%0 Generic %D 2024 %T Exploring the use of New Approach Methodologies in Belgium via the RE-Place database %A Mieke Van Mulders %A Maude Everaert %A Vera Rogiers %A Birgit Mertens %K 3Rs %K Knowledge sharing %K NAMs %K new approach methodologies %K open access database %K RE-Place %K regulation %B Advancing the 3Rs for Regulatory Testing of Medicines %I Federal Agency for Medicines and Health Products %C Antwerp, Belgium %8 31-01-2024 %G eng %N Federal Agency for Medicines and Health Products %0 Journal Article %J Arch Toxicol %D 2024 %T Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health. %A Louro, Henriqueta %A Ariane Vettorazzi %A Adela López de Cerain %A Anastasia Spyropoulou %A Anita Solhaug %A Anne Straumfors %A Anne-Cathrin Behr %A Birgit Mertens %A Bojana Žegura %A Fæste, Christiane Kruse %A Ndiaye, Dieynaba %A Eliana Spilioti %A Elisabeth Varga %A Estelle Dubreil %A Eszter Borsos %A Francesco Crudo %A Eriksen, Gunnar Sundstøl %A Igor Snapkow %A Jérôme Henri %A Julie Sanders %A Machera, Kyriaki %A Laurent Gaté %A Ludovic Le Hegarat %A Matjaž Novak %A Nicola M Smith %A Krapf, Solveig %A Sonja Hager %A Valerie Fessard %A Yvonne Kohl %A Silva, Maria João %A Hubert Dirven %A Jessica Dietrich %A Doris Marko %K Alternaria %K Food Contamination %K Humans %K Lactones %K Mutagens %K Mycotoxins %K Perylene %K Risk Assessment %X

Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.

%B Arch Toxicol %V 98 %8 2024 Feb %G eng %N 2 %R 10.1007/s00204-023-03636-8 %0 Generic %D 2024 %T PARERE: a network for discussing the regulatory need and relevance of new testing methods and approaches %A Birgit Mertens %K 3Rs %K NAMs %K PARERE %K regulators %B Advancing the 3Rs for Regulatory Testing of Medicines %I Federal Agency for Medicines and Health Products %C Antwerp, Belgium %8 31-01-2024 %G eng %N Federal Agency for Medicines and Health Products %0 Generic %D 2024 %T A Transcriptomic Biomarker to Classify Chemical-Induced Histone Deacetylase Inhibition in Human HepaRGTM Cells %A Julie Buick %A Eunnara Cho %A Anouck Thienpont %A Birgit Mertens %A Andrew Williams %A Carole Yauk %A Matthew Meier %K HepaRG cells %K histone deacetylase inhibition %K transcriptomic biomarker %B Health Canada Science Forum %C Ottawa, Canada %8 02/2024 %G eng %0 Generic %D 2023 %T The 3Rs Principle in the field of toxicology %A Birgit Mertens %A Mieke Van Mulders %K 3Rs %K animal testing %K RE-Place %K Toxicology %B COST Workshop “Animal models for lead selection against vector borne parasitic diseases within the One Health concept” %I COST %C Online Workshop %8 08/09/2023 %G eng %N COST %0 Generic %D 2023 %T Accelerating the (regulatory) uptake of New Approach Methodologies via the RE-Place project %A Mieke Van Mulders %A Maude Everaert %A Birgit Mertens %A Vera Rogiers %K 3Rs %K alternative methods to animal testing %K animal testing %K Database %K NAMs %K new approach methodologies %K Regulatory uptake %K replacement %K VALIDATION %B BelTox Annual Meeting ‘Advances in the risk assessment of chemical mixtures’ %C Brussels, Belgium %8 07/12/2023 %G eng %N BelTox %0 Generic %D 2023 %T An AOP-based IATA to pave the way toward animal-free genotoxicity testing %A Birgit Mertens %K adverse outcome pathways %K genotoxicity %K Integrated approaches to testing and assessment (IATA) %B Joint 3R Symposium 2023 %C Brussels, Belgium %8 19/09/2023 %G eng %0 Generic %D 2023 %T A Benchmark Dose-based strategy for evaluating the combined effects of genotoxic compounds %A Julie Sanders %A Roel Anthonissen %A George Johnson %A Tamara Vanhaecke %A Birgit Mertens %K benchmark dose modelling %K genotoxicity %K mixtures %B BelTox Annual Meeting %C Brussels, Belgium %8 07/12/2023 %G eng %0 Generic %D 2023 %T Building trust in new approach methodologies via the RE-Place project %A Mieke Van Mulders %A Maude Everaert %A Vera Rogiers %A Birgit Mertens %K 3Rs %K alternative approaches %K animal testing %K Database %K Knowledge sharing %K NAMs %K new approach methodologies %K RE-Place %B 12th World Congress on Alternatives and Animal Use in the Life Sciences %I World Congress on Alternatives and Animal Use in the Life Sciences %C Niagara Falls, Canada %8 29/08/2023 %G eng %0 Journal Article %J ALTEX %D 2023 %T Cardiotoxicity of chemicals: Current regulatory guidelines, knowledge gaps, and needs. %A Alexandra Schaffert %A Sivakumar Murugadoss %A Birgit Mertens %A Martin Paparella %K Cardiotoxicity %K environmental exposure %K Hazardous Substances %K Humans %B ALTEX %V 40 %8 2023 %G eng %N 2 %R 10.14573/altex.2301121 %0 Journal Article %D 2023 %T Cardiotoxicity of chemicals: Current regulatory guidelines, knowledge gaps, and needs. %A Alexandra Schaffert %A Sivakumar Murugadoss %A Birgit Mertens %A Martin Paparella %K Cardiotoxicity %K environmental exposure %K Hazardous Substances %K Humans %V 40 %8 2023 %G eng %N 2 %R 10.14573/altex.2301121 %0 Generic %D 2023 %T Development of an AOP-based IATA for genotoxicity %A E Demuynck %A T Vanhaecke %A A Thienpont %A V Rogiers %A LMT Winkelman %A JB Beltman %A A Reus %A F Macron %A C Bossa %A A Peijnenburg %A K Machera %A D Nikolopoulou %A V Hatzi %A M Paparella %A Y Kohl %A S Narui %A S Molerup %A M Dusinska %A E Runden-Pran %A N El Yamani %A EM Longhin %A C Svendsen %A A Gutleb %A J Pennings %A M Luijten %A C Adam-Guillermin %A O Laurent %A O Armant %A C Pachoulide %A H Bouwmeester %A G Raitano %A E Benfenati %A E Wyrzykowska %A M Stepnik %A T Puzyn %A M Audebert %A Birgit Mertens %K adverse outcome pathways %K genotoxicity %K Integrated approaches to testing and assessment (IATA) %B EEMGS meeting %8 05/2023 %G eng %0 Journal Article %J Heliyon %D 2023 %T Effects of long-term exposure to 50 Hz magnetic fields on cell viability, genetic damage, and sensitivity to mutagen-induced damage %A Nguyen, Ha %A Seppe Segers %A M. Ledent %A Anthonissen, Roel %A Luc Verschaeve %A Maurice Hinsenkamp %A Jean-Francois Collard %A Feipel, Veronique %A Birgit Mertens %B Heliyon %V 9 %8 Jan-03-2023 %G eng %N 3 %R 10.1016/j.heliyon.2023.e14097 %0 Journal Article %J Heliyon %D 2023 %T Effects of long-term exposure to 50 Hz magnetic fields on cell viability, genetic damage, and sensitivity to mutagen-induced damage. %A Ti Thu Ha Nguyen %A Seppe Segers %A M. Ledent %A Roel Anthonissen %A Luc Verschaeve %A M. Hinsenkamp %A J.-F. Collard %A Feipel, Veronique %A Birgit Mertens %X

Until today, it remains controversial whether long-term exposure to extremely low-frequency magnetic fields (ELF-MF) below the legislative exposure limits could result in adverse human health effects. In the present study, the effects of long-term MF exposure on three different study endpoints (cell viability, genetic damage, and sensitivity to damage induced by known mutagens) were investigated in the human B lymphoblastoid (TK6) cell line. Cells were exposed to 50 Hz MF at three selected magnetic flux densities (i.e., 10, 100, and 500 μT) for different exposure periods ranging from 96h up to 6 weeks. Cell viability following MF exposure was assessed using the ATP-based cell viability assay. Effects of MF exposure on cell genetic damage and cell sensitivity to mutagen-induced damage were evaluated using the alkaline comet assay and the cytokinesis block micronucleus assay. The results showed that long-term exposure up to 96h to 50 Hz MF at all tested flux densities could significantly increase TK6 cell viability. In contrast, long-term MF exposure did not affect cell genetic damage, and long-term pre-exposure to MF did not change cell sensitivity to damage induced by known mutagens. At certain time points, statistically significant difference in genotoxicity test results were observed between the MF-exposed cells and the control cells. However, these observations could not be confirmed in the repeat experiments, indicating that they are probably not biologically significant.

%B Heliyon %V 9 %8 2023 Mar %G eng %N 3 %R 10.1016/j.heliyon.2023.e14097 %0 Journal Article %J Heliyon %D 2023 %T Effects of long-term exposure to 50 Hz magnetic fields on cell viability, genetic damage, and sensitivity to mutagen-induced damage %A Nguyen, Ha %A Seppe Segers %A M. Ledent %A Anthonissen, Roel %A Luc Verschaeve %A Maurice Hinsenkamp %A J.-F. Collard %A Feipel, Veronique %A Birgit Mertens %B Heliyon %V 9 %8 Jan-03-2023 %G eng %N 3 %R 10.1016/j.heliyon.2023.e14097 %0 Generic %D 2023 %T The GENOMARK biomarker inhuman HepaRGTM cells: a new approach methodology for genotoxicity assessment %A Anouck Thienpont %A Stefaan Verhulst %A Leo van Grunsven %A Vera Rogiers %A Tamara Vanhaecke %A Birgit Mertens %K genotoxicity %K NAM %K transcriptomic biomarker %B SaferWorldByDesign webinar %C Online %8 02/2023 %G eng %0 Generic %D 2023 %T The GENOMARK transcriptomic biomarker: a new approach methodology for genotoxicity (Qualitative and quantitative aspects) %A Anouck Thienpont %A Eunnara Cho %A Andrew Williams %A Carole Yauk %A Stefaan Verhulst %A Vera Rogiers %A Tamara Vanhaecke %A Birgit Mertens %K genotoxicity %K NAMs %K transcriptomic biomarker %B Joint 3R Symposium 2023 %8 20/09/2023 %G eng %0 Generic %D 2023 %T The GENOMARK transcriptomic biomarker demonstrates a high predictivity for genotoxic hazards and utility in potency ranking in human HepaRGTM cells %A Anouck Thienpont %A Eunnara Cho %A Andrew Williams %A Matthew Meier %A Carole Yauk %A Vera Rogiers %A Tamara Vanhaecke %A Birgit Mertens %K benchmark dose modelling %K genotoxicity %K potency ranking %K transcriptomic biomarker %B EEMGS meeting %C Malaga, Spain %8 05/2023 %G eng %0 Generic %D 2023 %T How can we stimulate the use of alternatives to animal testing in Belgium? %A Mieke Van Mulders %A Maude Everaert %A Vera Rogiers %A Birgit Mertens %K 3Rs %K animal testing %K Knowledge sharing %K NAMs %K new approach methodologies %K RE-Place %K replacement %B Knowledge For Growth %C Antwerp, Belgium %8 1/6/2023 %G eng %N FlandersBio %0 Generic %D 2023 %T How will RE-Place contribute to the action plan of the Flemish government? %A Mieke Van Mulders %A Maude Everaert %A Vera Rogiers %A Birgit Mertens %K 3Rs %K alternatives %K animal testing %K Database %K Knowledge sharing %K NAMs %K new approach methodologies %B Studiedag Actieplan vermindering dierproeven %I Afdeling Dierenwelzijn %C Brussels, Belgium %8 08/11/2023 %G eng %N Afdeling Dierenwelzijn, Departement Omgeving %0 Generic %D 2023 %T Innovative non-animal based testing platform to detect chemical-induced cardiotoxicity - A roadmap for regulatory uptake %A Sivakumar Murugadoss %A Alexandra Schaffert %A Ronette Gehring %A Tom Roos %A Nunzia Linzalone %A Gabriele Donzelli %A Martin Paparella %A Birgit Mertens %K adverse outcome pathways %K Cardiotoxicity %K Integrated approaches to testing and assessment (IATA) %B 57th Congress of the European Societies of Toxicology %C Ljubljana, Slovenia %8 09/2023 %G eng %0 Generic %D 2023 %T Innovative non-animal based testing platform to detect chemical-induced cardiotoxicity - A roadmap for regulatory uptake %A Sivakumar Murugadoss %A Alexandra Schaffert %A Ronette Gehring %A Tom Roos %A Nunzia Linzalone %A Gabriele Donzelli %A Martin Paparella %A Birgit Mertens %K adverse outcome pathways %K Cardiotoxicity %K Integrated approaches to testing and assessment (IATA) %K pollutants %B Joint 3R Symposium %C Brussels, Belgium %8 09/2023 %G eng %0 Generic %D 2023 %T Knowledge sharing on Tissue engineering via the RE-Place database %A Maude Everaert %A Mieke Van Mulders %A Birgit Mertens %A Vera Rogiers %K 3Rs %K alternatives to animal testing %K Database %K Knowledge sharing %K NAMs %K new approach methodologies %K RE-Place %K replacement %B 10th Belgian Symposium on Tissue Engineering %C Liege, Belgium %8 06/12/2023 %G eng %N BSTE %0 Journal Article %J ALTEX %D 2023 %T Linking nanomaterial-induced mitochondrial dysfunction to existing adverse outcome pathways for chemicals. %A Sivakumar Murugadoss %A Ivana Vinković Vrček %A Alexandra Schaffert %A Martin Paparella %A Barbara Pem %A Anita Sosnowska %A Maciej Stępnik %A Marvin Martens %A Egon L Willighagen %A Tomasz Puzyn %A Mihaela Roxana Cimpan %A Frauke Lemaire %A Birgit Mertens %A Maria Dusinska %A Valerie Fessard %A Peter H Hoet %X

The Adverse Outcome Pathway (AOP) framework plays a crucial role in the paradigm shift of toxicity testing towards the development and use of new approach methodologies. AOPs developed for chemicals are in theory applicable to nanomaterials (NMs). However, only subtle efforts have been made to integrate information on NM-induced toxicity into existing AOPs. In a previous study, we identified AOPs in the AOP-Wiki associated with the molecular initiating events (MIEs) and key events (KEs) reported for NMs in scientific literature. In a next step, we analyzed these AOPs and found that mitochondrial toxicity plays a significant role in several of them at the molecular and cellular levels. In this study, we aimed to generate hypothesis-based AOPs related to NM-induced mitochondrial toxicity. This was achieved by integrating science-based information collected on NM-induced mitochondrial toxicity into all existing AOPs in the AOP-Wiki, which already includes mitochondrial toxicity as a MIE/KE. The results showed that several AOPs in the AOP-Wiki related to the lung, liver, cardiovascular and nervous system, with extensively defined KEs and key event relationships (KERs), could be utilized to develop AOPs that are relevant for NMs. Our results also indicate that the majority of the studies included in our literature review were of poor quality, particularly in reporting NM physico-chemical characteristics, and NM-relevant mitochondrial MIEs were scarcely reported. This study highlights the potential role of NM-induced mitochondrial toxicity in human-relevant adverse outcomes and identifies useful AOPs in the AOP-Wiki for the development AOPs that are relevant for NMs.

%B ALTEX %8 2023 Aug 08 %G eng %R 10.14573/altex.2305011 %0 Generic %D 2023 %T Mixtures of genotoxicants: does the principle of additivity apply? %A Julie Sanders %A Roel Anthonissen %A George Johnson %A Tamara Vanhaecke %A Birgit Mertens %K additivity %K benchmark dose modelling %K genotoxicity %K mixtures %K Mycotoxins %B EEMGS meeting %C Malaga, Spain %8 05/2023 %G eng %0 Generic %D 2023 %T Mixtures of genotoxicants: does the principle of additivity apply? %A Julie Sanders %A Roel Anthonissen %A George Johnson %A Tamara Vanhaecke %A Birgit Mertens %K additivity %K benchmark dose modelling %K genotoxicity %K mixtures %K Mycotoxins %B Joint 3R Symposium 2023 %C Brussels, Belgium %8 09/2023 %G eng %0 Journal Article %J ALTEX %D 2023 %T Novel prediction models for genotoxicity based on biomarker genes in human HepaRG™ cells. %A Anouck Thienpont %A Stefaan Verhulst %A Leo A Van Grunsven %A Rogiers, Vera %A Vanhaecke, Tamara %A Birgit Mertens %K Algorithms %K Animals %K Biomarkers %K DNA Damage %K Gene Expression Profiling %K Humans %K Supervised Machine Learning %X

Transcriptomics-based biomarkers are promising new approach methodologies (NAMs) to identify molecular events underlying the genotoxic mode of action of chemicals. Previously, we developed the GENOMARK biomarker, consisting of 84 genes selected based on whole genomics DNA microarray profiles of 24 (non-)genotoxic reference chemicals covering different modes of action in metabolically competent human HepaRG™ cells. In the present study, new prediction models for genotoxicity were developed based on an extended reference dataset of 38 chemicals including existing as well as newly generated gene expression data. Both unsupervised and supervised machine learning algorithms were used, but as unsupervised machine learning did not clearly distinguish between groups, the performance of two supervised machine learning algorithms, i.e., support vector machine (SVM) and random forest (RF), was evaluated. More specifically, the predictive accuracy was compared, the sensitivity to outliers for one or more biomarker genes was assessed, and the prediction performance for 10 misleading positive chemicals exposed at their IC10 concentration was determined. In addition, the applicability of both prediction models on a publicly available gene expression dataset, generated with RNA-sequencing, was investigated. Overall, the RF and SVM models were complementary in their classification of chemicals for genotoxicity. To facilitate data analysis, an online application was developed, combining the outcomes of both prediction models. This research demonstrates that the combination of gene expression data with supervised machine learning algorithms can contribute to the ongoing paradigm shift towards a more human-relevant in vitro genotoxicity testing strategy without the use of experimental animals.

%B ALTEX %V 40 %8 2023 %G eng %N 2 %R 10.14573/altex.2206201 %0 Generic %D 2023 %T The PARERE network in Belgium: increasing awareness on NAMs among regulators %A Birgit Mertens %K 3Rs %K alternative methods %K animal testing %K EU Dir 2010/63 %K NAMs %K new approach methodologies %K PARERE %B Proefdieren en alternatieven: de weg vooruit / Animaux et alternatives : la voie à suivre %I Leefmilieu Brussel/Bruxelles Environnement %C Brussels, Belgium %8 27/03/2023 %G eng %N Leefmilieu Brussel/Bruxelles Environnement %0 Journal Article %J ALTEX %D 2023 %T Pollutant exposure and myocardial injury: Protocol and progress report for a toxicological systematic mapping review. %A Tom Roos %A Cathalijn Leenaars %A Alexandra Schaffert %A Martin Paparella %A Sivakumar Murugadoss %A Birgit Mertens %A Nunzia Linzalone %A Gabriele Donzelli %A Merel Ritskes-Hoitinga %A Ronette Gehring %X

An increasing body of evidence identifies pollutant exposure as a risk factor for cardiovascular disease (CVD), while CVD incidence rises steadily with the aging population. Although numerous experimental studies are now available, the mechanisms through which lifetime exposure to environmental pollutants can result in CVD are not fully understood. To comprehensively describe and understand the pathways through which pollutant exposure leads to cardiotoxicity, a systematic mapping review of the available toxicological evidence is needed. This protocol outlines a step-by-step framework for conducting this review. Using the National Toxicology Program (NTP) Health Assessment and Translation (HAT) approach for conducting toxicological systematic reviews, we selected 362 out of 8111 (17%), (67%), and combined (16%) studies for 129 potential cardiotoxic environmental pollutants, including heavy metals (29%), air pollutants (16%), pesticides (27%), and other chemicals (28%). The internal validity of included studies is being assessed with HAT and SYRCLE Risk of Bias tools. Tabular templates are being used to extract key study elements regarding study setup, methodology, techniques, and (qualitative and quantitative) outcomes. Subsequent synthesis will consist of an explorative meta-analysis of possible pollutant-related cardiotoxicity. Evidence maps and interactive knowledge graphs will illustrate evidence streams, cardiotoxic effects and associated quality of evidence, helping researchers and regulators to efficiently identify pollutants of interest. The evidence will be integrated in novel Adverse Outcome Pathways to facilitate regulatory acceptance of non-animal methods for cardiotoxicity testing. The current article describes the progress of the steps made in the systematic mapping review process.

