Acute 3,4-methylenedioxy-N-ethylcathinone (ethylone) intoxication and related fatality: a case report with postmortem concentrations.

A 30-year-old man reportedly ingested pills and used illicit drugs with another person. They both fell asleep that night and the following afternoon the other person found him dead. There were used hypodermic needles and a metal spoon with dark tarry substance at the death scene, and two recent puncture sites were found on his body. It was uncertain if he had a history of illicit drug use. Postmortem blood initially screened borderline positive for methamphetamine by ELISA. An alkaline drug screen-detected ethylone which was subsequently confirmed and quantified by a specific GC-MS SIM analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (0.39 mg/L), central blood (0.38 mg/L), liver (1.4 mg/kg), vitreous (0.58 mg/L), urine (20 mg/L) and gastric contents (12 mg). Other compounds detected in peripheral blood were morphine (0.05 mg/L), alprazolam (<0.05 mg/L), delta-9-THC (<1 ng/mL), delta-9-carboxy-THC (3.6 ng/mL) and naproxen (<5 mg/L). A urine screen (GC-MS) also confirmed 6-monoacetylmorphine, codeine and sildenafil. The cause of death was certified due to mixed ethylone, heroin and alprazolam intoxication. The manner of death was certified as accident.

Ethylone-Related Deaths: Toxicological Findings.

Synthetic cathinones are an emerging class of designer drugs, frequently with deceptive labels and a multitude of analogs to circumvent drug control regulations. Research regarding the pharmacological effects and toxicity of these amphetamine derivatives is scarce, heightening the risk to the public health and safety. The composition of synthetic cathinone products continually changes and laboratories began to notice ethylone-positive products in late 2011. This report presents nine postmortem cases in whom ethylone was identified. Ethylone was isolated using solid-phase extraction and detected by gas chromatography-mass spectrometry. Seven of the cases had measurable concentrations of ethylone in blood, ranging from 38 to 2,572 ng/mL; ethylone was detected in the blood sample of one case with a concentration below the assay limit of quantification (25 ng/mL), and one case did not have detectable ethylone in blood. Besides ethylone, all but one case were also positive for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol; seven cases had other drugs quantified in blood, including ethanol, alprazolam, benzoylecgonine, diphenhydramine, morphine and tramadol. In five cases where ethylone was present at blood concentrations >400 ng/mL, no other drugs excluding ethanol, cannabis metabolite and doxylamine (one case) were found. The assay also tested for mephedrone, methylone and three dimethoxyamphetamine analogs; no case was positive for these analytes. The present report documents postmortem blood concentrations of ethylone, a novel synthetic cathinone, along with other concurrently identified substances. The findings provide valuable information for developing analytical assays and evaluating a toxic concentration range of ethylone.

Elimination half-life of acetone in humans: case reports and review of the literature.

Two instances of finding abnormally high concentrations of acetone in urine (0.10 g/dL and 0.052 g/dL) without any measurable amounts of ethanol (<0.005 g/dL) or isopropanol (<0.005 g/dL) prompted a survey of the elimination kinetics of isopropanol and its metabolite acetone in humans. In a hospital patient who had ingested denatured alcohol, the elimination half-life (t(1/2)) of acetone during detoxification was 27 h and not 3-5 h as reported by other workers. Several other literature reports of individuals who had ingested isopropanol as well as controlled studies after administration of moderate amounts of acetone and/or isopropanol support the notion of a long elimination half-life of 17-27 h for acetone compared with a t(1/2) of 1-3 h for isopropanol.

Neuropathy in an artist exposed to organic solvents in paints: a case study.

A 61-year-old artist in Israel had been painting for 30 years in his home studio. He had been healthy until he reached the age of 59.5 years, at which time he began complaining of weakness and paresthesia in both hands and legs. He also complained that he had difficulty concentrating, and his memory was impaired. His work was unusual in that he painted large posters (i.e., 2 x 3 m) with different mixtures of organic solvents, including toluene, xylene, benzene, methyl ethyl ketone, toluene diisocyanate, acetone, and thinner. He did not use any protective gloves and did not wear a mask. He was evaluated with several methods and was diagnosed as having peripheral and central neuropathy, including ototoxic hearing loss as a result of long exposures to organic solvents. The authors were unable to find any similar case report in the literature.

