Suchergebnisse

Risk assessments serve as the foundation of policy decisions on whether to take measures to reduce a risk or not. However, different risk assessors frequently come to divergent estimates of the magnitude and even the nature of risks. Few attempts has been made in the past to describe and understand the reasons for these differences. This thesis reports the results from a detailed comparison of 30 different cancer risk assessments made of one and the same chemical substance, namely the chlorinated solvent trichloroethylene (CAS no. 79-01-6). The purpose of the present study is to discuss (1) why risk assessors come to different conclusions, (2) how scientific data are used in risk assessment, and (3) how scientific uncertainty is handled in the process. The overall objective is to contribute to increase the transparency and reliability of risk assessments so that they better serve the needs of risk managers and the public. In the first part of this study the different conclusions drawn in these risk assessment documents are identified and described. This is made within the framework of a proposed cancer risk assessment index (CRAI). The CRAI categorization shows that these risk assessors come to divergent conclusions about the trichloroethylene potential to cause cancer. To enable an analysis of the reasons for these differences, detailed information from the trichloroethylene risk assessment documents was stored in a database. This information made it possible to compare the risk assessment documents in terms of data availability (a time dependent factor), data selection, data interpretation, data quality evaluation, and (animal to human) extrapolation of data, and to analyse how these parameters influenced the overall conclusions. The analysis of these data indicates that the differences in conclusions cannot exclusively be explained by an evolving database (data availability). The data sets utilized by the trichloroethylene risk assessors are surprisingly diverse and incomplete, and biased data selection may have influenced some of the risk assessors conclusions. The TCE risk assessors often interpret and evaluate scientific data in different ways. These differences are considered to be within the scope of the scientifically acceptable. In the second part of this case study the European Union regulatory process for classification and labeling served as study object of the risk assessment process in a setting where risk assessors from different affiliations evaluated exactly the same data. This part of the study indicates that there is a scope of possible interpretations of the primary data in relation to the classification criteria and thus that there may be more than one possible alternative for classification of individual substances. The main controversies in this process are also identifed and they are found to concern issues that include policy considerations and thus are not readily resolved by ftirther research. It is concluded that the uncertainty inherent in scientific data opens up a scope of possible interpretations and conclusions and that differences in the assessment and handling of this scientific uncertainty have the potential to influence the overall assessment of risk. It is furthermore concluded that even if an enormous amount of resources were spent on testing and assessment of individual substances (orders of magnitude more than what is required according to existing and proposed regulations), significant uncertainty about their potential to cause harm may still remain.

This important contribution to the scientific understanding of chemical risk regulation offers a coherent, comprehensive and updated multidisciplinary analysis, written by leading experts in toxicology, ecotoxicology, risk analysis, media and communication, law, and political science.

Abstract

Background
Standard test data are still preferred and recommended for regulatory environmental risk assessments of pharmaceuticals even though data generated by non-standard tests could improve the scientific basis of risk assessments by providing relevant and more sensitive endpoints.
The aim of this study was to investigate if non-standard ecotoxicity data can be evaluated systematically in risk assessments of pharmaceuticals. This has been done by evaluating the usefulness of four reliability evaluation methods, and by investigating whether recently published non-standard ecotoxicity studies from the open scientific literature fulfill the criteria that these methods propose.


Results
The same test data were evaluated differently by the four methods in seven out of nine cases. The selected non-standard test data were considered reliable/acceptable in only 14 out of 36 cases.


Conclusions
The four evaluation methods differ in scope, user friendliness, and how criteria are weighted and summarized. This affected the outcome of the data evaluation.
The results suggest that there is room for improvements in how data are reported in the open scientific literature. Reliability evaluation criteria could be used as a checklist to ensure that all important aspects are reported and thereby increasing the possibility that the data could be used for regulatory risk assessment.

AbstractHumans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real‐life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs ("bad actors")—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a "typical" mixture consisting of the "bad actors" identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of "sufficient similarity" to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a "similar mixture risk indicator" (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound‐by‐compound strategy (1.6%).

Background The regulatory approach used by SKI has an impact on the licensee and, therefore, indirectly on the safety of the nuclear facilities. The regulatory policy and its implementation also influences the way SKI is working and the competency needed by the regulator as well as by the industry. One of SKI´s tasks is to be able adjust the regulatory approach to current and future needs. Little research is available on the use of regulatory strategies, methods and activities used by regulatory agencies in their work (to assure safety), as well as their impacts. To address this gap in knowledge, SKI has contracted two separate research projects. This project, where the focus is on comparing inspection policies in Swedish government agencies, and another one where regulatory strategies across selected countries, are studied and compared. SKI´s purpose and goals The goal of this research project is to gain knowledge about selected Swedish agencies and their inspection policies. All the selected agencies are working with issues regarding health, environmental protection or safety. A number of persons at each agency have been interviewed about the regulatory work at their organizations. A questionnaire was developed as a first part of the project, and it was used during the interviews. In addition to provide insights as a basis for improvement within SKI, the purpose has been to promote exchange of experience between agencies with similar tasks. By this study SKI also wanted to contribute to the development of competency in this field of research. Results A lot of information has been gathered and analyzed during the project. The focus of the research is on comparing agencies and their practices. The report includes an analysis regarding similarities and differences in a number of areas across the agencies. The report also provides information and evidence on the problems related to comparison between agencies, partly due to the difference in the use of definitions. The recommendations resulting from this study focus on improving cooperation among Swedish agencies and on improving inspection methodologies, areas where further analysis is suggested. The conclusions and recommendations in the report belong to the persons participating in this work, and are not necessarily the same as the once drawn by SKI.

This paper presents 10 recommendations for improving the European Medicines Agency's guidance for environmental risk assessment of human pharmaceutical products. The recommendations are based on up-to-date, available science in combination with experiences from other chemical frameworks such as the REACH-legislation for industrial chemicals. The recommendations concern: expanding the scope of the current guideline; requirements to assess the risk for development of antibiotic resistance; jointly performed assessments; refinement of the test proposal; mixture toxicity assessments on active pharmaceutical ingredients with similar modes of action; use of all available ecotoxicity studies; mandatory reviews; increased transparency; inclusion of emission data from production; and a risk management option. We believe that implementation of our recommendations would strengthen the protection of the environment and be beneficial to society. Legislation and guidance documents need to be updated at regular intervals in order to incorporate new knowledge from the scientific community. This is particularly important for regulatory documents concerning pharmaceuticals in the environment since this is a research field that has been growing substantially in the last decades.

Abstract The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.

The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU. ; ISSN:1476-069X

The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.

The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.

Abstract: The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU. ; Keywords: Endocrine disrupting chemicals, Environment, Health, Precautionary principle, Regulatory toxicology. ; Springer Open.