Review the List of Psyciological Effects That Dnp
J Med Toxicol. 2011 Sep; 7(3): 205–212.
ii,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death
Johann Grundlingh
Emergency Medicine, Whittington Hospital, London, UK
Paul I. Dargan
Guy'southward and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK
Male monarch's College London, London, Uk
Marwa El-Zanfaly
Emergency Medicine, Northwick Park Hospital, London, Uk
David M. Woods
Guy's and St Thomas' NHS Foundation Trust and Male monarch's Wellness Partners, London, United kingdom
Rex'due south College London, London, UK
Medical Toxicology Office, second Floor, Bermondsey Wing, Guy'southward Hospital, Great Maze Swimming, London, SE1 9RT UK
Abstract
2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant adverse effects. DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid. Information technology causes uncoupling of oxidative phosphorylation; the classic symptom complex associated with toxicity of phenol-based products such equally DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death. Fatalities related to exposure to DNP have been reported since the turn of the twentieth century. To engagement, in that location have been 62 published deaths in the medical literature attributed to DNP. In this review, we volition describe the design and pathophysiology of DNP toxicity and summarise the previous fatalities associated with exposure to DNP.
Keywords: Dinitrophenol, Weight loss, Toxicity, Fatality
Introduction
The pharmacologic handling of obesity has been challenging. Previously, amphetamine derivatives, such as dexflenfluramine, fenfluramine and phentermine, were used as centrally active appetite suppressants; however, their utilize is associated with valvular heart illness and the development of pulmonary hypertension. Sibutramine (Reductil™ Abbott Laboratories), a newer centrally active appetite suppressant and the lipase inhibitor orlistat (Xenical™, Roche) are currently being used as 'diet pills', but have unpleasant side effects. Withal, for the majority of individuals with morbid obesity (body mass index >35 kg/m2), obesity surgery ('gastric banding') is ofttimes the treatment modality of option, specially in those associated severe co-morbidities [1]. Regular utilise of 2,4-dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant side effects [two].
The first decease due to DNP (C6H4Due north2O5) was reported in 1918 and was secondary to occupational exposure [3]. Currently marketing of DNP, which is predominately through the internet, is targeted towards primarily trunk builders who are attempting to lose fat merely retain musculus majority. Additionally, information technology is widely available on the net and is marketed every bit a 'rubber weight loss' drug. Individuals are able to purchase 'large quantities', such as kilograms of DNP pulverization or hundreds/thousands of DNP-containing tablets. There are many regimes for taking the drug, all of which rely on the metabolic stimulatory effects of the drug [4, 5]. It has a small therapeutic index and is extremely dangerous in overdose. In this review, nosotros volition summarise the pharmacology of DNP, the potential mechanisms for its toxicity and the clinical evidence of harm associated with the utilize of DNP.
Search Strategy
The National Center for Biotechnology Information (PubMed) system was searched utilising the search terms 'dinitrophenol', 'dinitrophenol overdose' and 'dinitrophenol expiry' in titles and abstracts. All the relevant abstracts were screened by i author (JG) and those that did not describe expiry(s) due to DNP were excluded from the pool of results. All the remaining articles were retrieved and scrutinized to ensure they convincingly described death(s) due to DNP. All articles describing deaths due to other compounds similar to DNP (e.chiliad. dinitro-crescol) were excluded. Citations and references of the remaining articles were searched, retrieved and evaluated in the same way as the original search results. Additional online searches for suppliers of DNP were done using an net search engine (Google) with the terms 'dinitrophenol' and 'dinitrophenol weight loss'.
History of Dinitrophenol
The French used DNP in the industry of munitions during the Beginning World State of war [6, vii]. Since and then, it has besides been used as a dye, wood preserver, herbicide and photographic programmer. It was Maurice Tainter at Stanford University in 1933 who discovered that the human consumption of DNP led to meaning weight loss and soon it was popularised as a weight loss drug [viii]. It was included in over-the-counter medications and was sold to the public without requiring a prescription.
Its use for those wishing to lose weight was encouraged by reports of rapid, prophylactic weight loss [7, 8]. DNP can cause a significant increase in the basal metabolic rate [vii, 8]. This leads to weight loss by burning more than fat and carbohydrates [nine], and weight loss of upward to i.five kg per week is reported without significant side effects. However, there seems to be significant variation in private responses with an average metabolic charge per unit increase of 11% for every 100 mg of DNP when taken regularly [10–12]. As more side effects, especially cataracts, were reported, DNP was labelled equally 'extremely dangerous and not fit for human consumption' by the Federal Nutrient, Drug and Cosmetic Act of 1938 [ii, xiii].
