2-Methoxy-5-Methylaniline

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

H350: May cause cancer [Danger Carcinogenicity]

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

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

H319 (23.7%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H350 (99.4%): May cause cancer [Danger Carcinogenicity]

P203, P264, P264+P265, P270, P280, P301+P317, P305+P351+P338, P318, P330, P337+P317, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 173 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

H315: Causes skin irritation [Warning Skin corrosion/irritation]

H319: Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H351: Suspected of causing cancer [Warning Carcinogenicity]

H371: May cause damage to organs [Warning Specific target organ toxicity, single exposure]

P203, P260, P264, P264+P265, P270, P280, P301+P317, P302+P352, P305+P351+P338, P308+P316, P318, P321, P330, P332+P317, P337+P317, P362+P364, P405, and P501 (click each P-code to see the statement)

Fresh air, rest.

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. Refer 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.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital.

OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

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.

Extinguishant: Foam, carbon dioxide, dry chemical. /o-Anisidine/

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/

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

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/

1. Ventilate area of spill or leak. 2. Collect spilled material in most convenient and safe manner for reclamation or for disposal. Liquids containing anisidine should be absorbed in vermiculite, dry sand, earth, or a similar material. Large quantities may be reclaimed; however, if this is not practical, dissolve in flammable solvent (such as alcohol) and atomize in a suitable combustion chamber equipped with an appropriate effluent gas cleaning device.

Cover with the 9:1 mixture of sand and soda ash. After mixing, transfer into a paper carton, stuffed with ruffled paper. Burn in an open furnace with the utmost care or in the furnace with afterburner and scrubber.

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 P-CRESIDINE (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 P-CRESIDINE (12 total), please visit the HSDB record page.

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.

STORAGE PRECAUTIONS: You should keep this material in a tightly closed container under an inert atmosphere, and store it at refrigerated temperatures. STORE AWAY FROM SOURCES OF IGNITION. (NTP, 1992)

Separated from strong oxidants and food and feedstuffs.

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/

carcinogen category: 2

No indication can be given about the rate at which a harmful concentration of this substance in the air is reached on evaporation at 20 °C.

This substance is possibly carcinogenic to humans.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

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/

Wear butyl rubber gloves, plastic coveralls, and self-contained breathing apparatus. /o-Anisidine/

Respirator selection: 2.5 mg/cu m or less: Any dust and mist respirator, except single use. 5 mg/cu m or less: Any dust and mist respirator, except single use or quarter mask respirator. Any supplied air respirator or any self contained breathing apparatus. 25 mg/cu m or less: Any high efficiency particulate filter respirator with full facepiece. Any supplied air respirator with a full facepiece, helmet, or hood or any self contained breathing apparatus with full facepiece. 50 mg/cu m or less: A powered air purifying respirator with high efficiency particulate filter or a Type C supplied air respirator operated in pressure demand or other positive pressure or continuous flow mode. Greater than 50 mg/cu m or entry and escape from unknown concentrations: Self contained breathing apparatus with full facepiece operated in pressure demand or other positive pressure mode or a combination respirator which includes a Type C supplied air respirator with a full facepiece operated in pressure demand or other positive pressure or continuous flow mode and an auxiliary self contained breathing apparatus operated in pressure demand or other positive pressure mode. /o-Anisidine/

Employees should be provided with and required to use dust- and splash-proof safety goggles where solid or liquid anisidine or liquids containing anisidine may contact the eyes. /o-Anisidine/

If employee's clothing ... contaminated ... change /them/ ... . Clothing contaminated with anisidine should be placed into closed containers for storage until it can be discarded or until provision is made for removal of anisidine from the clothing. If the clothing is to be laundered or otherwise cleaned to remove the anisidine, the person performing the operation should be informed of anisidine's hazardous properties. /o-Anisidine/

NO open flames. Closed system, dust explosion-proof electrical equipment and lighting. Prevent deposition of dust.

See EFFECTS OF LONG-TERM OR REPEATED EXPOSURE. AVOID ALL CONTACT!

Use local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear safety spectacles or eye protection in combination with breathing protection.

Do not eat, drink, or smoke during work. Wash hands before eating.

P-cresidine appears as white to silver-gray odorless crystals. (NTP, 1992)

Dry Powder

White solid; [Hawley]

WHITE CRYSTALS.

White crystals

455 °F at 760 mmHg (NTP, 1992)

126 to 129 °F (NTP, 1992)

greater than 230 °F (NTP, 1992)

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

Slightly soluble in water, chloroform. Soluble in ether, benzene, petroleum ether, and ethanol.

