2-메틸-4,6-디니트로페놀

Hazardous Air Pollutants (HAPs)

Reactive agents - 4th degree

Acaricides, Fungicides, Herbicides, Insecticides

Active substance -> EU Pesticides database: Not approved

Pesticide

Semi-Volatile Organic Compound (SVOC) (Pesticide/Semi-Volatile Organic Compound (SVOC))

log Kow = 2.13

2.14

greater than 1.1 at 68 °F (est) (USCG, 1999)

1.58 g/cu cm at 20 °C

1.58 @ 20°C

Yellow prisms or needles from alcohol

Yellow prisms from alcohol

Yellow solid

0.01 % (NIOSH, 2024)

In water, 198 mg/L at 20 °C

In water, 130 mg/L at 15 °C

Slightly soluble in water

Slightly soluble in petroleum ether; soluble in ethanol, ether, acetone, chloroform

For more Solubility (Complete) data for 4,6-Dinitro-o-cresol (7 total), please visit the HSDB record page.

594 °F at 760 mmHg (EPA, 1998)

312 °C

220 °C @760 [mm Hg]

When heated to decomposition it emits toxic fumes of /nitrogen oxides/.

In water, DNOC degrades very slowly, DT50 >1 yr. Photolysis DT50 /about/ 253 hr (20 °C).

190 °F (NIOSH, 2024)

86 °C

MP: 83-85 °C /Technical/

86.5 °C

Danger

H300: Fatal if swallowed [Danger Acute toxicity, oral]

P203, P260, P261, P262, P264, P264+P265, P270, P271, P272, P273, P280, P284, P301+P316, P302+P352, P304+P340, P305+P354+P338, P316, P317, P318, P320, P321, P330, P332+P317, P333+P317, P361+P364, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

H300+H310+H330 (70.7%): Fatal if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]

P203, P260, P261, P262, P264, P264+P265, P270, P271, P272, P273, P280, P284, P301+P316, P302+P352, P304+P340, P305+P354+P338, P316, P317, P318, P320, P321, P330, P332+P317, P333+P317, P361+P364, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Hazard Traits - Environmental tox; Hepatotoxicity and Digestive System Toxicity; Nephrotoxicity and Other Toxicity to the Urinary System; Neurotoxicity

99/164/EC

REACH registered substance: 2-methyl-4,6-dinitro-phenol (EC: 208-601-1)

4,6-Dinitro-o-cresol: HSNO Approval: HSR002979 Approved with controls

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

4,6-Dinitro-o-cresol (DNOC) was used as a pesticide until 1991. It is extremely toxic to humans. Symptoms of acute (short-term) and chronic (long-term) toxicity include profuse sweating, increased pulse and respiratory rates, thirst, fatigue, headache, appetite loss, and greenish-yellow pigmentation of the conjunctivae in humans. Bilateral cataracts and blindness have been observed in individuals chronically exposed to DNOC by ingestion. Effects to the respiratory, cardiovascular, gastrointestinal, and central nervous system (CNS) of chronically exposed workers have been reported. No information is available on the reproductive, developmental, or carcinogenic effects of DNOC in humans. EPA has not classified DNOC for potential carcinogenicity.

NIOSH; Criteria Document: Dinitro-o-cresol (1978) DHEW Pub. NIOSH 78-131.

USEPA/ODW; Health Advisories for 50 Pesticides (8/88), NTIS No. PB88-245931

U.S. Dept Health & Human Services/Agency for Toxic Substances Disease Registry; Toxicological Profile for Dinitrocresols (1995) NTIS # PB/95/264321

P047; As stipulated in 40 CFR 261.33, when 4,6-dinitro-o-cresol, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. 4,6-Dinitro-o-cresol is found on List B. Case No: 2190; Pesticide type: insecticide, fungicide, herbicide, antimicrobial; Case Status: No products containing the pesticide are actively registered. Therefore, we are characterizing the case as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects.; Active ingredient (AI): 4,6-dinitro-o-cresol; AI Status: The active ingredient is no longer contained in any registered products ... "cancelled."

