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Toxnet NIH Tidbits on DNP

Toxnet: NIH Tidbits on DNP

 /HUMAN EXPOSURE STUDIES/ In an experimental study in which four volunteers were placed on various diets (balanced, high carbohydrate, high fat, or high protein) and given an average dose of 3.53 mg/kg/day 2,4-DNP for 7-16 days, the average weight loss during 2,4-DNP treatment was approx 2 pounds (0.92 kg). The type of diet did not appear to influence the degree of weight loss.

/HUMAN EXPOSURE STUDIES/ In an experimental study to determine if 2,4-DNP would be beneficial in the treatment of depression, various responses were observed among 18 psychiatric patients with listlessness, indifference, mild depression, or lethargy. No psychological change was found for 8 patients, lethargy and depression increased in severity in 4 patients, while alertness increased and depression decreased in 6 patients. Discontinuation of the drug resulted in marked retrogression in three of the 6 patients that benefitted from the treatment.

 

/SIGNS AND SYMPTOMS/ The Food Standards Agency /issued/ urgent advice to the public, and people in the bodybuilding community in particular, following the identification of a serious problem with 'fat-burner' capsules containing DNP (2,4-Dinitrophenol). This industrial chemical is known to have serious short-term and long-term effects on human health when eaten. Independent toxicological experts advise that these capsules are extremely dangerous to human health. Taking as few as three or four of these capsules (or 1000 mg of DNP) in one dose could result in death. Smaller amounts (less than one capsule a day) taken over longer periods of time are known to have caused serious human health effects, such as cataracts. The Food Standards Agency is therefore advising consumers not to take any product containing DNP at any level, as this chemical is not suitable for human consumption ... The Finnish National Food Agency informed the FSA of a problem via the European Commission. This followed the hospitalization of a Finnish bodybuilder after taking yellow 'fat-burner' capsules containing DNP, which were purchased via the Internet. Capsules tested by the Finnish authorities contained as much as 380 mg of DNP.

 

/SIGNS AND SYMPTOMS/ Effects of short-term exposure: The substance may cause effects on metabolism, resulting in very high body temperature. Exposure may result in death. Effects of long-term exposure: Repeated or prolonged contact with skin may cause dermatitis. The substance may have effects on the peripheral nervous system. The substance may have effects on the eyes, resulting in cataracts.

 

/SIGNS AND SYMPTOMS/ The characteristic effects of 2,4-DNP are elevation of the basal metabolic rate (often measured indirectly as oxygen consumption), elevation of body temperature, and increased perspiration (humans). The body compensates for these effects by increasing the respiratory rate to deliver more oxygen to the tissues. As body temperature rises, peripheral vasodilation occurs as a cooling mechanism and the pulse rate rises to maintain the circulation.

 

/SIGNS AND SYMPTOMS/ ... A small percentage of humans ingesting 2,4-DNP or its sodium salt for weight loss developed peripheral neuritis, life-threatening agranulocytosis, serious skin reactions, or cataracts leading to blindness. Most of these effects were not observed in other mammalian species exposed orally, although cataracts were induced in yellow adipose mice and in guinea pigs on a vitamin C-deficient diet. There does not seem to be a most sensitive target organ in animals; however, in humans, the hematopoietic, ocular, and nervous systems seem to be more sensitive than other body organ systems. 2,4-DNP inhibits mitochondrial function and affects all cells in the body. The increased sensitivity of certain human organ systems to 2,4-DNP suggests that their proper function is critically dependent on optimal ATP production.

 

/SIGNS AND SYMPTOMS/ Short Term Exposure: Dinitrophenol can affect you when breathed and by passing through skin. Contact with the 2,4-isomer can cause severe irritation and burns to the eyes and skin. May affect the metabolism, causing very high body temperature. May affect the peripheral nervous system causing numbness, «pins and needles,» and/or weakness of the hands and feet. Exposure can cause a bluish color to skin and lips, headaches, temperature rise, dizziness, collapse, convulsions, coma, and even death. Exposure may irritate the lungs, causing caoughing and shortness of breath. Higher levels can cause a build up of fluid in the lungs, a medical emergency which can cause death. Long Term Exposure: Repeated or prolonged contact with skin may cause dermatitis with rash and drying and itching of the skin. Dinitrophenol may have effects on the eyes, causing cataracts. Exposure can damage the liver and kidneys, and affect the thyroid gland. May cause lung irritation and the development of bronchitis with coughing and shortness of breath. May damage the nervous system. High exposure may damage the developing fetus. Repeated exposure to the 2,4-isomer can damage blood cells, causing anemia.

