Cyanide Poisoning and Lactate in Smoke Inhalation.

House fires can lead to cyanide poisoning and an associated elevated serum lactate level. Because of delays in obtaining serum cyanide levels, clinical symptoms and serum lactate are often used to guide clinical decision making and antidote administration. However, as this case report identifies, lower levels of serum lactate may in fact correlate with higher levels of serum cyanide that could benefit from treatment with an antidote.

Assessment of blood 2-aminothiazoline-4-carboxylic acid concentrations: Age and sex differences, and correlation with carboxyhemoglobin in fire victims.

Recently, 2-aminothiazoline-4-carboxylic acid (ATCA), a cyanide (CN) metabolite, has been proposed as a stable diagnostic marker of CN poisoning. In this study, liquid chromatography coupled with electrospray ionization - tandem mass spectrometry was used to quantify ATCA concentrations in human postmortem blood samples, and differences in ATCA concentrations according to age and sex were determined. Both age and sex had significant effects on blood ATCA concentrations. Although ATCA concentrations exhibited an inverted U shape with increasing age in men, in women ATCA concentrations plateaued at around 40-59 years of age. There were significant differences between the sexes in ATCA concentrations for the 20-39 and 40-59 year age groups (P < 0.05 and P < 0.01, respectively). Correlations between ATCA concentrations and carboxyhemoglobin (CO-Hb) saturation were also examined in fire victims. ATCA concentrations increased significantly with increasing CO-Hb saturation (r = 0.382, P < 0.01). In addition, ATCA concentrations were also correlated to CN concentrations (r = 0.309, P < 0.05). The results of our study may provide novel information about the contribution of CN poisoning to the cause of death at fire scenes.

Konzo risk factors, determinants and etiopathogenesis: What is new? A systematic review.

Konzo is a toxico-nutritional upper motor neuron disease causing a spastic paraparesis in schoolchildren and childbearing women in some African countries. Almost a century since the first description of konzo, its underlying etiopathogenic mechanisms and causative agent remain unknown. This paper aims at refreshing the current knowledge of konzo determinants and pathogenesis in order to enlighten potential new research and management perspectives. Literature research was performed in PubMed and Web of Science databases according to the PRISMA methodology. Available data show that cassava-derived cyanide poisoning and protein malnutrition constitute two well-documented risk factors of konzo. However, observational studies have failed to demonstrate the causal relationship between konzo and cyanide poisoning. Thiocyanate, the current marker of choice of cyanide exposure, may underestimate the actual level of cyanide poisoning in konzo patients as a larger amount of cyanide is detoxified via other unusual pathways in the context of protein malnutrition characterizing these patients. Furthermore, the appearance of konzo may be the consequence of the interplay of several factors including cyanide metabolites, nutritional deficiencies, psycho-emotional and geo-environmental factors, resulting in pathophysiologic phenomena such as excitotoxicity or oxidative stress, responsible for neuronal damage that takes place at sparse cellular and/or subcellular levels.

Intoxicación por cianuro como método suicida: reporte de caso / Cyanide poisoning as a suicide method: case report

Resumen Las intoxicaciones derivan de la presencia en el organismo de un tóxico o veneno, la muerte por intoxicación es una muerte violenta y por tanto requiere de la realización de una autopsia medico legal, la misma puede darse en el contexto de una exposición accidental ya sea en el hogar o laboral o sucitada por un intento de autoeliminación. La intoxicación por cianuro puede ser intencional (suicidio u homicidio) o accidental, los hallazgos en la autopsia medico legal son inespecíficos por lo que son importantes los datos aportados en el informe sobre muerte en investigación, el informe del escenario de muerte en caso de que un médico forense se hiciera presente al mismo y el resultado de los análisis toxicológicos, los cuales actualmente no se realizan en la sección de toxicología del poder judicial. Se realizó una revisión bibliográfica en diferentes bases de datos, de los artículos publicados referentes al tema de los últimos cinco años, con el objetivo de revisar las caracteristicas del químico, el metabolismo y la intoxicación como tal, tanto por sus secuelas como por sus implicaciones letales. Se concluye que para mejorar la pericia médico legal ante casos de intoxicacion por cianuro es fundamental conocer el mecanismo de acción y los posibles hallazgos presentes tanto al examen externo como interno, así como implementar que dicho escrutinio se incluya dentro del listado de sustancias a analizar.

