Structure of the hair in thallium poisoning

The alterations in the hair roots discovered by Widy in 1956 were interpreted as accumulations of pigment which form as a consequence of a catalytic action of the poison. The goal of the present investigation was to clarify the structure of these inclusions. Hair from the heads of six victims who were involved in the poisoning of Würzburg medical students in January 1983 was available as investigation material. In the investigation in transmitted light and in polarized light, the black zones typical for thallium intoxication were found filling to varying extents the root and hair shaft near the root. Their intensity corresponded to the degree of severity of the intoxication. When examined under reflected light, the inclusions were shown up with a white color. They thus showed the same optical behavior as the air-filled medullary strand of normal hairs. This indicates that gaseous constituents are involved. This hypothesis could be confirmed by further investigations. After mechanical damage to the hair (pressing under high pressure), the gaseous inclusions disappeared and with them the "thallium strip." The same effect was attained by the chemical action of various acids, embedding agents, and dye solutions. This process was especially rapid after exposure to thioglycolic acid; the escape of the gas bubbles can be directly observed here. Scanning electron microscopic investigations on transverse sections of hair revealed a loosening of the spindle-shaped elements of the fiber layer as signs of structural disturbance. The gaseous constituents in thallium hair arise as the result of a trophic disorder in keratin formation. The structural alteration due to this leads to alopecia.     

铊（TI）投毒案检验

目的　通过 11例中毒者分析研究铊中毒的症状 ,达到了解和认识铊中毒的目的。方法　收集 11例铊中毒的相关资料 ,分析铊中毒的特征。结果　铊中毒的共同特征是出现症状的时候都有四肢疼痛或麻木 ,同时伴有严重脱发。结论　铊中毒依个体的年龄、性别、状态及中毒量不同 ,其发病前具有一定潜伏期。但性别、年龄与死亡的时间关系目前尚不清     

Human Fatality Due to Thallium Poisoning: Autopsy,Microscopy, and Mass Spectrometry Assays,

Thallium has been responsible for many intoxications since its discovery; however, toxicological profiles for thallium in human fatalities have not been updated recently. Autopsy, microscopic investigations, and toxicological analyses were performed on a married couple who died from thallium sulfate intended homicidal poisoning. The distribution of thallium was established by inductively coupled plasma mass spectrometry with hair samples showing the highest thallium concentration. Electron microscopy revealed a dystrophic condition of hair with disorganized cuticle and atrophy of the hair bulb. Thallium interacts with cells at different levels, with prominent ultrastructural injuries in the mitochondria and endoplasmic reticulum, and high concentration of electron dense granules observed in the cytoplasm and mitochondria of several organs. Alopecia, toxic encephalopathy, and peripheral neuropathy were diagnosed in the victims and suggested to be crucial implications for thallium poisoning. The analytical procedures used in this case are of considerable forensic importance in the diagnosis of thallium poisoning.     

Exhumation examination to confirm suspicion of fatal lead poisoning

Acute poisonings with inorganic lead compounds are exceptionally rare. In all cases of diagnosis, there are two possible sources of error: failing to recognise lead poisoning when it is present, and mistaking other diseases for lead poisoning. If exposure history is carefully taken and proper laboratory techniques are employed, the diagnosis of lead poisoning should not be difficult. In the described case of the death of a 41-year-old-man, no enzymatic disturbances characteristic of congenital erythropoietic porphyria were ascertained, and furthermore, a considerable concentration of lead was found in antemortem material, 5 months before death (blood: 1584 microg/l, urine: 531 microg/24 h). Postmortem tissue lead content in the biological material, exhumed 6 months after death, were as follows: liver, 47.6 microg/g; kidney, 4.75 microg/g; bone, 103 microg/g of sacral vertebra, 20.4 microg/g of femoral bone, 112 microg/g of pelvis; hair, 30.2 microg/g of scalp hair, 33.7 microg/g of pubic hair; nails, 13.6 microg/g. The results indicated a case of acute lead poisoning (with lead(II) oxide, as it later turned out), which manifested as acute intermittent porphyria.     

