Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 51-28-5 (2,4-Dinitrophenol) Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Human Toxicity Excerpts

  • SYMPTOMATOLOGY: 1. MARKED FATIGUE, TREMENDOUS THIRST, PROFUSE SWEATING, FLUSHING OF FACE. 2. NAUSEA, VOMITING, ABDOMINAL PAIN AND OCCASIONALLY DIARRHEA. 3. RESTLESSNESS, ANXIETY, EXCITEMENT, OCCASIONALLY LEADING TO CONVULSIONS. 4. A RISE IN BODY TEMPERATURE, WHICH IS ROUGHLY PROPORTIONAL TO THE TOXIC DOSE, MAY CULMINATE IN SEVERE HYPERPYREXIA. 5. TACHYCARDIA, HYPERPNEA, DYSPNEA, CYANOSIS AND SOMETIMES MUSCLE CRAMPS. 6. LOSS OF CONSCIOUSNESS, CESSATION OF BREATHING AND DEATH. 7. LATE COMPLICATIONS: A. DECR URINE OUTPUT WITH ALBUMINURIA, CASTS, PIGMENT, SOMETIMES BLOOD CELLS, DUE TO TOXIC NEPHRITIS. B. JAUNDICE & TENDERNESS IN LIVER REGION DUE TO TOXIC HEPATITIS. 8. OCCASIONAL HYPERSENSITIVITY REACTIONS AFTER REPEATED EXPOSURES (OR IN CHRONIC POISONING) INCLUDE AGRANULOCYTIC ANGINA, SKIN RASHES, PERIPHERAL /NEUROPATHY/ ... AND CATARACT FORMATION. /DINITROPHENOL/ [Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980., p. III-157]**PEER REVIEWED**
  • IN ACUTE INDUSTRIAL POISONING, NYSTAGMUS /INVOLUNTARY RAPID MOVEMENT OF THE EYE/ ... SAID TO BE PRESENT IN CASES OF MODERATE POISONING, & DILATED PUPILS WERE NOTED IN SEVERE CASES WITH POOR PROGNOSIS. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 358]**PEER REVIEWED**
  • In a poisoned person, the result is an almost immediate incr in oxygen consumption, body temp, 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 soln 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 resp 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/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-157]**PEER REVIEWED**
  • ESTIMATES OF INCIDENCE OF CATARACTS AMONG PEOPLE TAKING DINITROPHENOL FOR REDUCING /WEIGHT/ VARIED FROM 0.1% TO 1%. ONSET OF CATARACT OCCURRED SEVERAL MO 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 & 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./ [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 358]**PEER REVIEWED**
  • IN ACUTE POISONING FROM INGESTION: SKIN BECOMES HOT & FLUSHED, & PROFUSE PERSPIRATION, INTENSE THIRST, SEVERE HEADACHE, NAUSEA, VOMITING, ABDOMINAL PAIN, RESTLESSNESS, ANXIETY, DELIRIUM, & GENERALIZED WEAKNESS OCCUR. EXCESSIVE HYPERPYREXIA, ACIDOSIS, & DEHYDRATION MAY BE FOLLOWED BY CIRCULATORY OR RESP COLLAPSE & DEATH. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 977]**PEER REVIEWED**
  • 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./ [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 237]**PEER REVIEWED**
  • Hematologic alterations in humans resulting from 2,4-dinitrophenol exposure include hemolytic anemia, neutropenia, and eosinophilia. [USEPA; Chemical Hazard Information Profile: 2,4-Dinitrophenol p.5 (1981) EPA-560/2-76-010]**PEER REVIEWED**
  • ... 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. [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 237]**PEER REVIEWED**
  • DUST: POISONOUS IF INHALED OR IF SKIN IS EXPOSED. SOLID: POISONOUS IF SWALLOWED. LIQ OR SOLID IRRITANT CHARACTERISTICS: CAUSES SMARTING OF SKIN & FIRST-DEGREE BURNS ON SHORT EXPOSURE; MAY CAUSE SECOND-DEGREE BURNS ON LONG EXPOSURE. [U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5., p. ]**PEER REVIEWED**
  • DUST & VAPOR OF DINITROPHENOL ... REPORTED TO BE IRRITATING TO MUCOUS MEMBRANE IN INDUSTRIAL EXPOSURE, BUT NO CONTACT INJURIES ... REPORTED. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 358]**PEER REVIEWED**
  • 2,4-Dinitrophenol causes maculopapular dermatitis. [ITII. Toxic and Hazarous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1982., p. 198]**PEER REVIEWED**
  • FIRST-DEGREE BURNS ON SHORT EXPOSURE; MAY CAUSE SECOND-DEGREE BURNS ON LONG EXPOSURE. [U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5., p. ]**PEER REVIEWED**
  • Dermatitis may be due to either primary irritation or allergic sensitivity. [Sittig, M. Handbook of Toxic And Hazardous Chemicals. Park Ridge, NJ: Noyes Data Corporation, 1981., p. 185]**PEER REVIEWED**
  • 2,4-Dinitrophenol signs and symptoms are fever/hyperthemia (increased metabolic rate), skin discoloration (pseudojaundice), acidosis (metabolic, delayed), hypotension, cataract (subcapsular), hearing impairment (delayed). [Kimbrough, R.D., P. Grandjean, D.D. Rutstein. Clinical Effects of Environmental Chemicals. New York, NY: Hemisphere Publishing Corp., 1989., p. 20]**PEER REVIEWED**
