Occurrence
Contained in Peru balsam and in the concrete and absolute of tuberose flowers, hyacinth, Narcissus jonquilla
L., and Dianthus caryophillus L.; also in the oil of ylang-ylang and in Tolu balsam. Reported found in American cranberry, cinnamon
bark, cassia leaf, corn oil and hog plum (Spondias mombins L.).
Definition
ChEBI: Benzyl benzoate is a benzoate ester obtained by the formal condensation of benzoic acid with benzyl alcohol. It has been isolated from the plant species of the genus Polyalthia. It has a role as a scabicide, an acaricide and a plant metabolite. It is a benzyl ester and a benzoate ester. It is functionally related to a benzoic acid.
Indications
Benzyl benzoate: 20% to 25%. This agent is relatively nontoxic and is widely
used in developing countries to treat scabies and pediculosis capitis and pubis.
Only a veterinary preparation is available in the United States. Benzyl benzoate is
synthetically derived from the esterification of benzoic acid with benzyl alcohol. Its
mechanism of action is unknown. It is toxic to Sarcoptes scabei and may be toxic
to Pediculosis capitis and Phthirus pubis. No resistance has been demonstrated
to date.
Benzyl benzoate can be used in a 5% emulsion to repel many arthropods and can
be used as a lotion to treat sarcoptic mange and canine pediculosis.
Production Methods
BENZYL BENZOATE is produced by the Cannizzaro reaction from benzaldehyde, by esterifying benzyl alcohol with benzoic acid, or by treating sodium benzoate with benzyl chloride. It is purified by distillation and crystallization. Benzyl benzoate is used as a fixative and solvent for musk in perfumes and flavors, as a plasticizer, miticide, and in some external medications. The compound has been found effective in the treatment of scabies and pediculosis capitis (head lice, Pediculus humanus var. capitis).
Brand name
Pharmaceutic necessity for
Dimercaprol [Injection]. Benylate (Sterling Winthrop).
Taste threshold values
Taste characteristics at 30 ppm: balsamic, fruity with powdery and berry nuances.
General Description
Benzyl benzoate is an aromatic ester that is used as a food flavoring agent. It has been identified as one of the main volatile aroma component of cranberry, mango and Egyptian Jasminum sambac flowers.
Hazard
Irritant to eyes, skin.
Flammability and Explosibility
Notclassified
Pharmaceutical Applications
Benzyl benzoate is used as a solubilizing agent and nonaqueous
solvent in intramuscular injections at concentrations of
0.01–46.0% v/v, and as a solvent and plasticizer for cellulose
and nitrocellulose. It is also used in the preparation of spray-dried
powders using nanocapsules.
However, the most widespread pharmaceutical use of benzyl
benzoate is as a topical therapeutic agent in the treatment of
scabies. Benzyl benzoate is also used therapeutically as a
parasiticide in veterinary medicine.
Other applications of benzyl benzoate include its use as a
pediculicide, and as a solvent and fixative for flavors and perfumes
in cosmetics and food products.
Biochem/physiol Actions
Benzyl benzoate is the condensation product of benzoic acid and benzyl alcohol. It is utilized for treating human scabies as well as kills house dust mite.
Clinical Use
Benzyl benzoate is a naturally occurring ester obtained fromPeru balsam and other resins. It is also prepared syntheticallyfrom benzyl alcohol and benzoyl chloride. The ester isa clear colorless liquid with a faint aromatic odor. It is insolublein water but soluble in organic solvents.
Benzyl benzoate is an effective scabicide when appliedtopically. Immediate relief from itching probably resultsfrom a local anesthetic effect; however, a complete cureis frequently achieved with a single application of a 25%emulsion of benzyl benzoate in oleic acid, stabilized withtriethanolamine. This preparation has the additionaladvantage of being essentially odorless, nonstaining, andnonirritating to the skin. It is applied topically as a lotionover the entire dampened body, except the face.
Safety
Benzyl benzoate is metabolized by rapid hydrolysis to benzoic acid
and benzyl alcohol. Benzyl alcohol is then further metabolized to
hippuric acid, which is excreted in the urine.
Benzyl benzoate is widely used as a 25% v/v topical application
in the treatment of scabies and as an excipient in intramuscular
injections and oral products. Adverse reactions to benzyl benzoate
include skin irritation and hypersensitivity reactions. Oral ingestion
may cause harmful stimulation of the CNS and convulsions. Benzyl
benzoate should be avoided by perople with perfume allergy.
LD50 (cat, oral): 2.24 g/kg
LD50 (dog, oral): 22.44 g/kg
LD50 (guinea pig, oral): 1.0 g/kg
LD50 (mouse, oral): 1.4 g/kg
LD50 (rabbit, oral): 1.68 g/kg
LD50 (rabbit, skin): 4.0 g/kg
LD50 (rat, oral): 0.5 g/kg
LD50 (rat, skin): 4.0 g/kg
Synthesis
This colorless liquid is formally the condensation product of benzoic acid and benzyl alcohol. It can also be generated from benzaldehyde by the Tishchenko reaction.
Environmental Fate
Benzyl benzoate acts as a local irritant. At high levels of exposure,
free benzoic acid may sequester significant amounts of
acetyl coenzyme A (CoA), which could disrupt cholinergic
signaling. Recent findings suggest that benzyl benzoate may
have estrogenic properties.
Metabolism
Benzyl benzoate, a relatively non-toxic liquid widely used for the treatment of scabies, is converted into benzoic acid in vivo (Williams, 1959).
storage
Benzyl benzoate is stable when stored in tight, well-filled, lightresistant
containers. Exposure to excessive heat (above 408℃)
should be avoided.
Toxicity evaluation
Acute oral LD50 for rats: 1,700 mg/kg
Incompatibilities
Benzyl benzoate is incompatible with alkalis and oxidizing agents.
Regulatory Status
Included in the FDA Inactive Ingredients Database (IM injections
and oral capsules). Included, as an active ingredient, in nonparenteral
medicines licensed in the UK. Included in the Canadian List
of Acceptable Non-medicinal Ingredients.