 

/SIGNS AND SYMPTOMS/ Symptomatology: Marked fatigue, tremendous thirst, profuse sweating, flushing of face. Nausea, vomiting, abdominal pain and occasionally diarrhea. Restlessness, anxiety, excitement, occasionally leading to convulsions. A rise in body temperature, which is roughly proportional to the toxic dose, may culminate in severe hyperpyrexia. Tachycardia, hyperpnea, dyspnea, cyanosis and sometimes muscle cramps. Loss of consciousness, cessation of breathing and death. Late complications: a. Decreased urine output with albuminuria, casts, pigment, sometimes blood cells, due to toxic nephritis. b. Jaundice and tenderness in liver region due to toxic hepatitis. Occasional hypersensitivity reactions after repeated exposures (or in chronic poisoning) include agranulocytic angina, skin rashes, peripheral /neuropathy/ ... and cataract formation. /Dinitrophenol/

 

/SIGNS AND SYMPTOMS/ In acute industrial poisoning, nystagmus /involuntary rapid movement of the eye/ ... said to be present in cases of moderate poisoning, and dilated pupils were noted in severe cases with poor prognosis.

 

/SIGNS AND SYMPTOMS/ In a poisoned person, the result is an almost immediate increase in oxygen consumption, body temperature, breathing rate, and heart rate. Because circulation and resp do not accelerate in proportion to the metabolic demand, anoxia and acidosis develop. ... It is a milder corrosive to skin and mucous membranes than phenol, but concentrated solutions have produced corrosion of the oropharyngeal, esophageal and gastric mucous membranes. It exerts direct actions on the cerebrum and lower brain centers, consisting of stimulation followed by depression. In the kidney, it may produce necrotizing tubular injury. If the acute phase of poisoning is survived, the patient usually tolerates later complications, which may include renal insufficiency and toxic hepatitis. The fulminating type of poisoning is characterized by sudden onset, severe symptoms, and prompt death (within 24 hours). Death is due to respiratory or circulatory collapse, especially the former. Many factors undoubtedly contribute to this collapse, notably hyperpyrexia, ... dehydration, muscle rigor (due to heat and/or lactic acid), and occasionally pulmonary edema. ... In subacute poisoning due to repeated daily exposures, some individuals complain of lassitude, headache, and malaise, while others experience a disarming sense of well-being, energy, and drive. /Dinitrophenol/

 

/SIGNS AND SYMPTOMS/ /In acute poisoning from ingestion/ skin becomes hot and flushed, profuse perspiration, intense thirst, severe headache, nausea, vomiting, abdominal pain, restlessness, anxiety, delirium, and generalized weakness occur. Excessive hyperpyrexia, acidosis, and dehydration may be followed by circulatory or respiratory collapse and death.

 

/SIGNS AND SYMPTOMS/ Hematologic alterations in humans resulting from 2,4-dinitrophenol exposure include hemolytic anemia, neutropenia, and eosinophilia.

 

/SIGNS AND SYMPTOMS/ 2,4-Dinitrophenol signs and symptoms are fever/hyperthemia (increased metabolic rate), skin discoloration (pseudojaundice), acidosis (metabolic, delayed), hypotension, cataract (subcapsular), hearing impairment (delayed).

 

/CASE REPORTS/ ... /The deaths of / two individuals, one in Tacoma, WA, and the second in San Diego, CA, ... were attributed to ingestion of 2,4-dinitrophenol (2,4-DNP) ... By uncoupling mitochondrial oxidative phosphorylation, /2,4-DNP/ causes a marked increase in fat metabolism that has led to its use to aid weight loss. Both cases reported here involved its use for this purpose. Features common to both cases included markedly elevated body temperature, rapid pulse and respiration, yellow coloring of the viscera at autopsy, history of use of weight loss or body building supplements, and presence of a yellow powder at the decedent's residence. Because of its acidic nature, the drug is not detected in the basic drug fraction of most analytical protocols, but it is recovered in the acid/neutral fraction of biological extracts and can be measured by high-performance liquid chromatography or gas chromatography-mass spectrometry. The concentration of 2,4-DNP in the admission blood samples of the two deaths reported here were 36.1 and 28 mg/L, respectively. Death in both cases was attributed to 2,4-DNP toxicity. Review of information available on the internet suggests that, although banned, 2,4-DNP is still illicitly promoted for weight loss.

