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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2006.04.003 Byline: F. Papin (a), F. Clarot (b), C. Vicomte (b), J.M. Gaulier (c), C. Daubin (d), F. Chapon (e), E. Vaz (b), B. Proust (b) Keywords: Rodenticide; Chlorophacinone; Poisoning; Anticoagulant; Cerebral vein thrombosis Abstract: Superwarfarin exposure is a growing health problem, described in many countries. The authors report a case of suspicious chlorophacinone poisoning with a problematic diagnosis. They review the literature and discuss particularities of anticoagulant rodenticide intoxication, as well as the apparent contradiction between anticoagulant intoxication and lethal thrombosis. Author Affiliation: (a) Forensic Department, Caen University Hospital, Caen, France (b) Medical Forensic Institute, Rouen University Hospital, Charles Nicolle, Rouen, France (c) Pharmacokinetic and Toxicology Laboratory, Limoges University Hospital, Limoges, France (d) Intensive Care Unit, Caen University Hospital, Caen, France (e) Neuropathology Department, Caen University Hospital, Caen, France Article History: Received 9 February 2006; Revised 4 April 2006; Accepted 9 April 2006

Les dérivés synthétiques de la cathinone (DSC) constituent une famille de stimulants (et/ou pour certains, hallucinogènes) reprenant la structure de phényléthylamine des amphétamines et font partie des New Psychoactive Substances (NPS). Cet article se propose de présenter les DSC et de positionner la réalisation des analyses toxicologiques dans le cadre de l'identification et de la prise en charge des abus et des risques associés à leur usage. En France actuellement, c'est surtout (mais pas exclusivement) dans le périmètre du chemsex (usage de substances psychoactives avant ou pendant le sexe, essentiellement dans la population d'hommes ayant des rapports sexuels avec des hommes) que se situent les risques sanitaires en lien avec les DSC, principalement la 3-méthylmethcathinone (3-MMC). L'analyse toxicologique présente un intérêt dans la veille et l'alimentation en données des systèmes de surveillance de la circulation des DSC, la documentation des dossiers biologiques ou médico-légaux des cas d'intoxication, la prise en charge en addictologie et en démarche de réduction des risques. Les méthodes pour l'analyse des échantillons biologiques (sang, urine et cheveux) reposent essentiellement sur la chromatographie liquide avec détection par spectrométrie de masse exacte, la chromatographie gazeuse avec détection par spectrométrie de masse ; avec, pour l'analyse des produits, la résonance magnétique nucléaire. Cathinone derivatives (CD) are psychostimulant (and/or hallucinogenic for some of them) drugs with the phenylethylamine structure of amphetamine compounds, and belong to new psychoactive substances (NPS). This manuscript aims to introduce DC and to draw toxicological analysis situation in patterns of identification and management of abuse and hazards associated to CD. Currently in France, CD-related health hazards mainly (but not exclusively) take place in the chemsex area (refer to the use of psychoactive drugs in sexual parties, and is particularly prevalent among the community of men who have sex with men) where the leading CD seems likely to be 3-methylmethcathinone (3-MMC). Toxicological analysis take place in early warning systems for CD, medical or forensic case of acute intoxication related to CD use, follow-up addiction care and harm reduction policy. Analysis of biological samples (blood, urine and hair) are performed using liquid chromatography with high resolution mass spectrometry detection and gas chromatography with mass spectrometry detection methods, together with nuclear magnetic resonance methods for powders analysis. [ABSTRACT FROM AUTHOR]

Most trace metals exhibit a dual role in marine waters, acting as nutrients at low concentration and being toxic at high concentration. But besides concentration range, speciation is also an important factor. They both show both seasonal and spatial variations. A thorough comparison between total dissolved and particulate concentrations estimated from manual sampling and an assessment of the bioavailability using Diffusive Gradients in Thin Films (DGT) has been performed in this work for Cd, Co, Cu, Ni and Pb, at several sampling points of the Belgian Coastal Zone (BCZ). Additional information to trace back the origin and identify the anthropogenic fingerprint of Suspended Particulate Matter (SPM) was measured using stable carbon isotope measurements in particulate organic matter. Our results show that: (i) particulate and total dissolved metal concentrations are higher at two stations, one in the harbor of Oostende and one offshore; (ii) dissolved and particulate trace metal concentrations do not correlate with the dissolved labile fractions; and (iii) SPM in the harbor zone is likely from allochthonous sources, while in the offshore station marine origin has been evidenced. Our results indicate that, even though contamination is higher in the harbor zones, the trace metal toxicity, which is linked to the metal bioavailability, is most likely not higher than in the open sea. However, with increasing acidification of the ocean, a shift from particulate to dissolved phase might lead to increasing adverse effects on the coastal environment. Unlabelled Image • Trace metal (TM) speciation was assessed using DGT and active sampling techniques. • DGT gives labile fractions and shows different trends than the dissolved non-labile. • TM speciation shows both seasonal and spatial variation on the Belgian Coastal Zone. • δ13C signatures was used to trace the origin suspended organic matter. [ABSTRACT FROM AUTHOR]

