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BENZOPHENONE 4
Benzophenone 4 (BP 4) is a white or pale yellow powder. Benzophenone 4 is used in bath products, makeup products, hair products, sunscreens and skin care products to protect cosmetics and personal care products from deterioration by absorbing, reflecting, or scattering UV rays. When used as a sunscreen ingredient, Benzophenone 4 protects the skin from UV rays.
CAS No. : 4065-45-6
EC No. : 223-772-2
Synonyms:
Sulisobenzone; BP-4; BP4; BP 4; benzofenon4; benzofenon 4; benzofenon-4; 4-Hydroxy-2-methoxy-5-(oxo-phenylmethyl)benzenesulfonic acid; 5-Benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid; benzenesulfonic acid, 5-benzoyl-4-hydroxy-2-methoxy-; benzophenone 4; 5-benzoyl-4-hydroxy-2-methoxybenzene sulfonic acid; 5-benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid; 3- benzoyl-4-hydroxy-6-methoxybenzenesulfonic acid; 2- benzoyl-5-methoxy-1-phenol-4-sulfonic acid; 4- hydroxy-2-methoxy-5-(phenylcarbonyl)benzenesulfonic acid; 2- hydroxy-4-methoxybenzophenone-5-sulfonic acid; 2- hydroxy-4-methoxybenzophenone-5-sulfonicacid; 2- hydroxy-4-methoxybenzophenone-5-sulphonic acid; 1- phenol-4-sulfonic acid, 2-benzoyl-5-methoxy-; seesorb 101S; spectra-sorb UV 284; sulisobenzona; Benzophenone 4; sulisobenzone; sulisobenzonum; benzophenon 4; benzophenone 4; benzophenone-4; benzophenone4; sungard; syntase 230; uv absorber HMBS; uval; uvinuc MS 40; uvinul; Sulisobenzone; Benzophenone-4; 4065-45-6; Benzophenone-4; 5-Benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid; Sungard; 2-Hydroxy-4-methoxybenzophenone-5-sulfonic acid; Benzophenone 4; Uval; Benzenesulfonic acid, 5-benzoyl-4-hydroxy-2-methoxy-; Sulisobenzona; Sulisobenzonum; Uvinul; Seesorb 101S; Syntase 230; Uvinul MS 40; Spectra-Sorb UV 284; Uvinuc ms 40; 2-HYDROXY-4-METHOXY-5-SULFOBENZOPHENONE; MS 40; Sulisobenzonum [INN-Latin]; Sulisobenzona [INN-Spanish]; UNII-1W6L629B4K; HSDB 7422; Uvinul MS-40 substanz; EINECS 223-772-2; NSC 60548; BRN 2889165; 1-Phenol-4-sulfonic acid, 2-benzoyl-5-methoxy-; 1W6L629B4K; 3-Benzoyl-4-hydroxy-6-methoxybenzenesulfonic acid; 2-Hydroxy-4-Methoxy-5-sulfonylbenzophenone(BP-4); 5-Benzoyl-4-hydroxy-2-methoxybenzene sulfonic acid; Uval sodium salt; 2-Benzoyl-5-methoxy-1-phenol-4-sulfonic acid; 5-Benzoyl-4-hydroxy-2-methoxybenzolsulfonsaeure; BP4; bp 4; 4-hydroxy-2-methoxy-5-(phenylcarbonyl)benzenesulfonic acid; Uvinul MS 40 sodium salt; Cyasorb UV 284 sodium salt; Benzophenone 4; Sulisobenzone [USAN:INN]; Sulfisobenzone; Sulisobenzone [USAN:USP:INN]; Sungard (TN); HMBS; Uvinul MS-40; Uval (*sodium salt*); Benzophenone-4; Sulisobenzone (USP/INN); EC 223-772-2; Spectra-Sorb U.V. 284; SCHEMBL16330; 5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonic acid; MLS004734662; Sulisobenzone 4065-45-6; Cyasorb UV 284 (Salt/Mix); 1-Phenol-4-sulfonic acid, 2-benzoyl-5-methoxy- (6CI); Sulisobenzone, analytical standard; Uvinul MS 40 (*sodium salt*); ALBB-025816; Cyasorb UV 284 (*sodium salt*); Benzophenone-4; bp 4; Sulisobenzone (USAN) (*sodium salt*); 5-benzoyl-4-hydroxy-2-methoxy-besylic acid; 2-benzoyl-5-methoxy-1-phenol-4-sulphonic acid; 5-Benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid ammoniate; 1-Phenol-4-sulfonic acid, 2-benzoyl-5-methoxy-, sodium salt; 4-hydroxy-2-methoxy-5-(oxo-phenylmethyl)benzenesulfonic acid; Benzenesulfonic acid, 5-benzoyl-4-hydroxy-2-methoxy-, sodium salt; Sulisobenzone, United States Pharmacopeia (USP) Reference Standard; 5-Benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid, >=97.0% (HPLC)
Benzophenone 4
Sulisobenzone (benzophenone 4) is an ingredient in some sunscreens which protects the skin from damage by UVB and UVA ultraviolet light.