%B ALTEX %8 2023 Nov 20 %G eng %R 10.14573/altex.2304111 %0 Generic %D 2023 %T Progress of the RE-Place project %A Mieke Van Mulders %A Maude Everaert %A Birgit Mertens %A Vera Rogiers %K 3Rs Principle %K alternative methods to animal testing %K animal testing %K Database %K Knowledge sharing %K NAMs %K new approach methodologies %K RE-Place %B Proefdieren en alternatieven: de weg vooruit / Animaux et alternatives : la voie à suivre %I Leefmilieu Brussel/Bruxelles Environnement %C Brussels, Belgium %8 27/03/2023 %G eng %U https://leefmilieu.brussels/pro/milieubeheer/dierenwelzijn-garanderen/proefdieren-en-alternatieven-de-weg-vooruit %N Leefmilieu Brussel/Bruxelles Environnement %0 Generic %D 2023 %T Reducing the Burden on Animals and the Heart: An Evidence-Based Approach to Cardiotoxicity Assessment %A Alexandra Schaffert %A Sivakumar Murugadoss %A Birgit Mertens %A Tom Roos %A Ronette Gehring %A Nunzia Linzalone %A Gabriele Donzelli %A Martin Paparella %K adverse outcome pathways %K Cardiotoxicity %K Integrated approaches to testing and assessment (IATA) %B 12th World Congress on Alternatives and Animal Use in the Life Sciences %C Nigara falls, Canada %8 08/2023 %G eng %0 Generic %D 2023 %T RE-PLACE: a bottom-up approach to collect the existing expertise on NAMs in Belgium %A Mieke Van Mulders %A Maude Everaert %A Birgit Mertens %A Vera Rogiers %K 3Rs %K alternatives to animal testing %K NAMs %K new approach methodologies %K RE-Place %B Joint 3R Symposium themed 'Emerging Fields in 3Rs' %8 19-21/09/2023 %G eng %N Innovation Centre 3Rs (IC-3Rs), RE-Place and EU-TWINALT %0 Generic %D 2023 %T RE-Place: a tool to promote the use of alternatives to animal testing %A Maude Everaert %A Mieke Van Mulders %A Birgit Mertens %A Vera Rogiers %K 3Rs %K animal testing %K Knowledge sharing %K NAMs %K new approach methodologies %B Summer School Dierenwelzijn 2023 %C Merelbeke, Belgium %8 11/09/2023 %G eng %N Duurzaam.org %0 Generic %D 2023 %T RE-PLACE: an ambitious project collecting the available expertise on New Approach Methodologies in Belgium in one central database %A Mieke Van Mulders %A Maude Everaert %A Birgit Mertens %A Vera Rogiers %K 3Rs %K alternative methods %K New Approach Methodologies (NAMs) %K RE-Place %B VLARIP workshop: Dossier en stof evaluaties – Gebruik & impact alternatieve testmethodes %I Essenscia %C Online %8 26/01/2023 %G eng %N Essenscia %0 Generic %D 2023 %T The RE-Place Database: a Project that Centralizes Animal-Free NAMs in Belgium %A Vera Rogiers %A Mieke Van Mulders %A Maude Everaert %A Birgit Mertens %K alternative methods %K animal testing %K New Approach Methodologies (NAMs) %K RE-Place %B 7th ERPA Annual Congress on Regulations and Compliance for Cosmetics %I European cosmetics Responsible Person Association %C Brussels, Belgium %8 03/02/2023 %G eng %N European cosmetics Responsible Person Association %0 Conference Proceedings %D 2023 %T RE-Place launches new initiatives to promote the use of alternative methods to animal testing %A Mieke Van Mulders %A Maude Everaert %A Vera Rogiers %A Birgit Mertens %K 3Rs %K alternative methods %K animal testing %K Database %K Knowledge sharing %K NAMs %K new approach methodologies %K RE-Place %I Sciensano Press Corner %C https://www.sciensano.be/en/press-corner/re-place-launches-new-initiatives-promote-use-alternative-methods-animal-testing %8 10/10/2023 %U https://www.sciensano.be/en/press-corner/re-place-launches-new-initiatives-promote-use-alternative-methods-animal-testing %0 Generic %D 2023 %T The SILIFOOD application: a new tool to support risk assessment of non-evaluated food contact materials substances %A Camille Streel %A Ilse Van Overmeire %A Gianluca Selvestrel %A Alessandra Roncaglioni %A Emilio Benfenati %A Alessio Sommovigo %A Alberto Manganaro %A Els Van Hoeck %A Birgit Mertens %K Chemical risk assessment %K food contact materials %K QSAR %B 57th Congress of the European Societies of Toxicology (Eurotox 2023) %C Ljubljana, Slovenia %8 09/2023 %G eng %0 Generic %D 2023 %T A Systematic Review on Pollutant Induced Cardiotoxicity: Providing a Toxicological Foundation for NAM Development and Regulatory Acceptance %A T. Roos %A C. Leenaars %A A. Schaffert %A M. Paparella %A Sivakumar Murugadoss %A Birgit Mertens %A N. Linzalone %A G. Donzelli %A M. Ritskes-Hoitinga %A R. Gehring %K Cardiotoxicity %K pollutants %K systematic review %K toxicological evidence %B 12th World Congress on Alternatives and Animal Use in the Life Sciences %C Nigara falls, Canada %8 08/2023 %G eng %0 Generic %D 2023 %T Towards Characterization and genotoxicity assessment of mycotoxin mixtures present in food. %A Julie Sanders %A George Johnson %A Roel Anthonissen %A Pierre Becker %A Emmanuel Tangni %A Julien Masquelier %A Tamara Vanhaecke %A Birgit Mertens %K additivity %K benchmark dose modelling %K genotoxicity %K mixtures %K Mycotoxins %B BelTox Annual Meeting %C Brussels, Belgium %8 07/12/2023 %G eng %0 Generic %D 2023 %T Unlocking the power of transcriptomic biomarkers in qualitative and quantitative genotoxicity assessment of chemicals %A Anouck Thienpont %A Eunnara Cho %A Andrew Williams %A Matthew Meier %A Carole Yauk %A Vera Rogiers %A Tamara Vanhaecke %A Birgit Mertens %K benchmark dose modelling %K genotoxicity %K potency ranking %K transcriptomic biomarker %B 57th Congress of the European Societies of Toxicology (Eurotox 2023) %C Ljubljana, Slovenia %8 09/2023 %G eng %0 Conference Proceedings %D 2023 %T VUB verhoogt inzet op 3V-principe in dierproevenbeleid %A Mieke Van Mulders %A Birgit Mertens %A Tamara Vanhaecke %A Vera Rogiers %K 3V %K alternatieven %K dierproeven %K ethiek %K proefdieren %I VUB Press %C https://press.vub.ac.be/vub-verhoogt-inzet-op-3v-principe-in-dierproevenbeleid %8 22/09/2023 %U https://press.vub.ac.be/vub-verhoogt-inzet-op-3v-principe-in-dierproevenbeleid %0 Generic %D 2022 %T Current status of the RE-Place database %A Mieke Van Mulders %A Maude Everaert %A Vera Rogiers %A Birgit Mertens %K 3Rs %K alternative methods to animal testing %K Knowledge sharing %K NAMs %K new approach methodologies %K open access database %B 6th IC-3Rs Symposium %8 Sep 2022 %G eng %N IC-3Rs %0 Generic %D 2022 %T Design and Application of a Semi-automated Workflow including In Silico Models to support the Risk Assessment of Food Contact Material Substances %A Camille Streel %A Ilse Van Overmeire %A Gianluca Selvestrel %A Alessandra Roncaglioni %A Emilio Benfenati %A Alessio Sommovigo %A Alberto Manganaro %A Els Van Hoeck %A Birgit Mertens %K (Q)SAR %K Chemical risk assessment %K food contact materials %B BelTox Annual Meeting %C Antwerp, Belgium %8 12/2022 %G eng %0 Conference Proceedings %D 2022 %T Expérimentation animale à Bruxelles: la plate-forme sur les alternatives améliorée %A Mieke Van Mulders %A Birgit Mertens %A Nancy Liodo Missigba %A Vera Rogiers %K 3Rs %K alternative methods %K new approach methodologies %K RE-Place %I LaMeuse %C https://lameuse.sudinfo.be/894547/article/2022-01-16/experimentation-animale-bruxelles-la-plate-forme-sur-les-alternatives-amelioree %8 16/01/2022 %U https://lameuse.sudinfo.be/894547/article/2022-01-16/experimentation-animale-bruxelles-la-plate-forme-sur-les-alternatives-amelioree %0 Conference Proceedings %D 2022 %T Flanders and Brussels join forces to tackle animal testing %A Mieke Van Mulders %A Birgit Mertens %A Nancy Liodo Missigba %A Vera Rogiers %K 3Rs %K alternative methods to animal testing %K new approach methodologies %K RE-Place %X

The Flemish and Brussels regional governments are working together in search of alternatives to animal testing to reduce reliance on such experiments.

As part of this collaboration, the regions will launch a new, optimised version of the RE-Place platform for scientists, which gathers all existing knowledge on alternative methods to animal testing and paints a realistic picture of what is possible today with such methods.

The platform was created as part of a previous collaboration between Brussels Minister for Animal Welfare Bernard Cleryfayt and his Flemish counterpart Ben Weyts several years ago to ensure that, in the long term, the project could “contribute to a structural reduction in the number of
animal experiments.”

It does so by promoting the use of non-animal testing methods by putting the emphasis on sharing knowledge, and by bringing together experts from institutions and research fields with each other.

A new and improved version of the RE-Place platform which was recently launched makes it even easier to collect the available expertise in Brussels and Flanders. As part of this launch, both regions are calling on scientists to share their expertise on the platform.

“I want to prevent the suffering of laboratory animals as much as possible. This can be done by development, stimulation and support of alternative methods,” Weyts said.

Human materials and computer models

In Belgium, about half a million test animals are used for scientific purposes every year, most often in biomedical research into new therapies for diseases such as cancer.

In addition, the use of laboratory animals is sometimes required by law, for example for the safety of medicines and vaccines. Such practices are strictly controlled by ethics committees and the regional authorities for animal welfare.

“Some animal tests remain a necessary evil. The focus in our policy lies on a thorough application of the ‘3Rs policy’: reduction, refinement, replacement,” Weyts stated.

As part of the project, the coordinators of the RE-Place project, Sciensano and the Vrije Universiteit Brussel, developed an online tool that has already collected 170 methods from various research fields and research fields and institutions.

This includes using human material in cell and tissue cultures (in vitro), or computer models (in silico). “These new, innovative techniques play a very important role in answering questions that follow from a regulatory framework or biomedical research,” a press release stated.

%I The Brussels Time %C https://www.brusselstimes.com/belgium-all-news/201812/flanders-and-brussels-combine-forces-to-tackle-animal-testing %8 16/01/2022 %U https://www.brusselstimes.com/belgium-all-news/201812/flanders-and-brussels-combine-forces-to-tackle-animal-testing %0 Generic %D 2022 %T GENOMARK, a promising new approach methodology for genotoxicity testing in the cosmetic industry %A Anouck Thienpont %A Stefaan Verhulst %A Leo van Grunsven %A Tamara Vanhaecke %A Birgit Mertens %A Vera Rogiers %K genotoxicity %K NAM %K transcriptomic biomarker %B 6th International cosmetic congress %C Antalya, Turkey %8 12/2022 %G eng %0 Conference Proceedings %D 2022 %T Het RE-Place project focust op het bevorderen van alternatieve methoden die dierproeven kunnen helpen vervangen %A Nancy Liodo Missigba %A Vera Rogiers %K 3Rs %K alternative methods %K new approach methodologies %K RE-Place %X

Het Brussels en Vlaams Gewest lanceren een nieuwe, geoptimaliseerde versie van het RE-Place platform. Dit platform verzamelt alle bestaande kennis over alternatieve methoden voor dierproeven en laat toe om een realistisch beeld te geven over wat vandaag mogelijk is met dergelijke methoden.

Enkele jaren geleden sloegen het Brussels en Vlaams Gewest de handen in elkaar voor de oprichting van RE-Place, een platform voor alternatieve methoden voor dierproeven, om de toegang tot betrouwbare informatie over het gebruik van (nieuwe) alternatieve methoden te verbeteren. RE-Place wil het gebruik van proefdiervrije methoden bevorderen door maximaal in te zetten op kennisdeling, en door experten uit verschillende instellingen en onderzoeksdomeinen met elkaar in contact te brengen.Bovendien fungeert RE-Place als een centraal informatiepunt waar alle belanghebbenden actuele informatie over alternatieven kunnen terugvinden. Op termijn moet dit project bijdragen aan een structurele vermindering van het aantal dierproeven.

“Ik wens het lijden van proefdieren zoveel mogelijk te voorkomen. Dit kan door het ontwikkelen, stimuleren en ondersteunen van alternatieve methoden. Als we vandaag precies weten hoeveel dieren voor wetenschappelijk onderzoek worden gebruikt, lijkt het mij van essentieel belang dit aantal te doen verminderen”, zegt Bernard Clerfayt.

In België worden jaarlijks ongeveer een half miljoen proefdieren gebruikt voor verschillende wetenschappelijke doeleinden. Ze worden het vaakst ingezet in biomedisch onderzoek naar nieuwe therapieën voor ziekten zoals kanker. Daarnaast is het gebruik van proefdieren soms wettelijk verplicht, bijvoorbeeld voor de veiligheid van geneesmiddelen en vaccins. Het gebruik van proefdieren staat onder strenge controle van de ethische commissies en de overheidsinstanties Dierenwelzijn.

Het Brussels en Vlaams Gewest stimuleren het gebruik van alternatieven voor dierproeven waar mogelijk. De laatste jaren is er op Europees niveau immers veel vooruitgang geboekt in de ontwikkeling van proefdiervrije methoden. Onderzoekers maken onder andere gebruik van menselijk materiaal in cel- en weefselculturen (in vitro), of van computermodellen (in silico). Deze nieuwe, innovatieve technieken spelen een zeer belangrijke rol bij het beantwoorden van vragen die volgen uit een regelgevend kader of het biomedisch onderzoek.

De coördinators van het RE-Place project, Sciensano en de Vrije Universiteit Brussel, ontwikkelden een online tool waarmee reeds 170 methoden werden verzameld, afkomstig uit verschillende onderzoeksdomeinen en instellingen. Door de lancering van deze nieuwe, verbeterde versie van het RE-Place platform kan expertise nog gemakkelijker worden verzameld. Die kan nu ook worden gekoppeld aan bepaalde onderzoeksgroepen of organisaties. Het Brussels en Vlaams Gewest roepen wetenschappers dan ook op om hun expertise maximaal te delen via het RE-Place platform!

Voor meer informatie over het project kunt u terecht op www.RE-Place.be of via info@RE-Place.be.

Meer info? 
Pauline Lorbat - 0485 89 47 45

 

%I Kabinet Bernard Clerfayt, dienst Dierenwelzijn %C https://clerfayt.brussels/nl/dierenwelzijn %8 16/01/2022 %U https://clerfayt.brussels/nl/dierenwelzijn %0 Generic %D 2022 %T How to increase the visibility of expertise on New Approach Methodologies in Belgium %A Mieke Van Mulders %A Maude Everaert %A Vera Rogiers %A Birgit Mertens %K 3R %K animal testing %K Knowledge sharing %K NAMs %K new approach methodologies %K open access database %K RE-Place %K replacement %B The 9th Belgian Symposium on Tissue Engineering %I BSTE %C Antwerp %8 2/12/2022 %G eng %N BSTE %0 Generic %D 2022 %T Identification of flavouring substances of genotoxic concern in e-liquids %A Sophia Barhdadi %A Vanhaecke, Tamara %A Birgit Mertens %A Eric Deconinck %K e-cigarette %K genotoxicity %B BfR Consumer Protection Forum "Opportunities and Risks of the e-cigarette" %I BfR %C Berlin, Germany %8 28-29 April 2022 %G eng %0 Journal Article %J Mutagenesis %D 2022 %T Impact of experimental design factors on the potency of genotoxicants in in vitro test %A Julie Sanders %A Anouck Thienpont %A Roel Anthonissen %A Vanhaecke, Tamara %A Birgit Mertens %X

Previous studies have shown that differences in experimental design factors may alter the potency of genotoxic compounds in in vitro genotoxicity tests. Most of these studies used traditional statistical methods based on the lowest observed genotoxic effect levels, whereas more appropriate methods, such as the benchmark dose (BMD) approach, are now available to compare genotoxic potencies under different test conditions. We therefore investigated the influence of two parameters, i.e. cell type and exposure duration, on the potencies of two known genotoxicants [aflatoxin B1 and ethyl methanesulfonate (EMS)] in the in vitro micronucleus (MN) assay and comet assay (CA). Both compounds were tested in the two assays using two cell types (i.e. CHO-K1 and TK6 cells). To evaluate the effect of exposure duration, the genotoxicity of EMS was assessed after 3 and 24 h of exposure. Results were analyzed using the BMD covariate approach, also referred to as BMD potency ranking, and the outcome was compared with that of more traditional statistical methods based on lowest observed genotoxic effect levels. When comparing the in vitro MN results obtained in both cell lines with the BMD covariate approach, a difference in potency was detected only when EMS exposures were conducted for 24 h, with TK6 cells being more sensitive. No difference was observed in the potency of both EMS and aflatoxin B1 in the in vitro CA using both cell lines. In contrast, EMS was more potent after 24 h exposure compared with a 3 h exposure under all tested conditions, i.e. in the in vitro MN assay and CA in both cell lines. Importantly, for several of the investigated factors, the BMD covariate method could not be used to confirm the differences in potencies detected with the traditional statistical methods, thus highlighting the need to evaluate the impact of experimental design factors with adequate approaches.