Phenols do not behave as organic alcohols, as one might guess from the presence of a hydroxyl (-OH) group in their structure. Instead, they react as weak organic acids. Phenols and cresols are much weaker as acids than common carboxylic acids (phenol has pKa = 9.88). These materials are incompatible with strong reducing substances such as hydrides, nitrides, alkali metals, and sulfides. Flammable gas (H2) is often generated, and the heat of the reaction may ignite the gas. Heat is also generated by the acid-base reaction between phenols and bases.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

If material on fire or involved in fire: Extinguish fire using agent suitable for type of surrounding fire. (Material itself does not burn or burns with difficulty.) Keep run-off water out of sewers and water sources.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Environmental considerations: Land spill: Dig a pit, pond lagoon, holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Cover solids with a plastic sheet to prevent dissolving in rain or fire fighting water.

Environmental considerations: Water spill: Use natural deep water pockets, excavated lagoons; or sand bag barriers to strap material at bottom. Remove trapped material with suction hoses.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P047, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

Dinitrocresol is a waste chemical stream constituent which may be subjected to ultimate disposal by controlled incineration. Incinerate (1,000 °F minimum) with adequate scrubbing and ash disposal facilities.

A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

For more Preventive Measures (Complete) data for 4,6-Dinitro-o-cresol (19 total), please visit the HSDB record page.

8 hr Time Weighted Avg (TWA): 0.2 mg/cu m, skin.

Peak Exposure Recommendation: Transient increases in workers' exposure levels may exceed 3 times the value of the TLV-TWA level for no more than 15 minutes at a time, on no more than 4 occasions spaced 1 hour apart during a workday, and under no circumstances should they exceed 5 times the value of the TLV-TWA level. In addition, the 8-hour TWA is not to be exceeded for an 8-hour work period.

0.60 [mg/m3]

0.65 [mg/m3]

5.0 [mg/m3]

Excerpt from NIOSH Pocket Guide for Dinitro-o-cresol:

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

For more Personal Protective Equipment (PPE) (Complete) data for 4,6-Dinitro-o-cresol (10 total), please visit the HSDB record page.

LD50; Species: Anas platyrhynchos (Mallard duck) 5-7 month old males; oral 22.7 mg/kg (95% confidence limit: 18.0-28.5 mg/kg)

LC50; Species: Coturnix japonica (Japanese Quail) juvenile, 14 days posthatch; chemical incorporated into food (ad libitum) >5000 ppm for 5 days

LC50; Species: Eisenia fetida (Earthworm) adult, age >2 months, weight 300-400 mg; dermal 1.6 ug/sq cm for 48 hr

LC50; Species: Eisenia fetida (Earthworm) adult, age >2 months, weight 300-400 mg; ground spray (in artificial soil, 83.5% sand, 5% clay, pH 7, 10.5% organic matter, 35% moisture) 21 mg/kg soil for 28 days

For more Ecotoxicity Values (Complete) data for 4,6-Dinitro-o-cresol (30 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 300(2) to 23(3) indicate that 4,6-dinitro-o-cresol is expected to have moderate to very high mobility in soil(SRC). The pKa of 4,6-dinitro-o-cresol is 4.31(4), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). The results of an aquifer field study indicates the anionic form of 4,6-dinitro-o-cresol is more mobile in soil than the neutral form(6). Volatilization of the neutral species from moist soil surfaces is expected to be an important fate process(SRC) given a Henry's Law constant of 1.4X10-6 atm-cu m/mol at 25 °C(7). 4,6-Dinitro-o-cresol is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.00012 mm Hg at 25 °C(8). In soil, the nitro groups are reduced to amino groups; soil half-lives are reported to range from 0.1-15 days(8). Utilizing the Japanese MITI test, 4% of the Theoretical BOD was reached in 4 weeks(9) indicating that biodegradation is not an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), Koc values of 300(2) to 23(3) indicate that 4,6-dinitro-o-cresol is expected to adsorb to suspended solids and sediment(SRC). Volatilization of 4,6-dinitro-o-cresol from moist soil surfaces is expected to be an important fate process(SRC) given a Henry's Law constant of 1.4X10-6 atm-cu m/mole(5). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 37 and 273 days, respectively(SRC). According to a classification scheme(6), BCF values ranging from 56-64(7) and <2.9(8) suggest bioconcentration in aquatic organisms is moderate to low(SRC). 4,6-Dinitro-o-cresol is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(4). The half-life for the photolysis of 4,6-dinitro-o-cresol in water has been reported as approximately 253 hours at 20 °C(9). Utilizing the Japanese MITI test, 4% of the Theoretical BOD was reached in 4 weeks(8) indicating that biodegradation is not an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4,6-dinitro-o-cresol, which has a vapor pressure of 0.00012 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. At temperatures below 20 °C, a gas/particle partitioning model predicts that 4,6-dinitro-o-cresol will exist in both the vapor and particulate phases. Vapor-phase 4,6-dinitro-o-cresol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 53 days(SRC), calculated from its rate constant of 3.0X10-13 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 4,6-dinitro-o-cresol may be removed from the air by wet and dry deposition(SRC). 4,6-Dinitro-o-cresol absorbs UV light at wavelenghts extending beyond 400(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

