아니시딘

Hazardous Air Pollutants (HAPs)

Nitrogen Compounds -> Amines, Aromatic

Carcinogens

Dye

log Kow = 1.18

1.18

1.18

1.0923 at 68 °F (NTP, 1992) - Denser than water; will sink

1.0923 g/cu cm at 20 °C

Volatile with steam; density: 1.098 at 15 °C

Density (at 20 °C): 1.09 g/cm³

Relative density of the vapour/air-mixture at 20 °C (air = 1): 1.0

1.092 @ 20°C

Dynamic viscosity: 2.211 mPa-s at 55 °C

2.028 mm²/s at 55 °C

Yellowish liquid; becomes brownish on exposure to air

Reddish or yellowish colored oil

Colorless to pink liquid

Red to yellow, oily liquid [Note: A solid below 41 degrees F].

less than 0.1 mg/mL at 66 °F (NTP, 1992)

Miscible with ethanol, benzene, diethyl ether and acetone

Soluble in ethanol, ethyl ether, acetone, benzene

Soluble in dilute mineral acid, alcohol, and ether; insoluble in water

In water, 1.3X10+4 mg/L at 25 °C

Solubility in water, g/100ml at 20 °C: 1.5 (moderate)

210 °F (NTP, 1992)

118 °C

118 °C, 244 °F (open cup)

107 °C c.c.

(oc) 244 °F

437 °F at 760 mmHg (NTP, 1992)

224 °C

224-225 °C

224 °C @760 [mm Hg]

437 °F

When heated to decomposition it emits toxic fumes of /nitroxides/.

Toxic gases and vapors (such as ... carbon monoxide) may be released when anisidine decomposes.

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

P203, P261, P262, P264, P270, P271, P280, P301+P316, P302+P352, P304+P340, P316, P318, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

H301+H311+H331 (40.5%): Toxic if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]

P203, P260, P261, P262, P264, P270, P271, P273, P280, P301+P316, P302+P352, P304+P340, P316, P318, P319, P321, P330, P361+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Chemical: Benzenamine, 2-methoxy-

Hazard Traits - Carcinogenicity; Dermatotoxicity; Neurotoxicity

Benzenamine, 2-methoxy- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzenamine, 2-methoxy- 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: 21-06-2012 https://echa.europa.eu/registration-dossier/-/registered-dossier/1695

Substance: 2-Methoxyaniline, o-Anisidine

2-Anisidine: Does not have an individual approval but may be used under an appropriate group standard

This chemical is combustible. (NTP, 1992)

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

o-Anisidine is used in the manufacture of dyes. Workers in the dye industry may be occupationally exposed to it. Acute (short-term) exposure to o-anisidine results in skin irritation in humans. Workers exposed to o-anisidine by inhalation for 6 months developed headaches, vertigo, and effects on the blood. Animal studies have reported effects on the blood from chronic (long-term) dermal exposure to o- anisidine. No information is available on the reproductive, developmental, or carcinogenic effects of o- anisidine in humans. Animal studies have reported tumors of the urinary bladder from oral exposure to o- anisidine. EPA has not classified o-anisidine for carcinogenicity. The International Agency for Research on Cancer (IARC) has classified o-anisidine as a Group 2B, possible human carcinogen.

Hematologic changes, anemia, nephrotoxicity, and bladder cancer occur in animal studies. Workers exposed at 0.4 ppm for 3.5 hours/day for six months did not develop anemia, but did have methemoglobinemia and Heinz bodies as well as complaints of headache and vertigo. Listed in the table Examples of Industrial Chemicals for Which Methemoglobin Formation is NOT the Principal Cause of Toxicity; [ACGIH] Evidence of liver injury in high-dose feeding studies of rats; [HSDB] See 2021 (Volume 127) monograph at IARC.

Bioassay of o-Anisidine hydrochloride for Possible Carcinogenicity (1978) Technical Rpt Series No. 89 DHEW Pub No. (NIH) 78-1339, U.S. Department of Health Education and Welfare, National Cancer Institute, Bethesda, MD 20014

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-Anisidine Hydrochloride (134-29-2) is listed as reasonably anticipated to be a human carcinogen. /o-Anisidine Hydrochloride/[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s014oani.pdf]

WHO/IARC Monograph on the Evaluation of the Carcinogenic Risks to Humans; Some Chemicals that Cause Tumours of the Kidney or Urinary Bladder in Rodents and Some Other Substances (1999), pp. 49-58. IARC Monographs provide critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations.[Available from, as of May 5, 2010: http://monographs.iarc.fr/index.php]