%B Mutagenesis %V 37 %8 30 November 2022 %G eng %N 5-6 %R 10.1093/mutage/geac025 %0 Book %B In silico methods for chromosome damage %D 2022 %T In silico methods for chromosome damage %A D. Baderna %A Ilse Van Overmeire %A G.J. Lavado %A D. Gadaleta %A Birgit Mertens %X

Due to the link with serious adverse health effects, genotoxicity is an important toxicological endpoint in each regulatory setting with respect to human health, including for pharmaceuticals. To this extent, a compound's potential to induce gene mutations as well as chromosome damage needs to be addressed. For chromosome damage, i.e. the induction of structural or numerical chromosome aberrations, several in vitro and in vivo test methods are available. In order to rapidly collect toxicological data without the need for test material, several in silico tools for chromosome damage have been developed over the last years. In this chapter, a battery of freely available in silico chromosome damage prediction tools for chromosome damage is applied on a dataset of pharmaceuticals. Examples of the different outcomes obtained with the in silico battery are provided and briefly discussed. Furthermore, results for coumarin are presented in more detail as a case study. Overall, it can be concluded that, although they are in general less developed than those for mutagenicity, in silico tools for chromosome damage can provide valuable information, especially when combined in a battery.

%B In silico methods for chromosome damage %7 2nd %I Humana %C New York %V 2425 %8 02/2022 %@ 978-1-0716-1960-5 %G eng %N 8 %9 Methods in Molecular Biology Series %) Benfenati, E. %R 10.1007/978-1-0716-1960-5_8 %0 Journal Article %J Methods Mol Biol %D 2022 %T In Silico Methods for Chromosome Damage. %A Diego Baderna %A Ilse Van Overmeire %A Giovanna J Lavado %A Domenico Gadaleta %A Birgit Mertens %K Chromosome Aberrations %K Chromosomes %K DNA Damage %K Humans %K Mutagenicity Tests %K Mutagens %K Mutation %X

Due to the link with serious adverse health effects, genotoxicity is an important toxicological endpoint in each regulatory setting with respect to human health, including for pharmaceuticals. To this extent, a compound potential to induce gene mutations as well as chromosome damage needs to be addressed. For chromosome damage, i.e., the induction of structural or numerical chromosome aberrations, several in vitro and in vivo test methods are available. In order to rapidly collect toxicological data without the need for test material, several in silico tools for chromosome damage have been developed over the last years. In this chapter, a battery of freely available in silico chromosome damage prediction tools for chromosome damage is applied on a dataset of pharmaceuticals. Examples of the different outcomes obtained with the in silico battery are provided and briefly discussed. Furthermore, results for coumarin are presented in more detail as a case study. Overall, it can be concluded that although they are in general less developed than those for mutagenicity, in silico tools for chromosome damage can provide valuable information, especially when combined in a battery.

%B Methods Mol Biol %V 2425 %8 2022 %G eng %R 10.1007/978-1-0716-1960-5_8 %0 Generic %D 2022 %T The Innovation Centre 3Rs (IC-3Rs) in Belgium %A Mieke Van Mulders %A Birgit Mertens %A R. Marcelino Rodrigues %A Joery De Kock %A Tamara Vanhaecke %A Vera Rogiers %K 3Rs %K alternative methods to animal testing %K Knowledge sharing %K NAMs %K new approach methodologies %B 23rd European Congress on Alternatives to Animal Testing %C Linz, Austria %8 sep 2022 %G eng %N EUSAAT %0 Conference Proceedings %D 2022 %T Meer alternatieven voor dierenproeven %A Vera Rogiers %A Nancy Liodo Missigba %K 3Rs %K alternative methods to animal testing %K new approach methodologies %X

Enkele jaren geleden lanceerden het Vlaams en Brusselse Gewest Re-Place, een platform voor wetenschappers dat alternatieven voor dierenproeven bundelt. Er komt nu een geoptimaliseerde versie van het platform, met een online tool waarmee reeds 170 alternatieve testmethoden werden verzameld en een betere uitwisseling van expertise.

In België worden jaarlijks ongeveer een half miljoen proefdieren gebruikt voor wetenschappelijke doeleinden. Ze worden het vaakst ingezet in biomedisch onderzoek naar nieuwe therapieën voor ziekten zoals kanker. Daarnaast is het gebruik van proefdieren soms wettelijk verplicht, bijvoorbeeld voor de veiligheid van geneesmiddelen en vaccins. Het gebruik van proefdieren staat onder strenge controle van de ethische commissies en de regionale instanties voor Dierenwelzijn.

Vermindering, verfijning en vervanging

“Er bestaan steeds meer alternatieven voor dierproeven en Vlaanderen kan ook op dat vlak een voortrekkersrol opnemen. Al blijven sommige dierproeven nog steeds een noodzakelijk kwaad. De focus in ons beleid ligt op een doorgedreven toepassing van het ‘3V-beleid’: vermindering, verfijning, vervanging”, zegt Weyts. “We blijven gaan voor een maximale daling van het aantal proeven op dieren.”

170 alternatieven op dierenproeven

De coördinators van het RE-Place project, Sciensano en de Vrije Universiteit Brussel, ontwikkelden een online tool waarmee reeds 170 methoden werden verzameld, afkomstig uit verschillende onderzoeksdomeinen en instellingen. Door de lancering van deze nieuwe, verbeterde versie van het RE-Place platform kan de beschikbare expertise nog gemakkelijker worden verzameld in Brussel en Vlaanderen. Die kan nu ook worden gekoppeld aan bepaalde onderzoeksgroepen of organisaties. Het Vlaams en Brussels Gewest roepen wetenschappers dan ook op om hun expertise maximaal te delen via het RE-Place platform!

%I Vlaamse overheid, Departement Dierenwelzijn %C Press release %8 16/01/2022 %U https://www.benweyts.be/nieuws/meer-alternatieven-voor-dierenproeven?pq=nieuws&page=0#views-row-2 %0 Journal Article %J Food and Chemical Toxicology %D 2022 %T Modeling the migration of chemicals from food contact materials to food: The MERLIN-expo/VERMEER toolbox %A P., Ciffroy %A Birgit Mertens %A Els Van Hoeck %A Ilse Van Overmeire %A E., Johansson %A B., Alfonso %A D., Baderna %A G., Selvestrel %A E., Benfenati %K food contact material %K Migration model %K Uncertainty analysis %X

Evaluating the migration of chemicals from food contact materials (FCM) into food is a key step in the safety assessment of such materials. In this paper, a simple mechanistic model describing the migration of chemicals from FCM to food was combined with quantitative property-property relationships (QPPRs) for the prediction of diffusion coefficients and FCM-Food partition coefficients. The aim of the present study was to evaluate the performance of these operational models in the prediction of a chemical's concentration in food in contact with a plastic monolayer FCM. A comparison to experimental migration values reported in literature was conducted. Deterministic simulations showed a good match between predicted and experimental values. The tested models can be used to provide insights in the amount and the type of toxicological data that are needed for the safety evaluation of the FCM substance. Uncertainty in QPPRs used for describing the processes of both diffusion in FCM and partition at the FCM-Food interface was included in the analysis. Combining uncertainty in QPPR predictions, it was shown that the third quartile (75th percentile) derived from probabilistic calculations can be used as a conservative value in the prediction of chemical concentration in food, with reasonable safety factors.

%B Food and Chemical Toxicology %V 166 %8 Jan-08-2022 %G eng %R 10.1016/j.fct.2022.113118 %0 Journal Article %J Food Chem Toxicol %D 2022 %T Modeling the migration of chemicals from food contact materials to food: The MERLIN-expo/VERMEER toolbox. %A P. Ciffroy %A B. Mertens %A Els Van Hoeck %A Ilse Van Overmeire %A E. Johansson %A B. Alfonso %A D. Baderna %A G. Selvestrel %A E. Benfenati %K Diffusion %K Food Contamination %K Food Packaging %K Neurofibromin 2 %K plastics %X

Evaluating the migration of chemicals from food contact materials (FCM) into food is a key step in the safety assessment of such materials. In this paper, a simple mechanistic model describing the migration of chemicals from FCM to food was combined with quantitative property-property relationships (QPPRs) for the prediction of diffusion coefficients and FCM-Food partition coefficients. The aim of the present study was to evaluate the performance of these operational models in the prediction of a chemical's concentration in food in contact with a plastic monolayer FCM. A comparison to experimental migration values reported in literature was conducted. Deterministic simulations showed a good match between predicted and experimental values. The tested models can be used to provide insights in the amount and the type of toxicological data that are needed for the safety evaluation of the FCM substance. Uncertainty in QPPRs used for describing the processes of both diffusion in FCM and partition at the FCM-Food interface was included in the analysis. Combining uncertainty in QPPR predictions, it was shown that the third quartile (75th percentile) derived from probabilistic calculations can be used as a conservative value in the prediction of chemical concentration in food, with reasonable safety factors.

%B Food Chem Toxicol %V 166 %8 2022 Aug %G eng %R 10.1016/j.fct.2022.113118 %0 Conference Proceedings %D 2022 %T Nieuw kennisplatform moet alternatieven voor dierenproeven bevorderen: «We blijven gaan voor maximale daling van aantal dierenproeven» %A Mieke Van Mulders %A Birgit Mertens %A Vera Rogiers %I Metro %C MetroTime %8 17/01/2022 %U https://nl.metrotime.be/algemeen/nieuw-kennisplatform-moet-alternatieven-voor-dierenproeven-bevorderen-we-blijven-gaan-voor-maximale-daling %0 Journal Article %J ALTEX %D 2022 %T Novel prediction models for genotoxicity based on biomarker genes in human HepaRGTM cells %A Anouck Thienpont %A Stefaan Verhulst %A Leo A. van Grunsven %A Vera Rogiers %A Tamara Vanhaecke %A Birgit Mertens %K genetic toxicology GENOMARK biomarker predictive toxicology human health risk assessment new approach methodologies (NAMs) %X

Transcriptomics-based biomarkers are promising new approach methodologies (NAMs) to identify molecular events underlying the genotoxic mode of action of chemicals. Previously, we developed the GENOMARK biomarker, consisting of 84 genes selected based on whole genomics DNA microarray profiles of 24 (non-)genotoxic reference chemicals covering different modes of action in metabolically competent human HepaRG™ cells. In the present study, new prediction models for genotoxicity were developed based on an extended reference dataset of 38 chemicals including existing as well as newly generated gene expression data. Both unsupervised and supervised machine learning algorithms were used, but as unsupervised machine learning did not clearly distinguish both groups, the performance of two supervised machine learning algorithms, i.e., support vector machine (SVM) and random forest (RF), was evaluated. More specifically, the predictive accuracy was compared, the sensitivity to outliers for one or more biomarker genes was assessed, and the prediction performance for 10 misleading positive chemicals exposed at their IC10 concentration was determined. In addition, the applicability of both prediction models on a publicly available gene expression dataset, generated with RNA-sequencing, was investigated. Overall, the RF and SVM models were complementary in their classification of chemicals for genotoxicity. To facilitate data analysis, an online application was developed, combining the outcomes of both prediction models. Furthermore, this research demonstrates that the combination of gene expression data with supervised machine learning algorithms can contribute to the ongoing paradigm shift towards a more human-relevant in vitro genotoxicity testing strategy without the use of experimental animals.

%B ALTEX %8 Nov 4, 2022 %G eng %R 10.14573/altex.2206201 %0 Journal Article %J Food Chem %D 2022 %T Occurrence of (suspected) genotoxic flavoring substances in Belgian alcohol-free beers. %A Alexandre Dusart %A Birgit Mertens %A Els Van Hoeck %A M Simon %A Séverine Goscinny %A S Collin %K beer %K Belgium %K DNA Damage %K Flavoring Agents %K Gas Chromatography-Mass Spectrometry %X

The regulatory landscape of flavorings is evolving, thereby putting pressure on control laboratories to develop analytical methods for a wide range of compounds in various types of food and drinks. In order to improve the monitoring of flavoring substances, a versatile and accurate analytical method using the solvent-assisted flavor evaporation (SAFE) technique coupled to GC-MS(SIM) was developed and validated. Focus was put on authorized flavoring substances requiring specific attention due to a genotoxic concern based on information from European risks assessment reports. Thirty-seven (suspected) genotoxic flavoring substances were analyzed in a selection of ten alcohol-free beers. Five suspected genotoxic compounds (i.e. 1-(2-furyl)-2-propanone, 2-acetylfuran, 2-acetyl-5-methylfuran, 2-acetyl-3,5-dimethylfuran, hex-2-eno-1,4-lactone) as well as two confirmed genotoxic flavoring substances (p-mentha-1,8-dien-7-al, 2,4-pentanedione) were identified and quantified among the selected samples. Low concentrations and natural occurrences of the identified compounds suggested that these were not added as such but rather originated from heat-treatments or from plant-based extracts.

%B Food Chem %V 369 %8 2022 Feb 01 %G eng %R 10.1016/j.foodchem.2021.130917 %0 Journal Article %J Frontiers in Pharmacology: Predictive Toxicology %D 2022 %T RE-Place: A Unique Project Collecting Expertise on New Approach Methodologies %A Mieke Van Mulders %A Nancy Liodo Missigba %A Birgit Mertens %A Vera Rogiers %K 3Rs %K animal testing %K Database %K Knowledge sharing %K NAMs %K new approach methodologies %K Open access %K RE-Place %X

By applying “New Approach Methodologies (NAMs)” based on innovative technologies such as computer modeling, high throughput testing, omics, and sophisticated cell cultures, the use of experimental animals in the life sciences can be reduced or sometimes even completely avoided. Stimulating NAMs may benefit from a bottom-up approach, i.e., local initiatives mapping the available NAMs and promoting their use. An example of such an initiative in Belgium is the RE-Place project, which collects the available NAMs in one central database, and links this knowledge with the names of experts and research centers. To this extent, a template was created to collect the information of interest in a fast and consistent manner. Based on this template, a web-based application was developed to facilitate the entry of information, which was evaluated in a pilot study by experts in the field of NAMs. After integration of their feedback, a revised version of the RE-Place online tool was launched to the public. Aspects such as user-friendliness, quality of submitted information, protection of personal data and Intellectual Property (IP) rights were all considered in the development process. Hurdles like incentives for collaboration were also taken into account. Information submitted with the online tool is directly integrated in the RE-Place open access database. By consulting the database, scientists from various disciplines can easily identify the different types of NAMs and the experts using them in Belgium. As such, the RE-Place database contributes to building trust in the use of NAMs and stimulating their use and regulatory uptake.

%B Frontiers in Pharmacology: Predictive Toxicology %8 22/06/2022 %G eng %R 10.3389/fphar.2022.930148 %0 Generic %D 2022 %T RE-Place: an open access database collecting expertise on New Approach Methodologies in Belgium %A Mieke Van Mulders %A Maude Everaert %A Vera Rogiers %A Birgit Mertens %K 3Rs %K alternative methods to animal testing %K Knowledge sharing %K NAMs %K new approach methodologies %K open access database %B ReThink3R 2.0 Summer School %C Berlin, Germany %8 Aug 2022 %G eng %0 Generic %D 2022 %T The RE-Place open access database provides insight into the use of New Approach Methodologies in Belgium %A Mieke Van Mulders %A Maude Everaert %A Birgit Mertens %A Vera Rogiers %K 3Rs %K animal testing %K Knowledge sharing %K NAMs %K new approach methodologies %K open access database %K RE-Place %K replacement %B BelTox Annual Meeting %I BelTox %C Antwerp, Belgium %8 07/12/2022 %G eng %N BelTox %0 Generic %D 2022 %T The RE-Place project %A Mieke Van Mulders %E Maude Everaert %E Vera Rogiers %E Birgit Mertens %K 3Rs %K alternatives to animal testing %K Knowledge sharing %K NAMs %K new approach methodologies %K open access database %K RE-Place %K replacement %B One Health Symposium themed "Health challenges of the 21st century" %I Sciensano %C Brussels, Belgium %8 8/12/2022 %G eng %N Sciensano %0 Conference Proceedings %D 2022 %T RE-Place project: Reducing animal research through alternative methods %A Mieke Van Mulders %A Birgit Mertens %A Vera Rogiers %I BioVox %C BioVox %8 16/03/2022 %U https://biovox.eu/re-place-project-reducing-animal-research-through-alternative-methods/?utm_source=newsletter&utm_medium=email&utm_campaign=20220317 %0 Generic %D 2022 %T RE-Place: stimulating knowledge sharing on New Approach Methodologies via an open access database in Belgium. %A Mieke Van Mulders %A Maude Everaert %A Vera Rogiers %A Birgit Mertens %K 3Rs %K alternative methods to animal testing %K Knowledge sharing %K NAMs %K new approach methodologies %K open access database %B 23rd European Congress on Alternatives to Animal Testing %8 Sep 2022 %G eng %N EUSAAT %0 Book %B Validated alternative methods available for human Health and Safety assessment of cosmetic products and their ingredients in the European Union %D 2022 %T Validated alternative methods available for human Health and Safety assessment of cosmetic products and their ingredients in the European Union %A Rogiers, Vera %A Anouck Thienpont %A Mona Delagrange %A Birgit Mertens %A Vanhaecke, Tamara %X

No abstract available

%B Validated alternative methods available for human Health and Safety assessment of cosmetic products and their ingredients in the European Union %7 5th %I Taylor & Francis %C London %8 06/2022 %@ 9780429099311 %G eng %9 Handbook of Cosmetic Science and Technology %) André O. Barel, Marc Paye, Howard I. Maibach %0 Conference Proceedings %D 2022 %T Vlaams en Brussels Gewest zoeken samen naar alternatieven dierenproeven %A Mieke Van Mulders %E Birgit Mertens %E Nancy Liodo Missigba %E Vera Rogiers %K 3Rs %K alternative methods to animal testing %K NAM %K RE-Place %X

Brussels minister van Dierenwelzijn Bernard Cleryfayt (Défi) en zijn Vlaamse collega Ben Weyts (N-VA) slaan de handen in elkaar in de strijd tegen dierproeven, met een geoptimaliseerde versie van het RE-Place platform. Dat platform verzamelt alle bestaande kennis over alternatieve methoden voor dierproeven.

In België worden jaarlijks ongeveer een half miljoen proefdieren gebruikt voor verschillende wetenschappelijke doeleinden. Ze worden het vaakst ingezet in biomedisch onderzoek naar nieuwe therapieën voor ziekten zoals kanker. Daarnaast is het gebruik van proefdieren soms wettelijk verplicht, bijvoorbeeld voor de veiligheid van geneesmiddelen en vaccins.

Om het aantal dierproeven te verminderen, richtten het Brussels en Vlaams Gewest enkele jaren geleden RE-Place op, een platform voor alternatieve methoden voor dierproeven, om de toegang tot betrouwbare informatie over het gebruik van nieuwe alternatieve methoden te verbeteren. Dat platform werd nu vernieuwd. Daarmee willen de gewesten het gebruik van proefdiervrije methoden bevorderen door in te zetten op kennisdeling, en door experten uit verschillende instellingen en onderzoeksdomeinen met elkaar in contact te brengen.

Minder dierproeven

"Ik wil het lijden van proefdieren zoveel mogelijk te voorkomen," zegt Brussels minister voor Dierenwelzijn Bernard Clerfayt (Défi). "Dit kan door het ontwikkelen, stimuleren en ondersteunen van alternatieve methoden. Als we vandaag precies weten hoeveel dieren voor wetenschappelijk onderzoek worden gebruikt, lijkt het mij van essentieel belang dit aantal te doen verminderen."

Ook Vlaams minister van Dierenwelzijn Ben Weyts (N-VA) wil het aantal dierproeven sterk verminderen. "Er bestaan steeds meer alternatieven voor dierproeven en Vlaanderen kan ook op dat vlak een voortrekkersrol opnemen. Al blijven sommige dierproeven nog steeds een noodzakelijk kwaad. De focus in ons beleid ligt op een doorgedreven toepassing van het ‘3V-beleid’: vermindering, verfijning, vervanging."