Solubility in water: poor

1 (NTP, 1992)

4.7 (calculated) (NTP, 1992) - Heavier than air; will sink (Relative to Air)

0.02 [mmHg]

Vapor pressure, Pa at 25 °C: 1.4

log Kow= 1.74

When heated to decomposition it emist toxic fumes of /nitrogen oxides/.

Liquid anisidine will attack some forms of plastics, rubber, and coatings. /o-Anisidine/

Nitrogen Compounds -> Amines, Aromatic

Carcinogens

Insoluble in water.

Amines, Aromatic

P-CRESIDINE is sensitive to moisture and temperatures greater than 104 °F. Incompatible with strong oxidizing agents (NTP, 1992).

Contact with strong oxidizers may cause fires and explosions. /o-Anisidine/

Classification of carcinogenicity: 1) evidence in humans: no data; 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/

p-Cresidine: reasonably anticipated to be a human carcinogen.

para-Cresidine

Group 2B: Possibly carcinogenic to humans

Volume 27: (1982) Some Aromatic Amines, Anthraquinones and Nitroso Compounds, and Inorganic Fluorides Used in Drinking-water and Dental Preparations

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

p-Cresidine

TR-142: Bioassay of p-Cresidine for Possible Carcinogenicity (CASRN 120-71-8) (1979 )

06/29/78

Clear Evidence

Under the conditions of this bioassay, p-cresidine was carcinogenic to Fischer 344 rats, causing increased incidences of carcinomas and of papillomas of the urinary bladder in both sexes, increased incidences of olfactory neuroblastomas in both sexes, and of liver tumors in males. p-Cresidine was also carcinogenic in B6C3F1 mice, causing carcinomas of the urinary bladders in both sexes and hepatocellular carcinomas in females.

The substance can be absorbed into the body by inhalation and by ingestion.

Redness.

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect

IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.

NTP Carcinogen - Reasonably anticipated to be a human carcinogen.

LD50 Rat oral 1450 mg/kg

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

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/

A NUMBER OR SUBSTITUTED ANILINES, PARTICULARLY WHERE THE SUBSTITUTION IS BY AN ORTHO-METHYL GROUP, ARE WEAKLY CARCINOGENIC. LIKE ANILINE, THEY INDUCE SPLENIC SARCOMAS AND, IN ADDITION ... ORTHO-ANISIDINE AND PARA-CRESIDINE ALSO INDUCED CANCER IN THE URINARY BLADDER /OF ANIMALS/, THOUGH AT HIGH DOSE LEVELS. ... SIGNIFICANCE OF CARCINOGENIC EFFECTS OF SINGLE RING AROMATIC AMINES IN RELATION TO POSSIBLE HUMAN EXPOSURE TO THESE RELATIVELY WEAK CARCINOGENS REQUIRES FURTHER EVALUATION.

Dinitro-o-cresol formulations inhibited in soil microorganisms glucose induced short term respiration, dehydrogenase activity and the potential nitrification stronger with increasing doses, whereas nitrogen transformation (ammonification + nitrification) was stimulated depending on the dose. The overall effects of dinitro-o-cresol were similar to effects known from other dinitrophenol containing pesticides.

p-Cresidine was administered in the feed at either of two concentrations (0.5 and 1.0%) to groups of 50 male and 50 female F344 rats for 104 weeks. Fifty animals of each sex were placed on test as controls and fed only the basic laboratory diet. All animals were observed for up to 2 weeks after discontinuation of treatment. In treated rats of both sexes, statistically significant numbers of adenomas, adenocarcinomas and squamous cell carcinomas were diagnosed in the nasal cavity. Most of the neoplasms were seen in the high dose male and female rats. 22 male rats (49%) showed poorly differentiated adenocarcinomas infiltrating the skull and brain. Only two male rats (4%) had a squamous cell carcinoma, whereas 8 female rats (17%) had squamous cell carcinomas and 14 female rats (30%) were diagnosed as having adenocarcinomas of the nasal cavity.

