1,4-Naphthoquinone

log Kow = 1.71

1.8

1.422 (NTP, 1992) - Denser than water; will sink

1.422

1.4 g/cm³

1.422 no temp

Yellow triclinic needles from alcohol or petroleum ether

YELLOW POWDER

Yellow crystals

less than 1 mg/mL at 70 °F (NTP, 1992)

Sol in alkali hydroxide soln; sparingly sol in cold water; slightly sol in petroleum ether; freely sol in carbon disulfide, acetic acid, hot alcohol, ether, benzene, and chloroform

Very soluble in alkali hydroxide solutions.

Volatile with steam.

In water, 0.35 g/100 ml at 25 °C

Solubility in water, g/100ml at 25 °C: 0.35

Sublimes below 212 °F (NTP, 1992)

Sublimes

277 °F (NTP, 1992)

128.5 °C

126 °C

128.5 °C

5.46 (NTP, 1992) - Heavier than air; will sink (Relative to Air)

Relative vapor density (air = 1): 5.5

0.00018 [mmHg]

2.6 Pa at 50 °C (= 0.0195 mm Hg at 50 °C)

Vapor pressure, Pa at 50 °C: 2.6

0.0195 [mm Hg] @50 °C

1,4-naphthoquinone appears as yellow needles or brownish green powder with an odor of benzoquinone. (NTP, 1992)

Dry Powder

Yellow solid with a pungent odor; [ICSC] "Begins to sublimes below 100 deg C." [Merck Index]

YELLOW CRYSTALS OR FLAKES WITH PUNGENT ODOUR.

This chemical does not meet GHS hazard criteria for 0.8% (5 of 620) of reports.

Danger

H301 (99.2%): Toxic if swallowed [Danger Acute toxicity, oral]；H314 (32.3%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]；H315 (66.9%): Causes skin irritation [Warning Skin corrosion/irritation]；H317 (88.4%): May cause an allergic skin reaction [Warning Sensitization, Skin]；H318 (30.3%): Causes serious eye damage [Danger Serious eye damage/eye irritation]；H319 (66.9%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H330 (95%): Fatal if inhaled [Danger Acute toxicity, inhalation]；H334 (17.1%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]；H335 (81.6%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]；H400 (95%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410 (37.3%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P233, P260, P261, P264, P264+P265, P270, P271, P272, P273, P280, P284, P301+P316, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P351+P338, P305+P354+P338, P316, P317, P319, P320, P321, P330, P332+P317, P333+P317, P337+P317, P342+P316, P362+P364, P363, P391, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 620 reports by companies from 34 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 5 of 620 reports by companies.；There are 33 notifications provided by 615 of 620 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Chemical: 1,4-Naphthalenedione

Regulation (EC) No 1107/2009 (amended)

1,4-Naphthalenedione is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1,4-Naphthalenedione are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 11-11-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/22758；Status: Cease Manufacture Update: 24-11-2017 https://echa.europa.eu/registration-dossier/-/registered-dossier/21265

1,4-Naphthoquinone: Does not have an individual approval but may be used under an appropriate group standard

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.)

Flash point data for this compound are not available; however, it is probably combustible. (NTP, 1992)

Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

A skin, eye, and respiratory tract irritant; [ICSC] Very toxic after ingestion, inhalation, or skin contact; Effects on experimental animals include somnolence, weight loss, liver injury, methemoglobinemia, tumors, and reproductive changes; [MSDSonline]

U166; As stipulated in 40 CFR 261.33, when 1,4-naphthoquinone, 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 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).

1,4-NAPHTHOQUINONE may react with many acids and bases liberating heat and flammable gases (e.g., H2). The heat may be sufficient to start a fire in the unreacted portion of the ketone. May react with reducing agents such as hydrides, alkali metals, and nitrides to produce flammable gas (H2) and heat. Incompatible with isocyanates, aldehydes, cyanides, peroxides, and anhydrides. May react violently with aldehydes, HNO3, HNO3 + H2O2, and HClO4.

Fires involving this material can be controlled with a dry chemical, carbon dioxide, foam, or Halon extinguisher. (NTP, 1992)

Use water spray, powder, foam, carbon dioxide.

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Give one or two glasses of water to drink. Induce vomiting (ONLY IN CONSCIOUS PERSONS!). Give a slurry of activated charcoal in water to drink. Refer for medical attention .