Résumé Le cannabis est aujourd’hui un produit de grande consommation, spécialement en France. En conséquence, le biologiste se trouve confronté à des demandes croissantes concernant le dépistage et le suivi du sevrage des consommateurs. De plus, de nouvelles questions de santé publique émergent, telles que celle concernant l’exposition des enfants des parents consommateurs. Ce manuscrit propose d’évoquer les outils analytiques à même de répondre à ces questions, et d’évoquer les écueils de l’interprétation des résultats. Summary Today, cannabis derivatives are products of general consumption, especially in France. Consequently, biologists are facing with an increase of requests about screening test for cannabis, and monitoring the withdrawal process of consumers. In addition, new questions related to public health are arising (i.e. regular exposure of children of parents who consume cannabis). The aim of this manuscript is to set out the available analytical tools, and the pitfalls of the interpretation. [ABSTRACT FROM AUTHOR]

The accuracy of two different analytical methods dedicated to the speciation of mercury in liquid hydrocarbons is discussed in the present paper. A first step involving the comparison of a modified UOP 938 method—based on filtration, purge and extraction—with size exclusion chromatography coupled to ICP-HR MS (SEC-ICP-HR MS) was carried out on specific synthetic model mercury compounds. The modified UOP 938 method (defined here as operational speciation) allowed various mercury compounds to be grouped into different families, i.e. particulate, volatile, ionic and organic non-ionic mercury, whereas SEC-ICP-HR MS provided size distribution profiles of mercury-containing molecules. In a second step, comparison of the two different approaches was then performed with real hydrocarbon feeds, such as crude oil, condensate and straight-run gasoline samples. It was demonstrated that even though elemental Hg was present for the North Sea condensate, all of them contained ionic Hg associated to molecules containing few to many tens of carbon atoms. [ABSTRACT FROM AUTHOR]

Deaths due to ingesting rachacha, which is a homemade paste obtained by decocting poppy heads, are very rare. No fatalities have been recorded in scientific publications. This product is not considered to be very dangerous by its users. We are reporting the first deaths (a 30-year-old man and a 28-year-old woman), after ingesting rachacha balls and alcohol consumption during an evening with a friend. Signs compatible with acute anoxia were observed during autopsy. Toxicological analyses highlighted the presence of morphine and codeine in the blood, urine and bile, with an absence of 6-acetylmorphine. Concomitant consumption of alcohol certainly played a role in the occurrence of death. The black paste found at the scene was identified as rachacha. The mean of consumption (orally) was confirmed by the presence of morphine and codeine in the gastric contents of both victims. The analysis of hair samples was performed to reveal the substance consumption history. Therefore, a possibility of contamination by sweat and/or putrefactive liquids in the post-mortem period must be considered for the interpretation of the results. These two cases show that taking rachacha can be dangerous, especially when combined with the consumption of substances which could potentiate respiratory depression induced by morphine. [ABSTRACT FROM AUTHOR]

For several years, hair analyses have become a powerful tool to investigate past exposure towards xenobiotics. In the case of illicit drugs and more precisely of cannabis exposure, four compounds are usually investigated: ▵ 9-tetrahydrocannabinol (THC), the main active compound of cannabis, one of its metabolites [11-nor-▵ 9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH)] and two cannabinoids (cannabinol and cannabidiol). Up until now, the hair determination of the carboxylic metabolite of THC, which has been described as the only marker allowing distinguishing consumption and passive exposure, has been performed using a gas chromatography-tandem mass spectrometry method. The aim of this study was to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantitative determination of the four markers. The sample preparation was based on an alkaline hydrolysis of hair samples followed by a liquid-liquid extraction of compounds in acidic conditions using a hexane/ethyl acetate mixture. The method was validated and the results were satisfactory: intra- and inter-assay accuracies below 9% and relative standard deviation below 15% for the four compounds. Moreover, the limit of quantification for THC-COOH, the most challenging compound, was validated at 0.2 pg/mg. This concentration is in accordance with the recommendations made by a scientific society which specializes in hair testing. It makes it possible to distinguish the kind of exposure to cannabis. [ABSTRACT FROM AUTHOR]