Abstract Poisoning derives from the presence of a toxic substance or poison in the body, death by poisoning is a violent death and requires a legal medical autopsy, it may occur in the context of an accidental exposure at home or work, or caused by an attempt of self-elimination. Cyanide poisoning can be intentional (suicide / homicide) or accidental, the findings in the autopsy are unspecific, so data provided in the report of death in investigation, the report of the death scene (in case a forensic doctor was present) and the result of the toxicological analyzes, which are not currently performed in the toxicology section of the judiciary, are important. A bibliographic review was carried out in different databases of articles published in the last five years on the subject, with the objective of reviewing the chemical characteristics, the metabolism and the intoxication, as well, including their sequels and lethal implications. It is concluded that to improve the medical legal expertise in cases of cyanide poisoning, it is essential to know the mechanism of action and the possible findings in the external and internal examination; and to implement such scrutiny in the list of substances to be analyzed.

Can isosorbide dinitrate oral spray serve as an immediate bridging therapy for a mass cyanide poisoning?

OBJECTIVE: In this proof-of-concept study, the aim was to evaluate the short-term clinical effectiveness of isosorbide dinitrate (ISDN) oral spray in non-anaesthetized cyanide-poisoned swine. METHODS: A comparative study was conducted using domestic swine. Animals were intravenously poisoned with potassium cyanide (KCN), either 2 mg/kg or 4 mg/kg dose. Two control groups (one for each cyanide dose) were not further treated. Two other groups (one for each cyanide dose) were treated within 1 min after poisoning with ISDN oral spray: 3 spray actuations (averaging a total of 3.75 mg) after the lower cyanide dose and 4 spray actuations (averaging a total of 5.0 mg) after the higher dose. The study outcomes were clinical score, time to death, and blood tests including pH, lactate, and methemoglobin levels. RESULTS: All the animals started to convulse within 20 to 30 sec after KCN poisoning, then became unresponsive and hemodynamically depressed after another 20 to 30 sec. After the KCN 2 mg/kg dose, 3 of 4 control animals survived, while all treated animals survived. Compared with control animals, ISDN-treated animals displayed significantly better clinical scores starting 5 min after KCN poisoning. Acidosis was significantly more pronounced in the untreated animals. After the KCN 4 mg/kg dose, similar survival rates were observed for control and ISDN-treated groups (1/4), but treated animals had longer time to death and better pH and lactate levels. CONCLUSION: ISDN oral spray administration following KCN poisoning in this porcine model did not result in statistically significant increased survival. However, based on clinical scores and clinical laboratory values, ISDN may benefit as a bridging countermeasure until currently-available specific cyanide antidotes can be administered. Further research is warranted to better characterize this potential role of ISDN in cyanide poisoning.

Water-Soluble α-Amino Acid Complexes of Molybdenum as Potential Antidotes for Cyanide Poisoning: Synthesis and Catalytic Studies of Threonine, Methionine, Serine, and Leucine Complexes.

Water-soluble complexes are desirable for the aqueous detoxification of cyanide. Molybdenum complexes with α-amino acid and disulfide ligands with the formula K[(L)Mo2O2(µ-S)2(S2)] (L = leu (1), met (2), thr (3), and ser (4)) were synthesized in a reaction of [(DMF)3MoO(µ-S)2(S2)] with deprotonated α-amino acids; leu, met, thr, and ser are the carboxylate anions of l-leucine, l-methionine, l-threonine, and l-serine, respectively. Potassium salts of α-amino acids (leu (1a), met (2a), thr (3a), and ser (4a)) were prepared as precursors for complexes 1-4, respectively, by employing a nonaqueous synthesis route. The ligand exchange reaction of [Mo2O2(µ-S)2(DMF)6](I)2 with deprotonated α-amino acids afforded bis-α-amino acid complexes, [(L)2Mo2O2(µ-S)2] (6-8). A tris-α-amino acid complex, [(leu)2Mo2O2(µ-S)2(µ-leu + H)] (5; leu + H is the carboxylate anion of l-leucine with the amine protonated), formed in the reaction with leucine. 5 crystallized from methanol with a third weakly bonded leucine as a bridging bidentate carboxylate. An adduct of 8 with SCN- coordinated, 9, crystallized and was structurally characterized. Complexes 1-4 are air stable and highly water-soluble chiral molecules. Cytotoxicity studies in the A549 cell line gave IC50 values that range from 80 to 400 µM. Cyclic voltammetry traces of 1-8 show solvent-dependent irreversible electrochemical behavior. Complexes 1-4 demonstrated the ability to catalyze the reaction of thiosulfate and cyanide in vitro to exhaustively transform cyanide to thiocyanate in less than 1 h.

