[Recreational use of cannabis: From effects to harm. Epidemiological data]. / L'usage récréatif du cannabis : des effets aux méfaits. Données épidémiologiques.

As the medical use of so-called "therapeutic cannabis" is in the process of being approved in France, the opening to its recreational use is the next logical step, as it has been always the chronology followed in all countries. Indeed, those who have legalized the drug have previously approved its therapeutic use. This "justifying a project phase" stage seems unavoidable. Therefore, it is appropriate to recall the effects and misdeeds of the drug during its recreational use. The general population surveys carried out in France for 25 years by public health France and the French Observatory of Drugs and Drug Addiction, have followed the evolution of psychoactive substances consumption. Particular attention was focused on cannabis use, which, in a context of wide dissemination for a quarter of a century, rose steadily higher among younger generations, but also among older adults. France is the European country with the highest prevalence of cannabis use among young people and adults. Last 25 years, its diffusion has continued to expand, and the experimentation rate multiplied by near 4. Estimated at 12.7% in 1992, it reached 44.8% in 2017. Moreover, 25% of users in the year aged from 18 to 64 years old were at high risk of problematic use or dependence in 2017. This figure is worrying because it is constantly increasing; it affects 3% of 18-64-year-old, just over a million people.

[Pharmacokinetics, metabolism, and analytical methods of ethanol]. / Éthanol : pharmacocinétique, métabolisme et méthodes analytiques.

Alcohol is a licit substance whose significant consumption is responsible for a major public health problem. Every year, a large number of deaths are related to its consumption. It is also involved in various accidents, on the road, at work, as well as during acts of violence. Ethanol absorption and its fate are detailed. It is mainly absorbed in the small intestine. It accompanies the movements of the water, so it diffuses in all the tissues uniformly with the exception of bones and fat. The major route of ethanol detoxification is located into the liver. Detoxification is a saturable two-step oxidation. During the first stage ethanol is oxidized into acetaldehyde, under the action of alcohol dehydrogenase. During the second stage acetaldehyde is oxidized into acetate. Genetic factors or some drugs are able to disturb the absorption and the metabolism of ethanol. The analytical methods for the quantification of alcohol in man include analysis in exhaled air and in blood. The screening and quantification of ethanol for road safety are performed in exhaled air. In hospitals, blood ethanol determination is routinely performed by enzymatic method, but the rule for forensic samples is gas chromatography.

Accidental potassium dichromate poisoning. Toxicokinetics of chromium by ICP-MS-CRC in biological fluids and in hair.

Intoxications by chromium (Cr) compounds are very life threatening and often lethal. After oral ingestion of 2 or 3g of hexavalent Cr (Cr(VI)), gastrointestinal injury, but also hepatic and renal failure, often occurs which each leads to a fatal outcome in most patients. Cellular toxicity is associated with mitochondrial and lysosomal injury by biologically Cr(VI) reactive intermediates and reactive oxygen species. After Cr(VI) has been absorbed, there is not much that can be done except to control the main complications as the treatment is only symptomatic. The biotransformation of Cr(VI) to Cr(III) reduces the toxicity because the trivalent form does not cross cellular membranes as rapidly. In fact, more than 80% of Cr(VI) is cleared in urine as Cr(III). We report the case of a 58-year-old male patient who was admitted to hospital after accidental oral ingestion of a 30 g/L potassium dichromate (the estimated amount of ingested Cr is about 3g). ICP-MS equipped with a collision/reaction cell (CRC) and validated methods were used to monitor plasma (P), red blood cells (RBCs), urine (U) and hair chromium. For urine the results were expressed per gram of creatinine. After 7 days in the intensive care unit, the patient was discharged without renal or liver failure. P, RBC and U were monitored during 49 days. During this period Cr decreased respectively from 2088 µg/L to 5 µg/L, 631 µg/L to 129 µg/L and 3512 µg/g to 10 µg/g. The half-life was much shorter in P than in RBC as the poison was more quickly cleared from the P than from the RBC, suggesting a cellular trapping of the metal. Hair was collected 2 months after the intoxication. We report a very rare case of survival after accidental Cr poisoning which has an extremely poor prognosis and usually leads to rapid death. For the first time, this toxicokinetic study highlights a sequestration of chromium in the RBC and probably in all the cells.

[A new medical concept: the metallic profile]. / Le profil métallique : un nouveau concept médical.