European Commission, ESIS; IUCLID Dataset, o-Anisidine (90-04-0) (2000 CD-ROM edition) contains information on use, toxicology, and environmental effects of this chemical as supplied to the European Union by industry.[Available from, as of May 18, 2010: http://esis.jrc.ec.europa.eu/]

European Chemicals Bureau; Risk Assessment for o-Anisidine (CAS No 90-04-0) Final Report (2002). Risk assessment reports provide scientific support to the development and implementation of EU polices related to health and consumer protection.[Available from, as of April 27, 2010: http://esis.jrc.ec.europa.eu/]

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

Use water spray, foam, powder, carbon dioxide.

Fresh air, rest. Administration of oxygen may be needed. Refer immediately for medical attention.

Administration of oxygen may be needed. Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer immediately for medical attention.

Rinse with plenty of water (remove contact lenses if easily possible).

Administration of oxygen may be needed. Rinse mouth. Do NOT induce vomiting. Give one or two glasses of water to drink. Refer immediately 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.

(General first aid procedures)

Store only in original container. Keep in a well-ventilated room. Separated from strong oxidants, acids, chloroformates and food and feedstuffs. Store in an area without drain or sewer access. Provision to contain effluent from fire extinguishing.

Use dry chemical, carbon dioxide, or alcohol foam extinguishers. Vapors are heavier than air and will collect in low areas. Vapors may travel long distances to ignition sources and flashback. Vapors in confined areas may explode when exposed to fire. Storage containers and parts of containers may rocket great distances, in many directions. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors or shows any signs of deforming), withdraw immediately to a secure position ... The only respirators recommended for fire fighting are self-contained breathing apparatuses that have full facepieces and are operated in a pressure-demand or other positive-pressure mode. /Anisidines/

Water or foam may cause frothing when applied on flammable liquids having flash points above 212 °F (100 °C) or the boiling point of water. This remark is included only as a precaution and does not indicate that water or foam should not or could not be used in fighting fires in such liquids. The frothing may be quite violent and could endanger the life of the fire fighter particularly when solid streams are directed into the hot burning liquid. On the other hand, water spray carefully applied has been ... used with success in extinguishing such fires by causing the frothing to occur only on the surface ... .

If material is 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. /Anisidines/

Store in tightly closed containers in a cool, well ventilated area. Protect against sunlight and strong oxidizers. Metal containers involving the transfer of this chemical should be grounded and bonded. Where possible, automatically pump liquid from drums or other storage containers to process containers. Drums must be equipped with self-closing valves, pressure vacuum bungs, and flame arresters. Use only nonsparking tools and equipment, especially when opening and closing containers of this chemical. Sources of ignition, such as smoking and open flames, are prohibited where this chemical is used, handled, or stored in a manner that could create a potential fire or explosion hazard. A regulated, marked area should be established where this chemical is handled, used, or stored ... /Anisidines/

/Store/ separated from strong oxidants, acids, chloroformates and food and feedstuffs. Store in an area without drain or sewer access.

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 ... experimenst 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/

Spill handling: Evacuate persons not wearing protective equipment from area of spill or leak until clean-up is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area of spill or leak. Cover with sand and soda ash (9:1). After mixing, collect material in the most convenient and safe manner and deposit in sealed containers. Keep o-anisidine out of confined spaces, such as a sewer, because of the potential for an explosion, unless the sewer is designed to prevent the buildup of explosive concentrations. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. It may be necessary to contain and dispose of this chemical as a hazardous waste. Contact your Department of Environmental Protection or your regional office of the federal EPA for specific recommendations. /Anisidines/

Do NOT let this chemical enter the environment. Collect leaking liquid in sealable containers. Absorb remaining liquid in sand or inert absorbent and remove to safe place.

Environmental considerations - land spill: Dig a pit, pond, lagoon, holding area to contain fluid 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. Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete. Absorb bulk liquid with fly ash, cement powder or commercial respondents. /Anisidines/

Environmental considerations - water spill: Use natural barriers or oil spill control booms to limit spill travel. Use natural deep water pockets, excavated lagoons, or sand bag barriers to trap material at bottom. Remove trapped material with suction hoses. /Anisidines/

For more Cleanup Methods (Complete) data for o-Anisidine (6 total), please visit the HSDB record page.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. Then, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol 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.

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.

