The analysis and detection of new psychoactive substances in biological matrices

New psychoactive substances (NPSs) have appeared on the recreational drug market at an unprecedented rate in recent years. Many are not new drugs but failed products of the pharmaceutical industry. The speed and variety of drugs entering the market poses a new complex challenge for the forensic toxicology community. The detection of these substances in biological matrices can be difficult as the exact compounds of interest may not be known. Many NPS are sold under the same brand name and therefore users themselves may not know what substances they have ingested. The majority of analytical methods for the detection of NPSs tend to focus on a specific class of compounds rather than a wide variety. In response to this, a robust and sensitive method was developed for the analysis of various NPS by solid phase extraction (SPE) with gas chromatography mass spectrometry (GCMS). Sample preparation and derivatisation were optimised testing a range of SPE cartridges and derivatising agents, as well as derivatisation incubation time and temperature. The final gas chromatography mass spectrometry method was validated in accordance with SWGTOX 2013 guidelines over a wide concentration range for both blood and urine for 23 and 25 analytes respectively. This included the validation of 8 NBOMe compounds in blood and 10 NBOMe compounds in urine. This GC-MS method was then applied to 8 authentic samples with concentrations compared to those originally identified by NMS laboratories. The rapid influx of NPSs has resulted in the re-analysis of samples and thus, the stability of these substances is crucial information. The stability of mephedrone was investigated, examining the effect that storage temperatures and preservatives had on analyte stability daily for 1 week and then weekly for 10 weeks. Several laboratories identified NPSs use through the cross-reactivity of these substances with existing screening protocols such as ELISA. The application of Immunalysis ketamine, methamphetamine and amphetamine ELISA kits for the detection of NPS was evaluated. The aim of this work was to determine if any cross-reactivity from NPS substances was observed, and to determine whether these existing kits would identify NPS use within biological samples. The cross- reactivity of methoxetamine, 3-MeO-PCE and 3-MeO-PCP for different commercially point of care test (POCT) was also assessed for urine. One of the newest groups of compounds to appear on the NPS market is the NBOMe series. These drugs pose a serious threat to public health due to their high potency, with fatalities already reported in the literature. These compounds are falsely marketed as LSD which increases the chance of adverse effects due to the potency differences between these 2 substances. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was validated in accordance with SWGTOX 2013 guidelines for the detection for 25B, 25C and 25I-NBOMe in urine and hair. Long-Evans rats were administered 25B-, 25C- and 25I-NBOMe at doses ranging from 30-300 µg/kg over a period of 10 days. Tail flick tests were then carried out on the rats in order to determine whether any analgesic effects were observed as a result of dosing. Rats were also shaved prior to their first dose and reshaved after the 10-day period. Hair was separated by colour (black and white) and analysed using the validated LC-MS/MS method, assessing the impact hair colour has on the incorporation of these drugs. Urine was collected from the rats, analysed using the validated LC-MS/MS method and screened for potential metabolites using both LC-MS/MS and quadrupole time of flight (QToF) instrumentation.

Is there a relation between environmental exposure to teratogenic substances during pregnancy and congenital anomalies in the newborn? A pilot study in Portugal

Background: Maternal occupation as a proxy of environmental exposure has been consistently associated with specific congenital anomalies (CA) in the foetus and newborn. On the other hand, geographical location of the mother such as place of residence and place of work have not been used as proxy for environmental exposures during pregnancy. We designed a pilot study aiming to investigate the association between maternal place of residence and workplace during pregnancy and CA in Portugal. Methods: Cases and controls are identified in the maternity unit. Cases are all live births with at least one CA delivered in the Barreiro hospital located in a heavy industrial area near Lisboa. Controls are the two normal births following each case. Residents outside the study area, stillbirths and women who decline to participate or are incapable of giving consent are excluded. A health professional interviews the mothers using a questionnaire adapted from the registry form of the Portuguese national registry of CA and includes information on places during pregnancy (residence, workplace, leisure), and demographic characterization as place of birth, infant sex, weight, description of CA, age of mother, ethnicity, maternal birth place. Maternal health and obstetric history, education, smoking, alcohol, drugs and medication use is also collected as potential confounders. Results: The pilot study started in January 2016 and at the moment two cases and four controls have been recruited without refusals. The study will continue to be implemented and it is proposed to start in other hospital units during 2016.

Report to the director, National Center for Radiological Health, Public Health Service, on environmental contamination by radioactive substances, December 1, 1967.