Groups of 50 male and female B6C3F mice, six weeks of age, were fed diets containing para-cresidine (of indeterminate purity, with at lease three impurities detected by TLC) dissolved in acetone. Low-dose males and females were fed 5000 mg/kg of diet for 21 weeks and 1500 mg/kg for 83 additional weeks, followed by an observation period of two weeks. High-dose males and females mice received diets containing 10,000 mg/kg for 21 weeks and 3000 mg/kg for 71 weeks (males) or 83 weeks (females); females were observed for an additional two weeks. ... A group consisting of 50 animals of each sex served as matched controls. ... Mortality was dose-related and associated with the development of bladder tumors. Of the males, 98% of the controls, 50% of the low-dose mice and 10% of the high-dose mice lived longer than 75 weeks; of the females, 90% of the controls, 78% of the low-dose mice and 28% of the high-dose mice survived past 75 weeks. The incidence of squamous-cell or transitional-cell carcinoma of the urinary bladder was dose-related (P<0.001): 0/50 in control males, 40/42 in low-dose males (P<0.001), 31/31 in high-dose males (P<0.001), 0/45 in control females, 41/46 in low-dose females (P<0.001) and 44/46 in high-dose females (P<0.001). Most of the bladder carcinomas were squamous-cell carcinomas; several metastasized to the lung or peritoneal cavity. A few mice also had sarcomas of the urinary bladder. Malignant tumors of the nasal cavity were found in 0/50 control males, 2/47 low-dose males, 1/41 high-dose males, 0/47 control females, 0/47 low-dose females and 1/48 high-dose females. Hepatocellular carcinomas or adenomas were found in 0/45 control females, 14/44 low-dose females (13 carcinomas) (P<0.001) and 6/40 high-dose females (6 carcinomas) (P=0.009); one of these carcinomas (in a low-dose female) metastasized to the lung.

Groups of 50 male and 50 female Fischer 344 rats, six weeks of age, were fed diets containing 5000 or 10000 mg/kg para-cresidine /of indeterminate purity, with at least three impurities detected by TLC/ dissolved in acetone for 104 weeks and were observed for an additional one or two weeks. ... A group of 50 animals of each sex served as matched controls. There was a dose-related depression in mean body weight gain throughout the study. By 75 weeks, 94, 96 and 62% of males, and 96, 98 and 76% of females were still alive in the control low dose and high-dose groups, respectively. Mortality was associated with the development of tumors of the urinary bladder and nasal cavity. Carcinomas of the urinary bladder, primarily of the transitional-cell type, were found in a dose-related trend in 0/48 control males, 16/48 low-dose males, 41/47 high-dose males, 0/47 control females, 31/49 low-dose females and 41/46 high-dose females. Bladder papillomas were found in 0/48 control males, 14/48 low-dose males, 3/47 high-dose males, 0/47 control females, 6/49 low-dose females and 2/46 high-dose females. A few rats had leiomyosarcomas of the bladder; and most of the treated rats did not have bladder neoplasms had bladder epithelial hyperplasia. Olfactory neuroblastomas were found in 0/48 control males, 1/50 low-dose males and 21/47 high-dose males (P<0.001), and in 0/50 control females, 0/50 low-dose females and 11/49 high-dose females (P<0.001). A few treated rats had other types of malignant nasal tumors or epithelial hyperplasia of the nasal epithelium. Neoplastic liver nodules, hepatocellular carcinomas or hepato-/cholangiocarcinomas were found in 0/48 control males, 13/49 low-dose males (P<0.001) and 2/46 high-dose males; and neoplastic liver nodules were found in 0/50 control females, 4/48 low-dose and 0/48 high-dose females.

Levels of Evidence of Carcinogenicity: Male Rats: Positive; Female Rats: Positive; Male Mice: Positive; Female Mice: Positive.

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=120-71-8]

A bioassay of p-cresidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. p-Cresidine was admin in the feed, at either of two concentrations, to groups of 50 male and 500 female animals of each species. The dietary concentrations used in the chronic bioassay for low and high dose rats were 0.5 and 1.0%, respectively. The time weighted avg concentrations fed to low dose male, low dose female, high dose male and high dose female mice were 0.22, 0.22. 0.46, and 0.44%, respectively. All dosed animals, except for high dose male mice, were administered p-cresidine in the diet for 104 wk and then observed for an additional period of up to 2 wk. All high dose male mice were dead by the end of wk 92. For each species, 50 animals of each sex were placed on test as controls and fed only the basal diet. ... Under the conditions of this bioassay, p-cresidine was carcinogenic to Fischer 344 rats, causing increased incidences of carcinomas and papillomas of the urinary bladder in both sexes, increased incidences of olfactory neuroblastomas in both sexes, and of liver tumors in males. p-Cresidine was also carcinogenic in B6C3F1 mice, causing carcinomas of the urinary bladders in both sexes and hepatocellular carcinomas in females. Levels of Evidence of Carcinogenicity: Male Rats: Positive; Female Rats: Positive; Male Mice: Positive; Female Mice: Positive.

