Absorption, Distribution and Excretion
The percutaneous absorption was determined in vivo in rhesus monkeys. Absorption through occluded skin was high (56-80 %) in 24 hr. No correlation was seen between skin penetration and the octanol-water partition coefficient. Under unoccluded conditions skin penetration was reduced (32 %), because of evaporation of the compound.
High levels of benzyl alcohol (5-500 ug/10 mL plasma) were found in uremic patients on hemodialysis; benzyl alcohol was not detected in normal controls.
Rabbits given 1 g of benzyl alcohol sc eliminated 300-400 mg of hippuric acid within the following 24 hr. Within 6 hr after oral administration of 0.40 g benzyl alcohol/kg bw, rabbits eliminated 65.7% of dose as hippuric acid in the urine.
In humans and animals, benzyl alcohol was readily absorbed from the gastrointestinal tract. Percutaneous absorption was high following topical use. Rhesus monkeys absorbed 56-80% of a topical dose administered under occlusive conditions in 24 hours; absorption was less under unoccluded conditions due to evaporation. Benzyl alcohol rapidly disappeared from the injection site following intramuscular administration in rats; the disappearance half-life was estimated to be less than 10 minutes. ...
For more Absorption, Distribution and Excretion (Complete) data for BENZYL ALCOHOL (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Benzyl alcohol is normally oxidized rapidly to benzoic acid, conjugated with glycine in the liver, and excreted as hippuric acid. However, this metabolic pathway may not be well developed in premature infants. The benzyl alcohol may therefore have been metabolized to benzoic acid, which could not be conjugated by the immature liver but accumulated, causing metabolic acidosis ... .
When metabolized, benzyl alcohol is converted to benzoic acid by simple oxidation. The relevant data, therefore, relate to benzoic acid and sodium benzoate.
Benzyl alcohol was an intermediate product in the metabolic pathway of benzyl acetate; the subsequent metabolism was identical to that of benzyl alcohol.
In adults, benzyl alcohol is oxidized to benzoic acid, conjugated in the liver with glycine, and excreted in the urine as hippuric acid. The immature metabolic capacities of infants diminish their ability to metabolize and excrete benzyl alcohol. Preterm babies have a greater ability to metabolize benzyl alcohol to benzoic acid than do term babies, but are unable to convert benzoic acid to hippuric acid, possibly because of glycine deficiency. This results in the accumulation of benzoic acid.
For more Metabolism/Metabolites (Complete) data for BENZYL ALCOHOL (8 total), please visit the HSDB record page.
Benzyl alcohol is a known human metabolite of toluene.

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Biological Half-Life
The plasma half-life of benzyl alcohol administered as 2.5% solution in saline was found to be approximately 1.5 hr in dogs injected iv at doses of 52 and 105 mg/kg.
Benzyl alcohol rapidly disappeared from the injection site following intramuscular administration in rats; the disappearance half-life was estimated to be less than 10 minutes. ...

Toxicity Summary
IDENTIFICATION: Benzyl alcohol is an aromatic organic alcohol, water-white in color with a faint aromatic odor and a sharp burning taste; it is a preservative, a solvent, and a local anesthetic. It is used in a wide variety of products including photographic developer for color movie films; dyeing nylon filament, textiles, and sheet plastics; solvent for dyestuffs, cellulose esters, casein, waxes; heat-sealing polyethylene films; intermediate for benzyl esters and ethers; bacteriostatic; cosmetics, ointments, emulsions; ball point pen inks; stencil inks. HUMAN EXPOSURE AND TOXICITY: Benzyl alcohol has been found to be irritating to the skin at levels 3% or greater. Patch test with 0.65% benzyl alcohol did not produce irritation of the skin. Benzyl alcohol poisoning can cause the gasping syndrome in neonates. The infants had a typical course of gradual neurologic deterioration, severe metabolic acidosis, the striking onset of gasping respirations, thrombocytopenia, hepatic and renal failure, hypotension, cardiovascular collapse and death. In every infant, unmetabolized benzyl alcohol was identified in the urine. Hypersensitivity reactions may occur after parenteral or dermal exposure to benzyl alcohol. Acute reactions include urticaria, erythema, palpable edema, fatigue, nausea, diffuse angioedema, maculopapular rash, and fever. A delayed hypersensitivity reaction characterized by erythema, edema, and vesiculation may appear in 2 to 3 days after an immediate reaction to a single benzyl alcohol challenge in the same patient. Reports are available contraindicating the use of neuromuscular blocking agents containing benzyl alcohol. Use of these agents was not advised in neonates or in the epidural space. Benzyl alcohol 0.225 mg/mL, the clinically relevant concentration in triamcinolone acetonide (TA) following intravitreal injection, caused ultrastructural damage and impaired human retinal pigment epithelial cell function at 2 hr. Benzyl alcohol 9.0 mg/mL, the concentration in commercial TA suspensions, was toxic within 5 minutes. ANIMAL STUDIES: In a primary irritation study 10% benzyl alcohol applied in a 24-hour occlusive patch to the back of eight male albino rabbits did not cause irritation. Undiluted benzyl alcohol was moderately irritating when applied to the depilated skin of guinea pigs for 24 hr. Acute intravenous toxicity of benzyl alcohol was determined in mice. Clinical signs were convulsion, dyspnea and reduced motility in all strains for 24 hours. The slight decrease in body weight in the first week following treatment returned to normal in the second week. Microscopic examination revealed local nerve degeneration when 5% benzyl alcohol was injected into the side of a cat's face; at 10% local anesthesia was produced. In another experiment, rats were given oral doses of 50, 100, 200, 400, and 800 mg/kg for 13 weeks. The high dose produced clinical signs indicative of neurotoxicity including staggering, respiratory difficulty, and lethargy. Reduction in weight gain was noted in males at 800 mg/kg and females at equal to or greater than 200 mg/kg. The high dose animals also showed hemorrhages around the mouth and nose, and histological lesions in the brain, thymus, skeletal muscle, and kidney. Fifty pregnant mice were given 750 mg/kg/day benzyl alcohol in water by gavage on days 6-13 of gestation and were allowed to deliver. A decrease in the birth weight and weight gain in the pups was observed, but the chemical was not toxic to the mothers and had no effect on pup viability. Benzyl alcohol was tested for genotoxicity in 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of metabolic activation. The highest ineffective dose tested without toxicity in any S. typhimurium strains was 5.0 mg/plate. Slight inhibition of the background bacterial lawn occurred in cultures at 6.666 mg/plate but no significant change was seen in the results. In a mammalian cell genotoxicity assay using CHO cells, benzyl alcohol was negative without metabolic activation and positive with metabolic activation.

