European Chemicals Agency ECHA

Helsinki, Finland

European Chemicals Agency ECHA

Helsinki, Finland
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Van Dorst B.,University of Antwerp | Van Dorst B.,Belgium Institute for Agricultural and Fisheries Research | Mehta J.,University of Antwerp | Mehta J.,Belgium Institute for Agricultural and Fisheries Research | And 8 more authors.
Toxicology in Vitro | Year: 2010

cDNA phage display is frequently used in drug development to screen for cellular target of drugs. However, in toxicology, cDNA phage display remains unexplored, although it has large potential in this field. In this study, cDNA phage display is demonstrated as a novel tool to screen for interactions between chemical compounds and cellular targets. The knowledge of these target interactions is valuable to have a more complete understanding of the mechanisms of action of chemical compounds.Bisphenol A (BPA) was selected as a model compound for this study. By selection of the cellular proteins that bind BPA with cDNA phage display, it was possible to identify a known cellular target of BPA, tubulin α and a possible novel cellular target of BPA, transforming acidic coiled-coil containing protein 3. Both these cellular proteins are involved in the mechanism of cell division. The disruption of cell division is a known non-genomic effect of BPA. Non-genomic effects are not mediated by differences in gene expression and therefore important mechanistic information might be missed with the widely used differential gene expression techniques for mode of action research. This cDNA phage display technique can provide important additional information about the interaction of chemical compounds with cellular targets that mediates these non-genomic actions and therefore gives complementary information to toxicogenomic studies to obtain a more complete understanding of the mechanism of action of chemical compounds. © 2010 Elsevier Ltd.


Rheinberger C.M.,European Chemicals Agency ECHA | Treich N.,French National Institute for Agricultural Research
Environmental and Resource Economics | Year: 2016

In light of climate change and other global threats, policy commentators sometimes urge that society should be more concerned about catastrophes. This paper reflects on what society’s attitude toward low-probability, high-impact events is, or should be. We first argue that catastrophe risk can be conceived of as a spread in the distribution of losses. Based on this conception, we review studies from decision sciences, psychology, and behavioral economics that explore people’s attitudes toward various social risks. Contray to popular belief, we find more evidence against than in favor of catastrophe aversion—the preference for a mean-preserving contraction of the loss distribution—and discuss a number of possible behavioral explanations. Next, we turn to social choice theory and examine how various social welfare functions handle catastrophe risk. We explain why catastrophe aversion may be in conflict with equity concerns and other-regarding preferences. Finally, we discuss current approaches to evaluate and regulate catastrophe risk. © 2016 Springer Science+Business Media Dordrecht


PubMed | Brown University, Purdue University, University of California at Santa Barbara, ETH Zurich and 20 more.
Type: Journal Article | Journal: Environmental science & technology | Year: 2016

Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects. Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant concentrations-where observing outcomes is difficult-versus higher ENM doses, where responses are observable. What exposure conditions are typically used in assessing ENM hazards to populations? What conditions are used to test ecosystem-scale hazards? What is known regarding actual ENMs in the environment, via measurements or modeling simulations? How should exposure conditions, ENM transformation, dose, and body burden be used in interpreting biological and computational findings for assessing risks? These questions were addressed in the context of this critical review. As a result, three main recommendations emerged. First, researchers should improve ecotoxicology of ENMs by choosing test end points, duration, and study conditions-including ENM test concentrations-that align with realistic exposure scenarios. Second, testing should proceed via tiers with iterative feedback that informs experiments at other levels of biological organization. Finally, environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia.


Gissi A.,European Chemicals Agency ECHA | Louekari K.,European Chemicals Agency ECHA | Hoffstadt L.,European Chemicals Agency ECHA | Bornatowicz N.,European Chemicals Agency ECHA | Aparicio A.M.,European Chemicals Agency ECHA
Altex | Year: 2017