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.；SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.；INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.；INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.；STORAGE PRECAUTIONS: You should protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

[40 CFR 240-280, 300-306, 702-799 (7/1/2005)] Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U166, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Good candidate for rotary kiln incineration, with a temperature range of 820 to 1,600 °C and a residence time of seconds. Also a good candidate for fluidized bed incineration, with a temp range of 450 to 980 °C and a residence time of seconds.

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Sweep spilled substance into covered containers. Carefully collect remainder. Then store and dispose of according to local regulations.

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:；IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.；SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.；FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

The addition of sublytic concentrations of both naphthoquinones and heme leads to a synergistic lysis of the organisms /Trypanosoma brucei/ in vitro. /Naphthoquinones/

The mechanisms of toxicity of 1-naphthol and two of its metabolites 1,2-, and 1,4-naphthoquinone, to freshly isolated rat hepatocytes was studied. 1-Naphthol and both naphthoquinones exhibited a dose-dependent toxicity to hepatocytes. (14)C-1-Naphthol was metabolized by hepatocytes predominantly to its glucuronate and sulfate conjugates, but small amounts of covalently bound products were also formed. Blebbing on the surface of the hepatocytes was observed following exposure to 1-naphthol and the naphthoquinones, together with a dose-dependent decr in intracellular GSH, which preceded the onset of cytotoxicity. The toxicity of 1-naphthol and the naphthoquinones was potentiated by dicoumarol, an inhibitor of DT-diaphorase (NADPH:quinone oxidoreductase). This enhanced toxicity was accompanied by a greater amount of surface blebbing, an increased depletion of intracellular GSH, particularly in the case of 1-naphthol and 1,4-naphthoquinone, and a decreased metabolism of 1-naphthol to its conjugates with variable effects on the amount of covalently bound products formed. Apparently, the toxicity of 1-naphthol may be mediated by the formation of 1,2-naphthoquinone and/or 1,4-naphthoquinone, which may then be metabolized by 1-electron reduction to naphthoquinone radicals. These, in turn, may covalently bind to important cellular macromolecules or enter a redox cycle with molecular oxygen thereby generating active oxygen species. Both of these processes appear to play a role in producing the cytotoxic effects of 1-naphthol.

1,4-Naphthoquinone completely inhibited the gametotoxic effect of human chorionic gonadotropin in toads.

A study determined whether taurine would protect isolated rat hepatocytes against the cytotoxic effects of three different toxic compounds, carbon-tetrachloride (CCl4), hydrazine, and 1,4-naphthoquinone. Hepatocytes were isolated from male Sprague-Dawley-rats and exposed to vapor from 7.5, 10, and 15 uL of CCl4. Only those exposed to the highest level demonstrated a marked loss of viability (70%) and lactate-dehydrogenase (LDH) leakage (35%). The addition of taurine showed a dose related protection against cytotoxicity measured as leakage of LDH after 45 minutes. Cells exposed to 1,4-naphthoquinone demonstrated a dose related decrease in hepatocyte viability, a corresponding increase in LDH leakage, and a decrease in ATP after 180 minutes of incubation. Taurine caused an attenuation of the cytotoxicity with the dose response relationship being shifted to the right with a statistically significant difference in viability, LDH leakage, and ATP depletion compared to 1,4-naphthoquinone alone at an exposure level of 100 umol. Hepatocytes incubated with various concentrations of hydrazine demonstrated a dose dependent loss of cell viability and an increase in leakage of LDH. Taurine (15 mM) significantly reduced this trypan-blue uptake and LDH leakage after exposure to 20 mM and 24 mM hydrazine. Taurine had no effect on depletion of ATP at any hydrazine concentration. The authors conclude that taurine is able to protect hepatocytes against cytotoxicity caused by different compounds.

