reptides / 2,4-dinitrophenol (DNP)

2,4-dinitrophenol (DNP)

DNP can reduce weight, but it can also produce uncontrollable heat, organ failure, and fatal cardiovascular collapse through the same mechanism. It is not FDA approved, there is no established antidote, and suspected ingestion is an emergency.

Small-molecule mitochondrial protonophore

  • Industrial chemical, not a peptide
  • Formula C6H4N2O5; CAS 51-28-5
  • Historical efficacy evidence predates modern randomized drug trials
What is DNP? What after exposure? Does it cause weight loss? Why does it make heat? Is any exposure safe? What do 46 h and 26 h mean? Is it approved or legal?

What is 2,4-dinitrophenol, and is it a peptide or medicine?

DNP is a small industrial chemical that shuttles protons across mitochondrial membranes. It is not a peptide, hormone, supplement ingredient, or FDA-approved drug.

The relevant compound is the 2,4 isomer with CAS 51-28-5, not every dinitrophenol or dinitrocresol. Putting the industrial chemical into a capsule does not make it an approved medicine.

ATSDR profile · human toxicity and mechanism

Official toxicological profile

Agency for Toxic Substances and Disease Registry, 2021

The profile documents fatal oral, inhalational, and dermal exposures; rapid progression from fever, sweating, tachypnea, and tachycardia to hyperthermia and cardiac collapse; and weight loss through oxidative-phosphorylation uncoupling. It explains that electron-transport energy is released as heat instead of being stored as ATP.

  • Industrial and occupational exposure routes can also poison
  • Ambient heat can worsen uncoupler toxicity
  • Historical human reports do not establish a safe intentional exposure
Participants / model
Human case reports and historical clinical reports, plus animal and mechanistic evidence
Treatment
Oral, inhalational, dermal, and experimental exposures reviewed
Follow-up
Evidence through the final August 2021 profile
Study design
Government toxicological evidence synthesis
Funding
U.S. Department of Health and Human Services

A synthesis rather than a controlled treatment trial; many human data are old case reports with uncertain exposure estimates.

Read the original source
FDA enforcement · 110 DNP websites in 2016

FDA enforcement announcement

U.S. Food and Drug Administration, June 9, 2016

FDA said DNP had never been approved as a drug and identified 110 websites selling it as a weight-loss product during the 2016 enforcement action.

  • Never FDA approved as a drug
  • The 110 figure is specific to the 2016 sweep
Participants / model
U.S.-directed online drug sales
Treatment
Not applicable
Follow-up
Operation conducted May 31 through June 7, 2016
Study design
Regulatory and law-enforcement announcement
Funding
U.S. Food and Drug Administration

The 110-site count applies only to the 2016 enforcement sweep.

Read the original source

What should someone do after taking DNP or developing overheating symptoms?

Treat suspected ingestion as an emergency. In the United States, call Poison Help at 1-800-222-1222 immediately and do not wait for symptoms. Call 911 for trouble breathing, seizure, collapse, unresponsiveness, or rapidly rising temperature.

Do not try to manage this at home

Go to an emergency department after DNP ingestion. Do not give activated charcoal or improvise a cooling or drug regimen at home. Bring the container or product information if that can be done safely. Outside the United States, contact the local poison center or emergency service now.

Early symptoms can include profuse sweating, flushed skin, thirst, nausea, vomiting, agitation, rapid breathing, and a fast or irregular heartbeat. Severe poisoning can accelerate into extreme hyperthermia, muscle rigidity, seizures, acidosis, organ injury, cardiovascular collapse, and death. A person can look relatively stable before deteriorating.

How often was severe or fatal toxicity reported to poison centers?

A 2021 analysis identified 204 systemic DNP exposures reported to U.S. and U.K. poison centers from 2007 through 2018. The case-fatality proportion among those reports was 11.6% in the United States and 16.9% in the United Kingdom. These are selected reports, not the risk per user or the population incidence. Acidosis, tachycardia, agitation or confusion, and hyperpyrexia independently predicted death in the dataset.

Poison-center series · 204 systemic exposures

Retrospective poison-center study

Potts et al., Clinical Toxicology, 2021

Among 204 systemic exposures reported from 2007 through 2018, the reported case-fatality proportions were 11.6% in the United States and 16.9% in the United Kingdom. Acidosis, tachycardia, agitation or confusion, and hyperpyrexia independently predicted death.

  • 86 U.S. and 118 U.K. reports
  • Reported cases were predominantly male and younger than 40
Participants / model
204 systemic DNP exposures reported to U.S. and U.K. poison centers
Treatment
Not an intervention study
Follow-up
Reports from 2007 through 2018
Study design
Retrospective analysis of poison-center records

Poison-center cases are selected and undercount total exposures; the case-fatality proportion is not a per-user risk estimate.

Read the original source
What did the Chinese occupational poisoning cohort show?

