Benzyl Salicylate

1.175 at 68 °F (NTP, 1992) - Denser than water; will sink

1.175 g/m cu at 20 °C

1.173-1.183

Thick liquid

Colorless liquid

Slightly soluble (NTP, 1992)

In water, 8.8 mg/L at 20 °C, pH 6.8-7.1 /OECD Guideline 105 (Water Solubility)/

Slightly soluble in water

Miscible with alcohol or ether

Soluble in 9 vols of 90% alcohol

insoluble in water, glycerol; soluble in organic solvents, oils

180 °C (356 °F) - closed cup

>212 °F (>100 °C) - closed cup

406 °F at 26 mmHg (NTP, 1992)

320 °C

BP: 211 °C at 2.67 kPa

208.00 °C. @ 26.00 mm Hg

300 °C

75 °F (NTP, 1992)

24 °C

23.4 °C

Index of Refraction: 1.580-1.581

1.573-1.584

Benzyl salicylate is a colorless liquid. Melting point near room temperature (18-20 °C). (NTP, 1992)

CBI; Other Solid; Liquid

Solid

colourless oily liquid or opaque crystalline mass (tendency to supercool) with a faint, sweet, floral odour

Warning

H317: May cause an allergic skin reaction [Warning Sensitization, Skin]

P261, P272, P280, P302+P352, P321, P333+P317, P362+P364, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 0.4% (9 of 2207) of reports.

Chemical: Benzoic acid, 2-hydroxy-, phenylmethyl ester

Hazard Traits - Fragrance Allergen；Authoritative List - Annex III of the EU Cosmetics Regulation No. 1223/2009 - Fragrance Allergens；Report - if present in a rinse-off cosmetic product at a concentration at or above 0.01 percent (100 parts per million) or in a leave-on cosmetic product at a concentration at or above 0.001 percent (10 parts per million)

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Benzoic acid, 2-hydroxy-, phenylmethyl ester is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzoic acid, 2-hydroxy-, phenylmethyl ester are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 07-04-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/16100

Benzoic acid, 2-hydroxy-, phenylmethyl ester: Does not have an individual approval but may be used under an appropriate group standard

Benzyl salicylate is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

0 - Materials that, under emergency conditions, would offer no hazard beyond that of ordinary combustible materials.

1 - Materials that must be preheated before ignition can occur. Materials require considerable preheating, under all ambient temperature conditions, before ignition and combustion can occur.

0 - Materials that in themselves are normally stable, even under fire conditions.

Skin Sens. 1B (99%)；Eye Irrit. 2 (76.2%)；Aquatic Chronic 2 (24.1%)；Aquatic Chronic 3 (68.4%)

Eye irritation - category 2A；Skin sensitisation - category 1

Serious eye damage/eye irritation - Category 2B；Skin sensitization - Category 1B；Reproductive toxicity - Category 2；Hazardous to the aquatic environment (Acute) - Category 2；Hazardous to the aquatic environment (Long-term) - Category 2

Skin Sens. 1B

Incompatible materials: Strong oxidizing agents.

Incompatible with oxidizing materials.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.；SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.；INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.；INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.；STORAGE PRECAUTIONS: You should store this chemical under refrigerated temperatures and away from mineral acids and bases. (NTP, 1992)

