Levels of GHB in hair after regular application.

Gamma hydroxybutyrate (GHB) is a central nervous system depressant that is an approved drug for the treatment of narcolepsy with cataplexy and other syndromes. Due to its dose dependent stimulating, relaxing or sedative effects, illicit abuses include recreational use by young people and cases of drug-facilitated crime (DFC). Since GHB is also produced endogenously, for forensic questions, it is important to be able to differentiate between endogenous GHB and elevated levels due to additional intake. In this study, we measured GHB concentrations in hair of patients with narcolepsy receiving daily GHB treatment. The results were compared to endogenous concentrations and concentrations after chronic intake presented in several former studies. The aim of this study was to investigate whether a regular intake of a known dosage of GHB leads to elevated levels of GHB concentration in hair. We collected hair samples of 19 patients (14 female, 5 male) with narcolepsy under regular GHB treatment and examined the hair samples segmentally by digestion of the hair followed by liquid-liquid extraction and analysis using a Shimadzu LC20 UFLC system coupled with an AB Sciex API 4000 Qtrap tandem mass spectrometer. All volunteers received daily treatment with different doses of sodium oxybate (sodium salt of GHB) ranging between 3 and 9g per night. The observed mean value of GHB concentration in hair was 2.69ng GHB per mg hair for the 5 male participants, 1.56ng/mg for the 14 female participants giving an overall mean value of 1.86ng/mg for all participants. Our results showed no correlation between the daily dose or the duration intake of GHB and the measured concentration of GHB in hair. Although we did find a significant (p<0.01) difference between published endogenous levels of GHB in hair and GHB levels in hair of patients with regular daily GHB intake, the forensic relevance however is disputable. We hypothesise this narrow margin or even overlap to be the reason why analytical results from hair analysis in some cases fail to provide a reliable prove of a single exposition.

Liquid silicone embolism syndrome (SES) in lungs and liver - A case report.

Silicone embolism syndrome (SES) is a well known complication after injection of silicone gel as well as liquid silicone. Rarely, men use physiologic salt solution or liquid silicone injected into the subcutaneous tissue of the scrotum, the penis, the upper genital or the inguinal region. Those men, who call themselves "siliconers", want to get a larger penis and scrotum, also visible when wearing clothes. Injections of liquid silicone in the mentioned regions can lead to liquid silicone embolism in the lungs and also the liver, sometimes eventually leading to death via right heart failure as in the present case. Autopsy revealed "frog spawn"-like vacuoles in the subcutaneous tissue of the genital region and liquid silicone embolism in lungs and liver. Additionally, toxicological analyses revealed different liquid silicones. Smaller oligomers were transported into lung and liver, larger ones showed local enrichment at the injection site. The seized Polydimethylsiloxane (PDMS) could not be detected in abdominal fat, blood or urine, potentially due to low perfusion of fat tissue, the aqueous character of blood and urine or the time span between last injection and death.

GHB related acids are useful in routine casework of suspected GHB intoxication cases.

GHB related acids (3,4-dihydroxy butyric acid, 2,4-dihydroxy butyric acid and glycolic acid) are produced through oxidative GHB metabolism. These analytes could be potential biomarkers to ensure the diagnosis of a GHB intoxication and even prolong the detection window. Within this study, forensic routine cases were measured to consider the potential of additional gas chromatographic mass spectrometric analysis on these acids. 17 GHB positive real cases (10 serum samples and 7 urine samples) and 40 cases with suspicion of drugging in DFC cases and negative GHB results (21 serum samples and 19 urine samples) were evaluated. Increased GHB related acid concentrations were detected in all serum and most urine samples positive on GHB. In some GHB negative cases, especially in serum samples, concentrations of GHB related acids gave hints that GHB actually was taken. We recommend to use the following cut-offs for a more reliable interpretation of potential GHB intoxication cases: 3,4-OH-BA:>3 mg/L in serum and>50 mg/L in urine; 2,4-OH-BA:>2 mg/L in serum and>25 mg/L in urine; GA:>5 mg/L in serum and>400 mg/L in urine.

Estimates of Non-Alcoholic Food-Derived Ethanol and Methanol Exposure in Human.

