Scientific Institute of Public Health IPH

Brussels, Belgium

Scientific Institute of Public Health IPH

Brussels, Belgium
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Ates G.,Vrije Universiteit Brussel | Steinmetz F.P.,Liverpool John Moores University | Doktorova T.Y.,Scientific Institute of Public Health IPH | Madden J.C.,Liverpool John Moores University | Rogiers V.,Vrije Universiteit Brussel
Regulatory Toxicology and Pharmacology | Year: 2016

To characterize the risk of cosmetic ingredients when threshold toxicity is assumed, often the "margin of safety" (MoS) is calculated. This uncertainty factor is based on the systemic no observable (adverse) effect level (NO(A)EL) which can be derived from in vivo repeated dose toxicity studies. As in vivo studies for the purpose of the cosmetic legislation are no longer allowed in Europe and a validated in vitro alternative is not yet available, it is no longer possible to derive a NO(A)EL value for a new cosmetic ingredient. Alternatively, cosmetic ingredients with a low dermal bioavailability might not need repeated dose data, as internal exposure will be minimal and systemic toxicity might not be an issue. This study shows the possibility of identifying compounds suspected to have a low dermal bioavailability based on their physicochemical properties (molecular weight, melting point, topological polar surface area and log P) and their in vitro dermal absorption data. Although performed on a limited number of compounds, the study suggests a strategic opportunity to support the safety assessor's reasoning to omit a MoS calculation and to focus more on local toxicity and mutagenicity/genotoxicity for ingredients for which limited systemic exposure is to be expected. © 2016 Elsevier Inc..


Vlieghe E.R.,Institute of Tropical Medicine | de Smet B.,Institute of Tropical Medicine | Bertrand S.,Scientific Institute of Public Health IPH | Vanhoof R.,Scientific Institute of Public Health IPH | And 3 more authors.
PLoS Neglected Tropical Diseases | Year: 2012

Background: Salmonella enterica is a frequent cause of bloodstream infection (BSI) in Asia but few data are available from Cambodia. We describe Salmonella BSI isolates recovered from patients presenting at Sihanouk Hospital Centre of Hope, Phnom Penh, Cambodia (July 2007-December 2010). Methodology: Blood was cultured as part of a microbiological prospective surveillance study. Identification of Salmonella isolates was performed by conventional methods and serotyping. Antibiotic susceptibilities were assessed using disk diffusion, MicroScan and E-test macromethod. Clonal relationships were assessed by Pulsed Field Gel Electrophoresis; PCR and sequencing for detection of mutations in Gyrase and Topoisomerase IV and presence of qnr genes. Principal Findings: Seventy-two Salmonella isolates grew from 58 patients (mean age 34.2 years, range 8-71). Twenty isolates were identified as Salmonella Typhi, 2 as Salmonella Paratyphi A, 37 as Salmonella Choleraesuis and 13 as other non-typhoid Salmonella spp. Infection with human immunodeficiency virus (HIV) was present in 21 of 24 (87.5%) patients with S. Choleraesuis BSI. Five patients (8.7%) had at least one recurrent infection, all with S. Choleraesuis; five patients died. Overall, multi drug resistance (i.e., co-resistance to ampicillin, sulphamethoxazole-trimethoprim and chloramphenicol) was high (42/59 isolates, 71.2%). S. Typhi displayed high rates of decreased ciprofloxacin susceptibility (18/20 isolates, 90.0%), while azithromycin resistance was very common in S. Choleraesuis (17/24 isolates, 70.8%). Two S. Choleraesuis isolates were extended spectrum beta-lactamase producer. Conclusions and Significance: Resistance rates in Salmonella spp. in Cambodia are alarming, in particular for azithromycin and ciprofloxacin. This warrants nationwide surveillance and revision of treatment guidelines. © 2012 Vlieghe et al.