After 1938, medical prescription of DNP stopped and cases of poisoning due to medical intake were no longer reported, but instance reports of deaths associated with the ingestion of DNP still emerged [14, 15]. It is anecdotally reported to have been prescribed to the Russian soldiers during World War Two to continue them warm [xvi].
In 1981, a medico (Dr. Bachynsky) in TX, USA processed industrial DNP into tablets which he marketed/dispensed under the merchandise proper noun 'Mitcal' through his private weight loss clinic [xvi]. He advertised that weight loss occurred using 'Mitcal' through a machinery he called intracellular hyperthermia therapy. Information technology is alleged in subsequent courtroom proceedings that over xiv,000 people were treated by Dr. Bachynsky. Individuals using Mitcal started reporting agin effects, such every bit fever, shortness of breath and sweating, to the Usa Nutrient and Drugs Administration in late 1982. Additionally, there was a fatality associated with an intentional overdose of 'Mitcal' in 1984. Following further investigation, Dr. Bachynsky was convicted in 1986 of drug law violations, fined and prohibited from dispensing DNP to any patients. Yet, he continued to employ DNP for a variety of unlike 'medicinal claims' and was somewhen jailed for fraud in 2008 in the USA in relation to the marketing of a company that was developing DNP being used in Europe as a cancer treatment known as intracellular hyperthermia therapy [17].
The UK Nutrient Standard Agency issued a warning in 2003, labelling DNP as 'not fit for man consumption'. This warning was aimed specifically at bodybuilders, to avert its use due to significant potential for curt-term and long-term damage, following the hospitalisation of a Finish bodybuilder later on having taken DNP [18].
Despite this, DNP remains widely available and as discussed beneath in more particular, tin be purchased over the internet, particularly from online pharmacies. Additionally, there are instructions for the synthesis of DNP online for self-industry. As noted to a higher place, DNP has been banned as a weight loss drug in the United states of america, and in the United kingdom, it has been labelled as a hazardous chemical under the Clean Air Act [2, 18]. Despite this legislation and warnings of harm associated with its use, reports of deaths due to the use of DNP take increased in the last few years (Fig.1), and the final decade has seen the highest number of case reports from death due to intentional dinitrophenol overdose (Table1).
Graphical presentation of DNP-related deaths past decade
Table 1
Summary of previously published fatalities relating to exposure to DNP including basic demographics, amount of exposure and maximal temperature recorded pre-death
| Sex activity | Age | Type of exposure | Dose | Time to death | Maximum temperature | Year [reference] |
|---|---|---|---|---|---|---|
| 1000 | NR | Occupational | North/A—occupational | 14 h 30 min | 40.5°C (104.9°F) | 1916 [86] |
| M | NR | Occupational | Northward/A—occupational | Unknown | Unknown | 1918 [three] |
| 36 workers | N/A | Occupational | N/A—occupational | Unknown | 43°C (109.4°F) | 1919 [6] |
| M | Weight loss | 2.5–5 g | 10 h 10 min | > 43°C (>110°F) | 1933 [67] | |
| F | 46 | Weight loss | 300 mg over 6 weeks | N/A | xl.iv°C (104.8°F) | 1934 [71] |
| F | 31 | Weight loss | 6.06 g in 4 days | 16 days later on outset of trial | 38.ix°C (102°F) | 1934 [57] |
| F | 25 | Weight loss | 2.88 g over 5 days | 7 days after first dose | 38.9°C (102°F) | 1934 [46] |
| F | NR | Weight loss | ∼10 chiliad over 6 weeks | 5 days afterward admission | 41°C (105.8°F) | 1934 [61] |
| Yard | 37 | Weight loss | 9 grand over vii days | 11 h | twoscore.nine°C (105.7°F) | 1934 [51] |
| F | 13 | Weight loss | 5.4 g over 46 days | xx h after access | 40.ix°C (105.6°F) | 1936 [47] |