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapor or mist.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Disinfection of swimming pool water is essential to inactivate pathogenic microorganisms. However chlorine based disinfectants, the most commonly used, are known to lead to the formation of disinfection by-products (DBPs), some of which have been associated with adverse health effects. Precursors of DBPs include the organic matter present in the water used to fill the swimming pool, human body fluids and personal care products (PCPs) used by swimmers and bathers. The increased use, in the last years, of PCPs lead to an increased concern about the fate of PCPs in swimming pool waters and potential health risks of formed DBPs. In this study, the chemical transformations of two salicylates, benzyl salicylate (BzS) and phenyl salicylate (PS), incorporated in several PCPs, in chlorinated water were investigated. High-performance liquid chromatography (HPLC) with UV-diode-array detection (HPLC-UV-DAD) was used to follow the reaction kinetics and HPLC with mass spectrometry (HPLC-MS) was used to tentatively identify the major transformation by-products. Under the experimental conditions used in this work both salicylates reacted with chlorine following pseudo-first order kinetics: rate constant k = (0.0038 +/- 0.0002) min(-1) and half-life t1/2 = (182 +/- 10) min for BzS and rate constant k = (0.0088 +/- 0.0005) min(-1) and half-life t1/2 = (79 +/- 4) min for PS (mean =/- standard deviation). The reactions of the two salicylates in chlorinated water led to the formation of DBPs that were tentatively identified as mono- and dichloro- substituted compounds. Most probably they result from an electrophilic substitution of one or two hydrogen atoms in the phenolic ring of both salicylates by one or two chlorine atoms.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3300(SRC), determined from a structure estimation method(2), indicates that benzyl salicylate is expected to have slight mobility in soil(SRC). Volatilization of benzyl salicylate from moist soil surfaces may be an important fate process(SRC) given an estimated Henry's Law constant of 2.7X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 7.8X10-5 mm Hg(3), and water solubility, 8.8 mg/L(3). However, adsorption to soil is expected to attenuate volatilization(SRC). Benzyl salicylate is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Utilizing the Manometric Respirometry test, 93% of the Theoretical BOD was reached in 4 weeks indicating that biodegradation is an important environmental fate process in soil(3).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3300(SRC), determined from a structure estimation method(2), indicates that benzyl salicylate is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces may occur(3) based upon an estimated Henry's Law constant of 2.7X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 7.8X10-5 mm Hg(3), and water solubility, 8.8 mg/L(3). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 14 and 160 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. According to a classification scheme(5), an estimated BCF of 320(SRC), from an estimated log Kow of 4.31(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Utilizing the Manometric Respirometry test, 93% of the Theoretical BOD was reached in 4 weeks indicating that biodegradation is an important environmental fate process in water(3).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), benzyl salicylate which has a vapor pressure of 7.8X10-5 mm Hg at 20 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase benzyl salicylate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 22 hours(SRC), calculated from its rate constant of 1.7X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase benzyl salicylate may be removed from the air by wet and dry deposition(SRC). Benzyl salicylate contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The CIR Expert Panel concluded that Benzyl Salicylate is safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating and non-sensitizing, which may be based on a quantitative risk assessment (QRA).

Safe for use in cosmetics, with qualifications

IDENTIFICATION AND USE: Benzyl salicylate is a thick colorless liquid. Benzyl salicylate is widely used in soap and cosmetic industry as fragrance; also effective in absorbing UV light, and can be used in protective sunscreen lotions. Benzyl salicylate is also used in deodorant sprays. HUMAN STUDIES: Benzyl salicylate has a very low potential to induce hypersensitivity or to elicit reactions presumably attributable to pre-existing sensitization. Estrogenic potential of benzyl salicylate was tested using an in vitro human estrogen receptor alpha(hERalpha)-coactivator recruiting assay. Benzyl salicylate showed obvious in vitro hERalpha agonistic activities and exhibited a higher estrogenic activity compared to bisphenol A. Estrogenic activity was also demonstrated in assays using the estrogen-responsive MCF7 human breast cancer cell line. ANIMAL STUDIES: Benzyl salicylate was not irritating in the isolated bovine cornea test. Erythema was observed in the rabbit skin test. Estrogenic potential of benzyl salicylate was tested using an in vivo immature rodent uterotrophic bioassay. The uterine weights were significantly increased in mice treated with 11.1, 33.3, 100 and 300 mg/kg/day benzyl salicylate and rats treated with 3.7, 11.1, 33.3 and 100 mg/kg/day for 3 days. Benzyl salicylate was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 with or without metabolic activation. ECOTOXICITY STUDIES: Zebra fish (Danio rerio) were exposed to benzyl salicylate at 0, 0.7, 1.0, 1.4, 2.0 or 2.8 mg/L under static-renewal conditions for 96 hours. Mortalities were noted at 2.0 and 2.8 mg/L. Fish at these concentrations exhibited normal swimming behavior. No effects were seen at concentrations </= 1.4 mg/L.