A full English-language report from Zhejiang University described 16 hospital patients from a 2009 non-oral workplace and household exposure incident in China. All 16 reported heavy sweating first; 14 had shortness of breath with activity. Two severely affected patients developed temperatures of 40.7 and 39.8 °C with convulsions, rigidity, and impaired consciousness, and both died within 12 hours after symptoms began. The exposure levels were not measured, so this cohort cannot define a dose-response curve.

Zhejiang cohort · 16 non-oral poisonings

Retrospective Chinese clinical cohort

Lu, Jiang, and Huang, Journal of Zhejiang University Science B, 2011

The full English-language report described 16 patients from a Chinese occupational and secondary-contact incident. All reported heavy sweating first, 14 had exertional dyspnea, and two with severe hyperthermia, convulsions, rigidity, and altered consciousness died within 12 hours after symptom onset. Fourteen survivors received multiple supportive treatments and hemoperfusion.

  • 12 male and 4 female patients; mean age 36.6 years
  • Onset ranged from 2 to 30 hours after exposure
  • Fourteen survivors were discharged after four to six weeks
Participants / model
16 Chinese patients after non-oral workplace or household contact exposure
Treatment
Supportive care, cooling, hemoperfusion, glucocorticoids, and other cointerventions
Follow-up
Hospitalization with three-month follow-up reported for survivors
Study design
Retrospective uncontrolled case series

Exposure was not quantified, treatment was not randomized, and the two deaths occurred before the survivor treatment analysis. Treatment efficacy cannot be isolated.

Read the original source
Poison Help · immediate U.S. action

Official poison-control guidance

Health Resources and Services Administration.

U.S. Poison Help says to call 1-800-222-1222 right away after a possible poisoning and not wait for symptoms. It says to call 911 when the person is not breathing and not to give activated charcoal without poison-control direction.

  • Call Poison Help immediately
  • Do not wait for symptoms
  • Do not give activated charcoal on your own
Participants / model
People with suspected poisoning in the United States
Treatment
Immediate poison-center triage
Study design
Federal public-health guidance
Funding
U.S. Department of Health and Human Services

General poisoning guidance; DNP-specific emergency conclusions are also supported by the cited toxicology sources.

Read the original source
Poison Control · DNP emergency guidance

Clinical toxicology guidance

National Capital Poison Center, medically reviewed 2026

The toxicologist-reviewed page directs anyone who swallows DNP to an emergency room immediately. It describes rapid heart and breathing rates, seizures, coma, dangerous hyperthermia, organ failure, and the absence of an antidote.

  • Emergency assessment after ingestion
  • No antidote
Participants / model
People with DNP ingestion or suspected poisoning
Treatment
Emergency evaluation and supportive toxicology care
Study design
Poison-center clinical guidance

The source provides emergency guidance rather than comparative treatment outcomes.

Read the original source
ATSDR profile · human toxicity and mechanism

Official toxicological profile

Agency for Toxic Substances and Disease Registry, 2021

The profile documents fatal oral, inhalational, and dermal exposures; rapid progression from fever, sweating, tachypnea, and tachycardia to hyperthermia and cardiac collapse; and weight loss through oxidative-phosphorylation uncoupling. It explains that electron-transport energy is released as heat instead of being stored as ATP.

  • Industrial and occupational exposure routes can also poison
  • Ambient heat can worsen uncoupler toxicity
  • Historical human reports do not establish a safe intentional exposure
Participants / model
Human case reports and historical clinical reports, plus animal and mechanistic evidence
Treatment
Oral, inhalational, dermal, and experimental exposures reviewed
Follow-up
Evidence through the final August 2021 profile
Study design
Government toxicological evidence synthesis
Funding
U.S. Department of Health and Human Services

A synthesis rather than a controlled treatment trial; many human data are old case reports with uncertain exposure estimates.

Read the original source

Does DNP cause weight loss, and how strong is that evidence?

Yes, DNP can cause weight loss. The familiar result comes from uncontrolled 1930s clinical experience, not a modern randomized efficacy and safety trial.

In their 1934 primary-era survey, Tainter, Cutting, and Stockton said an earlier obese-patient report had produced losses of 2 to 3 pounds per week and that three smaller clinical groups had reported similar results. The survey pooled heterogeneous physician experience, lacked random assignment and a concurrent control group, and predates current standards for adverse-event collection, product control, and informed consent.

The historical record shows that DNP can reduce weight, but it provides no reliable estimate for a current online product. It also cannot predict who will develop catastrophic hyperthermia, cataracts, blood-cell toxicity, neuropathy, or delayed organ injury.

1934 survey · uncontrolled weight loss

Primary-era uncontrolled clinical survey

Tainter, Cutting, and Stockton, American Journal of Public Health, 1934

The authors said their preliminary report in obese patients produced weight losses of 2 to 3 pounds per week and that three smaller groups had reported similar experience. The article surveys uncontrolled practice before modern randomized trials and modern drug-safety requirements.