Its sodium salt, sulisobenzone sodium, is also referred to as benzophenone-5.
Properties of Benzophenone-4
Chemical formula C14H12O6S
Molar mass 308.31 g/mol
Appearance Light-tan powder
Melting point 145 °C (293 °F; 418 K)
Solubility in water 1 g per 4 mL
BENZOPHENONE 4 is classified as :
Uv absorber
Uv filter
CAS Number of Benzophenone-4 4065-45-6
EINECS/ELINCS No: 223-772-2
Restriction (applies to EU only): VII/22
COSING REF No: 32143
INN Name: sulisobenzone
Chem/IUPAC Name: 5-Benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid
What Is Benzophenone-4?
Benzophenone-1, -3, -4, -5, -9 and-11 are compounds made from 2-hydroxybenzophenone. These compounds are powders. In cosmetics and personal care products, Benzophenone-1 and Benzophenone-3 are used mostly in the formulation of nail polishes and enamels. These Benzophenone ingredients are also used in bath products, makeup products, hair products, sunscreens and skin care products.
Why is Benzophenone-4 used in cosmetics and personal care products?
Benzophenone-1, Benzophenone-3, Benzophenone 4, Benzophenone-5, Benzophenone-9 and Benzophenone-11 protect cosmetics and personal care products from deterioration by absorbing, reflecting, or scattering UV rays. When used as sunscreen ingredients, Benzophenone-3 and Benzophenone 4 protect the skin from UV rays.
Scientific Facts of Benzophenone-4:
Benzophenone ingredients absorb and dissipate UV radiation, which serves to protect cosmetics and personal care products. As part of sunscreen products, which are OTC drugs in the United States, Benzophenone-3 (Oxybenzone) and Benzophenone 4 (Sulisobenzone) protect the skin from the harmful effects of the sun.
Exposing unprotected skin to UV light (primarily in the UV-B range) can result in sunburn and can promote premature aging of the skin and skin cancer.
Odor of Benzophenone-4: characteristic
Use of Benzophenone-4: Benzophenone 4 is a water soluble UVB absorber and is also commonly used to protect formulations from degradation due to UV exposure. In combination with UVA absorbers, it offers broad spectrum protection against UV radiation for skin and hair.
Benzophenone 4 is approved by the FDA in concentrations of up to 10% and in Canada, is approved by Health Canada at the same concentrations. It works to filter out both UVA and UVB rays, protecting the skin from sun UV damage. The UV-filter substance, Benzophenone 4 (BP-4) is widely used an ingredient in sunscreens and other personal care products,. It falls under the drug category of benzophenones. The benzophenones are a group of aromatic ketones that have both pharmaceutical and industrial applications. Benzophenones may be found organically in fruits such as grapes. Benzophenones are used as photoinitiators, fragrance enhancers, ultraviolet curing agents, and, occasionally, as flavor ingredients; they are also used in the manufacture of insecticides, agricultural chemicals, and pharmaceuticals and as an additive for plastics, coatings, and adhesives. As a group, benzophenones may be used to delay photodegradation or extend shelf life in toiletries and plastic surface coatings.