Dissolve in combustible solvent (alcohols, benzene, etc.) and spray solution into furnace equipped with afterburner and scrubber or burn spill residue on sand and soda ash absorbent in a furnace. /Anisidines/

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 o-Anisidine (7 total), please visit the HSDB record page.

Evacuate danger area! Consult an expert! Personal protection: chemical protection suit including self-contained breathing apparatus. Do NOT let this chemical enter the environment. Do NOT wash away into sewer. Collect leaking liquid in sealable containers. Absorb liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

Where exposure of ... body to solid or liquid anisidine or liquids containing anisidine may occur, facilities for quick drenching of the body should be provided within the immediate work area ... .

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for o-Anisidine (18 total), please visit the HSDB record page.

LC50; Species: Brachydanio rerio (zebrafish); Conditions: static; Concentration: >100 mg/L for 96 hr

LC50; Species: Leuciscus idus (Ide); Conditions: static; Concentration: 80 mg/L for 96 hr

LC50; Species: Poecilia reticulata (guppy); Conditions: static; Concentration: 165 mg/L for 14 days

LC50; Species: Oryzia latipes (medaka); Conditions: flow-through; Concentration: 100 mg/L for 14 days;

For more Ecotoxicity Values (Complete) data for o-Anisidine (14 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 46(SRC), determined from a log Kow of 1.18(2) and a regression-derived equation(3), indicates that o-anisidine is expected to have very high mobility in soil(SRC). The pKa of o-anisidine is 4.53(4), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of o-anisidine from moist soil surfaces may be an important fate process(SRC) given an estimated Henry's Law constant of 9.3X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(6). o-Anisidine is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 8.0X10-2 mm Hg(7). After 2 weeks, a 40-69.1% of theoretical BOD using activated sludge in the Japanese MITI test(8) suggests that biodegradation is an important environmental fate process in soil(SRC), provided microorganisms are not killed by high concentrations of the compound(9,10).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 46(SRC), determined from a log Kow of 1.18(2) and a regression-derived equation(3), indicates that o-anisidine is not expected to adsorb to suspended solids and sediment(SRC). o-Anisidine may react with either photochemically generated oxidants found in natural sunlit water or it may bond strongly with any humic materials found in suspended solids and sediments(4). The typical half-life for reaction of aromatic amines with photochemical generated hydroxyl radicals and alkylperoxy radicals is estimated to be on the order of 19-30 hours in natural sunlit water(5). Volatilization from water surfaces is expected(6) based upon an estimated Henry's Law constant of 9.3X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(7). Using this Henry's Law constant and an estimation method(6), volatilization half-lives for a model river and model lake are 44 days and 320 days, respectively(SRC). According to a classification scheme(8), an estimated BCF of 2(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). After 2 weeks, a 40-69.1% of theoretical BOD using activated sludge in the Japanese MITI test(9) suggests that biodegradation is an important environmental fate process in water(SRC), provided microorganisms are not killed by high concentrations of the compound(10,11).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), o-anisidine, which has a vapor pressure of 8.0X10-2 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase o-anisidine 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 4.1 hours(SRC), calculated from its rate constant of 1.2X10-10 cu cm/molecule-sec at 25 °C(3). Aromatic amines such as aniline have weak absorption bands that extend beyond 290 nm(4); therefore, o-anisidine may be susceptible to direct photolysis, but the kinetics of this reaction are unknown(SRC).

The substance can be absorbed into the body by inhalation of its vapour, through the skin and by ingestion.

inhalation, skin absorption, ingestion, skin and/or eye contact

Blue lips, fingernails and skin. Headache. Dizziness.

MAY BE ABSORBED! Further see Inhalation.

Redness. Pain.

Nausea. Further see Inhalation.

headache, dizziness; cyanosis; red blood cell Heinz bodies; [potential occupational carcinogen]

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. /o-Anisidine hydrochloride/[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=134-29-2]

o-Anisidine has been detected (0.023 ug/L) in the Rhine Delta near Werkendam, Netherlands which is downstream from industrial activity(1). o-Anisidine has been identified in the surface water of effluents from chemical plants and oil refineries in the US(2). Anisidine (isomer not specified) has been identified in the effluent from chemical industries located in Kingsport, TN (Sept 1974), Morristown, TN (Sept 1974) and on the Upper Catawba River, TN (Aug 1974)(3). o-Anisidine has been identified in the effluent from a chemical industry located on the Upper Catawba River, TN (Aug 1973)(3).

