Absorption, Distribution and Excretion
The metabolic pathways of phenoxyethanol in rats and humans have been investigated. In male Colworth rats, over 90% of the dose of (2-(14)C)phenoxyethanol was excreted in the urine within 24 hours after oral administration of 16, 27, or 160 mg/kg body weight. In female rats, approximately 90% of the dose was also excreted in the urine within 24 hours after oral administration of 27 mg/kg body weight. Approximately 2% and 1.3% of the ingested dose were recovered in the exhaled breath of female and male rats, respectively. Pharmacokinetic studies of phenoxyethanol (PE) and its major metabolite phenoxyacetic acid (PAA) were conducted using mass spectrometry to simultaneously analyze rat plasma, urine, and seven different tissues. The absolute local bioavailability of PE was 75.4% and 76.0% in the emulsion and lotion, respectively. The conversion of PE to PAA was high, with mean AUCPA/AUCPE ratios of 4.4 and 5.3 in the emulsion and lotion, respectively. The steady-state tissue/plasma concentration ratio (Kp) of PE was greater than 1 in the kidneys, spleen, heart, brain, and testes, while the Kp value was lower in the lungs and liver (0.6); the Kp value of metabolites was greater than 1 in the kidneys, liver, lungs, and testes, while the Kp value was lower in other tissues (0.3). Following oral administration of 11 mg of unlabeled 2-phenoxyethanol to a healthy male volunteer, all of it was excreted in the urine as 2-phenoxyacetic acid. Most of the acid was excreted in an unconjugated form. The metabolism of 2-phenoxyethanol in rats and humans has been studied. In male Colworth rats, after gavage administration of 16, 27, or 160 mg/kg body weight of (2-(14)C)phenoxyethanol, more than 90% of the dose was excreted in the urine within 24 hours. In female rats, after gavage administration of a dose of 27 mg/kg body weight, approximately 90% of the dose was also excreted in the urine within 24 hours. Approximately 2% and 1.3% of the ingested dose were recovered from the exhaled breath of female and male rats, respectively. Intestinal absorption was rapid, with 60-70% of excreted (14)C detected within 3 hours, and over 95% of total (14)C detected in urine over 4 days within the first 24 hours. Trace radioactivity was detected in feces. Four days after administration, only trace amounts of radioactive material remained in the cadavers, primarily in the liver (<0.2% of the dose), fat, and muscle. The concentration of (14)C in the blood was only 0.001 after four days. …It is poorly absorbed through the skin and exhibits acute toxicity. 2-Phenoxyethanol (0.1-0.5 mL/L) can sedate or anesthetize fish within minutes, provided the fish are immersed in the solution. When administered in this manner, the anesthetic is absorbed into the bloodstream through the gill filaments. Metabolism/Metabolites Changes in phenoxyethanol in rats and humans have been studied. Intestinal absorption is rapid; 60-70% of excreted 14C can be detected within 3 hours, and over 95% of the total 14C in urine can be detected within 24 hours after 4 days. Trace radioactivity was detected in feces. Four days after administration, only trace radioactivity remained in the carcass, mainly in the liver (<0.2% of the dose), fat, and muscle. At 4 days, the blood 14C concentration was only 0.001. The main metabolite of phenoxyethanol is phenoxyacetic acid.
2-Phenoxyethanol is rapidly absorbed and oxidized to phenoxyacetic acid upon hydrolysis…
Phenol is produced in Coniophora, Pleurotus, and Polystictus… /Excerpt from table/
The toxicity of glycol ethers is related to their oxidation to the corresponding aldehydes and alkoxyacetic acids by cytosolic alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; 1.2.1.3). Skin contact with these compounds can lead to local or systemic toxicity, including skin sensitization and irritation, reproductive, developmental, and hematological effects. Previous studies have shown that the skin has the ability to locally metabolize topical chemicals. Therefore, the metabolism of these compounds during skin absorption must be considered when conducting risk assessments in humans. Cytoplasmic fractions of rat liver, intact skin, and dermatome isolated skin were prepared by differential centrifugation. In addition, cytoplasmic fractions of rat skin after repeated skin exposure to dexamethasone, ethanol, or 2-butoxyethanol (2-BE) were also prepared. The conversion of NAD+ to NADH was detected at 340 nm using ultraviolet spectrophotometry. The rates of conversion of ethanol, 2-ethoxyethanol (2-EE), ethylene glycol, 2-phenoxyethanol (2-PE), and 2-phenylethyl ether (2-BE) to alkoxyacetic acid via ADH/ALDH catalysis were continuously monitored in these components. The oxidation rate of ADH in rat liver cytosol was highest for ethanol, followed by 2-EE > ethylene glycol > 2-PE > 2-BE. However, when using cytosol fractions from intact and sliced rat skin, the metabolic order