니트로아니솔

Nitrogen Compounds -> Other Aromatics (Nitrogen)

Carcinogens

log Kow = 1.73

1.73

2.0

1.2540 g/cu cm at 20 °C

Relative density (water = 1): 1.25 (20 °C)

Colorless to yellowish liquid

Light reddish or amber liquid

Miscible with ethanol, ethyl ether; soluble in carbon tetrachloride

In water, 1.69X10+3 mg/L at 30 °C

Solubility in water, g/l at 30 °C: 1.69 (slightly soluble)

124 °C

142 °C closed cup

142 °C c.c.

277 °C; 144 °C at 4 mm Hg

Boiling point range: 268-271 °C

277 °C

10.5 °C

10.5 °C

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Hazard Traits - Carcinogenicity

2-Nitroanisole: 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.)

Inhalation of high concentrations can cause methemoglobinemia; The substance may have effects on the blood, resulting in anaemia. [ICSC] An irritant; Effects in high-dose animal studies include methemoglobinemia; [MSDSonline] See 2021 (Volume 127) monograph at IARC.

DHHS/NTP; Toxicology & Carcinogenesis Studies of o-Nitroanisole in F344/N Rats and B6C3F1 Mice (Feed Studies) Technical Report Series No. 416 (1993) NIH Publication No. 93-3147

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, vol 65, p. 376 (1998)[Available at: http://monographs.iarc.fr/index.php]

Advisory Committee on Existing Chemicals of Environmental Relevance (BUA). o-Nitroanisole (1-methoxy-2-nitrobenzene). S. Hirzel Verlag, Stuttgart Germany 1993. This document reviews the currently available data on the environmental behavior of o-nitroanisole along with ecotoxic effects and toxicological data. ...

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. o-Nitroanisole (91-23-6) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s120onit.pdf]

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. o-Nitroanisole is produced, as an intermediate or a final product, by process units covered under this subpart.

/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Health: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. /Nitroanisoles; Nitroanisoles, liquid; Nitroanisoles, solid/

/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. /Nitroanisoles; Nitroanisoles, liquid; Nitroanisoles, solid/

/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Public Safety: CALL Emergency Response Telephone Number ... As an 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. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. /Nitroanisoles; Nitroanisoles, liquid; Nitroanisoles, solid/

/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. /Nitroanisoles; Nitroanisoles, liquid; Nitroanisoles, solid/

For more DOT Emergency Guidelines (Complete) data for 2-Nitroanisole (8 total), please visit the HSDB record page.

Acute Tox. 4 (100%)

Carcinogenicity - category 1B

Self-reactive substances and mixtures - Type G

Acute toxicity (Oral) - Category 4

Self-reactive substances and mixtures - Type G

Carcinogens

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./

The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.

The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

UN 2730; Nitroanisoles, liquid[United Nations; Recommendations on the Transport of Dangerous Goods. Model Regulations. Vol. I, 16th Revised Edition (2009). Available from, as of November 29, 2010: http://www.unece.org/trans/danger/publi/unrec/rev16/16files_e.html]

UN 3458; Nitroanisoles, solid[United Nations; Recommendations on the Transport of Dangerous Goods. Model Regulations. Vol. I, 16th Revised Edition (2009). Available from, as of November 29, 2010: http://www.unece.org/trans/danger/publi/unrec/rev16/16files_e.html]

IMO 6.1; Nitroanisole

Fresh air, rest. Artificial respiration may be needed. Refer for medical attention.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

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

Rinse mouth. Give a slurry of activated charcoal in water to drink. Rest. Refer for medical attention .

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special protective equipment for fire-fighters: 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.) Use water in flooding quantities as fog. Use foam, dry chemical, or carbon dioxide. Keep run-off water out of sewers and water sources. /Nitroanisole/

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage.

Well closed.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

Collect leaking liquid in sealable containers. Absorb remaining liquid in sand or inert absorbent and remove to safe place.

ACCIDENTAL RELEASE MEASURES. Personal precautions: Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity 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 and plant life; and conformance with environmental and public health regulations.

Product: Observe all federal, state, and local environmental regulations. 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.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for 2-Nitroanisole (7 total), please visit the HSDB record page.

Personal protection: chemical protection suit and filter respirator for organic gases and vapours adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

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

If inhaled ..., move person into fresh air. If not breathing give artificial respiration. Consult a physician. In case of skin contact, wash off with soap and plenty of water. Consult a physician. In case of eye contact, rRinse thoroughly with plenty of water for at least 15 minutes and consult a physician. If swallowed, never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary. Attempt to stop leak if without undue personnel hazard. /Nitroanisole/

For more Preventive Measures (Complete) data for 2-Nitroanisole (13 total), please visit the HSDB record page.

