EU Chemicals Regulation Research Articles

A Battle of the Norms in EU Chemicals Regulation Space: Reflections on the Court of Justice Decision on the Concept of “Articles” Under REACH

Judgment of the Court (Third Chamber) delivered on 10 September 2015 in Case C-106/14, Fédération des entreprises du commerce et de la distribution (FCD) and Fédération des magasins de bricolage et de l’aménagement de la maison (FMB) v Ministre de l’écologie, du développement durable et de lʼénergie.

Optimization of the CULTEX(®) radial flow system for in vitro investigation of lung damaging agents.

Exposure of the respiratory tract to airborne particles is gaining more and more importance due to the ubiquitous application of these particles in the field of industry, pharmacy and in daily life. Remarkably, the toxic properties and the underlying pathomechanisms with regard to inhalable substances have been insufficiently investigated so far. Thus, the EU Chemicals Regulation demands toxicological data (including the identification of potential inhalation hazards) for all chemicals placed on the market until 2018 (REACH). This requires extensive, technically complex and expensive inhalation toxicology studies that are usually generated in animal experiments. However, the legislation demands the consideration of the "3Rs" principle. Thus, in vitro-based test systems for the assessment of pulmonary toxicity are required. One promising approach to assess acute pulmonary toxicity of airborne particles is the CULTEX(®) RFS methodology that allows exposure of human lung epithelial cells at the air-liquid interface mimicking the alveolar situation. A prevalidation study showed the general applicability of this method. However, the clean air exposure group, which served as unexposed controls, exhibited some variations with regard to cell viability compared to the incubator control group. The aim of this study was therefore the identification of the possible causes and the improvement of methodological aspects. Several parameters including the general workflow, adjustment of airflow parameters, and cleaning procedures were investigated and adapted. Finally, our results showed the successful optimization of the CULTEX(®) RFS methodology for clean air exposure of A549 cells. However, although viability data in incubator controls and clean air exposures were equal, a distinct difference in cell morphology was observed that required further optimization. Additional experiments identified that open-wall cell culture inserts with a 2-fold pore density were found to be superior compared to the standard inserts and thus the deciding factor for the improvement of cell morphology. The presented findings are an important step in providing the CULTEX(®) RFS methodology as a promising alternative method to current in vivo testing in inhalation toxicology.

A critical appraisal of existing concepts for the grouping of nanomaterials

The grouping of substances serves to streamline testing for regulatory purposes. General grouping approaches for chemicals have been implemented in, e.g., the EU chemicals regulation. While specific regulatory frameworks for the grouping of nanomaterials are unavailable, this topic is addressed in different publications, and preliminary guidance is provided in the context of substance-related legislation or the occupational setting. The European Centre for Ecotoxicology and Toxicology of Chemicals Task Force on the Grouping of Nanomaterials reviewed available concepts for the grouping of nanomaterials for human health risk assessment. In their broad conceptual design, the evaluated approaches are consistent or complement each other. All go beyond the determination of mere structure–activity relationships and are founded on different aspects of the nanomaterial life cycle. These include the NM’s material properties and biophysical interactions, specific types of use and exposure, uptake and kinetics, and possible early and apical biological effects. None of the evaluated grouping concepts fully take into account all of these aspects. Subsequent work of the Task Force will aim at combining the available concepts into a comprehensive ‘multiple perspective’ framework for the grouping of nanomaterials that will address all of the mentioned aspects of their life cycles.

Great Expectations: Reviewing 50 Years of Chemicals Legislation in the EU

This article is about how we look at EU chemicals law. It brings together the past and present of five decades of EU chemicals law in the hope that it may lead to a better understanding of the future potential and evolution of law in the area. The article tells a story of EU legislative centralisation, colonisation and standardisation. We argue that these historical trends have aroused certain expectations about the role and functioning of modern EU chemicals regulation in REACH. These expectations, we argue, are often unrealistically high, misplaced or at times unnecessarily low. The challenges set out in our article suggest that EU chemicals regulation in its current form is set up largely to fail. Moreover, we argue that these problems make a case for the radical reorientation of regulatory goals, values and practices and indicate that the biggest challenge in chemicals policymaking is not necessarily to meet expectations but to manage them more effectively.

Laws in Progress? Reconceptualizing Accountability Strategies in the Era of Framework Norms

AbstractEU law is teeming with framework norms – ‘laws in progress’. They provide little clarity for those to whom they apply, engendering rule-making in networks to assist those charged with implementing and applying laws at the national level. Taking as its specific focus the particular process through which the concept of an ‘article’ was constructed and constituted in a set of negotiations around the EU Chemicals Regulation, REACH, this article shows that networks not only make framework norms operational but also transform them in the process. The fact that networks have an important role in laying out what the law says throws the effectiveness of traditional forms of accountability in doubt. In particular, judicial control is in need of rethinking in order to accommodate norms that change and the networks that change them. This article suggests looking at the connections between internal peer control and externally operating judicial control as a way to keep up with the progress of laws in progress.