Isopropanol poisoning.

INTRODUCTION: Isopropanol is a clear, colorless liquid with a fruity odor and a mild bitter taste. Most commonly found domestically as rubbing alcohol, isopropanol is also found in numerous household and commercial products including cleaners, disinfectants, antifreezes, cosmetics, solvents, inks, and pharmaceuticals. AIM: The aim of this review is to critically review the epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, diagnosis, and management of isopropanol poisoning. METHODS: OVID MEDLINE and ISI Web of Science were searched to November 2013 using the words "isopropanol", "isopropyl alcohol", "2-propanol", "propan-2-ol", and "rubbing alcohol" combined with the keywords "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", or "intoxication". These searches identified 232 citations, which were then screened via their abstract to identify relevant articles referring specifically to the epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, diagnosis, and management of isopropanol poisoning; 102 were relevant. Further information was obtained from book chapters, relevant news reports, and internet resources. These additional searches produced eight non-duplicate relevant citations. EPIDEMIOLOGY: The majority of isopropanol exposures are unintentional and occur in children less than 6 years of age. Although isopropanol poisoning appears to be a reasonably common occurrence, deaths are rare. TOXICOKINETICS: Isopropanol is rapidly absorbed following ingestion with peak plasma concentrations occurring within 30 min. It can also be absorbed following inhalation or dermal exposure. Isopropanol is widely distributed with a volume of distribution of 0.45-0.55 L/kg. Isopropanol is metabolized by alcohol dehydrogenase to acetone, acetol and methylglyoxal, propylene glycol, acetate, and formate with conversion of these metabolites to glucose and other products of intermediary metabolism. The elimination of isopropanol is predominantly renal, though some pulmonary excretion of isopropanol and acetone occurs. In one case 20% of the absorbed dose was eliminated unchanged in urine, with the remainder excreted as acetone and metabolites of acetone. The elimination half-life of isopropanol is between 2.5 and 8.0 h, whereas elimination of acetone is slower with a half-life following isopropanol ingestion of between 7.7 and 27 h. MECHANISMS OF TOXICITY: While the exact mechanism of action of isopropanol has not been fully elucidated, brain stem depression is thought to be the predominant mechanism. While the clinical effects are thought to be mostly due to isopropanol, acetone may also contribute. CLINICAL FEATURES: The major features of severe poisoning are due to CNS and respiratory depression, shock, and circulatory collapse. The most common metabolic effects are an increased osmol (osmolal) gap, ketonemia, and ketonuria. Diagnosis. Poisoning can be diagnosed using the measurement of isopropanol serum concentrations, though these may not be readily available. Diagnosis is therefore more typically made on the basis of the patient's history and clinical presentation. An osmol gap, ketonemia, and/or ketonuria without metabolic acidosis, along with a fruity or sweet odor on the breath and CNS depression support the diagnosis. Management. Supportive care is the mainstay of management with primary emphasis on respiratory and cardiovascular support. Hemodialysis enhances elimination of isopropanol and acetone and should be considered in very severe poisoning. CONCLUSIONS: Severe isopropanol poisoning results in CNS and respiratory depression and circulatory collapse. Treatment primarily consists of symptom-directed supportive care. Although hemodialysis increases the elimination of isopropanol and acetone substantially, it should only be considered in severe life-threatening poisonings. Patients usually make a full recovery provided they receive prompt supportive care.

Acute acetone intoxication in a pediatric patient.

The widespread presence of fingernail polish remover in the home makes the product a common source of ingestion, as evidenced by recent poison center data. Its principal component, acetone, is present in relatively high concentration. The syndrome of acetone intoxication presents as generalized central nervous system/respiratory depression, hyperglycemia, and ketosis. Despite its ubiquitous presence and high potential for severe intoxication, no reports are found describing the toxicity and supportive care following its ingestion by children. The authors present a 30-month-old patient with severe acetone intoxication secondary to fingernail polish remover ingestion. Also noted is the need to include acetone ingestion in the differential diagnosis of apparent diabetic ketoacidosis.