%I BRUZZ %C https://www.bruzz.be/samenleving/vlaams-en-brussels-gewest-zoeken-samen-naar-alternatieven-dierenproeven-2022-01-16 %8 16/01/2022 %U https://www.bruzz.be/samenleving/vlaams-en-brussels-gewest-zoeken-samen-naar-alternatieven-dierenproeven-2022-01-16 %0 Conference Proceedings %D 2022 %T Vlaams-Brussels platform rond alternatieven voor dierproeven geoptimaliseerd %A Mieke Van Mulders %A Birgit Mertens %A Vera Rogiers %A Nancy Liodo Missigba %K 3Rs %K alternative methods %K animal testing %K new approach methodologies %I HLN %C https://www.hln.be/binnenland/vlaams-brussels-platform-rond-alternatieven-voor-dierproeven-geoptimaliseerd~a085ddcc/ %8 16/01/2022 %U https://www.hln.be/binnenland/vlaams-brussels-platform-rond-alternatieven-voor-dierproeven-geoptimaliseerd~a085ddcc/ %0 Conference Proceedings %B VUB Today %D 2022 %T VUB, Sciensano, Vlaams en Brussels Gewest roepen wetenschappers op om expertise alternatieve testmethoden maximaal te delen via RE-Place. %A Mieke Van Mulders %A Birgit Mertens %A Vera Rogiers %B VUB Today %I VUB %C VUB Today %8 28/02/2022 %U https://today.vub.be/nl/artikel/alternatieven-voor-dierproeven-gebundeld %0 Conference Proceedings %D 2022 %T Œuvrer à moins de souffrance animale en science est un devoir éthique %A Mieke Van Mulders %A Birgit Mertens %A Vera Rogiers %K 3Rs %K alternative methods %K animal testing %K new approach methodologies %K RE-Place %X

Éviter au maximum l’usage d’animaux de laboratoire en science, c’est possible. La plateforme RE-Place, améliorée, permet l’échange de savoirs entre scientifiques. Entretien avec sa responsable.

En Belgique, environ un demi-million d'animaux de laboratoire sont utilisés chaque année à des fins scientifiques. Pour réduire ce chiffre, en 2018, les Régions flamande et bruxelloise - la Région wallonne a été contactée mais les tractations n'ont pas abouti - lançaient RE-Place, une plateforme permettant aux chercheurs de partager leur expertise sur les alternatives à l'expérimentation animale. Désormais, celle-ci dispose aussi d'une nouvelle version optimisée, notamment via un outil en ligne permettant un meilleur échange de l'expertise existante. Les ministres du Bien-être animal flamand et bruxellois, qui financent le projet,...

%I La Libre %C https://www.lalibre.be/planete/sante/2022/03/25/oeuvrer-a-moins-de-souffrance-animale-en-science-est-un-devoir-ethique-44UWC4VV7JHLVJFSX2N6UILBC4/ %8 25/03/2022 %U https://www.lalibre.be/planete/sante/2022/03/25/oeuvrer-a-moins-de-souffrance-animale-en-science-est-un-devoir-ethique-44UWC4VV7JHLVJFSX2N6UILBC4/ %0 Journal Article %J Food and Chemical Toxicology %D 2021 %T Assessment of hazards and risks associated with dietary exposure to mineral oil for the Belgian population %A Birgit Mertens %A Annelies Van Heyst %A Heidi Demaegdt %A Imke Boonen %A Kathy Van Den Houwe %A Séverine Goscinny %A Elskens, Marc %A Els Van Hoeck %K CALUX® bioassay %K endocrine activity %K genotoxicity %K Mineral oil aromatic hydrocarbons %K Mineral oil saturated hydrocarbons %K Modified Ames test %X

Recently collected dietary exposure data on mineral oil saturated (MOSH) and aromatic (MOAH) hydrocarbons were used to evaluate the risks associated with exposure to mineral oil through food for the Belgian population. For MOSH, the no observed adverse effect level (NOAEL) value of 19 mg kg−1 bw day−1 based on the hepatic inflammation-associated granulomas found in a 90-day oral study in F-344 rats was used as point of departure (PoD). Due to existing toxicological uncertainties, the margin of exposure (MOE) approach was applied. In all investigated scenarios, the MOE values were well above 100, indicating that there is no direct health concern related to MOSH exposure for the Belgian population. Nevertheless, more appropriate risk assessment approaches for MOSH based on adequate PoD are needed. For dietary exposure to MOAH, which are potentially genotoxic and carcinogenic, no MOE values could be calculated due to the lack of adequate dose-response carcinogenicity data. In two investigated worst-case scenarios, a health concern related to MOAH exposure could not be excluded, highlighting that more data are needed to perform an adequate risk assessment. The possibility to use in vitro bioassays to collect such additional toxicological information for MOAH present in food samples was also investigated.

%B Food and Chemical Toxicology %V 149 %8 Jan-03-2021 %G eng %R 10.1016/j.fct.2021.112034 %0 Conference Proceedings %D 2021 %T Brussels region finances VUB research into alternatives to animal experiments %A Mieke Van Mulders %A Birgit Mertens %A Nancy Liodo Missigba %A Vera Rogiers %K 3Rs %K alternative methods to animal testing %K new approach methodologies %K RE-Place %X

The Brussels regional government has approved a grant of €110,000 for research into alternatives to experimentation on animals, minister Bernard Clerfayt, responsible for animal welfare, has announced.

The Free University of Brussels (VUB) has a long history of carrying out research into alternatives to animal experimentation, and is considered a reference point in the sector, Clerfayt’s department said announcing the decision on Sunday.

“To support this, the Brussels Region previously financed the Re-Place project, which drew up an inventory of all alternative methods for animal testing” the department said. “Now inventory needs to be promoted and publicised, and the alternatives to animal testing must be publicised.” That part of the grant amounts to €50,000.

Along those lines, VUB researchers are currently investigating the possibility of using in-vitro models for toxicological research, which would not use living animals at all. Instead, the tests would be carried out on cultures of human cells. The ultimate aim of that research is to find a treatment for fibrosis of the liver – the most common form of liver disease.

This research receives a grant of €60,000.

“Science has evolved and has provided alternatives that do not involve laboratory animals, are based on human cells and which produce more relevant results for humans,” Clerfayt said.

In many cases, tests on animals are not entirely suitable to determine the results on humans, but are nevertheless seen as the only acceptable alternative to tests on humans.

“So it is fundamental that these kinds of method can be developed. And even if in certain cases animal experiments remain a necessary evil, we must keep in mind the objective of drastically reducing their numbers,” he said.

%I The Brussels Time %C https://www.brusselstimes.com/belgium-all-news/197443/brussels-region-finances-vub-research-into-alternatives-to-animal-experiments %8 12/12/2021 %U https://www.brusselstimes.com/belgium-all-news/197443/brussels-region-finances-vub-research-into-alternatives-to-animal-experiments %0 Generic %D 2021 %T Current status of the RE-Place database comprising expertise on the use of NAMs in Belgium %A Mieke Van Mulders %A Nancy Liodo Missigba %A Rogiers, Vera %A Birgit Mertens %B The 11th edition of the World Congress on Alternatives and Animal Use in the Life Sciences %8 23/08/2021 %G eng %0 Journal Article %J Food and Chemical Toxicology %D 2021 %T Identification of flavouring substances of genotoxic concern present in e-cigarette refills %A Sophia Barhdadi %A Birgit Mertens %A Melissa Van Bossuyt %A Jolien Van de Maele %A Roel Anthonissen %A Michael Canfyn %A Patricia Courselle %A Rogiers, Vera %A Eric Deconinck %A Vanhaecke, Tamara %K (Q)SAR methodologies %K e-cigarettes %K genotoxicity %K mutagenicity %X

E-cigarettes have become very popular, a trend that has been stimulated by the wide variety of available e-liquid flavours. Considering the large number of e-liquid flavours (>7000), there is an urgent need to establish a screening strategy to prioritize the flavouring substances of highest concern for human health. In the present study, a prioritization strategy combining analytical screening, in silico tools and literature data was developed to identify potentially genotoxic e-liquid flavourings. Based on the analysis of 129 e-liquids collected on the Belgian market, 60 flavourings with positive in silico predictions for genotoxicity were identified. By using literature data, genotoxicity was excluded for 33 of them whereas for 5, i.e. estragole, safrole, 2-furylmethylketon, 2,5-dimethyl4-hydroxyl-3(2H)-furanone and transhexanal, there was a clear concern for in vivo genotoxicity. A selection of 4 out of the remaining 22 flavourings was tested in two in vitro genotoxicity assays. Three out of the four tested flavourings induced gene mutations and chromosome damage in vitro, whereas equivocal results were obtained for the fourth compound. Thus, although there is a legislative framework which excludes the use of CMR compounds in e-liquids, flavourings of genotoxic concern are present and might pose a health risk for e-cigarette users.

%B Food and Chemical Toxicology %V 147 %8 jan 2021 %G eng %N 111864 %R 10.1016/j.fct.2020.111864 %0 Journal Article %J Trends in Food Science & Technology %D 2021 %T Mineral oil risk assessment: Knowledge gaps and roadmap. Outcome of a multi-stakeholders workshop %A Andrea Hochegger %A Sabrina Moret %A Lucie Geurts %A Thomas Gude %A Erich Leitner %A Birgit Mertens %A Susan O'Hagan %A Fátima Poças %A Thomas J. Simat %A Giorgia Purcaro %B Trends in Food Science & Technology %V 113 %8 Jan-07-2021 %G eng %R 10.1016/j.tifs.2021.03.021 %0 Journal Article %J Food Chemistry %D 2021 %T Occurrence of (suspected) genotoxic flavoring substances in Belgian alcohol-free beers %A Alexandre Dusart %A Birgit Mertens %A Els Van Hoeck %A Margaux Simon %A Séverine Goscinny %A Sonia Collin %K Alcohol-free beers %K Flavoring substances %K GC–MS %K genotoxicity %K SAFE %X

The regulatory landscape of flavorings is evolving, thereby putting pressure on control laboratories to develop analytical methods for a wide range of compounds in various types of food and drinks. In order to improve the monitoring of flavoring substances, a versatile and accurate analytical method using the solvent-assisted flavor evaporation (SAFE) technique coupled to GC–MS(SIM) was developed and validated. Focus was put on authorized flavoring substances requiring specific attention due to a genotoxic concern based on information from European risks assessment reports. Thirty-seven (suspected) genotoxic flavoring substances were analyzed in a selection of ten alcohol-free beers. Five suspected genotoxic compounds (i.e. 1-(2-furyl)-2-propanone, 2-acetylfuran, 2-acetyl-5-methylfuran, 2-acetyl-3,5-dimethylfuran, hex-2-eno-1,4-lactone) as well as two confirmed genotoxic flavoring substances (p-mentha-1,8-dien-7-al, 2,4-pentanedione) were identified and quantified among the selected samples. Low concentrations and natural occurrences of the identified compounds suggested that these were not added as such but rather originated from heat-treatments or from plant-based extracts.

%B Food Chemistry %8 19/08/2021 %G eng %R 10.1016/j.foodchem.2021.130917 %0 Generic %D 2021 %T Status of the RE-Place database comprising expertise on the use of NAMs in Belgium %A Mieke Van Mulders %A Nancy Liodo Missigba %A Birgit Mertens %A Rogiers, Vera %B Knowledge for Growth, Flanders Bio %8 27/09/2021 %G eng %0 Conference Proceedings %B Daily Science %D 2021 %T Une base de données informe les chercheurs des alternatives à l’expérimentation animale %A Birgit Mertens %A Mieke Van Mulders %B Daily Science %8 13/10/2021 %0 Journal Article %J Food and Chemical Toxicology %D 2020 %T Assessing the receptor-mediated activity of PAHs using AhR-, ERα- and PPARγ- CALUX bioassays %A I. Boonen %A A. Van Heyst %A Van Langenhove, K. %A Els Van Hoeck %A Birgit Mertens %A M.S. Denison %A Elskens, M. %A Heidi Demaegdt %K CALUX bioassay %K Endocrine disrupting compounds (EDCs) %K Environmental chemistry %K In vitro toxicology %K Polycyclic aromatic hydrocarbons (PAHs) %X

Polycyclic aromatic hydrocarbons (PAH) are a complex group of organic compounds, consisting of at least three fused aromatic rings, which are formed during combustion of organic matter. While some PAHs have been reported to have carcinogenic and/or mutagenic properties, another possible negative health impact is their endocrine disrupting potential. Therefore, the aim of this study was to determine both the agonistic and antagonistic endocrine activity of 9 environmentally relevant PAHs using three different CALUX bioassays: The AhR-CALUX, The ERα-CALUX and PPARγ-CALUX. For the PPARγ-CALUX anthracene, fluoranthene, pyrene and fluorene showed weak agonistic activity, whilst benzo(a)pyrene (B(a)P) was the only one exhibiting weak antagonistic activity. For the AhR-CALUX, chrysene was the only PAH that showed relatively strong agonist activity (except for B(a)P which was used as a standard). Pyrene, anthracene and fluoranthene showed weak AhR agonist activity. In the ERα-CALUX bioassay, fluoranthene had agonistic activity whilst B(a)P exhibited both agonistic and antagonistic activity (lowering E2 activity by 30%). Phenanthrene and anthracene had weak ERα agonist activities. These results indicate that certain PAHs have multiple modes of action and can activate/inhibit multiple receptor signaling pathways known to play critical roles in mediating endocrine disruption.

%B Food and Chemical Toxicology %V 145 %8 Jan-11-2020 %G eng %R 10.1016/j.fct.2020.111602 %0 Journal Article %J Environmental Science and Pollution Research %D 2020 %T Assessment of natural coagulants to remediate Tunisian textile wastewater by combining physicochemical, analytical, and toxicological data %A Nosra Methneni %A Anthonissen, Roel %A Jolien Van de Maele %A Fatma Trifa %A Luc Verschaeve %A Mansour, Hedi Ben %A Birgit Mertens %K Analytical chemistry %K Bioassays %K Biocoagulants %K Physicochemical properties %K Textile effluents %X

Due to the complexity and variability of textile wastewater composition, a constant search for new treatment strategies that are efficient, eco-friendly, and cost-effective is mandatory. In the present study, the efficiency of coagulation-flocculation using biocoagulants derived from cactus Opuntia ficus indica and eggplant Solanum melongena to remove toxic compounds from Tunisian textile wastewater samples was evaluated by combining assays to investigate physicochemical properties and in vitro (geno)toxicity with analytical chemistry. Both natural coagulants could significantly improve the physicochemical properties of the textile wastewater samples compared to the traditionally used chemical coagulant. The highest rate of decolorization was achieved after treatment with the cactus-derived coagulant. The analytical study revealed the presence of only crystal violet dye (CV) in only one sample. Both natural coagulants were able to remove CV, which may (partially) explain the decolorization of the treated samples. Only one untreated textile effluent induced a genotoxic response in the VITOTOX® assay. The genotoxic effect was not linked to the presence of CV and was no longer observed after treatment with each of the natural coagulants, suggesting the effectiveness of the remediation treatments to remove potentially genotoxic compound(s). However, in the other genotoxicity tests, no biologically relevant effects were observed for any of the tested samples. In conclusion, although the physicochemical data indicate that the use of natural coagulants (cactus and eggplant) could be an interesting alternative treatment process to the chemical coagulant for detoxifying textile effluents, these results were only partially supported by the toxicological and analytical data.

%B Environmental Science and Pollution Research %V 27 %8 Jan-11-2020 %G eng %N 32 %R 10.1007/s11356-020-10000-1 %0 Journal Article %J BioVox %D 2020 %T Belgian initiatives boosting animal-free innovation %A Mieke Van Mulders %A E. Gustafson %A N Liodo Missigba %A Birgit Mertens %A V. Rogiers %B BioVox %8 26/02/2020 %G eng %0 Journal Article %J MethodsX %D 2020 %T In vitro 50 Hz magnetic field long-term exposure: Cytogenetic tests on human lymphoblastoid TK6 cells and validation of the test environment %A Ti Thu Ha Nguyen %A M. Ledent %A Véronique Beauvois %A Anthonissen, Roel %A Luc Verschaeve %A Jean-Francois Collard %A Maurice Hinsenkamp %A Veronique Feipel %A Birgit Mertens %K Background magnetic field %K Comet Assay %K Extremely low-frequency magnetic fields %K Micronucleus test %K Shielding system %X

Potential health effects of extremely low-frequency (electro)magnetic fields (ELF-(E)MFs) have long been investigated, but the results are still inconclusive. With respect to genotoxicity, sound data related to the effects of long-term exposure to ELF-(E)MFs on the genetic material and the impact of long-term pre-exposure to ELF-(E)MFs on the sensitivity of cells to the damage induced by known mutagens are needed. In this manuscript, an optimized protocol for a combined in vitro comet/micronucleus study to investigate these effects in a human lymphoblastoid cell line (TK6) is provided including the description of a well-validated exposure system. Furthermore, the use of a shielding system to limit background ELF-MFs inside the incubator is described as well.

 

%B MethodsX %V 7 %8 Jan-01-2020 %G eng %R 10.1016/j.mex.2020.101071 %0 Journal Article %J Journal of Toxicology %D 2020 %T In Vitro and In Vivo Toxicity Studies on Cymbopogon giganteus Chiov. Leaves Essential Oil from Benin %A Habib Toukourou %A Francine Uwambayinema %A Yousof Yakoub %A Birgit Mertens %A Anatole Laleye %A Lison, Dominique %A Joelle Quetin-Leclercq %A Fernand Gbaguidi %X

Cymbopogon giganteus Chiov. (Poaceae) is a medicinal plant used to treat various diseases in traditional medicine in several African countries. The present study aims to evaluate the oral and inhalation toxicity as well as the mutagenic effects of the essential oil of Cymbopogon giganteus leaves (EOCG) from a sample collected in Benin. Mutagenic potential was assessed by the Ames test using Salmonella typhimurium strains TA98 and TA100. Oral acute toxicity was carried out by administration of a single dose of 2000 mg/kg b.w. to Wistar rats while oral subacute toxicity was assessed by daily administration of 50 and 500 mg/kg of EOCG for 28 days. Finally, inhalation toxicity was assessed by administration of a single dose of 0.125%, 0.5%, 2% or 5% v/v of EOCG emulsions in 0.05% v/v lecithin solution in sterile water for the first experiment, and in a second one by administration of single dose of 0.125% or 0.5% v/v. A broncho-alveolar lavage was performed after 3 h or 24 h, respectively. The results show that EOCG is not mutagenic on Salmonella typhimurium strains at the highest concentration tested (200 μg/plate). In the acute oral toxicity study, EOCG induce neither mortality nor toxicity, showing that the LD50 is greater than 2000 mg/kg. The subacute oral toxicity study at both doses did not show any significant difference in body weight, relative organ weight, hematological and/or biochemical parameters or histopathology as compared to the control group. EOCG induced mortality and inflammation in lungs 3 h after administration of a single dose of 5% or 2% v/v. Single doses of 0.125% or 0.5% v/v did not induce inflammation, cell recruitment nor cytotoxicity in lungs 3 h or 24 h after administration, suggesting safety at these concentrations. This first report on the in vivo toxicity will be useful to guide safe uses of EOCG.