/AQUATIC SPECIES/ Zebra fish (Danio rerio) were exposed to benzyl 2-hydroxybenzoate at 0, 0.7, 1.0, 1.4, 2.0 or 2.8 mg/L under static-renewal conditions for 96 hours. Test concentrations were measured by GC prior to and after 24 hours for 2 days. Mortalities were noted at 2.0 and 2.8 mg/L. Fish at these concentrations exhibited normal swimming behavior. No effects were seen at concentrations </= 1.4 mg/L.

/OTHER TERRESTRIAL SPECIES/ Variation in the components of soft lining materials, i.e. the size of polymer particles, the ethyl alcohol content of the liquids and the type of plasticizer, were investigated with respect to their effects on the growth and colonization of Candida albicans. Inhibitory effects on fungal growth and/or acid production were found to vary depending upon the components of soft lining materials. In particular, two plasticizers, benzyl benzoate (BB) and benzyl salicylate (BS), significantly decreased the growth rate, whereas the size of polymer particle had little effect on fungal growth. Ethyl alcohol content of liquid significantly affected the fungal growth and/or acid production depending upon the plasticizer used. For instance, in the case of BS, the antifungal effect was related to ethyl alcohol contents, whereas a reverse effect was observed with benzyl n-butyl phthalate (BBP). Further examination using scanning electron microscopy revealed that Candida blastospores colonized lining materials in the following two ways depending on the plasticizers used. On the BS and dibutyl phthalate (DBP) specimen, the blastospore of this yeast associated loosely, whereas, in the case of BB, BBP and butyl phthalyl butyl glycorate (BPBG), fungal blastospore tightly and invasively colonized onto the specimens. These results clearly demonstrated a relationship between components of soft lining materials and fungal growth and colonization.

/PLANTS/ Despite the increase in recent decades in herbicide research on the potential of native plants, current knowledge is considered to be low. Very few studies have been carried out on the chemical profile or the biological activity of the Brazilian savanna (Cerrado) species. In the study reported here, the allelopathic activity of AcOEt and MeOH extracts of leaves, stems, and roots from Ocotea pulchella Nees was evaluated. The extracts were assayed on etiolated wheat coleoptiles. The AcOEt leaf extract was the most active and this was tested on standard target species (STS). Lycopersicon esculentum and Lactuca sativa were the most sensitive species in this test. A total of eleven compounds have been isolated and characterized. Compounds 1, 2, 4, and 6 have not been identified previously from O. pulchella and ocoteol (9) is reported for the first time in the literature. Eight compounds were tested on wheat coleoptile growth, and spathulenol, benzyl salicylate, and benzyl benzoate showed the highest activities. These compounds showed inhibitory activity on L. esculentum. The values obtained correspond to the activity exhibited by the extract and these compounds may therefore be responsible for the allelopathic activity shown by O. pulchella.

Benzyl salicylate was identified, not quantified, in the essential oil of clove buds, Eugenia caryophyllus(1). Fresh flowers from honeysuckle plants (Lonicera japonica) contained trace concentrations of benzyl salicylate; honeysuckle flowers which had been open for 12 and 24 hours prior to collection contained methyl phenylacetate at 65 ug/kg and trace concentrations, respectively(2). Benzyl salicylate was identified as 0.4% of the content of essential oil from an evergreen bush, Rhododendron caucasicum(3). Benzyl salicylate was identified as a constituent of the essential oil from leaf stem and roots samples of Alpinia menghaiensis and Alpinia maclurei from Vietnam(4). Benzyl salicylate was identified as a constituent of the essential oil of meadowsweet flowers (Filipendula sp)(5). Benzyl salicylate occurs naturally in balsams of Peru amd Tolu(5).