Inhaler intoxications developed during autopsy of the corpse due to cyanide intake: Case series.

The primary cause of cyanide intake is suicidal attempts, most of which result in death. People who interfere with suspicion of cyanide intoxication may also be exposed to cyanide poisoning. During the autopsy of the corpse in the morning of that day, five people in the autopsy room within the hospital were admitted to the ED with suspicion of cyanide intoxication. Meanwhile, a 36-year-old patient who had come into contact with the patient at night also presented to the ED. Some of the precautionary measures to be taken against inhalation of cyanide may be wearing appropriate masks as well as suitable clothes and keeping the surroundings below 28 °C when exposed to cyanide.

Smoke inhalation injury in a 2-year-old domestic fire victim.

Smoke inhalation injury is common in victims of domestic fires, among whom children are the most vulnerable. Cyanide poisoning may occur in addition to carbon monoxide poisoning and is challenging to diagnose. In France, the recommended antidotes are hydroxocobalamin for cyanide and hyperbaric oxygen for carbon monoxide. We managed a 26-month-old girl who sustained smoke inhalation injury with both carbon monoxide and cyanide poisoning during a house fire. Despite hydroxocobalamin and sodium thiosulfate therapy combined with hyperbaric oxygen, she had residual neurological impairments 3 months after the injury. The treatment challenges and detailed neurological follow-up data are described.

Carbon monoxide poisoning.

Despite established exposure limits and safety standards as well as the availability of carbon monoxide (CO) alarms, each year 50,000 people in the United States visit emergency departments for CO poisoning. Carbon monoxide poisoning can occur from brief exposures to high levels of CO or from longer exposures to lower levels. Common symptoms can include headaches, nausea and vomiting, dizziness, general malaise, and altered mental status. Some patients may have chest pain, shortness of breath, and myocardial ischemia, and may require mechanical ventilation and treatment of shock. Individuals poisoned by CO often develop brain injury manifested by neurological problems, including cognitive sequelae, anxiety and depression, persistent headaches, dizziness, sleep problems, motor weakness, vestibular and balance problems, gaze abnormalities, peripheral neuropathies, hearing loss, tinnitus, Parkinsonian-like syndrome, and other problems. In addition, some will have cardiac issues or other ailments. While breathing oxygen hastens the removal of carboxyhemoglobin (COHb), hyperbaric oxygen (HBO2) hastens COHb elimination and favorably modulates inflammatory processes instigated by CO poisoning, an effect not observed with breathing normobaric oxygen. Hyperbaric oxygen improves mitochondrial function, inhibits lipid peroxidation transiently, impairs leukocyte adhesion to injured microvasculature, and reduces brain inflammation caused by the CO-induced adduct formation of myelin basic protein. Based upon three supportive randomized clinical trials in humans and considerable evidence from animal studies, HBO2 should be considered for all cases of acute symptomatic CO poisoning. Hyperbaric oxygen is indicated for CO poisoning complicated by cyanide poisoning, often concomitantly with smoke inhalation.

Toxic inhalational injury.

A middle-aged patient presented with toxic inhalational injury, and was resuscitated prehospitally and treated in the emergency department for smoke inhalation, carbon monoxide (CO) exposure and cyanide poisoning with the use of antidotes. Due to the CO effects on spectrophotometry, an anaemia initially identified on blood gas analysis was thought to be artefactual, but was later confirmed by laboratory testing to be accurate. In addition, cyanide can confound haemoglobin testing due to its use in the analytical process and non-cyanide analysis is required when there is suspected exposure. Although no consensus exists on a first-line cyanide antidote choice, hydroxocobalamin is the only antidote without a serious side effect profile and/or deleterious cardiovascular effects. We propose prehospital enhanced care teams consider carrying hydroxocobalamin for early administration in toxic inhalational injury.

Carbon Monoxide and Cyanide Intoxication: An Association to Remember.

