Chemical Properties
white crystalline solid
Uses
Antioxidant 264 as general antioxidants is used widely in polymer materials, petroleum products and food processing industries. Antioxidant 264 is commonly used rubber antioxidant, heat, oxygen aging have some protective effect, but also can inhibit copper harm. This product does not change color, not pollution. Antioxidants 264 high solubility in oil, no precipitation, less volatile, non-toxic and non-corrosive.
Definition
ChEBI: A member of the class of phenols that is 4-methylphenol substituted by tert-butyl groups at positions 2 and 6.
Uses
Antioxidant for food, animal feed, petroleum products, synthetic rubbers, plastics, animal and vegetable oils, soaps. Antiskinning agent in paints and inks.
General Description
White crystalline solid.
Reactivity Profile
Phenols, such as BUTYLATED HYDROXYTOLUENE(128-37-0), do not behave as organic alcohols, as one might guess from the presence of a hydroxyl (-OH) group in their structure. Instead, they react as weak organic acids. Phenols and cresols are much weaker as acids than common carboxylic acids (phenol has Ka = 1.3 x 10^[-10]). These materials are incompatible with strong reducing substances such as hydrides, nitrides, alkali metals, and sulfides. Flammable gas (H2) is often generated, and the heat of the reaction may ignite the gas. Heat is also generated by the acid-base reaction between phenols and bases. Such heating may initiate polymerization of the organic compound. Phenols are sulfonated very readily (for example, by concentrated sulfuric acid at room temperature). The reactions generate heat. Phenols are also nitrated very rapidly, even by dilute nitric acid. Nitrated phenols often explode when heated. Many of them form metal salts that tend toward detonation by rather mild shock. May react with oxidizing materials.
Air & Water Reactions
Insoluble in water.
Potential Exposure
DBPC is used as a food and feed additive,
flavor, and packaging material; as an antioxidant in human
foods and animal feeds. It is also used as an antioxidant to sta-
bilize petroleum fuels, rubber and vinyl plastics.
Fire Hazard
This chemical is combustible.
First aid
Move victim to fresh air. Call 911 or emergency
medical service. Give artificial respiration if victim is not
breathing. Do not use mouth-to-mouth method if victim
ingested or inhaled the substance; give artificial respira-
tion with the aid of a pocket mask equipped with a one-way
valve or other proper respiratory medical device.
Administer oxygen if breathing is difficult. Remove and
isolate contaminated clothing and shoes. In case of contact
with substance, immediately flush skin or eyes with run-
ning water for at least 20 minutes. For minor skin contact,
avoid spreading material on unaffected skin. Keep victim
warm and quiet. Effects of exposure (inhalation, ingestion,
or skin contact) to substance may be delayed. Ensure that
medical personnel are aware of the material(s) involved
and take precautions to protect themselves. Medical obser-
vation is recommended for 24 to 48 hours after breathing
overexposure, as pulmonary edema may be delayed. As
first aid for pulmonary edema, a doctor or authorized para-
medic may consider administering a drug or other inhala-
tion therapy.
Shipping
UN2811 Toxic solids, organic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials, Technical
Name Required.
Incompatibilities
Contact with oxidizers may cause fire
and explosion hazard.
Occurrence
Not reported found naturally.
Preparation
BHT is produced commercially by the alkylation of para-cresol with isobutylene. BHT is also produced by several western
European manufacturers, production/processing plants in Germany, France, the Netherlands, United Kingdom and Spain.
Production Methods
Prepared by the reaction of p-cresol with isobutene.
Health Hazard
2,6-Di-tert-butyl-p-cresol or
BHT is of relatively low acute toxicity in
animals, and there is no evidence of either
acute or chronic effects among exposed
workers.
Flammability and Explosibility
Nonflammable
Pharmaceutical Applications
Butylated hydroxytoluene is used as an antioxidant in
cosmetics, foods, and pharmaceuticals. It is mainly used to
delay or prevent the oxidative rancidity of fats and oils and to
prevent loss of activity of oil-soluble vitamins.
Butylated hydroxytoluene is also used at 0.5–1.0% w/w
concentration in natural or synthetic rubber to provide enhanced
color stability.
Butylated hydroxytoluene has some antiviral activity and has
been used therapeutically to treat herpes simplex labialis.