Desmedt B.,Scientific Institute of Public Health IPH | Desmedt B.,Vrije Universiteit Brussel | Rogiers V.,Vrije Universiteit Brussel | Courselle P.,Scientific Institute of Public Health IPH | And 3 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2013

During the last years, the EU market is flooded by illegal cosmetics via the Internet and a so-called "black market". Among these, skin-bleaching products represent an important group. They contain, according to the current European cosmetic legislation (Directive 76/768/EEC), a number of illegal active substances including hydroquinone, tretinoin and corticosteroids. These may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. To control this market there is a need for a fast screening method capable of detecting illegal ingredients in the wide variety of existing bleaching cosmetic formulations.In this paper the development and validation of an ultra high pressure liquid chromatographic (UHPLC) method is described. The proposed method makes use of a Waters Acquity BEH shield RP18 column with a gradient using 25. mM ammonium borate buffer (pH 10) and acetonitrile.This method is not only able to detect the major illegal (hydroquinone, tretinoin and six dermatologic active corticosteroids) and legal whitening agents, the latter having restrictions with respect to concentration and application (kojic acid, arbutin, nicotinamide and salicylic acid), but can also quantify these in a run time of 12. min.The method was successfully validated using the "total error" approach in accordance with the validation requirements of ISO-17025.During the validation a variety of cosmetic matrices including creams, lotions and soaps were taken into consideration. © 2013 Elsevier B.V.


Deconinck E.,Scientific Institute of Public Health IPH | Crevits S.,Scientific Institute of Public Health IPH | Baten P.,Scientific Institute of Public Health IPH | Courselle P.,Scientific Institute of Public Health IPH | De Beer J.,Scientific Institute of Public Health IPH
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011

A fully validated UHPLC method for the identification and quantification of folic acid in pharmaceutical preparations was developed. The starting conditions for the development were calculated starting from the HPLC conditions of a validated method. These start conditions were tested on four different UHPLC columns: Grace Vision HT™ C18-P, C18, C18-HL and C18-B (2 mm × 100. mm, 1.5 μm). After selection of the stationary phase, the method was further optimised by testing two aqueous and two organic phases and by adapting to a gradient method. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests.A UHPLC method was obtained for the identification and quantification of folic acid in pharmaceutical preparations, which will cut analysis times and solvent consumption. © 2010 Elsevier B.V.


Desmedt B.,Scientific Institute of Public Health IPH | Desmedt B.,Vrije Universiteit Brussel | Van Hoeck E.,Scientific Institute of Public Health IPH | Rogiers V.,Vrije Universiteit Brussel | And 4 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

An important group of suspected illegal cosmetics consists of skin bleaching products, which are usually applied to the skin of the face, hands and décolleté for local depigmentation of hyper pigmented regions or more importantly, for a generalized reduction of the skin tone. These cosmetic products are suspected to contain illegal active substances that may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. In that respect, illegal and restricted substances in cosmetics, known to have bleaching properties, are in particular hydroquinone, tretinoin and corticosteroids. From a legislative point of view, all cosmetic products containing a prohibited whitening agent are illegal and must be taken off the EU market. A newly developed screening method using ultra high performance liquid chromatography-time off flight-mass spectrometry allows routine analysis of suspected products.163 suspected skin whitening cosmetics, collected by Belgian inspectors at high risk sites such as airports and so-called ethnic cosmetic shops, were analyzed and 59% were classified as illegal. The whitening agents mostly detected were clobetasol propionate and hydroquinone, which represent a serious health risk when repeatedly and abundantly applied to the skin. © 2013 Elsevier B.V.


Deconinck E.,Scientific Institute of Public Health IPH | Sacre P.Y.,Scientific Institute of Public Health IPH | Baudewyns S.,Scientific Institute of Public Health IPH | Courselle P.,Scientific Institute of Public Health IPH | De Beer J.,Scientific Institute of Public Health IPH
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011

A fully validated UHPLC method for the identification and quantification of pharmaceutical preparations, containing paracetamol and/or acetyl salicylic acid, combined with anti-histaminics (phenylephrine, pheniramine maleate, diphenhydramine, promethazine) and/or other additives as quinine sulphate, caffeine or codein phosphate, was developed. The proposed method uses a Waters Acquity BEH C18 column (2. mm × 100. mm, 1.7 μm) with a gradient using an ammonium acetate buffer pH 4.0 as aqueous phase and methanol as organic modifier. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were respectively smaller than 1.5% and 2%, the β-expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were smaller than 5% for all of the considered components. A UHPLC method was obtained for the identification and quantification of these kind of pharmaceutical preparations, which will significantly reduce analysis times and workload for the laboratories charged with the quality control of these preparations. © 2011 Elsevier B.V.


