Nitrites: An Old Poison or a Current Hazard? Epidemiology of Intoxications Covering the Last 100 Years and Evaluation of Analytical Methods

Abstract

In recent times, there has been a concerning and noteworthy rise in the global use of sodium nitrite for suicidal purposes. This is facilitated either through the employment of specialized “suicide kits” or by acquiring sodium nitrite through alternative means. Additionally, another occurrence contributing to nitrite poisoning is the recreational utilization of nitrites in the form of volatile aliphatic esters of nitrous acid, commonly referred to as “poppers”. Based on current available papers and reports on the subject of nitrates, nitrites, and poppers intoxications, an epidemiological analysis and evaluation of analytical methods were performed. A total of 128 papers, documenting a collective count of 492 intoxication cases, were identified. Additionally, in order to complete the epidemiological profile of nitrite poisoning, the authors briefly examined six cases of nitrite intoxication that were under investigation in our laboratory. Furthermore, a review of nitrite poisoning cases over the past 100 years shows that the old poison is still in use and poses a substantial risk to society.

Systematic Review of Fatal Sodium Nitrite Ingestion Cases: Toxicological and Forensic Implications

“…However, two primary derivatization techniques yield thermally stable and volatile products suitable for analysis through this method: nitration and alkylation with pentafluorobenzyl bromide (PFB-Br). The nitration method relies on the nitrate-specific reaction of an aromatic compound with a nitrate anion under acidic conditions [ 18 , 62 , 63 ]. A significant drawback of this method is the use of concentrated sulfuric acid as a catalyst, with studies indicating positive interference in nitrate determination due to the decomposition and release of nitrate from endogenous compounds in the plasma, such as various nitroso compounds [ 18 , 62 , 63 ].…”

“…The nitration method relies on the nitrate-specific reaction of an aromatic compound with a nitrate anion under acidic conditions [ 18 , 62 , 63 ]. A significant drawback of this method is the use of concentrated sulfuric acid as a catalyst, with studies indicating positive interference in nitrate determination due to the decomposition and release of nitrate from endogenous compounds in the plasma, such as various nitroso compounds [ 18 , 62 , 63 ]. Moreover, working with concentrated sulfuric acid demands careful handling due to the release of substantial heat in addition to the aqueous phase.…”

“…However, relying solely on methemoglobinemia to ascertain the cause of poisoning is not advisable due to its association with various other substances, and the determination of MetHb itself may present challenges. Moreover, reported MetHb concentrations in fatal poisoning cases vary widely, frequently falling below the minimum reference lethal saturation of 60% as described in the literature [ 18 , 66 , 67 , 68 ]…”

“…However, relying solely on methemoglobinemia to ascertain the cause of poisoning is not advisable due to its association with various other substances, and the determination of MetHb itself may present challenges. Moreover, reported MetHb concentrations in fatal poisoning cases vary widely, frequently falling below the minimum reference lethal saturation of 60% as described in the literature [18,[66][67][68] Multiple studies have illustrated that the ingestion of dietary nitrate leads to statistically significant increases in circulating nitrite concentrations. Nevertheless, it has been noted that a tenfold rise in circulating nitrate levels achieved through dietary intake results in only an approximately twofold increase in circulating nitrite concentrations [65].…”

“…The autopsy should be carefully performed to detect common indicators of hypoxia or nonspecific signs of sodium nitrite toxicity. However, sodium nitrite intoxication is still an open challenge, given the variety of detection methods and different diagnostic algorithms in use in various forensic settings [ 18 ]. In this regard, this systematic review summarizes the most crucial evidence regarding the fatal toxicity of sodium nitrite.…”