| F | 21 | Weight loss | four.5 g | 9 h 10 min | 41.1°C (106°F) | 1936 [56] |
| Grand | NR | Overdose | Unknown | Approx. 12 h | Unknown | 1953 [68] |
| M | 61 | Adventitious | Unknown | 24 h | Unknown | 1960 [15] |
| F | 17 | Weight loss | Unknown | ? 28 h | 38.5°C (101.4°F) | 2002 [75] |
| M | 22 | Weight loss | 2.4 thousand over 4 days | 17 h later on terminal dose | 38.9°C (102°F) | 2004 [28] |
| F | 17 | Overdose | ii.three–2.88 g | 10 h | > 40°C (>104°F) | 2005 [69] |
| M | 24 | Bodybuilding | Unknown | Unknown | 40.viii°C(105.5°F) | 2005 [72] |
| F | 17 | Bodybuilding | Unknown | 3 h after presentation | 39.4°C (103°F) | 2006 [73] |
| K | 28 | Bodybuilding | Unknown | 50 min afterward presentation | 41.1°C (106°F) | 2006 [73] |
| M | 30 | Bodybuilding | Unknown | Unknown | Unknown | 2007 [74] |
| F | 27 | Weight loss | Unknown over 1 week | eight h after presentation | 38°C (100.4°F) | 2009 [21] |
| G | 46 | Overdose | 2.8 g | 21 h | 37.8°C (100.0°F) | 2010 [four] |
| G | NR | Overdose | 2.8 g | 15 h | 39.five°C (103.1°F) | 2010 [22] |
| F | 49 | Occupational | N/A—cutaneous | 15 h | 38.9°C (102°F) | 2010 [33] |
| Yard | 41 | Occupational | N/A—cutaneous | 9 h | 38.5°C (101.3°F) | 2010 [33] |
NR (not recorded)
The Role of the Cyberspace in Sourcing and Supplying Dinitrophenol
Present, DNP is sold by and large over the net nether a number of dissimilar names such as 'DNP', 'Dinosan', 'Dnoc', 'Solfo Black', 'Nitrophen', 'Aldifen' and 'Chemox'. The chemical is a yellow crystalline powder that has a sweetness, musty odour and is soluble in water. The dose of DNP per capsule varies from website to website but information technology is most commonly sold as either 100- or 200-mg capsules. Some internet sites accept DNP bachelor in bulk quantities, allowing users to purchase kilograms of DNP powder or hundreds/thousands of DNP-containing tablets, likewise as offering free anabolic steroids and thyroxine to employ in combination with the DNP [v, 19].
Websites often offer some advice for users around the use of DNP, although this is often targeted towards bodybuilders rather than for generic weight loss. A typical regimen would include starting with 1 capsule of DNP for the starting time few days followed by increasing doses to a recommended maximum of 400 mg/solar day, which is and so used for upwardly to 2 weeks in duration [5, xix]. These regimens may likewise include the use of anabolic steroids and/or thyroxine to increment muscle majority. In that location is also the suggestion that 'crystalline' DNP is more stiff than 'regular' DNP and therefore users should ensure they are aware of which type they are using and additionally, should limit the dose of crystalline DNP to no more than 200 mg/solar day. These websites additionally describe the potential toxicity associated with the use of DNP including the potential for hyperthermia and death. Advice is provided to users on how to prevent hyperthermia developing, including utilise of ac/fans and only exercising in cool areas whilst on the DNP stage of a 'treatment cycle' and carrying a thermometer to monitor body temperature [5]. They recommend that should body temperature rise above 38.9°C (102°F), the user should 'lower the DNP dose, take a very common cold bath and ensure adequate hydration with water and juice-based drinks'.
The marketed and desired beneficial upshot of weight loss is reportedly not rapid plenty for some individuals, and therefore they may take higher and potentially toxic doses in society 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 [iv, 22].
Potential Mechanisms of Toxicity
The archetype symptom complex observed by overdose of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea [four, 21, 22]. There are idea to exist several physiological mechanisms involved in the development of toxicity of DNP, which are summarised below.