  • Biological weight loss was observed
  • No randomized comparator
  • Historical product and monitoring conditions do not define current use
Participants / model
People treated for obesity or nutritional disorders in 1930s clinical practice
Treatment
Varied oral dinitrophenol use reported across historical series
Follow-up
Varied across reports
Study design
Narrative critical survey of uncontrolled clinical experience
Funding
Rockefeller Fluid Research Fund and American Medical Association research grant, as reported

The 2 to 3 pound figure is a historical report, not a placebo-adjusted estimate or a safe expected result.

Read the original source
ATSDR profile · human toxicity and mechanism

Official toxicological profile

Agency for Toxic Substances and Disease Registry, 2021

The profile documents fatal oral, inhalational, and dermal exposures; rapid progression from fever, sweating, tachypnea, and tachycardia to hyperthermia and cardiac collapse; and weight loss through oxidative-phosphorylation uncoupling. It explains that electron-transport energy is released as heat instead of being stored as ATP.

  • Industrial and occupational exposure routes can also poison
  • Ambient heat can worsen uncoupler toxicity
  • Historical human reports do not establish a safe intentional exposure
Participants / model
Human case reports and historical clinical reports, plus animal and mechanistic evidence
Treatment
Oral, inhalational, dermal, and experimental exposures reviewed
Follow-up
Evidence through the final August 2021 profile
Study design
Government toxicological evidence synthesis
Funding
U.S. Department of Health and Human Services

A synthesis rather than a controlled treatment trial; many human data are old case reports with uncertain exposure estimates.

Read the original source

Why can the same mechanism reduce weight and cause lethal hyperthermia?

DNP dissipates the proton gradient that mitochondria normally use to make ATP. Fuel oxidation continues, but less energy becomes usable ATP and more escapes as heat.

  • DNP acts as a lipophilic weak acid and carries protons across the inner mitochondrial membrane.
  • The electrochemical gradient becomes less available to ATP synthase, so cells must oxidize more fuel for less captured energy.
  • The uncaptured energy appears as heat. If heat production outruns heat loss, temperature and metabolic demand can rise into a self-amplifying crisis.
  • Tachycardia, rapid breathing, sweating, and increased oxygen demand are compensations, not proof that the exposure is controlled.

The mechanism does not contain a clean switch between fat loss and poisoning. Ambient heat, exertion, repeated exposure, product content, and individual physiology can change the margin, while measured blood concentration does not supply a home-use safety rule.

ATSDR profile · human toxicity and mechanism

Official toxicological profile

Agency for Toxic Substances and Disease Registry, 2021

The profile documents fatal oral, inhalational, and dermal exposures; rapid progression from fever, sweating, tachypnea, and tachycardia to hyperthermia and cardiac collapse; and weight loss through oxidative-phosphorylation uncoupling. It explains that electron-transport energy is released as heat instead of being stored as ATP.

  • Industrial and occupational exposure routes can also poison
  • Ambient heat can worsen uncoupler toxicity
  • Historical human reports do not establish a safe intentional exposure
Participants / model
Human case reports and historical clinical reports, plus animal and mechanistic evidence
Treatment
Oral, inhalational, dermal, and experimental exposures reviewed
Follow-up
Evidence through the final August 2021 profile
Study design
Government toxicological evidence synthesis
Funding
U.S. Department of Health and Human Services

A synthesis rather than a controlled treatment trial; many human data are old case reports with uncertain exposure estimates.

Read the original source
Medical-toxicology review · deaths and no antidote

Systematic clinical toxicology review

Grundlingh et al., Journal of Medical Toxicology, 2011

The review identified 62 published deaths up to its 2011 search and described hyperthermia, tachycardia, diaphoresis, tachypnea, cardiovascular collapse, and death. It found no specific antidote and said management evidence rested on case reports and expert opinion.

  • The 62-death count is a dated literature minimum
  • No specific antidote
  • Specific-treatment evidence was low quality
Participants / model
Published human poisonings and deaths
Treatment
Supportive and experimental management described across case reports
Follow-up
Literature searched through 2011
Study design
Structured literature review

Publication and reporting bias prevent estimating the total number of exposures or risk per user.

Read the original source

Is there an established safe therapeutic exposure or antidote?

No supported therapeutic threshold or established antidote makes intentional DNP use safe. Treatment is urgent supportive toxicology care, and evidence for specific interventions comes mainly from case reports and uncontrolled cohorts.

A 2011 medical-toxicology review found at least 62 published deaths up to that review date and described no specific antidote. The count is a dated literature minimum, not the current worldwide total. Reports of survival after cooling, ventilation, fluids, sedation, or extracorporeal treatment do not prove that any one intervention reverses uncoupling.

Did hemoperfusion work in the Chinese reports?

The 2011 Zhejiang report retrospectively described 14 survivors who received supportive care and hemoperfusion after the two most severe patients died. A later full report measured plasma DNP in those 14 survivors and compared five people assigned routine hemoperfusion with nine assigned more intensive treatment. The groups were selected by clinical severity rather than randomized, all received multiple other treatments, and only survivors entered the concentration analysis. Those conditions prevent attributing survival to hemoperfusion or glucocorticoids.