Food-derived alcohol is almost not in question due to its low concentration. Nevertheless, could it pose a problem for some risk groups and forensic cases? To answer this, we aimed to simultaneously evaluate ethanol and methanol ingredients of a variety of non-alcoholic foods in two different countries and estimate their possible health and forensic consequences. Alcohols in foods were analysed by headspace gas chromatography (HS-GC). Human average acute daily food consumptions and food-derived blood alcohol concentrations (BAC) were determined by using the data of the EFSA Nutrition Survey. Methanol and ethanol ingredients of similar foods varied between the two cities. Most foods produce higher methanol concentrations than the Maximum Allowable Dose Level (23 mg). Especially fruit juices lead to the critical level of ethanol for children (6.0 mg/kg bw). Based on the results, adult daily intake of selected food groups does not bear ethanol that exceeds the legal limit of BAC or the limit not allowed by the religious and does not lead to acute alcohol toxicity. But these low levels of ethanol and methanol consumed via non-alcoholic foods for life can raise the vulnerability to chronic health problems (cancer, liver cirrhosis, Alzheimer's disease, autism, ocular toxicity, alterations in fetal development), and may lead to positive ethanol metabolite results (e. g. Ethyl glucuronide) when a low cut-off level is used. Therefore, studies on the alcohol contents of various natural and processed non-alcoholic foods along with their effects on humans, and new regulations on labeling the food products and conscious food consumption are in particular importance. It would also be important to consider unintentional alcohol consumption via non-alcoholic foods in the evaluation of clinical and forensic cases.

Variation of intraindividual levels of endogenous GHB in segmented hair samples.

Gamma-hydroxybutyrate (GHB) belongs to a group of substances that may be used in drug-facilitated crime (DFC). It is also an endogenous substance. There is a dispute whether or not a single exposure to GHB can be detected in hair. The first aim of this study was to develop and validate a method for the sensitive detection of base levels of GHB in hair. The second aim was to collect analytical data of 88 volunteers (62 females/26 males) not claiming any exposure to GHB and discuss the results in the context of the identification of a potential single exposure in cases of DFC. Furthermore hair samples from a male volunteer, who took GHB twice within 8 weeks, were analysed and the results were discussed with regard to mean values of endogenous GHB analysed in this study. Hair was digested under alkaline conditions, and GHB was isolated using liquid-liquid extraction. LC-MS/MS was performed using Electrospray ionization in the negative mode, multiple reaction monitoring, and a deuterated internal standard (GHB-D6). Segmental hair analysis revealed mean concentrations of 0.673ng/mg or 0.676ng/mg (without first segment) in females and 0.935ng/mg or 0.932ng/mg (without first segment) in males. Combined mean values were 0.751ng/mg and 0.752ng/mg (without first segment). In one individual's hair single doses of 2g GHB did not lead to an increase compared to his base levels. The limits of detection and quantitation in human hair were 0.1ng/mg and 0.3ng/mg, respectively. Accuracy at 0,25ng/mg, 2,5ng/mg and 25ng/mg was determined to be 94% or higher for all levels and intra-assay CVs at these concentrations were always lower than 7% (n=5). ß-hydroxybutyrate (BHB) and glycine did not produce an interference. Recovery at 1ng/mg and 25ng/mg GHB was 23% and 13% and Matrix effects were calculated to be 77% and 89% respectively.

Cannabis use as a risk factor for causing motor vehicle crashes: a prospective study.

AIM: We conducted a responsibility analysis to determine whether drivers injured in motor vehicle collisions who test positive for Δ-9-tetrahydrocannabinol (THC) or other drugs are more likely to have contributed to the crash than those who test negative. DESIGN: Prospective case-control study. SETTING: Trauma centres in British Columbia, Canada. PARTICIPANTS: Injured drivers who required blood tests for clinical purposes following a motor vehicle collision. MEASUREMENTS: Excess whole blood remaining after clinical use was obtained and broad-spectrum toxicology testing performed. The analysis quantified alcohol and THC and gave semiquantitative levels of other impairing drugs and medications. Police crash reports were analysed to determine which drivers contributed to the crash (responsible) and which were 'innocently involved' (non-responsible). We used unconditional logistic regression to determine the likelihood (odds ratio: OR) of crash responsibility in drivers with 0 < THC < 2 ng/ml, 2 ng/ml ≤ THC < 5 ng/ml and THC ≥ 5 ng/ml (all versus THC = 0 ng/ml). Risk estimates were adjusted for age, sex and presence of other impairing substances. FINDINGS: We obtained toxicology results on 3005 injured drivers and police reports on 2318. Alcohol was detected in 14.4% of drivers, THC in 8.3%, other drugs in 8.9% and sedating medications in 19.8%. There was no increased risk of crash responsibility in drivers with THC < 2 ng/ml or 2 ≤ THC < 5 ng/ml. In drivers with THC ≥ 5 ng/ml, the adjusted OR was 1.74 [95% confidence interval (CI) = 0.59-6.36; P = 0.35]. There was significantly increased risk of crash responsibility in drivers with blood alcohol concentration (BAC) ≥ 0.08% (OR = 6.00;95% CI = 3.87-9.75; P < 0.01), other recreational drugs detected (OR = 1.82;95% CI = 1.21-2.80; P < 0.01) or sedating medications detected (OR = 1.45; 95%CI = 1.11-1.91; P < 0.01). CONCLUSIONS: In this sample of non-fatally injured motor vehicle drivers in British Columbia, Canada, there was no evidence of increased crash risk in drivers with Δ-9-tetrahydrocannabinol < 5 ng/ml and a statistically non-significant increased risk of crash responsibility (odds ratio = 1.74) in drivers with Δ-9-tetrahydrocannabinol ≥ 5 ng/ml.

