4-Chlor-o-toluidin

Nitrogen Compounds -> Amines, Aromatic

Carcinogens

greater than 1.1 at 68 °F (est) (USCG, 1999)

1.19 g/cm³

Relative density of the vapour/air-mixture at 20 °C (air = 1): 1.00

>1.1 (estimated)

Crystalline, fused, grayish-white solid (commercial product)

LEAVES FROM ALCOHOL

less than 1 mg/mL at 68 °F (NTP, 1992)

SOL IN HOT ALCOHOL

SPARINGLY SOL IN WATER, SOL IN ETHANOL & DILUTE ACIDS

Solubility in water, g/100ml at 25 °C: 0.095 (very poor)

320 °F (NTP, 1992)

99 °C c.c.

320 °F

466 °F at 760 mmHg (NTP, 1992)

241 °C @ 760 MM HG

241 °C

466 °F

72 °F (NTP, 1992)

30 °C

29-30 °C

72 °F

0.04 [mmHg]

Vapor pressure, Pa at 25 °C: 5.5

Danger

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

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

Danger

H301 (98.3%): Toxic if swallowed [Danger Acute toxicity, oral]

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

Chemical: Benzenamine, 4-chloro-2-methyl-

Hazard Traits - Carcinogenicity

S - indicates a substance that is identified in a final Significant New Use Rule.

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.)

Special Hazards of Combustion Products: Toxic oxides of nitrogen and hydrochloric acid fumes may form. (USCG, 1999)

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

4-Chloro-2-toluidine is known to cause methemoglobinemia in humans. Two of three cohort studies showed high relative risks for workers exposed to this chemical in dye and chlordimeform production. [IARC] Induces genetic damage in germ cells of humans or animals (3A); [MAK]

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. p-Chloro-o-toluidine (95-69-2) and p-Chloro-o-toluidine Hydrochloride are listed as reasonably anticipated to be human carcinogens. /p-Chloro-o-toluidine and p-Chloro-o-toluidine Hydrochloride/[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s043pcot.pdf]

4-CHLORO-O-TOLUIDINE is incompatible with acids, acid chlorides, acid anhydrides, chloroformates and strong oxidizing agents. (NTP, 1992). A halide- and amine-substituted aromatic compound. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.

Fire Extinguishing Agents: Water, dry chemical (USCG, 1999)

Use water spray, dry powder, carbon dioxide.

Fresh air, rest. Refer immediately for medical attention.

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

Rinse with plenty of water for several minutes (remove contact lenses if easily possible). Refer for medical attention.

Rinse mouth. 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.

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/

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: 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: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

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/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for 4-CHLORO-O-TOLUIDINE (6 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 4-CHLORO-O-TOLUIDINE (9 total), please visit the HSDB record page.

4-Chloro-o-toluidine was detected in the urine of workers in Australia exposed to N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine, as a metabolic breakdown product of the acaricide; reverse-phase HPLC with UV detection has a detection limit of 0.4 to 10 ug/ml of 4-chloro-o-toluidine(1).

TERRESTRIAL FATE: Photolysis of 4-chloro-o-toluidine on soil surfaces may occur; 4-chloro-o-toluidine spotted onto silica gel plates and exposed to sunlight resulted in 10 photolytic degradation products(1). An estimated Koc value of 410(2,SRC) indicates that 4-chloro-o-toluidine should have moderate mobility in soil(SRC), based upon a recommended classification scheme(3). In an experimental soil system, however, it was shown that a considerable portion, about 50%, of this compound bound very strongly to the soil medium and that this was possibly due to interactions between the aromatic amine and humic/organic materials in the soil(4,5); soils with very little organic matter may not bind 4-chloro-o-toluidine strongly(5,SRC). Biodegradation of 4-chloro-o-toluidine may occur and may be a major fate process of this compound in soil; 20% mineralization of 4-chloro-o-toluidine in soil was reported over a 6 week time period(6). A polymerizing transformation of 4-chloro-o-toluidine to the corresponding azobenzene was shown in the presence of pure enzymes derived from a soil fungus(7).

AQUATIC FATE: As 4-chloro-o-toluidine has an absorption maximum at a wavelength of 296 nm(1), it will absorb radiation from natural sunlight and may degrade photolytically(SRC). 4-Chloro-o-toluidine in ethanol solution exposed to short wavelength UV light gave a mixture of photolytic degradation products(2). Volatilization of 4-chloro-o-toluidine from water surfaces will be slow based on an estimated Henry's Law constant of 2X10-6 atm-cu m/mole(3,SRC). Sorption of this compound to organic material in the water column may be a significant fate process; soil with added 4-chloro-o-toluidine retained about 50% of this compound as a strongly bound residue following Soxhlet extraction(4,5). Interaction of the aromatic amine with organic matter in the soil was believed to be responsible for this binding(4,5). Biodegradation of this compound in water may be possible; from an industrial wastewater 7% removal of TOC was seen but with GC analysis, structural changes to this compound were also detected resulting in higher levels of measured biodegradation of the parent compound(6). Bioconcentration of 4-chloro-o-toluidine in aquatic organisms is not an important fate process(7).