LC50; Species: Coturnix japonica (Japanese quail); Conditions: oral feed; Concentration: >1300 mg/kg /o-Nitroanisole 99% purity/ /Translated from German/

LC50; Species: Oryzia latipes (Japanese medaka); Conditions: static; Concentration: 25 mg/L/48 hr.

LC50; Species: Pimephales promelas (Fathead minnow); Conditions: static; Concentration: 216.1 mg/L/96 hr

EC50; Species: Scenedesmus subspicatus (algae); Conditions: OECD Guideline 201; Concentration: 48.6 mg/L/72 hr; Endpoint: growth rate

For more Ecotoxicity Values (Complete) data for 2-Nitroanisole (11 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a log Kow of 1.73(2) and a regression-derived equation(3), indicates that 2-nitroanisole is expected to have high mobility in soil(SRC). Volatilization of 2-nitroanisole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.3X10-7 atm-cu m/mole(SRC) derived from its vapor pressure, 3.6X10-3 mm hg(4), and water solubility, 1.69X10+3 mg/L(5). 2-Nitroanisole is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(5). The compound required more than 64 days to biodegrade in a soil microflora inoculum(6) indicating that biodegradation is not an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a log Kow of 1.73(2) and a regression-derived equation(3), indicates that 2-nitroanisole is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 4.3X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 3.6X10-3 mm Hg(5), and water solubility, 1.69X10+3 mg/L(6). According to a classification scheme(7), a BCF range of 1.4-5.2(8) suggests the potential for bioconcentration in aquatic organisms is low(SRC). Utilizing the Japanese MITI test, 0% of the Theoretical BOD was reached in 2 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), 2-nitroanisole, which has a vapor pressure of 3.60X10-3 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 2-nitroanisole 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 4.6 days(SRC), calculated from its rate constant of 3.5X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). 2-Nitroanisole absorbs light at wavelengths up to 429 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

Blue lips, fingernails and skin. Dizziness. Headache. Nausea. Confusion.

Dry skin.

See Inhalation.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=91-23-6]

The Koc of 2-nitroanisole is estimated as 140(SRC), using a log Kow of 1.73(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that 2-nitroanisole is expected to have high mobility in soil.

/SIGNS AND SYMPTOMS/ May be harmful if inhaled. May cause respiratory tract irritation. May be harmful if absorbed through skin. May cause skin irritation. May cause eye irritation. Harmful if swallowed.

/GENOTOXICITY/ The aim of the study was to detect single-strand breaks in deoxyribonucleic acid (DNA) in mononuclear blood cells of fire fighters exposed to o-nitroanisole and other substances released into the environment during an accident in a chemical plant. The level of DNA single-strand breaks in mononuclear blood cells was detected by alkaline elution. The results were compared for 16 fire fighters who worked in a contaminated area for about 8 hr and two reference groups (one of fire fighters who had not worked in the contaminated area, group I, and one of persons without any apparent occupational exposure to genotoxic substances, group II). The mean normalized elution rate (nER) 19 d after the accident was slightly but statistically significantly (P < 0.05) higher for the exposed fire fighters [mean 1.48 +/- 95% confidence interval (95% CI) 0.21] than for reference group I (mean 1.21 +/- 95% CI 0.21) or reference group II (mean 1.17 +/- 95% CI 0.18). No statistically significant difference was found between reference groups I and II. Another analysis was performed three months after the first. The level of DNA single-strand breaks (mean nER 1.12 +/- 95% CI 0.11) was no longer increased in comparison with the levels of the reference groups ...

AEROBIC: 2-Nitroanisole is considered non-biodegradable(1). o-Nitroanisole, present at 100 mg/L, reached 0% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(2). Greater than 64 days were required to degrade 2-nitroanisole by a soil microflora inoculum from a Niagara silt loam in a mineral salts medium(3).

SEDIMENT: 2-Nitroanisole was reported 4.3% of 70 samples at an average concentration of 0.69 ppm in samples collected from 1974-1976 from the industrial zone along the Pacific coast of Japan which included Tokyo Bay, Ise Bay, Osaka Bay, the Seto Inland Sea, and areas along the Japan Sea coast(1).

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. o-Nitroanisole is produced, as an intermediate or a final product, by process units covered under this subpart.