Mode of access: Internet.

Étude d’évaluabilité et évaluation des processus et des effets d’un programme de prévention de l’usage de substances psychoactives lors de la transition primaire-secondaire

La mise en œuvre d’activités de prévention de la consommation de substances psychoactives (SPA) (tabac, alcool et cannabis) en milieu scolaire est une stratégie couramment utilisée pour rejoindre un grand nombre de jeunes. Ces activités s’inspirent, soit de programmes existant, soit d’innovations dictées par le contexte d’implantation ou l’existence de données de recherche. Dans un cas comme dans l’autre, l’évaluation de ces programmes représente la meilleure voie pour mesurer leur efficacité et/ou connaître comment ceux-ci sont implantés. C’est cet impératif qui a motivé une commission scolaire du Québec a recommandé l’évaluation de l’Intervention en Réseau (IR), un programme développé en vue de retarder l’âge d’initiation et de réduire la consommation problématique de SPA chez les élèves. Ce programme adopte une approche novatrice avec pour principal animateur un intervenant pivot (IP) qui assure le suivi des élèves de la 5e année du primaire jusqu’en 3e secondaire. Inspiré des modèles en prévention de la santé et de l’Approche École en santé (AES), le rôle de l’IP ici se démarque de ceux-ci. Certes, il est l’interface entre les différents acteurs impliqués et les élèves mais dans le cadre du programme IR, l’IP est intégré dans les écoles primaires et secondaires qu’il dessert. C’est cet intervenant qui assure la mobilisation des autres acteurs pour la mise en œuvre des activités. Cette thèse vise à rendre compte de ce processus d’évaluation ainsi que des résultats obtenus. L’approche d’évaluation en est une de type participatif et collaboratif avec des données quantitatives et qualitatives recueillies par le biais de questionnaires, d’entrevues, de groupes de discussion, d’un journal de bord et de notes de réunions. Les données ont été analysées dans le cadre de trois articles dont le premier concerne l’étude d’évaluabilité (ÉÉ) du programme. Les participants de cette ÉÉ sont des acteurs-clés du programme (N=13) rencontrés en entrevues. Une analyse documentaire (rapports et journal de bord) a également été effectuée. Cette ÉÉ a permis de clarifier les intentions des initiateurs du programme et les objectifs poursuivis par ces derniers. Elle a également permis de rendre la théorie du programme plus explicite et de développer le modèle logique, deux éléments qui ont facilité les opérations d’évaluation qui ont suivi. Le deuxième article porte sur l’évaluation des processus en utilisant la théorie de l’acteur-réseau (TAR) à travers ses quatre moments du processus de traduction des innovations (la problématisation, l’intéressement, l’enrôlement et la mobilisation des alliés), l’analyse des controverses et du rôle des acteurs humains et non-humains. Après l’analyse des données obtenues par entrevues auprès de 19 informateurs-clés, les résultats montrent que les phases d’implantation du programme passent effectivement par les quatre moments de la TAR, que la gestion des controverses par la négociation et le soutien était nécessaire pour la mobilisation de certains acteurs humains. Cette évaluation des processus a également permis de mettre en évidence le rôle des acteurs non-humains dans le processus d’implantation du programme. Le dernier article concerne une évaluation combinée des effets (volet quantitatif) et des processus (volet qualitatif) du programme. Pour le volet quantitatif, un devis quasi-expérimental a été adopté et les données ont été colligées de façon longitudinale par questionnaires auprès de 901 élèves de 5e et 6e année du primaire et leurs enseignants de 2010 à 2014. L’analyse des données ont montré que le programme n’a pas eu d’effets sur l’accessibilité et les risques perçus, l’usage problématique d’alcool et la polyconsommation (alcool et cannabis) chez les participants. Par contre, les résultats suggèrent que le programme pourrait favoriser la réduction du niveau de consommation et retarder l’âge d’initiation à l’alcool et au cannabis. Ils suggèrent également un effet potentiellement positif du programme sur l’intoxication à l’alcool chez les élèves. Quant au volet qualitatif, il a été réalisé à l’aide d’entrevues avec les intervenants (N=17), de groupes de discussion avec des élèves du secondaire (N=10) et d’une analyse documentaire. Les résultats montrent que le programme bénéficie d’un préjugé favorable de la part des différents acteurs ayant participé à l’évaluation et est bien acceptée par ces derniers. Cependant, le roulement fréquent de personnel et le grand nombre d’écoles à suivre peuvent constituer des obstacles à la bonne marche du programme. En revanche, le leadership et le soutien des directions d’écoles, la collaboration des enseignants, les qualités de l’IP et la flexibilité de la mise en œuvre sont identifiés comme des éléments ayant contribué au succès du programme. Les résultats et leur implication pour les programmes et l’évaluation sont discutés. Enfin, un plan de transfert des connaissances issues de la recherche évaluative est proposé.

