Benzyl salicylate does not have a specific molecular target but functions as a fragrance and UV-absorbing agent. As a salicylate ester, it may have mild anti-inflammatory properties related to salicylic acid, but its primary use is in cosmetic and personal care products. It exhibits antioxidant and antimicrobial activity in vitro. Its mechanism of action is related to its ability to absorb UV light and provide fragrance. Its role is primarily formulation-based rather than pharmacologically active.

In vitro, benzyl salicylate exhibits antioxidant activity, as demonstrated by its ability to scavenge free radicals. It also shows antimicrobial activity against various microorganisms. The compound's activity is concentration-dependent, with effective concentrations typically in the mg/mL range. Its antioxidant and antimicrobial properties make it a potential candidate for research on natural preservatives and skin protection. However, its primary in vitro application is as a fragrance and UV-absorbing ingredient in cosmetic formulations.

In vivo, benzyl salicylate is used in cosmetic and personal care products applied topically to the skin. It acts as a fragrance ingredient and UV light absorber. When applied to the skin, it is generally well-tolerated at typical use concentrations. It may be absorbed through the skin to a limited extent and metabolized to salicylic acid and benzyl alcohol. The compound is not used as a therapeutic agent. Its in vivo effects are primarily related to its sensory and UV-protective properties.

The in vitro assays for benzyl salicylate typically involve antioxidant and antimicrobial activity testing. For antioxidant assays, the compound is tested for its ability to scavenge free radicals using DPPH, ABTS, or ORAC assays. The compound is dissolved in suitable solvent and diluted at varying concentrations (typically 0.01 to 10 mg/mL). For antimicrobial assays, the compound is tested against bacterial and fungal strains using broth microdilution or agar diffusion methods. The minimum inhibitory concentration (MIC) is determined. For quality control, the compound is analyzed by GC or HPLC for purity and identity.

For in vitro cellular assays, skin cells (e.g., keratinocytes, fibroblasts) are treated with benzyl salicylate at concentrations ranging from 0.01 to 10 mg/mL for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays to evaluate potential cytotoxicity. Inflammatory markers (IL-1α, IL-6, TNF-α) are measured by ELISA. For UV protection studies, cells are exposed to UV radiation in the presence or absence of the compound. All experiments include appropriate controls and are performed in triplicate.

For in vivo dermal safety studies, benzyl salicylate is typically tested in skin irritation and sensitization models. The compound is applied topically to the skin of rabbits or guinea pigs at concentrations typical of cosmetic formulations (typically 1-10%) for 24-48 hours. Skin irritation is assessed by visual scoring of erythema and edema. In repeat-dose studies, the compound is applied daily for 28 days, and skin condition is monitored. For absorption studies, radiolabeled benzyl salicylate may be applied to skin, and systemic absorption is measured. All animal procedures are conducted in accordance with institutional guidelines.

Metabolism / Metabolites
Salicylates can be used as flavorings and tasters in food, as UV absorbers, and in pharmaceuticals. This study investigated the hydrolytic metabolism of phenylsalicylic acid and benzylsalicylic acid in various tissue microsomes, rat plasma, and human liver and small intestinal microsomes. Both salicylates were rapidly hydrolyzed by tissue microsomes, primarily in the small intestine, followed by the liver, but phenylsalicylic acid was hydrolyzed much faster than benzylsalicylic acid. Bis(4-nitrophenyl)phosphate completely inhibited the activity of liver and small intestinal microsomal hydrolases, and these enzymes could be extracted using Triton X-100. Anion-exchange column chromatography analysis of Triton X-100 extracts from liver and small intestinal microsomes revealed co-elution of phenylsalicylic acid hydrolases and carboxylesterases. Expression of rat liver and small intestinal carboxylesterase isoenzymes Ces1e and Ces2c (AB010632) in COS cells significantly enhanced the hydrolytic activity of phenylsalicylic acid, with specific activities comparable to those of liver and small intestinal microsomes, respectively. Human small intestinal microsomes also exhibited higher hydrolytic activity towards these salicylates than liver microsomes. Both human CES1 and CES2 isoenzymes expressed in COS cells effectively hydrolyzed phenylsalicylic acid, but CES2 showed higher activity than CES1. These results suggest that in vivo microsomal hydrolysis of phenylsalicylic acid and benzylsalicylic acid may produce significant amounts of salicylic acid. The potential pharmacological and toxicological effects of salicylic acid released from salicylates in commercially available products should be considered.

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The pharmacokinetic properties of benzyl salicylate have been partially characterized. When applied topically, the compound is absorbed through the skin to a limited extent. It is metabolized by esterases to salicylic acid and benzyl alcohol, which are further metabolized and excreted. The compound's molecular weight of 228.25 and lipophilic nature influence its skin penetration. Due to its use as a cosmetic ingredient, comprehensive PK data are limited. The compound is not used as a therapeutic agent.