铊中毒的法医毒理学研究进展

由于铊盐溶液无色无味,且毒性剧烈,所以近年来利用铊盐投毒的案例时有报道。利用铊盐投毒隐匿性强,给案件的侦破带来很大难度,同时也因诊断不及时而耽误治疗。本文结合文献,从中毒方式、毒代动力学、毒理作用、中毒症状、中毒致死量、尸体检查所见、法医学鉴定及鉴别诊断等方面,对铊中毒的法医毒理学研究进展进行综述。     

Hair analysis of opiates in mothers and newborns for evaluating opiate exposure during pregnancy

The increasing interest in toxicological hair analysis as a marker of human exposure to xenobiotics such as illicit substances or therapeutic drugs, has been made feasible by the extension of mass spectrometry, a highly sensitive method of detection. A newborn exposed to drugs in utero can suffer from a varying degree of withdrawal syndrome, a few days after birth. If of opiate origin, the withdrawal syndrome can be treated with morphine, among other therapeutics, but it is not easy to diagnose because of atypical symptoms presented by neonates and especially when maternal drug addiction has not been revealed. To assess and measure toxicological factors linked with the appearance and the severity of this syndrome, maternal and neonatal matrices such as urine, meconium and hair were collected during a protocol approved by the ethical committee. Opiates in particular were measured with GC-MS and potential combined dependences (cannabis, cocaine, amphetamine, LSD and benzodiazepines) and/or substitutive therapeutics (methadone or buprenorphine) were also assessed in 17 mother/neonate couples. Gestational opiate exposure profiles were drawn up and linked with the observed withdrawal syndromes. A withdrawal syndrome seems to appear more frequently after foetal exposure to an association of opiates/substitutive molecules (8 out of 10 withdrawal syndromes observed in this study), although the impact of cocaine and benzodiazepines must also be taken into account. The results obtained in neonatal hair make it possible to affirm foetal drug exposure and are in accordance, for the majority, with the appearance of a neonatal withdrawal syndrome (NWS). Neonatal hair analysis could contribute to assess in utero exposure to opiates, particularly when results in urine and meconium are negative or when these matrices are not available.     

Weather-induced changes in cannabinoid content of hair

Authentic hair samples from Cannabis users and a drug free hair sample which was separately spiked with tetrahydrocannabinol (THC), cannabidiol (CBD) or cannabinol (CBN) were exposed outside as well as to natural sunlight at prevailing and elevated humidity in quartz glass tubes during 8 weeks. In addition, authentic and spiked hair samples were exposed to xenon arc radiation in a light exposure cabinet for 24 hours. Stability of THC, CBD and CBN in authentic samples differed from that of the spiked hair. The radiation experiment revealed that CBN could not be measured in hair which had been spiked with THC. Under all conditions chosen the concentrations of THC, CBD and CBN decreased. At high humidity the concentrations declined more rapidly. In both authentic and spiked samples THC was most unstable compared to CBD and CBN. Therefore, in hair analysis determination of CBD and CBN seems promising to detect Cannabis exposure even under unfavorable conditions.     

Windows of detection of zolpidem in urine and hair: application to two drug facilitated sexual assaults

A LC-MS/MS method for the detection of zolpidem in hair was developed to detect this drug after a single dose in possible drug facilitated sexual assaults. To determine the window of detection of zolpidem in both urine and hair, three volunteers received a 10 mg dose. Urine specimens were collected each 12 h for 144 h. Hair was sampled 3-5 weeks after exposure. Hair and urine extracts were separated on a Xterra MS C18 column using a gradient of acetonitrile and formate buffer. For each compound, detection was related to two daughter ions. Zolpidem was detected for up to 60 h in urine with peak concentrations obtained at 12 h. A single exposure to zolpidem was detected in hair at concentrations ranging from 1.8 to 9.8 pg/mg. Hair analysis was applied to two possible criminal cases. In the first case, zolpidem tested positive in the corresponding hair segment at 4.4 pg/mg. In the other case, zolpidem was detected in all the segments analyzed, demonstrating likely previous drug use in addition to recent exposure associated with a positive blood result.     