Reduction capability of soil humic substances from the Rio Negro basin, Brazil, towards Hg(II) studied by a multimethod approach and principal component analysis (PCA)

This paper characterizes humic substances (HS) extracted from soil samples collected in the Rio Negro basin in the state of Amazonas, Brazil, particularly investigating their reduction capabilities towards Hg(II) in order to elucidate potential mercury cycling/volatilization in this environment. For this reason, a multimethod approach was used, consisting of both instrumental methods (elemental analysis, EPR, solid-state NMR, FIA combined with cold-vapor AAS of Hg(0)) and statistical methods such as principal component analysis (PCA) and a central composite factorial planning method. The HS under study were divided into groups, complexing and reducing ones, owing to different distribution of their functionalities. The main functionalities (cor)related with reduction of Hg(II) were phenolic, carboxylic and amide groups, while the groups related with complexation of Hg(II) were ethers, hydroxyls, aldehydes and ketones. The HS extracted from floodable regions of the Rio Negro basin presented a greater capacity to retain (to complex, to adsorb physically and/or chemically) Hg(II), while nonfloodable regions showed a greater capacity to reduce Hg(II), indicating that HS extracted from different types of regions contribute in different ways to the biogeochemical mercury cycle in the basin of the mid-Rio Negro, AM, Brazil. (c) 2007 Published by Elsevier B.V.

Direct determination of Cu, Cd, Ni and Pb in aquatic humic substances by graphite furnace atomic absorption spectrometry

A method has been developed for the direct determination of Cu, Cd, Ni and Pb in aquatic humic substances (AHS) by graphite furnace atomic absorption spectrometry. AHS were isolated from water samples rich in organic matter, collected in the Brazilian Ecological Parks. All analytical curves presented good linear correlation coefficient. The limits of detection and quantification were in the ranges 2.5-16.7 mu g g(-1) and 8.5-50.0 mu g g(-1), respectively. The accuracy was determined using recovery tests, and for all analytes recovery percentages ranged from 93 - 98 %, with a relative standard deviation less than 4 %. The results indicated that the proposed method is a suitable alternative for the direct determination of metals in AHS.

Characterization of the Interactions between Endocrine Disruptors and Aquatic Humic Substances from Tropical Rivers

Interactions between two endocrine disruptors (ED) and aquatic humic substances (AHS) from tropical rivers were studied using an ultrafiltration system equipped with a 1 kDa cut-off cellulose membrane to separate free ED from the fraction bound in the AHS. Quantification of 17 alpha-ethynylestradiol and bisphenol A was performed using gas chromatography-mass spectrometry (GC-MS). The times required for establishment of equilibrium between the AHS and the ED were ca. 30 min, and complexation capacities for 17 alpha-ethynylestradiol and bisphenol A were 18.53 and 2.07 mg g(-1) TOC, respectively. The greater interaction of AHS with 17 alpha-ethynylestradiol, compared to bisphenol A, was due to the presence of hydrogen in the structure of 17 alpha-ethynylestradiol, which could interact with ionized oxygenated groups of the AHS. The results indicate that AHS can strongly influence the transport and reactivity of endocrine disruptors in aquatic systems.

Thermal Decomposition Kinetics of Humic Substances Extracted from Mid-Rio Negro (Amazon Basin) Soil Samples

In this work humic substances (HS) extracted from non-flooded (Araca) and flooded (Iara) soils were characterized through the calculation of stability and activation energies associated with the dehydration and thermal decomposition of HS using TGA and DTA, electronic paramagnetic resonance and C/H, C/N and C/O atomic ratios. For HS extracted from flooded soils, there was evidence for the influence of humidity on the organic matter humification process. Observations of thermal behaviour, with elemental analysis, indicated the presence of fossilized organic carbon within clay particles, which only decomposed above 800 C. This characteristic could explain the different thermal stability and pyrolysis activation energies for Iara HS compared to Araca HS.