The REACH Regulation requires information on acute oral toxicity for substances produced or imported in quantities greater than one ton per year. When registering, animal testing should be used as last resort. The standard acute oral toxicity test requires use of animals. Therefore, the European Chemicals Agency examined whether alternative ways exist to generate information on acute oral toxicity. The starting hypothesis was that low acute oral toxicity can be predicted from the results of low toxicity in oral sub-acute toxicity studies. Proving this hypothesis would allow avoiding acute toxicity oral testing whenever a sub-acute oral toxicity study is required or available and indicates low toxicity. ECHA conducted an analysis of the REACH database and found suitable studies on both acute oral and sub-acute oral toxicities for 1,256 substances. 415 of these substances had low toxicity in the sub-acute toxicity study (i.e., NO(A)EL at or above the limit test threshold of 1,000 mg/kg). For 98% of these substances, low acute oral toxicity was also reported (i.e., LD50 above the classification threshold of 2,000 mg/kg). On the other hand, no correlation was found between lower NO(A)ELs and LD50. According to the REACH Regulation, this approach for predicting acute oral toxicity needs to be considered as part of a weight of evidence analysis. Therefore, additional sources of information to support this approach are presented. Ahead of the last REACH registration deadline, in 2018, ECHA estimates that registrants of about 550 substances can omit the in vivo acute oral toxicity study by using this adaptation.


PubMed | University of Amsterdam, European Center for Ecotoxicology and Toxicology of Chemicals, University of Newcastle, Hill International and 9 more.
Type: Journal Article | Journal: Environmental science & technology | Year: 2015

The bioavailability of organic chemicals in soil and sediment is an important area of scientific investigation for environmental scientists, although this area of study remains only partially recognized by regulators and industries working in the environmental sector. Regulators have recently started to consider bioavailability within retrospective risk assessment frameworks for organic chemicals; by doing so, realistic decision-making with regard to polluted environments can be achieved, rather than relying on the traditional approach of using total-extractable concentrations. However, implementation remains difficult because scientific developments on bioavailability are not always translated into ready-to-use approaches for regulators. Similarly, bioavailability remains largely unexplored within prospective regulatory frameworks that address the approval and regulation of organic chemicals. This article discusses bioavailability concepts and methods, as well as possible pathways for the implementation of bioavailability into risk assessment and regulation; in addition, this article offers a simple, pragmatic and justifiable approach for use within retrospective and prospective risk assessment.


Van Dorst B.,University of Antwerp | Van Dorst B.,Belgium Institute for Agricultural and Fisheries Research | Mehta J.,University of Antwerp | Mehta J.,Belgium Institute for Agricultural and Fisheries Research | And 9 more authors.
Biosensors and Bioelectronics | Year: 2010

A sensitive monitoring of contaminants in food and environment, such as chemical compounds, toxins and pathogens, is essential to assess and avoid risks for both, human and environmental health. To accomplish this, there is a high need for sensitive, robust and cost-effective biosensors that make real time and in situ monitoring possible. Due to their high sensitivity, selectivity and versatility, affinity-based biosensors are interesting for monitoring contaminants in food and environment. Antibodies have long been the most popular affinity-based recognition elements, however recently a lot of research effort has been dedicated to the development of novel recognition elements with improved characteristics, like specificity, stability and cost-efficiency. This review discusses three of these innovative affinity-based recognition elements, namely, phages, nucleic acids and molecular imprinted polymers and gives an overview of biosensors for food and environmental applications where these novel affinity-based recognition elements are applied. © 2010 Elsevier B.V.


Vanparys C.,University of Antwerp | Depiereux S.,University of Namur | Nadzialek S.,University of Namur | Robbens J.,University of Antwerp | And 4 more authors.
Science of the Total Environment | Year: 2010