Variability of simulants used in recreating stab events

Formic acid (FA) concentration was measured in post-mortem blood and urine samples as methyl formate using a headspace in-tube extraction gas-chromatography-mass-spectrometry method. A total of 113 cases were analyzed, each including a blood and urine sample fortified with 1% sodium fluoride. The cases were divided into three groups: regular (n=59), putrefied (n=30), and methanol-positive (n=22) cases. There was no evidence of ante-mortem methanol consumption in the regular and putrefied cases. In regular cases, the mean (and median) FA concentrations were 0.04 g/l (0.04 g/l) and 0.06 g/l (0.04 g/l) in blood and urine, respectively. In putrefied cases, the mean (and median) FA concentrations were substantially higher, 0.24 g/l (0.22 g/l) and 0.25 g/l (0.15 g/l) in blood and urine, respectively. In three putrefied cases, FA concentration in blood exceeded 0.5 g/l, a level associated with fatal methanol poisoning. Ten putrefied cases were reanalyzed after 3-4 months storage, and no significant changes in FA concentrations were seen. These observations suggest that FA was formed by putrefaction during the post-mortem period, not during sample storage when sodium fluoride was added as a preservative. In methanol-positive cases, the mean (and median) FA concentrations were 0.80 g/l (0.88 g/l) and 3.4 g/l (3.3 g/l) in blood and urine, respectively, and the concentrations ranged from 0.19 to 1.0 g/l in blood and from 1.7 to 5.6 g/l in urine. The mean (and median) methanol concentrations in methanol-positive cases were 3.0 g/l (3.0 g/l) and 4.4 g/l (4.7 g/l) in blood and in urine, respectively. The highest methanol concentrations were 6.0 g/l and 8.7 g/l in blood and urine, respectively. No ethyl alcohol was found in the methanol-positive blood samples. Poor correlation was shown between blood and urine concentrations of FA. Poor correlations were also shown, in both blood and urine, between methanol and FA concentrations.     

Determination of bromazepam, clonazepam and metabolites after a single intake in urine and hair by LC-MS/MS. Application to forensic cases of drug facilitated crimes

The number of reports on drug facilitated crimes is increasing these last years. Apart from ethanol and cannabis, benzodiazepines (BZD) and analogs are the most common drugs reported to be used probably due to their amnesic and sedative properties. We have developed a rapid and sensitive method using LC-MS/MS triple stage quadrupole (TSQ) for the determination of single exposure to bromazepam (Lexomil, 6 mg) and clonazepam (Rivotril, 2 mg) in urine and hair of healthy volunteers. Chromatography was carried out on a Uptisphere ODB 5 microm, 2.1 mm x 150 mm column (Interchim) with a gradient of acetonitrile and formate 2 mM buffer, pH 3. Urine was extracted with Toxitube A (Varian) and allowed the detection of bromazepam, 3-hydroxy-bromazepam, clonazepam and 7-Aminoclonazepam for more than 6 days. Head hair, collected 1 month after the exposure, was treated by incubation with Soerensen buffer pH 7.6, followed by liquid-liquid extraction with dichloromethane for common BZD. A specific pre-treatment for amino-BZD, with an incubation of 15 min at 95 degrees C in 0.1 N NaOH before liquid-liquid extraction with dichloromethane, gave better recoveries and repeatability. After single exposure, bromazepam was present in powdered hair at 28 pg/mg and 7-Aminoclonazepam at 22 pg/mg in the first 1-cm segment, while no clonazepam was detectable. This method was applied in two forensic cases. It allowed us to determine bromazepam in urine 3 days after the alleged offense and in cut head hair at a concentration of 6.7 pg/mg only in the 2-cm proximal segment. The other case showed the presence of clonazepam and 7-Aminoclonazepam in urine a few hours after the offense and the presence of 7-Aminoclonazepam at about 3.2 pg/mg in axillary hair 4 months later.     