Carbon monoxide and cyanide are toxins that induce cellular hypoxia; both can be produced in the context of domestic fires and may have a synergistic effect. We present the case of a man, victim of a house fire, who was initially diagnosed as having carbon monoxide poisoning, but that afterwards also presented signs and symptoms compatible with cyanide poisoning. He was successfully treated with an antidote. We want to highlight this relatively frequent association of poisonings and the need for urgent empirical treatment.

O monóxido de carbono e o cianeto são toxinas que induzem hipóxia celular; ambos podem ser produzidos em contexto de incêndios domésticos e podem exercer um efeito tóxico sinérgico. Apresentamos o caso de um homem, vítima de incêndio doméstico, que foi inicialmente diagnosticado como intoxicação por monóxido de carbono, mas que posteriormente apresentou também sinais e sintomas compatíveis com intoxicação por cianeto, tendo sido tratado com sucesso com antídotos dirigidos. Pretendemos alertar para esta associação de intoxicações relativamente frequente e para a necessidade de tratamento empírico urgente.

Diagnosis of cyanide poisoning using an automated, field-portable sensor for rapid analysis of blood cyanide concentrations.

Cyanide (both HCN and CN- are represented by CN) has multiple industrial applications, is commonly found in some foods, and is a component of fire smoke. Upon exposure, CN blocks production of adenosine triphosphate, causing cellular hypoxia and cytotoxic anoxia, which can eventually result in death. Considering CN's quick onset of action and the long analysis times associated with current techniques, the objective of this study was to develop and validate a rapid and field-portable sensor to detect blood CN concentrations focusing on both concentration and diagnostic accuracy. The sensor takes advantage of the chemical properties of CN by converting it exclusively to HCN via acidification of whole blood. High-speed headspace transfer is used to deliver HCN to a capture solution where it is reacted with naphthalene dialdehyde and taurine to produce a fluorescent ß-isoindole product. Simple spectrofluorometric analysis of the product provides quantitative analysis of CN from whole blood in 60 s and requires only 25 µL of blood (obtainable via fingerstick). A limit of detection of 5 µM, a linear range of 10-200 µM (with ≥15 µM considered CN exposed), and excellent accuracy (100 ± 15%) and precision (≤15.2% relative standard deviation) were obtained. To evaluate the diagnostic accuracy of the sensor, rabbit blood samples (N = 190, including 24 blinded samples) were analyzed by both the sensor and a lab-based spectrophotometric method. An excellent positive correlation was obtained between the sensor and the lab-based method (R2 ˃ 0.995) confirming the concentration accuracy of the CN sensor. Moreover, the sensor produced no false positives or negatives when diagnosing CN poisoning.

Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning.

Background: Dicobalt edetate and hydroxocobalamin are widely used to treat hydrogen cyanide poisoning. However, comparative and quantitative efficacy data are lacking. Although post-exposure treatment is typical, it may be possible to administer these antidotes before exposure to first attenders entering a known site of cyanide release, as supplementary protection to their personal protective equipment.Methods: We established an anaesthetised Gottingen minipig model of lethal bolus potassium cyanide (KCN) injection to simulate high dose hydrogen cyanide inhalation. Doses were similar to human lethal doses of KCN. Dicobalt edetate and hydroxocobalamin were administered shortly before KCN and their effect on metabolic and cardiovascular variables and survival time were measured.Results: Increases in arterial lactate were similar after 0.08 and 0.12 mmol/kg KCN. KCN 0.08 mmol/kg was survived by 4/4 animals with moderate cardiovascular effects, while the 0.12 mmol/kg dose was lethal in 4/4 animals, with a mean time to euthanasia of 28.3 (SEM: 13.9) min. Administration of dicobalt edetate (0.021 mmol/kg, 8.6 mg/kg) or hydroxocobalamin (0.054 mmol/kg, 75 mg/kg) at clinically licenced doses had modest effect on lactate concentrations but increased survival after administration of KCN 0.12 mmol/kg (survival: dicobalt edetate 4/4, hydroxocobalamin 2/4) but not 0.15 mmol/kg (0/4 and 0/4, respectively). In a subsequent larger study, doubling the dose of hydroxocobalamin (0.108 mmol/kg, 150 mg/kg) was associated with a modest but inconsistent increased survival after 0.15 mmol/kg KCN (survival: control 0/8, 75 mg/kg 1/10, 150 mg/kg 3/10) likely due to variable pharmacokinetics.Conclusions: In this porcine study of cyanide exposure, with pre-exposure antidote administration, licenced doses of dicobalt edetate and hydroxocobalamin were effective at just lethal doses but ineffective at less than twice the estimated LD50. The efficacy of a rapidly-administered double-dose of hydroxocobalamin was limited by variable pharmacokinetics. In clinical poisoning scenarios, with delayed administration, the antidotes are likely to be even less effective. New antidotes are required for treatment of cyanide exposures appreciably above the minimum lethal dose.