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Toxicity Data
LCLo (rat) = 1,000 ppm/8h

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Interactions
Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in industrialized countries. Understanding the mechanisms of APAP-induced liver injury as well as other forms of sterile liver injury is critical to improve the care of patients. Recent studies demonstrate that danger signaling and inflammasome activation play a role in APAP-induced injury. The aim of these investigations was to test the hypothesis that benzyl alcohol (BA) is a therapeutic agent that protects against APAP-induced liver injury by modulation of danger signaling. APAP-induced liver injury was dependent, in part, on Toll-like receptor (TLR)9 and receptor for advanced glycation endproducts (RAGE) signaling. BA limited liver injury over a dose range of 135-540 ug/g body weight or when delivered as a pre-, concurrent, or post-APAP therapeutic. Furthermore, BA abrogated APAP-induced cytokines and chemokines as well as high-mobility group box 1 release. Moreover, BA prevented APAP-induced inflammasome signaling as determined by interleukin (IL)-1(beta), IL-18, and caspase-1 cleavage in liver tissues. Interestingly, the protective effects of BA on limiting liver injury and inflammasome activation were dependent on TLR4 signaling, but not TLR2 or CD14. Cell-type-specific knockouts of TLR4 were utilized to further determine the protective mechanisms of BA. These studies found that TLR4 expression specifically in myeloid cells (LyzCre-tlr4-/-) were necessary for the protective effects of BA. BA protects against APAP-induced acute liver injury and reduced inflammasome activation in a TLR4-dependent manner. BA may prove to be a useful adjunct in the treatment of APAP and other forms of sterile liver injury.

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Non-Human Toxicity Values
LD50 Mouse sc 950 mg/kg bw
LD50 Rat sc 1700 mg/kg bw
LD50 Guinea pig ip > 400-800 mg/kg bw
LD50 Rat ip > 400-800 mg/kg bw
For more Non-Human Toxicity Values (Complete) data for BENZYL ALCOHOL (20 total), please visit the HSDB record page.

[1]. Benzyl alcohol increases membrane fluidity and modulates cyclic AMP synthesis in intact renal epithelial cells. Biochim Biophys Acta. 1987 Oct 2;903(2):341-8.

[2]. Benzyl alcohol protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes but causes mitochondrial dysfunction and cell death at higher doses. Food Chem Toxicol. 2015 Dec;86:253-61.

[3]. Benzyl alcohol attenuates acetaminophen-induced acute liver injury in a Toll-like receptor-4-dependent pattern in mice. Hepatology. 2014 Sep;60(3):990-1002.

Benzyl alcohol appears as a clear colorless liquid with a pleasant odor. Slightly denser than water. Flash point 194 °F. Boiling point 401 °F. Contact may irritate skin, eyes, and mucous membranes. May be slightly toxic by ingestion. Used to make other chemicals.
Benzyl alcohol is an aromatic alcohol that consists of benzene bearing a single hydroxymethyl substituent. It has a role as a solvent, a metabolite, an antioxidant and a fragrance.
Benzyl alcohol is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
Benzyl alcohol is a Pediculicide.
Benzyl Alcohol has been reported in Camellia sinensis, Nymphaea rudgeana, and other organisms with data available.
benzyl alcohol is a metabolite found in or produced by Saccharomyces cerevisiae.
A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with LIDOCAINE injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring.
See also: Benzyl alcohol; zinc chloride (component of); Benzyl Alcohol; Lidocaine Hydrochloride (component of); Benzyl alcohol; camphor (synthetic); menthol (component of) ... View More ...