Differential burns of head and pubic hair

A woman, who was hospitalized with extensive burns in the genital and perineal region, accused her husband who lived apart from her to have inflicted the injuries with a lighter and a burning candle out of jealousy. The husband denied the accusations and stated that he wanted to singe off the pubic hair with the lighter during sadomasochist sexual practices performed in mutual agreement. As he did so extensive flames suddenly developed--something he had not expected--thus causing the burns. To check the statement cut off tufts of head and pubic hair were set on fire with a lighter to compare their burning behaviour. Pubic hair was easily inflammable and burnt almost completely within about 10 seconds developing up to 10 cm high flames, whereas straight head hair developed only minor flames and the singed hairs stopped burning spontaneously some seconds later already.     

Compared interest between hair analysis and urinalysis in doping controls. Results for amphetamines, corticosteroids and anabolic steroids in racing cyclists

In France during a famous bicycle race, the newspapers documented the degree in which doping seemed to be supervised in some teams by managers and doctors. Use of anabolic steroids and other substances was officially banned in the mid-seventies by sports authorities. This policy has been enforced through urine testing before competition. It is well known, however, that a latency period is all that is necessary to defeat these tests. Nevertheless, hair analysis could be a promising tool when testing for periods that are not accessible to urinalysis any more. We have developed different sensitive methods for testing hair for amphetamines, anabolic steroids and their esters and corticosteroids. For amphetamines, 50 mg of hair were digested with 1 M NaOH, extracted with ethyl acetate, derivatized with TFA and analyzed by gas chromatography positive chemical-ionization mass spectrometry. For corticosteroids, 50 mg of powdered hair were treated with methanol in an ultrasonic bath and subsequently purified using a C18 solid phase extraction column. Analysis was realized by high performance liquid chromatography coupled to electrospray-ionization tandem mass spectrometry. For anabolic steroids and their esters, 100 mg of powdered hair were treated with methanol in an ultrasonic bath for extraction of esters, then alkaline digested with 1 M NaOH for an optimum recovery of other drugs. The two liquid preparations were subsequently extracted with ethyl acetate, pooled, then finally highly purified using a twin solid phase extraction on aminopropyl and silica cartridges. Residue was derivatized with MSTFA prior to injection. Analysis was conducted by gas chromatography coupled to a triple quadrupole mass spectrometer. Thirty cyclists were sampled and tested both in hair and in urine. Amphetamine was detected 10 times in hair (out of 19 analyses) compared to 6 times in urine (out of 30 analyses). Corticosteroids were detected 5 times in hair (methylprednisolone 1 case, triamcinolone acetonide 3 cases and hydrocortisone acetate 1 case) in hair (out of 12 analyses) compared to 12 times (triamcinolone acetonide 10 cases and betamethasone 2 cases) in urine (out of 30 analyses). Anabolic steroids were detected twice (nandrolone 1 case, and testosterone undecanoate 1 case) in hair (out of 25 analyses) compared to none in urine (out of 30 analyses).     

Using DNA-barcoding to make the necrobiont beetle family Cholevidae accessible for forensic entomology

Although many cases of fatal hydrogen sulfide poisoning have been reported, in most of these cases, it resulted from the accidental inhalation of hydrogen sulfide gas. In recent years, we experienced 17 autopsy cases of fatal hydrogen sulfide poisoning due to the inhalation of intentionally generated hydrogen sulfide gas. In this study, the concentrations of sulfide and thiosulfate in blood, urine, cerebrospinal fluid and pleural effusion were examined using GC/MS. The sulfide concentrations were blood: 0.11-31.84, urine: 0.01-1.28, cerebrospinal fluid: 0.02-1.59 and pleural effusion: 2.00-8.59 (μg/ml), while the thiosulfate concentrations were blood: 0-0.648, urine: 0-2.669, cerebrospinal fluid: 0.004-0.314 and pleural effusion: 0.019-0.140 (μmol/ml). In previous reports, the blood concentration of thiosulfate was said to be higher than that of sulfide in hydrogen sulfide poisoning cases, although the latter was higher than the former in 8 of the 14 cases examined in this study. These results are believed to be strongly influenced by the atmospheric concentration of hydrogen sulfide the victims were exposed to and the time interval between exposure and death.     

Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse

Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been used as a marker of alcohol abuse in both urine and hair. This study investigated the value of EtG testing in post-mortem hair for diagnostic improvement of alcohol abuse in forensic medicine. Material from 70 consecutive medico-legal autopsies was collected in accordance with the recommendations on ethics by the Swedish National Board of Forensic Medicine. A method for determination of EtG in hair samples was developed using ultra performance liquid chromatography/electrospray tandem mass spectrometry (UPLC/ESI-MS/MS; LOQ, 2.5 pg/mg). The result of the EtG analysis was compared with the findings of phosphatidylethanol (PEth) in femoral whole blood, as measured by high performance liquid chromatography with an evaporative light-scattering detector (HPLC-ELSD; LOQ, 0.22 micromol/l). Evaluation of liver histology and anamnestic evidence of alcohol abuse of the deceased were taken in consideration for the interpretation. Measurable levels of EtG were present in 49 of the 70 autopsy cases whereas PEth was present in 36. Thirty-nine cases had EtG levels above the cutoff limit (> or = 30 pg/mg) compared with 29 for PEth (> or = 0.7 micromol/l). Fifteen cases had EtG as exclusive indicator for alcohol abuse compared with four cases for PEth. These findings suggest that measurements of EtG in hair may provide improved diagnostic information on alcohol abuse, due to a long retrospective time-window for detection and stability of EtG in hair in the decaying cadaver. However, an EtG level below the cutoff does not completely exclude previous alcohol abuse.     

微波消解ICP-MS法检测生物检材中汞元素

目的 建立生物检材中汞的电感耦合等离子体质谱分析方法.方法 采用微波消解法处理样品,以铟(115In)作内标,用电感耦合等离子体质谱仪对血液、尿液和头发中的汞含量进行分析.选择金与汞形成金汞齐,对金消除汞记忆效应的能力进行考察.结果 方法检出限为0.01μg/L,准确度为97.0%～107.1%.检测中添加金质量浓度在...     

Diagnostic implication of blood and urine morphine content in alcohol intoxication

A total of 198 cases of acute parenteral poisoning with opiates are characterized. The range of concentrations of opiates metabolites in the blood and urine, main causes of death due to opiate poisoning in alcohol intoxication are analysed. Opiates toxicity was assessed with the logit-regression method and dose-effect curves valid for analysis of relationships between probability of death and opiate metabolites concentration in blood and urine. Correlation between probability of death and detection of morphine and ethanol in biological media of the victims is considered. Concentrations of morphine in blood and urine definitely indicating opiates poisoning in alcohol intoxication as a cause of death are determined.     

The atlas of dialkylphosphates; assessment of cumulative human organophosphorus pesticides' exposure