... An intravenous dose of 25 mg/kg bw was used for pharmacokinetic studies. Following a 25 mg/kg bw intravenous injection of [14C]2-nitroanisole, blood, tissues and excreta were collected at times ranging from 15 min to seven days. ... The subsequent elimination of 14C was rapid and biphasic. The initial elimination phase in all tissues had a half-life of 1-2 hr, and the terminal phase half-lives for all tissues ranged from 2.5 to 6.2 days. Elimination of parent 2-nitroanisole from the blood was biphasic with initial and terminal half-lives of 30 min and 2.2 hr, respectively. Monophasic elimination of 2-nitroanisole from the liver, kidneys and small intestine occurred with half-lives of 0.35, 0.55, and 0.68 hr, respectively...

Male F344 rats were injected iv with 25 mg/kg bw (14)C-labeled o-nitroanisole. 15 Min post-administration maximum tissue concentration was reached. Elimination bi-phasic. The first elimination phase had a half-life of 1-2 hr, the second elimination phase was longer and was tissue-dependent. /Translated from German/

... The detoxifying metabolism of a potent rodent carcinogen, 2-nitroanisole (2-NA) by human, rabbit and rat cytochromes P450 (P450) was investigated ... HPLC with UV detection was employed for the separation and characterization of 2-NA metabolites formed by hepatic microsomes, human recombinant P450s and purified rat and rabbit P450s. An O-demethylated metabolite of 2-NA, 2-nitrophenol (2-NP), and two oxidation products of this metabolite [2,5-dihydroxynitrobenzene (2,5-DNB) and 2,6-dihydroxynitrobenzene (2,6-DNB)] were generated by microsomes and P450s from the species investigated, but at different levels. All the metabolites are detoxication products. 2-NP is the major metabolite generated by rabbit and rat microsomes, but 2,5-DNB is the predominant product in human microsomes. Using human recombinant P450s and purified rodent P450s, we found that human P450 2E1, 1A1 and 2B6 as well as orthologous animal P450s were the most efficient enzymes oxidizing 2-NA to 2-NP, while P450 2E1 and 1A1 were the most effective in the formation of 2,5-DNB and 2,6-DNB. In human hepatic microsomes, 2-NA was oxidized mainly by P4502E1. 2-NA and its reductive metabolite o-anisidine induced rat hepatic and renal P450 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1), thus modifying their own detoxication and/or activation pathways. The data demonstrated the participation of orthologous P450s in 2-NA oxidation by all species and indicated that the rat and rabbit might serve as suitable models to mimic 2-NA oxidation in /humans/.

2-Nitrophenol (2-NP) is the major detoxification metabolite of ... 2-nitroanisole (2-NA). Characterization of the products of 2-NP metabolism by rat hepatic microsomes containing cytochromes P450 (CYPs) and identification of the major CYP enzymes participating in this process are aims of this study ... Rat hepatic microsomes oxidize 2-NP to its hydroxylated metabolite, 2,5-dihydroxynitrobenzene (2,5-DNB). No nitroreductive metabolism leading to the formation of o-aminophenol was evident when using rat hepatic microsomes. Selective CYP inhibitors and hepatic microsomes of rats pre-treated with specific CYP inducers were used to characterize CYPs oxidizing 2-NP in rat livers. Based on these studies, we attribute most of 2-NP oxidation in rat liver to CYP2E1 and 3A, followed by CYP2D and 2C. Among recombinant rat CYP enzymes tested in this study, CYP2E1 and 2C11 were the most effective enzymes oxidizing 2-NP. Oxidation of 2-NP by rat CYP2E1 exhibits the Michaelis-Menten kinetics, having the Km value of 0.35 mM. The results found in this study ... demonstrate that CYP2E1 is the major enzyme oxidizing this compound in rat liver.

... The ability of hepatic microsomal samples from different species including human to metabolize 2-nitroanisole (2-NA) /was compared/ ... Human hepatic microsomes generated a pattern of 2-NA metabolites, reproducing that formed by hepatic microsomes of rats and rabbits. An O-demethylated metabolite of 2-NA (2-nitrophenol) and two ring-oxidized derivatives of this metabolite (2,6-dihydroxynitrobenzene and 2,X-dihydroxynitrobenzene) were produced. No nitroreductive metabolism leading to the formation of o-anisidine was evident with hepatic microsomes of any species. Likewise, no DNA binding of 2-NA metabolite(s) measured with either tritium-labeled 2-NA or the (32)P-postlabeling technique was detectable in microsomes. Therefore, hepatic microsomal P450 enzymes participate in the detoxication reactions of this environmental carcinogen. Using hepatic microsomes of rabbits pretreated with specific P450 inducers, microsomes from Baculovirus transfected insect cells expressing recombinant human P450 enzymes, purified P450 enzymes, and selective P450 inhibitors, /the authors/ found that human recombinant P450 2E1, 1A1, and 2B6, as well as orthologous rodent P450 enzymes, are the most efficient enzymes metabolizing 2-NA. The role of specific P450 enzymes in the metabolism of 2-NA in human hepatic microsomes was investigated by correlating specific P450-dependent reactions with the levels of 2-NA metabolites formed by the same microsomes and by examining the effects of specific inhibitors of P450 enzymes on 2-NA metabolism. On the basis of these studies, ... most of the 2-NA oxidation metabolism in human microsomes /was attributed/ to P450 2E1. These results ... clearly demonstrate that P450 2E1 is the major human enzyme oxidizing this carcinogen in human liver.

