tert-Butylhydroxyanisole

180.24000

180.12000

204-442-7

62RAC24292

DTXSID7040788

29093090

29.5

3.2

Butylated hydroxyanisole appears as white, beige or slightly yellow waxy solid with an aromatic odor and a slightly bitter burning taste. (NTP, 1992)

0.9976 (rough estimate)

48-55 °C

264-270 °C @ Press: 733 Torr

313° F (NTP, 1992)

H2O: <0.1 g/100 mL at 18.5 ºC;less than 1 mg/mL at 65.3° F (NTP, 1992)

Exposure to light causes discoloration and loss of activity. Butylated hydroxyanisole should be stored in a well-closed container, protected from light, in a cool, dry place.

LD50 in mice, rats (mg/kg): 2000, 2200 orally (Lehman)

Insoluble in water.

Ethers

BUTYLATED HYDROXYANISOLE degrades with prolonged exposure to sunlight. Exhibits antioxidant properties and synergism with acids, BHT, propyl gallate, hydroquinone, methionine, lecithin and thiodipropionic acid. It exhibits antioxidant properties as a scavenger of free radicals. It is incompatible with oxidizing agents and ferric salts. (NTP, 1992)

Ⅲ

3077

2

9

S26;S36/37/39

SL1945000

Xn

Stable, combustible. Incompatible with oxidizing agents, ferric salts. Degrades on long exposure to sunlight.

P261-P281-P305 + P351 + P338

H302-H315-H319-H335-H351

Substances classified as antioxidants, when migrating from food-packaging material (limit of addition to food, 0.005 percent) include butylated hydroxyanisole.|Butylated hydroxyanisole used as a chemical preservative in food for human consumption is generally recognized as safe when the total content of antioxidants is not over 0.02 percent of fat or oil content, including essential (volatile) oil content of food, provided the substance is used in accordance with good manufacturing practice.|Butylated hydroxyanisole used as a chemical preservative in animal drugs, feeds, and related products is generally recognized as safe when the total content of antioxidants is not over 0.02 percent of fat or oil content, including essential (volatile) oil content of food, provided the substance is used in accordance with good manufacturing or feeding practice.

This chemical is combustible. (NTP, 1992)

Not Classified| |Danger|H302 (57.46%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P273, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P310, P312, P321, P330, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 952 companies from 47 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H317: May cause an allergic skin reaction [Warning Sensitization, Skin]|P201, P202, P261, P272, P280, P281, P302+P352, P308+P313, P321, P333+P313, P363, P405, and P501|H303: May be harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P271, P272, P280, P281, P302+P352, P304+P340, P308+P313, P312, P321, P333+P313, P363, P403+P233, P405, and P501

Fires involving this compound can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

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 protect this material from exposure to light. Keep it away from oxidizing materials and store it at ambient temperatures. (NTP, 1992)

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)

IDENTIFICATION AND USE: 3-tert-Butyl-4-hydroxyanisole is a component of Butylated Hydroxyanisole which is a commonly used food preservative. This material is an oxidation inhibitor and has been accepted for the use in foods where Butylated hydroxytoluene is restricted. This chemical is used as a food preservative for human consumption. HUMAN EXPOSURE AND TOXICITY: There is no human studies concerning.3-tert-Butyl-4-hydroxyanisole ANIMAL STUDIES: The mutagenicity of 3-tert-butyl-4-hydroxyanisole and its metabolites was determined in the reverse mutation assay using Salmonella typhimurium, strains and in the chromosomal aberration test in vitro using the Chinese hamster fibroblast cell line, the chemical did not show any mutagenic activity. 3-tert-Butyl-4-hydroxyanisole induced chromosomal aberrations only in the presence of S9 mix.