We reported one non fatal case (42 month old boy) of intoxication with diazinon following accidental ingestion. Diazinon and three of its metabolites (2 common metabolites with other organophosphate pesticides: diethylphosphate and diethylthiophosphate; one specific metabolite: 2-isopropyl-4-methyl- 6-hydroxypyrimidine) were determined in serum and in urine, respectively, using three liquid chromatography-tandem mass spectrometry methods. Diazinon was detected in serum while its metabolites were detected in urine. The concentrations of diazinon and its common metabolites were compared to concentrations previously described in literature in the same intoxication context and were discussed. The concentration of the specific metabolite was compared to concentrations highlighted in occupational exposure, because to the best of our knowledge, we reported here the first urinary concentration of this metabolite in an acute intoxication context. [ABSTRACT FROM AUTHOR]

Case history and presentation Two non-human primates ( Macaca fascicularis), weight 3.5 kg, enrolled in an experimental protocol received a 25 μg hour−1 transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis. Management and follow-up Attempted reversal with naloxone was ineffective. After several hours of ventilation, both primates eventually died, 7 and 15 hours after ketamine injection, respectively. In both cases, the patch was discovered in the animal's cheek pouch. Subsequent fentanyl serum concentration measurements (8.29 and 14.80 μg L−1) confirmed fentanyl overdose. Conclusions This report of two fatal intoxications in non-human primates secondary to ingestion of a transdermal fentanyl patch demonstrates that this method of analgesia is inappropriate for non-human primates, because of their tendency to chew almost anything they can reach. [ABSTRACT FROM AUTHOR]

Abstract: We reported two non-fatal cases of intoxication with pesticides namely alachlor and carbofuran. Hair stand samples were collected from two men approximately 1 year after alachlor intoxication for case 1, and 14 days after the last exposure for case 2. Hair analysis was performed using a liquid chromatography-tandem mass spectrometry method. In case 1, alachlor was detected in the 5 analysed hair segments (concentrations between 12 and 136pg/mg) and its metabolites were not detected. In case 2, carbofuran and its main metabolite (3-hydroxycarbofuran) were detected in the hair strand (global analysis) at the concentrations of 207 and 164pg/mg, respectively. However, additional data are required in order to interpret such results. [Copyright &y& Elsevier]

Texte reçu le 10 décembre 2002 ; accepté le 1er avril 2003 Mots clés : propafénone, métabolites, intoxications, dosage plasmatique Keywords: propafenone, metabolites, intoxications, plasma assay [ABSTRACT FROM AUTHOR]

The biogeochemical behavior of Cd, Co, Cr, Cu, Ni and Pb along the historically polluted Scheldt estuary (Belgium - The Netherlands) was investigated in this study. As never studied before in this area, labile trace metals were measured using the passive sampling technique of Diffusive Gradients in Thin-films (DGT), while total dissolved and particulate trace metal concentrations were assessed using classic active sampling techniques. This dual approach allowed us to highlight the variations of trace metal speciation and distribution in the estuarine surface waters, considering environmental and physicochemical gradients along the transect. The large data set obtained was then compared with literature data of historical measurements along the Scheldt (from 1980 until now), but also from other estuaries. As emphasized by our results, trace metal mobility and partitioning along the Scheldt estuary was mainly driven by biogeochemical reactions which were strongly influenced by gradients of specific estuarine physico-chemical parameters, such as salinity, turbidity, temperature and so on. Hence, all species of trace metals displayed a non-conservative behavior. More precisely, dissolved labile fractions of trace metals showed higher levels in the middle estuary, where many solubilization and remobilization processes occurred due to turbulent mixing mechanisms and an increasing salinity. Our study confirmed the decreasing trend historically observed for particulate metals along the Scheldt, as well as the rising concentrations recorded for dissolved trace metals which might also lead to an increase of their labile fraction measured by the DGT. Finally, these preliminary results suggested that a more regular monitoring of labile metal along the Scheldt estuary is essential to have an in-depth understanding of trace metal speciation and to review bioavailability of trace metals within estuarine ecosystems. Unlabelled Image • Trace metal (TM) speciation was assessed using DGT and active sampling techniques. • The lability of all studied TM increases in the middle estuary. • All studied TM are mainly bound to particles in the upper part of the estuary. • A decrease is historically observed for particulate TM, while dissolved TM increase. • In Europe, the Scheldt estuary remains one of the most contaminated estuaries. [ABSTRACT FROM AUTHOR]