Uncoupling of Oxidative Phosphorylation
DNP decreases the formation of loftier-energy phosphate bonds in mitochondria and at the same time stimulates systemic oxygen consumption [23]. This dissociative effect is known as uncoupling of oxidative phosphorylation. Adenosine triphosphate (ATP) product is the final production of the tricarboxylic acid (Krebs) bike in mitocondria along with CO2 and H2O. During glycolysis, there is a internet production of two ATP molecules, just the majority of free energy-rich phosphate bonds (38 in total) are produced during the final oxidative phosphorylation procedure. During this concluding stage, ATP synthetase converts adenosinediphosphate to ATP with the addition of an inorganic phosphate molecule. DNP interferes with the final energy production pathway by preventing the uptake of inorganic phosphate molecules into the mitochondria [24, 25]. This results in the inhibition of all energy-requiring processes and the extra-mitochondrial accumulation of inorganic phosphate [26]. DNP too acts every bit a chemical ionophore, stopping the final energy conversion by exporting the proton ions (H+) needed for ATP production across the mitochondrial membrane past increasing the basal leak of protons [12]. This shift in the proton electrochemical gradient and so results in potential energy dissipating as estrus, instead of existence converted to ATP, with rapid consumption of calories [27, 28]. The heat product represents a failure in thermoregulatory homeostasis, leading to uncontrolled hyperthermia [29].
Stimulation of Glycolysis
El-Guindy et al. concluded that dinitrophenol produces its glycolytic effect through its upshot on the muscle contraction process [30]. Saccharide consumption markedly increases in the presence of dinitrophenol which allows for rapid weight loss when dinitrophenol is taken in small doses [26]. Pyruvic acid is aerobically metabolised to H2O and CO2, simply results in the production of lactic acid when metabolised anaerobically. The discrepancy between the stimulation of glycolysis and the inhibition of oxidative phosphorylation results in a rapid rise in the production of pyruvic acid, leading to an increased production of lactic acrid [24, 26, 31].
Potassium and Phosphate Aggregating
Mudge showed that potassium accumulates in rabbit kidney slices as the concentration of dinitrophenol is increased [32]. The aggregating of potassium continues even after cellular respiration is inhibited [32] and hyperkalaemia has contributed to toxicity [33]. Due to the uncoupling of oxidative phosphorylation, inorganic phosphate is no longer absorbed into the mitochondria and aggregating takes place, but whether this contributes to the clinical presentation is unknown [25, 34].
Teratogenicity, Carcinogenicity and Other Toxicity
In animal studies, DNP has been shown to be teratogenic, mutagenic and carcinogenic; developmental and reproductive toxicity has also been reported [35].
Clinical Features of DNP Toxicity
Routes of Exposure
The oral road is currently the most common route of therapeutic and suicidal exposure. Dermal exposure can crusade xanthous staining and may have mild corrosive effects on the pare. Absorption through the skin may pb to systemic effects similar to those seen post-obit ingestion of DNP, although only mild symptoms are commonly experienced. Exposure to the eyes may crusade yellow discoloration of the sclera with conjunctival injection and irritation. Dermal exposure is the most common route of unintentional exposure [6, 33]. DNP is used in the chemical manufacture in wood preservatives, herbicides and dyes and may leak onto industrial sites through landfill and storage tanks. Adventitious spills during manufacture and transport are possible and exposure is normally through exposure to the water or dirt that it has leaked on. Although at that place have been no reports of this occurring, at that place have been two fatalities related to individuals recycling nylon bags that had previously contained DNP [33]. Inhalational exposure can happen by breathing contaminated air at DNP-containing waste sites or from incineration fumes. Inhalation of DNP fumes may lead to meaning systemic furnishings, similar to those seen with ingestion.
Organ Systems Affected by Therapeutic Utilize
There is a small margin between the benign effects and the toxic effects of DNP. The most mutual side effect reported with the therapeutic use of DNP is a rash [6, 36–38]. This rash can be maculo-papular, urticarial, angio-oedematous or a severe exfoliative dermatitis [39–41]. There is often accompanying pruritis and subsequent desquamation [39, 41, 42]. Prolonged peripheral neuritis has been reported, oft affecting the hands and feet and associated with skin changes [11, 43, 44]. A mutual complaint is that of yellow discoloration of the skin, sclera and urine [45–48]. This aforementioned yellow discoloration is oft seen at autopsy and has been confused with jaundice due to reports of liver damage [36, 45, 49–52].
T wave and ST segment abnormalities take been noted and some of the before autopsied example reports recorded heart muscle impairment [46, l, 53]. Gastroenteritis and anorexia accept been reported in high doses [11, 36]. Acute kidney injury, as evidenced past acute tubular necrosis, has been found at dissection and also reported in ii other cases [46, 54, 55]. Confusion, agitation, convulsion and coma are the most common neurological effects reported [50, 56, 57].
