Center for Safety of Substances and Products
Center for Safety of Substances and Products
Brand W.,Center for Safety of Substances and Products |
Noorlander C.W.,Center for Safety of Substances and Products |
Giannakou C.,National Institute for Public Health and the Environment RIVM |
Giannakou C.,Maastricht University |
And 7 more authors.
International Journal of Nanomedicine | Year: 2017
Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs) may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API) in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs). However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of) potential nanomedicine-specific effects need to be considered carefully. Results from the comparison of side effects of five sets of drugs (mainly liposomes and/or cytostatics) confirmed the induction of pseudo-allergic responses associated with specific NMPs in the literature, in addition to the side effects common to both nanoformulations and regular formulations, eg, with liposomal doxorubicin, and possibly liposomal daunorubicin. Based on the available data, immunotoxicological effects of certain NMPs cannot be excluded, and we conclude that this end point requires further attention. © 2017 Brand et al.
Ehret J.,Helmholtz Center for Environmental Research |
Vijver M.,Leiden University |
Peijnenburg W.,Leiden University |
Peijnenburg W.,Center for Safety of Substances and Products
ATLA Alternatives to Laboratory Animals | Year: 2014
Nanoparticles (NPs) are increasingly used throughout the world for many purposes. The resulting exposure increases the relevance of efforts to assess their effects. The activities of NPs are related to many structural features, including their shape, composition and size. Applying Quantitative Structure-Activity Relationship (QSAR) methods to nanoscale systems becomes challenging, due to the lack of data and insight into the fate and effects of NPs. In this study, the possible use of QSAR methods on NPs is investigated. To this intent, several ways of representing and describing NPs were tested by using different data mining methods. The main conclusion is that QSAR methods are relevant for the study of the activity of NPs, but this should be confirmed by using larger and more diverse sets of data. Moreover, representing the constitution of NPs (in terms of core, coating and surface modification) significantly increases the prediction accuracy of the models. In our case, the most significant features to be represented were found to be the core and surface modification.
Bruinen de Bruin Y.,Center for Safety of Substances and Products |
Peijnenburg W.,Leiden University |
Vermeire T.,Center for Safety of Substances and Products |
Posthuma L.,Center for Sustainability |
And 2 more authors.
Journal of Cleaner Production | Year: 2015
The European Union's REACH regulation has introduced Socio-Economic Analyses as a new decision support tool in the domain of chemical policy-making. This paper presents a pragmatic method to review the replacement of chemicals in processes or products in terms of the environmental impact. The aim of this work is to develop a broadly accepted method for environmental impact assessment as part of Socio-Economic Analyses. The method consists of a stepwise and tiered approach for Environmental Impact Assessment whereby the expected impact of the replacement of chemicals is assessed via Risk Characterization Ratios and toxic pressure quantification (expressed as a Potentially Affection Fraction of species), and - if relevant - via a Persistency, Bioaccumulation potential and Toxicity score. The working of the method is demonstrated by the replacement of chemical substances in detergents, gutters and Expanded Polystyrene. Of the three replacements, for gutters, the reduction of the toxic pressure on the aquatic compartment was highest. Based on 50% effect concentrations the Potentially Affection Fraction of species due to the use of zinc gutters was relatively high (15%), while it was 0.6% after replacement by PVC gutters. This indicates that PVC gutters have a lower direct impact on aquatic biodiversity than zinc gutters. This paper demonstrates that even with limited data the proposed method can be used to move from risk indicators to impact indicators. The tiered approach allows finding the most appropriate level of analysis in a cost and resource efficient way. The method allows comparison of results of different scenarios and as such allows selecting the most preferable alternative from an environmental perspective. This is useful in the context of socio-economic analysis and as such, this method is available as a decision-support tool under REACH and other chemical policy frames such as the United Nations Environment Program. © 2015 Elsevier Ltd.
Piersma A.H.,Center for Health Protection |
Ezendam J.,Center for Health Protection |
Luijten M.,Center for Health Protection |
Muller J.J.A.,Center for Safety of Substances and Products |
And 3 more authors.
Critical Reviews in Toxicology | Year: 2014
Regulatory toxicology urgently needs applicable alternative test systems that reduce animal use, testing time, and cost. European regulation on cosmetic ingredients has already banned animal experimentation for hazard identification, and public awareness drives toward additional restrictions in other regulatory frameworks as well. In addition, scientific progress stimulates a more mechanistic approach of hazard identification. Nevertheless, the implementation of alternative methods is lagging far behind their development. In search for general bottlenecks for the implementation of alternative methods, this manuscript reviews the state of the art as to the development and implementation of 10 diverse test systems in various areas of toxicological hazard assessment. They vary widely in complexity and regulatory acceptance status. The assays are reviewed as to parameters assessed, biological system involved, standardization, interpretation of results, extrapolation to human hazard, position in testing strategies, and current regulatory acceptance status. Given the diversity of alternative methods in many aspects, no common bottlenecks could be identified that hamper implementation of individual alternative assays in general. However, specific issues for the regulatory acceptance and application were identified for each assay. Acceptance of one-in-one replacement of complex in vivo tests by relatively simple in vitro assays is not feasible. Rather, innovative approaches using test batteries are required together with metabolic information and in vitro to in vivo dose extrapolation to convincingly provide the same level of information of current in vivo tests. A mechanistically based alternative approach using the Adverse Outcome Pathway concept could stimulate further (regulatory) acceptance of non-animal tests. © 2014 Informa Healthcare USA, Inc.