Querci M.,European Commission - Joint Research Center Ispra | Van Den Bulcke M.,Scientific Institute of Public Health IPH | Zel J.,Slovenian National Institute of Biology | Van Den Eede G.,European Commission - Joint Research Center Ispra | Broll H.,Federal Institute for Risk Assessment BfR
Analytical and Bioanalytical Chemistry | Year: 2010

The steady rate of development and diffusion of genetically modified plants and their increasing diversification of characteristics, genes and genetic control elements poses a challenge in analysis of genetically modified organisms (GMOs). It is expected that in the near future the picture will be even more complex. Traditional approaches, mostly based on the sequential detection of one target at a time, or on a limited multiplexing, allowing only a few targets to be analysed at once, no longer meet the testing requirements. Along with new analytical technologies, new approaches for the detection of GMOs authorized for commercial purposes in various countries have been developed that rely on (1) a smart and accurate strategy for target selection, (2) the use of high-throughput systems or platforms for the detection of multiple targets and (3) algorithms that allow the conversion of analytical results into an indication of the presence of individual GMOs potentially present in an unknown sample. This paper reviews the latest progress made in GMO analysis, taking examples from the most recently developed strategies and tools, and addresses some of the critical aspects related to these approaches. © 2009 Springer-Verlag.


Deconinck E.,Scientific Institute of Public Health IPH | Sacre P.Y.,Scientific Institute of Public Health IPH | Sacre P.Y.,University of Liège | Coomans D.,Vrije Universiteit Brussel | De Beer J.,Scientific Institute of Public Health IPH
Journal of Pharmaceutical and Biomedical Analysis | Year: 2012

Classification trees built with the Classification And Regression Tree algorithm were evaluated for modelling infrared spectroscopic data in order to discriminate between genuine and counterfeit drug samples and to classify counterfeit samples in different classes following the RIVM classification system.Models were built for two data sets consisting of the Fourier Transformed Infrared spectra, the near infrared spectra and the Raman spectra for genuine and counterfeit samples of respectively Viagra ® and Cialis ®.Easy interpretable models were obtained for both models. The models were validated for their descriptive and predictive properties. The predictive properties were evaluated using both cross validation as an external validation set. The obtained models for both data sets showed a 100% correct classification for the discrimination between genuine and counterfeit samples and 83.3% and 100% correct classification for the counterfeit samples for the Viagra ® and the Cialis ® data set respectively. © 2011 Elsevier B.V.


Deconinck E.,Scientific Institute of Public Health IPH | Verlinde K.,Scientific Institute of Public Health IPH | Courselle P.,Scientific Institute of Public Health IPH | De Beer J.O.,Scientific Institute of Public Health IPH
Journal of Pharmaceutical and Biomedical Analysis | Year: 2012

A fully validated UHPLC-DAD method for the identification and quantification of pharmaceutical preparations, containing molecules frequently found in illegal slimming products (sibutramine, modafinil, ephedrine, nor-ephedrine, metformin, theophyllin, caffeine, diethylpropion and orlistat) was developed. The proposed method uses a Vision HT C18-B column (2 mm × 100 mm, 1.5 μm) with a gradient using an ammonium acetate buffer pH 5.0 as aqueous phase and acetonitrile as organic modifier. The obtained method was fully validated based on its measurement uncertainty (accuracy profile). Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were respectively smaller than 3.0% and 1.5%, the β-expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were smaller than 3% for all of the considered components. A UHPLC-DAD method was obtained for the identification and quantification of these kind of pharmaceutical preparations, which will significantly reduce analysis times and workload for the laboratories charged with the quality control of these preparations and which can, if necessary, be coupled to a MS-detector for a more thorough characterisation. © 2011 Elsevier B.V.


Cochez C.,Queen Astrid Military Hospital | Ducoffre G.,Scientific Institute of Public Health IPH | Vandenvelde C.,Queen Astrid Military Hospital | Luyasu V.,Catholic University of Leuven | Heyman P.,Queen Astrid Military Hospital
Ticks and Tick-borne Diseases | Year: 2011

Human granulocytic anaplasmosis (HGA) is a tick-borne rickettsial infection of neutrophils caused by Anaplasma phagocytophilum. Although the pathogen was known as a veterinary agent as early as 1932, the link with human disease was first established in 1990. In the past decennium, the involvement of HGA as an important and frequent cause of fever with a history of tick bite was increasingly recognized in many regions of Europe.This paper presents a 10-year A. phagocytophilum serosurveillance (2000-2009), wherein 1672 serum samples were tested and 418 were found positive. A total of 111 patients had a history of tick bite, fever, and at least a 4-fold rise in titre and are thus considered to be confirmed cases. These findings suggest that Belgium is a hot spot for HGA infections. © 2011 Elsevier GmbH.

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