%B Journal of Toxicology %V 2020 %8 28/01/2020 %G eng %R 10.1155/2020/8261058 %0 Journal Article %J Toxicology Letters %D 2020 %T New QSAR models to predict chromosome damaging potential based on the in vivo micronucleus test %A Melissa Van Bossuyt %A Raitano, Giuseppa %A Honma, Masamitsu %A Els Van Hoeck %A Vanhaecke, Tamara %A Rogiers, Vera %A Birgit Mertens %A Benfenati, Emilio %K Chromosome damage %K genotoxicity %K In silico model %K In vivo micronucleus %K QSAR %X

A large number of computer-based prediction methods to determine the potential of chemicals to induce mutations at the gene level has been developed over the last decades. Conversely, only few such methods are currently available to predict potential structural and numerical chromosome aberrations. Even fewer of these are based on the preferred testing method for this endpoint, i.e. the micronucleus test. For the present work, in vivo micronucleus test results of 718 structurally diverse compounds were collected and applied for the construction of new models by means of the freely available SARpy in silico model building software. Multiple QSAR models were created using parameter variation and manual verification of (non-) alerting structures. To this extent, the original set of 718 compounds was split into a training (80 %) and a test (20 %) set. SARpy was applied on the training set to automatically extract sets of rules by generating and selecting substructures based on their prediction performance whereas the test set was used to evaluate model performance. Five different splits were made randomly, each of which had a similar balance between positive and negative substances compared to the full dataset. All generated models were characterised by an overall better performance than existing free and commercial models for the same endpoint, while demonstrating high coverage.

%B Toxicology Letters %V 329 %8 1 sep 2020 %G eng %& 80 %R 10.1016/j.toxlet.2020.04.016 %0 Journal Article %J MethodsX %D 2020 %T RE-Place: A local initiative to pave the road towards international recognition and promotion of new approach methodologies %A Mieke Van Mulders %A Missigba, N. Liodo %A Rogiers, V. %A Birgit Mertens %K 3Rs %K alternative methods %K Database %K Knowledge sharing %K NAM %K Open access %K replacement %B MethodsX %V 7 %8 Jan-01-2020 %G eng %R 10.1016/j.mex.2020.101129 %0 Generic %D 2019 %T Assessing the endocrine activity of PAHs using the DRE-, ERE- and PPARγ CALUX bioassays %A Imke Boonen %A Annelies Van Heyst %A Van Langenhove, Kersten %A Els Van Hoeck %A Birgit Mertens %A Elskens, Marc %A Heidi Demaegdt %X

Introduction
Mineral oils are a complex mixture of organic compounds, consisting of two main types: the saturated hydrocarbons (MOSH) and the aromatic hydrocarbons (MOAH). The occurrence of mineral oil in food has been reported in the past, with concentrations that often reach 0.1% and can even approach 1% in some exceptional cases. These compounds can enter the food chain either intentionally (as an authorized food contact material or additive), or unintentionally (printing inks, recycling, lubricating oils, …). The biggest concern for mineral oil regarding human health is the MOAH fraction, since these compounds are potentially genotoxic, carcinogenic and may have endocrine disrupting properties. An important group of compounds in the MOAH fraction are the polycyclic aromatic hydrocarbons (PAHs). PAHs consist of fused benzene rings, which are formed during incomplete combustion of organic matter (e.g. in engines, incinerators, forest fires…). An important concern linked to PAHs is their potential endocrine disrupting activity. Endocrine disrupting chemicals (EDCs) are a structurally diverse class of both synthetic and natural compounds which can interfere with our hormonal system by binding to endocrine receptors, resulting in adverse health effects such as reproductive damage, developmental impairment, obesity, diabetes and cancers. The aim of this study was to determine the endocrine activity of 9 PAHs using three different CALUX bioassays: DRE-CALUX, ERE-CALUX and PPARγ CALUX.
Materials and methods
Three CALUX (chemically activated luciferase gene expression) bioassays were used to determine the endocrine activity: 1)The PPARy CALUX® system of BioDetection systems (BDS, Amsterdam) uses U‐2OS cells (human osteoblast) that are stably transfected with human PPARy2. 2)DRE-CALUX (dioxin responsive element) uses a third H1L7.5c1 generation cell line, derived from the mouse hepatoma hepa1c1c7 wild‐type cells, which contain the AhR receptor and 3) The ERE-CALUX (estrogen responsive element) uses a human breast cancer cell line (VM7Luc4E2), which contains the estrogen receptor. All three cell lines are also stably transfected with the firefly luciferase reporter gene. Potential activity is determined by measuring light emission after exposure to the compounds and adding luciferin.
Results and discussion
1)PPARy CALUX®: Anthracene, fluoranthene, pyrene and fluorene showed a weak agonistic activity for the PPARy receptor. Only BaP showed a weak antagonistic activity. In both the agonistic and antagonistic tests, no effects were observed in presence of S9 metabolic fraction. Larger compounds like chrysene and benzo(ghi)perylene did not show any activity on the PPARy receptor which may be the result of sterical hindrance preventing them to interact with this receptor (>4 rings). 2)DRE-CALUX: BaP is known to have an AhR agonistic effect and was used as reference compound. Out of the other eight non‐alkylated PAHs, only chrysene exhibited significant agonistic activity. 3) The ERE-CALUX: So far, only preliminary range finding results were obtained, showing that phenanthrene, naphthalene, chrysene, fluoranthene and pyrene all show agonistic estrogenic activity.

%B IMEKOFOODS 4 %8 16/09/2019 %G eng %0 Generic %D 2019 %T Combining a genotoxin-specific qPCR method with the ToxTracker to evaluate the genotoxic potential of high priority printed paper and board food contact material substances %A Melissa Van Bossuyt %A G Hendriks %A R Derr %A TY Doktorova %A Els Van Hoeck %A T Vanhaecke %A V Rogiers %A Birgit Mertens %X

presentation at the EEMGS meeting 2019, Rennes (France)

%B EEMGS meeting 2019, Rennes (France) %8 2019 may 1 %G eng %U https://www.eemgs.eu/past-meetings/eemgs-2019/#:~:text=The%202019%20annual%20EEMGS%20meeting,Genotoxicity%20of%20nanomaterials %0 Generic %D 2019 %T Combining a transcriptomics-based gene expression biomarker with the ToxTracker to evaluate the genotoxic potential of high priority printed paper and board food contact material substances %A Melissa Van Bossuyt %A G Hendriks %A R Derr %A TY Doktorova %A A Thienpont %A Els Van Hoeck %A T Vanhaecke %A V Rogiers %A Birgit Mertens %K Biomarkers %K food contact materials %K Gene Expression %K genotoxicity %K Transcriptomics %X

presentation at Beltox SCIENTIFIC MEETING 2019 PROGRAMME Brussels, Belgium

%B Beltox meeting %8 2019 nov 1 %G eng %U https://beltox.be/beltox-annual-meeting-2019-programme/ %0 Journal Article %J Food Additives & Contaminants: Part A %D 2019 %T Dietary exposure of the Belgian population to mineral oil %A A. Van Heyst %A Séverine Goscinny %A Sarah Bel %A Stefanie Vandevijvere %A Birgit Mertens %A Elskens, Marc %A Els Van Hoeck %K dietary exposure assessment %K Mineral oil %K MOAH %K MOSH %K Spade %X

Recently, presence of mineral oil in numerous foods has been detected. The analysis of mineral oil in food is convoluted since it comprises MOSH (saturated hydrocarbons) and variable amounts of mainly alkylated MOAH (aromatic hydrocarbons). Both fractions have a different toxicological profile and therefore they need to be assessed separately. For Belgium, occurrence data are available comprising concentrations of 217 food samples. These data were used, in combination with the 2014/15 Belgian Food Consumption Survey data, in a lower bound scenario to evaluate the dietary exposure of the Belgian population. Exposure to mineral oil was much lower compared to the results previously reported by EFSA and RIVM. The main contributors in Belgium were similar to previous studies (i.e. cereal products and oils), but an important additional contribution of non-alcoholic drinks was identified due to the presence of mineral oil in coffee. However, the concentration of mineral oil was determined from the dry product by applying a dilution factor with transfer rate of 100%, and not in the prepared coffee.

This study gives an account of the dietary exposure of the Belgian population to mineral oil for the first time and reports the associated uncertainties.

%B Food Additives & Contaminants: Part A %8 07 nov 2019 %G eng %R 10.1080/19440049.2019.1684573 %0 Thesis %D 2019 %T Genotoxic evaluation of the liquids present in electronic cigarettes %A Britt Buffaerts %A Birgit Mertens %A Sophia Barhdadi %X

[Background]  The electronic cigarette (e-cigarette) is a battery-powered device that vaporizes liquid for inhalation by the user. In general, the e-cigarette is perceived as being healthier than the conventional cigarette because no combustion process (and subsequently no formation of hazardous substances related to this process) occurs. However, the absence of the combustion process does not directly imply that the e-cigarette is a healthy substitute compared to the tobacco cigarette. While some studies indicate that the e-cigarette may be up to 95% healthier than the conventional cigarette, an important amount of hazardous substances are still present in the e-liquid, albeit at lower concentrations. Exposure to e-liquid substances has been associated with molecular changes, carcinogenicity and diseases such as heart malfunctions, delayed cellular differentiation and impaired immunological responses in animal models. Whether these findings are also relevant to humans remains unclear.

[Aim]  The genotoxic potential of flavouring substances present in e-cigarettes was studied using animal-free approaches. In addition, the applicability of the Ames test and the in vitro micronucleus test to evaluate the genotoxic potential of e-liquids mixtures was investigated.

[Methods]  The study was performed with flavouring substances that have previously been identified in e-liquids. First, the genotoxic potential of these compounds was assessed using in silico prediction software Derek and Sarah Nexus. For substances that showed a structural alert for genotoxicity in one of the models, genotoxicity data (if available) were collected from the databases of the European Food Safety Authority and European CHemicals Agency. In a next step, compounds for which no data were found and that were commercially available were studied in the Ames test and the in vitro micronucleus test (i.e. b-phellandrene, 2,3-pentanedione). However, for the majority of the compounds, no standard could be obtained and consequently, the Ames test and the in vitro micronucleus test were performed on the e-liquid mixtures. In order to assess the applicability of the in vitro tests for the e-liquid mixtures, three 2,3-pentanedione-containing e-liquids (i.e. Nutella Shake, Hyprtonic Mercedes, Miller’s Chocolate) and an e-liquid containing no substances with structural alerts for genotoxicity (i.e. Dark Turtle) were first tested. In a next step, two e-liquids containing components with a structural alert for genotoxicity but without in vitro or in vivo data (i.e. Ice Ice Baby, Candy Shop) were studied in the Ames test and the in vitro micronucleus test.

[Results and discussion]  Based on the predictions obtained with the in silico models and the availability of genotoxicity data, 28 compounds detected in e-liquids were selected for in vitro genotoxicity testing. However, only two of these compounds were commercially available. b-phellandrene showed a slightly genotoxic effect in the in vitro micronucleus test in the presence of S9 metabolic fraction but was clearly negative in the Ames test. In contrast, 2,3-pentanedione induced a clear dose-dependent genotoxic effect, both in the Ames test and the in vitro micronucleus test. The effect did not require metabolic activation. All three 2,3-pentadione-containing e-liquids showed a negative result in the Ames test. However, they all induced a positive effect in the in vitro micronucleus test that was clearly more pronounced than the effect induced by the propylene glycol/glycerol matrix. Dark Turtle, an e-liquid containing solely nicotine, showed no or little additional genotoxic effect when compared to the matrix. This e-liquid was also negative in the Ames test. The results indicate that e-liquids containing potentially genotoxic compounds can be picked up in the in vitro micronucleus test. Interestingly, out of the two e-liquids containing components with a structural alert for genotoxicity, one was clearly positive whereas the other was negative in the in vitro micronucleus test. Both were also negative in the Ames test.

[Conclusion]  Known and unknown potentially genotoxic compounds can be present in e-liquids. Furthermore, genotoxic effects of e-liquid mixtures can be picked up with the in vitro micronucleus test. Consequently, this test could be useful for ranking e-liquids based on their genotoxic concern. However, further research should be conducted.

%P 61 %8 2019 %G eng %0 Generic %D 2019 %T Hazard characterization and risk assessment of mineral oils: Case study with information obtained in Belgian MinOil study %A Birgit Mertens %B ILSI workshop ‘Mineral Oil Risk Assessment: Knowledge Gaps and Roadmap’, Brussels (Belgium) %8 2019 feb 1 %G eng %0 Report %D 2019 %T Migration of mineral oil from cardboard packaging for food: Identification of the hazards and assessment of the exposure of the Belgian population %A Birgit Mertens %A A. Van Heyst %A Séverine Goscinny %A Elskens, M %A Heidi Demaegdt %A Stefanie Vandevijvere %A Sarah Bel %A I Boonen %A Els Van Hoeck %X

Mineral oil can enter the food via different routes. In order to obtain more insights in the extent of the mineral oil food contamination problem in Belgium, an extensive market survey was conducted including a wide variety of matrices. As  saturated hydrocarbons (MOSH) and aromatic hydrocarbons (MOAH) have a different toxicological profile, the two fractions were quantified separately using an online combination of liquid chromatography and gas chromatography with flame ionization detection (online LC-GC-FID). The detected MOSH and MOAH concentrations were then compared to the action thresholds set by the Scientific Committee (SciCom) of the Belgian Food Safety Agency (FASFC) in 2017. Only one sample exceeded the threshold for MOSH, while the threshold for MOAH was exceeded in 23 samples. For the samples exceeding the action threshold, further investigation is needed to identify the contamination source.

Next, the dietary exposure of the Belgian population to mineral oil was assessed by combining the analytical results with consumption data of the Belgian Food Consumption Survey. Overall, the exposure to MOSH and MOAH was  much lower compared to the results previously reported. Afterwards, the possible risks for the Belgian population were assessed by combining the outcome of the exposure assessment with hazard-related information. Based on the margin of exposure (MOE) approach, there is no health concern related to MOSH exposure for the Belgian population. For MOAH, which may be potentially genotoxic and carcinogenic, no adequate dose-response carcinogenicity data are available and consequently, no MOE-based risk assessment could be performed.  Two worst‐case scenarios were applied to obtain some preliminary insights in the possible health risks associated with MOAH exposure. Based on these scenarios, adverse human health effects could not be excluded highlighting the need for more data to perform a more adequate risk assessment. In order to fill some of the existing gaps in the toxicological knowledge on MOAH, data on their endocrine activity and genotoxic potential were collected.  Several interesting results were obtained, including further evidence that highly alkylated polycyclic aromatic hydrocarbons (PAHs) (which are important constituents of the MOAH fraction) are not metabolized into DNA‐reactive compounds due to steric hindrance. Furthermore, preliminary results suggest the possible use of bioassays based on activation of the Aryl receptor as a fast screening procedure to detect the presence of MOAH, but more research is needed to further investigate this hypothesis.

%8 2019 %G eng %M D/2019/14.440/8 %0 Report %D 2019 %T Mineral oil migration from cardboard food contact materials: Hazard identification and exposure assessment of the Belgian population %A Annelies Van Heyst %A Birgit Mertens %A Séverine Goscinny %A M Elskens %A Heidi Demaegdt %A Karin De Ridder %A Kathy Van Den Houwe %A I Boonen %A K Van Langenhove %A J Van de Maele %A M Michielsen %A Annick Evrard %A Stefanie Vandevijvere %A Sarah Bel %A Els Van Hoeck %X

Op Belgisch niveau heeft het Nationaal Referentielaboratorium voor Contactmaterialen, Sciensano, een wetenschappelijk onderzoeksproject uitgevoerd over de migratie van minerale olie uit kartonverpakkingen, het Minoil project (Mineral oil migration from cardboard food contact materials: Hazard identification and exposure assessment of the Belgian population). De verkregen analyseresultaten werden in het kader van de Aanbeveling (EU) 2017/84 aan de EFSA gerapporteerd.

%8 2019 %G eng %0 Generic %D 2019 %T Overview of OECD Process to Evaluate Miniaturized Ames Assays %A Birgit Mertens %B EMGS workshop “OECD Assessment of Miniaturized Ames Assays: Results and Recommendations”, Washington (US) %8 2019 sep 1 %G eng %0 Generic %D 2019 %T RE-Place: a database compiling New Approach Methodologies %A Birgit Mertens %A Mieke Van Mulders %A N. Liodo Missigba %A V. Rogiers %B Animals in research, no unless %C Leuven, Belgium %8 2019 %G eng %N KU Leuven %0 Generic %D 2019 %T RE-Place: a database compiling New Approach Methodologies %A Birgit Mertens %E Mieke Van Mulders %E N. Liodo Missigba %E V. Rogiers %B Research Day %C Antwerp, Belgium %8 2019 %G eng %N University of Antwerp %0 Generic %D 2019 %T RE-Place: a project to collect the available Belgian expertise on New Approach Methodologies in one central database %A Mieke Van Mulders %A N. Liodo Missigba %A Birgit Mertens %A V Rogiers %B Beltox/IC-3Rs/Invitrom Scientific Meeting, Brussels (Belgim) %8 2019 nov 1 %G eng %0 Generic %D 2019 %T RE-PLACE: an ambitious project to collect animal-free methodologies in one central database %A V Rogiers %A Mieke Van Mulders %A N. Liodo Missigba %A Birgit Mertens %B BCLAS %C Blankenberge, Belgium %8 2019 %G eng %N BCLAS %0 Generic %D 2019 %T The RE-Place database %A Birgit Mertens %A Mieke Van Mulders %A N Liodo Missigba %A V Rogiers %B IC-3Rs workshop ‘Designing research projects according to the 3R’, Brussels (Belgium) %8 2019 nov 11 %G eng %0 Generic %D 2019 %T The RE-Place database %A Birgit Mertens %A Mieke Van Mulders %A N. Liodo Missigba %A V. Rogiers %B IC-3Rs workshop ‘Designing research projects according to the 3R’ %G eng %N IC-3Rs %0 Journal Article %J Food Additives & Contaminants: Part A %D 2018 %T Analysis of mineral oil in food: results of a Belgian market survey %A A. Van Heyst %A Mathias Vanlancker %A Joeri Vercammen %A Kathy Van Den Houwe %A Birgit Mertens %A Elskens, Marc %A Els Van Hoeck %K action thresholds %K food contact materials %K Market survey %K Mineral oil %K online LC-GC %X Recently, migration of mineral oil components from food contact materials into various foods has been reported. The analysis of mineral oil in food is complicated since it consists of mineral oil saturated hydrocarbons (MOSH) comprising a complex mixture of linear, branched and cyclic compounds and variable amounts of mineral oil aromatic hydrocarbons (MOAH), mainly alkylated. Both MOSH and MOAH form ‘humps’ of unresolved peaks in the chromatograms with the same range of volatility. Since these two fractions have a different toxicological relevance, it is important to quantify them separately. Occurrence data on mineral oil are available only for a limited number of food groups and only from few countries. In Belgium, data on the contamination of food by mineral oil are lacking. In this contribution, an in-house validated online combination of liquid chromatography with gas chromatography (LC–GC) with flame ionisation detection (FID) was used for the quantification of MOSH and MOAH. Totally, 217 packed food samples were selected using a well-defined sampling strategy that targeted food categories which are highly consumed and categories suspected to contain mineral oil. For 19 samples, the method was not applicable. For the 198 remaining samples, MOSH was detected in 142 samples with concentrations up to 84.82 mg kg−1. For the MOAH fraction, there are 175 samples with a concentration below the limits of quantification (LOQ), while 23 samples had a higher concentration ranging from 0.6 to 2.24 mg kg−1. Finally, these results were compared with the action thresholds as proposed by the Scientific Committee (SciCom) of the Belgian Food Safety Agency (FAVV-AFSCA). Only one sample exceeded the threshold for MOSH, while the threshold for MOAH was exceeded in 23 samples. For the samples exceeding the action threshold, further investigation is needed to identify the contamination source. %B Food Additives & Contaminants: Part A %V 35 %8 Mar-10-2018 %G eng %N 10 %R 10.1080/19440049.2018.1512758 %0 Report %D 2018 %T Arsenic in food for infants and young children. Advice SHC 9252 of the Superior Health Council %A Pussemier, L %A Goyens,P. %A Birgit Mertens %A J. Rigo %A Ann Ruttens %A Christiane Vleminckx %A Van de Wiele, Tom %K Arsenic %K food legislation %K Food Safety %K rice %K Risk Assessment %G eng %0 Generic %D 2018 %T Identification of Flavouring Substances of Genotoxic Concern Present in E-Cigarette Refills %A Sophia Barhdadi %A Birgit Mertens %A Melissa Van Bossuyt %A Michael Canfyn %A Patricia Courselle %A Rogiers, Vera %A Eric Deconinck %A Vanhaecke,T. %K e-cigarettes %K flavourings %K genotoxicity %X

Over the last years, the popularity of electronic e-cigarettes has increased significantly. An important contributor to this trend is the availability of a wide variety of flavours used in e-liquid refills. However, the role of these flavouring components in the potential toxicity of e-cigarette vapours remains unclear. Considering the large number of e-liquid flavours available on the market (> 7000), there is an urgent need to establish an efficient screening strategy to prioritize the substances of highest concern for human health. In this context, genotoxicity is a key (toxicological) endpoint as it is related to a broad range of adverse human health effects including cancer. Therefore, in this study, a prioritization strategy based on a combination of analytical screening, in silico prediction and literature consultation was developed for identifying potentially genotoxic substances in e-liquid flavours.