Role of Hemodialysis in the Management of Cyanide Intoxication From Apricot Kernels in a 3-Year-Old Child.

Cyanide (CN) is one among the most potent and rapidly acting lethal poisons, and it may cause death unless immediately diagnosed and treated. We report an unusual case of pediatric CN poisoning after ingestion of apricot kernels containing amygdalin, who survived with antidotal therapy and hemodialysis. A 3-year-old girl presented with respiratory distress and coma following tonic-clonic convulsions after ingestion of 3 apricot kernels. She had severe metabolic acidosis (pH 6.91, bicarbonate [HCO3] 5.6 mEq/L, base excess -26.0 mEq/L). Her blood CN level was measured 3.15 mg/L, 3 hours after ingestion. Hydroxocobalamin could not be administered immediately because it had to be brought from a medical center 4 hours apart. Therefore, a 3-hour hemodialysis session was carried out, following which she showed some clinical improvement. In addition, when hydroxocobalamin was obtained, it was then administered. During follow-up, she was completely asymptomatic with blood pressure, and other hemodynamic parameters normalized. This case presents hemodialysis as a way to correct metabolic derangements from CN poisoning and suggests that it may have a role in select cases of pediatric CN poisoning, especially when CN-scavenging antidotes may be unavailable.

A Case of Hydroxocobalamin-Induced False Blood Leak Alarm on Dialysis Machine.

Hemodialysis machines are equipped with a blood leak detector/alarm to prevent loss of blood following rupture of semipermeable membrane; the blood leak alarms could also be triggered by sensor malfunction or presence of air bubbles in the system. Hydroxocobalamin is a Food and Drug Administration-approved rapid-acting antidote to cyanide poisoning that converts cyanide to nontoxic cyanocobalamin. Side effects are reddish discoloration of skin and body fluids, urticarial rash, and rarely anaphylaxis. In this article, a case of false blood leak alarm following treatment of cyanide poisoning with hydroxocobalamin is reported, wherein the blood leak detector in dialysis machines prevented the patient from undergoing hemodialysis by repeatedly activating blood leak alarms. Continuous renal replacement therapy was used to overcome this problem. As the use of hydroxocobalamin increases, health care professionals should be educated about its potential to interfere with hemodialysis.

Outbreak of Cyanide Poisoning Caused by Consumption of Cassava Flour - Kasese District, Uganda, September 2017.

Cassava (Manihot esculenta), an edible tuberous root that is resistant to drought, diseases, and pests, is a major source of carbohydrates in tropical areas, the second most widely grown and consumed food in Uganda after bananas, and a staple in the diet for approximately 57% of the Uganda population (Figure 1) (1). On September 5, 2017, a funeral was held in Kasese District in western Uganda. Following the funeral, 33 persons with symptoms that included diarrhea, vomiting, and abdominal pains were admitted to Bwera Hospital in Kasese District. On September 8, the Uganda Ministry of Health received notification from the Kasese District health team regarding this outbreak of suspected food poisoning. An investigation to determine the cause of the outbreak and recommend control measures revealed that the outbreak resulted from consumption of a cassava dish made by combining hot water with cassava flour. The implicated batch of cassava flour was traced back to a single wholesaler and found to contain high cyanogenic content. Informed by the investigation findings, police confiscated all cassava flour from retailers identified as the patients' source of the flour. Health education about cyanide poisoning from cassava and the need to adequately process cassava to reduce cyanogenic content was conducted by public health officials.

Chemical and Clinical Aspects of Metal-Containing Antidotes for Poisoning by Cyanide.