Analyte: Benzophenone 4; matrix: chemical purity; procedure: dissolution in water; addition of dehydrated isopropyl alcohol; potentiometric titration with tetrabutylammonium hydroxide to two endpoints
Benzophenone 4's production and use as an ultraviolet absorber in cosmetics, sunscreens and shampoos and in leather and textile fabrics(1,2) may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.3X10-11 mm Hg at 25 °C indicates Benzophenone 4 will exist solely in the particulate phase in the atmosphere. Particulate-phase Benzophenone 4 will be removed from the atmosphere by wet and dry deposition. Benzophenone 4 absorbs at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight. If released to soil, Benzophenone 4 is expected to have high mobility based upon an estimated Koc of 67. The estimated pKa values of the sulfonic acid are -2.4 and 7.6, indicating that this compound will exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Benzophenone 4 is not expected to volatilize from dry soil surfaces based upon its vapor pressure. No relevant data were available to assess the importance of biodegradation in soil or water. If released into water, Benzophenone 4 is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected based upon the estimated pKa values. An estimated BCF of 3.2 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Sensitized photolysis may have some importance in natural waters exposed to sunlight. Occupational exposure to Benzophenone 4 may occur through dermal contact with this compound at workplaces where Benzophenone 4 is produced or used. The general population may be exposed to Benzophenone 4 via dermal contact with this compound in consumer products, such as sunscreens and cosmetics, containing Benzophenone 4.
Based on a classification scheme, an estimated Koc value of 67, determined from a structure estimation method, indicates that Benzophenone 4 (BP-4) is expected to have high mobility in soil. The estimated pKa values of Benzophenone 4 (BP 4) are -2.4 and 7.6, indicating that this compound will exist almost entirely in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Benzophenone 4 (BP-4) is not expected to volatilize from dry soil surfaces based upon an estimated vapor pressure of 1.3X10-11 mm Hg at 25 °C, determined from a fragment constant method. No relevant data were available to assess the importance of biodegradation in the environment.
The rate constant for the vapor-phase reaction of Benzophenone 4 (BP-4) with photochemically-produced hydroxyl radicals has been estimated as 7.5X10-11 cu cm/molecule-sec at 25 °C using a structure estimation method. This corresponds to an atmospheric half-life of about 5.2 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm. Benzophenone 4 (BP-4) is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups. Benzophenone 4 (BP-4) absorbs at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight. Phenols are susceptible to sensitized photolysis in natural waters exposed to sunlight through reaction with hydroxy and peroxy radicals(4); therefore sensitized photolysis may have some importance in the environment.
An estimated BCF of 3 was calculated for Benzophenone 4 (BP-4), using an estimated log Kow of 0.37 and a regression-derived equation. According to a classification scheme, this BCF suggests the potential for bioconcentration in aquatic organisms is low.
Using a structure estimation method based on molecular connectivity indices, the Koc of Benzophenone 4 (BP-4) can be estimated to be 67. According to a classification scheme, this estimated Koc value suggests that Benzophenone 4 (BP-4) is expected to have high mobility in soil. The estimated pKa values of Benzophenone 4 (BP-4) are -2.4 and 7.6, indicating that this compound will exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).
The estimated pKa values of -2.4 and 7.6 indicate Benzophenone 4 (BP-4) will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces is not expected to be an important fate process. Benzophenone 4 (BP-4) is not expected to volatilize from dry soil surfaces based upon an estimated vapor pressure of 1.3X10-11 mm Hg, determined from a fragment constant method.
In surface seawater samples collected from Folly Beach, South Carolina in the summer of 2010, Benzophenone 4 (BP-4) was not detected in any samples from four sites (detection limit 1 ng/L) while other UV filter compounds (avobenzone, octocrylene, octinoxate, and padimate-O) were detected at concentrations ranging from 10 to 2013 ng/L.
According to the 2006 TSCA Inventory Update Reporting data, the number of persons reasonably likely to be exposed in the industrial manufacturing, processing, and use of Benzophenone 4 (BP-4) is 1 to 99; the data may be greatly underestimated.
NIOSH (NOES Survey 1981-1983) has statistically estimated that 91,292 workers (38,820 of these were female) were potentially exposed to Benzophenone 4 (BP-4) in the US. Occupational exposure to Benzophenone 4 (BP-4) may occur through dermal contact with this compound at workplaces where Benzophenone 4 (BP-4) is produced or used. The general population may be exposed to Benzophenone 4 (BP-4) via dermal contact with this compound in consumer products, such as sunscreens and cosmetics, containing Benzophenone 4 (BP-4).