77 e-liquids, representative for the different flavour categories, were collected on the Belgian market and screened for their chemical composition using GC-MS. By using the National Institute of Standards and Technology (NIST) research library, 436 individual components could be identified. Next, the genotoxic potential of these individual components was investigated in silico with two complementary (quantitative) structure-activity relationship ((Q)SAR) models (Derek Nexus, Sarah Nexus). In total, 57 flavouring components were identified with a structural alert for genotoxicity in at least one of the two (Q)SAR models. For these substances, genotoxicity data was collected from previous European safety evaluations in different regulatory domains (e.g. by the European Chemical Agency (ECHA) and the European Food Safety Authority (EFSA)). Genotoxicity could be excluded for only 12 of the 57 components, whilst for 2 of them there is a clear concern for genotoxic potential. Data for the remaining components was missing or ambiguous and hence additional toxicological data is required in order to be able to exclude genotoxic potential.

The above findings indicate that the use of flavoring components might thus pose a potential health risk for e-cigarette users. Further research might explore to which extent these flavouring substances are transferred from the e-liquid into the e-cigarette vapours.

%B EUROTOX 2018 %I Toxicology Letters %C Brussels, Belgium %8 05/09/2018 %G eng %0 Journal Article %J Archives of Toxicology %D 2018 %T A novel genotoxin-specific qPCR array based on the metabolically competent human HepaRG™ cell line as a rapid and reliable tool for improved in vitro hazard assessment %A Ates, Gamze %A Birgit Mertens %A Heymans, Anja %A Luc Verschaeve %A Milushev, Dimiter %A Vanparys, Philippe %A Nancy Roosens %A Sigrid C.J. De Keersmaecker %A Rogiers, Vera %A Tatyana Y. Doktorova %K genotoxicity %K HepaRG %K In vitro screening %K mutagenicity %K qPCR array %K Toxicogenomics %X

Although the value of the regulatory accepted batteries for in vitro genotoxicity testing is recognized, they result in a high

number of false positives. This has a major impact on society and industries developing novel compounds for pharmaceutical,

chemical, and consumer products, as afflicted compounds have to be (prematurely) abandoned or further tested on

animals. Using the metabolically competent human HepaRG

™ cell line and toxicogenomics approaches, we have developed

an upgraded, innovative, and proprietary gene classifier. This gene classifier is based on transcriptomic changes induced by

12 genotoxic and 12 non-genotoxic reference compounds tested at sub-cytotoxic concentrations, i.e., IC10 concentrations

as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The resulting gene classifier

was translated into an easy-to-handle qPCR array that, as shown by pathway analysis, covers several different cellular

processes related to genotoxicity. To further assess the predictivity of the tool, a set of 5 known positive and 5 known negative

test compounds for genotoxicity was evaluated. In addition, 2 compounds with debatable genotoxicity data were tested

to explore how the qPCR array would classify these. With an accuracy of 100%, when equivocal results were considered

positive, the results showed that combining HepaRG

™ cells with a genotoxin-specific qPCR array can improve (geno)toxicological

hazard assessment. In addition, the developed qPCR array was able to provide additional information on compounds

for which so far debatable genotoxicity data are available. The results indicate that the new in vitro tool can improve human

safety assessment of chemicals in general by basing predictions on mechanistic toxicogenomics information.

%B Archives of Toxicology %8 Jun-02-2018 %G eng %R 10.1007/s00204-018-2172-5 %0 Journal Article %J Toxicological Sciences %D 2018 %T Performance of in silico models for mutagenicity prediction of food contact materials %A Melissa Van Bossuyt %A Els Van Hoeck %A Raitano, Giuseppa %A Vanhaecke, Tamara %A Benfenati, Emilio %A Birgit Mertens %A Rogiers, Vera %K (Q)SAR %K food contact materials %K In silico %K mutagenicity %K VALIDATION %X

In silico methodologies, such as (quantitative) structure-activity relationships ((Q)SARs), are

available to predict a wide variety of toxicological properties and biological activities for

structurally diverse substances. To obtain insights in the scientific value of these predictions,

the capacity of the prediction models to generate (sufficiently) reliable results for a particular

type of compounds needs to be evaluated. In the current study, performance parameters to

predict the endpoint ‘bacterial mutagenicity’ were calculated for a battery of common

(Q)SAR tools, namely Toxtree, Derek Nexus, VEGA Consensus and Sarah Nexus. Printed

paper and board food contact material (FCM) constituents were chosen as study substances

since many of these lack experimental data, making them an interesting group for in silico

screening. Accuracy, sensitivity, specificity, positive predictivity, negative predictivity and

Matthews correlation coefficient for the individual models and for the combination of VEGA

Consensus and Sarah Nexus were determined and compared. Our results demonstrate that

performance varies among the four models, but can be increased by applying a combination

strategy. Furthermore, the importance of the applicability domain is illustrated. Limited

performance to predict the mutagenic potential of substances that are new to the model (i.e.

not included in the training set) is reported. In this context, the generally poor sensitivity for

these new substances is also addressed.

%B Toxicological Sciences %V 163 %8 2018 mar 20 %G eng %N 2 %R 10.1093/toxsci/kfy057 %0 Journal Article %J ALTEX %D 2018 %T Prioritizing substances of genotoxic concern for in-depth safety evaluation using non-animal approaches: The example of food contact materials. %A Melissa Van Bossuyt %A Els Van Hoeck %A Vanhaecke, Tamara %A Rogiers, Vera %A Birgit Mertens %X

Due to the exponentially growing number of substances requiring safety evaluation, efficient prioritisation strategies are needed to identify those of highest concern. To limit unnecessary animal testing, such strategies should respect the 3R principles (Replacement, Reduction, Refinement). In the present study, a strategy based on non-animal approaches was developed to prioritize non-evaluated printed paper and board food contact material (FCM) substances for further in-depth safety evaluation. Within the strategy, focus was put on genotoxicity, a key toxicological endpoint when evaluating safety. By combining in silico predictions with existing in vitro and in vivo genotoxicity data from publicly available literature sources and results from in vitro gene mutation experiments, the 106 study substances could all be assigned to one of the four priority classes (ranging from low to very high concern). Importantly, 19 substances were considered of very high concern due to in vivo genotoxicity. Five of these are furthermore listed as a Substance of Very High Concern (SVHC) by the European Chemicals Agency (ECHA), in addition to demonstrating physicochemical properties linked to a high migration potential as well as oral bioavailability and being used in primary food packaging materials. The current animal-free strategy proved useful for the priority ranking of printed paper and board FCM substances, but it can also be considered to prioritize other substances of emerging concern.

%B ALTEX %V 2 %8 2019 apr 10 %G eng %N 26 %R 10.14573/altex.1810011 %0 Generic %D 2018 %T RE-Place: Alternative Methods to Animal Testing %A Mieke Van Mulders %A Birgit Mertens %A Rogiers, Vera %K 3R %K alternative methods %K Database %K in chemico %K In silico %K in vitro %K new approach methodologies %B Tuesday Seminar %I CODA-CERVA %C Brussels, Belgium %8 30/01/2018 %G eng %N CODA-CERVA %0 Generic %D 2018 %T RE-Place: centralizing information on alternative methods to animal testing to promote knowledge sharing %A Mieke Van Mulders %A Birgit Mertens %A Rogiers, Vera %K 3R %K alternative methods %K Database %K in chemico %K In silico %K in vitro %K new approach methodologies %K replacement %B EUROTOX %C Brussels, Belgium %8 03/09/2018 %G eng %0 Generic %D 2018 %T RE-Place: Creation of a database for alternative methods to animal testing in the Flemish and Brussels region %A Mieke Van Mulders %A Birgit Mertens %A Rogiers, Vera %K 3R %K alternative methods %K Database %K in chemico %K In silico %K in vitro %K new approach methodologies %K replacement %B Knowledge For Growth %C Ghent, Belgium %8 17-05-2018 %G eng %N FlandersBio %0 Conference Proceedings %B Biotechniek %D 2018 %T Studiedag rond alternatieve methoden voor dierproeven in Vlaanderen. Het Kick-off symposium van RE-Place %A Mieke Van Mulders %A Birgit Mertens %A Eveline Roose %A Rogiers, Vera %K 3R %K alternative methods %K Database %K in chemico %K In silico %K in vitro %K new approach methodologies %K replacement %B Biotechniek %I Biotechniek %8 02/2018 %0 Journal Article %J Food Chem Toxicol %D 2017 %T Coatings in food contact materials: Potential source of genotoxic contaminants? %A Birgit Mertens %A Melissa Van Bossuyt %A Fraselle, S %A Marie-Noelle Blaude %A T Vanhaecke %A Rogiers, V %A Luc Verschaeve %A Els Van Hoeck %K Consumer Product Safety %K Food Contamination %K Food Packaging %K Humans %K Mutagenicity Tests %K Mutagens %X

Up till now, no harmonized EU regulation exists on chemicals used in coatings for food contact materials (FCM). Therefore, these substances need to comply with the general provisions of EU Regulation 1935/2004 and, if present, with national legislation. Different 'inventory lists' of compounds that might be present in coatings are available, but for hundreds of these substances, the potential human health impact of their use in FCM coatings has not (recently) been evaluated. Since detailed evaluation of all compounds is not feasible, a pragmatic approach was developed to identify substances with a potential concern for human health. First, an inventory was assembled containing all substances potentially used in coatings. Afterwards, the genotoxic potential of the non-evaluated substances was predicted in silico using two structure-activity relationship (SAR) software programs. For substances yielding structural alerts in both models, genotoxicity data were collected from previous European evaluations in a non-FCM context and from the European CHemicals Agency (ECHA) website. In total, 53 substances were identified as genotoxic in both in silico models, of which ten were considered to be of high concern. For most of the substances, additional toxicological information is needed.

%B Food Chem Toxicol %V 106 %P 496-505 %8 2017 Aug %G eng %N Pt A %1 https://www.ncbi.nlm.nih.gov/pubmed/28583787?dopt=Abstract %& 496 %R 10.1016/j.fct.2017.05.071 %0 Generic %D 2017 %T Current status of the RE-Place project %A Mieke Van Mulders %A Birgit Mertens %A Rogiers, Vera %K 3R %K alternative methods %K Database %K in chemico %K In silico %K in vitro %K new approach methodologies %B Study day concerning the use of laboratory animals in the Flemish region, organised by the Flemish government %I Departement Omgeving, Dienst Dierenwelzijn %C Brussels, Belgium %8 05/10/2017 %G eng %0 Generic %D 2017 %T Printed paper and board: Priority setting strategy for toxicological assessment %A Melissa Van Bossuyt %A Els Van Hoeck %A Vanhaecke,T. %A Rogiers,V. %A Birgit Mertens %B Food Packaging Forum Workshop on Scientific Challenges in the risk assessment of Food Contact Materials %G eng %0 Journal Article %J Food Chem Toxicol %D 2017 %T (Q)SAR tools for priority setting: A case study with printed paper and board food contact material substances. %A Melissa Van Bossuyt %A Els Van Hoeck %A Raitano, Giuseppa %A Serena Manganelli %A Braeken, Els %A Ates, Gamze %A Vanhaecke, Tamara %A Van Miert, Sabine %A Benfenati, Emilio %A Birgit Mertens %A Rogiers, Vera %K Computer Simulation %K Food Packaging %K Mutagenicity Tests %K Organic Chemicals %K Paper %K Quantitative Structure-Activity Relationship %K SOFTWARE %X

Over the last years, more stringent safety requirements for an increasing number of chemicals across many regulatory fields (e.g. industrial chemicals, pharmaceuticals, food, cosmetics, …) have triggered the need for an efficient screening strategy to prioritize the substances of highest concern. In this context, alternative methods such as in silico (i.e. computational) techniques gain more and more importance. In the current study, a new prioritization strategy for identifying potentially mutagenic substances was developed based on the combination of multiple (quantitative) structure-activity relationship ((Q)SAR) tools. Non-evaluated substances used in printed paper and board food contact materials (FCM) were selected for a case study. By applying our strategy, 106 out of the 1723 substances were assigned 'high priority' as they were predicted mutagenic by 4 different (Q)SAR models. Information provided within the models allowed to identify 53 substances for which Ames mutagenicity prediction already has in vitro Ames test results. For further prioritization, additional support could be obtained by applying local i.e. specific models, as demonstrated here for aromatic azo compounds, typically found in printed paper and board FCM. The strategy developed here can easily be applied to other groups of chemicals facing the same need for priority ranking.

%B Food Chem Toxicol %V 102 %P 109-119 %8 2017 Apr %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/28163056?dopt=Abstract %& 109 %R 10.1016/j.fct.2017.02.002 %0 Book %D 2017 %T Reference Module in Food Science: A Safety Evaluation of Printed Paper and Board Contaminants: Photo-Initiators as a Case Study %A Els Van Hoeck %A Kathy Van Den Houwe %A Melissa Van Bossuyt %A Vanhaecke, T. %A Rogiers, V. %A Birgit Mertens %K contaminants %K dry food %K exposure %K food contact materials %K hazard identification %K in silico tools %K Market survey %K paper and board %K printing ink %K Risk Assessment %K toxtree %K TTC %X Abstract Consumers are exposed to a number of substances that could have a detrimental impact on their health. Several food crises at the end of the previous decade highlighted the need for more information about compounds used in food contact materials (FCMs). The current study discussed the issues related to printed paper and board. Afterward, a risk assessment was carried out for the specific class of photo-initiators. The current study illustrates how the Threshold of Toxicological Concern (TTC) approach can be used to perform a preliminary risk assessment of substances migrating from FCM. However, the safety evaluation of these migrants remains challenging. %I Elsevier %C ? %8 26/08/2017 %@ 9780081005965 %G eng %9 Reference module in food science %R 10.1016/B978-0-08-100596-5.21463-7 %0 Journal Article %J Arch Toxicol %D 2017 %T Safeguarding human health using in silico tools? %A Melissa Van Bossuyt %A Els Van Hoeck %A Vanhaecke, Tamara %A Rogiers, Vera %A Birgit Mertens %K Computer Simulation %K Humans %K Toxicity Tests %K Toxicology %B Arch Toxicol %V 91 %P 2705-2706 %8 2017 Jul %G eng %N 7 %1 https://www.ncbi.nlm.nih.gov/pubmed/28180947?dopt=Abstract %& 2705 %R 10.1007/s00204-017-1931-z %0 Generic %D 2017 %T A safety evaluation of printed paper and board contaminants: Photo-initiators as a case study %A Kathy Van Den Houwe %A Els Van Hoeck %A Melissa Van Bossuyt %A Birgit Mertens %B International Conference on Food Safety and Regulatory %G eng %0 Journal Article %J Food Chem Toxicol %D 2016 %T Evaluation of the potential health risks of substances migrating from polycarbonate replacement baby bottles. %A Birgit Mertens %A Els Van Hoeck %A Marie-Noelle Blaude %A Simon, Coraline %A Onghena, Matthias %A Vandermarken, Tara %A Van Langenhove, Kersten %A Heidi Demaegdt %A Karine Vandermeiren %A Covaci, Adrian %A Scippo, Marie-Louise %A Elskens, Marc %A Joris Van Loco %K Air Pollutants, Occupational %K Benzhydryl Compounds %K Bottle Feeding %K Endocrine disruptors %K Food Contamination %K Humans %K Infant %K Phenols %K Plasticizers %K plastics %K Polycarboxylate Cement %K Polymers %K Risk Assessment %X

Since the European Commission prohibited the use of bisphenol A in the production of polycarbonate (PC) baby bottles, many other materials have replaced PC for the manufacture of this type of food contact materials. In the present study, the potential migration risks associated with these alternative materials were investigated. First, all substances were evaluated for endocrine disruptive (ED) activity by using different existing lists of (suspected) ED chemicals. Next, the potential non-ED risks were assessed. A distinction was made between migrants listed in Annex I of European Regulation 10/2011 and the unlisted substances (e.g. non-intentionally added substances). For the listed substances, concentrations in the migration solutions were compared to their respective specific migration limits (SML) (when applicable). Migration of all substances was shown to be below their SML. The unlisted substances were evaluated using toxicological information from previous evaluations, or if not available, by applying the Threshold of Toxicological Concern (TTC) approach. In case the estimated exposure to the unlisted substance exceeded the human exposure TTC value, a more indepth risk assessment was performed. Based on the results of both parts of the study, four baby bottles were considered of high concern because of the potential toxicity of migrating compounds.