Benzyl salicylate in plants(1).[Table#8427]

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of July 27, 2017: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for benzyl salicylate is available.[Available from, as of June 20, 2017: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

Benzyl salicylate was identified, not quantified, in wastewaters and sludge collected from Iona Island treatment plant in Vancouver BC in 1983(1). Benzyl salicylate was identified as an emerging pollutant found in wastewaters in Spain(2). Benzyl salicylate was identified in influent, primary effluent and final effluent, collected at sites near Cincinnati OH in 1997, at concentrations of 8,960, 3,310, and 117 ng/L, respectively(3). Benzyl salicylate was identified in US and European influent samples, collected between 1997-1999, at average concentrations of 10.2 and 11.3 ug/L, respectively(4). Benzyl salicylate was identified in 2/4 samples of STP effluent collected at concentrations of 107 and 169 ng/L, collected from Saitama Prefecuture, Japan, in September and August 2008(5). Benzyl salicylate was identified, not quantifed, in samples from the Mario Zucchelli WWTP Terra Nova Bay, Antarctica(6).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of benzyl salicylate can be estimated to be 3300(SRC). According to a classification scheme(2), this estimated Koc value suggests that benzyl salicylate is expected to have slight mobility in soil.

INDOOR: Benzyl salicylate was detected at concentrations ranging from not below the detection limit to 0.17 ng/m cu in air samples collected in residential rooms that had been treated with aerosols, electrical diffusion units, as well as different common cleaning products of general domestic use in Spain; it was not detected in air samples taken inside a car(1).

/HUMAN EXPOSURE STUDIES/ The potential of benzyl salicylate, an important fragrance and flavor ingredient, to induce hypersensitivity or to elicit reactions to pre-existing hypersensitivity in the general population was evaluated by analyzing patch-test data. Results obtained from fragrance and formulator companies for a total of 10,538 patch tests on benzyl salicylate alone, on a variety of household and personal care consumer products and on fragrance blends containing benzyl salicylate were analyzed as part of this survey. No induced or elicited responses directly attributable to benzyl salicylate were observed in the 35 patch tests on benzyl salicylate alone, or in the 10,503 patch tests on consumer products or fragrance blends containing benzyl salicylate. The highest concentration of benzyl salicylate tested in the consumer-product tests was 2 x 10(-1)%, and benzyl salicylate alone was tested at 10% in ethanol. This study indicates that benzyl salicylate has a very low potential to induce hypersensitivity ('induced' reactions) or to elicit reactions presumably attributable to pre-existing sensitization ('elicited' reactions) and thus supports the safe use of benzyl salicylate in consumer products and fragrance blends.

/ENDOCRINE MODULATION/ Salicylate esters (SEs), a class of chemicals extensively used as flavor and fragrance additives in foods, beverages and a wide variety of consumer products, are suspected to have estrogenic activity based on chemical analysis of in silica molecular docking. We evaluated the estrogenic potentials of phenyl salicylate (PhS), benzyl salicylate (BzS), phenethyl salicylate (PES), ethyl salicylate (ES) and methyl salicylate (MS) using an in vitro human estrogen receptor alpha(hERalpha)-coactivator recruiting assay and in vivo immature rodent uterotrophic bioassays. We found that PhS, BzS and PES showed obvious in vitro hERalpha agonistic activities; BzS in particular exhibited a higher estrogenic activity compared to bisphenol A (BPA). The uterine weights were significantly increased in mice treated with 11.1, 33.3, 100 and 300 mg/kg/day BzS and 33.3 mg/kg/day PES and rats treated with 3.7, 11.1, 33.3 and 100 mg/kg/day BzS for 3 days (P<0.05). Finally, we transformed the daily intakes and the dermal exposures of SEs in the real world into estradiol equivalent concentrations (EEQs). ...

