Detection of S-methylfenitrothion, aminofenitrothion, aminofenitroxon and acetylaminofenitroxon in the urine of a fenitrothion intoxication case

A 23-year-old male attempted suicide by ingesting approximately 50 ml of 5% fenitrothion emulsion, and vomited soon afterwards. He was admitted to a hospital about 3 h after ingestion. He recovered and was discharged from hospital 3 days after admission. The serum cholinesterase activity (normal range: 175-440 I.U.) was only 29 at 3 h, 32 at 1 day, 59 at 2 days and 75 at 3 days after ingestion. Fenitrothion and its metabolites in the body fluids were extracted by an Extrelut column extraction method, detected by a gas chromatograph equipped with either a hydrogen flame ionization detector or a flame photometric detector, and confirmed by a gas chromatograph-mass spectrometer. Fenitrothion concentration in the blood was 169.5 ng/g at 3 h after ingestion. The half life of blood fenitrothion concentration was found to be about 4.5 h. Fenitrothion metabolites, 3-methyl-4-nitrophenol, aminofenitrothion, aminofenitroxon, acetylaminofenitroxon and S-methylfenitrothion, were detected in the urine samples. All of them except S-methylfenitrothion were detected in the urine samples collected up to 62 h after ingestion. It would appear therefore that fenitrothion poisoning can be determined by detection and analysis of the metabolites in urine even if fenitrothion has not been detected in the blood.     

Fatal and non-fatal methomyl intoxication in an attempted double suicide

A 79-year-old man and his 73-year-old wife attempted double suicide by ingesting methomyl powder. The woman died 19 h after ingestion in spite of intensive care. At autopsy a large number of miliary hemorrhages were found in both thalami of the brain. Her husband, however, recovered after 10 days of treatment. Methomyl (CAS No. 16752-77-5, Lannate) in the biological materials was analyzed by gas chromatography-mass spectrometry. The methomyl concentration was 44 micrograms/g in the wife's serum sample collected 1 h after ingestion, and 0.2 microgram/g in the blood sample collected at autopsy. The methomyl concentration in the husband's blood sample collected 28 h after ingestion was from 0.01 to 0.1 microgram/g. It is suggested that prompt and adequate intensive care including a direct hemoperfusion is necessary to effect the recovery of patients with lethal blood levels of methomyl. The miliary hemorrhages found in the thalami of the brain are suspected to have been caused by asphyxia induced by methomyl intoxication.     

A case of death from prothiophos poisoning

A 62-year-old male, a farmer, who had ingested prothiophos (Tokuthion), died after 21 h of intensive care. Prothiophos in the tissues of the victim was extracted and purified by Extrelut column extraction. A gas chromatograph equipped with a flame photometric detector, and a gas chromatograph-mass spectrometer were used to detect prothiophos. The concentration of prothiophos was 10.9 micrograms/g in the brain, 8.6 micrograms/g in the kidney, 418 micrograms/g in the liver, 2.96 mg/g in the gastric contents and 4.69 mg/g in the intestinal contents. The case history and the distribution of prothiophos indicated that the cause of death was acute prothiophos poisoning.     

Correlation between 'on admission' blood toluene concentrations and the presence or absence of signs and symptoms in solvent abusers

For 1 year, from June 1987 to June 1988, toluene concentrations in blood samples of patients admitted to a psychiatric hospital after inhaling solvent vapor, collected on admission and 4 h later, were analyzed by gas chromatograph. Toluene levels in the first urine samples collected after admission were also analyzed and case histories were kept listing age, sex and physical and psychiatric effects. In all, 51 cases were studied--34 males and 17 females. (1) The average age of the males was 21.4 years and of the female 16.2 years. (2) The toluene concentrations in the blood collected on admission ranged from 0.3 to 22.8 micrograms/g. (3) Physical signs were observed in 9 patients with an "on admission" blood toluene concentrations of more than 3.0 micrograms/g; twice as many subjects (18), however, with blood toluene concentration greater than 3.0 micrograms/g were without physical signs. (4) The blood toluene concentrations of three cases in the condition known as twilight state were more than 10.0 micrograms/g. (5) In 24 cases with blood toluene concentrations below 3.0 micrograms/g, there were no physical signs. (6) Five subjects with blood toluene concentrations in the 0.8-5.2 micrograms/g range showed neuropsychiatric effects; however, 23 subjects in the same blood toluene concentration range did not exhibit psychiatric effects, and none of the subjects with blood toluene concentrations greater than 5.2 micrograms/g, 15 in all, had such effects.     