Toxicity Summary
Identification and Uses: Benzyl salicylate is a colorless, viscous liquid. It is widely used in the soap and cosmetic industries as a fragrance; it also effectively absorbs ultraviolet light and can be used in sunscreens. Benzyl salicylate is also used in deodorant sprays. Human Studies: Benzyl salicylate has an extremely low likelihood of inducing hypersensitivity reactions or triggering reactions that may be caused by existing sensitization. The estrogenic activity of benzyl salicylate was tested using an in vitro human estrogen receptor α (hERα) coactivator recruitment assay. Benzyl salicylate showed significant in vitro hERα agonist activity and higher estrogenic activity compared to bisphenol A. Its estrogenic activity was also confirmed in assays using the estrogen-responsive MCF7 human breast cancer cell line. Animal Studies: Benzyl salicylate did not show irritation in in vitro bovine cornea assays. Erythema was observed in rabbit skin assays. The estrogenic activity of benzyl salicylate was detected using an in vivo uterine nutrition bioassay in immature rodents. Mice were administered benzyl salicylate at doses of 11.1, 33.3, 100, and 300 mg/kg/day, and rats were administered doses of 3.7, 11.1, 33.3, and 100 mg/kg/day for 3 consecutive days, all of which resulted in a significant increase in uterine weight. Benzyl salicylate was not mutagenic to Salmonella Typhimurium strains TA98, TA100, TA1535, and TA1537, regardless of metabolic activation. Ecotoxicity studies: Zebrafish (Danio rerio) were exposed to benzyl salicylate solutions at concentrations of 0, 0.7, 1.0, 1.4, 2.0, or 2.8 mg/L for 96 hours under static regeneration conditions. Death was observed at concentrations of 2.0 and 2.8 mg/L. At these concentrations, the fish exhibited normal swimming behavior. No effects were observed at concentrations ≤ 1.4 mg/L.

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Interaction
Disinfection of swimming pool water is crucial for the inactivation of pathogenic microorganisms. However, the most commonly used chlorine-based disinfectants are known to lead to the formation of disinfection byproducts (DBPs), some of which are associated with adverse health effects. Precursors to DBPs include organic matter present during pool filling, bodily fluids, and personal care products (PCPs) used by swimmers and bathers. The increased use of PCPs in recent years has raised growing concerns about the fate of PCPs in swimming pool water and the potential health risks of the resulting disinfection byproducts (DBPs). This study investigated the chemical transformation of two salicylates—benzyl salicylate (BzS) and phenyl salicylate (PS)—in chlorinated water, both of which are components of various PCPs. Reaction kinetics were tracked using high-performance liquid chromatography-ultraviolet diode array detector (HPLC-UV-DAD), and major transformation byproducts were preliminarily identified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Under the experimental conditions, the reactions of both salicylates with chlorine followed pseudo-first-order kinetics: the rate constant for benzothiazolinone (BzS) was k = (0.0038 ± 0.0002) min⁻¹, and the half-life t₁/₂ was (182 ± 10) min; the rate constant for hydroquinone (PS) was k = (0.0088 ± 0.0005) min⁻¹, and the half-life t₁/₂ was (79 ± 4) min (mean ± standard deviation). The reaction of both salicylates in chlorinated water produced disinfection byproducts (DBPs), preliminarily identified as monochloro and dichloro compounds. The most likely reason is that one or two hydrogen atoms on the phenolic ring of both salicylates were electrophilically substituted by one or two chlorine atoms.

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Non-human toxicity values
Oral LD50 in rats: 2227 mg/kg

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The toxicology of benzyl salicylate has been evaluated for safety assessment. In topical application studies, the compound is generally well-tolerated and does not cause significant skin irritation at typical use concentrations. In acute oral toxicity studies, the compound shows low toxicity, with LD50 values typically >2,000 mg/kg in rodents. The compound is not genotoxic in standard in vitro assays. Benzyl salicylate is approved for use in cosmetic products and is considered safe for its intended uses.

[1]. Sensitization to benzyl salicylate and other allergens in patients with frontal fibrosing alopecia. Contact Dermatitis. 2021 Jun;84(6):423-430.

Benzyl salicylate is a colorless liquid with a melting point close to room temperature (18-20°C). (NTP, 1992)
Benzyl salicylate is a benzoic acid ester, belonging to the phenolic class of compounds, and its function is similar to that of salicylic acid.
Benzyl salicylate has been reported to exist in the Chinese mitten crab (Desmos chinensis), the red frangipani (Plumeria rubra), and other organisms with relevant data.

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Benzyl salicylate is an ester of benzyl alcohol and salicylic acid with a molecular formula of C14H12O3. It is commonly used in the cosmetic industry as a fragrance ingredient and UV light absorber. It exhibits antioxidant and antimicrobial activity. The compound is not approved as a therapeutic agent but is widely used in cosmetic and personal care products. It is available as a high-purity research reagent for laboratory use.

C14H12O3

228.2433

228.078

118-58-1

Benzyl salicylate-d4;1219802-40-0

8363

Colorless to light yellow liquid

1.2±0.1 g/cm3

320.0±0.0 °C at 760 mmHg

75 °F (NTP, 1992)
24 °C
23.4 °C

146.4±13.7 °C

0.0±0.7 mmHg at 25°C

1.607

3.2

1

3

4

17

246

0

ZCTQGTTXIYCGGC-UHFFFAOYSA-N

InChI=1S/C14H12O3/c15-13-9-5-4-8-12(13)14(16)17-10-11-6-2-1-3-7-11/h1-9,15H,10H2

benzyl 2-hydroxybenzoate

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 (~438.14 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.95 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 (10.95 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 (10.95 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.)