Argumentation Analysis of Risk Assessments: The Case of Perfluorooctanoic Acid.

Risk assessment of chemicals can be based on toxicology and/or epidemiology. The choice of toxicological or epidemiological data can result in different health-based guidance values (HBGVs). Communicating the underlying argumentation is important to explain these differences to the public and policymakers. In this article, we explore the argumentation used to justify the use of toxicological or epidemiological data in the derivation of HBGVs in four different risk assessments for the chemical Perfluorooctanoic acid (PFOA). The pragma-dialectical argumentation theory (PDAT) is hereby applied. The argumentations to select relevant health endpoints or certain studies to infer causality appeared mainly based on "symptomatic relations," that is, study results are used as characteristic of what was claimed to be a causal relation without delving into the actual causal argumentation that preceded it. Starting points that are at the basis of the chain of arguments remained implicit. Argumentation to use epidemiological and/or toxicological data was only briefly mentioned and the underlying argumentative foundation that led to the conclusion was seldom found or not addressed at all. The decision to include/exclude information was made based on the availability of data, or the motives for the choice remained largely unclear. We conclude that more depth in argumentation and a subordinative chain of arguments is needed to better disclose the underlying reasoning leading to a certain health-based guidance value (HBGV). More explicit identification and discussion of starting points could be a valuable addition to general risk assessment frameworks for maximum use of toxicological and epidemiological data and shared conclusions of the assessment.

Sera from different age cohorts in Belgium show limited cross-neutralization between the mumps vaccine and outbreak strains.

OBJECTIVES: Mumps used to affect children between 2 and 15 years old. The mumps-measles-rubella (MMR) vaccine is available, with vaccine coverage rate of about 85% after two vaccine doses. Recently new mumps outbreaks have emerged in highly vaccinated populations; the causes for these new outbreaks are yet unknown. We tested if a difference in seroneutralizing capacity against the vaccine and wild-type viruses existed and if waning immunity could be detected. METHODS: In this study, 570 serum samples (age group 2-3 years (n = 96), 8-9 years (n = 95), 13-14 years (n = 94), 18-20 years (n = 96), 24-26 years (n = 92) and 50 + years (n = 97)) in Belgium were tested in the rapid fluorescent foci inhibition test for their neutralizing capacity against the vaccine and wild-type viruses. RESULTS: Neutralizing antibodies against the vaccine strain were present in 84% (81/97) of the 2-3-year, 74% (70/95) of the 8-9-year, 81% (76/94) of the 13-14-year, 76% (73/96) of the 18-20-year, 67% (62/92) of the 24-26-year and 77% (75/97) of the 50+-year age group serum samples. For all age groups, only about half of these serum samples were also positive for the wild-type virus. The geometric mean titres for the vaccine and wild-type virus for all younger age groups, except for 24-26 years, were significantly different, demonstrating poor in vitro cross-neutralization. CONCLUSIONS: A possible contribution of antigenic differences between the genotype A and G mumps virus as well as other immune factors, in addition to lower-than-optimal vaccination coverage and waning immunity, could explain the poor in vitro cross-neutralization and should be further studied.

Relative parameter sensitivity in prenatal toxicity studies with substances classified as developmental toxicants.

Developmental toxicity testing according to the globally standardized OECD 414 protocol is an important basis for decisions on classification and labeling of developmental toxicants in the European Union (EU). This test requires relatively large animal numbers, given that parental and offspring generations are involved. In vitro assay designs and systems biology paradigms are being developed to reduce animal use and to improve prediction of human hazard. Such approaches could benefit from the long-term experience with animal protocols and more specifically from information on the relevance of effects observed in these tests for developmental toxicity. Therefore, we have analyzed relative parameter sensitivity in 22 publicly available developmental toxicity studies, representing about one third of all classified developmental toxicants under European legislation. Maternal and fetal weight effects and fetal survival were most often affected parameters at the developmental Lowest Observed Adverse Effect Level (dLOAEL), followed by skeletal malformations. Specific end points such as cleft palate were observed in fewer studies at dLOAEL, but if observed may have been crucial in classification and labeling decisions. These results are similar to earlier studies using different selections of chemicals, indicating that in general classified developmental toxicants have a similar pattern of effects at the dLOAEL as chemicals in general. These findings are discussed within the perspective of the development of innovative alternative approaches to developmental hazard assessment.

European union system for the evaluation of substances: the second version.

This publication presents major changes in the assessment of the risks of chemicals to human health and the environment as implemented in the second version of the European Union System for the Evaluation of Substances, EUSES 2.0. EUSES is a harmonised quantitative risk assessment tool for chemicals. It is the PC-implementation of the technical guidelines developed within the framework of EU chemical legislation for industrial chemicals and biocides. As such, it is designed to support decision making by risk managers in government and industry and to assist scientific institutions in the risk assessment for these substances. The development of EUSES 2.0 is a co-ordinated project of the European Chemicals Bureau, EU Member States and the European chemical industry. Several model concepts, the technical background and the user interface of EUSES have been improved considerably. Major changes in the environmental assessment such as the implementation of emission scenario documents for industrial chemicals and biocides, the addition of the marine risk assessment, the enhancement of the regional model to include global scales, and improvements in the secondary poisoning and environmental effects modelling will be discussed. The update of the human risk assessment module in EUSES focuses on the risk characterisation for both threshold and non-threshold substances with, among others, the introduction of assessment factors. The performance of EUSES is illustrated in an example showing the human and environmental risk assessment of a sanitation disinfectant for private use.

Evaluation of EU risk assessments existing chemicals (EC Regulation 793/93).