 

/CASE REPORTS/ Fatal cases of 2,4-DNP poisoning were reported among workmen in the munitions industry in France /during WW I/. These men were exposed to airborne vapor and dust of 2,4-DNP and had direct dermal contact with the chemical in solid form. There was poor quantitation in this study since neither duration nor level of exposure was reported. Fatal cases were noted especially among alcoholics or workers with renal or hepatic disease. The deaths were preceded by sudden onset of extreme fatigue, elevation of the body temperature to >/= 40 deg C, and other clinical signs of 2,4-DNP poisoning, such as profuse sweating, thirst, and labored respiration. No characteristic lesions were found at autopsy. Incidence data were not available. Following the institution of better ventilation, use of masks, and other industrial hygiene measures to minimize exposure, the numbers of deaths per 10,000 tons 2,4-DNP manufactured per year decreased approx 14-fold.

 

/CASE REPORTS/ ... Two workers exposed to mists and dust of 2,4-DNP in a US chemical plant for a few months developed signs of toxicity (fever, profuse sweating, restlessness); following treatment and rest, then a return to the job, both collapsed, and died. The warmer weather during the second period of exposure (duration not specified) was thought to be a contributing factor because of the greater skin exposure and potential for increased dermal absorption, and may have exacerbated the effects. Workroom air levels, determined after the deaths occurred, were «normally» at least 40 mg/cu m, but this value may underestimate breathing zone levels. In addition, significant dermal exposure and even oral absorption may have contributed to the total dose.

 

/CASE REPORTS/ ... Cases of death from agranulocytosis ... have been attributed to 2,4-DNP. These cases occurred during the usual dosing regimens for weight loss, employing increasing doses in one case from 2.9 to 4.3 mg/kg/day of 2,4-DNP for 6 weeks; a dose of 1.03 mg/kg/day 2,4-DNP for 46 days in another case; and in another, from 0.62 to 3.8 mg/kg/day 2,4-DNP as sodium 2,4-DNP for 41 days. In all cases, the patients were under medical supervision. Several clinical studies regarding the effects of 2,4-DNP or its sodium salt in obese and non-obese humans taking the drug for an intermediate duration at doses of 3.5-5.27 mg/kg/day 2,4-DNP have reported no deaths from this treatment. A woman who took 3-5 tablets a day of 2,4-DNP for several months, discontinued its use for 3 months, and then resumed taking 5 tablets a day for 1 week, became ill only after resumption of dosing and subsequently died.

 

Estimates of incidence of cataracts among people taking dinitrophenol for reducing /weight/ varied from 0.1% to 1%. Onset of cataract occurred several months after drug had been used. Cataracts were of uniform sort occurring in both eyes, appearing first in anterior cortex as fine gray cloudy opacities associated with a spotty lusterless appearance of the anterior lens capsule. In posterior cortex, golden granular opacities appeared, with polychromatic specular reflections. With rapid progress of the cataract, the lenses became swollen and embryonic suture lines were separated by dark clefts. Soon the whole lens became opaque with mature cataract. /SRP: No longer used as a medicine in the USA./

 

/FORMER/ TYPICAL TREATMENT REGIMEN FOR WT CONTROL CONSISTED OF 1 CAPSULE CONTAINING 75 MG OF 2,4-DINITROPHENOL OR 100 MG OF THE SODIUM SALT TAKEN 3 TIMES DAILY AFTER MEALS (2-5 MG/KG/DAY). ... NINE DEATHS /REPORTED AS/ RESULTING FROM USE OF DINITROPHENOL AS WT REDUCING AGENT. /SRP: NOT IN CURRENT USE IN THE USA./

 

... 27 REPORTED CASES OF FATAL OCCUPATIONAL DINITROPHENOL POISONING IN UNITED STATES BETWEEN 1914 & 1916. ... TWO CASES OF DINITROPHENOL POISONING DURING MFR OF PICRIC ACID, WHEN 2,4-DINITROPHENOL WAS PRODUCED AS INTERMEDIATE.

 

Populations at Special Risk:

Some human subpopulations that are predisposed to a syndrome known as malignant hyperthermia may be more likely to develop fatal hyperthermia following exposure to 2,4-DNP. Malignant hyperthermia is an inherited disease of skeletal muscle characterized by a drug-induced hyperpyrexia. Humans with this inherited disease are predisposed to acute hyperthermic reactions triggered by stress or drugs (such as inhalation anesthetic agents, skeletal muscle relaxants, and amide local anesthetics)

 

http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+51-28-5

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