Potential valorization as fertilizers of Humic Substances extracted from landfill leachate

In this study, four leachates samples from 3 different landfills localized in the north of Portugal were characterized and fractionated, to understand the decomposition degree and to evaluate their potential as an agent for fertilization. Humic substances (HS) were extracted, quantified, chemical characterized and further fractionated in humic acid (HA) and fulvic acid (FA). Keeping in mind the purpose to use these fractions as fertilizers, the phytotoxicity of HS, HA and FA solutions was evaluated on cress seed germination. The HS concentration was similar for all the leachates evaluated and was higher than 780 mg/L of total organic carbon. All the leachates analysed registered higher FA concentration than HA. The chemical characterization indicated that HA had a relatively higher aromatic character than the FA obtained from same sources. These results suggest that the HS from landfill leachates were in an early stage of humification, once the degree of humification increase as the landfilling age increase. Overall, the HS extracts showed absence of phytotoxicity, with germination index greater than 80% for samples treated to achieve low electric conductivity values. This suggests that the HS from the leachate may be used to produce liquid organic fertilizers.

Hazardous alcohol consumption among university students in Ireland: a cross-sectional study

Objective: There is considerable evidence of a cultural shift towards heavier alcohol consumption among university students, especially women. The aim of this study is to investigate the prevalence and correlates of hazardous alcohol consumption (HAC) among university students with particular reference to gender and to compare different modes of data collection in this population. Setting: A large Irish university. Design: A cross-sectional study using a classroom distributed paper questionnaire. Participants: A total of 2275 undergraduates completed the classroom survey, 84% of those in class and 51% of those registered for the relevant module. Main outcome measures: Prevalence of HAC measured using the Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) and the proportion of university students reporting 1 or more of 13 adverse consequences linked to HAC. HAC was defined as an AUDIT-C score of 6 or more among males and 5 or more among females. Results: In the classroom sample, 66.4% (95% CI 64.4 to 68.3) reported HAC (65.2% men and 67.3% women). In women, 57.4% met HAC thresholds for men. Similar patterns of adverse consequences were observed among men and women. Students with a hazardous consumption pattern were more likely to report smoking, illicit drug use and being sexually active. Conclusions: The findings highlight the high prevalence of HAC among university students relative to the general population. Public policy measures require review to tackle the short-term and long-term risks to physical, mental and social health and well-being.

Caracterización de las condiciones de salud y de trabajo y su relación con lesiones cutáneas en los orfebres artesanales de Mompox Bolivar-Colombia 2015

