madman
Super Moderator
ABSTRACT
A complete case example of a fatal 2,4-dinitrophenol (DNP) overdose involving a 23-year-old male is described. Included are details of not only the patient’s presenting symptoms and treatment, but also the subsequent findings of the coronial investigation process including the autopsy, post-mortem computed tomography (PMCT) scanning and toxicological analysis and results. The patient presented with elevated temperature, heart rate, and blood pressure. Multiple treatments were conducted to counteract these symptoms, however, the patient died approximately 1.5 hours after hospital admission and some 4.5 hours after the DNP was initially consumed. An autopsy revealed the presence of cardiovascular disease that was contributory to death and post-mortem computed tomography showed evidence of decompositional intravascular gas in the neck, head, face, lower abdomen, heart, and hepatic systems. The toxicological analysis was completed by protein precipitation with methanol and subsequent instrumental analysis by LC/MS/MS in negative ion mode. The antemortem blood specimen showed the presence of tadalafil, two anabolic steroids, and a DNP concentration of 110 mg/kg which is consistent with other reported DNP fatalities. Despite the small amount of time between the antemortem specimen collection and death, the DNP concentration identified in the femoral blood post-mortem specimen was comparably low (5.5 mg/kg). DNP concentrations also reduced during an extended period of specimen storage prior to analysis indicating some instability in biological specimens even when refrigerated or frozen. DNP was found to be distributed primarily in the aqueous tissues (blood, vitreous, bile) rather than solid matrices (liver, kidney, muscle).
1. Introduction
2,4-Dinitrophenol (DNP) exists at room temperature as a crystalline substance with a distinctive bright yellow coloration and musty odor.1 Since the early 1900s DNP has been used in the manufacture of a variety of different commercial products including; explosives, dyes, photography developers, wood preservatives, and pesticides.2 The earliest DNP reported deaths were due to occupational exposure related to these uses.3–5
In the 1930s DNP was found to cause significant weight loss when taken orally and was soon being marketed as a weight-loss drug.6,7 In the human body DNP acts by ‘uncoupling’ mitochondrial glycolytic oxidative phosphorylation. DNP disrupts the formation of adenosine triphosphate (ATP), the major final product in the Krebs cycle, by inhibiting both the uptake of inorganic phosphate into the mitochondria and through its action as a chemical ionophore which impairs the energy conversion gradient required for ATP production. The potential energy is instead dissipated as heat leading to hyperthermia.5 The use of energy reserves from adipose tissues is stimulated in the body which results in an increased metabolic rate and overall weight loss.8 DNP was associated with multiple adverse effects, including cataracts, severe hyperthermia, nausea, vomiting, sweating, dizziness, and headaches, and its use as a drug was subsequently banned in the United States in 1938.2
In the last two decades, DNP has had a resurgence as an unregulated weight loss aid that can be easily sourced by the public over the internet. The use of DNP for weight reduction is particularly prevalent in the body-building community.1 Reports of toxicity incidents involving DNP have increased substantially in recent years9 and there have been multiple cases of DNP related fatalities reported1,2,10–15
In Australia, due to ongoing reports of toxicity, the substance was up scheduled in 2017 to Schedule 10 of the Poisons Standard “substances of such danger to health as to warrant prohibition of sale, supply, and use”.
Since this time there have been a further two known DNP fatalities in Australia,16 the case presented here and another involving a male after the apparent consumption of DNP in what was mistakenly thought to be capsules containing MDMA (methylenedioxymethamphetamine).17 In this paper we describe a complete case example of a fatal DNP overdose involving a 23-year-old male. We include details of not only the patient’s presenting symptoms and treatment, but also the subsequent findings of the coronial investigation process. The results of the autopsy and post-mortem computed tomography (PMCT) scanning are described with an emphasis on the toxicological analysis and results.
2. Clinical presentation
3. Autopsy findings
4. Toxicology
4.1. Materials and methods
4.2. Sample preparation
4.3. Instrumental analysis
4.2. Sample preparation
4.5. Other testing
5. Results and discussion
6. Conclusion
The cause of death was certified as dinitrophenol toxicity. Coronary atherosclerosis was another significant condition that may have contributed to death in the context of cardiovascular collapse. The manner of death was suicide. Dinitrophenol is a highly toxic compound with a long history of causing adverse health events. While this case involved the intentional ingestion of a large dose of DNP there are multiple reports that it is being increasingly used as a weight-loss supplement that is apparently easily obtainable over the internet. As such it is advisable for emergency departments to be alert for the potential symptoms of DNP toxicity and for laboratories to consider its inclusion into toxicological screening procedures.