4,6-Dinitro-o-cresol was detected on Romanian plums at harvest time; however, residues were below tolerance limits(1). Residues were detected on potatoes taken from East German fields treated with the compound, but it was suggested that cooking would remove most of the dinitrocresol because it is steam-volatile(2).

IDENTIFICATION: 4,6-Dinitro-ortho-cresol (DNOC) is a yellow crystalline solid. It is partly soluble in water. DNOC was fungicide, herbicide and insecticide that is no longer registered for use in the U.S. HUMAN STUDIES: Symptoms of DNOC toxicity include restlessness, a sensation of heat, flushed skin, sweating, thirst and deep rapid respiration and tachycardia, severe increase in body temperature, cyanosis leading to collapse, coma and death. Effects are enhanced at high temperatures. Cardiovascular effects have been noted secondary to cellular anoxia but do not appear to be consistent cardinal signs of DNOC exposure in humans. Elevated pulse rates, tachycardia, and palpitations were observed in several patients. Negative results were found in human lymphocytes for sister chromatid exchanges and unscheduled DNA synthesis in both the presence and the absence of metabolic activation at doses up to 50 ug/mL. ANIMAL STUDIES: Dietary administration of DNOC for up to 90 days decreased body weight gain in rats, mice and dogs, usually without significant alteration in food consumption. At high doses, the liver is affected , as shown by an increased activity of liver enzymes. Blood urea levels were also increased at high doses. Environmental temperatures influenced the mortality rate among rats orally dosed with DNOC. Six of 12 rats died after receiving 20 mg/kg at 37-40 °C, while only 2 of 12 rats died after receiving twice the dose (40 mg/kg) at 20-22 °C. Application of DNOC to skin of rabbits induced edema. It was a skin sensitizer in the guinea pig and corrosive to the eyes of the rabbit. Diets containing 0.25% DNOC (or 2500 mg/kg feed) were administered for 2 days to 5-day-old white Peking ducklings. Cataracts were produced within 24 hr in all the birds. This concentration induced 56% mortality the first day and 100% the second day. At high doses, DNOC has a slight effect on reproduction in the form of reduction of body weight and litter size. Other reproduction parameters were not affected. DNOC did not induce any teratogenic effects in pregnant rats receiving oral doses from gestation day 6 to day 15. In rabbits treated orally, the high dose was maternally toxic, inducing mortality. At this high dose level, teratogenic effects included microphthalmia and hydroencephaly or microencephaly. Pregnant rabbits exposed to a cutaneous application of DNOC during gestation, induced maternal toxicity at a high dose resulting in some embryotoxicity but not teratogenicity. No evidence of teratogenicity or embryotoxicity were noted in mice treated orally or by ip administration during pregnancy. DNOC has been shown to have mutagenic potential in bacterial mutagenicity systems (strains TA98 and TA100) both in the presence and absence of metabolic activation. The mutagenic response obtained in the Ames test was markedly reduced or abolished when the nitroreductase strains TA98NR and TA100NR were used, indicating involvement of nitroreductase. ECOTOXICITY STUDIES: DNOC has little effect on soil microorganisms. Acute toxicity to aquatic organisms is variable. Fish were the most sensitive species in laboratory tests. DNOC is acutely toxic for birds, mammals and honeybees.

4,6-Dinitro-o-cresol is an uncoupler of oxidative phosphorylation. It is believed to cause an acceleration of metabolic processes that are part of the tricarboxylic acid (TCA) cycle. DNOC produces its accelerative effect by increasing the permeability of the inner mitochondrial membrane to Ca+, altering the proton electrochemical gradient and thus interrupting the phosphate transfer to adenosine diphosphate (ADP) to form ATP. Uncoupling allows electron transport to proceed unchecked even when ATP synthesis is inhibited. As a consequence, more ADP and inorganic phosphate are available to drive the TCA cycle, and most of the energy produced from catabolism of glucose is not stored in high energy phosphate bonds as ATP but is given off as heat. This results in the elevated body temperature and related effects characteristic of DNOC toxicity. (L198)

/BIRDS and MAMMALS/ Acute symptoms: ataxia, wings crossed high over back, and tail tremors or shivering... tachypnea, dyspnea, ruffed or unkempt feathers, tetany with legs extended posteriorly. Symptoms persisted in a few survivors for up to 2 wk /in 5-7 month old male mallards, oral admin/.