Influence of the EU Chemicals Regulation on the US Policy Reform Debate: Is a ‘California Effect’ within REACH?

AbstractIn 2006, the EU adopted the REACH Regulation – the world’s most demanding chemicals regime so far. Even before it entered into force, the European Commission declared its ambition to make REACH a global standard, and several authors see a potential for far-reaching influence via the ‘California effect’, as conceptualized by David Vogel. Economic preconditions are indeed fulfilled with the chemicals industry being highly globalized, the EU as an attractive export market and REACH applying to imports. Following Vogel, firms exporting to the EU might have an incentive to lobby for similar requirements in their country. This article examines whether American chemical producers do, indeed, push for EU-like provisions in the debate on US policy reform. While there is some influence on the US, it is shown that REACH does not (yet) trigger a ‘California effect’. The business case does not seem to be strong enough.

Risk assessment of local dermal effects and skin sensitisation under the EU Chemicals Regulation REACH: A proposal for a qualitative, exposure scenario specific, approach

Within the framework of REACH, an assessment regarding local dermal effects and skin sensitisation should be performed for substances. Quantitative hazard information for these effects is often not available. Furthermore, it is difficult to relate the way in which animals are exposed in dermal toxicity studies directly to dermal exposure in practice. In the absence of quantitative information, a qualitative assessment for dermal effects is the most reasonable option. The qualitative approach as proposed in the REACH guidance recommends only general risk management measures (RMM) for three categories with a low, moderate and high identified hazard, without specifying which RMM are needed for a specific exposure scenario. We propose to differentiate frequency of exposure based on differences in activities and to compare measured and estimated local skin exposure levels with rules of thumb for evaluation of control of risks per hazard category. For workers, specific RMM regimes are assigned to each combination of hazard category and process category (PROC). For consumers, a strategy in which RMM are arranged from product-integrated measures to the use of personal protective equipment (PPE) is presented. Our approach may be transferred into automated assessment tools like Chesar and CEFIC GES.

Precautionary regulation of chemical risk: How REACH confronts the regulatory challenges of scale, uncertainty, complexity and innovation

In this article, we provide an in-depth analysis of the Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). Measured by the economic importance of the European chemicals industry and the environmental and health risks associated with it, the Regulation probably represents the most important piece of EU environmental regulation to date. We argue that the precautionary approach embodied in REACH has triggered a radical departure from past regulatory efforts that failed effectively to engage with contemporary regulatory challenges of scale, uncertainty, complexity and innovation. In effect, REACH is shaping a promising EU regime of responsive co-regulation that is without precedent in the forty-year history of EU environmental law. We believe that the success of this regime will not only determine the effectiveness of EU chemicals regulation, but more generally will come to determine the way in which EU regulation is likely to respond to a host of new technologies that shape our technological modernity.

Comparison of chemical-induced transcriptional activation of fish and human estrogen receptors: Regulatory implications

Under the current EU chemical regulation REACH (Registration, Evaluation, Authorization and Restriction of Chemicals), revised plant protection products and biocides directives, evaluation of endocrine disrupting properties of chemicals becomes a regulatory need. Transcriptional activation (TA) testing of estrogen receptors (ERs) could be one important first step in the screening and testing of endocrine disrupting chemicals (EDCs) for regulatory purposes. However up to now there is no consensus on which species or subtype of ERs should be used for TA testing. This study collected data from publications on TA testing with fish and human ERs for 90 chemicals, covering strong, moderate, and weak or non-ER binders. Each chemical has been reported at least twice, with differential ER TA values that result from different cellular contexts, from intra-/inter-species and subtypes of ERs and from intra-/inter-laboratory differences. All assays could distinguish the differential transcriptional activity induced by chemicals of strong, moderate, and weak or non-ER binders. It is concluded that transactivation of ERs in one vertebrate species or one subtype of ERs could be extrapolated to other species or subtypes of ERs for the purpose of chemical screening. It is emphasized that results from ER TA assays can only be used in a weight-of-evidence approach for further testing in regulatory programs. These results are of importance for regulatory testing strategies and decision making for EDCs.

Hazard v. Risk in EU Chemicals Regulation

Hazard is the potential of something to cause harm; risk is the likelihood of harm occurring. Chemicals regulation is largely focused on minimising risks associated with chemicals — and rightly so. However, in the EU the hazard classification of individual chemicals can impact significantly the regulation of products containing those chemicals, regardless of the actual risks that the products may pose to human health or the environment. This can lead to undesirable consequences, such as restrictions on the use of safe products, substitution towards less safe products, and disincentives to innovate. Such hazard-based regulation tends to be at odds with World Trade Organization rules and has raised significant concern with EU trading partners. This journal is an ideal forum for discussing how the EU can move towards a better and more coordinated legal framework for the regulation of chemicals.