After receiving either 5 mg/kg bw or 50 mg/kg bw (14)C-labeled o-nitroanisole p.o. (male F344 rats), metabolites in the urine after 7 days included 63% o-nitrophenylsulfate, 11% o-nitrophenylglucuronide, 1.5% o-nitrophenol, 0.6% o-anisidine. /Translated from German/

For more Metabolism/Metabolites (Complete) data for 2-Nitroanisole (11 total), please visit the HSDB record page.

Male F344 rats were injected iv with 25 mg/kg bw (14)C-labeled o-nitroanisole. 15 min post-administration maximum tissue concentration was reached. Elimination bi-phasic. The first elimination phase had a half-life of 1-2 hr, the second elimination phase was longer and was tissue-dependent. /Translated from German/

Male F344 rats received 4 or 50 mg/kg bw (14)C-labeled o-nitroanisole p.o. Within 24 hr 73% of the 5 mg/kg bw dose and 69% of the 50 mg/kg bw dose was eliminated in the urine. Within 7 days 71-78% in the urine and 7% in the feces was eliminated. /Translated from German/

Skin absorption in humans is possible. An increase in the substance can be detected in the urine in skin studies. Metabolites are formed by hydrolytic cleavage and are derivatives of o-nitrophenol. /Translated from German/

... An intravenous dose of 25 mg/kg bw was used for pharmacokinetic studies. Following a 25 mg/kg bw intravenous injection of (14C)2-nitroanisole, blood, tissues and excreta were collected at times ranging from 15 min to seven days. The distribution of 2-nitroanisole derived 14C to tissues (muscle, 20%; skin, 10%; fat, 6.8%; blood, 6.5%; liver, 4.8%; plasma, 3.1 %; kidney, 2.8%; and small intestine, 1.9%) occurred rapidly following administration. Peak tissue concentrations were reached in all tissues within 15 min. Urinary and fecal elimination were similar to that found after oral administration (urine, 86% by seven days; feces, 9% by seven days). ... Biliary excretion was similar to fecal elimination, indicating a lack of enterohepatic recirculation. Urine collected for 24 hr after intraperitoneal administration of 25 mg/kg bw 2-nitroanisole had a profile similar to that observed after oral administration (63% 2-nitrophenyl sulfate, 11 % 2-nitrophenyl glucuronide, 1.5% 2-nitrophenol and 0.6% ortho-anisidine).

Used in organic synthesis to produce pharmaceuticals and dyes; [Hawley]

o-Isomer as dye intermediate; in organic syntheses.

CHEM INT FOR DYE INTERMEDIATES, EG, O-ANISIDINE

2-Nitroanisole is used primarily as a precursor to o-anisidine, which is prepared by direct nitro-reduction. o-Anisidine is used extensively in the synthesis of azo dyes either directly after being converted to a diazonium salt or as a precursor for the preparation of dianisidine, which is diazotized and coupled. Directly or indirectly, o-anisidine is used in the manufacture of over 100 azo dyes.

2-Nitroanisole has also been used as an intermediate for various pharmaceuticals.

(1976) 3.19X10+8 G (PRINCPL CUSTMS DISTS)

(1978) 2.46X10+8 G (PRINCPL CUSTMS DISTS)

(1977) PROBABLY GREATER THAN 2.27X10+6 GRAMS

(1978) PROBABLY GREATER THAN 2.27X10+6 GRAMS

From o-nitrophenol by methylation or from o-nitrochlorobenzene by action of methanol and caustic soda

2-Nitroanisole is prepared by slowly adding methanolic sodium hydroxide to a solution of 2-chloronitrobenzene in methanol at 70 °C and then, to complete the reaction, by gradually heating the mixture under pressure to 95 °C. After dilution with water, the product is separated as an oil, at a 90% yield; methanol can be recovered from the aqueous layer.