%B Food Chem Toxicol %V 97 %P 108-119 %8 2016 Nov %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/27591929?dopt=Abstract %R 10.1016/j.fct.2016.08.019 %0 Generic %D 2016 %T Human biomonitoring as a tool for objective exposure assessment: A case-study of a major train accident with acrylonitrile in Belgium %A An Van Nieuwenhuyse %A De Smedt,T. %A Smons,K. %A Stove,C. %A De Paepe,P. %A Nemery,B. %A Bader,M. %A Christiane Vleminckx %A Ilse Van Overmeire %A Sébastien Fierens %A Birgit Mertens %A Koen De Cremer %A T. Goen %A Schettgen,T. %A Herman Van Oyen %A Joris Van Loco %K accident %K acrylonitrile %K approach %K AS %K assessment %K biomonitoring %K exposure %K exposure assessment %K health %K Human %K Human biomonitoring %K International %K Objective %K Science %K Societies %K Society %B Interdisciplinary Approaches for Health and the Environment %I NA %C NA %8 10/9/2016 %G eng %N International Society of Exposure Science ISES, %1 2516 %2 9-13/10/2016 %0 Generic %D 2016 %T Human biomonitoring in the Wetteren incident %A An Van Nieuwenhuyse %A De Smedt ,T. %A Simons,K. %A Stove,C. %A De Paepe,P. %A Nemery,B. %A Bader,M. %A Christiane Vleminckx %A Ilse Van Overmeire %A Sébastien Fierens %A Birgit Mertens %A Koen De Cremer %A T. Goen %A Schettgen,T. %A Herman Van Oyen %A Joris Van Loco %K biomonitoring %K Cost %K Diagnosis %K European %K exposure %K Human %K Human biomonitoring %K Monitoring %K prevention %K Wetteren %B European COST project DiMoPEX, Diagnosis, monitoring, prevention of exposure related non-communicable diseases %I NA %C NA %8 0/0/2016 %G eng %N DiMoPEX %1 2642 %2 October 18, 2016. %0 Journal Article %J Mutagenesis %D 2016 %T In silico tools and transcriptomics analyses in the mutagenicity assessment of cosmetic ingredients: a proof-of-principle on how to add weight to the evidence. %A Ates, Gamze %A Raitano, Giuseppa %A Heymans, Anja %A Melissa Van Bossuyt %A Vanparys, Philippe %A Birgit Mertens %A Chesne, Christophe %A Roncaglioni, Alessandra %A Milushev, Dimiter %A Benfenati, Emilio %A Rogiers, Vera %A Doktorova, Tatyana Y %K Cosmetics %K In silico %K Mutagenicity Tests %K Transcriptomics %X

Prior to the downstream development of chemical substances, including pharmaceuticals and cosmetics, their influence on the genetic apparatus has to be tested. Several in vitro and in vivo assays have been developed to test for genotoxicity. In a first tier, a battery of two to three in vitro tests is recommended to cover mutagenicity, clastogenicity and aneugenicity as main endpoints. This regulatory in vitro test battery is known to have a high sensitivity, which is at the expense of the specificity. The high number of false positive in vitro results leads to excessive in vivo follow-up studies. In the case of cosmetics it may even induce the ban of the particular compound since in Europe the use of experimental animals is no longer allowed for cosmetics. In this article, an alternative approach to derisk a misleading positive Ames test is explored. Hereto we first tested the performance of five existing computational tools to predict the potential mutagenicity of a data set of 132 cosmetic compounds with a known genotoxicity profile. Furthermore, we present, as a proof-of-principle, a strategy in which a combination of computational tools and mechanistic information derived from in vitro transcriptomics analyses is used to derisk a misleading positive Ames test result. Our data shows that this strategy may represent a valuable tool in a weight-of-evidence approach to further evaluate a positive outcome in an Ames test.

%B Mutagenesis %V 31 %P 453-61 %8 2016 Jul %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/26980085?dopt=Abstract %& 453 %R 10.1093/mutage/gew008 %0 Journal Article %J Food Chem Toxicol %D 2016 %T Investigation of the genotoxicity of substances migrating from polycarbonate replacement baby bottles to identify chemicals of high concern. %A Birgit Mertens %A Simon, Coraline %A Melissa Van Bossuyt %A Onghena, Matthias %A Vandermarken, Tara %A Van Langenhove, Kersten %A Heidi Demaegdt %A Els Van Hoeck %A Joris Van Loco %A Karine Vandermeiren %A Covaci, Adrian %A Scippo, Marie-Louise %A Elskens, Marc %A Luc Verschaeve %K Benzhydryl Compounds %K Food Contamination %K Humans %K Infant %K Mutagens %K Phenols %K Polycarboxylate Cement %X

Due to the worldwide concern that bisphenol A might act as an endocrine disruptor, alternative materials for polycarbonate (PC) have been introduced on the European market. However, PC-replacement products might also release substances of which the toxicological profile--including their genotoxic effects--has not yet been characterized. Because a thorough characterization of the genotoxic profile of all these substances is impossible in the short term, a strategy was developed in order to prioritize those substances for which additional data are urgently needed. The strategy consisted of a decision tree using hazard information related to genotoxicity. The relevant information was obtained from the database of the European Chemicals Agency (ECHA), in silico prediction tools (ToxTree and Derek Nexus(TM)) and the in vitro Vitotox(®) test for detecting DNA damage. By applying the decision tree, substances could be classified into different groups, each characterized by a different probability to induce genotoxic effects. Although none of the investigated substances could be unequivocally identified as genotoxic, the presence of genotoxic effects could neither be excluded for any of them. Consequently, all substances require more data to investigate the genotoxic potential. However, the type and the urge for these data differs among the substances.

%B Food Chem Toxicol %V 89 %P 126-37 %8 2016 Mar %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/26802677?dopt=Abstract %& 126 %R 10.1016/j.fct.2016.01.009 %0 Journal Article %J Crit Rev Food Sci Nutr %D 2016 %T Mechanisms Linking Colorectal Cancer to the Consumption of (Processed) Red Meat: A Review. %A Demeyer, Daniel %A Birgit Mertens %A De Smet, Stefaan %A Ulens, Michèle %K Animals %K Carcinogens %K Colorectal Neoplasms %K Diet %K Disease Models, Animal %K Food Handling %K Heterocyclic Compounds %K Humans %K Lipid Peroxidation %K Meat Products %K Polycyclic Aromatic Hydrocarbons %K Red Meat %K Risk Factors %X

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. The vast majority of CRC cases have been linked to environmental causes rather than to heritable genetic changes. Over the last decades, epidemiological evidence linking the consumption of red and, more convincingly, of processed red meat to CRC has accumulated. In parallel, hypotheses on carcinogenic mechanisms underlying an association between CRC and the intake of red and processed red meat have been proposed and investigated in biological studies. The hypotheses that have received most attention until now include (1) the presence of polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, two groups of compounds recognized as carcinogenic, (2) the enhancing effect of (nitrosyl)heme on the formation of carcinogenic N-nitroso compounds and lipid peroxidation. However, none of these hypotheses completely explains the link between red and processed red meat intake and the CRC risk. Consequently, scientists have proposed additional mechanisms or refined their hypotheses. This review first briefly summarizes the development of CRC followed by an in-depth overview and critical discussion of the different potential carcinogenic mechanisms underlying the increased CRC risk associated with the consumption of red and processed red meat.

%B Crit Rev Food Sci Nutr %V 56 %P 2747-66 %8 2016 Dec 09 %G eng %N 16 %1 http://www.ncbi.nlm.nih.gov/pubmed/25975275?dopt=Abstract %R 10.1080/10408398.2013.873886 %0 Journal Article %J Regul Toxicol Pharmacol %D 2016 %T Printed paper and board food contact materials as a potential source of food contamination. %A Melissa Van Bossuyt %A Els Van Hoeck %A Vanhaecke, Tamara %A Rogiers, Vera %A Birgit Mertens %K Checklist %K Consumer Product Safety %K Food Contamination %K Food Packaging %K Hazardous Substances %K Humans %K Ink %K Paper %K Printing %K Risk Assessment %K Toxicity Tests %X

Food contact materials (FCM) are estimated to be the largest source of food contamination. Apart from plastics, the most commonly used FCM are made of printed paper and board. Unlike their plastic counterparts, these are not covered by a specific European regulation. Several contamination issues have raised concerns towards potential adverse health effects caused by exposure to substances migrating from printed paper and board FCM. In the current study, an inventory combining the substances which may be used in printed paper and board FCM, was created. More than 6000 unique compounds were identified, the majority (77%) considered non-evaluated in terms of potential toxicity. Based on a preliminary study of their physicochemical properties, it is estimated that most of the non-evaluated single substances have the potential to migrate into the food and become bioavailable after oral intake. Almost all are included in the FACET tool, indicating that their use in primary food packaging has been confirmed by industry. Importantly, 19 substances are also present in one of the lists with substances of concern compiled by the European Chemicals Agency (ECHA). To ensure consumer safety, the actual use of these substances in printed paper and board FCM should be investigated urgently.

%B Regul Toxicol Pharmacol %V 81 %P 10-19 %8 2016 Nov %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/27389280?dopt=Abstract %& 10 %R 10.1016/j.yrtph.2016.06.025 %0 Journal Article %J Toxicol In Vitro %D 2016 %T Screening of endocrine activity of compounds migrating from plastic baby bottles using a multi-receptor panel of in vitro bioassays. %A Simon, Coraline %A Onghena, Matthias %A Covaci, Adrian %A Els Van Hoeck %A Joris Van Loco %A Vandermarken, Tara %A Van Langenhove, Kersten %A Heidi Demaegdt %A Birgit Mertens %A Karine Vandermeiren %A Scippo, Marie-Louise %A Elskens, Marc %K Animals %K Biological Assay %K Bottle Feeding %K Cell Line %K Cell Line, Tumor %K Endocrine disruptors %K Genes, Reporter %K Humans %K Infant Equipment %K mice %K Polycarboxylate Cement %K Receptors, Cytoplasmic and Nuclear %X

Endocrine activity of 65 compounds migrating from polycarbonate replacement plastic baby bottles was assessed using in vitro cell based assays (reporter gene assays) involving 7 nuclear receptors, i.e. human steroid hormones receptors (oestrogen, androgen, progesterone and glucocorticoid receptors), human thyroid beta and peroxisome proliferator-activated gamma receptors, and the mouse aryl hydrocarbon receptor. The chemicals were tested at 4 concentrations ranging from 0.001mM to 1mM. Only twelve chemicals did not show any activity towards any of the nuclear receptors, while fifty three compounds showed a possible endocrine activity. Most of the agonistic activities were observed towards the oestrogen receptor while the PPARγ was the target for most of the recorded antagonistic activities. Agonistic activities were recorded for several phthalates, benzophenones, aromatic hydrocarbons and phenols, while compounds such as benzaldehydes, ketones and esters of fatty acid showed antagonistic activities. Thirty five chemicals were able of agonistic activities on 1 to 4 receptors and antagonistic activities were recorded for 35 compounds as well, towards 1 to 7 receptors. Sixteen compounds were able of both agonistic and antagonistic activities, but not on the same receptors, except in 2 cases for the oestrogen receptor and 4 cases for the PPARγ.

%B Toxicol In Vitro %V 37 %P 121-133 %8 2016 Dec %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/27633901?dopt=Abstract %R 10.1016/j.tiv.2016.09.008 %0 Journal Article %J Environ Res %D 2016 %T Short-term health effects in the general population following a major train accident with acrylonitrile in Belgium. %A Simons, K %A De Smedt, T %A Stove, C %A De Paepe, P %A Bader, M %A Nemery, B %A Christiane Vleminckx %A Koen De Cremer %A Ilse Van Overmeire %A Sébastien Fierens %A Birgit Mertens %A Göen, T %A Schettgen, T %A Herman Van Oyen %A Joris Van Loco %A An Van Nieuwenhuyse %K acrylonitrile %K Adult %K Belgium %K Chemical Hazard Release %K cotinine %K Dose-Response Relationship, Drug %K Environmental Monitoring %K Female %K Headache %K Humans %K Irritants %K Male %K middle aged %K Nausea %K Railroads %K Self Report %K SMOKING %K Surveys and Questionnaires %K Tremor %K Valine %X

BACKGROUND: Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident.

OBJECTIVES: (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects.

METHODS: Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs).

RESULTS: The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose.

DISCUSSION AND CONCLUSION: The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure.

%B Environ Res %V 148 %P 256-263 %8 2016 Jul %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/27085497?dopt=Abstract %R 10.1016/j.envres.2016.03.031 %0 Report %D 2016 %T Toxicological evaluation of substances included in the Database of Substances known by Member States of Council of Europe and used in Food Contact Materials. %A Kamath,P. %A Els Van Hoeck %A Christiane Vleminckx %A Birgit Mertens %A Bolle,F. %K CONTACT %K council of europe %K Database %K Europe %K EVALUATION %K food %K food contact %K food contact material %K food contact materials %K State %I WIV-ISP %C Brussels %P 3 %8 0/0/2016 %G eng %1 2654 %0 Journal Article %J Mutation research %D 2016 %T The Vitotox and ToxTracker assays: a two-test combination for quick and reliable assessment of genotoxic hazards %A Ates, Gamze %A Favyts, Dorien %A Hendriks, Giel %A Derr, Remco %A Birgit Mertens %A Luc Verschaeve %A Rogiers, Vera %A Tatyana Yordanova Doktorova %K an %K analysi %K analysis %K approach %K AS %K assessment %K chemicals %K Combination %K cosmetic %K Development %K Europe %K Follow up %K FOLLOW-UP %K genotoxicity %K hazard %K health %K Human %K human health %K INFORMATION %K IS %K Less %K Paper %K performance %K result %K results %K SENSITIVITY %K Test %K variety %K Vitotox %X

To ensure human health, it is essential to characterize the genotoxic potential of new chemical entities such as pharmaceutical and cosmetic substances. In a first tier a battery of regulatory accepted in vitro tests is recommended. These tests have a relatively high sensitivity, but a low specificity. Furthermore, they are time-consuming, laborious and require large quantities of the individual chemicals. New assays overcoming these drawbacks are under development, the majority of them being reporter-based assays. In this paper we investigate the performance of two in vitro reporter-based assays, namely the Vitotox and the ToxTracker. A set of reference compounds were selected to cover not only different mechanisms of genotoxic action, but also a variety of applicability domains (e.g. pharmaceutical and cosmetic ingredients). Results show that both assays can be valuable tools in genotoxicity hazard assessment, especially when combined in a test battery. An interesting property of both assays for drug-development is the possibility of time-efficient analysis of a large amount of drug-candidates while using small quantities and high throughput (automatized) technologies. Furthermore, the tests are less laborious. For the cosmetic industry, the generated information can be added in a weight-of-evidence approach to derisk false positive results as in vivo follow-up testing is no longer allowed in Europe.

%B Mutation research %V 810 %8 1/11/2016 %G eng %& 13 %R j.mrgentox.2016.09.005 %0 Report %D 2015 %T Arsenic and other elements in algae and dietary supplements based on algae. Advice 9149 of the Superior Health Council. %A Witters, A. %A De Henauw, S. %A Maghuin-Rogister, G. %A Birgit Mertens %A Ann Ruttens %A Christiane Vleminckx %A Pussemier, L %K Arsenic %K Cadmium %K Food Supplements %K inorganic arsenic %K intake assessment %K Lead %K mercury %K Risk Assessment %K Trace Elements %I HGR-CSS %C Brussels, Belgium %P 50 %8 04/2015 %G eng %M NA %0 Report %D 2015 %T Evaluatie van de migratie van toxische chemicaliën uit vernis gebruikt voor voedselverpakkingen %A Stéphanie Fraselle %A Birgit Mertens %A Els Van Hoeck %K de %I WIV-ISP %C Brussel %P 73 %8 0/0/2015 %@ D/2015/2505/12 %G eng %1 2363 %0 Report %D 2015 %T Study on implications on the requirements for submission of toxicological information, restricitions and administrative consequences of the draft revised guideline on Food Contact Materials %A Els Van Hoeck %A Birgit Mertens %A Séverine Goscinny %A N'Goy,T. %A Van paemel,M. %A F. Bolle %A Christiane Vleminckx %K consequences %K CONTACT %K food %K food contact %K food contact material %K food contact materials %K implication %K IMPLICATIONS %K INFORMATION %K ON %K petition %K Requirements %K revised guidelines %K study %X The present document has been produced and adopted by the bodies identified above as author(s). In accordance with Article 36 of Regulation (EC) No 178/2002, this task has been carried out exclusively by the author(s) in the context of a grant agreement between the European Food Safety Authority and the author(s). The present document is published complying with the transparency principle to which the Authority is subject. It cannot be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Published date: 28 January 2016 Question number: EFSA‐Q‐2013‐00699 %I EFSA %C Parma, Italy %P 117 %8 0/0/2015 %G eng %1 2320 %R https://doi.org/10.2903/sp.efsa.2016.EN-671 %0 Journal Article %J Eur J Med Chem %D 2014 %T 2,4-Dialkyl-8,9,10,11-tetrahydrobenzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12(2H,4H)-tetraones as new leads against Mycobacterium tuberculosis. %A Claes, Pieter %A Davie Cappoen %A Uythethofken, Cynthia %A Jacobs, Jan %A Birgit Mertens %A Vanessa Mathys %A Luc Verschaeve %A Huygen, Kris %A De Kimpe, Norbert %K Animals %K Antitubercular Agents %K Cell Line %K Dose-Response Relationship, Drug %K Isoquinolines %K Macrophages %K mice %K Microbial Sensitivity Tests %K Molecular Structure %K Mycobacterium tuberculosis %K Pyrimidinones %K Quinones %K Structure-Activity Relationship %K Tuberculosis, Multidrug-Resistant %X

Given the re-emergence of tuberculosis in Europe and beyond, the search for novel bio-active compound classes against this disease is of utmost importance. As a result of a high intrinsic tolerance of the etiological agent, Mycobacterium tuberculosis, towards most antibiotics and xenobiotics, the search for such new compounds is far from trivial. Further exacerbated by the rapid generation and spread of drug resistant M. tuberculosis and fuelled by the HIV/AIDS pandemic, halting the tuberculosis epidemic is of paramount importance. As part of our program to design new 2-aza-anthraquinones with anti-mycobacterial activity, various dialkyltetrahydrobenzo[g]pyrimido[4,5-c]isoquinolinetetraones were designed and synthesised. The compounds were submitted to a biological evaluation in which the activity against M.tb H37Rv(lux) was observed, as well as the acute toxicity towards J774 A.1 macrophages. From these results, the selectivity index was calculated. Furthermore, the activity of the most promising compounds was further studied against a multi-drug resistant LAM-1 strain and against intracellular replicating M.tb. The study was further extended with a comet assay and a VITOTOX™ assay to investigate the possibility of observable genotoxic effects caused by these compounds.

%B Eur J Med Chem %V 77 %P 409-21 %8 2014 Apr 22 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/24681334?dopt=Abstract %R 10.1016/j.ejmech.2014.03.024 %0 Journal Article %J Toxicol Lett %D 2014 %T Acrylonitrile exposure assessment in the emergency responders of a major train accident in Belgium: a human biomonitoring study. %A An Van Nieuwenhuyse %A Sébastien Fierens %A De Smedt, T %A Koen De Cremer %A Christiane Vleminckx %A Birgit Mertens %A Ilse Van Overmeire %A Bader, M %A De Paepe, P %A Göen, T %A Nemery, B %A Schettgen, T %A Stove, C %A Herman Van Oyen %A Joris Van Loco %K acrylonitrile %K Adult %K Belgium %K Chemical Hazard Release %K Emergency Responders %K Environmental Monitoring %K Female %K Humans %K Male %K middle aged %K Occupational Exposure %K Railroads %K regression analysis %K Surveys and Questionnaires %K Valine %X

BACKGROUND: On May 4, 2013, a train transporting chemicals derailed in Wetteren, Belgium. Several tanks loaded with acrylonitrile (ACN) exploded, resulting in a fire and a leakage of ACN.

OBJECTIVES: To determine exposure to ACN and to assess discriminating factors for ACN exposure in the emergency responders involved in the on-site management of the train accident.

METHODS: The study population consisted of 841 emergency responders. Between May 21 and June 28, they gave blood for the determination of N-2-cyanoethylvaline (CEV) hemoglobin adducts and urine for the measurement of cotinine. They also filled in a short questionnaire.

RESULTS: 163 (26%) non-smokers and 55 (27%) smokers showed CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively. The 95th percentile in the non-smokers was 73 pmol/g globin and the maximum was 452 pmol/g globin. ACN exposure among the non-smokers was predicted by (1) the distance to the accident, (2) the duration of exposure, and (3) the occupational function.

DISCUSSION AND CONCLUSION: Emergency responders involved in the on-site management of the train accident were clearly exposed to ACN from the accident. However, the extent of exposure remained relatively moderate with CEV concentrations staying within the ranges described in literature as background for a smoking population. Moreover, the exposure was less pronounced in the emergency responders as compared to that in the local population.