A complete case example of a fatal 2,4-dinitrophenol (DNP) overdose involving a 23-year-old male is described. Included are details of not only the patient’s presenting symptoms and treatment, but also the subsequent findings of the coronial investigation process including the autopsy, post-mortem computed tomography (PMCT) scanning and toxicological analysis and results. The patient presented with elevated temperature, heart rate, and blood pressure. Multiple treatments were conducted to counteract these symptoms, however, the patient died approximately 1.5 hours after hospital admission and some 4.5 hours after the DNP was initially consumed. An autopsy revealed the presence of cardiovascular disease that was contributory to death and post-mortem computed tomography showed evidence of decompositional intravascular gas in the neck, head, face, lower abdomen, heart, and hepatic systems. The toxicological analysis was completed by protein precipitation with methanol and subsequent instrumental analysis by LC/MS/MS in negative ion mode. The antemortem blood specimen showed the presence of tadalafil, two anabolic steroids, and a DNP concentration of 110 mg/kg which is consistent with other reported DNP fatalities. Despite the small amount of time between the antemortem specimen collection and death, the DNP concentration identified in the femoral blood post-mortem specimen was comparably low (5.5 mg/kg). DNP concentrations also reduced during an extended period of specimen storage prior to analysis indicating some instability in biological specimens even when refrigerated or frozen. DNP was found to be distributed primarily in the aqueous tissues (blood, vitreous, bile) rather than solid matrices (liver, kidney, muscle).
1. Introduction
2,4-Dinitrophenol (DNP) exists at room temperature as a crystalline substance with a distinctive bright yellow coloration and musty odor.1 Since the early 1900s DNP has been used in the manufacture of a variety of different commercial products including; explosives, dyes, photography developers, wood preservatives, and pesticides.2 The earliest DNP reported deaths were due to occupational exposure related to these uses.3–5
In the 1930s DNP was found to cause significant weight loss when taken orally and was soon being marketed as a weight-loss drug.6,7 In the human body DNP acts by ‘uncoupling’ mitochondrial glycolytic oxidative phosphorylation. DNP disrupts the formation of adenosine triphosphate (ATP), the major final product in the Krebs cycle, by inhibiting both the uptake of inorganic phosphate into the mitochondria and through its action as a chemical ionophore which impairs the energy conversion gradient required for ATP production. The potential energy is instead dissipated as heat leading to hyperthermia.5 The use of energy reserves from adipose tissues is stimulated in the body which results in an increased metabolic rate and overall weight loss.8 DNP was associated with multiple adverse effects, including cataracts, severe hyperthermia, nausea, vomiting, sweating, dizziness, and headaches, and its use as a drug was subsequently banned in the United States in 1938.2
In the last two decades, DNP has had a resurgence as an unregulated weight loss aid that can be easily sourced by the public over the internet. The use of DNP for weight reduction is particularly prevalent in the body-building community.1 Reports of toxicity incidents involving DNP have increased substantially in recent years9 and there have been multiple cases of DNP related fatalities reported1,2,10–15
In Australia, due to ongoing reports of toxicity, the substance was up scheduled in 2017 to Schedule 10 of the Poisons Standard “substances of such danger to health as to warrant prohibition of sale, supply, and use”.
Since this time there have been a further two known DNP fatalities in Australia,16 the case presented here and another involving a male after the apparent consumption of DNP in what was mistakenly thought to be capsules containing MDMA (methylenedioxymethamphetamine).17 In this paper we describe a complete case example of a fatal DNP overdose involving a 23-year-old male. We include details of not only the patient’s presenting symptoms and treatment, but also the subsequent findings of the coronial investigation process. The results of the autopsy and post-mortem computed tomography (PMCT) scanning are described with an emphasis on the toxicological analysis and results.
2. Clinical presentation
3. Autopsy findings
4. Toxicology
4.1. Materials and methods
4.2. Sample preparation
4.3. Instrumental analysis
4.2. Sample preparation
4.5. Other testing
5. Results and discussion
6. Conclusion
The cause of death was certified as dinitrophenol toxicity. Coronary atherosclerosis was another significant condition that may have contributed to death in the context of cardiovascular collapse. The manner of death was suicide. Dinitrophenol is a highly toxic compound with a long history of causing adverse health events. While this case involved the intentional ingestion of a large dose of DNP there are multiple reports that it is being increasingly used as a weight-loss supplement that is apparently easily obtainable over the internet. As such it is advisable for emergency departments to be alert for the potential symptoms of DNP toxicity and for laboratories to consider its inclusion into toxicological screening procedures.