  • Administration of 2,4-dinitrophenol does not lead to the production of methemoglobin, whereas administration of the 2,3-, 2,5-, 2,6-, and 3,4-isomers does. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 463]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • TEST OF AQUEOUS SOLUTION OF 2,4-DINITROPHENOL ON RABBIT CORNEAS BY INJECTION INTO CORNEAL STROMA OR APPLICATION TO EYE AFTER REMOVING CORNEAL EPITHELIUM CAUSED NO SIGNIFICANT REACTION @ 0.012 MOLAR CONCN, BUT @ 0.05 MOLAR CAUSED MODERATE REACTION, GRADED 52 ON SCALE OF 1 TO 100. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 359]**PEER REVIEWED**
  • Ducklings fed 2,4-dinitrophenol at a concn of 2,500 ppm developed cataracts within 24 hr ... Chickens were also susceptible. Cataract was observed in duckling only 3.5 hr after crop intubation. With no further dosing, the lesion cleared within 3 days. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 466]**PEER REVIEWED**
  • USING IN VITRO LENS CULTURE SYSTEM ... 2,4-DINITROPHENOL AT ... 2X10-5 MOLAR CAUSED CATARACTS ... IN LENS OBTAINED FROM RABBITS 40 ... DAYS OF AGE. KNOWN METABOLITES OF DINITROPHENOL (2-AMINO-4-DINITROPHENOL; 2-NITRO-4-AMINOPHENOL; & 2,4-DIAMINOPHENOL) DID NOT PRODUCE THIS EFFECT EVEN AT ... 1X10-3 MOLAR. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 977]**PEER REVIEWED**
  • ... Produced fetal growth inhibition but no defects in rat fetuses after maternal doses of 8 to 40 mg/kg on gestational days 9, 10, or 11. /Other investigator/ ... used the cmpd orally (38.3 mg/kg) and intraperitoneally (13.6 mg/kg) on days 10 through 12 in the mouse and found no teratogenic action. [Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 212]**PEER REVIEWED**
  • INVESTIGATORS: ... STUDIED CHRONIC TOXICITY IN RATS FED DIETS CONTAINING 2,4-DINITROPHENOL AT 0, 100, 200, 500, 1000, & 2000 UG/G FOR 6 MO. ... RATS MAINTAINED ON DIETS CONTAINING ... 200 UG/G (10 MG/KG/DAY) GREW AT NORMAL RATE, & NO ADVERSE CHANGES WERE NOTED AT AUTOPSY. ... AT HIGHER DOSES OF ... (50 & 100 MG/KG/DAY), SOME RATS DIED & SURVIVORS RAPIDLY LOST WT. ENLARGED DARK SPLEENS, PATHOLOGICAL LESIONS OF LIVER & KIDNEY, & TESTICULAR ATROPHY WERE ALSO OBSERVED. [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 241]**PEER REVIEWED**
  • ... 2,4-DINITROPHENOL FAILED TO PROMOTE TUMOR DEVELOPMENT IN MICE. IN ANOTHER EXPT IN MICE ... /NO DETECTION OF/ TUMOR FORMATION DURING 6 MO ORAL ADMIN OF 2,4-DINITROPHENOL. ... /INVESTIGATORS/ ADMIN 2,4-DINITROPHENOL (20 MG/KG/DAY) TO FEMALE RATS FOR 8 DAYS BEFORE INTRODUCING MALES. ... THEN ADMIN ORALLY TWICE DAILY UNTIL LITTERS WERE WEANED. ... 25% OF OFFSPRING OF TREATED FEMALES WERE STILLBORN, COMPARED TO ONLY 6.8% OF THOSE BORN TO CONTROLS. ... MORTALITY DURING NURSING PERIOD ... WAS 30.9%, COMPARED TO 13.4% FOR THE YOUNG OF CONTROL MOTHERS. ... MALFORMATIONS SUCH AS HEMIOPHTHALMUS & CROSS BEAK WERE INDUCED IN CHICK EMBRYOS FOLLOWING ADMIN OF 0.5 UG ... /EGG INTO YOLK SAC AT 48TH HR OF INCUBATION. FOLLOWING EXAMINATION OF PURIFIED MYELIN IN MALFORMED EMBRYOS ... /IT WAS/ SUGGESTED THAT EXPOSURE ... RESULTED IN IMPAIRED EMBRYONIC MYELINATION. [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 243]**PEER REVIEWED**
  • AFTER INJECTION 2,4-DINITROPHENOL INTO PORTAL VEIN, CONFIGURATIONAL CHANGES IN HEPATOCYTE MITOCHONDRIA DID NOT DIFFER FROM THOSE OBSERVED IN CONTROLS. HEART MUSCLE SHOWED STRONGLY INJURED MITOCHONDRIA WITH DISINTEGRATED CRISTAE & PALE MATRIX WITH FLOCCULENT BODIES. [CIECIURA L, RYDZYNSKI K; ACTA MED POL 21 (4): 309-10 (1980)]**PEER REVIEWED**
  • The germination and formation of pollen tubes of Impatiens sultanii occurs rapidly in simple media at 25 deg C. The pollen tube growth rate of these flowering plants is linear for up to 1 hr under laboratory conditions. At 0.5-20 ppm, 2,4-dinitrophenol inhibited pollen germination and tube production. At 25 ppm, it inhibited tube growth. ... [Bilderback DE; Eviron Health Perspect 37: 95-103 (1981)]**PEER REVIEWED**
  • 2,4-Dinitrophenol (2,4-DNP) induced stickiness and clumping of chromosomes in the plant tissues of Nigelila sativa. 2,4-DNP inhibited DNA, RNA, and protein synthesis at all the concentrations used. Inhibition increased as the concentration increased from 0.25 mg/l to 2 mg/l. [Chand S, Roy SC; Nucleus 24 (3): 143-7 (1981)]**PEER REVIEWED**
  • The effects of 2,4-dinitrophenol (2,4-DNP) on the mechanical activity of guinea pig papillary muscles were studied. 1x10-4 M 2,4-DNP initially potentiated the contraction and subsequently suppressed the mechanical activity in about twelve minutes. During the negative inotropic phase, a contracture developed. Both of these effects were reversible. [Re GG, Ageno R; Bull Soc Ital Biol Sper 57 (17): 1789-92 (1981)]**PEER REVIEWED**
