Biomedical subjects

Christina Rudén

Publications and source records attributed to Christina Rudén.

15 recordsLinked to original sources

PubMed2006

The usefulness of the bioconcentration factor as a tool for priority setting in chemicals control.

The implementation of the REACH system will lead to the creation of a single, uniform legislation for industrial chemicals in Europe. An important aim of this legislation is to generate toxicity data for previously untested chemicals. Testing tens of thousands of chemicals can however not be done in one step, and criteria for priority setting is therefore an essential part of the proposed REACH system. In this study we investigate potential consequences of using bioaccumulation (B) data as a tool for priority setting in chemicals control. The results of this investigation suggests that the use of data for the bioconcentration factor (BCF, as an estimation of B) at first tier will not introduce bias towards a particular type of toxicity (i.e. carcinogenicity, reproductive toxicity or mutagenicity) in the priority setting process.

Carcinogens↗

PubMed2006

What influences a health risk assessment?

In this paper it is claimed that the health risk assessment process is influenced by (at least) four general factors, namely: the regulatory framework, the quality and availability of scientific data, general risk assessment principles, and case-by-case assumptions. Furthermore, the scientific basis of risk assessment relies on three overall types of methods for data generation: standardized animal experiments, epidemiology, and non-standardized mechanism data. In this paper, the use of the different types of data for risk assessment purposes are analyzed in the light of the factors claimed to influence the risk assessment process. It is concluded that the availability of pre-defined criteria for the interpretation and evaluation of data for regulatory health risk assessment purposes need to be further developed. Especially with the implementation of the new European chemicals legislation REACH.

Animals↗

PubMed2006

Ten challenges for improved ecotoxicological testing in environmental risk assessment.

New regulations, in particular the new European chemicals legislation (REACH), will increase the demands on environmental risk assessment (ERA). The requirements on efficient ecotoxicological testing systems are summarized, and 10 major issues for the improvement of ERA practices are discussed, namely: (1) the choice of representative test species, (2) the development of test systems that are relevant for ecosystems in different parts of the world, (3) the inclusion of sensitive life stages in test systems, (4) the inclusion of endpoints on genetic variation in populations, (5) using mechanistic understanding of toxic effects to develop more informative and efficient test systems, (6) studying disruption in invertebrate endocrine mechanisms, that may differ radically from those we know from vertebrates, (7) developing standardized methodologies for testing of poorly water-soluble substances, (8) taking ethical considerations into account, in particular by reducing the use of vertebrates in ecotoxicological tests, (9) using a systematic (statistical) approach in combination with mechanistic knowledge to combine tests efficiently into testing systems, and (10) developing ERA so that it provides the information needed for precautionary decision-making.

Animals↗

PubMed2006

Identification and evaluation of computer models for predicting environmental concentrations of pharmaceuticals and veterinary products in the Nordic environment.

According to European Union Council directive 2001/83, an application for the marketing authorization of a medicinal product shall be accompanied by an environmental risk assessment, including an exposure assessment. Computerized exposure models constitute an important tool in predicting environmental exposure to substances yet to be introduced on the market. This paper reports the process of identifying appropriate exposure models for estimating PECs (Predicted Environmental Concentrations) for pharmaceuticals and veterinary products, focusing on emissions to Swedish aquatic and terrestrial environments via water and sludge from sewage treatment plants. From a large number of information sources, a set of 181 potentially relevant exposure models was identified. A process of scrutinizing and testing these models resulted in a final selection of two models, namely SimpleTreat 3.1 that is used to estimate distribution and elimination of chemicals in sewage treatment plants (resulting in a PEC), and VetPec, suited for veterinary products, that estimates PEC in soil (including pore water), groundwater, and surface water. It is concluded that there is still potential for further development of exposure model(s) specifically designed for pharmaceutical emissions to the Nordic environment and climate. Furthermore, increased regulatory data requirements would facilitate the use of existing models, and improve the quality of the output data from these models.

Computer Simulation↗

PubMed2006

Science and policy in risk assessments of chlorinated ethenes.