/AQUATIC SPECIES/ /Toxicity threshold (cell multiplication inhibition test):/ bacteria (Pseudomonas putida) 16 mg/L for 16 hr; Green algae (Scenedesmus quadricauda) 13 mg/L for 7 days; Protozoa (Entosiphon sulcatum) 5.4 mg/L for 72 hr

/AQUATIC SPECIES/ Structural and functional alterations in heptocytes of the European eel, Anguilla anguilla, following a 4 week exposure to 5, 50, and 250 ug/L dinitro-o-cresol were investigated by means of electron microscopy and biochemistry. Whereas phenological parameters (growth, condition factor) are unaffected, ultrastructural and biochemical alterations are detectable at 50 and 5 ug/L DNOC, respectively. Structural modifications include: rounding up of the nuclei; fractionation and reduction of the rough endoplasmic reticulum; proliferation of the smooth endoplasmic reticulum mitochondria, peroxisomes, and lysosomes, bundles of rod shaped smooth endoplasmic reticulum profiles; annulate lamellae; membrane whorls within mitochondria; crystallization of the peroxisomal matrix and glycogen bodies; glycogen depletion and lipid augmentation. Structural changes can be correlated to an increase in hepatic lipid and protein contents as well as stimulation of mitochondrial (cytochrome c oxidase), peroxisomal (catalase, allantoinase, uricase), lysosomal (arylsulfatase), and microsomal (esterase) enzymes. An increase in NADPH-cytochrome c reductase and cytochrome P450 as well as UDP-glucuronyltransferase and arylsulfotransferase activities in the microsomal fraction document an induction of heptic biotransformation as a functional correlate to smooth endoplasmic reticulum proliferation. Maximum inducibility of biotransformation enzymes at 50 ug/L indicates a biphasic, concentration-dependent reaction of eel liver.

/PLANTS/ Very phytotoxic.

For more Ecotoxicity Excerpts (Complete) data for 4,6-Dinitro-o-cresol (7 total), please visit the HSDB record page.

Exposure to high levels of DNOC for short periods may cause convulsions, unconsciousness, and death. Exposure to low levels of DNOC may result in an increased basal metabolic rate, increased sweating, weight loss, and increased heart rate, breathing rate, and body temperature. Other effects from DNOC exposure may include difficulty in breathing, headache, drowsiness, dizziness, and a yellowing of skin and the whites of the eyes. (L198)

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of August 9, 2018: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for 4,6-dinitro-o-cresol is available.[Available from, as of August 8, 2018: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

4,6-Dinitro-o-cresol has been detected, not quantified in the wastewater effluents from two US chemical plants(1). It was qualitatively detected in the wastewater from the Oak Ridge Gaseous Diffusion Plant(2). 4,6-Dinitro-o-cresol has been detected not quantified in the wastewaters of a pest control plant in England and in the wastewaters of a specialty chemical plant at a concentration of 18 ppm(3). Water from fighting a fire at a chemical warehouse in Basel, Switzerland on Nov 1, 1986 discharged an estimated 5-8 tons of pesticides into the Rhine River(4,5). The warehouse stored 65.9 metric tons of 4,6-dinitro-o-cresol and the discharge to the Rhine River was estimated to be 660-2000 kg(4).

Medical surveilance shall be made available ... to all employees subject to occupational exposure to dinitro-o-cresol (DNOC). Preplacement examinations ... (a) Comprehensive medical and work histories with special emphasis directed towards any existing disorders, particularly of the lung, liver, kidney, thyroid gland, nervous and cardiovascular systems, skin, and eyes. (b) Urinalysis ... , complete blood count, hematocrit, and liver and kidney function test. (c) Evaluation of workers ability to use positive and negative pressure respirators.