changed to 2-BE > 2-PE > ethylene glycol > 2-EE > ethanol, and the specific activity in the sliced skin cytosol was approximately twice that of intact rat skin. This indicates that ADH and ALDH are localized in the epidermis, and the protein content of the epidermis in the sliced skin cytosol is higher than that in the intact skin cytosol. Pyrazole inhibited ADH oxidation in rat liver cytosol most strongly, followed by 2-EE > ethylene glycol > 2-PE > 2-BE, but its inhibition rate of ethanol metabolism was only 40% in skin cytosol. Disulfiram completely inhibited the metabolism of alcohols and glycol ethers in the liver and skin cytosol components. Although ADH1, ADH2, and ADH3 are all expressed in rat liver, only ADH1 and ADH2 are selectively inhibited by pyrazole; they constitute the major isoenzymes that preferentially metabolize short-chain alcohols rather than medium-chain alcohols. However, ADH1, ADH3, and ADH4 are dominant in rat skin, exhibiting varying sensitivities to pyrazole and responsible for the metabolism of glycol ethers. ALDH1 is the major isoenzyme in the rat liver and skin cytosol components, selectively inhibited by disulfiram, and its activity is correlated with the amount of aldehydes generated by the ADH isoenzymes expressed in these tissues. Therefore, the differences in the affinity of ADH and ALDH for alcohols and ethylene glycol ethers of different carbon chain lengths may reflect the relative expression levels of isoenzymes in rat liver and skin. After repeated local exposures, ethanol treatment showed the most significant increase in ethanol metabolism, while 2-BE treatment showed the most significant increase in 2-BE metabolism. Ethanol and 2-BE may induce specific ADH and ALDH isoenzymes, preferentially metabolizing short-chain alcohols (e.g., ADH1, ALDH1) and long-chain alcohols (e.g., ADH3, ADH4, ALDH1), respectively. Treatment with universal inducers such as dexamethasone enhanced the metabolism of ethanol and 2-phenylethylamine (2-BE), suggesting the induction of multiple ADH isoenzymes. The following studies were conducted… The in vitro hemolytic potential of ethylene glycol phenyl ether (EGPE) and its major metabolites was evaluated using rabbit erythrocytes (RBCs). Phenoxyacetic acid (PAA) was identified as the major blood metabolite of EGPE. In vitro exposure experiments using female rabbit erythrocytes showed that the hemolytic activity of EGPE was significantly higher than that of PAA. EGPE is oxidized to the corresponding aldehydes and alkoxyacetic acids 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 an ethylene glycol ether. Ethylene glycol ethers are oxidized to the corresponding aldehydes and alkoxyacetic acids by alcohol dehydrogenases (ADH; EC 1.1.1.1) and aldehyde dehydrogenases (ALDH; EC 1.2.1.3), respectively, thereby producing toxicity. (A15201) 2-Phenoxyethanol can reduce NMDA-induced membrane currents, indicating that 2-Phenoxyethanol has neurotoxicity. (A15202)

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Non-human toxicity values
Mouse intraperitoneal injection LD50 872 mg/kg body weight
Mouse intraperitoneal injection LD50 approximately 333 mg/kg body weight
Guinea pig dermal injection LD50 >22180 mg/kg body weight
Rabbit dermal injection LD50 >5000 mg/kg body weight
For more complete non-human toxicity data for 2-phenoxyethanol (of 27 values), 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. It is also used as a topical anti-infective agent and anesthetic. Phenoxyethanol possesses antibacterial properties and is effective against Pseudomonas aeruginosa strains even in the presence of 20% serum. Its antibacterial activity is poor against Proteus vulgaris, other Gram-negative bacteria, and Gram-positive bacteria. It has been used as a 1% preservative. A mixture of phenoxyethanol and parabens provides broader antibacterial activity. Phenoxyethanol can be used in 2.2% solutions or 2% creams to treat superficial wounds, burns, or abscesses infected with Pseudomonas aeruginosa. In skin infections, phenoxyethanol derivatives can be used in combination with cyclohexane or zinc undecenoate.
Local Disinfectant
Drug Warning
Peritonitis is the formal term for an infectious inflammation of the peritoneum, while serositis usually refers to aseptic inflammation of the serous cavities (including the peritoneum). Serositis can be metabolic, viral, autoimmune, drug-induced, hereditary, allergic, or granulomatous, and can also be caused by chemical disinfectants. In…gynecology, four patients developed peritonitis and ascites after exploratory laparotomy. According to the investigation…the solution used for peritoneal lavage (0.1% cintidinium dihydrochloride and 2% phenoxyethanol) played a role in causing tissue toxicity in chemical serositis with exudation.
Pharmacodynamics
This substance has broad-spectrum antibacterial activity against bacteria, yeasts, and fungi.

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.)