In this article the use of data obtained from standardized experimental methods, for example, as specified in OECD guidelines for the testing of chemicals, epidemiology data, and mechanism data obtained from nonstandardized experimental methods in carcinogen risk assessment is scrutinized using the most recent risk assessments made by International Agency for Research on Cancer (IARC), the MAK(MAK)-Kommission, World Health Organization (WHO), European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), and American Conference of Governmental Industrial Hygienists (ACGIH) for the four chlorinated ethenes as examples. The analysis shows that there was little controversy among these risk assessors about the interpretation of standardized animal data. On the other hand, they differ in their interpretation of epidemiology data, in particular in their assessment of statistical significance including the use of meta-analyses, and in quality evaluation of studies initiated on the basis of a priori concerns for carcinogenicity. The selection of mechanism data for species extrapolation is diverse among these risk assessors. Furthermore, in some cases they refrain from transparently motivating significant claims about mechanisms of toxicity by avoiding to give (explicit) references to the sources of information forming the basis of these claims or conclusions. This practice is not according to the scientific standards that should be required of a risk assessment document, and it makes it difficult to follow the argumentation and consequently to scrutinize the scientific accuracy of the conclusions drawn. In this article it is concluded that in some of these risk assessment documents, the use of mechanism data is not according to the scientific standards that should be required. It is furthermore concluded that if the use of mechanism data in these documents are representative of risk assessments in general, then there is an urgent need for further development and implementation of quality criteria for the use of mechanism data in species extrapolation.

Alkenes↗

PubMed2005

Priority setting in the REACH system.

Due to the large number of chemicals for which toxicological and ecotoxicological information is lacking, priority setting for data acquisition is a major concern in chemicals regulation. In the current European system, two administrative priority-setting criteria are used, namely novelty (i.e., time of market introduction) and production volume. In the proposed Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) system, the novelty criterion is no longer used, and production volume will be the main priority-setting criterion for testing requirements, supplemented in some cases with hazard indications obtained from QSAR modelling. This system for priority setting has severe weaknesses. In this paper we propose that a multicriteria system should be developed that includes at least three additional criteria: chemical properties, results from initial testing in a tiered system, and voluntary testing for which efficient incentives can be created. Toxicological and decision-theoretical research is needed to design testing systems with validated priority-setting mechanisms.

Chemical Industry↗

PubMed2005

Evaluating the risk decision process.

In order to ensure that risk assessment and risk management serve their purposes efficiently, it is essential to systematically evaluate actual practices. In this overview, it is proposed that such evaluation studies constitute an important field of study that should be recognized as a sub-discipline of regulatory toxicology with its own research issues and its own methodologies. Previous such evaluation studies are summarized. Methods are described that can be used for comparing different risk assessments of one of the same substance, for checking the consistency of harmonized classifications with the available data, for assessing the actual margin of safety (i.e. size of uncertainty factors) in exposure limits, and for comparing different lists of exposure limits. In conclusion, some important problem areas for future evaluation studies are pointed out.

Animals↗

PubMed2005

Improving REACH.

The European Commission has proposed a new system for chemicals control, the REACH system. The objectives of REACH with respect to risk assessment can be summarized in the form of two overarching goals. First, REACH aims at improved knowledge about the properties and the uses of individual chemical substances. Secondly, REACH is intended to increase the speed and efficiency of the risk assessment process and to make producers and importers of chemicals responsible for this process. The implementation of the REACH proposal will lead to increased availability of toxicological information but not to the extent that would be needed to achieve a sound scientific basis for risk assessment of individual substances. In this paper, we propose certain amendments of the current REACH proposal. The purpose of these proposals is to improve priority-setting and testing strategies and to simplify the risk assessment procedures.

Animals↗

PubMed2005

Principles and practices of health risk assessment under current EU regulations.

Risk assessments serve as the foundation of regulatory decision-making on whether to take actions to reduce (or otherwise manage) a toxicological or ecotoxicological risk or not. To understand the complex process that leads from the generation of scientific data, via risk assessment to risk management decision-making, close studies of the scientific basis and risk assessment methods must be undertaken. This paper consists of two main parts. In the first part the principles of the European Union process for risk assessments, as defined by legislations and official guidelines, are briefly outlined. In the second part the actual workings of this system are exemplified by the results from case studies of the risk assessment processes for trichloroethylene and for acrylamide. The analysis and comparison of these two cases illustrates: (1) that generation of a large amount of data does not ensure consensus among risk assessors, (2) that controversy can regard different levels of detail, (3) that controversy can arise at different organizational and theoretical levels, (4) that risk assessments may be subject to (public) criticism even if the experts agree, and (5) that "scientific" controversies have a significant policy component.

Acrylamide↗

PubMed2004

Indicators of uncertainty in chemical risk assessments.

For most of the chemical substances that are subject to regulatory and industrial decision making, important toxicological data are missing. The available dataset is often difficult to interpret, and the differences between alternative, scientifically reasonable interpretations may have major impact on decision making. Since such uncertainties are an important factor in decision making it is essential that they be reported in a transparent and understandable way. In order to clarify how toxicologists report uncertainties, 30 risk assessments for one and the same substance (trichloroethylene) from the years 1973-2001 were searched for phrases indicating uncertainty. These phrases can be divided between four categories: contentual, epistemic, conditionalising, and inferential uncertainty indicators. A typology of uncertainty indicators, based on these categories, is proposed. It is concluded that the use of uncertainty indicators in these texts is not transparent and that the development of standardised uncertainty indicators should significantly improve communications both within the scientific community and between scientists and policymakers.

