Absorption, Distribution and Excretion
The fate of phenoxyethanol in rats and humans has been investigated. More than 90% of an oral dose of 16, 27 or 160 mg/kg body weight of (2-(14)C)phenoxyethanol administered to male Colworth rats by was excreted in the urine within 24 hours of administration. A female rat also excreted about 90% of a dose of 27 mg/kg body weight in the urine within 24 hours. About 2% and 1.3% of the ingested dose was recovered from the exhaled air of female and male rats, respectively.
A pharmacokinetic study of phenoxyethanol was performed using a mass spectrometry model for simultaneous analysis of phenoxyethanol (PE) and its major metabolite, phenoxyacetic acid (PAA), in rat plasma, urine, and 7 different tissues. The absolute topical bioavailability of PE was 75.4% and 76.0% for emulsion and lotion, respectively. Conversion of PE to PAA was extensive, with the average AUCPAA-to-AUCPE ratio being 4.4 and 5.3 for emulsion and lotion, respectively. The steady-state tissue-to-plasma PE concentration ratio (Kp) was higher than unity for kidney, spleen, heart, brain, and testis and was lower (0.6) for lung and liver, while the metabolite Kp ratio was higher than unity for kidney, liver, lung, and testis and was lower (0.3) for other tissues.
... An entire oral dose of 11 mg of unlabelled 2-phenoxyethanol was accounted for in the urine of one healthy male volunteer as 2-phenoxyacetic acid. Most of the acid was excreted unconjugated.
The fate of 2-phenoxyethanol in rats and humans has been investigated. More than 90% of an oral dose of 16, 27 or 160 mg/kg bw of (2-(14)C)phenoxyethanol given to male Colworth rats by gavage was excreted in the urine within 24 hr. A female rat also excreted about 90% of a dose of 27 mg/kg bw in the urine within 24 hr. Approximately 2 and 1.3% of the ingested dose was recovered from expired air of female and male rats, respectively. The rate of intestinal absorption was rapid, with 60-70% of the excreted (14)C detected at 3 hr and > 95% of the total 4-day urinary (14)C detected within the first 24 hr. Trace amounts of radioactivity were detected in feces. Four days after dosing, only trace amounts of radioactivity remained in the carcass, primarily in the liver (< 0.2% of the dose), fat and muscle. At 4 days, the (14)C concentration in blood was only 0.001.
... NOT READILY ABSORBED THROUGH THE SKIN IN ACUTELY TOXIC AMT.
2-PHENOXYETHANOL (0.1-0.5 ML/L) SEDATED OR ANESTHETIZED FISH WITHIN MINUTES WHEN THE ANIMALS WERE IMMERSED IN THE AGENT. WHEN ADMIN IN THIS WAY, THE ANESTHETIC WAS ABSORBED INTO THE BLOOD STREAM THROUGH THE GILL LAMELLAE.

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Metabolism / Metabolites
The fate of phenoxyethanol in rats and humans has been investigated. The rate of intestinal absorption was rapid, with 60-70% of the excreted (14)C detected at 3 hours and > 95% of the total 4-day urinary (14)C detected within the first 24 hr. Trace amounts of radioactivity were detected in feces. Four days after dosing, only trace amounts of radioactivity remained in the carcass, primarily in the liver (< 0.2% of the dose), fat and muscle. At the 4 day point, the (14)C concentration in blood was measured to be only 0.001. The major metabolite of phenoxyethanol is phenoxyacetic acid.
Once hydrolyzed, 2-phenoxyethanol is rapidly absorbed and oxidized to phenoxyacetic acid ...
YIELDS PHENOL IN CONIOPHORA, IN PLEUROTUS, & IN POLYSTICTUS ... . /FROM TABLE/
The toxicity of glycol ethers is associated with their oxidation to the corresponding aldehyde and alkoxyacetic acid by cytosolic alcohol dehydrogenase (ADH; EC 1.1.1.1.) and aldehyde dehydrogenase (ALDH; 1.2.1.3). Dermal exposure to these compounds can result in localised or systemic toxicity including skin sensitisation and irritancy, reproductive, developmental and hematological effects. It has previously been shown that skin has the capacity for local metabolism of applied chemicals. Therefore, there is a requirement to consider metabolism during dermal absorption of these compounds in risk assessment for humans. Cytosolic fractions were prepared from rat liver, and whole and dermatomed skin by differential centrifugation. Rat skin cytosolic fractions were also prepared following multiple dermal exposure to dexamethasone, ethanol or 2-butoxyethanol (2-BE). The rate of ethanol, 2-ethoxyethanol (2-EE), ethylene glycol, 2-phenoxyethanol (2-PE) and 2-BE conversion to alkoxyacetic acid by ADH/ALDH in these fractions was continuously monitored by UV spectrophotometry via the conversion of NAD+ to NADH at 340 nm. Rates of ADH oxidation by rat liver cytosol were greatest for ethanol followed by 2-EE >ethylene glycol >2-PE >2-BE. However, the order of metabolism changed to 2-BE >2-PE >ethylene glycol >2-EE >ethanol using whole and dermatomed rat skin cytosolic fractions, with approximately twice the specific activity in dermatomed skin cytosol relative to whole rat skin. This suggests that ADH and ALDH are localised in the epidermis that constitutes more of the protein in dermatomed skin than whole skin cytosol. Inhibition of ADH oxidation in rat liver cytosol by pyrazole was greatest for ethanol followed by 2-EE >ethylene glycol >2-PE >2-BE, but it only inhibited ethanol metabolism by 40% in skin cytosol. Disulfiram completely inhibited alcohol and glycol ether metabolism in the liver and skin cytosolic fractions. Although ADH1, ADH2 and ADH3 are expressed at the protein level in rat liver, only ADH1 and ADH2 are selectively inhibited by pyrazole and they constitute the predominant isoforms that metabolise short-chain alcohols in preference to intermediate chain-length alcohols. However, ADH1, ADH3 and ADH4 predominate in rat skin, demonstrate different sensitivities to pyrazole, and are responsible for metabolising glycol ethers. ALDH1 is the predominant isoform in rat liver and skin cytosolic fractions that is selectively inhibited by disulfiram and responds to the amount of aldehyde formed by the ADH isoforms expressed in these tissues. Thus, the different affinity of ADH and ALDH for alcohols and glycol ethers of different carbon-chain length may reflect the relative isoform expression in rat liver and skin. Following multiple topical exposure, ethanol metabolism increased the most following ethanol treatment, and 2-BE metabolism increased the most following 2-BE treatment. Ethanol and 2-BE may induce specific ADH and ALDH isoforms that preferentially metabolise short-chain alcohols (i.e. ADH1, ALDH1) and longer chain alcohols (i.e. ADH3, ADH4, ALDH1), respectively. Treatment with a general inducing agent such as dexamethasone enhanced ethanol and 2-BE metabolism suggesting induction of multiple ADH isoforms.
Studies were conducted... to evaluate the in vitro hemolytic potential of / ethylene glycol phenyl ether/ EGPE and its major metabolite using rabbit red blood cells (RBC). Phenoxyacetic acid (PAA) was identified as a major blood metabolite of EGPE. In vitro exposure of female rabbit erythrocytes indicated EGPE to be considerably more hemolytic than PAA.
Oxidized to the corresponding aldehyde and alkoxyacetic acid by alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3), respectively. (A15201)