Over the past decade great progress has been made in metals and metalloids analysis. This analysis is a basic stage in toxicity assessment and is indispensable in achieving a realistic evaluation of substance toxicity. A recently introduced technique, inductively coupled plasma mass spectrometry (ICP-MS) is progressively replacing atomic absorption. This analysis permits multi-elementary determinations, approximately 30 elements, with an optimal gain in sensitivity in many biological matrices: i.e. whole blood, plasma, urine, hair, nail, biopsy samples. Moreover, this method allows semiquantitative determination with an additional 30 supplementary elements, which enables the toxicologist to sufficiently estimate the toxic levels and metal exposure. The authors demonstrate that the ICP-MS could be very useful for a wide range of clinical applications. Furthermore, this procedure offers new exploration possibilities in various fields such as clinical toxicology, forensic toxicology as well as work place testing or environmental exposure and permits epidemiologic studies. This analytical method in fact also provides a new scientific approach. To our knowledge we are the first to propose: the metallic profile.

MRI gadolinium-based contrast agents. Radiologists beware!

Gadolinium (Gd) is used in contrast agents as it enhances magnetic resonance imaging (MRI) signals. To reduce Gd toxicity, it is chelated into linear or macrocyclic complexes. Eight Gd-containing contrast agents have been approved by the European Medicines Agency (EMEA) for use in MRI, and six by the US Food and Drug Administration. Stability depends upon its physicochemical properties. When renal function is normal, the Gd is quickly cleared from the body by the kidneys. For patients with chronic kidney disease, the elimination is greatly reduced and Gd may be released from its chelate and deposit in body tissues, leading to nephrogenic systemic fibrosis (NSF). More than 200 cases of NSF have been reported in the world. NSF is characterized by an extensive fibrosis of skin and tissues, a very severe affection with possible lethal outcome. We propose recommendations to avoid the risk of NSF.

Application of inductively coupled plasma mass spectrometry multielement analysis in fingernail and toenail as a biomarker of metal exposure.

The application of inductively coupled plasma mass spectrometry (ICP-MS) to multielement analysis in fingernail and toenail as biological indices for metal exposure is presented. The ICP-MS measurements were performed using a Thermo Elemental X7CCT series. Fingernail specimens were obtained from 130 healthy volunteers, and paired fingernail and toenail samples from 50 additional healthy volunteers of both sexes were collected as well. After warm water and acetone decontamination, 20 mg fingernails and toenails were acid mineralized after a decontamination procedure, and 32-34 elements were simultaneously quantified after acid dilution following water calibration. Li, Be, B, Al, V, Cr, Mn, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Mo, Pd, Ag, Cd, Sn, Sb, Te, Ba, La, Gd, W, Pt, Hg, Tl, Pb, Bi, and U could be validated in fingernail and toenail samples. Linearity was excellent, and the correlation coefficients were above 0.999. Quantification limits ranged from 0.04 pg/mg or ng/g (U) to 0.1 ng/mg or microg/g (B). Because of the lack of available certified nail reference material, an adequate quality assessment scheme was ensured by comparison with an interlaboratory nail-testing procedure, and the results showed optimal consistency for elements tested. Results are presented and compared with published multielement data. Six cases of domestic exposure to lead were diagnosed based on fingernail analysis. Application of ICP-MS multielement analysis in fingernail and toenail as a biomarker of metal and nonmetal exposure permits greater noninvasive control of industrial, domestic, or environmental exposure and is very useful for epidemiological studies.

Evaluation of chromium contamination in water, sediment and vegetation caused by the tannery of Jijel (Algeria): a case study.

In order to evaluate the chromium (Cr) contamination due to the discharge of waste waters from the tannery of Jijel in the Mouttas river (Algeria), samples of water, sediment and vegetation (Agropyrum repens) were collected during a 6 month period in four stations located upstream (control) and downstream of the tannery. The total chromium was measured by atomic absorption spectrophotometry. Metal inputs were clearly related to effluent discharges from the tannery into the river. Although only traces of chromium were found in water samples upstream of the tannery, very high concentrations (up to 860 times higher) were detected downstream. The contamination was not limited to water of Mouttas River because a same difference in chromium concentrations was also found in sediments and plants Agropyrum repens that were sampled upstream and downstream of the tannery. This work showed that the treatment process used in the wastewater treatment plant of the tannery of Jijel is not able to remove the chromium detected in their influents. The occurrence and chromium levels detected in the aquatic environment represent a major problem concerning drinking water resources and environmental protection of water bodies.