Animals↗

PubMed2003

How accurate are the European Union's classifications of chemical substances.

The European Commission has decided on harmonized classifications for a large number of individual chemicals according to its own directive for classification and labeling of dangerous substances. We have compared the harmonized classifications for acute oral toxicity to the acute oral toxicity data available in the RTECS database. Of the 992 substances eligible for this comparison, 15% were assigned a too low danger class and 8% a too high danger class according to the RTECS data. Due to insufficient transparency-scientific documentations of the classification decisions are not available-the causes of this discrepancy can only be hypothesized. We propose that the scientific motivations of future classifications be published and that the apparent over- and underclassifications in the present system be either explained or rectified, according to what are the facts in the matter.

Animals↗

PubMed2003

Scrutinizing ACGIH risk assessments: the trichloroethylene case.

BACKGROUND: The American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit values (TLVs) for occupational exposure to chemicals and physical agents have been very influential in the setting of occupational exposure limits in many countries. METHODS: Three ACGIH risk assessments of the chlorinated solvent trichloroethylene (TCE) [ACGIH (1989): 5th edition; ACGIH (1992): 5th edition. Revised Vol II; ACGIH (1996): Suppl. 6th edition] are compared to 26 other risk assessments made of the same chemical substance. The documents are compared in terms of their overall conclusions and the data selected for assessment. RESULTS: It is shown that these ACGIH risk assessment documents were based on incomplete and biased data sets. CONCLUSIONS: The data on which the ACGIH [ACGIH (1996): Suppl. 6th edition] base their TCE risk assessment do not adequately reflect the available scientific knowledge about TCE toxicity and carcinogenicity. This may have influenced their conclusion that TCE is not carcinogenic in either animals or humans which stand out compared to contemporary risk assessments.

Animals↗

PubMed2002

The use of mechanistic data and the handling of scientific uncertainty in carcinogen risk assessments. The trichloroethylene example.

The purpose of this paper is to explore how risk assessors actually use mechanistic data in carcinogen risk assessment and to discuss how the handling of scientific uncertainty may affect the outcome of the risk assessment. The analysis is performed by comparing 29 trichloroethylene risk assessment documents in general and 2 of these, namely the ECETOC (1994, Trichloroethylene: Assessment of Human Carcinogenic Hazard, Technical Report No. 60) and the OECD/EU (1996, Initial Assessment Report for the 4th SIAM (Screening Information Data Set Initial Assessment Meeting), May 1996: Trichloroethylene, sponsor country, United Kingdom [Draft]), in more detail. It is concluded that in this example the ECETOC required less evidence for considering a carcinogenic mechanism irrelevant to humans than did the OECD/EU risk assessors. There are examples of when two risk assessors have selected different primary data for their argumentation and also examples of how one and the same primary publication was interpreted differently. Biased data selection and evaluation of primary data that correlate to the risk assessor's overall conclusions have also been identified. The general comparison of all 29 TCE risk assessment documents indicates that the assessment of scientific uncertainty in the mechanistic data affects the overall conclusions.

Animals↗

PubMedDate not supplied

Scrutinizing three trichloroethylene carcinogenicity classifications in the European Union--implications for the risk assessment process.

In this paper, carcinogenicity classifications of the chlorinated solvent trichloroethylene (TCE) made by the European Union Commission Expert Groups in 1976, 1988, and 2001 are scrutinized and alternative classifications are proposed. It is argued that the TCE database at these three points in time could have been interpreted to fulfill the criteria for stricter classifications than those actually made. Implications of this for the classification process are discussed.

Animals↗

PubMedDate not supplied

Science and transscience in carcinogen risk assessment--the European Union regulatory process for trichloroethylene.

This is a study of carcinogen risk assessment of the chlorinated solvent trichloroethylene within the European Union existing substances program and the classification and labeling process. The focus is on the most active and influential participants of this process, namely, those from the United Kingdom, Germany, and Sweden, and from industry. The member state and other experts have different opinions regarding the appropriate classification of trichloroethylene for mutagenicity (no classification or category 3) and carcinogenicity (category 3, 2, or 1). In this article these differences are described, as well as how the primary carcinogenicity and mutagenicity data have been interpreted and evaluated by these participants. It is concluded that underlying the different assessments are disagreements about issues that to some degree lie outside the scope of purely scientific considerations.

Carcinogens↗