/ENDOCRINE MODULATION/ In order to assess the estrogenic activities of plasticizers used in tissue conditioners and four commercial tissue conditioners, we carried out in vitro tests. Seven plasticizers and two metabolites were diluted to concentrations ranging from 10(-9) to 10(-4) M. Four commercial tissue conditioners were also diluted to concentrations ranging from 2 x 10(-8) to 2 x 10(-3) g/mL. Estrogenic activities were tested by the E-screen test using MCF-7 cells. When estrogen is present, the cells proliferate. Instead of counting the cells or nuclei directly, cell numbers were assessed by measurement of the total protein content using the sulforhodamine B assay. The liquid compositions of the four commercial tissue conditioners were examined by high-performance liquid chromatography. n-Butyl benzyl phthalate, dibutyl phthalate, n-butyl phthalyl n-butyl glycolate, di-2-ethylhexyl phthalate and benzyl salicylate significantly increased proliferation of MCF-7 cells. The remaining two plasticizers, di-2-ethylhexyl adipate and benzyl benzoate, as well as two metabolites of dibutyl phthalate and di-2-ethylhexyl phthalate, i.e. monobutyl phthalate and mono-2-ethylhexyl phthalate, respectively, did not increase proliferation of MCF-7 cells at the concentrations tested. ... Except for benzyl benzoate and di-2-ethylhexyl adipate, the plasticizers tested showed estrogenic activity. The four commercial tissue conditioners tested also showed estrogenic activity, and HC showed especially strong estrogenicity.

/ENDOCRINE MODULATION/ Benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) are added to bodycare cosmetics used around the human breast. We report here that all three compounds possess estrogenic activity in assays using the estrogen-responsive MCF7 human breast cancer cell line. At 3,000,000-fold molar excess, they were able to partially displace [(3)H]estradiol from recombinant human estrogen receptors ERalpha and ERbeta, and from cytosolic ER of MCF7 cells. At concentrations in the range of 5 x 10(-5) to 5 x 10(-4) m, they were able to increase the expression of a stably integrated estrogen-responsive reporter gene (ERE-CAT) and of the endogenous estrogen-responsive pS2 gene in MCF7 cells, albeit to a lesser extent than with 10(-8) m 17beta-oestradiol. They increased the proliferation of estrogen-dependent MCF7 cells over 7 days, which could be inhibited by the antiestrogen fulvestrant, suggesting an ER-mediated mechanism. Although the extent of stimulation of proliferation over 7 days was lower with these compounds than with 10(-8) m 17beta-oestradiol, given a longer time period of 35 days the extent of proliferation with 10(-4) m benzyl salicylate, benzyl benzoate or butylphenylmethylpropional increased to the same magnitude as observed with 10(-8) m 17beta-estradiol over 14 days. ...

Chemical: Benzoic acid, 2-hydroxy-, phenylmethyl ester

Hazard Traits - Fragrance Allergen；Authoritative List - Annex III of the EU Cosmetics Regulation No. 1223/2009 - Fragrance Allergens；Report - if present in a rinse-off cosmetic product at a concentration at or above 0.01 percent (100 parts per million) or in a leave-on cosmetic product at a concentration at or above 0.001 percent (10 parts per million)

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Benzoic acid, 2-hydroxy-, phenylmethyl ester is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzoic acid, 2-hydroxy-, phenylmethyl ester are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 07-04-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/16100

Benzoic acid, 2-hydroxy-, phenylmethyl ester: Does not have an individual approval but may be used under an appropriate group standard

Benzyl salicylate is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

Salicylates are used as fragrance and flavor ingredients for foods, as UV absorbers and as medicines. Here, we examined the hydrolytic metabolism of phenyl and benzyl salicylates by various tissue microsomes and plasma of rats, and by human liver and small-intestinal microsomes. Both salicylates were readily hydrolyzed by tissue microsomes, predominantly in small intestine, followed by liver, although phenyl salicylate was much more rapidly hydrolyzed than benzyl salicylate. The liver and small-intestinal microsomal hydrolase activities were completely inhibited by bis(4-nitrophenyl)phosphate, and could be extracted with Triton X-100. Phenyl salicylate-hydrolyzing activity was co-eluted with carboxylesterase activity by anion exchange column chromatography of the Triton X-100 extracts of liver and small-intestinal microsomes. Expression of rat liver and small-intestinal isoforms of carboxylesterase, Ces1e and Ces2c (AB010632), in COS cells resulted in significant phenyl salicylate-hydrolyzing activities with the same specific activities as those of liver and small-intestinal microsomes, respectively. Human small-intestinal microsomes also exhibited higher hydrolyzing activity than liver microsomes towards these salicylates. Human CES1 and CES2 isozymes expressed in COS cells both readily hydrolyzed phenyl salicylate, but the activity of CES2 was higher than that of CES1. These results indicate that significant amounts of salicylic acid might be formed by microsomal hydrolysis of phenyl and benzyl salicylates in vivo. The possible pharmacological and toxicological effects of salicylic acid released from salicylates present in commercial products should be considered.