Biological monitoring shall be provided to all employees engaged in the following agriculturally related occupations: mixers, loaders, ground and aerial applicators, and flaggers. This monitoring shall consist of weekly sampling and analysis of workers' blood for dinitro-o-cresol content during the period of expected exposure. ... Such monitoring shall be performed to insure that no worker absorbs an unacceptable amount of the compound. ... Unacceptable absorption of dinitro-o-cresol ... is demonstrated when the DNOC concentration equals or exceeds 20 ug/g of whole blood.

P047; As stipulated in 40 CFR 261.33, when 4,6-dinitro-o-cresol, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. 4,6-Dinitro-o-cresol is found on List B. Case No: 2190; Pesticide type: insecticide, fungicide, herbicide, antimicrobial; Case Status: No products containing the pesticide are actively registered. Therefore, we are characterizing the case as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects.; Active ingredient (AI): 4,6-dinitro-o-cresol; AI Status: The active ingredient is no longer contained in any registered products ... "cancelled."

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. 4,6-Dinitro-o-cresol is included on this list.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Dinitrocresol is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 10 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... . /Dinitrocresol/

Acute toxic effects are... related to DNOC acting directly on cell metabolism and interfering with oxidative phosphorylation. DNOC is believed to cause an acceleration of metabolic processes that are part of the tricarboxylic acid (TCA) cycle. During the TCA cycle, the energy produced from the catabolism of glucose is stored in the form of ATP. DNOC produces its accelerative effect by interrupting the phosphate transfer to adenosine diphosphate (ADP) to form ATP. Uncoupling allows electron transport to proceed unchecked even when ATP synthesis is inhibited. As a consequence, more ADP and inorganic phosphate are available to drive the TCA cycle, and most of the energy produced from catabolism of glucose is not stored in high energy phosphate bonds as ATP but is given off as heat.

...DNOC is a potent protonophore acting as a classical uncoupler of oxidative phosphorylation in rat liver mitochondria by dissipating the proton electrochemical gradient. Treatment of Ca2+-loaded mitochondria with uncoupling concentrations of DNOC results in mitochondrial permeability transition, associated with membrane protein thiol oxidation by reactive oxygen species.

DNOC, like other substituted dinitrophenols, is an uncoupler of mitochondrial oxidative phosphorylation. Oxidation and phosphorylation are tightly coupled because oxidation cannot proceed via the respiratory chain without concomitant phosphorylation of adenosine diphosphate (ADP) to adenosine triphosphate (ATP). The rate of mitochondrial respiration is therefore controlled by the concentration of ADP. By preventing phosphorylation of ADP without interfering with electron transfer, DNOC dissociates oxidation in the respiratory chain from phosphorylation. This results in respiration becoming uncontrolled since the concentrations of ADP and inorganic phosphate no longer limit the rate of respiration. Oxygen consumption and the release of energy in the form of heat therefore increase, because energy is no longer captured by ADP to form ATP. As a consequence the shortage of ATP in critical organs, such as heart and respiratory muscles, may lead to the blocking of their vital functions. Increased oxygen consumption and dissipation of energy in the form of heat represent the hallmark of the pharmacological and toxicological effects of DNOC.

Formulated DNOC was applied to the shaved skin of male and female rats in a single dose of 18.1 mg DNOC/kg b.w. and was kept in contact with the skin for 8 hr. Two formulations were used: water-based (621 g a.i./L) and oil-based (130 g a.i./L). ... The average half life absorption time (time from exposure required to reach 50% of DNOC blood peak concentration) was 15 hr for males and 13 hr for females. The average half life elimination time (time required for DNOC blood concentration to decrease to 50% of its peak value after reaching a peak) was 24 hr. ... When applied under the same conditions as an oily formulation, the peak plasma concentrations represent 5.0% of the applied dose in males and 5.8% in females (38-45 ug/mL of blood). The peak plasma level occurred after 8 hr in males and 24 hr in females. The average absorption half-liife was 2.8 hr and the average elimination half-life was 34 hr.

The major route of elimination is in the urine, with a half life in the rat of between 24 and 36 hours following oral administration of 0.4 mg/kg body weight (bw). A shorter half life of 6.5 hours has been reported in the rabbit. Excretion is reported to be slower in humans, and half lives ranging from 4 days to over 6 days have been reported in heavily exposed workers.

The half-life in man is 5.78 days.

DNOC appears to be metabolized to less toxic metabolites readily eliminated via the urine. Although small quantities of DNOC may be conjugated, most of the dose appears to be reduced to mono amino derivatives and then subsequently conjugated prior to excretion. These relatively harmless metabolites have been found in the urine and kidney of humans and animals exposed to DNOC.