  • Signs of intoxication are much the same in all species and include listlessness, loss of appetite and activity, deepened and more rapid respiration, sweating (in some animals only), thirst, oliguria, muscular weakness, prostration, dyspnea and death, with terminal hyperpyrexia. Signs may appear within a few min if large amt have been ingested, otherwise they may be delayed for several hr. /Dinitro cmpd/ [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 135]**PEER REVIEWED**
  • The effect of 10 different herbicides, ... /including/ 2,4-dinitrophenol was evaluated on the germinability of pollen of various flower forms of the F, F-24, F-48, and F-72 series of Petunia axillaris. All the herbicides stimulated pollen germination but to a varying degree. ... 2,4-Dinitrophenol was a poor stimulator. All herbicides stimulated pollen germination in the F series of the violet-flowered form, whereas only 2 herbicides stimulated in the F-24 series of white violet-flowered forms. As low as 10-17 ug/ml ... 2,4-dinitrophenol was toxic to pollen. ... All the herbicides stimulated tube growth. Acrolein and 2,4-dinitrophenol were the best stimulators. The stimulation of tube growth varied in the various forms of different series. [Salgare SA; Curr Pollut Res India: 317-29 (1985)]**PEER REVIEWED**
  • Injection of anesthetized rats with the uncoupling agent 2,4-dinitrophenol (2,4-DNP) (10 or 20 mg/kg) induced a systemic hyperammonemia unaccompanied by blood acid-base status changes, but related to an increased release of ammonia from the kidney into the renal vein. Ammonia excretion into the urine did not increase. The renal uptake of circulating glutamine rose. [Imler M et al; Eur J Pharmacol 123 (2): 175-9 (1986)]**PEER REVIEWED**
  • p-Nitrophenol (PNP), m-nitrophenol (MNP), 2,4-dinitrophenol (DNP), and catechol were tested for their effects on an algal population in a soil and on pure cultures of 2 algae isolated from soil. Both p-nitrophenol and m-nitrophenol, even at 0.5 kg/ha level, were toxic to the soil algae. Inhibition of algae was relatively higher with p-nitrophenol compared to the other two nitrophenols. Catechol treatment with less than or equal to 1.0 kg/ha led to an initial enhancement of algae growth with a subsequent toxic effect. The toxicity of the phenolic cmpd toward Chlorella vulgaris (a green alga) and Nostoc linckia (a blue-green alga) decreased in the order: m-nitrophenol > p-nitrophenol > 2,4-DNP > catechol. However, algicidal or algistatic effects of the test chemicals were fairly higher against C vulgaris, suggesting that the eukaryotic alga is highly sensitive to such soil pollutants compared to the prokaryotic alga. [Megharaj M et al; Plant Soil 96 (2): 197-203 (1986)]**PEER REVIEWED**
  • Bacterial isolates (166) from a polluted stream (Sugden Beck) and an unpolluted stream (Stubbs Beck) were exposed to 2,4-dinitrophenol and picric acid; all isolates were inhibited by both cmpd in a concn dependent manner. However, the isolates from Sugden Beck were more resistant to the 2 cmpd than those from Stubbs Beck. When 16 chlorophenols, nitrophenols, and phenoxyalkanoic acids were tested for toxicity with selected isolates from the streams, all the cmpd inhibited bacterial growth. ... Toxicity of nitrophenols decreased with increase in the degree of nitro substitution. ... [Milner CR, Goulder R; Bull Environ Contam Toxicol 37 (5): 714-8 (1986)]**PEER REVIEWED**
  • Formation of superoxide O2(-) radicals in the tissues of brain and liver of 2,4-dinitrophenol treated rats was increased 1.5 and 1.3 fold that of the control group, respectively. The content of hydrogen peroxide was slightly increased in both brain and liver tissues. The total specific activity of superoxide dismutase in the brain of animals given 2,4-dinitrophenol was enhanced less than or equal to 1.7 fold that of the control group. The total specific activity of superoxide dismutase in the livers from animals treated with 2,4-dinitrophenol was 4.68. The activities of manganese superoxide dismutase in the brain and liver tissues of animals treated with 2,4-dinitrophenol were increased to 2.2 and 2.0 fold those of the control group, respectively, but no significant change in the activity of a copper superoxide dismutase was observed. Thus, 2,4-dinitrophenol, which may act on all sites of oxidative phosphorylation, may cause an increase /in/ the O2(-) in the cells, and this may occur at state 4. [Oh CH et al; Chungang Uidaechi 10 (3): 271-80 (1985)]**PEER REVIEWED**
  • METABOLIC INHIBITOR SUCH AS ... 2,4-DINITROPHENOL ... STIMULATED CHLORAMBEN MOVEMENT IN EXCISED BEAN PETIOLE, ROOT, & HYPOCOTYL SECTIONS ... . [Kearney, P.C., and D. D. Kaufman (eds.) Herbicides: Chemistry, Degredation and Mode of Action. Volumes 1 and 2. 2nd ed. New York: Marcel Dekker, Inc., 1975., p. 561]**PEER REVIEWED**