Fatal meprobamate self-poisoning

A case involving a suicidal overdose resulting from the ingestion of 90 tablets (400 mg) of meprobamate is presented. The drug was quantified using a gas chromatograph equipped with a flame ionization detector (FID). While the blood level was 204.6 micrograms/ml, the maximum concentration was found in the heart (708 micrograms/g), confirming the cardiac toxicity of meprobamate. Other drugs were not detected.     

Screening test of stimulants in human urine utilizing headspace gas chromatography for field test

An accurate and simple screening method of stimulants in human urine using headspace gas chromatography utilizing heat of dissolution of potassium carbonate was developed. A 4.9-g portion of potassium carbonate was put into the vial prior to sending to the field, and a 5-ml aliquot of urine, suspected of containing stimulants and internal standard components was pipetted. After the vial was sealed and shaken by hand, 1 ml of its headspace gas was taken by disposable syringe and injected into the gas chromatograph. A compact gas chromatograph device with flame ionization detector and fused silica capillary column was developed for this experiment. Detection limits of methamphetamine and amphetamine were 1.0 micrograms/ml and 1.5 micrograms/ml, respectively.     

Suicide with acetylsalicylic acid

The authors report on a suicide of a 41-year-old man with acetylsalicylic acid. According to his own statement the man had taken about 200 tablets of Aspirin (65 g acetylsalicylic acid) and initially showed no symptoms of intoxication. 4-5 hours after ingestion he vomited twice, but clear intoxication symptoms like convulsions and cardiac arrhythmia occurred not earlier than 11 hours after ingestion. Resuscitation by the emergency physician was not successful. The chemical-toxicological analysis (HPLC-DAD) of blood samples taken in the hospital approximately 12 h after ingestion showed salicylate in concentrations of 475 mg/L to 557 mg/L. The post-mortem concentrations of salicylate were within the lethal-toxic range, i.e. 762 mg/L in heart blood and 215 mg/L in femoral blood. All tested organs contained equally lethal salicylate levels (e.g. 503 mg/L in the liver and 251 mg/L in the brain).     

A fatal interaction of methocarbamol and ethanol in an accidental poisoning

A case is presented of a fatal drug interaction caused by ingestion of methocarbamol (Robaxin) and ethanol. Methocarbamol is a carbamate derivative used as a muscle relaxant with sedative effects. Therapeutic concentrations of methocarbamol are reported to be 24 to 41 micrograms/mL. Biological fluids were screened for ethanol using the Abbott TDx system and quantitated by gas-liquid chromatography (GLC). Determination of methocarbamol concentrations in biological tissue homogenates and fluids were obtained by colorimetric analysis of diazotized methocarbamol. Blood ethanol concentration was 135 mg/dL (0.135% w/v) and urine ethanol was 249 mg/dL (0.249% w/v). Methocarbamol concentrations were: blood, 257 micrograms/mL; bile, 927 micrograms/L; urine, 255 micrograms/L; gastric, 3.7 g; liver, 459 micrograms/g; and kidney, 83 micrograms/g. The combination of ethanol and carbamates is contraindicated since acute alcohol intoxication combined with carbamate usage can lead to combined central nervous system depression as a result of the interactive sedative-hypnotic properties of the compounds.     

A fatal case of oral ingestion of toluene

A 51-year-old male ingested orally a large quantity of toluene and died about 30 min later. The presence of toluene in body fluids and tissues was confirmed by gas chromatography and gas chromatography/mass spectrometry. Tissue distribution of toluene showed that the liver detected the highest content of toluene (433.5 micrograms/g), except for the stomach contents, followed by pancreas (88.2 micrograms/g), brain (85.3 micrograms/g), heart (62.6 micrograms/g), blood (27.6 micrograms/g), fat (12.2 micrograms/g) and finally cerebrospinal fluid (11.1 micrograms/g).     

Gas chromatographic determination of cresols in the biological fluids of a non-fatal case of cresol intoxication

A simple and rapid method for analysis of free and conjugated cresols in biological fluids was developed. Prior to and following freeing of the conjugated cresols by acid hydrolysis in a sealed ampoule, free cresols were extracted by Extrelut column extraction, determined by gas chromatography, and confirmed by gas chromatography-mass spectrometry. In a non-fatal case of cresol intoxication a 46-year-old male had ingested about 100 ml of a saponated cresol soap solution. The concentrations of xylenol (2,4- and/or 2,5-dimethylphenol) and p- and m-cresol in the serum sample collected on admission were 15.8 micrograms/g, 43.3 micrograms/g and 73.8 micrograms/g, respectively. The total cresol concentration of 117 micrograms/g in the serum is within the range of fatal concentrations, and it is suspected therefore that the patient's recovery was due to adequate therapy alone.     