Evaluation of the risk of contamination of surgical personnel by vaporization of oxaliplatin during the intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC).

AIMS: To evaluate if oxaliplatin is likely to vaporize under HIPEC conditions and to see if it could be a source of pulmonary contamination for surgeons. METHODS: Three oxaliplatin concentrations (230, 460 and 920 mg oxaliplatin/l), 3 heating temperatures (41, 43 and 45 degrees C) and 3 bubbling durations (30, 60 and 90 min) were tested. Drug vaporization was evaluated by using inductively coupled plasma mass spectrometry (ICP-MS) to analyze platinum concentrations in the trap solutions. RESULTS: At all concentrations of oxaliplatin solutions, heating temperatures and bubbling trap periods, the quantities of vaporized platinum were always insignificantly lower than 1 microg/l. CONCLUSIONS: The experimental risk of pulmonary contamination of hospital staff during HIPEC procedure appears to be negligible. However a monitoring study with an analysis of samples of the operating theatre and urine from surgical personnel should be carried out to confirm these conclusions.

Simplified protocol for evaluating the genotoxic risk of hospital wastewater.

To evaluate the genotoxicity of hospital wastewater, we drew up a simplified protocol based on two well-known tests: the SOS chromotest and the Ames fluctuation test. Three concentrations of wastewater samples were directly tested without extraction or concentration. By fixing three significance levels in genotoxicity response for each test, we could classify the samples in five categories ranging from nongenotoxic to highly genotoxic. This simplified classification thus constitutes an invaluable help in making the nonscientist public aware of the genotoxic risk of hospital wastewater and can be applied in a screening approach to chemicals in the environment.

Hospital wastewater genotoxicity.

Hospitals represent an incontestable release source of many chemicals compounds in their wastewaters, and which may have an impact on the environment and human health. Indeed, some of the substances found in wastewaters are genotoxic and are suspected to be a possible cause of the cancers observed in the last decades. To study the toxicity and the risk associated with these releases biological tests, such as genotoxicity tests, can be used. An evaluation of the genotoxic potential of the wastewaters from a university hospital was performed with the SOS chromotest and the Salmonella fluctuation test. The samples were taken for six 1-week periods between May 2001 and April 2003. Out of a total of 38 samples tested, 31 were positive in at least one assay (82%). Distribution, proportion and intensity of the genotoxic response were different among the six sampling periods. The two genotoxicity tests had different sensitivities. It must be emphasized that whatever the sampling period, Monday samples were always genotoxic in at least one assay. This work shows that this hospital wastewaters samples are very often genotoxic, the response intensity being inflected by rain levels. Efforts must be undertaken by hospitals to integrate the knowledge and the control of their wastewaters in infection and environmental control programs.

Efficacy of two wastewater treatment plants in removing genotoxins.

The genotoxic potential of influents and effluents of two different wastewater treatment plants (WTP-A and WTP-B) located in the Rouen, France, area was evaluated by the SOS chromotest without metabolic activation (on Escherichia coli PQ37) and the Ames fluctuation test (on Salmonella typhimurium strains TA 98, 100, TA 102) with and without metabolic activation. The wastewater samples were taken during two 1-week periods in January and April 2003. The simultaneous use of the SOS chromotest and Ames fluctuation test allowed us to evaluate the efficacy of the wastewater treatment plants at removing genotoxins. Genotoxins were detected with the Ames test but not with the SOS chromotest. Out of a total of 24 influents tested (14 for WTP-A and 10 for WTP-B), almost all were genotoxic in at least one Ames test strain (71% for WTP-A and 100% for WTP-B). In contrast, all of the tested effluents were nongenotoxic. This work showed that the treatment process used in the 2 wastewater treatment plants studied (activated sludge) was able to remove the genotoxins detected in their influents. Nevertheless, studies could be undertaken to determine which step of the treatment process removes genotoxins and whether WTP sludge use could be a source of genotoxic contamination for humans and the environment.

Evaluation of industrial, hospital and domestic wastewater genotoxicity with the Salmonella fluctuation test and the SOS chromotest.