Organophosphorus pesticides (OPs) are a group of chemicals with significant health interest, due to their wide spectrum of action and their excessive use both indoors (household) and outdoors (occupationally). The non-specific metabolites of OPs, dialkylphosphates (DAPs), are the most commonly used indicators for the assessment of cumulative OP exposure in humans. This review presents studies on human biomonitoring of OPs in the general population and in occupationally exposed humans. Furthermore, cases of OP intoxication determined by the measurement of DAP metabolites in various biological samples are included. In many studies, urine samples from both the general population and exposed populations have been analyzed mainly in Europe and America, while other matrices such as amniotic fluid, meconium, hair and blood have been less studied. A variety of analytical techniques were used for the determination of DAPs in these matrices. In studies measuring DAPs in urine samples, the detected concentrations ranged from 18 to 830ppb for the general population, while the corresponding values for exposed populations ranged from 29 to 1370ppb. Studies on amniotic fluid indicated DAP levels of 0.3-2.8ppb. Studies on meconium samples showed a concentration range of 0.5-16,000ppb. DAP levels in hair samples ranged from 40 to 165ppb for the general population and from 181.7 to 812.9ppb for the exposed population. Each matrix provides specific information on OP exposure, namely acute, long-term, chronic or prenatal. Meconium and hair can indicate cumulative exposure, while amniotic fluid is an indicator of fetal exposure to xenobiotics. Thus, various biological samples provide a more comprehensive view of OP exposure. In general, dimethylphosphate (DMP) and diethylphosphate (DEP) levels were higher in mainly urine samples, than other methyl and ethyl phosphates. In addition, results in the existing literature are sufficient to demonstrate the difference in levels of DAPs in general and occupationally exposed populations, mainly in urine and hair samples. However, more studies are needed to measure DAP levels in matrices such as amniotic fluid, meconium and hair to add to the literature and confirm existing data.     

Accumulation of explosives in hair

The sorption of explosives (TNT, RDX, PETN, TATP, EGDN) to hair during exposure to their vapors is examined. Three colors of hair were simultaneously exposed to explosive vapor. Following exposure of hair, the sorbed explosive was removed by extraction with acetonitrile and quantified. Results show that sorption of explosives, via vapor diffusion, to black hair is significantly greater than to blond, brown or bleached hair. Furthermore, the rate of sorption is directly related to the vapor density of the explosive: EGDN > TATP >TNT > PETN > RDX. In some cases, the explosive-containing hair was subject to repeated washings with sodium dodecylsulfate or simply left out in an open area to determine the persistence of the explosive contamination. While explosive is removed from hair with time or washing, some persists. These results indicate that hair can be a useful indicator of explosive exposure/handling.     

Criminal poisoning of commuters in Bangladesh: prospective and retrospective study

Travel-related poisoning is an emerging social and public health emergency in Bangladesh but its cause and significance have not been determined. To investigate this syndrome we performed a prospective clinical study and retrospective analysis of hospital records in a general medicine unit of a public tertiary care teaching hospital in Dhaka, Bangladesh, using toxicological analysis by fluorescence polarization immunoassay (FPIA) and liquid chromatography coupled to time-of-flight mass spectrometry (LC-TOF MS). The participants of the prospective study were 130 consecutive patients aged 16-80 years who were admitted with central nervous system depression (Glasgow Coma Score 3-14) after using public transportation, in the absence of other abnormalities, from January through June 2004, and a convenience sample of 15 such patients admitted during 3 days in May 2006. In 2004-2006, travel-related poisoning increased from 6.1 to 9.5% of all admissions (210-309 of 3266-3843 per year), representing 46.6-55.7% of all admitted poisoning cases. Incidents were associated with bus (76%), taxi, train, and air travel, or local markets; 98% of patients remembered buying or accepting food or drinks before losing consciousness. Direct financial damage (missing property) was diverse and frequently existential. Among 94 urine samples analyzed by FPIA, 74% tested positive for benzodiazepines. Among 15 urine samples analyzed by LC-TOF MS, lorazepam was detected in all; five also contained diazepam or metabolites; nitrazepam was present in three. FPIA results obtained for these 15 samples were below the recommended cut-off in eight (53%; lorazepam only). Our findings show that the massive medicosocial emergency of travel-related poisoning in Bangladesh is the result of drug-facilitated organized crime and that benzodiazepine drugs are used to commit these crimes, suggesting modifications to the local emergency management of the victims of this type of poisoning. They also highlight the need for more research in the neglected field of acute poisoning in Bangladesh, and for criminal investigations of the use of benzodiazepine drugs in this country.