In this study, /investigators/ evaluate the effects of benzophenone-4 (BP-4) in eleuthero-embryos and in the liver, testis and brain of adult male fish on the transcriptional level by focusing on target genes involved in hormonal pathways to provide a more complete toxicological profile of this important UV-absorber. Eleuthero-embryos and males of zebrafish were exposed up to 3 days after hatching and for 14 days, respectively, to Benzophenone 4 (BP-4) concentrations between 30 and 3000 ug/L. In eleuthero-embryos transcripts of vtg1, vtg3, esr1, esr2b, hsd17beta3, cyp19b cyp19a, hhex and pax8 were induced at 3000 ug/L Benzophenone 4 (BP-4), which points to a low estrogenic activity and interference with early thyroid development, respectively. In adult males Benzophenone 4 (BP-4) displayed multiple effects on gene expression in different tissues. In the liver vtg1, vtg3, esr1 and esr2b were down-regulated, while in the brain, vtg1, vtg3 and cyp19b transcripts were up-regulated. In conclusion, the transcription profile revealed that Benzophenone 4 (BP-4) interferes with the expression of genes involved in hormonal pathways and steroidogenesis. The effects of BP-4 differ in life stages and adult tissues and point to an estrogenic activity in eleuthero-embryos and adult brain, and an antiestrogenic activity in the liver. The results indicate that Benzophenone 4 (BP-4) interferes with the sex hormone system of fish, which is important for the risk assessment of this UV-absorber.
Pharmacology of Benzophenone-4 (BP 4)
Benzophenone 4 sunscreens, applied topically, protect the skin from these harmful effects of ultraviolet light by chemically absorbing light energy (photons). Correct use of sunscreens serves to reduce the risk of sunburn. Sunscreen agents prevent the occurrence of squamous-cell carcinoma of the skin when used mainly during unintentional sun exposure. No conclusion can be drawn about the cancer-preventive activity of topical use of sunscreens against both basal-cell carcinoma and cutaneous melanoma. Use of sunscreens can extend the duration of intentional sun exposure, such as bathing in the sun.
Benzophenone's main metabolic pathway in the rabbit is by reduction to benzhydrol. A small amount (1%) is converted to p-hydroxybenzophenone 4 following oral administration to rats.
A surface coating of benzophenones decreases the amount of UV radiation absorbed by the skin by limiting the total amount of energy that reaches the skin. Benzophenone 4 sunscreens, applied topically, protect the skin from these harmful effects of ultraviolet light by chemically absorbing light energy (photons). As this occurs, the benzophenone molecule becomes activated to higher energy levels. As the excited molecule returns to its ground state, the energy is released in the form of thermal energy. The hydroxyl group in the ortho position to the carbonyl group is believed to be a structural requirement for the benzophenones' absorption of UV light. This structural arrangement also contributes to the electronic stability of the molecule. Benzophenone 4 absorb energy throughout the UV range, although the maximum UV absorbance is between 284 and 287 nm for the 2-hydroxybenzophenones.
Benzophenone 4 sunscreens, applied topically, protect the skin from these harmful effects of ultraviolet light by chemically absorbing light energy (photons). As this occurs, the Benzophenone 4 molecule becomes excited to higher energy levels. As the excited molecule returns to its ground state, the energy is released in the form of thermal energy. The hydroxyl group in the ortho position to the carbonyl group is believed to be a structural requirement for the Benzophenone 4's absorption of UV light. This structural arrangement also contributes to the electronic stability of the molecule. Thus, a surface coating of Benzophenones decreases the amount of UV radiation absorbed by the skin by limiting the total amount of energy that reaches the skin. Benzophenone 4 absorb energy throughout the UV range, though maximum absorbance is between 284 and 287 nm for the 2-hydroxybenzophenones.
Benzophenone-4 is prepared via sulfonation of Benzophenone-3. The product is purified by precipitation from aqueous HCl, isolated by centrifugation, washed with acidic water, and dried.
The maximum recommended levels of lead and arsenic impurities in Benzophenone-4 are /13 ppm and 1 ppm respectively/.
The FDA Panel on Review of Topical Analgesics has proposed that Benzophenones-3, -4, and -8 are safe and effective as active ingredients in sunscreens for over-the-counter (OTC) use at the following concentrations: Benzophenone-3, 2%-6%; Benzophenone-4, 5%-10%; and Benzophenone-8, 3%. The Panel proposed these concentration limits on a combined safety and efficacy basis (a concentration limit may reflect maximum efficacy and not necessarily an indication of toxicity at a higher concentration).