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Drug Indication
Ulesfia (benzyl alcohol) lotion is indicated for the topical treatment of head lice infestation in patients 6 months of age and older. Ulesfia Lotion does not have ovicidal activity.
FDA Label

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Mechanism of Action
Benzyl alcohol inhibits lice from closing their respiratory spiracles, allowing the vehicle to obstruct the spiracles and causing the lice to asphyxiate.

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Therapeutic Uses
Anesthetics, Local; Pharmaceutic Aids
/On April 9, 2009, the U.S. Food and Drug Administration approved a new prescription medication for the treatment of head lice ( Pediculosis capitis ) infestation. Benzyl Alcohol Lotion, 5%, received full market approval as a prescription medication, for use in patients 6 months of age and older. Benzyl Alcohol Lotion, 5%, is the first head lice product approved by the FDA with benzyl alcohol as the active pharmaceutical ingredient.
The safety and effectiveness of Benzyl Alcohol Lotion, 5%, was demonstrated in two studies of 628 people, 6 months of age and older, with active head lice infestation. The subjects received two, 10-minute treatments of either Benzyl Alcohol Lotion or a topical placebo, one week apart. Fourteen days after the final treatment, more than 75 percent of the subjects treated with Benzyl Alcohol Lotion, 5%, were lice free.
In each of two double-blind studies, 25 patients suffering from early progressive idiopathic cataracts, subcapsular or cortical in site, received one drop of saline containing 0.07% benzyl alcohol every 8 hours. The eyelid was held open for at least 2 minutes. Treatment continued for 22 months. In one study, a control group received placebo, whereas in the other study, the control group received an anticataract medication. Clinical findings were recorded every 30 days for the first 14 months, then patients were followed for up to 18 and 22 months. A significant (p < .01) increase in visual acuity (VA) was observed in patients treated with benzyl alcohol after 30 and 60 days as compared to those receiving either placebo or the medication. Compared to those placebo or medication treated, a significant (p < .01) decrease in lens opacity was noted in 19 and 17 patients treated with benzyl alcohol, respectively. In the course of the studies, a significant increase in the number of surgeries for cataracts was noted in patients not receiving benzyl alcohol. One patient treated with benzyl alcohol required surgery after 22 months compared to 38 total who had received either placebo or medication. benzyl alcohol was well tolerated except in two patients (4%) where tolerance was fair in one and poor in the other.
For more Therapeutic Uses (Complete) data for BENZYL ALCOHOL (12 total), please visit the HSDB record page.

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Drug Warnings
Common side effects of /Benzyl Alcohol Lotion, 5%/ include irritations of the skin, scalp, and eyes, and numbness at the site of application. As with all medications, it is important to use benzyl alcohol, 5%, as labeled to maximize benefits and minimize risks. The product should be applied only to the scalp or the hair attached to the scalp. It is not approved for use in children younger than six months. Use in premature infants could lead to serious respiratory, heart- or brain-related adverse events such as seizure, coma, or death.
It also seems prudent to avoid the use of products containing benzyl alcohol to pregnant patients within whom the benzyl alcohol molecule, given its small size, presumably crosses the placental barrier into immature fetal tissues as readily as it crosses the blood-brain barrier.
Premature neonates may receive multiple drugs in the neonatal intensive care unit, some of which may contain benzyl alcohol. As there may be no safe lower dose of benzyl alcohol in these patients, it would seem prudent to avoid the use of multiple dose vials containing benzyl alcohol whenever alternatives exist.
Benzyl alcohol is believe to have a role in the increased frequency of cerebral intraventricular hemorrhages and mortality reported in very-low-birth-weight (VLBW) infants (weight < 1000 g) who received flush solutions preserved with benzyl alcohol. An increased incidence of developmental delay and cerebral palsy is also noted in the same VLBW patient population, suggesting a secondary damaging effect of benzyl alcohol.
For more Drug Warnings (Complete) data for BENZYL ALCOHOL (6 total), please visit the HSDB record page.

C7H8O

108.1378

108.057

100-51-6

27134-46-9

244

Colorless to light yellow liquid

1.0±0.1 g/cm3

204.7±0.0 °C at 760 mmHg

-15 °C

93.9±0.0 °C

0.2±0.4 mmHg at 25°C

1.546

1.03

1

1

1

8

55.4

0

O([H])C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H]

WVDDGKGOMKODPV-UHFFFAOYSA-N

InChI=1S/C7H8O/c8-6-7-4-2-1-3-5-7/h1-5,8H,6H2

phenylmethanol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol :≥ 100 mg/mL (~924.73 mM)
H2O : ~20 mg/mL (~184.95 mM)
DMSO : ≥ 1.8 mg/mL (~16.65 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (23.12 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (23.12 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (23.12 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 33.33 mg/mL (308.21 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)