Agranulocytosis and neutropaenia have been associated with the therapeutic employ of DNP [36, 37, 45, 47, 58–61]. Cataracts tin develop quickly after the use of DNP, ordinarily leading to a permanent decrease in vision to light–dark perception in days to months [62–65]. Permanent deafness has been reported at doses considered to be therapeutic [66].
Intentional Overdose
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, fifteen, 22, 51, 56, 67–69]. The onset of symptoms was reported as early as 3 h and xxx min later on 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, 67–69]. However, there has been at least 1 case of survival following deliberate overdose in an 18-yr-former female person who adult typical features of DNP toxicity [tachycardia of 144 beats per infinitesimal, tachypnoea of 38–40 breaths per minute and hyperthermia of 39.7°C (103.4°F)] [70]. She was managed conservatively with intravenous fluids and water ice packs to maintain her temperature below 38.iii°C (101°F) and was discharged less than 48 h following admission to hospital with no adverse furnishings at the time of discharge. Ingestion of DNP was confirmed by analysis of gastric lavage contents.
DNP-Related Fatalities
Fatalities from the intake of DNP, whether adventitious or suicidal, have been reported since the turn of the twentieth century (Table1). To engagement, there accept been 62 published deaths attributed to DNP (Fig.ane). The largest publication of 36 deaths due to DNP was published in 1919 [6]. This was a report into the deaths in munition factories in Paris due to occupational exposure to DNP. It highlights the improvements made in the factory to prevent further deaths through elementary measures such as ventilation, personal protective equipment and better hygiene. This combined with changes in legislation brought the decease charge per unit down from 16.3 per x,000 t of DNP handled/produced to one.two per 10,000 t.
During the 1930s, reported DNP-related fatalities were all individuals who had taken information technology for weight loss [46, 47, 51, 56, 57, 61, 67, 71]. Later the 1930s, at that place have merely been 2 fatalities in the remainder of the twentieth century [xv, 68]. Ane related to deliberate ingestion of DNP [68] and the other was where an individual accidentally ingested a liquid he thought to be grape juice, simply in fact independent derivatives of DNP [15]. This further reject in fatalities may reflect the labelling of DNP as 'extremely dangerous and non fit for human being consumption' by the US Food and Drug Assistants in 1938.
Over the last decade, from 2001 to 2010, there have been 12 deaths related to exposure to DNP. These fatalities have been linked to deliberate overdose [4, 22, 69], accidental toxicity associated with use by bodybuilders or for weight loss [21, 28, 72–75] and accidental occupational exposure [33]. This resurgence in reported fatalities may reverberate the increased availability of DNP over the net, marketed particularly towards bodybuilders.
Preceding death, the patient is often profoundly hyperthermic and in that location may be associated methaemoglobinaemia. Death is normally secondary to massive cardiovascular collapse. At that place have been frequent reports of a rapid (within minutes) onset of generalised rigidity after death [6, eleven]. This profound muscle rigidity has also been seen to happen before death making mechanical ventilation very difficult [21]. This early on onset of generalised rigidity after death has been attributed to the release of calcium from the cytosol due to the depletion of ATP [22].
Ingestion is currently the most common route of exposure to the drug leading to decease. The lowest published lethal human oral dose of DNP is 4.three mg/kg [76]; the doses reported in the published acute and suicidal fatalities range from 2.8 g to an estimated 5 g. The highest reported dose taken in acute overdose associated with survival was a woman who took 2.4 g with no complications [lxx].
Options for Management
There is no specific antidote for DNP poisoning and all management strategies are based on example reports and skillful opinions, just the key to the management of DNP poisoning lies in early on recognition and a loftier index of suspicion [46]. Patients who have acutely overdosed on DNP in any form should be observed for at to the lowest degree 12 h, as no patient has been recorded to be asymptomatic across 10 h after an acute overdose [4]. During this time, their body temperature, cardiac rhythm, heart rate and oxygen saturation should be carefully monitored.