CIR ingredient: Benzyl Salicylate

As a fixer in perfumery; in sunscreen preparations.

Perfume fixative, solvent for synthetic musk, sunscreening lotions, soap odorant

Benzyl salicylate is used as a fixative and solvent for nitro musks and as a fragrance for detergents.

Benzyl salicylate is widely used in soap and cosmetic industry as fragrance; also effective in absorbing UV light, and can be used in protective sunscreen lotions. Benzyl salicylate is also used in deodorant sprays.

Reported uses (ppm):；Table: Reported uses (ppm): (Flavor and Extract Manufacturers' Association, 1994) [Table#8429]

2023: 10,000,000 - <25,000,000 lb；2022: 10,000,000 - <25,000,000 lb；2021: 10,000,000 - <25,000,000 lb；2020: 10,000,000 - <25,000,000 lb

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Benzoic acid, 2-hydroxy-, phenylmethyl ester. National Production Volume: 1,169,875 lb/yr.

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Benzoic acid, 2-hydroxy-, phenylmethyl ester:；Table: National Aggregate Production Volume (pounds) [Table#8428]

Benzyl salicylate

Benzoic acid, 2-hydroxy-, phenylmethyl ester; Benzyl 2-hydroxybenzoate; Benzyl o-hydroxybenzoate; 2-Hydroxybenzoic acid, benzyl ester; Phenylmethyl 2-hydroxybenzoate; Salicylic acid, benzyl ester

IFRA_STD_011.pdf

49

IFRA 51st Amendment - Guidance for the use of IFRA Standards

Restriction: This material should be used only in the limited quantity as stated in the Standard

By esterification of salicylic acid with benzyl alcohol.

Benzyl salicylate can be manufactured by reacting benzyl chloride with an alkali salicylate or by the transesterification of methyl salicylate with benzyl alcohol.

Cosmetics product ingredient: Benzyl salicylate；Benzyl salicylate is a fragrance allergen. Fragrance allergens are hazardous only to individuals who suffer from fragrance allergies. The Cosmetic Fragrance and Flavor Ingredient Right to Know Act of 2020 requires fragrance allergens included in Annex III of the EU Cosmetics Regulation No. 1223/2009 be reported to the California Department of Public Health. Fragrance allergens are only required to be reported if present in a rinse-off cosmetic product at a concentration at or above 0.01 percent (100 parts per million) or in a leave-on cosmetic product at a concentration at or above 0.001 percent (10 parts per million).；For more information, you can visit the fragrance allergens webpage on the California Safe Cosmetics Program website:；https://www.cdph.ca.gov/Programs/CCDPHP/DEODC/OHB/CSCP/Pages/FragranceAllergens.aspx；Product count: 15760

Information on 410 consumer products that contain Benzyl Salicylate in the following categories is provided:；• Auto Products；• Commercial / Institutional；• Home Maintenance；• Inside the Home；• Personal Care；• Pet Care

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Cosmetics -> Uv absorber

Wholesale and Retail Trade；Soap, Cleaning Compound, and Toilet Preparation Manufacturing；All Other Basic Organic Chemical Manufacturing；Food, beverage, and tobacco product manufacturing；All Other Chemical Product and Preparation Manufacturing；Not Known or Reasonably Ascertainable；Plastics Material and Resin Manufacturing

Benzoic acid, 2-hydroxy-, phenylmethyl ester: ACTIVE

1.3 [Products applied to the lips]

0.39 [Products applied to the axillae]

7.8 [Products applied to the face/body using fingertips]

7.3 [Products related to fine fragrances]

1.9 [Products applied to the body using the hands (palms), primarily leave-on (Body lotion)]

1.9 [Products applied to the face using the hands (palms), primarily leave-on (Face moisturizer)]