o-Toluidiniumchlorid

Nitrogen Compounds -> Amines, Aromatic

Carcinogens

less than 1 mg/mL at 72 °F (NTP, 1992)

VERY SOL IN WATER; SOL IN ALCOHOL

INSOL IN ETHER, INSOL IN BENZENE

468 °F at 760 mmHg (NTP, 1992)

242.2 °C

419 °F (NTP, 1992)

215 °C

O-toluidine hydrochloride appears as green crystals or white crystalline solid. Melting point 215-217 °F. Highly toxic.

Green or white solid; [CAMEO] Faintly grey powder; [MSDSonline] Colorless to white solid; [NTP]

Danger

H302 (24.1%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P318, 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 58 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard Traits - Carcinogenicity

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.)

SYMPTOMS: Symptoms of exposure to this compound include methemoglobinemia, cyanosis, central nervous system depression, vesiculation, anorexia, headache, weight loss, nausea, vomiting, diarrhea, dizziness, drowsiness, weakness, dyspnea, toxic psychosis, irritability, stupor, lethargy, unconsciousness, hemolytic anemia, kidney damage, anuria, liver damage, jaundice, bladder ulceration, hematuria and dermatitis. Symptoms of exposure to a related compound include anoxia. Eye burns may occur. Eye irritation may also occur. Other symptoms include skin irritation and coma. Inhalation may cause pallor, low-grade secondary anemia, fatigability and loss of appetite. Death may occur from severe exposure. Corneal damage has been reported.

DHEW/NCI; Bioassay of o-Toluidine Hydrochloride for Possible Carcinogenicity (1979) Technical Rpt Series No. 153 DHEW Pub No. (NIH) 79-1709

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-Toluidine and o-Toluidine Hydrochloride (636-21-5) are listed as reasonably anticipated to be human carcinogens. /o-Toluidine and o-Toluidine Hydrochloride/[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s178otol.pdf]

DHHS/NTP; NTP Technical Report on Comparative Toxicity Studies of o-Nitrotoluene and o-Toluidine Hydrochloride Administered in Feed to Male F344/N Rats. Toxicity Rpt Series No. 44 NIH Publication No. 96-3936 (1996)

U222; As stipulated in 40 CFR 261.33, when o-toluidine hydrochloride, 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).

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. Toluidines are produced, as an intermediate or final product, by process units covered under this subpart. /Toluidines/

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.

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/

1. VENTILATE AREA OF SPILL OR LEAK. 2. FOR SMALL QUANTITIES, ABSORB ON PAPER TOWELS. EVAPORATE IN SAFE PLACE (SUCH AS FUME HOOD). ALLOW SUFFICIENT TIME FOR EVAPORATING VAPORS TO COMPLETELY CLEAR HOOD DUCTWORK. BURN PAPER IN SUITABLE LOCATION AWAY FROM COMBUSTIBLE MATERIALS. /O-TOLUIDINE/

2. LARGE QUANTITIES CAN BE COLLECTED & ATOMIZED IN SUITABLE COMBUSTION CHAMBER EQUIPPED WITH APPROPRIATE EFFLUENT GAS CLEANING DEVICE. /O-TOLUIDINE/

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/

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, 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.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U222, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

BY ABSORBING IT IN VERMICULITE, DRY SAND, EARTH OR SIMILAR MATERIAL & DISPOSING IN SECURED SANITARY LANDFILL. /O-TOLUIDINE/

Controlled incineration (oxides of nitrogen are removed from the effluent gas by scrubbers and/or thermal devices). /Toluidine/

A potential candidate for liquid injection incineration at a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds. A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

For more Disposal Methods (Complete) data for 2-METHYLANILINE HYDROCHLORIDE (9 total), please visit the HSDB record page.

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/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for 2-METHYLANILINE HYDROCHLORIDE (9 total), please visit the HSDB record page.