Physiological metabolism of cyanide takes place by a single major pathway that forms non-toxic thiocyanate that is subsequently excreted. Rhodanese is the primary enzyme to execute metabolism of cyanide with minor pathways from other sulfurtransferases in vivo. The rhodanese enzyme depends on sulfur donor availability to metabolize cyanide and poisoning occurs at elevated cyanide concentrations in vivo. Cyanide interacts with over 40 metalloenzymes, but its lethal action is non-competitive inhibition of cytochrome c oxidase, halting cellular respiration and causing hypoxic anoxia. Only a handful of antidotes for treatment of cyanide poisoning are known; they are primarily inorganic compounds and metal complexes which are intended to intercept cyanide before it inhibits cellular respiration. The inorganic compounds manipulate hemoglobin, forming methemoglobin, or supply sulfur for the rhodanese enzyme. The metal complexes intercept the cyanide and bind it before reaching its target. Cobalt complexes of corrins and vitamin B12 derivatives are the state-of-the-art agents, while the longest employed complex, Co2EDTA, is designed to deliver "free" cobalt for binding of cyanide. Compounds that are in development are discussed from the point of how they are designed to intercept cyanide. The challenge of reversing the cyanide inhibition of cytochrome c oxidase is based on the catalytic active site structure and reactivity. General information about history and occurrence of poisoning and clinical symptoms is discussed and the challenges related to analytical methods available to analyze blood cyanide levels and to confirm the presence of cyanide poisoning.

Antidotal Effects of the Phenothiazine Chromophore Methylene Blue Following Cyanide Intoxication.

Our study was aimed at (1) determining the efficacy of the dye methylene blue (MB), following a rapidly lethal cyanide (CN) intoxication in un-sedated rats; (2) clarifying some of the mechanisms responsible for the antidotal properties produced by this potent cyclic redox dye. Sixty-nine awake rats acutely intoxicated by CN (IP, KCN 7 mg/kg) received saline, MB (20 mg/kg) or hydroxocobalamin (HyCo, 150 mg/kg) when in deep coma. Survival in this model was very low, reaching 9% at 60 min without any treatment. Methylene blue significantly increased survival (59%, p < .001) at 60 min, versus 37% with HyCo (p < .01). In addition, 8 urethane-anesthetized rats were exposed to a sublethal CN intoxication (KCN, 0.75 mg/kg/min IV for 4 min); they received MB (20 mg/kg, IV) or saline, 5 min after the end of CN exposure. All MB-treated rats displayed a significant reduction in hyperlactacidemia, a restoration of pyruvate/lactate ratio-a marker of NAD/NADH ratio-and an increase in CO2 production, a marker of the activity of the TCA cycle. These changes were also associated with a 2-fold increase in the pool of CN in red cells. Based on series of in vitro experiments, looking at the effects of MB on NADH, as well as the redox effects of MB on hemoglobin and cytochrome c, we hypothesize that the antidotal properties of MB can in large part be accounted for by its ability to readily restore NAD/NADH ratio and to cyclically re-oxidize then reduce the iron in hemoglobin and the electron chain complexes. All of these effects can account for the rapid antidotal properties of this dye following CN poisoning.

The potential use of 2-aminothiazoline-4-carboxylic acid (ATCA) as a forensic marker for cyanide exposure in medicolegal death investigation: A review.

Cyanide (CN) is one of the most toxic of all substances and can be found in various natural and anthropogenic sources. Sensitive and effective methods for the confirmation of CN exposure are crucial in medical, military, and forensic settings. Due to its high volatility and reactivity, direct detection of CN from postmortem samples could raise inconclusive interpretation issues that may hinder accurate determination of the cause of death. The detection of the alternative CN metabolites as markers to test CN exposure may offer a solution to reduce the potential for false-negative and false-positive results. 2-Aminothiazoline-4-carboxylic acid (ATCA) is a minor metabolite of CN and has been proposed to be a potential alternative forensic marker for the confirmation of CN exposure. According to the current state of knowledge, ATCA has not yet been associated with other metabolic pathways except for CN detoxification. Moreover, ATCA is stable under various conditions over time. This article reviews analytical methods developed for the analysis of ATCA as well as studies related to potential use of ATCA as a marker for the diagnosis of CN exposure. The need for research related to the use of ATCA as a reliable forensic marker for CN exposure in medicolegal death investigations is also discussed.