1,2-Naphthoquinone

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

1.450 at 25 °C

Golden yellow needles

Red needles from ether

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

Sol in alcohol, benzene, ether, 5% sodium hydroxide, 5% sodium bicarbonate; sol in concn sulfuric acid with green color; practically insol in water

SLIGHTLY SOL IN PETROLEUM ETHER

293 to 297 °F (Decomposes) (NTP, 1992)

145-7 °C (decomp)

1,2-naphthoquinone appears as golden yellow needles or brown powder. Decomposes to a bluish-black color on standing. (NTP, 1992)

Golden yellow solid; [Merck Index] May also be brown solid; Decomposes to a bluish-black color on standing; [CAMEO] Deep brown solid; [MSDSonline]

This chemical does not meet GHS hazard criteria for 6.2% (3 of 48) of reports.

Warning

H302 (89.6%): Harmful if swallowed [Warning Acute toxicity, oral]；H315 (93.8%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (93.8%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H335 (91.7%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 48 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 3 of 48 reports by companies.；There are 7 notifications provided by 45 of 48 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.

Ketones, such as 1,2-NAPHTHOQUINONE, are reactive with many acids and bases liberating heat and flammable gases (e.g., H2). The amount of heat may be sufficient to start a fire in the unreacted portion of the ketone. Ketones react with reducing agents such as hydrides, alkali metals, and nitrides to produce flammable gas (H2) and heat. Ketones are incompatible with isocyanates, aldehydes, cyanides, peroxides, and anhydrides. They react violently with aldehydes, HNO3, HNO3 + H2O2, and HClO4.

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)

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health 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)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.

...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.

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergi

EC50 Dunaliella bioculata (Green algae; general growth inhibition) 1 mg/L/50-72 hr (95% confidence limit: 0.8-2.5 mg/L); static /formulated product/

LD50 Peromyscus maniculatus (Deer mouse) oral 1600 mg/kg

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a structure estimation method(2), indicates that 1,2-naphthoquinone is expected to have very high mobility in soil(SRC). Volatilization of 1,2-naphthoquinone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.2X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 1,2-Naphthoquinone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-5 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2006).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a structure estimation method(2), indicates that 1,2-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 4.2X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 8.4(SRC), from an estimated log Kow of 2.11(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2006).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,2-naphthoquinone, which has an estimated vapor pressure of 9.9X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 1,2-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 30 hours(SRC), calculated from its rate constant of 1.3X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Vapor-phase 1,2-naphthoquinone is also degraded in the atmosphere by reaction with ozone; the half-life for this reaction in air is estimated to be about 13 hours(SRC), calculated from its rate constant of 2.1X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). 1,2-Naphthoquinone absorbs at wavelengths between 290 and 480 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC). Particulate-phase 1,2-naphthoquinone may be removed from the air by wet or dry deposition(SRC).

1,2-Naphthoquinone is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 1,2-naphthoquinone can be estimated to be 20(SRC). According to a classification scheme(2), this estimated Koc value suggests that 1,2-naphthoquinone is expected to have very high mobility in soil.

/SIGNS AND SYMPTOMS/ 1,2-naphthoquinone appears to be the metabolite in naphthalene poisoning that reacts with ocular tissues and is responsible for production of cataract and damage to the retina.