IN TESTS ON BENZO(A)PYRENE-INDUCED NEOPLASIA OF FORESTOMACH OF ICR/HA MOUSE, ADDN OF 3-TERT-BUTYL-4-HYDROXYANISOLE DECR NUMBER & INCIDENCE OF TUMOR FORMATION.|MICE MAINTAINED ON DIET CONTAINING 0.75% 2(3)-TERT-BUTYL-4-HYDROXYANISOLE (BHA) FOR 8 DAYS SHOWED 50% REDUCTION IN MAXIMAL ORNITHINE DECARBOXYLASE (ODC) INDUCTION FOLLOWING TREATMENT WITH TPA (12-O-TETRADECANOYLPHORBOL-13-ACETATE) WHEN COMPARED TO MICE FED CONTROL DIET. TOPICAL APPLICATION OF BHA (55 UMOLE) 30 MIN PRIOR TO TPA TREATMENT (17 NMOL) ELICITED 80% INHIBITION OF PROMOTER-INDUCED ODC ACTIVITY. BHA WAS INEFFECTIVE AS INHIBITOR WHEN ADMIN 16 HR BEFORE OR 2 HR AFTER THE PROMOTER. INHIBITION WAS DOSE DEPENDENT WITH A DOSE PRODUCING 50% INHIBITION OF ODC INDUCTION OF 6 UMOLE. A STRUCTURE-ACTIVITY STUDY SHOWED THAT HYDROXYL & TERT-BUTYL SUBSTITUENTS WERE IMPORTANT DETERMINANTS OF INHIBITORY ACTIVITY.|RATS WERE FED 2(3)-TERT-BUTYL-4-HYDROXYANISOLE (0.5% WT/WT) IN DIET WITH OR WITHOUT CIPROFIBRATE (10 MG/KG BODY WT) FOR 60 WK. 2(3)-TERT-BUTYL-4-HYDROXYANISOLE CAUSED SIGNIFICANT DECR IN INCIDENCE & NUMBER OF HEPATOCELLULAR CARCINOMAS THAT WERE LARGER THAN 5 MM. DATA SUGGEST THAT INHIBITORY EFFECT ON CIPROFIBRATE-INDUCED HEPATIC TUMORIGENESIS MAY BE DUE TO H2O2 & FREE RADICAL-SCAVENGING PROPERTY, SINCE IT DOES NOT PREVENT PEROXISOMES PROLIFERATION & INDUCTION OF H2O2-GENERATING PEROXISOMAL ENZYMES IN LIVERS OF RATS FED CIPROFIBRATE.|BHA LD50 was determined in mice and rats following ip or oral admin, using dimethylsulfoxide or olive oil as vehicle. When dimethylsulfoxide was used, BHA ip LD50 was about two orders of magnitude lower as compared to oral LD50. This difference was not so marked when BHA was administered in olive oil. /BHA/|/Both BHA and BHT have chemopreventive action when/ administered together with several carcinogens affecting diverse target organs. The antioxidants increase detoxifying enzymes for carcinogens, and many act as free radical trapping agents. The structure of these agents does not suggest a likely electrophile and tests for genotoxicity have been uniformly negative. Both BHA and BHT have been shown to inhibit cell-to-cell communication in culture. /BHA/

LD50 Rat oral 4000 mg/kg

CONCENTRATIONS OF 2-TERT-BUTYL-4-METHOXYPHENOL & 2,2'-DIHYDROXY-3,3'-DI-TERT-BUTYL-5,5'DIMETHOXY-DIPHENYL (DI-BHA) APPEARED AT DIFFERENT TIMES (0.15-24 HR) IN RAT PLASMA & INTESTINE FOLLOWING 2 G/KG SINGLE ORAL ADMIN OF 2-TERT-BUTYL-4-METHOXYPHENOL. PEAK CONCN IN ALL TISSUES ANALYZED WERE OBSERVED WITHIN 1 HR OF ADMIN. IN INTESTINE 2-TERT-BUTYL-4-METHOXYPHENOL LEVELS WERE APPROX 10 TIMES HIGHER THAN DI-BHA; IN PLASMA THEY WERE BETWEEN 100 & 15 TIMES HIGHER. THE RAT INTESTINE IS CAPABLE OF TRANSFORMING IN VIVO 2-TERT-BUTYL-4-METHOXYPHENOL INTO DI-BHA & MAY BE MAJOR SITE WHERE THIS TRANSFORMATION OCCURS.

FOLLOWING ORAL ADMIN OF 2 G/KG OF 2-TERT-BUTYL-4-METHOXYPHENOL TO RATS, THE METABOLITE 2,2'-DIHYDROXY-3,3'-DI-TERT-BUTYL-5,5'-DIMETHOXYDIPHENYL WAS DETECTED IN PLASMA & TISSUE 0.15-24 HR AFTER ADMIN.|DI-BHA (2,2'-DIHYDROXY-3,3'-DI-TERT-BUTYL-5,5'-DIMETHOXYDIPHENYL) WAS ISOLATED AS REACTION PRODUCT OF EITHER COMMERCIAL HORSERADISH PEROXIDASE OR PARTIALLY PURIFIED RAT INTESTINE PEROXIDASE & HYDROGEN PEROXIDE WITH 2-TERT-BUTYL-4-METHOXYPHENOL. CYCLIC COMPOUNDS (SUCH AS DI-BHA) POSSESSING A HYDROXY GROUP IN THE RING ARE COMPETITIVE INHIBITORS WITH RESPECT TO GUAIACOL & NON-COMPETITIVE INHIBITORS WITH RESPECT TO HYDROGEN PEROXIDASE IN A SYSTEM CONTAINING GUAIACOL, HYDROGEN PEROXIDASE & PEROXIDASE.