Distribution of dimethoate in the body after a fatal organophosphate intoxication

Many organophosphate pesticides (OPs) such as dimethoate are used to eradicate household pests, and those occurring in agriculture and forestry sectors. Combinations of two or more different insecticides have been manufactured to increase their effectiveness. A case of death is presented as suspected organophosphates intoxication. Autopsy was unremarkable except for grayish fluid in the stomach, with garlicky odor. A systematic toxicological analysis on post-mortem specimens revealed high concentrations of dimethoate in blood 38 microg/mL, urine 0.47 microg/mL, brain 2.2 microg/g, myocardial muscle 7.6 microg/g, liver 4.6 microg/g, lung 7.6 microg/g, skeletal muscle 21 microg/g, kidney 55 microg/g and gall bladder 31 microg/g. Blood alcohol was 2.85 g/L, cyclohexanone and cyclohexanol were also detected in the blood but not quantified. The cause of death was determined as organophosphate intoxication.     

Acute fatal poisoning cases due to furathiocarb ingestion.

Seven cases involving acute fatalities due to ingestion of furathiocarb, a carbamate insecticide, are presented. Furathiocarb was detected in the gastric contents using thin layer chromatography (TLC) and gas chromatography/mass spectrophotometry (GC/MS), and quantified in the blood using a gas chromatograph equipped with a nitrogen-phosphorus detector (NPD). The fatal levels of furathiocarb in the blood ranged from 0.1 to 21.6 micrograms/ml.     

Colchicine poisoning by accidental ingestion of meadow saffron (Colchicum autumnale): pathological and medicolegal aspects

Although intoxications with colchicine, the alkaloid of Colchicum autumnale (meadow saffron), are well known, in most cases the intoxications are evoked by oral or parenteral preparations traditionally used as medication against gout. The accidental ingestion of Colchicum autumnale, on the other hand, is a rare event and has to our knowledge only twice been described in detail. We report a further case in which two persons confused this highly poisonous plant with wild garlic (Allium ursinum), a popular spice in the Central European cuisine. While one person merely complained about a 3-day episode of nausea, vomiting and watery diarrhea, the second person died of multi-organ system derangements 48 h after the ingestion of the colchicum leaves. At autopsy hemorrhagic lung oedema, hypocellular bonemarrow, centrilobular fatty necrosis of the liver and necrosis of the proximal convoluted tubuli of the kidneys were observed. A colchicine concentration of 7.5 micrograms/ml was found in the bile whereas no substance was detected in the postmortem blood.     

Forensic medicine and toxicologic aspects of 2-propanol poisoning

Two cases of poisoning with 2-propanol (isopropylalcohol) are reported. In one case, nail polish remover was drunk by a 2-year-old child. The concentration of 2-propanol and its metabolite acetone in the blood could be observed over a period of approximately 50 h. The highest concentration of 2-propanol determined was 4.22 g/l. Acetone reached a maximum value of 2.27 g/l 12 h after ingestion. The child survived without any observable after-effects. In the second case, a 35-year-old man drank ethanol in addition to 2-propanol. The poisoning was lethal. The possible time of intake before death is discussed in relation to the estimated levels of ethanol, 2-propanol and acetone found in the blood and urine. The histomorphological findings are often important as well with regard to time of intake.     

Determination of formic acid tissue and fluid concentrations in three fatalities due to methanol poisoning

Three fatalities caused by methanol ingestion are reported. Admission blood methanol concentrations ranged from 0.28 to 4.6 g/L. Two patients had been admitted after a significant delay (>20 hours), and one patient was observed within 90 minutes following ingestion. Formic acid levels were determined in blood samples at admission and ranged from 302 to 680 mg/L. The patients died 44, 55, and 82 hours after poisoning. Formic acid determinations in postmortem tissues were performed by a gas chromatograph method. The authors found great variability in formic acid distribution among the patients and among organs.     