• Fine scale measurements in BCZ sediments reveal 2 mobilization mechanisms. • Fe plays a dominant role in both mobilization mechanisms in BCZ sediments. • Acidification in anoxic sediment causes cationic metal mobilization. • Fe-oxide dissolution controls oxyanion's mobilization in sub-oxic sediment. • Metal/Fe ratios in FeS are constant with an abundance sequence Ni > Cu > Pb > Co. Belgian coastal sediment serves as an important sink for trace elements, yet a systematic study covering a wide range of elements including redox-sensitive metals (Fe, Mn, and Co), cationic trace metals (Cd, Pb, Ni, Cu, and Zn), oxyanions (P, V, As, and Mo), and sulfide has not been performed and the mechanisms controlling their mobilization were not investigated. Here, a passive sampling technique, Diffusive Gradients in Thin-films (DGT), was used in situ to obtain high resolution concentration profiles of these elements in the sediment porewater. Our results revealed two mobilization mechanisms of cationic trace metals and oxyanions in Belgian coastal sediments, both strongly linked to the cycling of Fe. Mobilization of Co, Pb, Ni, and Cu is controlled by electrogenic sulfur oxidation, acidification of the porewater and dissolution of FeS, while that of oxyanions (P, V, and As) is controlled by reductive dissolution of Fe oxyhydroxides. Constant cationic trace metal to Fe molar ratios were established in FeS, while the oxyanion to Fe ratios in Fe oxyhydroxides differ significantly between sampling stations, which is primarily caused by competing effects. We found no evidence that cationic trace metal mobilization was related to Fe oxyhydroxides, or oxyanion mobilization to FeS. This suggests that particulate organic matter forms the major pathway for cationic trace metal input in coastal sediments and that oxyanions will not be incorporated in FeS but form their own oxyanion-sulfide compound. These findings will contribute to a better understanding of the mobilization mechanisms of cationic trace metals and oxyanions in coastal sediments, and of their biogeochemical cycling in coastal ecosystems. [ABSTRACT FROM AUTHOR]

Abstract: Lysergic acid diethylamide (LSD) is a potent hallucinogen, active at very low dosage and its determination in body fluids in a forensic context may present some difficulties, even more so in hair. A dedicated liquid chromatography–electrospray-tandem mass spectrometry (LC–ES-MS/MS) assay in hair was used to document the case of a 24-year-old man found dead after a party. Briefly, after a decontamination step, a 50mg sample of the victim''s pubic hair was cut into small pieces (<1mm length), and incubated overnight in 3mL of phosphate buffer pH 5 at room temperature. After a liquid–liquid extraction (dichloromethane/ether), the extract was analyzed using a LC–ES-MS/MS method exhibiting a limit of quantification of 0.5pg/mg for LSD. A LSD concentration of 0.66pg/mg of pubic hair was observed. However, this result remains difficult to interpret owing to the concomitant LSD presence in the victim''s post mortem blood and urine, the lack of previously reported LSD concentrations in hair, and the absence of data about LSD incorporation and stability in pubic hair. [Copyright &y& Elsevier]

Abstract: A novel three linear step synthesis of Celecoxib was achieved in 33% overall yield via a key regioselective direct C–H arylation reaction between a 1,3-disubstituted pyrazole and an aryl bromide. [Copyright &y& Elsevier]