Zhejiang cohort · 16 non-oral poisonings

Retrospective Chinese clinical cohort

Lu, Jiang, and Huang, Journal of Zhejiang University Science B, 2011

The full English-language report described 16 patients from a Chinese occupational and secondary-contact incident. All reported heavy sweating first, 14 had exertional dyspnea, and two with severe hyperthermia, convulsions, rigidity, and altered consciousness died within 12 hours after symptom onset. Fourteen survivors received multiple supportive treatments and hemoperfusion.

  • 12 male and 4 female patients; mean age 36.6 years
  • Onset ranged from 2 to 30 hours after exposure
  • Fourteen survivors were discharged after four to six weeks
Participants / model
16 Chinese patients after non-oral workplace or household contact exposure
Treatment
Supportive care, cooling, hemoperfusion, glucocorticoids, and other cointerventions
Follow-up
Hospitalization with three-month follow-up reported for survivors
Study design
Retrospective uncontrolled case series

Exposure was not quantified, treatment was not randomized, and the two deaths occurred before the survivor treatment analysis. Treatment efficacy cannot be isolated.

Read the original source
Zhejiang monitoring study · 14 survivors

Prospective measurements in an uncontrolled Chinese cohort

Zhao et al., Journal of Zhejiang University Science B, 2015

The full English-language report measured plasma DNP in 14 survivors from an occupational incident. Initial concentrations ranged from 0.25 to 41.88 µg/mL and correlated with temperature. DNP cleared slowly and remained detectable for as long as 25 days in most patients; intensive and routine hemoperfusion groups were not randomized.

  • Five routine and nine intensive hemoperfusion patients
  • Only survivors were included
  • Persistent poisoning data do not define routine oral pharmacokinetics
Participants / model
14 survivors of a Chinese occupational DNP poisoning incident
Treatment
Routine or intensive resin hemoperfusion plus multiple supportive treatments
Follow-up
Serial plasma monitoring for up to 25 days
Study design
Nonrandomized observational comparison with serial concentration measurements
Funding
National Natural Science Foundation of China and Zhejiang Province programs, as reported

Treatment allocation reflected clinical severity, two fatal cases were absent from the analysis, and the exposure was non-oral. It cannot prove treatment efficacy or a routine-use half-life.

Read the original source
Does an ATSDR minimal risk level define a safe weight-loss amount?

ATSDR's intermediate-duration oral minimal risk level is an environmental-health screening value derived from a mouse study with uncertainty factors. ATSDR found no suitable study below human lethal levels from which to derive an acute oral value. This screening level is not a drug dose, therapeutic window, or safety guarantee.

ATSDR worksheet · environmental screening only

Official environmental risk assessment

Agency for Toxic Substances and Disease Registry, 2021

ATSDR derived an intermediate-duration oral screening value from a mouse study with a 1,000-fold composite uncertainty factor. It did not derive an acute oral value because no suitable animal study was below levels associated with human lethality.

  • Environmental screening value
  • Mouse-derived with uncertainty factors
  • Not a therapeutic dose or safety guarantee
Participants / model
Environmental-health risk assessment using animal and human evidence
Treatment
Not a treatment study
Follow-up
Intermediate-duration exposure assessment
Study design
Government risk-assessment worksheet
Funding
U.S. Department of Health and Human Services

Minimal risk levels guide environmental screening; they are not approved doses and cannot be used to construct a weight-loss regimen.

Read the original source
Can the rat toxicology studies set a human safe range?

One rat reproductive-screening study found reduced parental weight gain, increased liver weight, and poorer live-pup outcomes at its highest tested exposure. Another five-day male-rat study found reduced body weight and a slight increase in tailless sperm at its highest DNP exposure. These gavage and laboratory oral exposures cannot set a safe human regimen.

Rat study · systemic and reproductive toxicity

Animal reproductive toxicology study

M. Takahashi et al., Environmental Toxicology, 2009

Rats received daily gavage at 0, 3, 10, or 30 mg/kg. At the highest exposure, parental weight gain fell, liver weight rose, and live-pup counts, live-birth index, and early pup weights were lower. The study's rat NOAEL cannot be treated as a human safe dose.

  • Males were exposed for 46 days
  • Females were exposed for 40 to 47 days
  • No increased malformation rate was reported under the study conditions
Participants / model
Male and female rats and their offspring
Treatment
Daily gavage at 0, 3, 10, or 30 mg/kg
Follow-up
46 days for males and 40 to 47 days for females
Study design
Controlled animal reproductive and developmental screening study
Funding
Japanese government research institute study

Animal toxicology study; its dose levels and NOAEL do not establish intentional human safety.