[Survival after poisoning due to intake of ten-times lethal dose of acetone]. / Uberlebte Vergiftung nach Einnahme der zehnfachen Letaldosis von Aceton.

HISTORY AND ADMISSION FINDINGS: A 42-year-old man was found unconscious, having swallowed 800 ml of an unknown liquid with suicidal intent. On admission, when his breath smelled strongly of acetone, he was intubated and ventilated, and several gastric lavages were performed. INVESTIGATION: The serum acetone concentration was 2000 mg/l, that in urine 2300 mg/l. The residue of the liquid in the bottle from which he had drunk was pure acetone. DIAGNOSIS, TREATMENT AND COURSE: Acetone poisoning having been established he was carefully hyperventilated, haemofiltration was performed over 16 hours and forced diuresis with high fluid intake was undertaken. His condition quickly improved and he was extubated after 14 hours. There was no subsequent evidence of organ damage. Repeated measurements of acetone in blood and urine indicated its elimination with a half-life of 11 hours. Literature search revealed that this was the second highest concentration of acetone in blood and urine followed by survival. CONCLUSION: This case demonstrates that, after acute acetone poisoning with an amount ten times the lethal dose, intensive care and rapid elimination of acetone can achieve sequelae-free survival.

Solvent exposure and ratings of well-being: dose-effect relationships and consistency of data.

Ratings on analog scales for dimensions of well-being provide information about the acute state of well-being during solvent exposure. In a study of volunteers and workers exposed to solvents, tension, tiredness, complaints, and annoyance were rated on seven-point scales. Dose-effect relationships were analyzed for several scenarios; data were collected in diaries during work hours. In two studies, 40 volunteers in an exposure laboratory were exposed to ethanol by inhalation at levels between 80 and 1900 parts per million (ppm). In two other studies, 32 volunteers were exposed to acetone and ethyl acetate in single exposures (1000 and 500 ppm, respectively) and combined exposures (500 ppm acetone + 200 ppm ethyl acetate). A field study of 8 exposed workers and 8 nonexposed controls involved exposures of up to 2100 ppm acetone. Dose-effect relationships were shown for ratings of annoyance by correlations of 0.36 (ethanol) and 0.58 (acetone). Similar coefficients were found for ratings of complaints. The dimensions tension and tiredness showed no stable relationship with exposure. The consistency of ratings was assessed by means of correlations between the ratings given during periods of nearly equal exposures. Ratings of annoyance for the different studies between the periods of nearly equal exposure showed average correlations from 0.68 to 0.84. For the ratings of complaints, the coefficients were 0.53 to 0.81. The coefficients for tension had similar stabilities; those for tiredness were lower.

Disposition of acetone, methyl ethyl ketone and cyclohexanone in acute poisoning.

A case of coma due to the drinking of a liquid cement for polyvinyl chloride resin, containing acetone, methyl ethyl ketone, cyclohexanone and polyvinyl chloride is described. The patient also simultaneously ingested the alcoholic beverage, sake. After gastric lavage, plasma exchanges and direct hemoperfusions, the patient recovered. The concentrations of these chemicals in plasma and urine were analyzed at various time intervals to estimate the clearance. The elimination half lives for acetone and methyl ethyl ketone were 18 hours and 10 hours, respectively. Although cyclohexanone made up the largest component in the solvents, the blood level was extremely low and a large amount of cyclohexanol, a metabolite of cyclohexanone was detected in the blood and urine. The glucuronide metabolite of cyclohexanol was also estimated after the hydrolysis with beta-glucuronidase. Since the conversion of cyclohexanone to cyclohexanol is known to be catalyzed by alcohol dehydrogenase, possible interactions between sake ingestion and cyclohexanone metabolism is proposed.