Benzyl Alcohol

(rINN)
Benzyl Alcohol Chemical formula
Synonyms: Alcohol bencílico; Alcohol benzylicus; Alcoholum Benzylicum; Alcool Benzylique; Alkohol benzylowy; Bensylalkohol; Bentsyylialkoholi; Benzenemethanol; Benzil-alkohol; Benzilo alkoholis; Benzylalkohol; Benzylique, alcool; Fenilmetanol; Phenylcarbinol; Phenylmethanol.
Cyrillic synonym: Бензиловый Спирт.

💊 Chemical information

Chemical formula: C6H5.CH2OH = 108.1.
CAS — 100-51-6.

Pharmacopoeias.

In Chin., Eur., Int., and Jpn. Also in USNF.

Ph. Eur. 6.2

(Benzyl Alcohol). A clear colourless, oily liquid. Soluble in water; miscible with alcohol, and with fatty and essential oils. Store under nitrogen in airtight containers at a temperature of 2° to 8°. Protect from light.

USNF 26

(Benzyl Alcohol). A clear, colourless, oily liquid. Sparingly soluble in water; freely soluble in alcohol (50%); miscible with alcohol, with chloroform, and with ether. It is neutral to litmus.

Incompatibility.

Benzyl alcohol is incompatible with oxidising agents and strong acids. The antimicrobial activity may be reduced by nonionic surfactants and benzyl alcohol may be lost from solutions stored in polyethylene containers.

Stability.

Benzyl alcohol oxidises to produce benzaldehyde and benzoic acid and oxidation may take place slowly on exposure to air. Benzaldehyde may also be produced on autoclaving.

💊 Adverse Effects and Precautions

There have been a few reports of hypersensitivity reactions to benzyl alcohol when used as a preservative. The pure alcohol is irritant and requires handling with care; ingestion or inhalation can cause nausea, vomiting, diarrhoea, headache, and vertigo. Overexposure results in respiratory failure and CNS depression. However, concentrations of benzyl alcohol normally used for preservation are not associated with such effects. There have been some instances of neurotoxic effects in patients given intrathecal injections that contained benzyl alcohol. A fatal toxic syndrome in premature infants was attributed to benzyl alcohol present as a preservative in solutions used to flush intravenous catheters. This has led to restriction on the use of benzyl alcohol in neonates and young children, (see below).

Effects on the lungs.

Severe bronchitis and haemoptysis was reported in a patient with obstructive pulmonary disease who, over a period of 2 years, had inhaled salbutamol nebuliser solution diluted with a bacteriostatic sodium chloride solution containing benzyl alcohol.1
1. Reynolds RD. Nebulizer bronchitis induced by bacteriostatic saline. JAMA 1990; 264: 35.

Effects on the nervous system.

Rapid development of flaccid areflexic paraplegia, total anaesthesia below the groin, and radicular abdominal pain occurred in a 64-year-old man after a lumbar intrathecal injection of cytarabine that contained 1.5% benzyl alcohol.1 The patient recovered fully after 100 mL of CSF was replaced with sodium chloride 0.9% and 40 mg of methylprednisolone. Intrathecal injections of cytarabine dissolved in sterile distilled water before and after the episode of paraplegia caused no neurologic symptoms. On reviewing 20 other cases of paraparesis associated with methotrexate or cytarabine intrathecal injections, benzyl alcohol had been used as a preservative in 7. Of these, 4 developed neurotoxicity immediately; in the other 3 it did not develop for between 6 and 48 hours. The duration varied. One patient did not improve, one made a partial recovery, a third took 6 weeks to recover, another took 5 days; yet 2 patients recovered within 1 ⁄ to 2 ⁄ hours while the final patient experienced only transient effects.
1. Hahn AF, et al. Paraparesis following intrathecal chemotherapy. Neurology 1983; 33: 1032–8.

Hypersensitivity.