Read the original source
Rat study · five-day male reproductive endpoints

Comparative animal toxicology study

K. L. Takahashi et al., Reproductive Toxicology, 2004

Male Sprague-Dawley rats received oral DNP at 7.5, 15, or 30 mg/kg for five days. The highest exposure reduced body weight during treatment and produced a slight increase in tailless sperm 14 days later; no DNP deaths occurred in this experiment.

  • Necropsy occurred 3 or 14 days after the last exposure
  • The study compared several dinitrophenolic chemicals
Participants / model
Sexually mature male Sprague-Dawley rats
Treatment
Oral DNP at 7.5, 15, or 30 mg/kg daily
Follow-up
Five consecutive days, with follow-up necropsy
Study design
Controlled comparative animal toxicology study

Animal study near toxic exposure levels; it does not establish human fertility effects or a human safety threshold.

Read the original source
Medical-toxicology review · deaths and no antidote

Systematic clinical toxicology review

Grundlingh et al., Journal of Medical Toxicology, 2011

The review identified 62 published deaths up to its 2011 search and described hyperthermia, tachycardia, diaphoresis, tachypnea, cardiovascular collapse, and death. It found no specific antidote and said management evidence rested on case reports and expert opinion.

  • The 62-death count is a dated literature minimum
  • No specific antidote
  • Specific-treatment evidence was low quality
Participants / model
Published human poisonings and deaths
Treatment
Supportive and experimental management described across case reports
Follow-up
Literature searched through 2011
Study design
Structured literature review

Publication and reporting bias prevent estimating the total number of exposures or risk per user.

Read the original source

Do the quoted 46-hour and 26-hour half-lives describe DNP in people?

The 46-hour and 26-hour values are terminal plasma half-life estimates for two DNP metabolites in mice, not parent DNP or human pharmacokinetics.

The 1985 experiment gave one oral exposure to 11 groups of six ICR mice and sampled different groups through 96 hours. It estimated 46.2 hours for 2-amino-4-nitrophenol and 25.7 hours for 4-amino-2-nitrophenol. The parent DNP estimate in the same mouse experiment was about 10.3 hours. None of those values supplies a human dosing interval.

The 2015 Zhejiang survivor cohort found slow, persistent plasma DNP after occupational poisoning, with DNP detectable for as long as 25 days in most patients during hospital monitoring and hemoperfusion. That is a poisoning cohort with non-oral exposure and treatment-dependent sampling, not a normal oral pharmacokinetic study or a stable human half-life estimate.

Mouse PK · metabolite half-lives

Animal pharmacokinetic study

Robert and Hagardorn, Journal of Chromatography, 1985

Eleven groups of six ICR mice received a single oral 22.5 mg/kg exposure and were sampled through 96 hours. Terminal plasma half-lives were estimated at 10.3 hours for parent DNP, 46.2 hours for 2-amino-4-nitrophenol, and 25.7 hours for 4-amino-2-nitrophenol.

  • 46.2 and 25.7 hours refer to metabolites
  • All estimates came from mice
  • The design used destructive sampling of different groups
Participants / model
66 ICR mice in 11 timepoint groups
Treatment
Single oral 22.5 mg/kg DNP exposure
Follow-up
Sampling from 0 through 96 hours
Study design
Animal pharmacokinetic study

These values are not human pharmacokinetics and cannot define a human dosing interval.

Read the original source
Zhejiang monitoring study · 14 survivors

Prospective measurements in an uncontrolled Chinese cohort

Zhao et al., Journal of Zhejiang University Science B, 2015

The full English-language report measured plasma DNP in 14 survivors from an occupational incident. Initial concentrations ranged from 0.25 to 41.88 µg/mL and correlated with temperature. DNP cleared slowly and remained detectable for as long as 25 days in most patients; intensive and routine hemoperfusion groups were not randomized.

  • Five routine and nine intensive hemoperfusion patients
  • Only survivors were included
  • Persistent poisoning data do not define routine oral pharmacokinetics
Participants / model
14 survivors of a Chinese occupational DNP poisoning incident
Treatment
Routine or intensive resin hemoperfusion plus multiple supportive treatments
Follow-up
Serial plasma monitoring for up to 25 days
Study design
Nonrandomized observational comparison with serial concentration measurements
Funding
National Natural Science Foundation of China and Zhejiang Province programs, as reported

Treatment allocation reflected clinical severity, two fatal cases were absent from the analysis, and the exposure was non-oral. It cannot prove treatment efficacy or a routine-use half-life.

Read the original source

Is DNP approved as a drug or lawful to sell for weight loss?

FDA has never approved DNP as a drug, and U.S. enforcement has treated sales for human weight loss as unlawful unapproved or misbranded drug distribution. Rules for possessing or handling the industrial chemical depend on the jurisdiction.

In 2016, FDA identified 110 websites selling DNP as a weight-loss product and stated that it had never been approved as a drug. A 2023 FDA-hosted Justice Department notice again stated that DNP had never been approved for human consumption and described a prison sentence for selling it as a misbranded drug. The number 110 belongs to that 2016 enforcement sweep; it is not a current market count.