  • An in vivo fish was adapted to monitor respiratory cardiovascular responses of spinally transected rainbow trout exposed to acutely toxic aqueous concentration of two uncouplers of oxidative phosphorylation, pentachlorophenol and 2,4-dinitrophenol. The most evident toxic response to the uncouplers was a rapid 150 to 200% increase in ventilation volume and oxygen consumption over the entire survival period. This caused an initial increase in total arterial oxygen content of the blood, which then fell slowly as the tissues used more and more oxygen to generate ATP. Arterial blood pressure and other blood measurements did not change appreciably in response to pentachlorophenol, yet 2,4-dinitrophenol causes increases in hematocrit and hemoglobin and slight decreases in total arterial carbon dioxide and arterial pH. ... The final phase of toxicity produced by the uncouplers appeared to eventually produce acute tissue hypoxia, with a generalized loss of respiratory cardiovascular coordination, and finally respiratory paralysis. [McKim JM et al; Environ Toxicol Chem 6 (4): 295-312 (1987)]**PEER REVIEWED**
  • The effect of 2,4-dinitrophenol on blood /flow/ of the skeletal muscle was studied in dogs. Mongrel dogs were anesthetized with sodium pentobarbital. Three injections of approximately 22.5 mg/kg 2,4-dinitrophenol were given at 30 minute intervals. Arterial, femoral venous, and mixed venous blood were taken simultaneously 20 minutes after injection and blood flow and oxygen uptake were determined. Blood gas tensions and pH were measured. Another group of dogs was given a gas mixture containing 12% oxygen and and 88% nitrogen throughout the experiment. After 30 minutes of hypoxia, the 2,4-dinitrophenol injections were given at 30 minute intervals and blood samples were taken. In the 2,4-dinitrophenol exposed group, limb oxygen uptake increased about 3 ml/kg/minute with each 2,4-dinitrophenol injection. The increase was the same in the 2,4-dinitrophenol/hypoxic group, but fell to 50% of the rate after the next two injections. Whole body oxygen in all animals given 2,4-dinitrophenol increased in a linear fashion to about 50% of the increase in the limb. Limb and whole body oxygen uptake did not change with time in controls. Cardiac output in controls tended to decrease with time and was parallel in the 2,4-dinitrophenol exposed group, but the hypoxic/ 2,4-dinitrophenol group showed a definite plateau for the last two periods. Limb blood flow in controls decreased with time and was matched after 2,4-dinitrophenol injection 1, but remained the same for injections 2 and 3. Limb flow did not change in the 2,4-dinitrophenol/hypoxic group until an increase occurred after 2,4-dinitrophenol injection 3. Limb vascular resistance decreased in both experimental groups when compared to controls. [Cain SM, Chapler CK; J Appl Physiol 59 (3): 698-705 (1985)]**PEER REVIEWED**
  • Rana gryilo (southern bullfrog) tadpole exposed to 5,520 ug/l/7 hr, toxic effect: increased respiration. /From table/ [Ambient Water Quality Criteria Doc: Nitrophenols p.B-17 (1980) EPA 440/5-80-063]**PEER REVIEWED**
  • Strongylocentrotus purpuratus (sea urchin) sperm exposed to 92,000 ug/l/1 hr, toxic effect: inhibition of respiration, and motility. /From table/ [Ambient Water Quality Criteria Doc: Nitrophenols p.B-18 (1980) EPA 440/5-80-063]**PEER REVIEWED**
  • Embryos of the inland silverside, Menidia beryllina, were exposed to three known (or suspected) teratogens: (1) 2,4-dinitrophenol; (2) "produced water" and (3) naphthalene. Tests were conducted by placing single embryos in glass tissue culture tubes containing 6 ml of saline exposure media. Twenty tubes were used for each exposure concentration and controls. A severity-index based upon craniofacial, cardiovascular and skeletal terata was used to rank responses each day. The compounds tested caused teratogenic expressions in embryos and larvae exposed from the 2 to 4 cell and blastula stage through 7 to 8 days post-fertilization. [Middaugh DP et al; Govt Reports Announcements & Index (GRA&I), Issue 24 (1988) EPA/600/J-88/107]**PEER REVIEWED**
