'Fatal 2,4-dinitrophenol poisoning... coming to a hospital near you'

Abstract

An adult man was brought into the emergency department after deliberate ingestion of dinitrophenol: an agent that uncouples mitochondrial oxidative phosphorylation. The patient rapidly developed a hyper-metabolic state with fever, respiratory failure and died within a few hours after admission. Dinitrophenol is used in the manufacture of dyes, pesticides and explosives. Sub-acute poisoning is associated with weight-loss and the substance had been prescribed for this purpose during the 1930s in the United States before being banned due to serious side effects. Although remaining unlicensed as a drug, dinitrophenol is widely available through mail-order websites and online pharmacies, which promote it as an anti-obesity treatment. This case highlights the need for awareness of possibly increasing rates of accidental poisoning with a growing obesity prevalence and availability of this unlicensed drug through the internet. Additionally, we discuss the use of dantrolene in dinitrophenol poisoning and question whether current Toxbase/UK National Poison Information Service treatment guidelines regarding the indication and dosing of this drug, the only relatively specific treatment in dinitrophenol poisoning presently recommended, could be revised.

2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death

“…The marketed and desired beneficial effect of weight loss is reportedly not rapid enough for some individuals, and therefore they may take higher and potentially toxic doses in order to hasten the weight loss effects [20,21]. Additionally, there have been a number of recent fatalities due to intentional ingestion of DNP as suicide attempts [4,22].…”

“…The classic symptom complex observed by overdose of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea [4,21,22]. There are thought to be several physiological mechanisms involved in the development of toxicity of DNP, which are summarised below.…”

“…The average time to presentation in the reported cases of acute or suicidal overdose is 7-8 h and the average time of death is 14 h [4,15,22,51,56,[67][68][69]. The onset of symptoms was reported as early as 3 h and 30 min after the overdose [56].…”

“…The usual complaint of the patient is that of profuse sweating [46]. The initial fever is not associated with a change in heart rate or blood pressure, but tachycardia, tachypnoea, shock, confusion, convulsions, cardiovascular collapse and pulseless electrical activity are the eventual consequence of the fatal, deliberate overdose, regardless of treatment [4,15,22,51,56,[67][68][69]. However, there has been at least one case of survival following deliberate overdose in an 18-year-old female who developed typical features of DNP toxicity [tachycardia of 144 beats per minute, tachypnoea of 38-40 breaths per minute and hyperthermia of 39.7°C (103.4°F)] [70].…”

“…These fatalities have been linked to deliberate overdose [4,22,69], accidental toxicity associated with use by bodybuilders or for weight loss [21,28,[72][73][74][75] and accidental occupational exposure [33]. This resurgence in reported fatalities may reflect the increased availability of DNP over the internet, marketed particularly towards bodybuilders.…”