Ethyl chloride (EC) or chloroethane is a flammable gas (b.p. 12 °C) with a strong ether-like odour that has been used as a refrigerant, solvent and chemical intermediate. Originally, it was proposed as a general anaesthetic, filling the gap between the weaker narcotic nitrous oxide and the more powerful drugs ether and chloroform, but too much after-effects were reported (McCardie 1905). Nowadays, it is employed therapeutically as a topical anaesthetic spray for the control of pain in athletic injuries and muscle spasm. Moreover, EC finds application into the piercing/tattoo industry to cool the skin down in order to limit pain related to piercing or tattoo procedures (Torfaen County Borough, Code of practice Body Piercing n.d.). This compound had been used as a recreational popular street drug in 1980s, but recently, its engagement as inhalant drug in recreative sniffing to “get high” is gaining renewed popularity among young people also in light to its wide availability (Ethyl Chloride, or EC, is new off-the-shelf high n.d.; Youths warned off sniffing ‘deadly’ new legal high Ethyl Chloride n.d.). For decades, volatile substances have been the least studied of misused substances because of low perception of social and health risks, high variability among products, and lack of attention in national and international research. These substances are highly volatile and are usually inhaled through nose and mouth, reaching rapidly the bloodstream and central nervous system. The type and pattern of substances abused vary. Among the volatile substances are aromatic hydrocarbons (e.g. toluene), halogenated compounds (e.g. ethyl chloride), ethers (e.g. diethyl ether), ketones (e.g. acetone) and alcohols. Inhalants produce different effects, temporary or permanent, depending on the chemical constituents, individual susceptibility, substance concentration and duration of exposure. Among volatiles, common effects include irritation of respiratory airways, impaired judgement, tremors, unsteady gait, blurred vision and memory impairment. Very high concentrations can produce anaesthesia, unconsciousness and even death (Cruz 2011). Deaths occurring after drug inhalation are collectively defined “sudden sniffing deaths” and have been reported after recreational butane (Kramp et al. 2018), trichloroethylene (Da Broi et al. 2015) and butane-propane gas mixture (Romolo et al. 2017) inhalation.
EC is a volatile misused for recreational purposes. Cold liquid EC is usually sprayed into a towel or piece of cloth ad evaporating fumes are inhaled through the nose and the mouth. Inhaled EC vapour is rapidly excreted by the lungs and breath out; however, because of its high solubility, part of EC remains in the blood and total elimination from the body takes some time (Murray Lawson 1965). Effects of EC exposure result in dizziness, euphoria, confusion, incoordination, hallucinosis, impairment of short-term memory and narcosis also for brief exposures at high concentrations (Baselt 2014). Toxicological effects on humans were mostly studied from cases of occupational medicine, where EC is known to produce central nervous system depression at 40,000 ppm (105.6 mg/L) and weak analgesia after 12 min at 19,000 ppm (50.4 mg/L) (Clayton and Clayton 1993–1994). Acute mortality generally does not occur at exposure below 50,000 ppm (Tomei Torres and Keith 2016; Winek et al. 2001). Chronic EC abuse has been also related to long-term severe neurological impairment, including hallucinations and ataxia. In particular, these latter effects have been reported in a subject inhaling EC two to three times per week over a 4-month period (IARC 1991). Other studies reported impairment of liver function and leukocyte phagocytosis in chronic EC abusers, while animal studies demonstrated fetotoxic and carcinogenic effects (Kuthiah and Er 2019). Although the pharmacokinetics of EC in human has not been investigated, experimental studies on mice confirm that EC is oxidatively dechlorinated in an NADPH- and O2-dependent reaction and P450-dependent metabolism, resulting in the formation of acetaldehyde (Fedtke et al. 1994a) or conjugated with glutathione (GSH) in a reaction catalysed by GSHS-transferases (Fedtke et al. 1994b). Disregarding data from occupational exposure, which may represent situations far from illicit uses, forensic cases reporting EC concentrations on blood and tissues after recreational use are scarce in the literature. Indeed, very few old cases have been reported so far (Broussard et al. 2000; Yacoub et al. 1993), hampering the forensic toxicologist in the diagnosis of EC intoxication. Recently, cases of acute reversible neurologic deficits on young adults due to voluntarily EC sniffing were studied (Al-Ajmi et al. 2018; Senussi and Chalise 2015), although blood concentration values were not reported. Literature about fatal EC inhalation is scant and the most recent case reporting data on post-mortem tissue distribution is dated back almost 20 years ago (Broussard et al. 2000). The paucity of toxicological data on this rare cause of death limit the forensic toxicologist interpretation and identification of fatal EC intoxications.
On these grounds, we describe a case of fatal intoxication due to EC sniffing, providing medico-legal considerations and toxicological findings on different tissues, contributing to the casuistic over the inhalant intoxications, which determination may be difficult if some precautions on sample collection and storage at the crime scene are missing.