ATMOSPHERIC FATE: Based on an estimated vapor pressure of 0.04 mm Hg at 25 °C(1,SRC), 4-chloro-o-toluidine will exist primarily in the vapor phase in the ambient atmosphere(2,SRC). 4-Chloro-o-toluidine will degrade by reaction with photochemically produced hydroxyl radicals with an estimated half-life of about 9 hours(3,SRC). Direct photolysis of 4-chloro-o-toluidine in the atmosphere may be possible(SRC) as indicated by experiments where 4-chloro-o-toluidine spotted onto silica gel plates and exposed to sunlight resulted in about 10 photolytic degradation products(4).

para-Chloro-ortho-toluidine has been isolated and identified in field samples of different plant materials treated with chlordimeform, @ concen of <0.1-0.2 ppm (mg/kg) in young bean leaves, 0.02 0.3 ppm in grape stems, 0.02-0.05 ppm in a mixture of grape stems and berries, and <0.04 ppm in prunes and apples ... .

Residues of chlordimeform and its metabolites were measured in rice plants ... following experimental field application (one to three treatments, with harvesting 42 days after the last treatment). Residue concentrations of para-chloro-ortho-toluidine were 3-61 ppb (ug/kg) in rice grains, 80-7200 ppb in straw parts ...

In another experimental field application of chlordimeform (one to three treatments, either sprayed or applied to the soil, with analysis 20-55 days after treatment), no residue of para-chloro-ortho-toluidine (<0.02 ppm) was found in rice grains or husks ... .

Cough. Red urine. Frequent, sudden and painful urination. Abdominal pain. Blue lips, fingernails and skin. Headache. Dizziness. Nausea. Drowsiness.

Redness. MAY BE ABSORBED! See Inhalation.

Redness. Pain.

See Inhalation.

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/

The Koc for 4-chloro-o-toluidine was estimated as 410(SRC), using a recommended regression-derived equation(1) and an estiamted log Kow of 2.27(2,SRC). According to a suggested classification scheme(3), this estimated Koc value suggests that 4-chloro-o-toluidine has moderate mobility in soil(SRC). 14C labelled 4-chloro-o-toluidine was added to autoclaved soil (pH 7.5, and organic matter, sand, silt, and clay contents of 3.4, 36.6, 28.2, and 35.2%, respectively) and incubated for several weeks; 12.2% of the radioactive label was removed as volatiles, 25% was recovered in a Soxhlet extract, and 55.1% of the radioactive label was obtained after Soxhlet extraction using Bleidner distillation (bound residue fraction)(4). This suggests that a significant portion of the 4-chloro-o-toluidine is bound strongly by this soil(4). Over a 24 hour time period, 34% of applied 4-chloro-o-toluidine was found in the bound residue fraction(5). Binding due to the high reactivity of the aromatic amino group to humus or soil organic matter rather than to clay particles is proposed as a reason for the soil binding ability of anilines(4,5). Low adsorption is observed at a neutral pH with pure clay minerals or soils for substituted anilines(5).

...HEMATURIA MAY BE OBSERVED IN MEN HANDLING...CHLORTOLUIDINES. ...MAY BE A HEMORRHAGIC CYSTITIS WITH PAINFUL & FREQUENT MICTURITION. THIS ACUTE PROBLEM IS OF NO LONG-TERM SIGNIFICANCE & CLEARS...ON CESSATION... IF HEMATURIA PERSISTS...OTHER PATHOLOGICAL URINARY TRACT PHENOMENA...CONSIDERED. /CHLOROTOLUIDINES/

...GROUP OF 35 MEN WHO PREPARED PARA-CHLORO-ORTHO-TOLUIDINE FROM ORTHO-TOLUIDINE DURING THE YEARS 1924-1953; NO BLADDER TUMORS WERE FOUND AMONG THESE MEN...

PARA-CHLORO-ORTHO-TOLUIDINE INHIBITED RNA SYNTHESIS IN HELA CELLS...

THE TOLUIDINES...MAY PRODUCE TRANSIENT HEMATURIA AS WELL AS METHEMOGLOBINEMIA AFTER HEAVY EXPOSURES, BUT THE CHLORO-DERIVATIVES ARE MORE POTENT IN THIS RESPECT... /CHLORO-TOLUIDINES/

For more Human Toxicity Excerpts (Complete) data for 4-CHLORO-O-TOLUIDINE (8 total), please visit the HSDB record page.