Toxicity Summary
2-Phenoxyethanol is a glycol ether. Glycol ethers can produce toxicity following oxidation to the corresponding aldehyde and alkoxyacetic acid by alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3), respectively. (A15201) 2-Phenoxyethanol causes reduction of NMDA-induced membrane currents, indicating a neurotoxic potential for 2-phenoxyethanol. (A15202)

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Non-Human Toxicity Values
LD50 Mouse ip 872 mg/kg bw
LD50 Mouse ip ca 333 mg/kg bw
LD50 Guinea pig dermal >22180 mg/kg bw
LD50 Rabbit dermal >5000 mg/kg bw
For more Non-Human Toxicity Values (Complete) data for 2-PHENOXYETHANOL (27 total), please visit the HSDB record page.

[1]. Safety Review of Phenoxyethanol When Used as a Preservative in Cosmetics. J Eur Acad Dermatol Venereol. 2019 Nov;33 Suppl 7:15-24.

Therapeutic Uses
Phenoxyethanol (PE) is a preservative added to cosmetics and pharmaceuticals such as antibiotic ointments and solutions, ear-drops, and vaccines.
Anti-Infective Agents, Local; Anesthetics
Phenoxyethanol has antibacterial properties and is effective against strains of Pseudomonas aeruginosa even in the presence of 20% serum. It is less effective against Proteus vulgaris, other Gram-negative organisms, and Gram-positive organisms. It has been used as a preservative at a concentration of 1%. A wider spectrum of antimicrobial activity is obtained with preservative mixtures of phenoxyethanol and hydroxybenzoates. Phenoxyethanol may be used as a 2.2% solution or a 2% cream for the treatment of superficial wounds, burns, or abscesses infected by Pseudomonas aeruginosa. In skin infection derivatives of phenoxyethanol are used with either cyclic acid or zinc undecenoate.
TOPICAL ANTISEPTIC

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Drug Warnings
Peritonitis is the established term for infective inflammation of the peritoneum, whereas serositis generally refers to aseptic inflammation of a serous cavity, including the peritoneum. Serositis may be metabolic, viral, autoimmune, drug induced, genetic, allergic or granulomatous, or due to chemical antiseptics. In ...gynecological department, 4 patients had peritonitis and ascites after laparotomy. Based on the investigation... the solution used for peritoneal lavage (0.1% octenidine dihydrochloride and 2% phenoxyethanol) played a role in the tissue toxicity that caused chemical serositis with effusion.

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Pharmacodynamics
This substance has broad-spectrum antimicrobial activity against bacteria, yeasts, and mold.

C8H10O2

138.17

138.068

122-99-6

Phenoxyethanol-d2;21273-38-1;Phenoxyethanol-d4;1219804-65-5

31236

Colorless to light yellow liquid

1.1±0.1 g/cm3

245.2±0.0 °C at 760 mmHg

11-13 °C

105.3±14.1 °C

0.0±0.5 mmHg at 25°C

1.526

1.16

1

2

3

10

77.3

0

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

QCDWFXQBSFUVSP-UHFFFAOYSA-N

InChI=1S/C8H10O2/c9-6-7-10-8-4-2-1-3-5-8/h1-5,9H,6-7H2

2-phenoxyethanol

NSC-1864; NSC 1864; Phenoxyethanol

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)

DMSO : ~100 mg/mL (~723.80 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (18.09 mM) (saturation unknown) in 10% DMSO + 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 DMSO 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 (18.09 mM) (saturation unknown) in 10% DMSO + 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 DMSO 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 (18.09 mM) (saturation unknown) in 10% DMSO + 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 DMSO stock solution to 900 μL of corn oil and mix evenly.

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