  • An in vivo fish model was adapted to monitor respiratory cardiovascular responses of spinally transected rainbow trout exposed to acutely toxic aqueous concentrations of two uncouplers of oxidative phosphorylation, pentachlorophenol and 2,4-dinitrophenol, and two narcotics, tricaine methanesulfonate and 1-octanol. Individual principal component analyses of the cardiovascular-respiratory responses of fish exposed to the first two principal components explained 68% to 76% of the variation in the 18 parameters analyzed. The general sets of responses described for these two fish acute toxicity syndromes have provided the initial information necessary to group similar responses caused by other chemicals into a fish uncoupler syndrome, a fish /CNS depression/ syndrome or some new syndrome. [USEPA/ERLD; Use of Respiratory-Cardiovascular Response of Rainbow Trout (Salmo gairdneri) in Identifying Acute Toxicity Syndrome in Fish: Part 1. Pentachlorophenol, 2,4-Dinitrophenol, Tricaine methanesulfonate and 1-Octanol (1987) EPA/600/J-87/067]**PEER REVIEWED**
  • The effect of the beta-blocker propranolol in sublethal poisoning with 2,4,-dinitrophenol was studied on carbohydrate kinetics in dogs. Parameters of glucose and lactate turnovers were measured by using a mixture of 3-3(H)-glucose and 14(C)-lactate according to the primed constant rate infusion technics. Participation of plasma glucose in lactate production (%L----G) and the rate of peripheral glycogenolysis was estimated in experiments using a mixture of 3-3(H)-glucose and 14(C)-glucose (U). Propranolol did not interfere with the 2,4-dinitrophenol-induced rise of body temperature (+ 4 deg C), but completely blocked the rise of lactate production, the lactacidemia and the rise of peripheral glycolgenolysis seen in 2,4-dinitrophenol treated controls. Propranolol significantly increased %L----G, prolonged the 2,4-dinitrophenol induced hyperphosphatemia and it caused a decline in plasma glucose. The effects of the beta-blocker could be overcome by increasing the rate of 2,4-dinitrophenol infusion. It is concluded that in 2,4-dinitrophenol poisoning the beta-adrenergic system plays a major role in the elevated peripheral glycogenolysis and it helps to compensate for the loss of mitochondrial synthesis of ATP by greatly accelerating its cytoplasmic synthesis. [Issekutz B Jr; Arch Int Pharmacodyn Ther 272 (2): 310-9 (1984)]**PEER REVIEWED**
  • The test series developed methods for testing a compliment of aquatic organisms in a single test that satisfies the freshwater acute toxicity requirements for setting water quality criteria. Species tested included fathead minnows (Pimephales promelas), rainbow trout (Salmo gairdneri), bluegill (Lepomis macrochirus), channel catfish (Ictalurus punctatus), goldfish (Carassius auratus), white sucker (Catostomus commersoni), daphnia (Daphnia magna), midge (Tanytarsus dissimilis), crayfish (Orconectes immunis), snail (Aplexa hypnorum), tadpole (Xenopus laevis), and leech (Nephelopsis obscura). Five to nine of the preceding species were simultaneously exposed in individual tests. The chemicals tested were acrolein, aniline, dibutylfumarate, 2,4-dinitrophenol, Guthion, nicotine sulfate, phenol, rotenone, silver, Systox, 1,2,4-trichlorobenzene, 2,4,6-trichlorophenol and o-xylene. The method of simultaneously exposing aquatic organisms in separate compartments of each exposure tank allows more accurate comparisons of species sensitivity with a tested chemical. [USEPA/ERLD; Simultaneous Multiple Species Testing: Acute Toxicity of 13 Chemicals to 12 Diverse Freshwater Amphibian, Fish and Invertebrate Families (1987) EPA/600/J-87/218]**PEER REVIEWED**
  • 83 (2): 283-9 (1986)] The effects of pharmacologically elevated metabolism on respiratory adjustments were studied in chickens. Adult female white leghorn chickens were decerebrated and allowed to recover from anesthesia. In experiment 1, birds were injected with 2.5 mg/kg 2,4-dinitrophenol. Respiratory and cardiovascular measurements were monitored continuously. After steady state conditions were reestablished, another 2.5 mg/kg 2,4-dinitrophenol injection was given and measurements were taken again. Injections and measurements continued until no further oxygen consumption increase occurred. Some birds received a single 5 mg/kg 2,4-dinitrophenol injection. Measurements were repeated every 5 minutes. In experiment 2, birds had control measurements and arterial blood samples taken at approximately 20 deg C. Birds were cooled to 2 deg C. After a steady respiratory response was established, measurements were taken. Successive 2,4-dinitrophenol doses caused a progressive oxygen consumption increase in the decerebrated chickens; a 7.5 to 10 mg/kg dose of 2,4-dinitrophenol elicited the maximal oxygen consumption response, approximately 275% of control values. A single 5 mg/kg 2,4-dinitrophenol injection increased oxygen consumption and the respiratory exchange ratio and increased minute ventilation. Ventilation significantly increased within 10 seconds of the start of 2,4-dinitrophenol injection. A steady state was reached approximately 10 minutes after the start of injection. Birds hyperventilated about 45 minutes after injection when the temperature reached approximately 42.3 deg C. The respiratory and cardiovascular effects of the increased metabolism during cold exposure was similar to the initial elevated metabolism responses elicited by 2,4-dinitrophenol. Oxygen consumption increased to approximately 185% of control values; V1 increased in a way that oxygen extraction remained unchanged. /It was concluded/ that 2,4-dinitrophenol induced hyper metabolism in the decerebrated chicken is an acceptable model to study respiratory control and gas exchange during exercise in birds. [Gleeson M; Compar Biochem Physiol [A]**PEER REVIEWED**