Biochem/physiol Actions
Butylated hydroxytoluene (BHT) is a phenolic antioxidant. It has been shown to inhibit lipid peroxidation. It causes lung injury and promotes tumors in mice, but this may be due to a metabolite of BHT, 6-tert-butyl-2-[2′-(2′-hydroxymethyl)-propyl]-4-methylphenol. Metabolites of BHT have also been reported to induce DNA strand breaks and internucleosomal DNA fragmentation (a characteristic of apoptosis) in cultured cells. In rats, a single intraperitoneal injection of BHT (60 mg/kg body mass) results in a significant increase in nuclear DNA methyl transferase activity in the liver, kidneys, heart, spleen, brain and lungs. Incubation of alveolar macrophages with BHT significantly reduced the level of TNF-α which may explain the mechanism by which this antioxidant reduces inflammation. Preincubation of aspirin-treated platelets with BHT inhibits the secretion, aggregation, and protein phosphorylation induced by protein kinase C activators. BHT was also found to inhibit the initiation of hepatocarcinogenesis by aflatoxin B1.
Carcinogenicity
The IARC has determined that there is
limited evidence for the carcinogenicity of
BHT in experimental animals.
BHT has given primarily negative results
in a large number of in vivo and in vitro genotoxic
assays.
No significant reproductive effects were
observed in three-generation toxicity studies in
mice administered up to 0.4% in the diet.6
The 2003 ACGIH threshold limit valuetime-
weighted average (TLV-TWA) for 2,6-ditert-
butyl-p-cresol is 2mg/m3.
Environmental Fate
The metabolites of BHT can bind to cellular macromolecules,
such as proteins and DNA, and cause toxicity.
Safety Profile
Poison by intraperitoneal andintravenous routes. Moderately toxic by ingestion. Anexperimental teratogen. Other experimental reproductiveeffects. A human skin irritant. A skin and eye irritant.Questionable carcinogen with experimental carcinogenicand.
Safety
Butylated hydroxytoluene is readily absorbed from the gastrointestinal tract and is metabolized and excreted in the urine mainly as glucuronide conjugates of oxidation products. Although there have been some isolated reports of adverse skin reactions, butylated hydroxytoluene is generally regarded as nonirritant and nonsensitizing at the levels employed as an antioxidant.
The WHO has set a temporary estimated acceptable daily intake for butylated hydroxytoluene at up to 125 μg/kg body-weight.
Ingestion of 4 g of butylated hydroxytoluene, although causing severe nausea and vomiting, has been reported to be nonfatal.
LD50 (guinea pig, oral): 10.7 g/kg
LD50 (mouse, IP): 0.14 g/kg
LD50 (mouse, IV): 0.18 g/kg
LD50 (mouse, oral): 0.65 g/kg
LD50 (rat, oral): 0.89 g/kg
storage
Exposure to light, moisture, and heat causes discoloration and a loss of activity. Butylated hydroxytoluene should be stored in a wellclosed container, protected from light, in a cool, dry place.
Purification Methods
Dissolve BHT in n-hexane at room temperature, then cool with rapid stirring, to -60o. The precipitate is separated, redissolved in hexane, and the process is repeated until the mother liquor is no longer coloured. The final product is stored under N2 at 0o [Blanchard J Am Chem Soc 82 2014 1960]. It has also been recrystallised from EtOH, MeOH, *benzene, n-hexane, methylcyclohexane or pet ether (b 60-80o), and is dried in a vacuum. [Beilstein 6 IV 3511.]
Toxicity evaluation
BHT is a white crystalline solid. It is insoluble in water and
alkalies; but soluble in most common organic solvents such
as alcohol and ether. Its melting point is 70°C, boiling point
is 265°C, flash point is 127°C, and specific gravity is 1.048
at 20°C.
Toxics Screening Level
The IRSL for Butylated hydroxytoluene is 1 μg/m3 based on annual averaging.
Regulatory Status
GRAS listed. Accepted as a food additive in Europe. Included in the
FDA Inactive Ingredients Database (IM and IV injections, nasal
sprays, oral capsules and tablets, rectal, topical, and vaginal
preparations). Included in nonparenteral medicines licensed in the
UK. Included in the Canadian List of Acceptable Non-medicinal
Ingredients.
References
[1] TUBA AK ?lhami G. Antioxidant and radical scavenging properties of curcumin[J]. Chemico-Biological Interactions, 2008, 174 1: Pages 27-37. DOI:
10.1016/j.cbi.2008.05.003[2] JORDI ROCA. Survival and Fertility of Boar Spermatozoa After Freeze-Thawing in Extender Supplemented With Butylated Hydroxytoluene[J]. Journal of andrology, 2013, 25 3: 397-405. DOI:
10.1002/j.1939-4640.2004.tb02806.x