Although in that location are no previous reports of its use, in line with the previously published American Academy of Clinical Toxicology/European Association of Poisons Centres and Clinical Toxciologists position statements on the use of oral activated charcoal, we would recommend consideration of a single dose of activated charcoal in those individuals who present within an hr of ingestion. Previous autopsies have reported a yellow coloured fluid in the intestines of some cases; there is no evidence that this fluid contains DNP rather than staining following ingestion. Therefore, at this time although there is no evidence to support the apply of multi-dose activated charcoal and/or whole bowel irrigation, nosotros feel that the potential benefit outweighs the potential risk. External decontamination, if appropriate, should be undertaken past washing to reduce dermal exposure. Based on the underlying pathophysiological principles and previous experience, information technology would be appropriate to avoid the use of salicylates as it may worsen the DNP-related toxidrome [77, 78]. Aggressive fluid resuscitation should be initiated, using cooled fluids in those with hyperthermia.
Seizures should exist controlled with benzodiazepines. These may also exist needed to command severely agitated patients, as their agitation will add to the hyperthermic land which may lead to circulatory collapse. External cooling measures with ice or cooling blankets should exist initiated to control hyperpyrexia [11, lxx, 79–81]. If benzodiazepines practice not control agitation or seizures, and so paralysis, intubation and ventilation should be considered. Dantrolene and ice baths have been used to control the severe hyperthermic state [46, 82]. There is the possibility for the apply of external cooling devices, such equally those used to induce therapeutic hypothermia post-obit an out of infirmary cardiac arrest, to rapidly reduce temperature; however, in that location have been no previous reports of using these devices in patients with DNP toxicity. Dantrolene has previously been recommended to manage the hyperthermia associated with the use of DNP. There is no evidence to back up this recommendation, simply it has been used successfully in a unmarried case written report [34, 82].
Intravenous vasopressors and/or inotropes should be considered accompanied with invasive arterial monitoring if fluid therapy fails to maintain the blood pressure. Cardiopulmonary resuscitation was performed in some of the cases of DNP overdose and in 1 case for up to an 60 minutes [69], but has never led to a return of spontaneous apportionment. Halothane should exist avoided as possible synergistic hyperthermia may cause deterioration and death [29].
Methaemoglobinaemia should ever be suspected and tested for. Levels exceeding xxx% should be treated with intravenous methylthioninium chloride (methylene blueish), but treatment may be started at lower serum methaemoglobin levels in the presence of other signs of shock and tissue hypoperfusion.
The use of continuous veno-venous haemofiltration (CVVH) has been recommended to manage hyperkalaemia and hyperthermia associated with DNP overdose [4, 83]. However, at that place are no published cases in which CVVH or similar therapies have been used in DNP poisoning.
Propranolol has been studied in dogs poisoned by DNP and a pregnant reduction in lactate levels was recorded [25], but its clinical use in humans cannot exist recommended due to the inhibitory issue on glucose production and unknown effect on mortality. Loftier-dose insulin and glucose may accept a beneficial issue through facilitation of glycolysis, but there is no animal or human data to support this treatment modality at this time [84]. Still, glucose administration alone may be useful since glycolysis would be the main source of ATP product in DNP-poisoned cells [85].
Summary
DNP has been available for over a century, initially in the industry of munitions, due to its explosive properties. From the 1930s onwards, there has been interest in its properties to increase the underlying metabolic rate, leading to an associated weight loss. Following a number of deaths in the 1930s, the United states of america Food and Drug Administration determined that DNP was 'extremely dangerous and not fit for human consumption'. There were very few reported deaths since the belatedly 1930s, until the last decade. Information technology appears that there has been increasing interest and availability of DNP-containing products on the internet. Whilst these appear to be largely targeted towards bodybuilders to try and reduce fat and improve muscle majority, at that place have been a number of deaths related to its use for more general weight loss. The main toxicity seen with DNP is similar to that seen with other phenol-based products and is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea with associated cardiovascular collapse/cardiac arrest and expiry. There is no specific management for individuals with DNP-related toxicity; it is imperative that the temperature is brought down as rapidly and as soon as possible to try and reduce systemic toxicity and/or death. Currently, DNP remains freely available on the net, with both detailed 'regimens' for its use and about the potential for acute toxicity and decease on the internet seller websites. Information technology is likely that some individuals, despite these warnings, will go on to purchase and apply DNP-containing products to aid with weight loss, with the potential gamble of acute toxicity and/or death.
Disharmonize of Interest
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