1. Initial Medical Examination: A complete history and physical examination: The purpose is to detect pre-existing conditions that might place the ... employee at increased risk, and to establish a baseline for further health monitoring. Examination of blood, kidneys, liver, and cardiovascular system should be stressed. A complete blood count: ... A complete blood count should be performed including a red cell count, a white cell count, a differential count of a stained smear, as well as hemoglobin and hematocrit. 2. Periodic Medical Examination: The aforementioned medical examinations should be repeated on an annual basis.

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date 3/11/94; Reporting date: 5/10/94.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. o-Anisidine is included on this list. Effective date 3/11/94; Sunset date: 6/30/98.

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. Anisidine is produced, as an intermediate or a final product, by process units covered under this subpart. /Anisidine/

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. o-Anisidine 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 100 lb or 45.4 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).

2-Methoxyaniline (o-anisidine) is an industrial and environmental pollutant and a bladder carcinogen for rodents. The mechanism of its carcinogenicity was investigated with 2 independent methods, (32)P-postlabeling and (14)C-labeled o-anisidine, to show that o-anisidine binds covalently to DNA in vitro after its activation by human hepatic microsomes ... The capacity of o-anisidine to form DNA adducts /was also investigated/ in vivo. Rats were treated ip with o-anisidine (0.15 mg/kg daily for 5 days) and DNA from several organs was analyzed by (32)P-postlabeling. Two o-anisidine-DNA adducts, identical to those found in DNA incubated with o-anisidine and human microsomes in vitro, were detected in urinary bladder (4.1 adducts per 10+7 nucleotides), the target organ, and, to a lesser extent, in liver, kidney and spleen. These DNA adducts were identified as deoxyguanosine adducts derived from a metabolite of o-anisidine, N-(2-methoxyphenyl)hydroxylamine. This metabolite was identified in incubations with human microsomes. With 9 human hepatic microsomal preparations, we identified the specific CYP catalyzing the formation of the o-anisidine metabolites by correlation studies and by examining the effects of CYP inhibitors. On the basis of these analyses, oxidation of o-anisidine was attributed mainly to CYP2E1. Using recombinant human CYP (in Supersomes) and purified CYPs, the participation of CYP2E1 in o-anisidine oxidation was confirmed. In Supersomes, CYP1A2 was even more efficient in oxidizing o-anisidine than CYP2E1, followed by CYP2B6, 1A1, 2A6, 2D6 and 3A4. The results ... strongly suggest a carcinogenic potential of this rodent carcinogen for humans.

The mechanism of DNA damage by a metabolite of the carcinogen o-anisidine in the presence of metals was investigated by the DNA sequencing technique using 32P-labeled human DNA fragments. The o-anisidine metabolite, o-aminophenol, caused DNA damage in the presence of Cu(II). The DNA damage was inhibited by catalase and bathocuproine, suggesting the involvement of H2O2 and Cu(I). The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by o-aminophenol increased in the presence of Cu(II). /The authors/ conclude that Cu(II)-mediated oxidative DNA damage by this o-anisidine metabolite seems to be relevant for the expression of the carcinogenicity of o-anisidine. o-Aminophenol plus Cu(II) caused preferential DNA damage at the 5'-site guanine of GG and GGG sequences. When CuZn-SOD or Mn-SOD was added, the DNA damage was enhanced and its predominant cleavage sites were changed into thymine and cytosine residues ... SOD may increase the frequency of mutations due to DNA damage induced by o-aminophenol and thus increase its carcinogenic potential.

The metabolism and mode of action of o-anisidine has not yet been fully elucidated. It seems, that like other aromatic amines, o-anisidine is oxidized to a N-hydroxy derivative, which interacts with the heme group of hemoglobin resulting in the formation of methemoglobin. As with other aromatic amines, N,O-acetylation may be involved in the metabolic activation of o-anisidine. In bacterial gene mutation assays with Salmonella typhimurium strains containing elevated levels of N- or O-acetyltransferase activity, mutagenic activity of o-anisidine could be detected. In vitro studies have suggested a possible role for peroxidation enzymes like prostaglandin H synthase in the metabolic activation of o-anisidine. Prostaglandin H synthase is broadly distributed in mammalian tissues including the urinary bladder. Using horseradish peroxidase as a model enzyme, the formation of reactive intermediates from o-anisidine, which were covalently bound to nucleic acids and protein, /was described/. The reactive intermediates formed included electrophilic diimine and quinoneimine metabolites. These metabolites were also formed with prostaglandin H synthase. Further, O-demethylation may occur in the metabolism of o-anisidine. In an in vitro study with microsomes from rat liver, the relative O-demethylation rate of o-anisidine as compared to the formation of formaldehyde from N,N-dimethylaniline was 13%.