An evaluation was performed on the first group (41) of completed risk assessments for chemicals of the EU priority lists (Existing Chemicals; EC Regulation 793/93). The evaluation focussed on the conclusions of the risk assessments. The EU risk assessment process detected a high number of substances of concern. Furthermore priority chemicals may pose potential risks to the whole range of protection goals of the risk assessment. The predictability of the risk assessments for priority chemicals was investigated. Our a priori knowledge on possible risks of priority chemicals is found to be poor, especially for consumers. Both for environment and human health the potential risks were linked with a broad spectrum of use patterns. It is concluded that no industry category can in advance be excluded from performing risk assessments. For a great number of chemicals, additional testing was found to be needed to finalize the risk assessment. This evokes questions about the completeness of the current base-set, but also about the suitability of some of the submitted human health tests that should initially fulfil the base-set needs. The results of this evaluation are useful for ongoing discussions on risk assessment processes for chemicals.

Opportunities for a probabilistic risk assessment of chemicals in the European Union.

In risk assessment of new and existing substances, it is current practice to characterise risk using a deterministic quotient of the exposure concentration, or the dose, and a no-effect level. A sense of uncertainty is tackled by introducing worst-case assumptions in the methodology. Since this procedure leads to an assessment with an unknown degree of conservatism, it is advisable to deal quantitatively with uncertainties. This paper discusses the advantages and possibilities of a probabilistic risk assessment framework, illustrated with an example calculation. Furthermore, representatives of EU Member States and the chemical industry were interviewed to find out their views on applying uncertainty analysis to risk assessment of industrial chemicals.

Assessment factors for human health risk assessment: a discussion paper.

The general goal of this discussion paper is to contribute toward the further harmonization of human health risk assessment. It first discusses the development of a formal, harmonized set of assessment factors. The status quo with regard to assessment factors is reviewed, that is, the type of factors to be identified, the range of values assigned, as well as the presence or absence of a scientific basis for these values. Options are presented for a set of default values and probabilistic distributions for assessment factors based on the state of the art. Methods of combining default values or probabilistic distributions of assessment factors are also described. Second, the effect parameter, the no-observed-adverse-effect level (NOAEL), is discussed. This NOAEL as selected from the toxicological database may be a poor substitute for the unknown, true no-adverse-effect level (NAEL). New developments are presented with respect to the estimation of the NAEL. The already widely discussed Benchmark Dose concept can be extended to obtain an uncertainty distribution of the Critical Effect Dose (CED). This CED distribution can be combined with estimated uncertainty distributions for assessment factors. In this way the full distribution of the Human Limit Value will be derived and not only a point estimate, whereas information on dose-response relations is taken into account. Finally, a strategy is proposed for implementation of the new developments into human health risk assessments.

European Union System for the Evaluation of Substances (EUSES). Principles and structure.

In the European Union, Directive 92/32/EC and EC Council Regulation (EC) 793/93 require the risk assessment of new and existing substances, respectively. Principles for this risk assessment have been laid down, supported by a detailed package of Technical Guidance Documents. Against this background the European Union System for the Evaluation of Substances (EUSES) has been developed. This software can be used to carry out tiered risk assessments of increasing complexity on the basis of increasing data requirements. The exposure assessment, effects assessment and risk characterisation are carried out for environmental populations as well as for human beings, including workers, consumers and man exposed through the environment. EUSES is the result of a co-ordinated effort of EU Member States, the European Commission and the European Chemical Industry.

Risk assessment and management of new and existing chemicals.

An evaluation was made of the recently developed risk assessment methodologies for new and existing chemicals in the European Communities. The evaluation also included the methodologies to prioritize chemicals and procedures for risk management, i.e., the (draft) guidance document for the development of strategies for risk reduction. The way in which chemicals are prioritized is accepted with only very few comments. Clear progress has been made in the development and harmonization of risk assessment methodologies and the application of estimation methodologies. Nevertheless, improvements are necessary for the estimation of consumer and occupational exposure, the derivation, use and transparency of assessment factors for chemicals and classes of chemicals based on the mode of toxic action, environmental exposure models and their validation and relation with monitoring data. As far as risk management is concerned it was recommended to improve the integration of the myriad of directives and regulations, to clarify definitions, to provide clear guidance on the determination and weighing of advantages and implications of risk reduction measures and to develop tools, including voluntary agreements, to speed up the slow chemical-by-chemical approach.

Uniform system for the evaluation of substances. I. Principles and structure.

In April 1994, the first version of the Uniform System for the Evaluation of Substances (USES 1.0) was launched to comply with an action point of the Netherlands National Environmental Policy Plan. USES is a tool for the rapid, quantitative assessment of the hazards and risks of chemical substances, including new substances, existing substances, agricultural pesticides and biocides. It was developed to be applied as a decision-support system by the central government, by industry and institutes in the private sector and by international fora. Since hazard and risk assessment must be transparent to all users and easy to perform, USES 1.0 is well documented and available as a computer program. An overview of this system will be presented including its objectives, the national and international framework, the general principles involved, as well as the structure and the content of the models used.

Health assessment of hazardous air pollutants The Netherlands.

In The Netherlands, risk assessment of air pollutants goes back to 1980. From 1985 onwards the risk assessment of chemicals has crystallized in a systematic multi-media approach taking into account air, water, soil, and food. Criteria Documents support the formulation of environmental quality standards. Until now, 23 documents were prepared. Some toxicological aspects of the risk assessment for man in these documents are discussed with emphasis on carcinogenicity. As examples the main aspects of the risk assessments of benzene and trichloroethylene are described. A list of proposed health based standards for air pollutants is added.