p-Cresidine's production and use as dye intermediate may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 2.5X10-2 mm Hg at 25 °C indicates p-cresidine will exist solely as a vapor in the ambient atmosphere. Vapor-phase p-cresidine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 2 hrs. If released to soil, p-cresidine is expected to have high mobility based upon an estimated Koc of 53. However, aromatic amines are expected to bind strongly to humus or organic matter in suspended solids and sediments due to the high reactivity of the aromatic amino group. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 1.2X10-7 atm-cu m/mole. p-Cresidine reached 0.7% of its theoretical BOD in 2 weeks using the Japanese MITI test, suggesting that biodegradation is not a fast environmental fate process. If released into water, p-cresidine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc but may bind strongly to humus and organic matter. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. This compound is expected to exist in the dissociated form in the environment and therefore volatilization of the cation from water surfaces is not expected to be an important fate process. A BCF of <4.6 suggests bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to p-cresidine may occur through inhalation and dermal contact with this compound at workplaces where p-cresidine is produced or used. (SRC)

p-Cresidine's production and use as a chemical intermediate in the produciton of dyes(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a log Kow of 1.74(2) and a regression-derived equation(3), indicates that p-cresidine is expected to have high mobility in soil(SRC). However, aromatic amines are expected to bind strongly to humus or organic matter in suspended solids and sediments due to the high reactivity of the aromatic amino group(4,5). Volatilization of p-cresidine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.2X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(6). p-Cresidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.5X10-2 mm Hg(SRC), determined from a fragment constant method(7). p-Cresidine reached 0.7% of its theoretical BOD in 2 weeks using the Japanese MITI test(8), suggesting that biodegradation is not a rapid environmental fate process in soils(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a log Kow of 1.74(2) and a regression-derived equation(3), indicates that p-cresidine is not expected to adsorb to suspended solids and sediment(SRC). However, aromatic amines are expected to bind strongly to humus or organic matter in suspended solids and sediments due to the high reactivity of the aromatic amino group(4,5). Volatilization from water surfaces may occur slowly(3) based upon an estimated Henry's Law constant of 1.2X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(6). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 23 and 169 days, respectively(SRC). According to a classification scheme(7), a BCF of <4.6(8), suggests bioconcentration in aquatic organisms is low(SRC). p-Cresidine reached 0.7% of its theoretical BOD in 2 weeks using the Japanese MITI test(8), suggesting that biodegradation is not a fast environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), p-cresidine, which has an estimated vapor pressure of 2.5X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase p-cresidine 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 2 hrs(SRC), calculated from its rate constant of 2.2X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3).

AEROBIC: p-Cresidine, present at 100 mg/l, reached 0.7% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test(1).

The rate constant for the vapor-phase reaction of p-cresidine with photochemically-produced hydroxyl radicals has been estimated as 2.2X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). p-Cresidine is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(2) nor to directly photolyze due to the lack of absorption in the environmental UV spectrum (>290 nm).

BCFs of <4.6 to 10 were measured for p-cresidine(1,2). In a bioconcentration test using orange-red killifish, p-cresidine was listed as a compound which is non accumulative or of low accumulation in aquatic organisms(3). According to a classification scheme(4), these BCF values suggest that bioconcentration in aquatic organisms is low.

The Koc of p-cresidine is estimated as 53(SRC), using a log Kow of 1.74(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that p-cresidine is expected to have high mobility in soil. However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(4,5), suggesting that mobility may be much lower in some soils(SRC).

The Henry's Law constant for p-cresidine is estimated as 1.24X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that p-cresidine is expected to be essentially nonvolatile from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 23 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 169 days(SRC). p-Cresidine's Henry's Law constant indicates that volatilization from moist soil surfaces may occur slowly(SRC). However, aromatic amines are expected to bind strongly to suspended solids and sediment in water due to the high reactivity of the aromatic amino group(3,4), suggesting that volatilization may be much lower in some soils(SRC). p-Cresidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.5X10-2 mm Hg(SRC), determined from a fragment constant method(5).