INTRODUCCIÓN Las alteraciones de la salud relacionadas con el trabajo (enfermedades y accidentes), pueden prevenirse desde las actividades bien enfocadas del Sistema de Gestión de Seguridad y Salud en el Trabajo (SGSST), realizando la identificación y control de los agentes causales en el ambiente de trabajo y la vigilancia de la salud de la población trabajadora. El proyecto desarrollado va dirigido a un grupo específico de artesanos orfebres en la ciudad de Mompox, Bolivar, en la que esta labor artesanal se centra en el arte de la filigrana, transmitido generacionalmente desde antaño En esta ciudad los artesanos orfebres, aunque corresponden a un sector informal de la economía, se encuentran agremiados principalmente en tres asociaciones ubicadas en la cabecera municipal. En el desempeño de sus labores, estos profesionales del arte de la filigrana manipulan agentes químicos como el ácido nítrico, el ácido sulfúrico, la plata y el mercurio, los cuales se utilizan en las diferentes etapas del proceso que incluye técnicas propias de esta labor. Teniendo en cuenta que la información disponible en la literatura científica describe principalmente los efectos de agentes químicos en otros oficios diferentes a la población orfebre y conociendo que la exposición a estas sustancias químicas puede generar variados efectos en el organismo, el interés de este proyecto se centra específicamente en las alteraciones cutáneas posiblemente relacionadas con las condiciones de trabajo de esta población del sector informal. MATERIALES Y METODOS La presente investigación es un estudio de corte trasversal, el cual realizó una selección por conveniencia de 114 trabajadores de orfebres Momposinos con el fin de identificar la relación de las condiciones de trabajo con la presencia de alteraciones cutáneas de los trabajadores que laboran en la orfebrería artesanal en la ciudad de Mompox, departamento de Bolívar, en el año 2015, de tal manera que dejando a consideración la descripción de los hallazgos encontrados, se posibiliten futuras y precisas investigaciones e intervenciones en este colectivo de trabajadores. Los instrumentos empleados para la recolección de la información y para el cumplimento de los objetivos fueron la encuesta Nacional de Condiciones de Trabajo del Instituto Nacional de Seguridad e Higiene en el trabajo de España (INSHT) que permite recolectar información sobre la caracterización de la población a nivel sociodemográfico y ocupacional, y para la determinación de patologías dermatológicas relacionadas con el trabajo se utilizó el Cuestionario NOSQ-2002 Nórdico- Enfermedades Cutáneas de origen Laboral, en su versión validada en español. Se describieron las variables categóricas con porcentajes y las continuas (cuantitativas) con medidas de tendencia central y dispersión La asociación entre los hallazgos de exposición ocupacional y los síntomas y signos en piel, fue estimada mediante riesgos relativos. RESULTADOS El 75,4% del total de la población correspondió al género masculino y el 67,5% reportó realizar sus labores como trabajadores independientes. Respecto a la identificación de condiciones de salud, la percepción por parte de los orfebres fue positiva, reportando muy buena salud en el 34% de los mismos. El 8% de la población manifestó alteraciones dermatológicas tipo eczema en los últimos seis meses y el 11% las presentó principalmente en manos. Respecto de la iniciación del eczema, el 97% de los trabajadores reportó que se iniciaba al contacto con sustancias químicas y el 98,7% manifestó que se encontraban realizando la labor de orfebrería cuando inició el eczema. La lesión prevalente fue mancha roja sin edema (8%), seguida de ronchas o manchas y ampollas pequeñas (3%) y de piel seca con escamas (2%). CONCLUSIONES Los resultados de la presente investigación mostraron la prevalencia de alteraciones cutáneas principalmente en las manos, tipo eczema (manchas rojas) o prurito (picor). Se recomienda la disminución de los tiempos de exposición, adecuación de jornadas y tiempos de descanso, sistemas de protección personal adecuados y la implementación de un programa de educación y participación para el control integral del riesgo.

Assessing the risk of groundwater contamination from organic substances in sewage sludge.

In this work, the risk of groundwater contamination from organic substances in sewage sludge from wastewater treatment stations was evaluated in its worst case. The sewage sludge was applied as fertilizer in corn culture, prioritizing the substances for monitoring. The assessing risk took place in a Typic Distrophic Red Latossol (TDRL) area, in the county district of Jaguariúna, SP. The simulators CMLS-94 and WGEN were used to evaluate the risk of twenty-eight organic substances in sewage sludge to leach to groundwater. The risk of groundwater contamination was accomplished for a single sludge dose application in a thousand independent and equally probable years, simulated to esteem the substances leaching in one year after the application date of the sludge. It is presented the substances that should be priorly monitored in groundwater.

Synergies among safety and security in the prevention of major accidents related to dangerous substances

Historical evidence shows that chemical, process, and Oil&Gas facilities where dangerous substances are stored or handled are target of deliberate malicious attacks (security attacks) aiming at interfering with normal operations. Physical attacks and cyber-attacks may generate events with consequences on people, property, and the surrounding environment that are comparable to those of major accidents caused by safety-related causes. The security aspects of these facilities are commonly addressed using Security Vulnerability/Risk Assessment (SVA/SRA) methodologies. Most of these methodologies are semi-quantitative and non-systematic approaches that strongly rely on expert judgment, leading to security assessments that are not reproducible. Moreover, they do not consider the synergies with the safety domain. The present 3-year research is aimed at filling the gap outlined by providing knowledge on security attacks, as well as rigorous and systematic methods supporting existing SVA/SRA studies suitable for the chemical, process, and Oil&Gas industry. The different nature of cyber and physical attacks resulted in the development of different methods for the two domains. The first part of the research was devoted to the development and statistical analysis of security databases that allowed to develop new knowledge and lessons learnt on security threats. Based on the obtained background, a Bow-Tie based procedure and two reverse-HazOp based methodologies were developed as hazard identification approaches for physical and cyber threats respectively. To support the quantitative estimation of the security risk, a quantitative procedure based on the Bayesian Network was developed allowing to calculate the probability of success of physical security attacks. All the developed methods have been applied to case studies addressing chemical, process and Oil&Gas facilities (offshore and onshore) proving the quality of the results that can be achieved in improving site security. Furthermore, the outcomes achieved allow to step forward in developing synergies and promoting integration among safety and security management.