Researchers noticed its effect on raising the basal metabolic rate in accidental exposure and developed it as one of the first weight loss drugs in the early twentieth century.
[6] DNP forms explosive salts with strong bases as well as ammonia, and emits toxic fumes of nitrogen dioxide when heated to decomposition.
[19] DNP raises energy expenditure by 30 to 40 percent and causes a weight loss of 0.7–0.9 kilograms (1.5–2.0 lb) per week.
[21] Although DNP is no longer in clinical use as a weight loss drug due to its dangerous side effects, its mechanism of action remains under investigation as a potential approach for treating obesity and non-alcoholic fatty liver disease.
[25] Despite health warnings from regulators, DNP is readily available online[25] sometimes under other names such as Dinosan, Dnoc, Solfo Black, Nitrophen, Aldifen, and Chemox.
[17] In living cells, DNP acts as a protonophore, an agent that can shuttle protons (hydrogen cations) across biological membranes.
[34] DNP has a low therapeutic index, meaning that the dosage at which toxicity occurs is not much larger than that required to produce a desired effect.
[1] In animal studies, DNP acted as a teratogen, mutagen, and carcinogen and caused developmental and reproductive harm.
[17] An unusually yellow coloring of the skin, mucous membranes, sclera, urine, stomach contents, and internal organs is an indication of DNP exposure, but does not occur in every case.
[17] Overdose is extremely dangerous;[17] cases reported to poison control centers had a 11.9 percent fatality rate between 2010 and 2020.
[27] Although the lowest published fatal ingested dose is 4.3 mg/kg,[17][16] a typical overdose death occurs at a higher level of exposure, around 20-50 mg/kg.
DNP can cause T wave and ST segment abnormalities; heart muscle, kidney, and liver damage have been found on autopsy.
[17] Treatment for overdose is supportive, and often involves aggressive cooling using methods such as ice baths and intravenous fluids.
[35][17] Grundlingh et al. recommend administering activated charcoal if the patient presents within an hour of ingestion and using intravenous vasopressors or inotropes to control blood pressure if necessary.
[17] During World War I, munitions workers in France fell ill and some died from DNP exposure.
[1][38] Although he was aware of DNP's narrow therapeutic index, Tainter tried the drugs on obese patients and published successful results in 1933; average weight loss was 20 pounds (9.1 kg) and most recipients did not report adverse effects.
In 1934, Tainter estimated that at least 100,000 people had been treated with DNP in the United States during its first year on the market and there had been three reported fatalities connected to the drug.
DNP was deemed so toxic as to be banned for human consumption and in 1940 the FDA reported that there was no evidence of continued sale for this purpose.
[35] William F. Loomis and Fritz Albert Lipmann discovered DNP's mechanism of action and reported it in a 1948 publication.
In February 2017, DNP was reclassified as Schedule 10, "Substances of such a danger to health as to warrant prohibition of sale, supply and use".
[25] However, Sousa et al. argue that publicity campaigns in the United Kingdom in the early and mid-2010s reduced DNP usage.
[25] In 1941, the Eastman Kodak Company, a bulk distributor of DNP, was investigated after some of its product was found in illegal diet pills.