8 hr Time Weighted Avg (TWA): 0.5 ppm, skin. /N-Methyl aniline/

Excursion Limit Recommendation: Excursions in worker exposure levels may exceed 3 times the TLV-TWA for no more than a total of 30 minutes during a work day, and under no circumstances should they exceed 5 times the TLV-TWA, provided that the TLV-TWA is not exceeded. /N-Methyl aniline/

8 hr Time Weighted Avg (TWA): 2 ppm, skin. /o-Toluidine/

Excursion Limit Recommendation: Excursions in worker exposure levels may exceed 3 times the TLV-TWA for no more than a total of 30 minutes during a work day, and under no circumstances should they exceed 5 times the TLV-TWA, provided that the TLV-TWA is not exceeded. /o-Toluidine/

For more Threshold Limit Values (TLV) (Complete) data for 2-METHYLANILINE HYDROCHLORIDE (6 total), please visit the HSDB record page.

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

PRECAUTIONS FOR "CARCINOGENS": ... dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... 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. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

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. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=636-21-5]

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/

CLINICAL SIGNS OF INTOXICATION INCL PHYSIOLOGICAL & PSYCHICAL DISTURBANCES & MARKED IRRITATION OF KIDNEYS & BLADDER. ACUTE POISONING ... MAY BE ACCOMPANIED BY METHEMOGLOBINEMIA & HEMATURIA. /O-TOLUIDINE/

Toxic effects of toluidines in humans ... include ... headache, difficulty in breathing. /Toluidines/

Cause-specific mortality of 906 workers first employed during 1922-1970 in a dyestuff factory in northern Italy ... a marked excess of bladder cancer was observed (36 observed vs 1.23 expected deaths). The mean latent period was 25 yr. The excess was higher among those with a longer duration of exposure. ... Mortality from bladder cancer was very much higher among those exposed in benzidine and naphthylamines manufacture than among those only exposed in use or intermittent contact. ... There is evidence that o-toluidine ... should be implicated in such excess mortality. Caution in handling ... is suggested. /2-Aminotoluene/

... BLADDER TUMORS /REPORTED/ IN WORKERS ENGAGED ON PRODN OF O-TOLUIDINE &/OR P-TOLUIDINE IN USSR IN 1960'S. CONCN RANGE OF ORTHO- ... MEASURED IN AIR ... WAS 0.5-28.6 MG/CU M. TWO CASES OF BLADDER TUMORS (PAPILLOMAS) ... FOUND WHEN 75/81 ... WORKERS EXAM CYSTOSCOPICALLY. /O-TOLUIDINE/

... /CASE REPORTS OF EPIDEMIOLOGICAL STUDIES INVOLVING/ OCCUPATIONAL EXPOSURE ... TO TOLUIDINES ... /IS/ SUGGESTIVE OF CARCINOGENIC EFFECT ... /TOLUIDINES /

Thirty-eight process wastewaters and 37 organic substances identified in the wastewater of the Kashima petrochemical complex were subjected to the activated sludge degradability test. The test used the activated sludge of the Fukashiba industrial wastewater treatment plant, which was acclimatized to the wastewater and organic substances. Water in the test container was sampled during aeration at 0 hr and 24 hr later. After 1 day of acclimation, 100 mg/l of 2-methylaniline resulted in a chemical oxygen demand (Mn) of 92% and 83% total organic carbon. /2-methylaniline/

o-Toluidine hydrochloride

TR-153: Bioassay of o-Toluidine Hydrochloride for Possible Carcinogenicity (CASRN 636-21-5) (1979 )

10/25/78

Clear Evidence

Clear Evidence

Clear Evidence

... MALE & FEMALE CHARLES RIVER (HA/ICR) CG-1 MICE GIVEN ORTHO-TOLUIDINE (PROBABLY AS HYDROCHLORIDE) AT TWO DOSE LEVELS IN DIET DEVELOPED VASCULAR TUMORS.

... FEEDING ... (PROBABLY AS HYDROCHLORIDE) TO 50 MALE CHARLES RIVER (SPRAGUE-DAWLEY DERIVED) CD RATS AT 2 DOSE LEVELS ... FOR 2 YR INCR ... SUBCUTANEOUS FIBROMAS & FIBROSARCOMAS TO 83% FROM 16% THAT OCCURRED SPONTANEOUSLY IN 111 CONTROL RATS. URINARY BLADDER CANCERS & HEPATOMAS WERE ALSO PRESENT IN TREATED ANIMALS.

