Bone as a biomarker of acute fluoride toxicity

The use of bone as a biomarker for chronic and acute exposure to fluoride salts has been suggested, but there are no data published about its use to evaluate lethal intoxication. One hundred and sixty rats were divided into eight groups that received a single oral intubation dose from 0 (control) to 90 mg F/kg as NaF. The animals' time of death was recorded and their femurs were removed for fluoride analysis. Acid-soluble fluoride was determined in the whole bone and on the surface (periosteal), using an ion specific electrode. The data showed a statistically significant relationship between fluoride dose and the number of deaths (P<0.0001). A statistically significant relationship was also found between fluoride dose and fluoride concentration ([F]) in either the whole femur (P<0.0017), on the surface (P<0.0001) or for the ratio periosteal [F]/whole [F] (P<0.0001). However, the [F] on the femur surface was more closely correlated with mortality than that in the whole bone, showing statistically significant differences among the lethal doses and control (P<0.05). The data suggest that the ratio [F] periosteal bone/[F] whole bone, is a biomarker for acute fluoride toxicity.     

Suicide by exposure to sulfuryl fluoride

The insecticide fumigant, sulfuryl fluoride, was used as an instrument of self destruction in at least two of the three fatal exposures detailed in this report. The autopsy findings, while nonspecific, have a confirmatory value. Toxicologic analysis should include a plasma and a urine fluoride level, since the toxic effects of exposure are probably related to this ion. Concentrations of fluoride in our cases were: 50.42 mg/L (Case 1) and 20 mg/L (Case 3). However, the values must be interpreted in light of all known information as a result of the paucity of reported cases of fatal sulfuryl fluoride exposures. The cases described provide a model for the investigation of tent fumigation deaths. Proper investigation of fumigant deaths requires knowledge of the insecticide, the fumigation procedure, and the implementation of warning devices. Guidelines are offered along with a procedural checklist for the investigation of tent fumigation deaths.     

Nutmeg (myristicin) poisoning--report on a fatal case and a series of cases recorded by a poison information centre

In literature, cases of nutmeg abuse have been described repeatedly, but only one fatal case of poisoning was reported [1]. In the present case, myristicin (4 microg/ml) was detected for the first time in the postmortal serum of a 55-year-old woman. Identification was achieved with the aid of UV-VIS spectroscopy and TLC; for quantification, HPLC was used. Because also flunitrazepam (0.072 microg/ml) was found, death had probably been due to the combined toxic effect of both substances. From 1996 to 1998, in a series of cases, seven poisonings with nutmeg were recorded by the Erfurt Poison Information Centre. Even where higher doses (20-80 g of powder) had been ingested, a life-threatening situation was never observed. In one of these cases, a myristicin blood level of 2 microg/ml was measured 8h after ingestion of two to three tablespoonful of nutmeg powder (approx. 14-21 g, or 280-420 mg/kg).     

A fatal case of poisoning with cantharidin.

A case of fatal poisoning due to voluntary ingestion of cantharides powder for aphrodisiac purposes is reported. Clinical history, autopsy and analytical findings are described. Blood and urine samples collected during the 30 h of survival, as well as the cantharides product, were analyzed by gas chromatography-mass spectrometry. On the basis of the percentage of the active principle measured in the powder, an ingested dose of 26-45 mg of cantharidin could be estimated.     

Effect of sodium fluoride on cholinesterase activity in postmortem blood

Thirty-two postmortem blood specimens, with and without sodium fluoride as preservative, were analyzed for cholinesterase activity by the Michel method. The fluoridated specimens, which contained from 0.7 to 31 mg/mL (average 6.3) of sodium fluoride, were found to exhibit cholinesterase activities that were 5 to 59% (average 25%) lower than the duplicate unfluoridated specimens. We concluded that, while this decrease is quite significant, a fluoridated postmortem blood specimen may be used for the measurement of cholinesterase activity when a non-fluoridated specimen is unavailable.     