  • A study was made to determine whether 2,4-dinitrophenyl groups are localized on Thy-1+ cells in the epidermis of male C3H/He mice following ear skin painting with 0.05 ml of 0.5% 2,4-dinitrochlorobenzene. Epidermal cell suspensions were double stained for Thy-1 protein (orange) and 2,4-dinitrophenol groups (green). Incidence of epidermal cells with 2,4-dinitrophenol groups was 82.7% on the average when the specimens were treated with anti-2,4-dinitrophenol followed by anti-Thy-1,2. An average of 1.7% of the epidermal cell stained intensely for Thy-1 protein, and 2,4-dinitrophenol groups were simultaneously detected on 77.8% of the Thy-1,2+ cells. Most of the Thy-1,2+ cells were round or oval, but a few were dendritic. Two color cells in the section treated with anti-2,4-dinitrophenol followed by anti-Thy-1,2 incubation were detected more frequently than cells treated with the antibodies in the reverse order. Binding of antibody to Thy-1 antigen in advance interrupted anti-2,4-dinitrophenol antibody in its reaction. The contamination of T-lymphocytes into the epidermal cell suspension was considered to be negligible. [Bang D et al; J Dermatol 15 (1): 27-31 (1988)]**PEER REVIEWED**
  • In a narcotized dog, the intravenous administration of 2,4-dinitrophenol at a dosage of 8.5-9 mg/kg increased the metabolic rate by 100-200%. A striking rise in plasma lactate and inorganic phosphate was observed. At the same time, the oxygen uptake of the muscle was shown to increase 5-6 fold, while its adenosine triphosphate and glycogen content decreased markedly. Death was caused by hyperthermia. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1194]**PEER REVIEWED**
  • Chromosome aberrations can occur by secondary mechanism(s) associated with cytotoxicity, induced by chemicals that do not attack DNA. Aberrations are formed from DNA double-strand breaks, and DSBs are known to be induced by nonmutagenic (Ames test negative) noncarcinogens at toxic levels. Here, 8 of 12 of these chemicals caused aberrations in CHO cells at cytotoxic doses, and often only when cell counts (survival) at 20 hr approached < or =50% of controls. Five of eight noncarcinogens (2,4,-dichlorophenol, dithiocarb, menthol, phthalic anhydride, and ethionamide) and one of two equivocal carcinogens (bisphenol A) caused aberrations, usually over a narrow dose range with steeply increasing cytotoxicity. ... Aberrations were also induced by metabolic poisons, 2,4-dinitrophenol, (uncouples oxidative phosphorylation), and sodium iodoacetate, (Nal; blocks ATP production). ... Clearly, chemicals can give "false-positive" results in the chromosome aberration assay at cytotoxic levels, though cytotoxicity does not always produce aberrations, so that further information (e.g., DNA reactivity) is needed to determine whether a result is a "false-positive." Primary DNA-damaging chemicals such as alkylators are also cytotoxic, but give strong increases in aberrations without marked initial toxicity by the measures used here, although the aberrations they induce do reduce long-term survival in colony-forming assays. [Hilliard CA et al; Environ Mol Mutagen 31 (4): 316-26 (1998)]**PEER REVIEWED**
  • Previous studies, using rhodamine 123 (R123), suggest that perturbation in mitochondrial ATP production via oxidative phosphorylation alters embryonic growth and development during neurulation in vitro. ... Studies were designed to ... evaluate the effects of altered mitochondrial metabolism on development. Mouse conceptuses (4-6 somites) were grown in whole embryo culture. To confirm the dysmorphogenic effect of altered oxidative phosphorylation, the effects of 2,4-dinitrophenol, an uncoupler, were evaluated. 