Acute oral toxicity (LD50): 3530 mg/kg [Rat]. This drug can cause skin and eye irritation. Drug-induced phototoxicity is a non-immunological inflammatory skin reaction, caused by concurrent topical or systemic exposure to a specific molecule and ultraviolet radiation. Most of the phototoxic compounds absorb energy particularly from UVA light leading to activated derivatives, which can induce cellular damage. Benzophenone 4s are ultraviolet light filters that have been documented to cause a variety of adverse skin reactions, including contact and photocontact dermatitis, contact and photocontact urticaria, and anaphylaxis. Recently, they have become especially well known for their ability to induce allergy and photoallergy. Topical sunscreens and other cosmetics are the sources of these allergens in the majority of patients, however reports of reactions secondary to use of industrial products also exist. Benzophenone 4s as a group have been named the American Contact Dermatitis Society's Allergen of the Year for 2014 to raise awareness of both allergy and photoallergy to these ubiquitous agents. The liver is the main target organ of benzophenone 4 toxicity in rats and mice, based on elevations n liver weights, hepatocellular hypertrophy, clinical chemistry changes, and induction of liver microsomal cytochrome P450 2B isomer. The kidney was also identified as a target organ of benzophenone 4 toxicity in rats only, which was based on exposure concentration-related increases in kidney weights and microscopic changes.
To determine the frequency of irritant reactions to 19 organic sunscreen filters in current use. Ninety-four healthy volunteers were photopatch tested using the European consensus methodology to three different concentrations (2%, 5%, and 10%) of 19 organic sunscreen filters at the Photobiology Unit in Dundee, UK. Of the 94 subjects recruited, 80 were analyzed after withdrawals and exclusions. Of the 19 organic sunscreen filters studied, only 2 compounds led to irritant reactions in > or =5% subjects. Five per cent and 10% benzophenone-4 led to irritant reactions in four and six subjects, respectively. Five per cent methylene bis-benzotriazolyl tetramethylbutylphenol led to irritant reactions in six subjects, but unlike benzophenone-4, this was not in a dose-dependent fashion. When performing photopatch testing according to the European consensus methodology with these 19 organic sunscreen filters, a 10% concentration is suitable for all filters, except benzophenone-4, which should be tested at a concentration of 2%.
Investigators/ tested the potential irritancy of Benzophenone-4 on six adult white humans. Patches containing 1% or 10% Benzophenone-4 in alcohol were applied to the subjects for 24 hours, after which time the patches were removed, the sites scored, and fresh patches applied. This procedure was repeated every other day, three days per week for seven weeks, until a total of 21 patches had been made. The mean cumulative irritation scores for 1% and 10% solutions were 8.6 and 53.1, respectively (maximum score = 84). The latter value is indicative of a primary irritant.
Benzophenones-4 (BP4) and -11 were tested for potential skin irritation in separate single insult patch tests. Each ingredient was applied at concentrations of 16, 8, and 4% in DMP /dimethyl phthalate/ and in petrolatum to the skin of each of 14 subjects. At a concentration of 16% in either base, Benzophenones-4 and -11 were irritating to four and two subjects, respectively. Neither ingredient was irritating at concentrations of 4% or 8% in either vehicle.
Acute Exposure/ A number of studies have determined the potential irritancy of Benzophenones to the eyes of rabbits. The test material (0.1 mL or 0.1 g) was instilled into one eye of each rabbit; the other eye served as an untreated control. Eyes were examined and scored for irritation daily for a period of three to ten days. Some test procedures included washing of the treated eyes with water four seconds after instillation of the test material. Results of eye irritation tests revealed that most Benzophenones at concentrations of 5%-100% were nonirritating when instilled into the eyes of rabbits. Benzophenones-1, -2, and -4 were slightly to moderately irritating at 100% concentration; however, ... Benzophenone-4 was irritating at concentrations of 8 and 16% in DMP /dimethyl phthalate/ or petrolatum, it was nonirritating when tested as a 5% solution in water.
Subchronic or Prechronic Exposure/ ...A 16-day cumulative test in rabbits /was used/ to study the irritation potential of Benzophenone-4. An alcohol solution containing either 10% or 1% Benzophenone-4 was applied uncovered to the depilated backs of six New Zealand albino rabbits. Twenty-four hours later the sites were scored for irritation, and the solution was reapplied. This procedure was repeated every other day for five weeks, until a total of 16 applications of Benzophenone-4 had been made. The average cumulative irritation score was then calculated (maximum score = 64); applications of Benzophenone-4 (10%) and Benzophenone-4(1%) produced scores of 3.6 and 0.3, respectively.