Hydrofluoric acid poisoning

A case of suicidal ingestion of hydrofluoric acid is presented. Death of the victim while in police custody was one of the more unique aspects of the case. This is the sixth case of poisoning of this type reported in Dade County. Clinical, pathological, and toxicological aspects of fluoride poisoning are discussed.     

Suicide of an adolescent girl with sodium nitrite ordered on the internet

Nitrites are commonly used in the chemical, pharmaceutical, and food industries. Recently, they have been identified in cases of voluntary intoxication. We report the case of a 13-year-old girl who was found lifeless on her bed next to a glass containing a white powder and a bottle containing a white powder with a moistened appearance. External examination and autopsy revealed a nonspecific asphyxia syndrome, which was confirmed by the pathological analysis. Analysis of the samples revealed metoclopramide in the peripheral blood at a concentration of 0.402 mg/L (LC–HRMS). An analysis of the gastric contents was carried out after sodium nitrite was detected in the powders found near the body (Raman spectrometry). Nitrites were found in the gastric fluid at a concentration of 30.9 mg/L. Death occurred secondary to anoxia, following ingestion of nitrites; suicide kits are available on the web and nitrites are relatively easy to source and inexpensive. Nitrites are delivered in powder form to be dissolved in liquid, which may then be consumed with metoclopramide (or an alternative anti-emetic drug) to maximize absorption and reduce emesis. The toxic effect of nitrites lies in their oxidizing power, causing the transformation of hemoglobin into methemoglobin, which, when it accumulates, induces tissue anoxia resulting in death. There has been an alarming increase in the number of cases linked to suicide using nitrites or a nitrite suicide kit. The fact that nitrites are readily available online underscores the importance of establishing effective preventive measures such as limiting the access and use of this chemical.     

Fatal intoxication with 1,4-butanediol: Case report and comprehensive review of the literature

A fatal case of 1,4-butanediol (1,4-BD) oral ingestion is reported here, in which a 51-year-old man was found dead in his bed. According to the police report, the deceased was a known drug user. A glass bottle labeled (and later confirmed to be) “Butandiol 1,4” (1,4-BD) was found in the kitchen. Furthermore, the deceased's friend stated that he consumed 1,4-BD on a regular basis. The autopsy and histological examination of postmortem parenchymatous organ specimens did not revealed a clear cause of death. Chemical-toxicological investigations revealed gammahydroxybutyrat (GHB) in body fluids and tissues in the following quantities: femoral blood 390 mg/L, heart blood 420 mg/L, cerebrospinal fluid 420 mg/L, vitreous humor 640 mg/L, urine 1600 mg/L, and head hair 26.7 ng/mg. In addition, 1,4-BD was qualitatively detected in the head hair, urine, stomach contents, and the bottle. No other substances, including alcohol, were detected at pharmacologically relevant concentrations. 1,4-BD is known as precursor substance that is converted in vivo into GHB. In the synoptic assessment of toxicological findings, the police investigations and having excluded other causes of death, a lethal GHB-intoxication following ingestion of 1,4-BD, can be assumed in this case. Fatal intoxications with 1,4-BD have seldom been reported due to a very rapid conversion to GHB and, among other things, non-specific symptoms after ingestion. This case report aims to give an overview to the published of fatal 1,4-BD-intoxications and to discuss the problems associated with detection of 1,4-BD in (postmortem) specimens.     

A diflunisal related fatality: a case report

A case is reported where the death of an individual resulted from the ingestion of diflunisal. Diflunisal was identified by a combination of liquid chromatography, UV spectrophotometry and colorimetry. Diflunisal was quantified in blood (260 mg/l), bile (71 mg/l), kidney (350 mg/kg), liver (400 mg/kg), stomach contents (34 mg) and urine (78 mg/l). No previous literature references discussing diflunisal related fatalities were available.     

A case of suicide by ingestion of sodium nitroprusside.