The major metabolic route in the rat and the rabbit following oral administration is by reduction to 6-amino-4-nitro-o-cresol (6-ANOC, 10 - 12% of administered dose) and, to a lesser extent, to 4-amino-6-nitro-o-cresol (4-ANOC), 4-ANOC conjugates and other minor metabolites.

In the rabbit, 5% of DNOC single oral doses of 20 or 30 mg/kg is excreted unchanged and 1% as conjugated DNOC in 2-day urine collection. The main metabolic pathway is the reduction of DNOC to 6-amino-4-nitro-o-cresol (6-ANOC), and to a lesser extent to 4-amino-6-nitro-o-cresol (4-ANOC). Urinary content of 6-ANOC accounted for 11-12% of the administered dose. Small amounts of other metabolites, such as 4-ANOC conjugates and 3-amino-5-nitrosalicylic acid (3-ANSA), which is produced via an oxidative pathway, are also excreted in the urine.

The metabolism of 4,6-dinitro-o-cresol (DNOC) was studied in rats and in the rabbit. Inbred Wistar-rats received labeled and unlabeled DNOC by gavage in doses of 0.4 to 10 mg/kg bw, with urine and feces being collected separately. When labeled DNOC was administered, blood, a number of organs, and the residual carcasses were collected at sacrifice 1 or 3 days after treatment for use in radioactivity measurements. A female albino white-New-Zealand-rabbit received 76 mg of unlabeled DNOC by gavage, with urine being collected via a catheter at regular intervals over the ensuing 24 hr. ...In rats receiving labeled DNOC in a dose of 0.4 mg/kg, radioactivity was eliminated with a half time of 1-1.5 days. Approximately 25% of the introduced dose was still contained in the body at sacrifice 3 days after treatment, with the major portion being concentrated in the residual carcass. Here, the introduced dose had little effect on the overall pattern of DNOC distribution. The metabolites detected in rat urine were identified as 4,6-diacetamido-o-cresol (DAAOC), 3,5-dinitro-2-hydroxybenzylalcohol, 4-acetamido-6-nitro-o-cresol, 6-acetamido-4-nitro-o-cresol, DNOC, and 6-amino-4-nitro-o-cresol, with 4-acetamido-6-nitro-o-cresol, 6-acetamido-4-nitro-o-cresol, 6-amino-4-nitro-o-cresol, and DAAOC also being present as conjugates. The metabolites detected in rabbit urine were identified as DAAOC, amino-nitro-o-cresol, acetamido-nitro-o-cresol, and 6-amino-4-nitro-o-cresol. The authors conclude that nitro group reduction, followed by acetylation or conjugation, constitutes the major pathway of DNOC biotransformation. When DNOC is administered with a methanol extract of wheat leaves, the major biotransformation reaction is methyl group oxidation.

DNOC was rapidly metabolized by rat cecal microorganisms and could /no/ longer be detected after 1 hr. Simultaneously, 6-ANOC (the monoamine derivative of DNOC) was detected in increasing amounts, reaching maximum levels after 1 hr, indicating an 80% DNOC conversion. Thereafter, the 6-ANOC concentration decreased until it represented only 3% of the initial DNOC concentration at 12 hr. DAOC (the diamine derivative) concentrations increased over the entire incubation period and reached maximum levels at 12 hr, when it represented 90% of the DNOC conversion. When incubated alone 6-ANOC concentrations decreased and DAOC concentrations increased in the same time-dependent manner observed in the DNOC experiments. Analogous experiments using DNBP (dinoseb) and 6-ANBP (the monamine derivative of dinoseb) gave similar results. However, the metabolic turnovers were slower. Rat cecal microorganisms metabolize DNOC and DNBP to the corresponding 6-amino compounds, which are in turn reduced to the diamino derivatives. Hematologic effects reported in rats exposed to DNBP may have been induced by amino metabolites formed in the intestine from DNBP metabolism.

4,6-Dinitro-o-cresol is absorbed via oral, inhalation, and dermal routes, then binds to albumin and is distributed to most tissues, including the lungs, heart, liver, kidney, brain, spleen, and muscle. Although small quantities of DNOC may be conjugated, most of it appears to be reduced to less toxic mono amino derivatives, such as 6-amino-4-nitro-o-cresol and 6-acetamido-4-nitro-o-cresol, and then subsequently conjugated. DNOC and its metabolites are eliminated primarily via the urine. (L198)

Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.