Possible antimutagenic activity of 26 vitamins and related compounds - ascorbic acid, beta-carotene, cyanocobalamin, folic acid, nicotinic acid, nicotinamide, pantothenic acid, pyridoxale, pyridoxamine, pyridoxine, retinal, retinol, retinoic acid, retinyl acetate, retinyl palmitate, riboflavin, riboflavin 5'-phosphate, flavin adenine dinucleotide (FAD), alpha-tocopherol, alpha-tocopherol acetate, vitamins K(1), K(3), K(4), 1,4-naphthoquinone, and coenzyme Q(10) - was tested against six heterocyclic amine (HCA) mutagens, i.e., 2-amino-3-methyl-imidazo[4, 5-f]quinoline (IQ), 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in the Salmonella/reversion assay using tester strains Salmonella typhimurium TA 98 and TA 100. Retinol, retinal, riboflavin, riboflavin 5'-phosphate, FAD, vitamins K(1), K(3), K(4), 1,4-naphthoquinone, and coenzyme Q(10) caused a concentration-dependent decrease in the mutagenicity of all six mutagens in both tester strains. Quantification of antimutagenic potencies by calculating ID(50)1000; vitamin K(1): 401-740; vitamin K(3) (menadione): 85-590; vitamin K(4): 45-313; 1,4-naphthoquinone: 170-290; coenzyme Q(10): 490-860. In general, there were no major differences between HCAs tested except in part with Trp-P-2 nor between the two tester strains. In enzyme kinetic experiments with Salmonella, retinol, vitamins K(3), and K(4) behaved as competitive inhibitors of IQ induced mutagenesis. However, at the highest concentration of menadione (200 nmol/plate) and of riboflavin 5'-phosphate (2000 nmol/plate), non-competitive inhibition was observed. At other concentrations of riboflavin 5'-phosphate and at all concentrations of FAD, meaningful interpretation of enzyme kinetics were not possible. Reduction of the activity of 7-eth

LD50 Peromyscus maniculatus (Deer mouse) oral 470 mg/kg

LC50 Abra aequalis (Common atlantic abra) 60 mg/L/14 days; static /formulated product/

LC50 Anabaena variabilis (Blue-green algae) >100 mg/L/14 days; static /formulated product/

LC50 Chlorella pyrenoidosa (Green algae) >100 mg/L/14 days; static /formulated product/

For more Ecotoxicity Values (Complete) data for 1,4-NAPHTHOQUINONE (9 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 16(SRC), determined from a structure estimation method(2), indicates that 1,4-naphthoquninone is expected to have very high mobility in soil(SRC). Volatilization of 1,4-naphthoquinone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.97X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 1,4-Naphthoquinone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.69X10-4 mm Hg(SRC), determined from a fragment constant method(4). 1,4-Naphthoquinone absorbs at wavelengths between 290 and 520 nm(5) and therefore is expected to be susceptible to direct photolysis by sunlight(SRC). 1,4-Naphthoquinone (at 500 mg/kg soil) required 9 days for complete biodegradation in chernozem soil(6). 1,4-Naphthoquinone (at 1000 mg/kg soil) was 80% degraded within 22 days in a chernozem soil(7) and had a half-life of 1.2 days in soil in another study(8).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 16(SRC), determined from a structure estimation method(2), indicates that 1,4-naphthoquinone is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.97X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 0.6(SRC), from its log Kow of 1.71(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 1,4-Naphthoquinone is oxidized in a standard biodegradability test utilizing a sewage inoculum, having a 5 day BOD of 38% of the theoretical value(8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,4-naphthoquinone, which has an estimated vapor pressure of 1.69X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. However, monitoring data have detected 1,4-naphthoquinone adsorbed to atmospheric particulate matter collected from urban air samples(3,4), waste incinerator fly ash(5), tailpipes of diesel and gasoline engines(6) and emissions from wood combustion(7,8). Vapor-phase 1,4-naphthoquinone 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 about 5 days(SRC), calculated from its rate constant of 3.1X10-12 cu cm/molecule-sec at 25 °C(9). Vapor-phase 1,4-naphthoquinone is also degraded in the atmosphere by reaction with ozone; the half-life for this reaction in air is estimated to be about 6.5 hours(SRC), calculated from its rate constant of 1.75E-18 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(10). 1,4-Naphthoquinone absorbs at wavelengths between 290 and 520 nm(11) and therefore is expected to be susceptible to direct photolysis by sunlight(SRC). Particulate-phase 1,4-naphthoquinone may be removed from the air by wet or dry deposition(SRC).

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.；Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect

Cough. Sore throat. Burning sensation.

Redness. Burning sensation. Pain.

Redness. Pain. Blurred vision.

