metal species determination has seen considerable evolution during the last decade. The issues addressed by total metal determinations using standard spectrochemical analyses deliver only a minimal amount of information required to appropriately inform decision making. In molecular analyses, coupled instrumentation systems allow us to obtain molecular information for assisting in identifying the compounds of interest. Metal species determinations will provide additional information beyond that available from total metal determinations. Many total metal determinations will be replaced with elemental speciation determinations when species-selective risk/benefit assessment is a priority. This paper discusses the differences between traditional inorganic metals analysis and metal species determinations and outlines new trends.     

Characterization of 235U targets for the development of a secondary neutron fluence standard

The MetroFission project, a Joint Research Project within the European Metrology Research Program, aims at addressing a number of metrological problems involved in the design of proposed Generation IV nuclear reactors. As part of this project a secondary neutron fluence standard is being developed and tested at the neutron time-of-flight facility GELINA of the JRCs Institute for Reference Materials and Measurements. Such a secondary standard will help to arrive at the neutron cross section measurement uncertainties required for the design and safety assessment of new generation power plants and fuel cycles. Such a neutron fluence device contains targets for which the neutron induced cross section is considered to be a standard. A careful preparation and characterization of these samples is an essential part of the development of the secondary standard. In this framework a set of ²³⁵U targets has been produced by vapour deposition of UF₄ on aluminium backings by IRMMs target preparation laboratory. These targets have been characterized for both their total mass and mass distribution over the sample area.     

Toxicogenomics in predictive toxicology in drug development

The goal of toxicology is the assessment of possible risk to man. An emerging technology with the potential to have a major impact on risk assessment is toxicogenomics. In this review, we provide an overview of the many possibilities for toxicogenomics including technology platforms, data interpretation, and regulatory perspective and we give examples of toxicogenomics investigations. Toxicogenomics is a powerful tool for compound classification, for mechanistic studies, and for the detection of toxicity markers. Thus, toxicogenomics helps in the extrapolation of findings across species and increases predictability. Biomarkers are valuable in the evaluation of compounds at earlier development phases, improving clinical candidate selection. Caution regarding the interpretation of the results is still necessary. Nevertheless, toxicogenomics will accelerate preclinical safety assessments and improve the prediction of toxic liabilities, as well as of potential risk accumulation for drug-drug or drug-disease interactions.     

Quantification,dissipation behavior and risk assessment of ethion in green pea by gas chromatography‐electron capture detector

Residue investigation was carried out to scrutinize the persistence, dissipation behavior, half‐life, and risk assessment of ethion on green pea fruit by spraying ethion at the fruiting stage followed by another application at 10 day intervals. The samples were extracted by using a quick, easy, low‐cost, effective, rugged, and safe method, and the residues of ethion were analyzed by gas chromatography with electron capture detection. Here we report a novel, accurate, and cost‐effective gas chromatography method for the determination of average deposits of ethion on green pea. The initial deposits were found to be 4.65 mg/kg following the application of insecticide. Residues of ethion reached below the detection limit of 0.10 mg/kg after 25 days at recommended dosage. The half‐life of ethion was found to be 4.62 days. For risk assessment studies, the 25th day will be safe for consumers for the consumption of green peas. The developed method is simple, sensitive, selective, and repeatable and can be extended for ethion‐based standardization of herbal formulations containing green pea and its use in pesticide industries.     

Dissipation and gas chromatographic method for the determination of profenofos residues in/on green pea and cucumber

Herein we report a novel, accurate and cost-effective gas chromatography method for the determination of average deposits of profenofos on green pea and cucumber following good agricultural practices. Additionally the risk assessment, dissipation and waiting period for profenofos were determined. The average initial deposits (2 h after spraying) of profenofos in/on green pea and cucumber were 3.41 and 3.62 mg kg⁻¹ respectively following two applications at a 10 day interval of profenofos 50EC formulation. Profenofos residues on both of the substrates were below the detection limit of 0.05 mg kg⁻¹ after 20 days at the recommended dosage. For risk assessment studies, the 20th day will be safe for consumers for consumption of green peas. The gas chromatography method was validated according to the SANTE guidelines using the various analytical parameters: linearity, accuracy, detection and quantification limits. The developed method is simple, selective and repeatable and can be extended for profenofos-based standardization of pesticide formulations for green pea/cucumber and their use as pesticides.     

