International Numbering System (INS) for Food Additives: 321
Food additives Europe numbers: E321
Functional Category
Antioxidant
Applications in Pharmaceutical Formulation
Butylated hydroxytoluene is used as an antioxidant (see Table I) in cosmetics, foods, and pharmaceuticals.(1–4) 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(5) and has been used therapeutically to treat herpes simplex labialis.(6)
Description
Butylated hydroxytoluene occurs as a white or pale yellow crystalline solid or powder with a faint characteristic phenolic odor
Stability and Storage Conditions
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
Incompatibilities
Butylated hydroxytoluene is phenolic and undergoes reactions characteristic of phenols. It is incompatible with strong oxidizing agents such as peroxides and permanganates. Contact with oxidizing agents may cause spontaneous combustion. Iron salts cause discoloration with loss of activity. Heating with catalytic amounts of acids causes rapid decomposition with the release of the flammable gas isobutene.
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.(7,8) The WHO has set a temporary estimated acceptable daily intake for butylated hydroxytoluene at up to 125 mg/kg body-weight.(9) Ingestion of 4 g of butylated hydroxytoluene, although causing severe nausea and vomiting, has been reported to be nonfatal.(10) LD50 (guinea pig, oral): 10.7 g/kg(11) 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