When o-anisidine was incubated with thyroid peroxidase, H2O2 and the thyroid peroxidase substrates guaiacol and iodide, the guaiacol and iodide oxidation was effectively inhibited (IC50: 1.9 uM). The persistent thyroid peroxidase inhibition with concomitantly decreased thyroid hormone formation is known to induce thyroid tumors, which might be one possible explanation for the increased incidence of follicular-cell tumors observed in male F344 rats in a two-year feeding study.

In a toxicokinetic study according to OECD Guideline 417, the dye 14C-FAT 92367/A was orally administered to Wistar rats (single oral administration at a target dose level of 7.4 mg/kg bw). Probably as a result of the bacterial breakdown of this compound in the gastrointestinal tract, o-anisidine could be detected in the plasma of male rats (1.5% of the administered (14)C-activity characterized as o-anisidine [0.017 ug/g]), in the urine of male rats (0.14% of the administered (14)C-activity) and in feces of male and female rats (0.9 or 1.1% of the administered (14)C-activity, respectively). Within 96 hr more than 93% of the administered (14)C-activity was excreted, mainly via urine; the major amount was excreted within the first 24 hr. The dye investigated (chrome based) does not belong to the class of the technically most important azo or naphthol pigments, for which no metabolism studies are available.

As intrinsic peroxidase activity is present in the urinary bladder, the peroxidative metabolism of o- and p-anisidine using horseradish peroxidase could be investigated as a model system. The main metabolite is a diimine which then reacts with water to form a quinonimine. The metabolites of o-anisidine were more reactive than those of p-anisidine in relation to protein and glutathione. Covalent binding to DNA was similar for both isomers. /Translated from German/

For more Metabolism/Metabolites (Complete) data for o-Anisidine (8 total), please visit the HSDB record page.

The substance can be absorbed into the body by inhalation of its vapor, through the skin and by ingestion.

... The tissue distribution and excretion of o-anisidine following i.p. administration of a single dose of 10 mg/kg was investigated using radiotracer [3H]. Metabolism of o-anisidine was investigated in the rats following ip administration of a single dose of 50 mg/kg using GC/MS technique ... After 72 hr, about 72% of the given dose was excreted in urine. As indicated, urine proved to be the main route of tritium excretion. In all examined tissues, the highest concentrations of tritium were found 12 hr after injection and the highest accumulation was detected in the liver, kidneys and in the muscle tissue. In urine, the following substances were identified and quantified by GC peak areas: N-acetyl-2-methoxyaniline and N-acetyl-4-hydroxy-2-methoxyaniline ...

o-Anisidine is used as an intermediate in the manufacture of dyes.

Used in the synthesis of azo dyes and guaiacol; [ACGIH]

Intermediate in the manufacturing of dyes, pharmaceuticals, and fragrances.

In manufacture of azo dyes and pigments

Used to prepare the expectorant guaiacol via diazotization and hydrolysis.

Couples with N-acetyl H acid to produce Acid Violet 12.

(1977) 165,000 lb /o-Anisidine hydrochloride/

(1979) 1.25 million lbs /Anisidines/

(1983) 1,251,857 lb

2023: <50,000 lb

(1979) 660,000 lbs /o-Anisidine hydrochloride/

Benzenamine, 2-methoxy- is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#3837]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Benzenamine, 2-methoxy-. Aggregated National Production Volume: 500,000 to < 1 million pounds.

... Produced from 2-methoxynitrobenzene by reduction with iron or by hydrogenation in the presence of precious-metal catalysts (platinum or palladium on activated carbon; solvent: toluene) or of Raney nickel (solvent: methanol or 2-propanol).

/It is/ prepared by reduction of o-nitroanisole with tin or iron and hydrochloric acid. ... /Prepared by/ heating o-aminophenol with potassium methyl sulfate.

Grade: 99% (1% max moisture)

ortho-Anisidine is available in western Europe as a liquid containing a minimum of 99% active ingredient and in Japan as ... liquid containing a minimum of 99% active ingredient and a maximum of 0.2% water, with a minimal feezing-point of 5 deg.

Synthetic Dye and Pigment Manufacturing

Benzenamine, 2-methoxy-: ACTIVE

Method of purification: Steam distillation.