Hypersensitivity reactions to benzyl alcohol have been reported.1-3
1. Grant JA, et al. Unsuspected benzyl alcohol hypersensitivity. N Engl J Med 1982; 306: 108
2. Shmunes E. Allergic dermatitis to benzyl alcohol in an injectable solution. Arch Dermatol 1984; 120: 1200–1
3. Wilson JP, et al. Parenteral benzyl alcohol-induced hypersensitivity reaction. Drug Intell Clin Pharm 1986; 20: 689–91.

Neonates.

During 1981 and 1982 reports were published from 2 centres in the USA1-3 of 20 deaths in low-birth-weight neonates attributed to the use of benzyl alcohol as a preservative in solutions used to flush their umbilical catheters and in some cases also to dilute their medication. The neonates suffered a toxic syndrome whose features included metabolic acidosis, symptoms of progressive encephalopathy, intracranial haemorrhage, and respiratory depression with gasping. These deaths prompted the FDA4 to recommend that benzyl alcohol should not be used in such flushing solutions; sodium chloride injection 0.9% without preservative should be used instead. The FDA had also advised against the use of benzyl alcohol or any preservative in fluids being used for the dilution or reconstitution of medicines for the newborn. Those reporting the deaths2,3 considered that the toxic syndrome could have been caused by the accumulation of the benzoic acid metabolite of benzyl alcohol, which could not be handled effectively by the immature liver; given the very low weight of the neonates they would have been receiving a comparatively high dose of benzyl alcohol. In commenting on the problem, the American Academy of Pediatrics5 agreed that the FDA’s warning was warranted, but pointed out that there was no evidence from controlled studies to confirm that benzyl alcohol was responsible.
1. Gershanik JJ, et al. The gasping syndrome: benzyl alcohol (BA) poisoning? Clin Res 1981; 29: 895A
2. Brown WJ, et al. Fatal benzyl alcohol poisoning in a neonatal intensive care unit. Lancet 1982; i: 1250
3. Gershanik J, et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med 1982; 307: 1384–8
4. Anonymous. Benzyl alcohol may be toxic to newborns. FDA Drug Bull 1982; 12: 10–11
5. American Academy of Pediatrics. Benzyl alcohol: toxic agent in neonatal use. Pediatrics 1983; 72: 356–7.

💊 Pharmacokinetics

Benzyl alcohol is metabolised to benzoic acid. This is conjugated with glycine in the liver to form hippuric acid which is excreted in the urine. Benzaldehyde and
benzoic acid are degradation products in vitro.

💊 Uses

Benzyl alcohol is used as an antimicrobial preservative. It is bacteriostatic mainly against Gram-positive organisms and some fungi. It is used in a range of pharmaceutical preparations in concentrations up to 2%. Concentrations of 5% or more are employed when it is used as a solubiliser. Benzyl alcohol is used as a preservative in foods and cosmetics. It is also used as a disinfectant at a concentration of 10%. In addition to its antiseptic properties, concentrations of benzyl alcohol of up to 10% possess weak local anaesthetic and antipruritic activity.

💊 Preparations

Proprietary Preparations

Canad.: Babys Own Teething Gel†; Zilactin Cold Sore Gel; USA: Zilactin. Multi-ingredient: Arg.: Standard XXI; Austral.: Coso; Soothe’n Heal; Austria: Dermaspray; Belg.: Dermaspray†; Purigel Crisp; Purigel NF; Chile: Aucusik; Medikem†; Medisept†; Denm.: Doloproct Comp; Fr.: Biseptine; Codotussyl Maux de Gorge; Dermaspraid Antiseptique; Pastilles Medicinales Vicks; Ger.: Autoderm Extra; Gelipur; Spitacid; India: Dicloran MS; Israel: Otomycin; Ital.: Borocaina; Foille Scottature; Foille Sole; Pitiren; Prurex; Skab 2; Singapore: Saak†; Spain: Acerbiol; Pastillas Antisep Garg M; UK: Sudocrem; USA: Itch-X; MouthKote O/R; Oragesic; Super Ivy Dry; Topic; Tucks.
Used as an adjunct in: Jpn: Panpurol†.
Published November 14, 2018.