The chemical is a yellow crystalline powder that has a sweet, musty odour and is soluble in water.
It has historically been used as a component of explosives, and as a pesticide and food/clothing dye. It was reported in 1933 that usage of Dinitrophenol led to weight loss and it became popularized as an obesity treatment. It was effective in doing so, and led to a reported loss of 1.5kg per week. Over time, as more side effects manifested, it was deemed ill-fit for human consumption by the Food, Drug, and Cosmetic act of 1938.
It had a second resurgence in 1981 when a Physician marketed a product with Dinitrophenol in it (under the name Mitcal) through his private clinic which resulted in one reported death and a large number of reported side effects.
Since then it has remained available online through some websites, and toxicity cases arise every now and then from misuse of Dinitrophenol despite the FDA advising for its cessation.
Under normal metabolic conditions, 1 ATP molecules are created during one passing of Acetyl-CoA through the Kreb's Cycle (The TCA) and many energy intermediates are produced in addition to the lone ATP; these energy intermediates go through oxidative phosphorylation in the mitochondria to produce an additional 11 ATP. Dinitrophenol is an oxidative phosphorylation inhibitor, and prevents these 11 additional ATP from being formed by interfering with inorganic phosphorus uptake into the mitochondria (needed for ATP synthesis) and also acting as an ionophore, which drastically hinders the electrochemical gradient in the mitochondria required for ATP synthesis. It is the shift in the electrochemical gradient that causes the fat loss, as the excess ions that carried potential energy (calories) are dissipated as heat.
Dinitrophenol, by mitochondrial uncoupling, is able to protect mitochondria from Reactive-Oxygen Species (ROS) mediated cell death by allowing energy to be lost through uncoupling rather than contained in the mitochondria to exert damage. This was demonstrated in an animal model injected with a toxic dose of quinolinic acid.
The usage of glucose as fuel markedly increases with low doses of Dinitrophenol This increase in glycolysis leads to an increase in pyruvic acid and lactic acid (via anaerobic metabolism) due to the lack of ATP from the oxidative phosphorylation inhibition.
Due to the lack of phosphate usage for ATP production in the mitochondria, phosphate also can accumulate in cells.
In rats given 3-30mg/kg DNP for a period of 46 days (14 days prior to mating) noted that while no significant toxicity occurred to either parent and no differences in implantation rates, that the number of live births and average weight of pup birth were both reduced at 30mg/kg (thought to be indicative of developmental/reproductive toxicity) but failed to find teratogenicity when measuring birth defect rates.
Dinitrophenol has been causatively linked to death in numerous occasions, with the causes of death usually related to hyperthermia and tachycardia (irregular heartbeat) paired with diaphoresis (excessive and unpredictable sweating and tachypnoea (rapid and irregular breathing).
The lethal dosages are sometimes unknown (ie. not reported in the case study or not otherwise known), but seem to range around 2,500mg or a bit higher for acute death (leading to death in under 24h) or taken over the course of 1-6 days; a death was once reported in a 46 year old woman at 300mg, which is within the recommended dosage range.
Numerous case studies linking DNP to death, with a fair bit of them placing DNP in a position of 'causative beyond a reasonable doubt'. Although most are associated with overconsumption of DNP (relative to the recommended intake range), at least one case study noted death associated with 300mg