In England, Wales, and Northern Ireland, DNP and sodium dinitrophenolate have been regulated poisons since October 1, 2023. Members of the public need an Explosives Precursors and Poisons licence to import, acquire, possess, or use them, and sale to the public without a valid licence is a criminal offence. The rule applies only to those named jurisdictions.

FDA enforcement · 110 DNP websites in 2016

FDA enforcement announcement

U.S. Food and Drug Administration, June 9, 2016

FDA said DNP had never been approved as a drug and identified 110 websites selling it as a weight-loss product during the 2016 enforcement action.

  • Never FDA approved as a drug
  • The 110 figure is specific to the 2016 sweep
Participants / model
U.S.-directed online drug sales
Treatment
Not applicable
Follow-up
Operation conducted May 31 through June 7, 2016
Study design
Regulatory and law-enforcement announcement
Funding
U.S. Food and Drug Administration

The 110-site count applies only to the 2016 enforcement sweep.

Read the original source
FDA/DOJ notice · U.S. misbranding case

Federal criminal-enforcement notice

U.S. Department of Justice notice hosted by FDA, June 1, 2023

The notice states that FDA has never approved DNP for human consumption and reports a 33-month sentence after conviction for selling it as a misbranded drug online.

  • U.S. criminal case
  • Not an approval or lawful medical product
Participants / model
U.S. enforcement against online DNP sales
Treatment
Not applicable
Follow-up
Conduct described through sentencing in 2023
Study design
Official enforcement notice
Funding
U.S. Department of Justice and FDA

The notice describes one U.S. criminal case and its federal charges.

Read the original source
UK guidance · regulated poison since 2023

Official government safety and legal guidance

UK Government.

The guidance says DNP and sodium dinitrophenolate became regulated poisons on October 1, 2023. In England, Wales, and Northern Ireland, a member of the public needs an EPP licence to import, acquire, possess, or use them, and sale to the public without a valid licence is a criminal offence.

  • Applies to England, Wales, and Northern Ireland
  • Immediate medical contact advised after taking DNP
Participants / model
Members of the public in the named UK jurisdictions
Treatment
Not applicable
Record date
Rule effective October 1, 2023
Study design
Government safety and regulatory guidance
Funding
UK Government

Jurisdiction-specific; Scotland and other countries require separate checks.

Read the original source

Studies and sources

ATSDR profile · human toxicity and mechanism

Official toxicological profile

Agency for Toxic Substances and Disease Registry, 2021

The profile documents fatal oral, inhalational, and dermal exposures; rapid progression from fever, sweating, tachypnea, and tachycardia to hyperthermia and cardiac collapse; and weight loss through oxidative-phosphorylation uncoupling. It explains that electron-transport energy is released as heat instead of being stored as ATP.

  • Industrial and occupational exposure routes can also poison
  • Ambient heat can worsen uncoupler toxicity
  • Historical human reports do not establish a safe intentional exposure
Participants / model
Human case reports and historical clinical reports, plus animal and mechanistic evidence
Treatment
Oral, inhalational, dermal, and experimental exposures reviewed
Follow-up
Evidence through the final August 2021 profile
Study design
Government toxicological evidence synthesis
Funding
U.S. Department of Health and Human Services

A synthesis rather than a controlled treatment trial; many human data are old case reports with uncertain exposure estimates.

Read the original source
Poison Help · immediate U.S. action

Official poison-control guidance

Health Resources and Services Administration.

U.S. Poison Help says to call 1-800-222-1222 right away after a possible poisoning and not wait for symptoms. It says to call 911 when the person is not breathing and not to give activated charcoal without poison-control direction.

  • Call Poison Help immediately
  • Do not wait for symptoms
  • Do not give activated charcoal on your own
Participants / model
People with suspected poisoning in the United States
Treatment
Immediate poison-center triage
Study design
Federal public-health guidance
Funding
U.S. Department of Health and Human Services

General poisoning guidance; DNP-specific emergency conclusions are also supported by the cited toxicology sources.

Read the original source
Poison Control · DNP emergency guidance

Clinical toxicology guidance

National Capital Poison Center, medically reviewed 2026

The toxicologist-reviewed page directs anyone who swallows DNP to an emergency room immediately. It describes rapid heart and breathing rates, seizures, coma, dangerous hyperthermia, organ failure, and the absence of an antidote.

  • Emergency assessment after ingestion
  • No antidote
Participants / model
People with DNP ingestion or suspected poisoning
Treatment
Emergency evaluation and supportive toxicology care
Study design
Poison-center clinical guidance

The source provides emergency guidance rather than comparative treatment outcomes.

Read the original source
Poison-center series · 204 systemic exposures

Retrospective poison-center study

Potts et al., Clinical Toxicology, 2021

Among 204 systemic exposures reported from 2007 through 2018, the reported case-fatality proportions were 11.6% in the United States and 16.9% in the United Kingdom. Acidosis, tachycardia, agitation or confusion, and hyperpyrexia independently predicted death.