Cyanide quantification in post-mortem biological matrices by headspace GC-MS

Cyanide is a powerful chemical asphyxiant found in some forensic cases following voluntary (suicide) or involuntary ingestion (fire, accidental exposure). A quantification method for cyanide that is specifically suited to post-mortem forensic purposes was developed. Determination was performed by headspace gas chromatography coupled to mass spectrometry using a GS-GASPRO column on an HP-6890 gas chromatograph with an HP-5973N mass detector. The biological sample was treated with an internal standard, frozen, glacial acetic acid was added and the sample was then incubated at 60°C for 15min. The headspace was sampled with a disposable syringe, and analyzed to quantify hydrogen cyanide. Isotopically labeled cyanide ((13)C(15)N) was used as the internal standard to minimize matrix effect and sampling error. The method produced an extended linear dynamic range (0.07-50μg/mL), and a method detection limit of 0.02μg/mL. Identical calibration curves were obtained when blood, gastric contents and aqueous solutions were used as the calibration standard matrix. This method was also successful in quantitating cyanide in gastric contents, one of the most variable biological fluids. The method has been validated and is being used for current forensic cases such as fire victims and suicides.     

Fatal colchicine poisoning by accidental ingestion of meadow saffron-case report

A 62-year-old male died of colchicine poisoning after accidental ingestion of Colchicum autumnale (meadow saffron). He ate a salad of plant with green leaves regarded as wild garlic (Allium ursinum). A few hours later he developed symptoms of gastroenteritis and was admitted to hospital. In spite of gastric lavage, activated charcoal and supportive measures, multi-organ system failure developed over the next two days. Laboratory analysis showed highly elevated blood concentrations of hepatic enzymes, creatine kinase, lactate dehydrogenase and blood urea nitrogen, as well as leukocytopenia and thrombocytopenia. Mechanical ventilation, dopamine, noradrenaline, crystalloid solutions and fresh frozen plasma were applied but despite treatment the patient died five days after the ingestion. Post-mortem examination revealed hepatic centrilobular necrosis, nephrotoxic acute tubular necrosis, petechial bleeding in fatty tissue, blunt and shortened intestinal villi and cerebral toxic edema. Botanical identification of incriminated plant gave Colchicum autumnale which confirmed colchicine poisoning. Although the accidental ingestion of Colchicum autumnale is rare and to our knowledge only five such cases have been described in detail, this is the second fatal case in Croatia described in the last 3 years.     

Toxicological analysis of a fatal baclofen (Lioresal) ingestion

A fatality following ingestion of the drug baclofen (Lioresal) is described. Baclofen was identified in urine by gas chromatography/mass spectrometry. After derivatization with trinitrobenzene sulfonic acid, baclofen was quantitated in serum and urine by high-performance liquid chromatography. The concentration of baclofen was 17 mg/L in serum and 760 mg/L in urine collected approximately 12 h after the overdose. To our knowledge, this is only the second reported fatality involving a baclofen overdose. The previous case did not include quantitation of baclofen in any biological fluid.     

A case of fatal poisoning with the aconite plant: quantitative analysis in biological fluid.

In recent years recorded cases of plant poisoning have become rare, this may in part be due to the possibility of plant ingestion not being indicated at the beginning of an investigation. Aconitum napellus (aconite, Wolfsbane, Monkshood) is one of the most poisonous plants in the UK. It contains various potent alkaloids such as aconitine, isoaconitine, lycaconitine and napelline. Ingestion of Aconitum plant extracts can result in severe, potentially fatal toxic effects. This paper describes the analytical findings in a recent death in the UK. resulting from deliberate ingestion of Aconitum napellus extract. The concentrations of aconitine measured by HPLC-DAD in the post mortem femoral blood and urine were 10.8 micrograms/L and 264 micrograms/L, respectively. The aconitine concentration in the ante mortem urine was 334 micrograms/L and was estimated to be 6 micrograms/L in the ante mortem serum. Hence, accidental, suicidal or homicidal poisoning due to the ingestion of plant material remains a possibility and should be borne in mind when investigating sudden or unexplained death.     

Toxicological study on intravenous thiopental anesthesia--interrelation between rate of injection and distribution of thiopental

A simple, rapid and accurate method to extract and clean thiopental in biological materials rich in fat was developed by using a separation column packed with Extrelut and Florisil. A Quantitative determination of thiopental by means of a gas chromatograph equipped with a flame photometric sulfur detector was attempted. The calibration curve was linear over the range of 5-200 micrograms/ml. Extraction of replicate tissues involving 3 micrograms of thiopental resulted in a recovery of the 99.7-101.8% range and a coefficient of deviation of the 0.3-1.9% range. Replicate extraction of five tissues from rats treated with thiopental resulted in a coefficient of deviation of below 6%. In rats given 40 mg/kg of thiopental and sacrificed after 5 min, the thiopental levels in fat were found to be higher after a slow intravenous injection than after a quick injection. The same tendency, however, was not observed in other tissues. It seems that the rate of intravenous thiopental injections might be estimated by comparison with thiopental levels in fat tissues.