... para-chloro-ortho-toluidine can be formed from chlordimeform, an insecticide and acaricide, by enzymes present in the leaves of apple seedlings ... as well as those of cotton plants ... .

4-Chloro-o-toluidine is produced for use in the production of azo dyes. It is also used as an intermediate for the production of pigments and for chlordimeform, a pesticide(1). The occurrence of 4-chloro-o-toluidine in the environment can be attributed to microbial and/or chemical degradation and photo-decomposition of various pesticides(2). 4-Chloro-o-toluidine is a photochemical degradation product of the acaricide, N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine (Galedron)(3).

...CAN BE FORMED FROM CHLORDIMEFORM, AN INSECTICIDE AND ACARICIDE, BY ENZYMES PRESENT IN THE LEAVES OF APPLE SEEDLINGS...AS WELL AS THOSE OF COTTON PLANTS...

OVER 97% OF (14)C-LABELED CHLORDIMEFORM APPLIED TO PRIMARY HUMAN EMBRYONIC LUNG CELLS IN CULTURE WAS CHANGED AFTER 72 HR OF INCUBATION, WITH MAJOR METABOLITES APPEARING AS N-FORMYL-4-CHLORO-O-TOLUIDINE (81.9%) AND 4-CHLORO-O-TOLUIDINE (2.3%).

RATS DEGRADED CHLORDIMEFORM INTO N-(4-CHLORO-2-METHYLPHENYL)-N'-METHYLFORMAMIDINE, N-FORMYL-4-CHLORO-2-METHYLANILINE, 4-CHLORO-2-METHYLANILINE, AND 5 OTHER UNKNOWN METABOLITES.

FORMS 4,4'-DICHLORO-2,2'-DIMETHYLAZOBENZENE IN HORSERADISH. /FROM TABLE/

For more Metabolism/Metabolites (Complete) data for 4-CHLORO-O-TOLUIDINE (7 total), please visit the HSDB record page.

Colorless, endogenous or exogenous pigment precursors that may be transformed by biological mechanisms into colored compounds; used in biochemical assays and in diagnosis as indicators, especially in the form of enzyme substrates. Synonym: chromogens (not to be confused with pigment-synthesizing bacteria also called chromogens).

(14)C-LABELED 4-CHLORO-O-TOLUIDINE, WHEN ORALLY ADMIN TO WHITE RATS, WAS DEGRADED AND ELIMINATED PRIMARILY IN URINE ALONG WITH RADIOACTIVE METABOLITES. RATE OF ABSORPTION & DEGRADATION WAS SLOWER THAN FOR CHLORDIMEFORM.

para-Chloro-ortho-toluidine has been detected in the urine of workers exposed to chlordimeform ... .

Following oral administration of ((14)C-methyl)-para-chloro-ortho-toluidine to male and female white rats, 71% of the administered radioactivity was eliminated in the urine and 24% in the faeces within 72 hr ... .

Binding of para-chloro-ortho-toluidine to hemoglobin was observed after oral administration of 85 mg/kg bw to female Wistar rats ... .

RADIOACTIVITY FROM 4-CHLORO-2-METHYLANILINE-METHYL-(14)C WAS EXTENSIVELY BOUND TO PROTEIN, DNA, AND RNA OF RAT LIVER. ENZYMIC ACTIVITY DEPENDENT UPON NADH & LEADING TO IRREVERSIBLE BINDING OF RADIOACTIVITY FROM LABELED CMPD TO MACROMOLECULES WAS PRESENT IN MICROSOMES.

Used in the past to manufacture azo dyes and chlordimeform; [IARC]

No longer in production or use in most countries since the 1980s; [IARC]

CHEM INT FOR CI AZOIC COUPLING COMPONENT 8, CI PIGMENT RED 7; AZOIC DIAZO COMPONENT FOR COTTON, SILK, ACETATE & NYLON

para-Chloro-ortho-toluidine has also been used since the 1960s in the manufacture of chlordimeform ... , an acaricide and insecticide ... .

AS INT FOR PRODN OF CI PIGMENT YELLOW 49

Substance listed with specific concentration in tattoo ink and/or permanent make up according to EU Commission Regulation 2020/2081. The concentration limit (by weight) is 0.0005%.

(1972) 2.11X10+7 GRAMS (PRINCPL CUSTMS DISTS)

(1976) 1.14X10+7 GRAMS (PRINCPL CUSTMS DISTS)

... US imports of para-chloro-ortho-toluidine through principal US customs districts amounted to 8.63X10+4 kg in 1973 ... 7.33X10+4 kg in 1974 ... and 2.4X10+3 kg in 1975 ... .

(1972) GREATER THAN 4.54X10+5 GRAMS

(1975) GREATER THAN 4.54X10+5 GRAMS