ORTHO-TOLUIDINE DID NOT INDUCE REVERSE MUTATIONS IN SALMONELLA TYPHIMURIUM TA 1535, TA 1537, TA 1538, TA 98 OR TA 100 IN PRESENCE OR ABSENCE OF RAT LIVER PREPARATION. /O-TOLUIDINE/

Toluidines were especially toxic to blue-green algae /PR-6 (Agmemellum quadruplicatum) and 17A (Coccochloris elabens)/ /Toluidines/

For more Non-Human Toxicity Excerpts (Complete) data for 2-METHYLANILINE HYDROCHLORIDE (8 total), please visit the HSDB record page.

The Human Health Assessment Group in EPA's Office of Health and Environmental Assessment has evaluated o-toluidine hydrochloride for carcinogenicity. According to their analysis, the weight-of-evidence for o-toluidine hydrochloride is group B2, which is based on inadequate evidence in humans and sufficient evidence in animals. As a group B2 chemical, o-toluidine hydrochloride is considered to be probably carcinogenic to humans.

Classification of carcinogenicity: 1) evidence in humans: insufficient; 2) evidence in animals: sufficient. Overall summary evaluation of carcinogenic risk to humans is Group 2B: The agent is possibly carcinogenic to humans. /From table; ortho-Toluidine/

A3; Confirmed animal carcinogen with unknown relevance to humans. /o-Toluidine/

o-Toluidine Hydrochloride: reasonably anticipated to be human carcinogens. /o-Toluidine and o-Toluidine Hydrochloride/

A bioassay of o-toluidine hydrochloride for possible carcinogenicity was conducted by admin the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each sex were admin o-toluidine hydrochloride at one of several doses, either 3,000 or 6,000 ppm for rats and either 1,000 or 3,000 ppm for the mice, for 101 to 104 wk. Matched controls consisted of 20 untreated rats of each sex and 20 untreated mice of each sex. All surviving rats and mice were /sacrificed/ at the end of admin of the test chemical. ... Under the conditions of this bioassay, o-toluidine hydrochloride was carcinogenic in both male and female F344 rats and B6C3F1 mice, producing a significant increased incidence of one or more types of neoplasms. ... Evidence of Carcinogenicity: Male Rats: Positive; Female Rats: Positive; Male Mice: Positive; Female Mice: Positive.

3.7e-05

CALEPA

0.13

CALEPA

LD50 Mouse oral 1100 mg/kg.

LD50 Rat oral 2951 mg/kg.

LD50 Rat ip 150 mg/kg.

LD50 Mouse ip 113 mg/kg.

LD50 Rat oral 0.94 g/kg. /2-Methylaniline/

4.20e+00

1.80e+01

7.60e-02

3.30e-01

6.00e-01

4.00e+01

U222; As stipulated in 40 CFR 261.33, when o-toluidine hydrochloride, 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).

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. Toluidines are produced, as an intermediate or final product, by process units covered under this subpart. /Toluidines/

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; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

N-oxidation is important in the induction of bladder and liver tumors by the single ring compounds /o-toluidine hydrochloride and o-nitrosotoluidine/ but ... other mechanisms could be involved in the induction of peritoneal, skin, spleen, and mammary tumors.

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.

Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499)

Following a single dose (400 mg/kg sc) of o-(methyl-(14)C-toluidine ... to male F344 rats, 56% of the (14)C was recovered in the 24 hr urine, 2.4% in the feces and 1% as exhaled (14)CO2. After 48 hr, 83.9% of the (14)C appeared in the urine, 3.3% in the feces and 1.4% was exhaled. /2-Aminotoluene/

Via the respiratory tract and skin. /2-Aminotoluene/

Used to make dyes; Last reported commercial production or import in 1975; One company in US thought to still produce as of 1982; [HSDB] Manufactured in the US by four companies as of 2001, with import data up to 1983; [NTP]

INTERMEDIATE IN MANUFACTURE OF DYES

(1974) 2.19X10+4 kg

(1975) 1.0X10+3 kg

Benzenamine, 2-methyl-, hydrochloride (1:1): ACTIVE

Commercial production of ortho-toluidine hydrochloride was last reported in the USA in 1975. One USA company is believed to produce this chemical currently /1982/

Imports of /ortho-toluidine/ hydrochloride were last reported in 1975, when one thousand kg were imported.