Chemicals used to destroy pests of any sort. The concept includes fungicides (FUNGICIDES, INDUSTRIAL); INSECTICIDES; RODENTICIDES; etc.

Chemical agents that uncouple oxidation from phosphorylation in the metabolic cycle so that ATP synthesis does not occur. Included here are those IONOPHORES that disrupt electron transfer by short-circuiting the proton gradient across mitochondrial membranes.

DNOC is rapidly absorbed following inhalation, ingestion and via skin contact. Skin absorption is more rapid when DNOC is applied in an oily formulation rather than in aqueous solution, peak plasma concentration is higher and occurs earlier, indicative of a solvent effect on skin penetration.

It was shown that the amount of DNOC absorbed from the gastrointestinal tract of the rat, and the resulting blood level, depend on the type of fat administered shortly after dosing with DNOC (olive oil or castor oil). Gastrointestinal uptake of DNOC increases when 0.2 mL of olive oil is given, whereas 1.0 mL has no influence. Castor oil in a non- purgative dose (0.2 mL) inhibits resorption, and then slows down the decrease of DNOC blood level over a period of 48 h. Rapeseed oil, which is more slowly absorbed than olive oil, shows only a slight inhibitory effect on DNOC digestive absorption.

Blood plasma analysis after dinitro-o-cresol dosing of cows showed at least 95% of the absorbed DNOC bound to plasma proteins; the fact that identical doses of DNOC in ruminants give far lower blood concentrations than in rats and rabbits may be explained by the extensive reduction of the compounds in the rumen.

When Hedolit (0.1 g) was applied dermally to guinea pigs, it could be detected in the blood serum and to a lesser extent in the testes and semen.

For more Absorption, Distribution and Excretion (Complete) data for 4,6-Dinitro-o-cresol (10 total), please visit the HSDB record page.

EPA cancelled DNOC's registration as a pesticide in 1991. DNOC was also used as a contact herbicide for the control of broad-leaf weeds in cereals and for the pre- harvest desiccation of potatoes and leguminous seed crops.

For 4,6-dinitro-o-cresol (USEPA/OPP Pesticide Code: 037507) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

USA: Not registered. Outside USA: Trifocide in The Netherlands.

The active ingredient is no longer contained in any registered pesticide products ... "cancelled."

Dormant spray for insect eggs, apple scab. The triethanolamine salt has promise as a complete dormant apple spray for light infestations of mite and aphid eggs as well as other pests. The sodium salt has been used as a weed killer and on apple, peach trees to thin fruit. /Former USA/

For more Uses (Complete) data for 4,6-Dinitro-o-cresol (9 total), please visit the HSDB record page.

(1984) 6.94X10+4 g.

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#3293]

Prepared by sulfonation of o-cresol followed by controlled nitration.

DNOC can be made by sulfonation of o-cresol followed by controlled nitration.

Premix Partners: Refined petroleum distillate.

Flakes, flowable, wettable powder.

Emulsifiable concentrate, wettable powder, flowable.

... Pastes of sodium or amine salts, ammonium sulfate being added as "activator"; solution in petroleum oil.

Tradenames: 'Ibertox' (Caffaro); 'Trifocide' (Cerexagri); ...'Selinon' (Bayer); 'Sandoline' (Sandoz). Discontinued names: 'Antinnonin' * (Bayer); 'Sinox' * (FMC, Truffaut) mixtures: 'Carbofort' * (+ anthracene oil) (Siegfried).

Phenol, 2-methyl-4,6-dinitro-: ACTIVE

The WHO Recommended Classification of Pesticides by Hazard identifies DNOC (technical grade) as Class IB: highly hazardous; Main Use: insecticide-applied to soil: not used with herbicides or plant growth regulators; herbicide. According to the PIC /Prior Informed Consent/ Convention, export of /DNOC and its salts/ can only take place with the prior informed consent of the importing Party.* The WHO Recommended Classification of Pesticides by Hazard identifies DNOC (technical grade) as Class IB: highly hazardous; Main Use: insecticide-applied to soil: not used with herbicides or plant growth regulators; herbicide.[WHO International Programme on Chemical Safety; The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 2009 p.22,51 (2010)] **PEER REVIEWED**

Of the six DNOC isomers, the 4,6-dinitro isomer is the most commercially important.

... Highly phytotoxic; cannot be used successfully on actively growing plants.