An evaluation of the genotoxic potential of different wastewaters collected in the Rouen area was performed with the SOS chromotest (on Escherichia coli PQ37) and the Salmonella fluctuation test on Salmonella typhimurium strains TA98, TA100 and TA102 with or without metabolic activation. The samples were taken during two 1-week periods, one in January and one in April 2003. Six sites were selected for wastewater sampling in order to allow a comparative study between an area of mixed discharge (industrial, hospital and domestic) and an area of primarily domestic discharge. Out of a total of 71 daytime samples tested, 46 (65%) were positive in at least one assay: 22 samples out of 33 in January (67%), and 24 samples out of 38 in April (63%). The two genotoxicity tests have different sensitivities. Indeed, the Salmonella fluctuation test allowed the detection of 56% of the samples as genotoxic in January (18 out of 33), and 63% in April (24 out of 38) while the SOS chromotest allowed the detection of 18% of the samples as genotoxic, whatever the sampling period. The samples collected in domestic wastewater are at least as genotoxic as the samples collected in mixed wastewater. The possible source of the detected genotoxicity (industrial, hospital or domestic) is discussed. The results of this study show that the different types of wastewaters present a genotoxic risk. Additional studies should be undertaken in the analytical field in order to try to identify and quantify the compounds responsible for the genotoxicity. This difficult task will be necessary in order to identify the sources of toxicants and thus to take preventive and/or curative measures to limit the toxicity of the wastewater.

Detection of hospital wastewater genotoxicity with the SOS chromotest and Ames fluctuation test.

The genotoxic potential of Rouen University Hospital wastewater was evaluated by the SOS chromotest (on Escherichia coli PQ37) and Ames fluctuation test on Salmonella typhimurium strains TA 98 and TA 100 without metabolic activation. The samples were taken during the hospital maximal activity period (8:00 a.m. to 6:00 p.m.) over three one-week periods of the year. The simultaneous use of SOS chromotest and Ames fluctuation test allows us to carry out a preliminary screening of the hospital wastewater and to gain some insight by which mechanism the genotoxic compounds act. Out of a total of 18 daytime unconcentrated samples tested, 10 (55%) are positive in at least one assay. The two tests have different sensitivity. Indeed, nine genotoxic samples (50%) are detected by the Ames test, and four (22%) by the SOS chromotest. Distribution and intensity of the genotoxic response are different at the three periods. In order to explain this phenomenon, the influence of the rain levels is discussed. This work showed that the hospital wastewater samples tested were overall genotoxic, the response intensity being inflected by the pluviometry. Efforts are now under way to try to identify one or several genotoxic compounds in order to take precautionary measures to limit their release in hospital wastewaters.

Comparison of 35 electronic databases for environmental risk assessment.

The objective of this work is to classify and evaluate the major factual electronic databases that could be efficiently questioned for environmental risk assessment of various chemicals. A series of 35 databases available on commercial CD-ROMs and/or freely accessible on the Internet were listed and compared for the presence or absence of information for 27 environmental criteria. A factorial correspondence analysis indicated that most of the 35 databases are specialized in physicochemical, toxicological or ecotoxicological data but a few of them are nonspecialized databases able to answer simultaneously in various areas. We then evaluated these 35 databases by querying them for 14 selected test chemicals. It appeared that the percentage of chemicals being listed in the databases was very unequal and none of the 35 databases obtained 14 positive responses. The quality of the responses was determined by calculating the number of criteria being documented for the previously listed chemicals in each database. It suggested that HSDB, DOSE, TOMES, IPCS are the most efficient databases to be used for an urgent search of environmental data.

Glutaraldehyde in hospital wastewater.

Glutaraldehyde (GA) solutions are widely used in hospitals to disinfect reusable fiber-optic endoscopes. These solutions are dumped after use in the aquatic environment without any particular safety precautions. Taking into account the quantity of GA consumed daily and the released water volume, the predicted hospital wastewater concentration was estimated at 0.50 mg/L. To measure the real GA concentration present in hospital wastewater, we developed an analytical technique that is simple, sensitive, and reliable. This method consists of a water sample concentration and purification by solid phase extraction and then a spectrophotometric determination. This analytical method was used for a 1-week surveillance program at Rouen University Hospital (2,600 beds). The wastewater tested showed the presence of a concentrated peak approximately eight times higher than the predicted wastewater concentration. The environmental impact of GA release into the aquatic environment was then studied. A predicted no-effect concentration (PNEC) < 1 microg/L was calculated. In most situations the predicted environmental concentration (PEC) was found to be <0.5 microg/L taking into account the hospital wastewater dilution in its way to the sewage treatment plant and GA biodegradation. The PEC/PNEC ratio is then < 1, showing that this release are not expected to present a significant risk to the aquatic environment. However in situations of insufficient dilution or of major release, the PEC/PNEC ratio become > 1, and an environmental risk should be expected. An internal prevention program of the various hospital departments to assure GA rational use, and a release spreading would give an additional safety margin to consider GA as safe in terms of environmental risk.