  • 86 U.S. and 118 U.K. reports
  • Reported cases were predominantly male and younger than 40
Participants / model
204 systemic DNP exposures reported to U.S. and U.K. poison centers
Treatment
Not an intervention study
Follow-up
Reports from 2007 through 2018
Study design
Retrospective analysis of poison-center records

Poison-center cases are selected and undercount total exposures; the case-fatality proportion is not a per-user risk estimate.

Read the original source
Zhejiang cohort · 16 non-oral poisonings

Retrospective Chinese clinical cohort

Lu, Jiang, and Huang, Journal of Zhejiang University Science B, 2011

The full English-language report described 16 patients from a Chinese occupational and secondary-contact incident. All reported heavy sweating first, 14 had exertional dyspnea, and two with severe hyperthermia, convulsions, rigidity, and altered consciousness died within 12 hours after symptom onset. Fourteen survivors received multiple supportive treatments and hemoperfusion.

  • 12 male and 4 female patients; mean age 36.6 years
  • Onset ranged from 2 to 30 hours after exposure
  • Fourteen survivors were discharged after four to six weeks
Participants / model
16 Chinese patients after non-oral workplace or household contact exposure
Treatment
Supportive care, cooling, hemoperfusion, glucocorticoids, and other cointerventions
Follow-up
Hospitalization with three-month follow-up reported for survivors
Study design
Retrospective uncontrolled case series

Exposure was not quantified, treatment was not randomized, and the two deaths occurred before the survivor treatment analysis. Treatment efficacy cannot be isolated.

Read the original source
1934 survey · uncontrolled weight loss

Primary-era uncontrolled clinical survey

Tainter, Cutting, and Stockton, American Journal of Public Health, 1934

The authors said their preliminary report in obese patients produced weight losses of 2 to 3 pounds per week and that three smaller groups had reported similar experience. The article surveys uncontrolled practice before modern randomized trials and modern drug-safety requirements.

  • Biological weight loss was observed
  • No randomized comparator
  • Historical product and monitoring conditions do not define current use
Participants / model
People treated for obesity or nutritional disorders in 1930s clinical practice
Treatment
Varied oral dinitrophenol use reported across historical series
Follow-up
Varied across reports
Study design
Narrative critical survey of uncontrolled clinical experience
Funding
Rockefeller Fluid Research Fund and American Medical Association research grant, as reported

The 2 to 3 pound figure is a historical report, not a placebo-adjusted estimate or a safe expected result.

Read the original source
Medical-toxicology review · deaths and no antidote

Systematic clinical toxicology review

Grundlingh et al., Journal of Medical Toxicology, 2011

The review identified 62 published deaths up to its 2011 search and described hyperthermia, tachycardia, diaphoresis, tachypnea, cardiovascular collapse, and death. It found no specific antidote and said management evidence rested on case reports and expert opinion.

  • The 62-death count is a dated literature minimum
  • No specific antidote
  • Specific-treatment evidence was low quality
Participants / model
Published human poisonings and deaths
Treatment
Supportive and experimental management described across case reports
Follow-up
Literature searched through 2011
Study design
Structured literature review

Publication and reporting bias prevent estimating the total number of exposures or risk per user.

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ATSDR worksheet · environmental screening only

Official environmental risk assessment

Agency for Toxic Substances and Disease Registry, 2021

ATSDR derived an intermediate-duration oral screening value from a mouse study with a 1,000-fold composite uncertainty factor. It did not derive an acute oral value because no suitable animal study was below levels associated with human lethality.

  • Environmental screening value
  • Mouse-derived with uncertainty factors
  • Not a therapeutic dose or safety guarantee
Participants / model
Environmental-health risk assessment using animal and human evidence
Treatment
Not a treatment study
Follow-up
Intermediate-duration exposure assessment
Study design
Government risk-assessment worksheet
Funding
U.S. Department of Health and Human Services

Minimal risk levels guide environmental screening; they are not approved doses and cannot be used to construct a weight-loss regimen.

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Zhejiang monitoring study · 14 survivors

Prospective measurements in an uncontrolled Chinese cohort

Zhao et al., Journal of Zhejiang University Science B, 2015

The full English-language report measured plasma DNP in 14 survivors from an occupational incident. Initial concentrations ranged from 0.25 to 41.88 µg/mL and correlated with temperature. DNP cleared slowly and remained detectable for as long as 25 days in most patients; intensive and routine hemoperfusion groups were not randomized.

  • Five routine and nine intensive hemoperfusion patients
  • Only survivors were included
  • Persistent poisoning data do not define routine oral pharmacokinetics
Participants / model
14 survivors of a Chinese occupational DNP poisoning incident
Treatment
Routine or intensive resin hemoperfusion plus multiple supportive treatments
Follow-up
Serial plasma monitoring for up to 25 days
Study design
Nonrandomized observational comparison with serial concentration measurements
Funding
National Natural Science Foundation of China and Zhejiang Province programs, as reported

Treatment allocation reflected clinical severity, two fatal cases were absent from the analysis, and the exposure was non-oral. It cannot prove treatment efficacy or a routine-use half-life.