In this work, /the authors/ evaluate whether in vitro systems are good predictors for in vivo estrogenic activity in fish. /Investigators/ focus on UV filters being used in sunscreens and in UV stabilization of materials. First, /investigators/ determined the estrogenic activity of 23 UV filters and one UV filter metabolite employing a recombinant yeast carrying the estrogen receptor of rainbow trout (rtERalpha) and made comparisons with yeast carrying the human hERalpha for receptor specificity. Benzophenone-1 (BP1), benzophenone-2 (BP2), 4,4-dihydroxybenzophenone, 4-hydroxybenzophenone (bp-4), 2,4,4-trihydroxy-benzophenone, and phenylsalicylate showed full dose-response curves with maximal responses of 81-115%, whereas 3-benzylidene camphor (3BC), octylsalicylate, benzylsalicylate, benzophenone-3, and benzophenone 4 displayed lower maximal responses of 15-74%. Whereas the activity of 17beta-estradiol was lower in the rtERalpha than the hERalpha assay, the activities of UV filters were similar or relatively higher in rtERalpha, indicating different relative binding activities of both ER. Subsequently, /investigators/ analyzed whether the in vitro estrogenicity of eight UV filters is also displayed in vivo in fathead minnows by the induction potential of vitellogenin after 14 days of aqueous exposure. Of the three active compounds in vivo, 3BC induced vitellogenin at lower concentrations (435 ug/L) than BP1 (4919 ug/L) and BP2 (8783 ug/L). The study shows, for the first time, estrogenic activities of UV filters in fish both in vitro and in vivo. Thus /investigators/ propose that receptor-based assays should be used for in vitro screening prior to in vivo testing, leading to environmental risk assessments based on combined, complementary, and appropriate species-related assays for hormonal activity.
Here /the authors/ report on acute and chronic effects of UV-filters 3-(4-methylbenzylidene-camphor) (4MBC), 2-ethyl-hexyl-4-trimethoxycinnamate (EHMC), benzophenone-3 (BP3) and benzophenone-4 (BP4) on Daphnia magna. The acute toxicity increased with log Pow of the compound. The LC50 values (48 hr) of 4MBC, EHMC, BP3 and BP4 were 0.56, 0.29, 1.9 and 50 mg/L, respectively. A tentative preliminary environmental risk assessment (ERA) based on a limited set of data indicates that individual UV-filters should undergo further ecotoxicological analysis, as an environmental risk cannot be ruled out. Consequently new data on the environmental occurrence and the effects of UV-filters are needed for a more accurate ERA. When regarded as a mixture occurring in surface waters they may pose a risk for sensitive aquatic organisms.
Benzophenone 4 (BP-4) is the organic compound with the formula (C6H5)2CO, generally abbreviated Ph2CO. It is a white solid that is soluble in organic solvents. Benzophenone 4 (BP-4) is a widely used building block in organic chemistry, being the parent diarylketone.
Uses of Benzophenone-4
Benzophenone 4 (BP-4) can be used as a photo initiator in UV-curing applications such as inks, imaging, and clear coatings in the printing industry. Benzophenone 4 (BP-4) prevents ultraviolet (UV) light from damaging scents and colors in products such as perfumes and soaps.
Benzophenone 4 (BP-4) can also be added to plastic packaging as a UV blocker to prevent photo-degradation of the packaging polymers or its contents. Its use allows manufacturers to package the product in clear glass or plastic (such as a PETE water bottle). Without it, opaque or dark packaging would be required.
In biological applications, Benzophenone 4 (BP-4)s have been used extensively as photophysical probes to identify and map peptide–protein interactions.
Benzophenone 4 (BP-4) is used as an additive in flavorings or perfumes for "sweet-woody-geranium-like notes."
Synthesis of Benzophenone-4
Benzophenone 4 (BP-4) is produced by the copper-catalyzed oxidation of diphenylmethane with air.
A laboratory route involves the reaction of benzene with carbon tetrachloride followed by hydrolysis of the resulting diphenyldichloromethane. It can also be prepared by Friedel–Crafts acylation of benzene with benzoyl chloride in the presence of a Lewis acid (e.g. aluminium chloride) catalyst: since benzoyl chloride can itself be produced by the reaction of benzene with phosgene the first synthesis proceeded directly from those materials.
Another route of synthesis is through a palladium(II)/oxometalate catalyst. This converts an alcohol to a ketone with two groups on each side.