Prevalence of alcohol and drug use in injured British Columbia drivers.

OBJECTIVES: Determine the prevalence of drug use in injured drivers and identify associated demographic factors and crash characteristics. DESIGN: Prospective cross-sectional study. SETTING: Seven trauma centres in British Columbia, Canada (2010-2012). PARTICIPANTS: Automobile drivers who had blood obtained within 6 h of a crash. MAIN OUTCOME MEASURES: We analysed blood for cannabis, alcohol and other impairing drugs using liquid chromatography/mass spectrometry (LCMS). RESULTS: 1097 drivers met inclusion criteria. 60% were aged 20-50 years, 63.2% were male and 29.0% were admitted to hospital. We found alcohol in 17.8% (15.6% to 20.1%) of drivers. Cannabis was the second most common recreational drug: cannabis metabolites were present in 12.6% (10.7% to 14.7%) of drivers and we detected Δ-9-tetrahydrocannabinol (Δ-9-THC) in 7.3% (5.9% to 9.0%), indicating recent use. Males and drivers aged under 30 years were most likely to use cannabis. We detected cocaine in 2.8% (2.0% to 4.0%) of drivers and amphetamines in 1.2% (0.7% to 2.0%). We also found medications including benzodiazepines (4.0% (2.9% to 5.3%)), antidepressants (6.5% (5.2% to 8.1%)) and diphenhydramine (4.7% (3.5% to 6.2%)). Drivers aged over 50 years and those requiring hospital admission were most likely to have used medications. Overall, 40.1% (37.2% to 43.0%) of drivers tested positive for alcohol or at least one impairing drug and 12.7% (10.7% to 14.7%) tested positive for more than one substance. CONCLUSIONS: Alcohol, cannabis and a broad range of other impairing drugs are commonly detected in injured drivers. Alcohol is well known to cause crashes, but further research is needed to determine the impact of other drug use, including drug-alcohol and drug-drug combinations, on crash risk. In particular, more work is needed to understand the role of medications in causing crashes to guide driver education programmes and improve public safety.

Deaths from exposure to paramethoxymethamphetamine in Alberta and British Columbia, Canada: a case series.

BACKGROUND: Paramethoxymethamphetamine (PMMA) is a ring-substituted amphetamine similar in structure to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"), but substantially more toxic. We describe the clinical features of fatal exposures in the provinces of Alberta and British Columbia, Canada. METHODS: We conducted a retrospective case series on deaths in Alberta and BC between June 2011 and April 2012 for which forensic toxicologic analysis was positive for PMMA and the drug was implicated as the primary toxic agent. Data collected included patient demographics, exposure history, clinical features, investigations, therapy provided and postmortem toxicologic findings. RESULTS: A total of 27 PMMA-associated deaths (20 in Alberta, 7 in BC) were reported in the 11-month period. The median age was 24 (range 14-52) years, and 22 (81%) were male. Ten patients were pronounced dead at the scene, and 17 died in hospital. The median time from exposure to death was 17 (range 5-264) hours. The median first-recorded vital signs (and ranges) were: heart rate 160 (86-201) beats/min, blood pressure 89/43 (69/30-162/83) mm Hg, respiratory rate 40 (26-48) breaths/min, oxygen saturation 81% (68%-100%) and temperature 39.4°C (34-43.8°C). Sixteen of the 17 people who died in hospital presented with clinical features consistent with serotonin syndrome. End-organ dysfunction included hepatic (30%) and acute kidney injury (85%), rhabdomyolysis (54%), coagulopathy (61%) and cardiac ischemia (15%). Other drugs identified on toxicologic analysis were MDMA (n = 27), cocaine or its metabolite benzoylecgonine (n = 14) and methamphetamine (n = 12). INTERPRETATION: Exposure to PMMA was characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. In addition to PMMA, multiple synthetic amphetamines were present on toxicologic analysis. When evaluating patients suspected of exposure to sympathomimetic drugs of abuse, clinicians must anticipate multiple clinical effects from the increased release of dopamine, serotonin, norepinephrine and other neurotransmitters.