After the exploitation of coal mines in the 19th and 20th centuries in northern France, many mining slag heaps (SH) were left without any particular management or monitoring. Currently, the influence of these SHs on the quality of surrounding wetlands is hardly known. The purpose of this work is to determine the water quality in the neighbourhood of two SHs located near the city of Douai and its influence on the distribution of aquatic invertebrates in local wetlands. Our approach involves (1) the spatial and temporal characterization of the water composition (anions, major elements, sulphide, DOC and alkalinity) and of the biological diversity (aquatic invertebrates) and (2), based on this chemical and biological screening, the establishment of relationships between water quality and biodiversity distribution through multivariate data analysis. The results clearly indicate that substantial leaching from the slag heaps occurs, given the very high concentrations of dissolved sulphates (in the range of 2 g L−1). While the pH remains weakly basic, indicating that the leaching water has been neutralized by the highly carbonated regional substratum, high levels of biodegradable organic matter and sulphate contents have been noticed. They sporadically cause significant drops in dissolved oxygen and the occurrence of dissolved sulphides that massively reduce biodiversity, qualitatively and quantitatively. In Summer, oxygen saturation is generally lower due to the higher rate of organic matter degradation, and the risk of anoxic episodes therefore increases. Finally, as wetlands are vulnerable environments, these preliminary results suggest that monitoring and management of these sites must be attempted quickly to avoid the degradation of those valuable habitats. Image 1 • Wetlands are widely enriched in sulphates, caused by slag heap leaching. • Impact of leaching on wetlands was assessed using chemical & biological approaches. • The water composition reveals a typical example of a neutralized acid mine drainage. • Combination of high S2−, low O 2 and pH may lead to a loss of biodiversity. • Variations in DOC and lixiviate composition induce spatio-temporal changes. Leaching of slag heaps introduces in the surrounding wetlands high amounts of sulphates that influences the aquatic biodiversity through redox processes. [ABSTRACT FROM AUTHOR]

Substance abuse (SA) among children is a recognized challenge for policymakers and law enforcement and has life-threatening consequences owing to the impact on the children's development and the consequent increase in vulnerability. This work outlines several important issues related to SA among children: (1) SA prevalence including onset, common examples, extent, and spectrum of SA; (2) the presence of new psychoactive substances, which are rapidly spreading worldwide with limitations regarding their prevalence, detection, and interventions; (3) street children and their recruitment in drug supply; (4) SA and substance use disorder pathways, risk and protective factors for the development of SA; (5) SA consequences in the case of early initiation, including deaths; and (6) current preventive interventions for the pediatric population. In conclusion, this challenge requires consistent and unremitting attention in order to execute effective prevention programs with continuous re-evaluation of the situation. [ABSTRACT FROM AUTHOR]

In seawater, trace metals occur in many forms: free ion, labile and non-labile complex, colloid, associated with particles, but only free ions and very labile metal complexes can cross the phytoplankton membrane and be assimilated. In this paper we review the most appropriate determination methods for those metal species, addressing particularly in situ speciation and preconcentration. Focus is on DGT-ICPMS, which is a technique that meets these criteria very well. In coastal environments, DGT probes are widely used for metal pollution monitoring, but in open ocean a carrier such as a glider, is required. In open ocean organic metal complexation has been studied using DGT-ICPMS and electrochemical methods. The use of DGTs with different diffusion domain thicknesses provides information to quantify labilities and dissociation rates of metal complex pools. Labilities of metal complexes in coastal waters appeared to be higher than in open sea. • Review of the most appropriate methods for determination of metal complex pools. • In situ speciation and preconcentration of metals in coastal and open ocean. • Electrochemical methods to assess metal organic complexes in open ocean. • DGT and SeaExplorer combination to assess metal complexes in open ocean. • Models to quantify labilities and dissociation rates of metal complex pools. [ABSTRACT FROM AUTHOR]

Non accidental intoxication due to child abuse is rare and its frequency is likely underestimated because it is difficult to diagnose. Here, we report a case of voluntary repeated exposure to lithium in an infant, for whom the clinical manifestations were convulsions. Toxicological analysis was very helpful for documenting lithium exposure during the assumed period of time. Interpreting the results of hair analysis, a simple and minimally invasive examination, is tricky at this age, but it can facilitate the differentiation of acute versus chronic exposure. Although infrequent and underestimated, lithium should be considered as a cause of intoxication in a previously healthy child with acute seizure. [ABSTRACT FROM AUTHOR]

Abstract: We present two non fatal cases of intoxication with carbofuran (CBF) documented by hair analysis. Carbofuran and 3-hydroxycarbofuran (OHCBF, its main metabolite) hair concentrations were determined using a liquid chromatography–tandem mass spectrometry method. The obtained results were surprising if we consider several hair analyses previously published and based on a theory of the presence of xenobiotic in the only segment that comprised its intake. Among the two intoxication cases, we noticed the presence of CBF and OHCBF in hair segments corresponding to 45 days before, and more than 100 days after, the day of intoxication. Additionally, repeated hair samplings and subsequent analysis revealed a decrease of the carbofuran''s concentration during the hair life. [Copyright &y& Elsevier]