Risk assessment,dissipation behavior and persistence of quinalphos in/on green pea by gas chromatography with electron capture detector

Chemical investigation was carried out to examine the risk assessment, dissipation behavior, persistence, and half‐life period of quinalphos in/on green pea fruit by spraying quinalphos at fruiting stage followed by another application after 10‐day interval. The samples were extracted by using the quick, easy, cheap, effective, rugged, and safe method, and the residues of quinalphos were analyzed by gas chromatography with electron capture detector. Herein, we report a novel, accurate, and cost‐effective gas chromatography method for the determination of average deposits of quinalphos in/on green pea. The initial deposits and half‐life of quinalphos were found to be 1.20 mg/kg and 2.77 days, respectively, following the application of insecticide. Residues of quinalphos reached below detection limit of 0.05 mg/kg after 10 days at recommended dosage. For risk assessment studies, the tenth day will be safe for consumers for consumption of green pea. The developed method is simple, selective, and repeatable, and it can be extended for quinalphos‐based standardization of herbal formulations containing green pea and its use in pesticide industries.     

Analytical methods for the determination of mixtures of bisphenols and derivatives in human and environmental exposure sources and biological fluids. A review

Bisphenol A (BPA) is ubiquitous in humans and the environment. Its potential adverse effects through genomic and non-genomic pathways have fostered BPA replacement by bisphenol analogs that, unfortunately, exert similar adverse effects. Many of these analogs, as well as their derivatives, have already found in humans and the environment and major concerns have arisen over their low dose- and mixture-related effects. This review aims to discuss the characteristics of the main analytical methods reported so far for the determination of mixtures of bisphenol analogs and/or derivatives in human and environmental exposure sources and biological fluids. Approaches followed for removal of background contamination, sample preparation and separation and detection of mixtures of bisphenols and derivatives are critically discussed. Sample treatment is matrix-dependent and common steps include analyte isolation, removal of interferences, evaporation of the extracts and solvent reconstitution. Separation and quantification has been almost exclusively carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS) or gas chromatography mass spectrometry (GC–MS), in the last case prior derivatization, but LC-fluorescence detection has also found some applications. Main characteristics, advantages and drawbacks of these methods will be comparatively discussed. Although at an early stage, some approaches for the assessment of the risk to mixtures of bisphenols, mainly based on the combination of chemical target analysis and toxicity evaluation, have been already applied and they will be here presented. Current knowledge gaps hindering a reliable assessment of human and environmental risk to mixtures of bisphenols and derivatives will be outlined.     

Structure-fate relationships of organic chemicals derived from the software packages E4CHEM and WHASSE

A risk assessment of chemicals is to be performed on the basis of the model EUSES, developed by the Commission of the European Union. The model package E4CHEM (Exposure Estimation for Potentially Ecotoxic Environmental Chemicals), developed in 1984-1992, is presented and applied in this paper as a model which allows a model-supported evaluation of chemicals. E4CHEM consequently does not have the wide applicability and technical comfort of the more recently developed model EUSES. The simulation models of E4CHEM characterize the chemical behavior in the environment by many aspects. Hence, there is a need to condense all of these aspects to get a clear impression of what will be the fate of the chemicals. Starting with the already published concept of exposure maps, we will discuss how partial orders may be helpful in establishing generalized structure-fate relationships. The software WHASSE is applied.     

Matrix effects in biological reference materials used in the standardization of cholesterol measurements

Summary The precise and accurate laboratory measurement of blood cholesterol has become a national public health priority in the diagnosis and management of patients at risk for coronary heart disease. Unreliable measurements can hamper the national program to control heart disease. The National Cholesterol Education Program (NCEP) recommends that manufacturers and clinical laboratories achieve traceability to the National Reference System for Cholesterol in order to reliably classify patients according to the NCEP guidelines for assessing coronary heart disease risk. Documenting the accuracy of certain clinical analytical systems for the measurement of cholesterol has been complicated by the occurrence of fluid matrix effects. The major difficulty is that some processed materials (including calibrators, controls, proficiency survey samples, and reference materials) may not be reliable and may result in inaccurate measurement of patient specimens. Similarly, use of such material in accuracy assessment or proficiency testing may yield erroneous conclusions regarding system accuracy. Here, we will review the problem of matrix effects in cholesterol materials and present the results of several studies evaluating sources of matrix error. An alternate approach to documenting accuracy, to be used until commutable materials free of matrix effects are available, will also be discussed.