Occupational exposure to p-cresidine may occur through inhalation and dermal contact with this compound at workplaces where p-cresidine is produced or used. (SRC)

p-Cresidine's production and use as dye intermediate may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 2.5X10-2 mm Hg at 25 °C indicates p-cresidine will exist solely as a vapor in the ambient atmosphere. Vapor-phase p-cresidine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 2 hrs. If released to soil, p-cresidine is expected to have high mobility based upon an estimated Koc of 53. However, aromatic amines are expected to bind strongly to humus or organic matter in suspended solids and sediments due to the high reactivity of the aromatic amino group. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 1.2X10-7 atm-cu m/mole. p-Cresidine reached 0.7% of its theoretical BOD in 2 weeks using the Japanese MITI test, suggesting that biodegradation is not a fast environmental fate process. If released into water, p-cresidine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc but may bind strongly to humus and organic matter. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. This compound is expected to exist in the dissociated form in the environment and therefore volatilization of the cation from water surfaces is not expected to be an important fate process. A BCF of <4.6 suggests bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to p-cresidine may occur through inhalation and dermal contact with this compound at workplaces where p-cresidine is produced or used. (SRC)

p-Cresidine's production and use as a chemical intermediate in the produciton of dyes(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a log Kow of 1.74(2) and a regression-derived equation(3), indicates that p-cresidine is expected to have high mobility in soil(SRC). However, aromatic amines are expected to bind strongly to humus or organic matter in suspended solids and sediments due to the high reactivity of the aromatic amino group(4,5). Volatilization of p-cresidine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.2X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(6). p-Cresidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.5X10-2 mm Hg(SRC), determined from a fragment constant method(7). p-Cresidine reached 0.7% of its theoretical BOD in 2 weeks using the Japanese MITI test(8), suggesting that biodegradation is not a rapid environmental fate process in soils(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a log Kow of 1.74(2) and a regression-derived equation(3), indicates that p-cresidine is not expected to adsorb to suspended solids and sediment(SRC). However, aromatic amines are expected to bind strongly to humus or organic matter in suspended solids and sediments due to the high reactivity of the aromatic amino group(4,5). Volatilization from water surfaces may occur slowly(3) based upon an estimated Henry's Law constant of 1.2X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(6). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 23 and 169 days, respectively(SRC). According to a classification scheme(7), a BCF of <4.6(8), suggests bioconcentration in aquatic organisms is low(SRC). p-Cresidine reached 0.7% of its theoretical BOD in 2 weeks using the Japanese MITI test(8), suggesting that biodegradation is not a fast environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), p-cresidine, which has an estimated vapor pressure of 2.5X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase p-cresidine 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 2 hrs(SRC), calculated from its rate constant of 2.2X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3).

AEROBIC: p-Cresidine, present at 100 mg/l, reached 0.7% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test(1).

The rate constant for the vapor-phase reaction of p-cresidine with photochemically-produced hydroxyl radicals has been estimated as 2.2X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). p-Cresidine is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(2) nor to directly photolyze due to the lack of absorption in the environmental UV spectrum (>290 nm).

BCFs of <4.6 to 10 were measured for p-cresidine(1,2). In a bioconcentration test using orange-red killifish, p-cresidine was listed as a compound which is non accumulative or of low accumulation in aquatic organisms(3). According to a classification scheme(4), these BCF values suggest that bioconcentration in aquatic organisms is low.

The Koc of p-cresidine is estimated as 53(SRC), using a log Kow of 1.74(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that p-cresidine is expected to have high mobility in soil. However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(4,5), suggesting that mobility may be much lower in some soils(SRC).

The Henry's Law constant for p-cresidine is estimated as 1.24X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that p-cresidine is expected to be essentially nonvolatile from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 23 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 169 days(SRC). p-Cresidine's Henry's Law constant indicates that volatilization from moist soil surfaces may occur slowly(SRC). However, aromatic amines are expected to bind strongly to suspended solids and sediment in water due to the high reactivity of the aromatic amino group(3,4), suggesting that volatilization may be much lower in some soils(SRC). p-Cresidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.5X10-2 mm Hg(SRC), determined from a fragment constant method(5).

Occupational exposure to p-cresidine may occur through inhalation and dermal contact with this compound at workplaces where p-cresidine is produced or used. (SRC)

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 P-CRESIDINE (6 total), please visit the HSDB record page.

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Health: TOXIC; inhalation, ingestion, or skin contact with material may cause severe injury or death. 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. /Anisidines; Anisidines, liquid; Anisidines, solid/

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. When heated, vapors may form explosive mixtures with air: indoors, outdoors, and sewers explosion hazards. Those substances designated with a "P" may polymerize explosively when heated or involved in a fire. Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. /Anisidines; Anisidines, liquid; Anisidines, solid/

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (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. Ventilate enclosed areas. /Anisidines; Anisidines, liquid; Anisidines, solid/

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (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. /Anisidines; Anisidines, liquid; Anisidines, solid/

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

UN 2431; o-Anisidine; Anisidines, liquid or solid.

IMO 6.1; o-Anisidine; Anisidines liquid or solid.

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/

Do not transport with food and feedstuffs.

Symbol: T; R: 45-22; S: 53-45; Note: E