In vitro estrogenicity screens are believed to provide a first prioritization step in hazard characterization of endocrine disrupting chemicals. When applied to complex environmental matrices or mixture samples, they have been indicated valuable in estimating the overall estrogen-mimicking load. In this study, the performance of an adapted format of the classical E-screen or MCF-7 cell proliferation assay was profoundly evaluated to rank pure compounds as well as influents and effluents of sewage treatment plants (STPs) according to estrogenic activity. In this adapted format, flow cytometric cell cycle analysis was used to allow evaluation of the MCF-7 cell proliferative effects after only 24h of exposure. With an average EC50 value of 2pM and CV of 22%, this assay appears as a sensitive and reproducible system for evaluation of estrogenic activity. Moreover, estrogenic responses of 17 pure compounds corresponded well, qualitatively and quantitatively, with other in vitro and in vivo estrogenicity screens, such as the classical E-screen (R2=0.98), the estrogen receptor (ER) binding (R2=0.84) and the ER transcription activation assay (R2=0.87). To evaluate the applicability of this assay for complex samples, influents and effluents of 10 STPs covering different treatment processes, were compared and ranked according to estrogenic removal efficiencies. Activated sludge treatment with phosphorus and nitrogen removal appeared most effective in eliminating estrogenic activity, followed by activated sludge, lagoon and filter bed. This is well in agreement with previous findings based on chemical analysis or biological activity screens. Moreover, ER blocking experiments indicated that cell proliferative responses were mainly ER mediated, illustrating that the complexity of the end point, cell proliferation, compared to other ER screens, does not hamper the interpretation of the results. Therefore, this study, among other E-screen studies, supports the use of MCF-7 cell proliferation as estrogenicity screen for pure compounds and complex samples. © 2010 Elsevier B.V.


Van Dorst B.,University of Antwerp | Van Dorst B.,Belgium Institute for Agricultural and Fisheries Research | De Coen W.,University of Antwerp | De Coen W.,European Chemicals Agency ECHA | And 3 more authors.
Environmental Toxicology and Chemistry | Year: 2010

In the present study the use of phage display as a screening tool to determine primary toxicological targets was investigated. These primary toxicological targets are the targets in the cell with which a chemical compound initially interacts and that are responsible for consecutive (toxic) effects. Nickel was used as model compound for the present study. By selection of Ni-binding peptides out of a 12-mer peptide phage library, it was possible to identify primary toxicological targets of Ni (and other metals). The selected Ni-binding peptides showed similarities to important primary toxicological targets of Ni, such as the hydrogenase nickel incorporation protein (hypB) and the Mg/Ni/Co transporter (corA). This shows that phage display, which is already widely used in other research fields, also has potential in ecotoxicology, as a novel screening tool with which to determine primary toxicological targets of chemical compounds. © 2009 SETAC.


Oberg T.,European Chemicals Agency ECHA
Journal of Risk Research | Year: 2014

The article focuses on several important issues concerning the current status and use of the substitution principle in chemicals regulation. Substitution of dangerous substances by less dangerous ones has become an important objective in the EU chemicals policy. Within the REACH regulation, substitution is often referred to in the context of authorization of substances of very high concern (SVHC) with the aim of eventual replacement by safer alternatives or technologies. However, important drivers for substitution also exist in other parts of REACH as well as in related legislation. Priority is normally given to include substances with PBT or vPvB properties or wide dispersive use or high volumes. Thus without attempting to do risk assessment, the potential for human and environmental exposure is clearly considered in setting the priorities for sending substances into the authorization regime.


PubMed | European Chemicals Agency ECHA
Type: | Journal: ALTEX | Year: 2016

The REACH Regulation requires information on acute oral toxicity for substances produced or imported in quantities greater than one tonne per year. When registering, animal testing should be used as last resort. The standard acute oral toxicity test requires use of animals. Therefore, the European Chemicals Agency examined whether alternative ways exist to generate information on acute oral toxicity. The starting hypothesis was that low acute oral toxicity can be predicted from the results of low toxicity in oral sub-acute toxicity studies. Proving this hypothesis would allow avoiding acute toxicity oral testing whenever a sub-acute oral toxicity study is required or available and indicates low toxicity. ECHA conducted an analysis of the REACH database and found suitable studies on both acute oral and sub-acute oral toxicities for 1,256 substances. 415 of these substances had low toxicity in the sub-acute toxicity study (i.e. NO(A)EL at or above the classification threshold of 1,000 mg/kg). For 98% of these substances, low acute oral toxicity was also reported (i.e. LD above the classification threshold of 2,000 mg/kg). On the other hand, no correlation was found between lower NO(A)ELs and LD. According to the REACH regulation, this approach for predicting acute oral toxicity needs to be considered as part of a weight of evidence analysis. Therefore, additional sources of information to support this approach are presented. Ahead of the last REACH registration deadline in 2018, ECHA estimates that registrants of about 550 substances can omit the in vivo acute oral study by using this adaptation.

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