Abdominal pain. Nausea. Vomiting.

1,4-Naphthoquinone was present in the flue gas following circulating fluid bed combustion of coal (Ruhr coal = 67,000 ng/normalized cu m; Poland coal = 6800 ng/normalized cu m; South Africa coal = 310 ng/normalized cu m; Spitsbergen coal = not detected)(1). 1,4-Naphthoquinone was qualitatively detected in incinerator fly ash from a municipal waste incinerator in Japan(2). 1,4-Naphthoquinone concn of 0.007-0.051 mg/g (organic carbon emitted) was detected in the fine particle emissions from fireplace combustion of six species of woods grown in the northern US (red maple, northern red oak, paper birch, eastern white pine, eastern hemlock, balsam fir)(3). 1,4-Naphthoquinone concn of 0.006-0.018 mg/g (organic carbon emitted) was detected in the fine particle emissions from fireplace combustion of six species of woods grown in the southern US (yellow poplar, white ash, sweet-gum, mockernut hickory, loblolly pine slash pine)(4).

1,4-Naphthoquinone was detected in particulate emissions collected from the tailpipes of diesel vehicles at concn of 4-8 ug/g (extract mass) and concn of 10 ug/g from gasoline engines in Japan(1).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 1,4-naphthoquinone can be estimated to be 16(SRC). According to a classification scheme(2), this estimated Koc value suggests that 1,4-naphthoquinone is expected to have very high mobility in soil.

URBAN/SUBURBAN: 1,4-Naphthoquinone was qualitatively detected in size-segregated atmospheric particles taken from air samples collected from a monitoring station roof in Kenmore Station, Boston, MA in the summer of 1994(1). 1,4-Naphthoquinone was qualitatively detected in particulates collected from urban air in Leeds, UK(2).

SOURCE DOMINATED: Air samples from a freeway tunnel in Japan contained a 1,4-naphthoquinone concn of 4 ug/g (extract mass)(1).

/SIGNS AND SYMPTOMS/ Quinones were ... suspected and shown to be responsible for brown discoloration of the cornea and exposed bulbar conjunctiva which gradually developed in workers ... long exposed to vapors associated with manufacturing and commercial application of synthetic aniline dyes ... /Quinones/

/SIGNS AND SYMPTOMS/ Chronic neurotoxic effects include vision disturbances. /From table; Quinones/

/BIOMONITORING/ Toxicological manifestations of 1,4-naphthoquinone include decreased number of erythrocytes in the blood, decresed sulfhydryl compounds and hemoglobin levels in the blood, hepatotoxicity, and depressed phagocytic activity of leukocytes. It also caused the appearance of methemoglobin and Heinz bodies in the blood.

Chemical: 1,4-Naphthalenedione

Regulation (EC) No 1107/2009 (amended)

1,4-Naphthalenedione is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1,4-Naphthalenedione are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 11-11-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/22758；Status: Cease Manufacture Update: 24-11-2017 https://echa.europa.eu/registration-dossier/-/registered-dossier/21265

1,4-Naphthoquinone: Does not have an individual approval but may be used under an appropriate group standard

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.)

U166; As stipulated in 40 CFR 261.33, when 1,4-naphthoquinone, 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 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).

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 5,000 lb or 2,270 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).

Quinones are alpha-beta-unsaturated ketones & react with sulfhydryl groups. ... Critical biochem lesion ... /involves/ -SH groups of enzymes such as amylase & carboxylase which are inhibited by quinones. Overall mechanism may involve binding of enzyme to quinone nucleus by substitution or addition at the double bond, an oxidative reaction with -SH group, & change in redox potential. /Quinones/

The mechanism of the toxicity of 1-naphthol in isolated rat hepatocyte was related to the formation of active oxygen species and the creation of an oxidative stress. Dicoumarol potentiated the cytotoxicity of 1-naphthoI by inhibiting DT-diaphorase and making more naphthoquinone metabolites available for redox cycling. /Naphthoquinone metabolites/