Fomepizole fails to prevent progression of acidosis in 2-butoxyethanol and ethanol coingestion.

INTRODUCTION: 2-butoxyethanol (2BE) is a solvent commonly incorporated into household and industrial cleaning products. Its ingestion causes rapid central nervous system depression, hypotension, and metabolic acidosis attributable to metabolism of the parent compound to butoxyacetic acid (BAA) by alcohol dehydrogenase. Lactic acidosis is also reported to develop in some cases. Published treatment strategies include the use of ethanol infusion, ethanol with concomitant dialysis, dialysis alone, and fomepizole. CASE REPORT: We present an unusual case of a coingestion of ethanol and 150-250 mL of pure 2BE, which resulted in rapid obtundation, severe airway edema, hypotension, and prolonged acidosis despite the coingestion of ethanol and the administration of a loading dose of fomepizole. Continuous veno-venous hemodialysis was employed to treat the acidosis. Ingestion was confirmed by gas chromatography and mass spectrometric determinaiton of 2BE and BAA. The patient recovered without sequelae. CONCLUSION: Alcohol dehydrogenase inhibitors may not be adequate to prevent acidosis in significant ingestions to 2BE and extracorporeal treatments may be necessary.

A lethal ingestion of a household cleaner containing pine oil and isopropanol.

This paper presents the case of a woman with a history of schizophrenia found deceased in her residence after she apparently ingested an unknown quantity of a pine oil-containing product. A strong lemon-pine odor emanated from the body. Autopsy revealed a large volume of oily fluid in the stomach. The lungs were heavy, hemorrhagic, and necrotic. There was no evidence of significant recent injury or pre-existing disease. The toxicological screening and quantitation of 1-alpha-terpineol in postmortem fluids was performed by gas chromatography-mass spectrometry. Isopropanol and its metabolite acetone were determined by means of flame-ionization gas chromatography. Postmortem blood, urine, and stomach content levels of 1-alpha-terpineol were 276 mg/L, 0.5 mg/L, and 4.0 g/total contents, respectively, and isopropanol levels were 730 mg/dL, 20 mg/dL, and 1000 mg/dL, respectively. No acetone could be detected. Her death was attributed to the combined toxicity of isopropanol and pine oil.

Intoxicaçäo experimental por cinco espécies de Senecio em bovinos e aves / Experimental poisoning of cattle and chicks by five Senecio species

Com o objetivo de determinar a toxicidade de espécies de Senecio existentes na regiäo, cinco espécies desse gênero de planta foram administradas experimentalmente a frangos e bovinos. Para os frangos, que receberam a planta dessecada misturada a 5% na raçäo durante 60 dias, todas as espécies resultaram tóxicas na seguinte ordem de toxicidade: Senecio brasiliensis, S. heterotrichius, S. cisplatinus, S. selloi e S. leptolobus. Aos bovinos, as plantas acima mencionadas foram administradas dessecadas nas doses de 22,5,45,90 e 180g/kg de peso vivo. S. leptolobus näo resultou tóxico nas doses utilizadas, e as outras 4 espécies foram tóxicas, o que evidencia que elas provavelmente participam na etiologia da seneciose em bovinos da regiäo, de vez que tem sido encontradas com evidências de terem sido consumidas. Foi realizada a determinaçäo química do conteúdo de alcalóides das espécies de Senecio utilizadas, observando-se integerrimina e retrorsina em Senecio brasiliensis (0,31% da matéria seca) e S. heterotrichius (0,19%); retrosina e senecionina em S. cisplatinus (0,16%) e S. selloi (0,10%) e neosenkirkina e florosenina em S. leptolobus (0,005%). Integerrimina, retrorsina, misturas de integerrimina e retrorsina e neosenkirkina e florosenina foram administradas a frangos, durante 45 dias, na dose de 50mg/kg de raçäo, sendo que as intoxicaçöes provocadas pelos alcalóides foram menos graves que as induzidas pelas plantas dessecadas, o que, provavelmente, foi devido à perda de alcalóides durante o processo de extraçäo e/ou durante a dessecaçäo e armazenagem das plantas