ADMIN OF 2(3)-TERT-BUTYL-4-HYDROXYANISOLE (BHA) TO RODENTS PROTECTS A VARIETY OF TARGET TISSUES AGAINST PRODUCTION OF TUMORS BY WIDE RANGE OF CHEMICAL CARCINOGENS. BHA REDUCES LEVELS OF MUTAGENIC METABOLITES PRODUCED FROM BENZO(A)PYRENE & NUMEROUS THERAPEUTIC AGENTS IN VIVO; IT ELEVATES HEPATIC ACTIVITIES OF MICROSOMAL EPOXIDE HYDRATASE & CYTOSOL GLUTATHIONE S-TRANSFERASE; IT ALTERS ACTIVITIES OF OTHER HEPATIC ENZYMES & AFFECTS LEVELS OF SOME HEPATIC CATALYTIC CONSTITUENTS; & IT INCREASES CONCN OF NONPROTEIN THIOL COMPOUNDS IN LIVER & SEVERAL OTHER TISSUES. /BHA/|EFFECTS OF BUTYLATED HYDROXYANISOLE (BHA) ON ARYL HYDROCARBON HYDROXYLASE (AHH) ACTIVITES IN LIVER, LUNG & SKIN OF RATS & MICE WERE STUDIED TO EXAMINE POSSIBLE MECHANISMS OF ANTICARCINOGENIC ACTIONS. AHH INDUCERS, 3-METHYLCHOLANTHRENE, PHENOBARBITAL &2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN WERE USED. IT WAS OBSERVED THAT 2-TERT-BUTYL-4-HYDROXYANISOLE, 3-TERT-BUTYL-4-HYDROXYANISOLE & BHA COMMERCIAL MIXTURE (85% 3-BHA & 15% 2-BHA) HAD ABOUT THE SAME POTENCY IN INHIBITING MICROSOMAL AHH, ALTHOUGH THE 2-ISOMER APPEARED TO BE SLIGHTLY MORE INHIBITORY. DATA SUGGEST THAT INHIBITORY ACTION OBSERVED IN COMMERCIAL BHA IS DUE TO THE COMBINED ACTION OF BOTH ISOMERS & IS DEPENDENT ON SPECIES OF ANIMAL, TISSUE TYPES & TREATMENT WITH INDUCERS.|/Both BHA and BHT have chemopreventive action when/ administered together with several carcinogens affecting diverse target organs. The antioxidants increase detoxifying enzymes for carcinogens, and many act as free radical trapping agents. The structure of these agents does not suggest a likely electrophile and tests for genotoxicity have been uniformly negative. Both BHA and BHT have been shown to inhibit cell-to-cell communication in culture. /BHA/

Arsenic, less than 3 ppm; heavy metal (as lead), less than 10 ppm; residual on ignition, less than 0.01% /BHA/

SYMPTOMS: Symptoms of exposure to this compound may include allergic contact dermatitis, exacerbation of vasomotor rhinitis, conjunctival irritation and redness, asthma, facial flushing, marked diaphoresis, headaches, dull retrosternal pain and somnolence. It may also cause hypersensitivity reactions after skin contact. ACUTE/CHRONIC HAZARDS: This compound is toxic by ingestion. When heated to decomposition this compound emits acrid smoke and irritating fumes. (NTP, 1992)|Carcinogens

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)

3-BHA

THE COMMERCIAL PREPN /OF BHA/ SOLD UNDER NAME OF TENOX BHA (EASTMAN CHEM INC) CONTAINS ABOUT 85% OF ... 3-TERT-BUTYL-4-HYDROXYANISOLE & 15% OF ... /2-TERT-BUTYL-4-HYDROXYANISOLE/.|Food Grade, 98.5+%.

All other basic organic chemical manufacturing|Phenol, (1,1-dimethylethyl)-4-methoxy-: ACTIVE|Phenol, 2-(1,1-dimethylethyl)-4-methoxy-: ACTIVE|Commercially available BHA is generally an 85:15 mixture of the 3-t-butyl- and 2-t-butyl-isomer.

HPLC, HPL & GC COMBINED WITH MASS SPECTROSCOPY WERE DEVELOPED TO DETECT 3-TERT-BUTYL-4-HYDROXYANISOLE & 2-TERT-BUTYL-4-HYDROXYANISOLE IN COMMERCIAL BUTYLATED HYDROXYANISOLE USED AS ANTIOXIDANT IN PHARMACEUTICALS & FOODS.|HPLC USED FOR DETECTION & ANALYSIS OF BUTYLATED HYDROXYANISOLE ISOMERS; INCLUDING 3-BHA IN FOOD.|Butylated hydroxyanisole is extracted from ready to eat breakfast cereals with carbon disulfide and determined by GC, using flame ionization detection.

METHOD IS DESCRIBED FOR DETECTION OF 3-TERT-BUTYL-4-HYDROXYANISOLE IN RAT PLASMA USING HIGH RESOLUTION CAPILLARY GC/MS WITH SELECTIVE ION MONITORING. 10 NG/ML CAN BE DETECTED IN 0.1 ML SAMPLES.

Food additives|Food Additives -> ANTIOXIDANT; -> JECFA Functional Classes|Health Hazards -> Carcinogens|Cosmetics -> Antioxidant

Food Additives -> ANTIOXIDANT;