The possible mechanisms of naphthoquinone-induced toxicity to isolated hepatocytes were investigated by using three structurally-related naphthoquinones, 1,4-naphthoquinone (1,4-NQ), 2-methyl-1,4-naphthoquinone, and 2,3-dimethyl-1,4-naphthoquinone (2,3-diMe-1,4-NQ). 1,4-NQ was more toxic than 2-Me-1,4-NQ whereas 2,3-diMe-1,4-NQ did not cause cell death solubility-limited concentrations used. All three naphthoquinones extensively depleted intracellular GSH. However, the depletion of GSH induced by 1,4-NQ and 2-Me-1,4-NQ prior to cell death was more rapid and extensive than that induced by the non-toxic 2,3-diMe-1,4-NQ. Further studies demonstrated that 2,3-diMe-1,4-NQ was cytotoxic in the presence of dicoumarol, a cmpd which also potentiates the cytotoxicity of 1,4-NQ and 2-Me-1,4-NQ. To investigate the differential cytotoxicity of these three naphthoquinones, their relative capacities to redox cycle and to bind covalently to cellular nucleophiles were assessed. Redox cycling was investigated by using rat liver microsomes where the order of potency for quinone-stimulated redox cycling was 1,4-NQ ... 2-Me-1,4-NQ ... and 2,3-diMe-1,4-NQ as indicated by non-stoichiometric amounts of NADPH oxidation and O consumption. NADPH-cytochrome p450 reductase was implicated as the enzyme primarily responsible for naphthoquinone-stimulated redox cycling. The reactivity of the naphthoquinones with GSH and, by implication, with other cellular nucleophiles was 1,4-NQ > 2-Me-1,4-NQ and much > 2,3-diMe-1,4-NQ. Overall, these studies indicate that 2,3-diMe-1,4-NQ is not cytotoxic (except in the presence of dicoumarol) and this lack of toxicity may be related either to its lesser capacity to redox cycle and/or its inability to react directly with cellular nucleophiles.

Mechanisms by which quinones of varying reactivity alter mitochondrial membrane permeability were examined. Rat liver mitochondria were incubated with 0 to 10-3 molar (M) menadione (MQ), 1,4-naphthoquinone (NQ), 1,4-benzoquinone (BQ), 2,3-dimethoxy-1,4-naphthoquinone (DiOMeNQ), or 2,3-dimethyl-1,4-naphthoquinone (DiMeNQ) for 3 minutes after which 0 or 20 uM calcium-chloride was added. Release of calcium-ion (Ca2+) was monitored for 28 minutes. The effects on the state of polarization of the mitochondrial membrane and induction of mitochondrial swelling were determined. MQ, NQ, BQ, DiOMeNQ, and DiMeNQ accumulated all of the added Ca2+, but then released it following a lag period which decreased with increasing concentration. The concentrations inducing 50% Ca2+ release were: NQ, 1.6 uM; BQ, 5.3 uM; MQ, 41.6 uM; DiOMeNQ, 89.9 uM; and DiMeNQ 232.7 uM. The release of Ca2+ was accompanied by depolarization of the membrane potential and induction of mitochondrial swelling. Rat liver mitochondria were pretreated with 0.2 millimolar potassium-cyanide, then treated with 0 to 10-3 M NQ, BQ, MQ, DiOMeNQ, or DiMeNQ. Redox recycling reactivity of the compounds was assessed by measuring the rates of cyanide insensitive oxygen consumption (CIOC). All compounds except BQ caused concentration dependent increases in CIOC. MQ, DiOMeNQ, and DiMeNQ at their EC50s for Ca2+ release induced similar rates of CIOC. BQ and NQ induced very little CIOC at their EC50s. Rat liver mitochondria were pretreated with 0 or 400 nanomolar cyclosporin-A (cycA) and then incubated with NQ, BQ, MQ, DiOMeNQ, or DiMeNQ at their EC50s for Ca2+ release. This was followed by addition of 70 uM calcium-chloride. CycA completely inhibited release of Ca2+ by NQ, MQ, DiOMeNQ, and DiMeNQ. BQ accumulated very little Ca2+ before releasing it; however, the rate of release was slowed by cycA. The authors conclude that quinones that can undergo redox recycling (DiOMeNQ, DiMeNQ, MQ, and NQ) can permeabilize mitochondrial me

...1,4-Naphthoquinone (a reactive metabolite of 1-naphthol) with reducing agents such as NADPH and glutathione led to the formation of semiquinone-free radicals, which were detected with electron spin resonance spectroscopy. In the presence of glutathione as a reducing agent, menadione and 1,4-naphthoquinone underwent net one-electron reduction and conjugation with glutathione. At higher concentrations of glutathione, 1,4-naphthoquinone formed the semiquinones of both the monoconjugate and the diconjugate. The naphthoquinone-glutathione conjugates should redox cycle in a manner already known for the menadione conjugate. The semiquinone intermediates could be detected only under a nitrogen atmosphere and are probably the primary oxygen-reactive species responsible for the redox cycling of menadione- and naphthoquinone-glutathione conjugates.