Effect of cadmium on reproduction of daphnids in a small aquatic microcosm.

Chlorella vulgaris colonies were grown as nutrient agar for one week, followed by addition of Daphnia magna in overlying water for a second week. A range of concentrations of cadmium were added to the Chlorella or to the Chlorella followed by higher cadmium concentrations in the overlying fluid. A dose-dependent reduction in reproduction was observed with increased cadmium. When parent daphnids were first exposed to a lower cadmium concentration, and their offspring of preconditioned juvenile daphnids then exposed to a higher concentration, cadmium tolerance in new-born daphnids was observed.

Acrolein toxicity: comparative in vitro study with lung slices and pneumocytes type II cell line from rats.

Toxicological effects of acrolein have been studied in precision-cut rat lung slices and in L2 cells, a rat pneumocyte II cell line. These two models were cultured for 24 h with or without acrolein (0-100 microM in L2 cells; 0-200 microM in lung slices). Treatment with this pneumotoxicant produced a concentration dependent decrease in intracellular ATP levels. Acrolein concentrations higher than 50 microM induced ATP decrease in slices, while this decrease occurred from 10 microM acrolein in L2 cells. Detoxification marker evaluations showed that mostly the glutathione pathway was altered after acrolein treatment in both models. Intracellular glutathione (GSH) levels were drastically increased with an acrolein concentration of 10 microM. This increase was concomitant with glutathione-S-transferase (GST) and glutathione reductase (GRED) activities in L2 cells. After this strong increase, these enzymatic activities as well as GSH levels were quickly decreased. In precision-cut rat lung slices, the induction of the glutathione pathway was less clear-cut. A bell-shaped dose response curve was observed with a maximum for 5 microM acrolein for GST and GRED activities. These differences between acrolein toxic ranges could be explained by the presence of an active detoxification pathway in slices compared to its relative lack in L2 cells.

Characterization of Precision-cut Rat Lung Slices in a Biphasic Gas/Liquid Exposure System: Effect of O(2).

Influence of oxygen on lung cell differentiation has been studied in precision-cut rat lung slice cultures. Rat lung slices were positioned on rolling inserts placed into vials with opened caps to allow free access to the gaseous phase. This system was placed into a continuous-flow rotating chamber with controlled pO(2), pCO(2) and hygrometry. Slices were cultured in a serum-free medium up to 3 days under an atmosphere of 21 or 70% oxygen. Cellular antioxidant markers demonstrated an oxygen concentration-dependent response. Slices cultured with 70% oxygen exhibited the highest specific activity of catalase, NADPH cytochrome c reductase and gamma-glutamyl transpeptidase (GGT) as well as the highest levels of intracellular glutathione after 48 or 72 hours of incubation. Moreover, hyperoxic exposure altered the expression of lung manganese-containing superoxide dismutase mRNA. Hyperoxia had little or no effect on intracellular ATP levels, which remained high in lung slices compared with freshly isolated tissue. The study of the pulmonary specific functions allowed to confirm maintenance of the in vitro cellular differentiation of lung slices incubated with 21% oxygen: (i) polyamine transport is preserved and exhibited kinetic properties similar to those observed in lung in vivo; (ii) ATP levels remained constant throughout the time course of incubation. This in vitro model proves to be a useful tool to study mechanisms involved after oxygen exposure and will probably be useful for the study of other environmental gaseous contaminants. Further developments in this method are under development.

[The history of Lipiodol (1901-1994) or How a medication may evolve with the times]. / Histoire du Lipiodol (1901-1994) ou Comment un médicament peut évolver avec son temps.

The history of Lipiodol, an iodized oil perfected in 1901 by Marcel Guerbet and Laurent Lafay, offers the example of a product with multiple indications which, initially destined for therapeutic usage, was later successfully turned to radiologic applications; then, sixty years later, returned to its initial purposes. This shows that (1) very often new products find usages which their developers never suspected; (2) research can extend beyond the original synthesis and commercialization of the product; (3) at some point research on a medication becomes multidisciplinary.