The study reports a case of suicide by ingestion of sodium nitroprusside which resulted in acute cyanide poisoning. Analyses carried out on body fluid yielded the quantitation of total (5.00 mg/L) and free (3.30 mg/L) cyanide in blood and of methemoglobin (blood = 10.5%). At the scene, some solid reddish-brown material was found in a glass, which on toxicological analysis was found to contain sodium nitroprusside; about 9 g of the same substance was identified in stomach contents. The detection and quantification of cyanide and methemoglobin in biological samples from the case indicated that the lethal effect was due to both metabolic products (cyanide and methemoglobin).     

Fatal Case of a 27‐Year‐Old Male After Taking Iboga in Withdrawal Treatment: GC‐MS/MS Determination of Ibogaine and Ibogamine in Iboga Roots and Postmortem Biological Material

We report the case of a man who died twelve hours after ingesting powdered iboga root, commonly taken for its stimulant and hallucinogenic properties. Ibogaine and ibogamine were quantified in the powder ingested and the victim's body fluids by GC‐MS/MS after liquid–liquid extraction (Toxi‐tubes A^®). The concentrations of ibogaine measured in the blood samples taken at the scene and in the peripheral blood, urine, and gastric fluid samples taken during the autopsy were 0.65, 1.27, 1.7, and 53.5 μg/mL, while the iboga content in the powder was 7.2%. Moreover, systematic toxicological analyses of biological samples showed the presence of diazepam and methadone in therapeutic concentrations. Death was attributed to the ingestion of a substantial quantity of iboga in the context of simultaneous methadone and diazepam consumption.     

Accidental boric acid poisoning following the ingestion of household pesticide

Borate-containing compounds were formerly used as topical antiseptics and were components of many medicinal preparations including skin powders and ointments used for the treatment of burns and diaper rash. These compounds were also used as irrigants for body cavities, including the pleural, vaginal, and rectal cavities. These applications were subsequently discontinued by the medical community when the toxicity and potential lethality of borates were recognized. Although documented cases of borate poisoning are now rare, the chemical is still an active component commonly used in high concentrations in household disinfectants/cleaners, pesticides, and wood preservatives. While the majority of documented borate-related deaths have occurred in infants, the toddler population is currently at risk due to possible exposure to these household products. We present the case of an 18-month-old child who died following the accidental ingestion of a boric acid-containing, commercially available roach pesticide product.     

Mixed drug intoxication involving zaleplon ("Sonata")

Zaleplon ("Sonata") is a pyrazolopyrimidine derivative approved for use in the United States for the treatment of insomnia. To date, there has been little data in the toxicological literature where zaleplon has been implicated as causing a fatal intoxication, either alone or in combination with other drugs. This report documents a case where zaleplon was identified in a suicide by multiple drug ingestion. The following zaleplon concentrations were found: heart blood 2.2mg/l; bile 8.6mg/l and urine 1.4mg/l. Zaleplon was also detected but not quantitated in the kidney and liver.     

Fatal Overdose of Gamma‐hydroxybutyrate Acid After Ingestion of 1,4‐Butanediol

We report a case of fatal intoxication from 1,4‐butanediol (1,4‐BD), which was ingested by a young and “naïve” gamma‐hydroxybutyrate (GHB) consumer during a party with the co‐ingestion of alcohol, cannabis, and methylene‐dioxy‐methamphetamine. The following drug concentrations were found using gas chromatography coupled with mass spectrometry on autopsy samples and on a cup and a glass found at the scene: 20,350 mg/L (bottle) for 1,4‐BD; 1020 mg/L (femoral blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L (vitreous humor) for GHB. The concentration of GHB is difficult to interpret in forensic cases due to the possibility of an endogenous production of GHB. The variable tolerance of the user may also modify the peri‐ and postmortem GHB concentrations. This case underscores the need to have many different sources of toxicology samples analyzed to avoid the hypothesis of endogenous production of GHB.     

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.     