2,4-dinitrophenol at concentrations as low as 250 uM produced neural tube defects. Eighty-six percent of embryos exhibited neural tube defects at 750 uM. Sodium azide was next employed because of its inhibition of electron transport by cytochrome oxidase. One hundred and 200 uM Azide did not alter development. In contrast, 500 uM produced neural tube defects in 75% (6/8) embryos and at 1,000 uM 100% were malformed. ... To determine if the source of substrates for oxidative phosphorylation (e.g. NADH) was of Krebs cycle or glycolytic origin ... the effects of fluoroacetate, a Krebs cycle enzyme inhibitor, were determined. High rates of neural tube defects were produced by fluoroacetate at 600 uM and 33% of embryos exhibited neural tube defects at 200 uM. These results ... suggest that oxidative phosphorylation is an important metabolic pathway during early neurulation and that Krebs cycle metabolism appears to be required for normal embryogenesis. [Hunter ES, Tugman JA; Teratology 47 (5): 410 (1993)]**PEER REVIEWED**
  • The rabbit adrenal gland was perfused with a modified Locke's medium and the mechanism of adrenaline secretion induced by nitrophenol cmpd was investigated. Prolonged exposure to 2,4-dinitrophenol or trinitrophenol caused an immediate and long-lasting increase in secretion only in the presence of calcium. The response to 2,4-DNP depended on the concn of calcium, but that to trinitrophenol was largest in the presence of 0.5 mM calcium. Re-addition of 2 mM calcium during prolonged exposure to 2,4-DNP or trinitrophenol produced a larger response than did the simultaneous addition of calcium and either 2,4-DNP or trinitrophenol. The response to 2,4-DNP in the presence of 2 mM calcium was markedly reduced by removal of external sodium, but the sodium dependency became less marked in the presence of 0.1 mM calcium. ... The response to 2,4-DNP was largely potentiated in the absence of most ions in the presence of only 0.1 mM calcium and that to trinitrophenol was potentiated in the presence of only 0.5 mM calcium under the same conditions. Re-addition of calcium 5 min after the removal of 2,4-DNP or trinitrophenol still caused substantial secretion. [Yamagami K, Sorimachi M; Jpn J Physiol 37 (4): 643-56 (1987)]**PEER REVIEWED**
  • The absorption of phloem-mobile 2,4-dinitrophenol and its accumulation by Cyclamen persicum conducting tissue was primarily caused by ion trapping; optimum absorption occurred at pH 4. The hyperbolic response of concn dependent uptake was due to an increasingly toxic effect at elevated 2,4-dinitrophenol; concn (> 10-4M). Active sucrose loading into conducting tissue was affected by treatment with 2,4-dinitrophenol (>10-4M) ... . [Grimm E et al; Biochem Physiol Pflanz 181 (2): 65-75 (1986)]**PEER REVIEWED**

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Human Toxicity Values

  • Lethal doses for orally ingested 2,4-dinitrophenol in humans have been reported to be 14 to 43 mg/kg ... . [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 237]**PEER REVIEWED**
  • FATAL DOSE IN ADULTS IS ABOUT 1 TO 3 G BY MOUTH; 3 G HAS ALSO PROVED FATAL IN DIVIDED DOSES OVER A PERIOD OF 5 DAYS. /DINITROPHENOL/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-157]**PEER REVIEWED**

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Non-Human Toxicity Values

  • LD50 Rat oral 30 mg/kg [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 518]**PEER REVIEWED**
  • LD50 Rat ip 28.5 to 35 mg/kg /From table/ [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 236]**PEER REVIEWED**
  • LD50 Mouse ip 26 to 36 mg/kg /From table/ [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 236]**PEER REVIEWED**
  • LD50 Rabbit oral 30 mg/kg /From table/ [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 236]**PEER REVIEWED**
  • LD50 Dog oral 20 to 30 mg/kg /From table/ [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 236]**PEER REVIEWED**
  • LD50 Dog intramuscular 20 mg/kg /From table/ [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 236]**PEER REVIEWED**
  • LD50 Rat ip 20 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1381]**PEER REVIEWED**
  • LD50 Rat sc 25 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1381]**PEER REVIEWED**
  • LD50 Mouse oral 45 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1381]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • IT IS READILY ABSORBED FROM SKIN & THROUGH RESP TRACT & GI TRACT. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 359]**PEER REVIEWED**
  • STUDIES OF BLOOD AQUEOUS BARRIER & DIFFERENCES OF PENETRABILITY OF 2,4-DINITROPHENOL INTO EYE FROM BLOOD IN DIFFERENT SPECIES ... SHOWN THAT DINITROPHENOL GETS INTO AQUEOUS HUMOR MORE READILY & REACHES HIGHER CONCN IN DUCKS THAT DEVELOP CATARACTS THAN ... RABBITS THAT DO NOT. ALSO, IN IMMATURE RABBITS, IN WHICH CATARACTS CAN BE PRODUCED, DINITROPHENOL ENTERED AQUEOUS HUMOR MORE READILY THAN IN MATURE RABBITS WHICH DID NOT DEVELOP CATARACTS. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 359]**PEER REVIEWED**