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Mouse PK · metabolite half-lives

Animal pharmacokinetic study

Robert and Hagardorn, Journal of Chromatography, 1985

Eleven groups of six ICR mice received a single oral 22.5 mg/kg exposure and were sampled through 96 hours. Terminal plasma half-lives were estimated at 10.3 hours for parent DNP, 46.2 hours for 2-amino-4-nitrophenol, and 25.7 hours for 4-amino-2-nitrophenol.

  • 46.2 and 25.7 hours refer to metabolites
  • All estimates came from mice
  • The design used destructive sampling of different groups
Participants / model
66 ICR mice in 11 timepoint groups
Treatment
Single oral 22.5 mg/kg DNP exposure
Follow-up
Sampling from 0 through 96 hours
Study design
Animal pharmacokinetic study

These values are not human pharmacokinetics and cannot define a human dosing interval.

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Rat study · systemic and reproductive toxicity

Animal reproductive toxicology study

M. Takahashi et al., Environmental Toxicology, 2009

Rats received daily gavage at 0, 3, 10, or 30 mg/kg. At the highest exposure, parental weight gain fell, liver weight rose, and live-pup counts, live-birth index, and early pup weights were lower. The study's rat NOAEL cannot be treated as a human safe dose.

  • Males were exposed for 46 days
  • Females were exposed for 40 to 47 days
  • No increased malformation rate was reported under the study conditions
Participants / model
Male and female rats and their offspring
Treatment
Daily gavage at 0, 3, 10, or 30 mg/kg
Follow-up
46 days for males and 40 to 47 days for females
Study design
Controlled animal reproductive and developmental screening study
Funding
Japanese government research institute study

Animal toxicology study; its dose levels and NOAEL do not establish intentional human safety.

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Rat study · five-day male reproductive endpoints

Comparative animal toxicology study

K. L. Takahashi et al., Reproductive Toxicology, 2004

Male Sprague-Dawley rats received oral DNP at 7.5, 15, or 30 mg/kg for five days. The highest exposure reduced body weight during treatment and produced a slight increase in tailless sperm 14 days later; no DNP deaths occurred in this experiment.

  • Necropsy occurred 3 or 14 days after the last exposure
  • The study compared several dinitrophenolic chemicals
Participants / model
Sexually mature male Sprague-Dawley rats
Treatment
Oral DNP at 7.5, 15, or 30 mg/kg daily
Follow-up
Five consecutive days, with follow-up necropsy
Study design
Controlled comparative animal toxicology study

Animal study near toxic exposure levels; it does not establish human fertility effects or a human safety threshold.

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FDA enforcement · 110 DNP websites in 2016

FDA enforcement announcement

U.S. Food and Drug Administration, June 9, 2016

FDA said DNP had never been approved as a drug and identified 110 websites selling it as a weight-loss product during the 2016 enforcement action.

  • Never FDA approved as a drug
  • The 110 figure is specific to the 2016 sweep
Participants / model
U.S.-directed online drug sales
Treatment
Not applicable
Follow-up
Operation conducted May 31 through June 7, 2016
Study design
Regulatory and law-enforcement announcement
Funding
U.S. Food and Drug Administration

The 110-site count applies only to the 2016 enforcement sweep.

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FDA/DOJ notice · U.S. misbranding case

Federal criminal-enforcement notice

U.S. Department of Justice notice hosted by FDA, June 1, 2023

The notice states that FDA has never approved DNP for human consumption and reports a 33-month sentence after conviction for selling it as a misbranded drug online.

  • U.S. criminal case
  • Not an approval or lawful medical product
Participants / model
U.S. enforcement against online DNP sales
Treatment
Not applicable
Follow-up
Conduct described through sentencing in 2023
Study design
Official enforcement notice
Funding
U.S. Department of Justice and FDA

The notice describes one U.S. criminal case and its federal charges.

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UK guidance · regulated poison since 2023

Official government safety and legal guidance

UK Government.

The guidance says DNP and sodium dinitrophenolate became regulated poisons on October 1, 2023. In England, Wales, and Northern Ireland, a member of the public needs an EPP licence to import, acquire, possess, or use them, and sale to the public without a valid licence is a criminal offence.

  • Applies to England, Wales, and Northern Ireland
  • Immediate medical contact advised after taking DNP
Participants / model
Members of the public in the named UK jurisdictions
Treatment
Not applicable
Record date
Rule effective October 1, 2023
Study design
Government safety and regulatory guidance
Funding
UK Government

Jurisdiction-specific; Scotland and other countries require separate checks.

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Why is 2,4-dinitrophenol (DNP) in F tier?

F tier follows documented weight loss alongside severe and sometimes fatal toxicity, no approved therapeutic use, no established antidote, and no supported self-selected safe range.

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