The Center for Alternatives to Animal Testing – Europe (CAAT-EU): a transatlantic bridge for the paradigm shift in toxicology

The Center for Alternatives to Animal Testing - Europe (CAAT-EU) was founded based collaboration between the Johns Hopkins Bloomberg School of Public Health and the University of Konstanz. CAAT-EU, housed at the University of Konstanz, will coordinate transatlantic activities to promote humane science in research and education, and participate, as partner or coordinator, in publicly and privately funded European projects. Thomas Hartung will serve as program liaison representing Johns Hopkins University and Marcel Leist as the University of Konstanz liaison. CAAT-EU aims to: 1) Set up transatlantic consortia for international research projects on alternative methods. 2) Establish a CAAT Europe faculty and advisory board composed of sponsor representatives and prominent academics from Europe . 3) Participate in the Transatlantic Think Tank for Toxicology (t4) devoted to conceptual work for the paradigm shift in toxicology. 4) Coordinate a series of information days in Europe on relevant developments in the US, similar to the 2009 series CAAT held in the US on EU issues (one on the 7th Amendment to the EU Cosmetics Directive and one on EU and US chemical regulation). 5) Support ALTEX as the official journal of CAAT and CAAT-EU. 6) Develop strategic projects with sponsors to promote humane science and new toxicology, especially with CAAT faculty members. 7) Develop a joint education program between Johns Hopkins and the University of Konstanz, such as e-courses and the existing Humane Science Certificate program developed by CAAT, a student exchange program, and collaboration with the International Graduate School "Cell-based Characterization of De- and Regeneration" in Konstanz.

From dermal exposure to internal dose

Exposure scenarios form an essential basis for chemical risk assessment reports under the new EU chemicals regulation REACH (Registration, Evaluation, Authorisation and restriction of Chemicals). In case the dermal route of exposure is predominant, information on both exposure and dermal bioavailability is necessary for a proper risk assessment. Various methodologies exist to measure dermal exposure, providing quantitative or semiquantitative information. Although these studies may provide very specific and relevant information, it should be realized that case by case in-depth exposure assessment would be a very expensive process. Dermal bioavailability data are most often obtained from in vitro studies or animal experiments. For the design of studies, which generate data relevant for chemical risk assessment, detailed information on the exposure conditions is crucial (skin surface exposed, exposure duration, dose and physical state of the chemical). Results from non-testing methods for skin absorption, such as (Q)SARs, have been used only to a very limited extent for regulatory purposes. Suggestions are made in order to extend the use these methods to dermal risk assessment of chemical substances, thereby improving the practicability of REACH.

NEMA sections merge / EU chemical regulations will require industry to provide safety data on 30,000 substances

NEMA sections merge / EU chemical regulations will require industry to provide safety data on 30,000 substances

Normal human keratinocyte assay to predict the human irritancy response

The potential to cause human skin irritation responses is part of the required information for the registration of new chemicals and for chemicals to conform to the new EU Chemical regulations under Registration, Evaluation, and Authorisation of Chemicals (REACH). The Fund for Replacement of Animals in Medical Experiments (FRAME) has developed an in vitro assay for potential human irritant responses via the skin, employing human passage 1-3 primary keratinocytes. The assay is based on two assessments: a direct assay of keratinocytes and an assay of the effect on macrophages of the mediators released by the keratinocytes. Keratinocyte activity is measured by the resazurin assay. Mediator activity is measured by assaying the release of nitric oxide (NO) following macrophage stimulation. It is also possible to measure release of interleukin-1alpha (IL-1alpha). Additional mediators are also released, but the precise range and composition of all these mediators are not clear at present. From time of exposure, this assay can be completed in 3-7 d; the exact timing is dependent on the rate and degree of recovery.

The Greens perspective on EU chemicals regulation and the White Paper.

Risk AnalysisVolume 23, Issue 2 p. 405-409 The Greens Perspective on EU Chemicals Regulation and the White Paper Inger Schörling, Corresponding Author Inger Schörling *Address Correspondance to Inger Schörling; ischorling@ europarl.eu.int. Inger Schörling is a member of European Parliament, the Committee on the Environment, Public Health and Consumer Policy, rapporteur for the White Paper on a Strategy for a Future Chemicals Policy.Search for more papers by this author Inger Schörling, Corresponding Author Inger Schörling *Address Correspondance to Inger Schörling; ischorling@ europarl.eu.int. Inger Schörling is a member of European Parliament, the Committee on the Environment, Public Health and Consumer Policy, rapporteur for the White Paper on a Strategy for a Future Chemicals Policy.Search for more papers by this author First published: 09 April 2003 https://doi.org/10.1111/1539-6924.00320Citations: 7Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume23, Issue2April 2003Pages 405-409 RelatedInformation

Swedish chemical regulation: an overview and analysis.

This article begins with a review of the regulation of chemicals in Sweden over the past 30 years, focusing particularly on the 1997 Government Environmental Quality Bill, which called for a toxic-free society by the year 2020. The second part of the article analyzes why Sweden has taken this route. The third and final section discusses Sweden's present role in formulating present EU chemical regulation, such as the recent EU Chemical White Paper, and hypothesizes future impacts of Swedish chemical regulations on the EU itself.