Yields 1,4-dihydroxynaphthalene in pig; in pea; in Escherichia coli; in desulfovibrio gigas. /From Table/

Yields 5-hydroxy-1,4-naphthoquinone in juglans; 1,4-naphthosemiquinone in Escherichia coli. /From Table/

By using HPLC with reductive electrochemical detection, it was shown that 1-naphthol is converted to naphthoquinone metabolites by rat liver microsomes. At least two metabolic pathways, independent of cytochrome p450, appear to be involved. Fe-dependent lipid peroxidation appears to be responsible for at least part of the conversion of 1-naphthol to predominantly 1,4-naphthoquinone, and it seems likely that superoxide anion radical generation by NADPH-cytochrome p450 reductase could also catalyze this conversion. 1-Naphthol therefore seems to be converted to cytotoxic naphthoquinone metabolites by mechanisms dependent upon the generation of free radicals in rat liver microsomes.

Carbonyl reductase, ... a cytosolic monomeric oxidoreductase of broad specificity for carbonyl compounds, was the main NADPH-dependent quinone reductase in human liver, whereas DT-diaphorase, the principal 2-electron-transferring quinone reductase in rat liver, contributed a very minor part to the quinone reductase activity of human liver. Carbonyl reductase provides the enzymic basis for the reduction of a great variety of natural and man-made quinones. Generally, oxo groups at chemically reactive positions (K-region) were more efficiently reduced than those at more inert positions. The best substrates were the K-region o-quinones of the polycyclic aromatic hydrocarbons phenanthrene, pyrene, benz(a)anthracene, and benzo(a)pyrene. ... non-K-region o-quinones, 1,2-naphthoquinone and 1,2-anthraquinone ... were the best substrates. ...

For more Metabolism/Metabolites (Complete) data for 1,4-NAPHTHOQUINONE (9 total), please visit the HSDB record page.

Used as a polymerization regulator, fungicide, algicide, and to make dyes and pharmaceuticals; [Hawley] Used as a chemical intermediate, corrosion inhibitor, and stabilizer for transformer oils; [HSDB]

Farming (Pesticides) [Category: Industry]

Polymerization regulator for rubber and polyester resins; synthesis of dyes and pharmaceuticals

Chemical intermediate for dichlone, a fungicide (non-US use)

Chemical intermediate for dithianon, a fungicide (non-US use)

1,4-Naphthoquinone is industrially significant as an intermediate in anthraquinone synthesis.

(1977) AT LEAST 4.63X10+8 G

(1982) 1.40X10+7 G (PRINCPL CUSTMS DISTS)

(1983) 2.78X10+7 g

2023: 88,184 lb；2022: 35,274 lb；2021: 108,025 lb；2020: 52,910 lb

(1978) NOT PRODUCED COMMERCIALLY IN US

(1982) NOT PRODUCED COMMERCIALLY IN US

(1986) 10 thousand-500 thousand pounds

(1990) 10 thousand-500 thousand pounds

For more U.S. Production (Complete) data for 1,4-NAPHTHOQUINONE (7 total), please visit the HSDB record page.

Oxidation of 4-amino-1-naphthol hydrochloride with potassium dichromate & sulfuric acid (non-U.S. method)

The most important process for the production of 1,4-naphthoquinone is the oxidation of naphthalene with air or gases containing molecular oxygen at 250-450 °C and 0.1-1 mega pascal, over a catalyst containing vanadium pentoxide.

1,4-Naphthoquinone can be obtained in the liquid phase in greater than 90% yield by oxidation of naphthalene or its derivatives.

Miscellaneous Manufacturing

1,4-Naphthalenedione: ACTIVE

Fungicidal activity is found in a variety of quinones in general order 1,4-naphthoquinone greater than phenanthraquinone greater than p-benzoquinone greater than anthraquinone.