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

/BIOMONITORING/ ...The utility of adducts formed by the reaction of the naphthalene metabolites naphthalene-1,2-oxide, 1,2-naphthoquinone (1,2-NPQ), and 1,4-naphthoquinone (1,4-NPQ) with serum albumin (Alb) as biomarkers of exposure to polycyclic aromatic hydrocarbons /was investigated/. Cysteinyl serum Alb adducts of 1,2- and 1,4-NPQ (1,2-NPQ-Alb and 1,4-NPQ-Alb, respectively) but not of naphthalene-1,2-oxide were detected in 28 coke oven workers and 22 controls from the steel industry of northern China. The median level of 1,2-NPQ-Alb in coke oven workers (76.6 pmol/g) was significantly higher than that observed in controls (44.9 pmol/g; P=0.0027). However, the median level of 1,4-NPQ-Alb in exposed subjects was not significantly different from that of controls (48.6 versus 44.2 pmol/g; P=0.296). Levels of 1,2-NPQ-Alb were significantly correlated with exposure category (controls, side and bottom workers, and top-of-oven workers) as well as with previously measured levels of urinary naphthalene, 1- and 2-naphthol, and 1-pyrenol in these subjects. Multiple linear regression analysis revealed that 35% of the variation in 1,2-NPQ-Alb could be explained by the work category and age. A negative relationship between 1,2-NPQ-Alb and age was observed, suggesting that cytochrome P450 c metabolism diminished with age at approximately 3%/year of life.

An estimated BCF of 8.4 was calculated for 1,2-naphthoquinone(SRC), using an estimated log Kow of 2.11(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

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.

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, and change in redox potential. /Quinones/

1,2-Naphthoquinone is metabolized to 1,2-dihydroxynaphthalene in pigs. /From Table/

1-Naphthol was metabolized by tyrosinase, polyphenol oxidase, primarily to 1,2-naphthoquinone and to small amounts of 1,4-naphthoquinone as well as to covalently bound products. The inhibition of covalent binding by ethylenediamine, which reacts specifically with 1,2-naphthoquinone but not 1,4-naphthoquinone, suggested that most of the covalent binding was due to 1,2-naphthoquinone or a metabolite of similar structure.

In rat liver microsomal preparations, 1-naphthol is metabolized by the cytochrome p450 mixed function oxidase to 1,4-naphthoquinone and covalently bound species. The major binding species are derived from 1,4-naphthoquinone but not 1,2-naphthoquinone. 1-Naphthol is also metabolized by tyrosinase (monophenol monooxygenase; polyphenol oxidase) primarily to 1,2-naphthoquinone and covalently bound products; most of the covalent binding was derived from a 1,2-naphthoquinone derivative.

The hepatic microsomal metabolism of 1-naphthol, 1,2- and 1,4-naphthoquinone has been shown to generate active oxygen species by using electron spin resonance spin-trapping techniques. 1-Naphthol, in the presence of NADPH, and 1,2- and 1,4-naphthoquinone, with either NADH or NADPH, caused a stimulation in both the rate of microsomal oxygen consumption and the formation of superoxide spin adduct, 5,5-dimethyl-2-hydroxyperoxypyrrolidino-1-oxyl (DMPO-OOH). Superoxide dismutase, but not catalase, prevented the formation of this spin adduct, further supporting the suggestion that the superoxide free radical was the major oxy-radical formed during the microsomal metabolism of 1-naphthol and the naphthoquinones. These results are compatible with the suggestion that 1-naphthol may exert its toxicity to isolated hepatocytes and other cellular systems by metabolism to naphthoquinones followed by their redox cycling with concomittant generation of active oxygen species, in particular superoxide free radicals.

...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.

Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure.

Used as a chemical reagent and intermediate; [Hawley] Used as a reagent for resorcinol and thalline; [Merck Index]

Chemical reagent and intermediate

Prepared by oxidation of 1-amino-2-naphthol with ferric chloride:...; by oxidation of naphthalene: Milas, US 2395638 (1946 to Research Corp.); by bacterial dissimilation of naphthalene:...; from tetrachloro-o-benzoquinone...

1,2-Naphthoquinone is obtained in 80% yield when 2-naphthol is oxidized by air in the liquid phase with copper(I) chloride as catalyst. Slightly lower yields are obtained when periodic acid and dimethyl formamide, iodosobenzene, or benzene seleninic anhydride is used as oxidant. A 95% yield can, however, be obtained with tetramethyloxopiperidinium chloride at low temperature. The quinone can also be obtained by the oxidation of 1-amino-2-hydroxynaphthalene hydrochloride with iron(III) chloride in hydrochloric acid.