Disopyramide and Mianserin Intoxication: A Unique Fatal Case – Review of the Literature

Lethal occurrence is exceptional after disopyramide or mianserin poisoning. A case of intentional lethal intoxication with these drugs was reported, as well as a review of the literature. Pre‐ and postmortem blood concentrations of disopyramide or mianserin were assessed in a woman who died from acute cardiac failure after ingestion. The premortem blood concentration of disopyramide alone was considered lethal, and a toxic premortem concentration of mianserin was observed that may have increased cardiovascular failure induced by disopyramide because the metabolism of both drugs is mediated via cytochrome P450. Moreover, it was shown that the postmortem redistribution of disopyramide was limited, as pre‐ and postmortem concentrations were 48 and 65 mg/L, respectively. As regards mianserin, redistribution was observed after death with pre‐ and portmortem concentrations at 0.23 and 0.79 mg/L, respectively. This case illustrates that if postmortem blood concentration of disopyramide is known, the premortem concentration can be deduced.     

Postmortem detection of isopropanol in ketoacidosis

Isopropanol (IPA) detected in deaths because of diabetic ketoacidosis (DKA) or alcoholic ketoacidosis (AKA) may cause concern for IPA poisoning. This study addressed this concern in a 15-year retrospective review of 260 deaths in which concentrations of acetone and IPA, as well as their ratios, were compared in DKA (175 cases), AKA (79 cases), and IPA intoxication (six cases). The results demonstrated the frequency of detecting IPA in ketoacidosis when there was no evidence of IPA ingestion. IPA was detectable in 77% of DKA cases with quantifiable concentrations averaging 15.1 ± 13.0 mg/dL; 52% of AKA cases with quantifiable concentrations averaging 18.5 ± 22.1 mg/dL; and in cases of IPA intoxication, averaging 326 ± 260 mg/dL. There was weak correlation of IPA production with postmortem interval in DKA only (r = -0.48). Although IPA concentrations were much higher with ingestion, potentially toxic concentrations were achievable in DKA without known ingestion.     

Determination of Nicotine,Cotinine and Trans‐3′‐Hydroxycotinine using LC/MS/MS in Forensic Samples of a Nicotine Fatal Case by Oral Ingestion of e‐cigarette Liquid,

Nicotine is a potent neurotoxin alkaloid and is used in e‐cigarette liquid. The LC/MS/MS method was linear over 0.01–1.0 mg/L (r² = 0.992–0.995). Limit of detection and limit of quantitation were 0.001 mg/L (S/N = 3) and 0.003 (S/N = 10). The inaccuracy and imprecision were <13.2%. The recoveries were >99.3%. A 39‐year‐old dentist was found dead lying on the floor under the couch in his dental clinic. The concentration of nicotine, cotinine, and trans‐3′‐hydroxycotinine (heart blood/peripheral blood) was analyzed as follows: 87.2/85.2 mg/L (ratio 1.0), 1.4/1.1 mg/L (ratio 1.3), and 0.012/0.0089 mg/L (ratio 1.3), respectively. The concentration of nicotine was determined to be 6734.8 mg/kg in gastric contents and 7262.0 mg/L in remaining e‐liquid. Only, high concentration of nicotine was detected in the gastric contents as well as the two pieces of evidence collected from the death scene. This fatal case resulted from oral ingestion of e‐cigarette liquid. It is estimated that at least 714 mg of nicotine was orally ingested.     

Urinary excretion of benzoylecgonine following ingestion of Health Inca Tea

Four males ingested one cup of Health Inca Tea which contained 1.87 mg of cocaine. Urine specimens collected for 36 h post-ingestion were analyzed for benzoylecgonine (BE) by EMIT-d.a.u., TDx and gas chromatography/mass spectrometry (GC/MS). Positive immunoassay results were obtained for 21-26 h post tea ingestion. Discrepant immunoassay results occurred with only one specimen: EMIT positive; TDx negative, 0.25 mg/l; GC/MS, 0.273 mg/l. Quantitative TDx results were well correlated with GC/MS results, r2 = 0.963, n = 45. Maximum urinary BE concentrations ranged from 1.4-2.8 mg/l, occurring from 4-11 h, post ingestion. Total BE excretion in 36 h ranged from 1.05 to 1.45 mg, 59-90% of the ingested cocaine dose. Urinary excretion rate constant (Km) ranged from -0.073 to 0.111/h. Health Inca Tea ingestion should be considered when interpreting urinary BE concentrations.