%B Toxicol Lett %V 231 %P 352-9 %8 2014 Dec 15 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/25128591?dopt=Abstract %R 10.1016/j.toxlet.2014.08.013 %0 Journal Article %J Toxicol Lett %D 2014 %T Acrylonitrile exposure in the general population following a major train accident in Belgium: a human biomonitoring study. %A De Smedt, T %A Koen De Cremer %A Christiane Vleminckx %A Sébastien Fierens %A Birgit Mertens %A Ilse Van Overmeire %A Bader, M %A De Paepe, P %A Göen, T %A Nemery, B %A Schettgen, T %A Stove, C %A Herman Van Oyen %A Joris Van Loco %A An Van Nieuwenhuyse %K acrylonitrile %K Adult %K Belgium %K Chemical Hazard Release %K environmental exposure %K Environmental Monitoring %K Female %K Humans %K Male %K middle aged %K Railroads %K Sewage %K Surveys and Questionnaires %K Valine %X

BACKGROUND: On Saturday May 4, 2013, a train transporting chemicals derailed in the village of Wetteren (Belgium) and caused a leak of acrylonitrile (ACN).

OBJECTIVES: To assess the human exposure to acrylonitrile in the local population with the highest suspected exposure.

METHODS: Between May 18-25, 242 residents participated in the study. N-2-cyanoethylvaline (CEV), a biomarker that is highly specific for ACN exposure, was measured in the blood. To account for potential influence by smoking, cotinine was determined in the urine. Participants also filled in a short questionnaire.

RESULTS: In the evacuated zone, 37.3% of the non-smokers and 40.0% of the smokers had CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively, at the time of the train accident. Spatial mapping of the CEV concentrations depending on the residential address showed a distribution pattern following the sewage system.

DISCUSSION AND CONCLUSION: The train derailment resulted in a highly atypical sequence-of-events. In addition to exposure in the direct vicinity of the site of the train derailment, exposure also occurred via the sewage system, into which acrylonitrile had entered shortly after the accident.

%B Toxicol Lett %V 231 %P 344-51 %8 2014 Dec 15 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/25223249?dopt=Abstract %R 10.1016/j.toxlet.2014.09.009 %0 Generic %D 2014 %T Steroid-like activity of migration products from non-polycarbonate plastic baby bottles %A Simon,C. %A Onghena,M. %A Covaci,A. %A Els Van Hoeck %A Joris Van Loco %A M. Elskens %A Vandermarken,T. %A Heidi Demaegdt %A Van Langenhove,K. %A Birgit Mertens %A Karine Vandermeiren %A Marie-Louise Scippo %K Activity %K Babies %K Baby bottles %K Congresses %K endocrine activity %K European %K Migration %K plastics %K PRODUCTS %K Societies %K Society %K Toxicology %B Eurotox 2014: 50th Congress of the European Societies of Toxicology %I NA %C NA %8 10/9/2014 %G eng %N British Toxicology Society %1 2301 %2 7-10/09/2014 %0 Report %D 2014 %T Study of the possible migration risks of food contact materials for children under 3 years %A Els Van Hoeck %A Birgit Mertens %A Luc Verschaeve %A Simon,C. %A Marie-Louise Scippo %A Onghena,M. %A Covaci,A. %A Heidi Demaegdt %A L. Pussemier %A Karine Vandermeiren %A Vandermarken,T. %A Van Langenhove,K. %A M. Elskens %A Joris Van Loco %K CHILDREN %K CONTACT %K food %K food contact %K food contact material %K food contact materials %K Migration %K risk %K risks %K study %I WIV-ISP %C Brussels %P 137 %8 30/10/2016 %G eng %M D/2016/2505/21 %1 2306 %0 Generic %D 2014 %T Study on the implications on the requirements for submission of toxicological information, restrictions of use and administrative consequences of a revised guidelines on Food Contact Materials. %A Els Van Hoeck %A Birgit Mertens %K consequences %K CONTACT %K food %K food contact %K food contact material %K food contact materials %K Group %K Guidelines %K implication %K IMPLICATIONS %K INFORMATION %K ON %K petition %K Requirements %K restriction %K restrictions %K revised guidelines %K study %K use %K working group %B Working Group on Food Contact Materials %I NA %C NA %8 19/6/2014 %G eng %N European Food Safety Authority %1 2303 %2 19/06/2014 %0 Report %D 2013 %T Advice of the Belgian Biosafety Advisory Council on the aplication EFSA/GMO/NL/2012/107 from Monsanto under regulation (EC) No 1829/2003 %A Birgit Mertens %A Smet,P. %K Belgian %K biosafety %K GMO %K ON %K regulation %K Toxicology %I Belgian Biosafety Advisory Council %C Brussels %P 6 %8 25/1/2013 %G eng %1 35237 %0 Generic %D 2013 %T In vitro model to study the endocrine disrupting activity of migration products from plastic food contact materials %A Simon, C. %A Onghena,M. %A Covaci,A. %A Els Van Hoeck %A Joris Van Loco %A Elskens, M. %A Heidi Demaegdt %A Birgit Mertens %A Scippo, M.L. %K Migration %K plastic material %K xenoestrogen %X

Bisphenol A (BPA) is a chemical compound mainly used for the manufacture of plastic such as polycarbonate. This transparent thermoplastic polymer is used for the fabrication of several food containers like baby bottle … BPA can migrate into food in contact with polycarbonate. There is a worldwide concern about BPA because several studies have shown endocrine disruptor potency of BPA causing possible adverse health effects.
In January 2011, the European Commission decided to ban the use of polycarbonate to manufacture baby feeding bottles. In a recent opinion, the Superior Health Council’s issued its concern regarding the currently use of alternatives to polycarbonate in these materials.
This work is part of the ALTPOLYCARB project which aims to study the migration products of alternative to polycarbonate and their endocrine disruptor activities.
The first part was to have an overview of the different polymers replacing polycarbonate, that are used on the Belgian market, it resulted in the conclusion that polymers used for the manufacture of baby bottles are mainly polypropylene, polyethersulfone, silicone, polyamide, polystyrene, and melamine. The second part of this work will be to evaluate the endocrine disruptor activity(ies) of global migration residues obtained from different kinds of baby bottles. This (these) activity(ies) will be explored using cell based transactivational assays also named “reporter gene assays. The MCF7 recombinant cells used here are genitically modified cells containing the firefly luciferase gene, as a reporter gene, and a DNA responsive element specific to the human oestrogen receptor. The biological activity of a chemical compound is monitored by the measurement of light emitted by the cells exposed to it (after addition of luciferin, the substrate of luciferase).
In a preliminary step, we first screened pure substances which were shown to migrate from plastic baby bottle, in a recent study performed by Simoneau & al, 2012 .
Human estrogen receptor agonistic and antagonistic activities of 25 pure compounds were measured using MCF7-ER cells (genetically modified MCF7 cells). After the first screening, some substances clearly show an activity such as BPA, Benzophenone, 2-Propenoic acid-2-ethylhexyl ester, Benzaldehyde-4-methylthio, Butylated hydroxytoluene and Dodecanoic acid, methyl ester whereas others ask an in-depth analysis to confirm their activity. For active substances only the study will be continued and a full dose-response curve will be performed in order to assess quantitatively the activity

%B 7th BioDetectors 2013 « Dioxins/PCBs/POPs, Endocrine disrupters (EDCs), obesogens and emerging pollutants » %I 7th BioDetectors 2013 « Dioxins/PCBs/POPs, Endocrine disrupters (EDCs), obesogens and emerging pollutants » %C Istanbul, Turkey %8 6/11/2013 %G eng %0 Journal Article %J Phytother Res %D 2013 %T Investigation into the genotoxicity of water extracts from Hypoxis species and a commercially available Hypoxis preparation. %A Luc Verschaeve %A Birgit Mertens %A Ndhlala, A R %A Anthonissen, R %A Gorissen, B %A Van Staden, J %K Comet Assay %K DNA Damage %K Humans %K Hypoxis %K Mutagenicity Tests %K Mutagens %K Plant Extracts %X

We performed an in vitro evaluation of the genotoxic potential of water extracts from four Hypoxis species (Hypoxis hemerocallidea, H. colchicifolia, H. rigidula, H. acuminata) and a commercial preparation thereof using the neutral red uptake (NRU) assay, the alkaline comet assay and the cytome assay in human hepatoma HepG2 cells. The relative cytotoxicity of these samples was established by determining their NI50 values (50% inhibition of NRU), and these results were used for dose-finding in genotoxicity tests. None of the tested extracts were identified as genotoxic in both the alkaline comet assay and cytome assay.

%B Phytother Res %V 27 %P 350-6 %8 2013 Mar %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/22592975?dopt=Abstract %R 10.1002/ptr.4732 %0 Generic %D 2013 %T Study of the estrogenicity of migration products from plastic contact materials %A Simon,C. %A Onghena,M. %A Covaci,A. %A Els Van Hoeck %A Joris Van Loco %A M. Elskens %A Heidi Demaegdt %A Birgit Mertens %A Marie-Louise Scippo %K analysi %K analysis %K Baby bottles %K CONTACT %K estrogenicity %K food %K Food Analysis %K Migration %K PRODUCTS %K study %K trend %K trends %X presentation at Symposium 'Trends in Food Analysis VII' 2013 Gent Belgium %B Trends in Food Analysis VII %I NA %C NA %8 19/9/2013 %G eng %N KVCV %1 2177 %2 19/09/2013 %0 Journal Article %J Eur.J.Med.Chem. %D 2013 %T Synthesis and antimycobacterial activity of analogues of the bioactive natural products sampangine and cleistopholine36497 %A Claes,P. %A Davie Cappoen %A Mbala,B.M. %A J. Jacobs %A Birgit Mertens %A Vanessa Mathys %A Luc Verschaeve %A K Huygen %A N. De Kimpe %K acute toxicity %K antibiotics %K Cleistopholine %K Pyridinium ylids %K Sampangine %K Tuberculosis %X

Identification and investigation of novel classes and compounds for the treatment of tuberculosis remains of utmost importance in the fight against the disease. Despite many efforts, the weakly gram positive Mycobacterium tuberculosis keeps demanding its toll in human lives. For this reason a small library of substituted and unsubstituted aza analogues of cleistopholine and sampangine were synthesized in a short and straightforward manner and tested in vitro against M.tb. The compounds showed promising activity against the M.tb H37Rv strain and Minimal Inhibitory Concentrations (MIC) could be observed as low as 0.88 muM. Accompanied by moderate acute toxicity against C3A hepatocytes, the therapeutic index showed an acceptable range. Further tests confirmed the inhibition by up to 74% of intracellular growth of M.tb inside macrophages conferred by 1-hydroxybenzo[g]isoquinoline-5,10-diones. Activity of the library against other clinically relevant mycobacterial species such as Mycobacterium bovis, Mycobacterium avium and Mycobacterium ulcerans was confirmed. Furthermore the activity against a multi-drug-resistant MDR LAM-1 M.tb strain was tested and the MIC value situated around 1 muM. The lacking genotoxicity of a group of enamine substituted cleistopholine analogues indicates this group as a hit and encourages their use as a scaffold for further studies

%B Eur.J.Med.Chem. %V 67 %P 98 - 110 %8 0/9/2013 %G eng %1

36497

%& 98 %R http://dx.doi.org/10.1016/j.ejmech.2013.06.010 %0 Report %D 2012 %T Advies van de Hoge Gezondheidsraad nr. 8310: Veiligheid van oliën en vetten: enkele praktische aanbevelingen %A D. Brasseur %A Carpentier,Y. %A Fondu,M. %A A Huyghebaert %A Kolanowski,J. %A Larondelle,Y. %A Maghuin-Rogister,G. %A Birgit Mertens %A J. Nève %A Paquot,M. %A L. Pussemier %A Joris Van Loco %A Vansant,G. %K aanbevelingen %K de %K olie %K vetten %K voedingsaanbevelingen %I Hoge Gezondheidsraad %C Brussel %P 4 %8 4/7/2012 %G eng %1 35217 %0 Journal Article %J Neuropharmacology %D 2012 %T Differential modulations of striatal tyrosine hydroxylase and dopamine metabolism by cannabinoid agonists as evidence for functional selectivity in vivo. %A Bosier,B. %A Muccioli,G.G. %A Birgit Mertens %A Sarre,S. %A Michotte,Y. %A Didier M. Lambert %A Hermans,E. %K access %K Activity %K Adult %K Agonist-selective coupling %K an %K analysi %K analysis %K AS %K brain %K cause %K CB1 cannabinoid receptor %K Control %K data %K Dopamine %K DRUG %K effect %K effects %K evidence %K exposure %K expression %K Functional %K G protein %K GPCR %K Increase %K IS %K metabolism %K metabolites %K ON %K rats %K Reduction %K regulation %K report %K response %K structure %K System %K Transmission %K trend %K Tyrosine hydroxylase %X It is generally assumed that cannabinoids induce transient modulations of dopamine transmission through indirect regulation of its release. However, we previously described a direct cannabinoid-mediated control of tyrosine hydroxylase (TH) expression, %B Neuropharmacology %V 62(7) %P 2328 - 2336 %8 13/2/2012 %G eng %1 35216 %& 2328 %R http://dx.doi.org/10.1016/j.neuropharm.2012.02.003 %0 Generic %D 2012 %T Genotoxicity of water extracts from hypoxis species %A R. Anthonissen %A Ndhlala,A.R. %A Birgit Mertens %A Van Staden,J. %A Luc Verschaeve %K Comet Assay %K cytome assay %K genotoxicity %K Hypoxis %X

There is a continuous search for new medication against many diseases. The main reason is that existing remedies have unwanted side-effects and that they may lose their efficacy with time. Traditional medicinal plants are seen as an important source of possible new and interesting therapeutic drugs. Many of these plants, or preparations thereof, have shown their efficacy over the years but they have not been screened for potential adverse health effects as is the practice for modern medicines. It is therefore important to test such plants or their extracts for potential effects on health. We therefore investigated the genotoxicity of a number of Hypoxis species. This is important as preparations from them were highly promoted in the popular press in South Africa as agents that can also boost immunity in HIV/AIDS patients. Yet, there are unconfirmed reports of toxic properties and hence warnings against the use of Hypoxis and their products.We performed an in vitro evaluation of the genotoxic potential of water extracts from the Hypoxis species Hypoxis hemerocallidea, H. colchicifolia, H. rigidula and H. acuminata and from a commercial preparation thereof using the neutral red uptake (NRU) assay, the alkaline comet assay and the cytome assay in human hepatoma HepG2 cells. The relative cytotoxicity of these samples was established by determining their NI50 values (50% inhibition of NRU), and these results were used for dose-finding in genotoxicity tests. None of the tested extracts were identified as genotoxic in both the alkaline comet assay and cytome assay.

%B ESTIV 2012 %C Lissabon, Portugal %8 0/0/2012 %G eng %N European Society of Toxicology in vitro %2

16-10-2012- 19-10-2012

%0 Report %D 2012 %T Publicatie van de Hoge Gezondheidsraad nr. 8666: Transvetzuren van industriële oorsprong %A D. Brasseur %A Carpentier,Y. %A G. De Backer %A S. De Henauw %A Fondu,M. %A A Huyghebaert %A Kolanowski,J. %A Larondelle,Y. %A Maghuin-Rogister,G. %A Birgit Mertens %A J. Nève %A Paquot,M. %A Paquot,N. %A Joris Van Loco %A Vansant,G. %K aanbevelingen %K de %K risico analyse %K transvetzuren %K transvetzuren van industriële oorsprong %K vetten %K vetzuren %K voeding %K voedingsaanbevelingen %K wetgeving voeding %I Hoge Gezondheidsraad %C Brussel %P 14 %8 4/7/2012 %G eng %1 35218 %0 Thesis %D 2012 %T Studie naar het effect van titaandioxide nanopartikels op oxidatieve stress in twee verschillende caco-2 celsystemen %A De Meuter,B. %E Birgit Mertens %E V Rogiers %K AAN %K blootstelling %K CaCo-2 %K de %K effect %K Hand %K in vitro celsysteem %K IS %K MEN %K nanopartikels %K oxidatieve stress %K Ratio %K stress %K voeding %X De bijzondere eigenschappen en kleine afmetingen in vergelijking met bulk materiaal maken nanopartikels interessant voor uiteenlopende toepassingen. Er wordt dan ook verwacht dat de blootstelling van de mens aan nanopartikels in de nabije toekomst sterk zal toenemen. Onderzoek naar de mogelijke schadelijke effecten van deze partikels is bijgevolg noodzakelijk. Door hun bijzondere eigenschappen kunnen nanopartikels zich immers anders gedragen wanneer ze in het menselijk lichaam terecht komen. Nanopartikels zijn door hun hoge oppervlakte-volume ratio bijvoorbeeld reactiever dan bulk materiaal waardoor ze de productie van ROS kunnen induceren. Indien een verstoord evenwicht tussen ROS en de antioxidans mechanismen van de cel ontstaat, kan dit resulteren in een toestand van oxidatieve stress met uiteindelijk celschade tot gevolg.Een domein waar het gebruik en de verwerking van nanopartikels een opmars maakt, is de voedingssector. TiO %7 55 %I Vrije Universiteit Brussel %C Brussel %P 55 %8 11/6/2012 %G eng %1 35223 %0 Journal Article %J South African Journal of Botany %D 2011 %T Toxic and mutagenic properties of extracts from Tunisian traditional medicinal plants investigated by the neutral red uptake, VITOTOX and alkaline comet assays %A Edziri, H. %A Mastouri, M. %A Mahjoub, A. %A R. Anthonissen %A Birgit Mertens %A Cammaerts, S. %A Gevaert, L. %A Luc Verschaeve %K Comet test; Marrubium alysson L. %K NRU test; Peganum harmala L. %K Retama raetam (Forsk.) Webb %K Tunisian medicinal plants %K Vitotox test %B South African Journal of Botany %V 77 %8 Jan-08-2011 %G eng %N 3 %& 703 %R 10.1016/j.sajb.2011.03.007 %0 Generic %D 0 %T Development of a semi-automated workflow including (Q)SAR models to support the risk assessment of non-evaluated food contact material substances %A Camille Streel %A Ilse Van Overmeire %A Gianluca Selvestrel %A Roncaglioni, Alessandra %A Benfenati, Emilio %A Els Van Hoeck %A Birgit Mertens %G eng %0 Generic %D 0 %T Development of a tool combining migration modelling and hazard predictions by QSAR models to support the risk assessment of substances migrating from food contact materials %A Ilse Van Overmeire %A G. Selvestrel %A P Ciffroy %A A Manganaro %A B Alfonso %A Camille Streel %A E. Benfenati %A Els Van Hoeck %A B Mertens %G eng %0 Generic %D 0 %T Integrating VEGA QSAR models in an automated tool to support the risk assessment of non-evaluated food contact material substances %A Ilse Van Overmeire %A Camille Streel %A G Selvestrel %A Roncaglioni, Alessandra %A Benfenati, Emilio %A A Sommovigo %A A Manganaro %A Els Van Hoeck %A Birgit Mertens %B QSAR2023 %8 2023 %G eng %0 Generic %D 0 %T VERMEER FCM: a tool combining migration modelling and in silico hazard predictions for substances migrating from food contact materials %A Ilse Van Overmeire %A G. Selvestrel %A P. Ciffroy %A A Manganaro %A B Alfonso %A Camille Streel %A E. Benfenati %A Els Van Hoeck %A Birgit Mertens %G eng