  • WHEN 2,4-DINITROPHENOL WAS ADMIN SUBCUTANEOUSLY TO RABBITS & RATS, CMPD WAS RAPIDLY ABSORBED & DISTRIBUTED. HIGHEST CONCN WAS IN SERUM. LARGE AMT WAS ALSO FOUND IN KIDNEY, LUNG, & LIVER. [Menzie, C.M. Metabolism of Pesticides. U.S. Department of the Interior, Bureau of Sport Fisheries and Wildlife, Publication 127. Washington, DC: U.S. Government Printing Office, 1969., p. 172]**PEER REVIEWED**
  • AFTER IP ADMIN: SERUM LEVELS ... IN MATURE RABBITS DECLINED TO LESS THAN 1% OF ORIGINAL MAXIMUM VALUE WITHIN 7 HR. RATE OF ELIMINATION IS SIGNIFICANTLY REDUCED IN IMMATURE RABBITS. [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 234]**PEER REVIEWED**
  • Five groups of 6 mice were given single oral doses of 22.5 mg/kg 2,4-dinitrophenol. Groups were sacrificed at 1, 3, 6, 12, and 24 hr post-treatment, and serum, liver, and kidney tissues were collected for analysis of 2,4-DNP content. Quantitation was performed via a capillary gas chromatography/mass spectrometry technique after liquid-liquid extraction of biological specimens spiked with trideuterated 2,4-DNP as the internal standard. Concentration versus time data for each tissue were subjected to pharmacokinetic analysis. Similar 2-compartment open models characterized most phases of the disposition of 2,4-DNP. The kidney appears to persistently maintain the lower concentration of 2,4-DNP. [Robert TA, Hagardorn AN; J Chromatog 276 (1): 77-84 (1983)]**PEER REVIEWED**
  • The dermal penetration of 2,4-dinitrophenol and 5 other pesticides was determined after application to a 1,2-sq cm area of the upperback of 7 to 8 wk old mice (1 mg/kg). The amounts of labeled pesticide were measured at the site of application and in the blood, liver, kidney, excreta and carcass. About 95% or greater, were recovered in all cases. These compounds penetrated much slower (21% or less in 24 hr) than was shown for a group of insecticides in previous reports. Slow penetration could be explained by low partition coefficients for most compounds. These compounds did not indicate any propensity for appreciable storage or binding in the tissues examined. The carcass contained the greatest amount of radioactivity at 24 hr. The fraction of each compound that penetrated was eliminated from the body at various rates, with excretion being highest for 2,4-dinitrophenol (93%) at 24 hr. [Grissom RE Jr et al; Pestic Biochem Physiol 24 (1): 119-23 (1985)]**PEER REVIEWED**
  • ... Is excreted unchanged and as metabolites. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1195]**PEER REVIEWED**
  • The major excretory product in human, dog, rat, and mouse is probably 2-amino-4-nitrophenol. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1195]**PEER REVIEWED**

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Metabolism/Metabolites

  • IN URINE OF /SC/ TREATED RABBITS, DINITROPHENOL GLUCURONIDE, 2-AMINONITROPHENOL & ITS ETHER SULFATE WERE FOUND. IN VITRO, BUT NOT IN VIVO, STUDIES INDICATED PRESENCE OF 4-AMINONITROPHENOL. LATTER WAS UNSTABLE ... . [Menzie, C.M. Metabolism of Pesticides. U.S. Department of the Interior, Bureau of Sport Fisheries and Wildlife, Publication 127. Washington, DC: U.S. Government Printing Office, 1969., p. 172]**PEER REVIEWED**
  • EXAMINATION OF URINE OF MAN FATALLY POISONED BY 2,4-DINITROPHENOL (2,4-DNP) SHOWED THAT IT CONTAINED 2-AMINO-4-NITROPHENOL, 4-AMINO-2-NITROPHENOL & DIAMINOPHENOL. ... /2,4-DNP IS ALSO/ EXCRETED BY MAMMALS ... PARTIALLY UNCHANGED, PARTIALLY CONJUGATED WITH GLUCURONIC ACID ... & PROBABLY /AS/ 2,4-DIAMINOPHENOL. RATS ORALLY DOSED ... EXCRETED BOTH FREE DINITROPHENOL (78%) & 2-AMINO-4-NITROPHENOL (17%). [National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 234]**PEER REVIEWED**
  • One study has indicated that enzyme systems in a few types of bacteria and fungi can reduce and detoxify dinitrophenolic compounds to 2-amino-4-nitrophenol and the 4-amino isomer. /Dinitrophenolic compounds/ [USEPA; Chemical Hazard Information Profile: 2,4,-Dinitrophenol p.2 (1981) EPA-560/2-76-010]**PEER REVIEWED**
  • ... Arthrobacter simplex, Pseudomonas sp, and Arthrobacter sp were able to metabolize 2,4-dinitrophenol and 2,4,6-trinitrophenol, forming nitrite. [Ambient Water Quality Criteria Doc: Nitrophenols p.A-9 (1980) EPA 440/5-80-063]**PEER REVIEWED**
  • It is metabolized in humans, dogs, and mice to 2-amino-4-nitrophenol, 2-nitro-4-aminophenol, and 2,4-diaminophenol and their glucuronic acid conjugates. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1195]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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