Another, less well-known reaction to produce Benzophenone 4 (BP-4) is the pyrolysis of anhydrous calcium benzoate.
Organic chemistry of Benzophenone-4
Benzophenone 4 (BP-4) is a common photosensitizer in photochemistry. It crosses from the S1 state into the triplet state with nearly 100% yield. The resulting diradical will abstract a hydrogen atom from a suitable hydrogen donor to form a ketyl radical.
Benzophenone 4 (BP-4) radical anion
Main article: Air-free technique
File:Making Benzophenone 4 (BP-4) radical anion.webm
Addition of a solution of Benzophenone 4 (BP-4) in THF to a vial containing THF, sodium metal, and a stir bar, yielding the deep blue Benzophenone 4 (BP-4) anion radical. Playback speed 4x original recording.
Alkali metals reduce Benzophenone 4 (BP-4) to the deeply blue colored radical anion, diphenylketyl:
M + Ph2CO → M+Ph2CO•−
Generally sodium is used as the alkali metal. Although inferior in terms of safety and effectiveness relative to molecular sieves, this ketyl is used in the purification of organic solvents, particularly ethers, because it reacts with water and oxygen to give non-volatile products. The ketyl is soluble in the organic solvent being dried, so it accelerates the reaction of the sodium with water and oxygen. In comparison, sodium is insoluble, and its heterogeneous reaction is much slower. When excess alkali metal is present a second reduction may occur, resulting in a color transformation from deep blue to purple:
M + M+Ph2CO•− → (M+)2(Ph2CO)2−
A solvent pot containing dibutyl ether solution of sodium Benzophenone 4 (BP-4) ketyl, which gives it its purple color.
Commercially significant derivatives and analogues
There are over 300 natural Benzophenone 4 (BP-4)s, with great structural diversity and biological activities. They are being investigated as potential sources of new drugs. Substituted Benzophenone 4 (BP-4)s such as oxybenzone and dioxybenzone are used in many sunscreens. The use of Benzophenone 4 (BP-4)-derivatives which structurally resemble a strong photosensitizer has been criticized (see sunscreen controversy).
Michler's ketone has dimethylamino substituents at each para position. The high-strength polymer PEEK is prepared from derivatives of Benzophenone 4 (BP-4).
Safety
It is considered as "essentially nontoxic." Benzophenone 4 (BP-4) is however banned as a food additive by the US Food and Drug Administration, despite the FDA's continuing stance that this chemical does not pose a risk to public health under the conditions of its intended use. Benzophenone 4 (BP-4) derivatives are known to be pharmacologically active. From a molecular chemistry point of view interaction of Benzophenone 4 (BP-4) with B-DNA has been demonstrated experimentally. The interaction with DNA and the successive photo-induced energy transfer is at the base of the Benzophenone 4 (BP-4) activity as a DNA photosensitizers and may explain part of its therapeutic potentialities.
In 2014, Benzophenone 4 (BP-4)s were named Contact Allergen of the Year by the American Contact Dermatitis Society.
Benzophenone 4 (BP-4) is an endocrine disruptor capable of binding to the pregnane X receptor.
Environmental Fate/Exposure Summary
Benzophenone 4 (benzophenone-4)'s production and use in organic synthesis, as an odor fixative, as a flavoring, soap fragrance; in the manufacture of pharmaceuticals, and as a polymerization inhibitor for styrene may result in its release to the environment through various waste streams. Its use as an inert ingredient in nonfood use pesticides may result in its direct release to the environment. Benzophenone 4 (benzophenone-4) occurs naturally in Merrill flowers. If released to air, a vapor pressure of 1.93X10-3 mm Hg at 25 °C indicates Benzophenone 4 (benzophenone-4) will exist solely as a vapor in the atmosphere. Vapor-phase Benzophenone 4 (benzophenone-4) will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 3 days. Benzophenone 4 (benzophenone-4) absorbs UV light at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, Benzophenone 4 (benzophenone-4) is expected to have moderate to low mobility based upon Koc values of 430 and 517. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 1.9X10-6 atm-cu m/mole. Benzophenone 4 (benzophenone-4) is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Utilizing the Japanese MITI test, 0% of the Theoretical BOD was reached in 2 weeks indicating that biodegradation is not an important environmental fate process in soil or water. If released into water, Benzophenone 4 (benzophenone-4) is not expected to adsorb to suspended solids and sediment based upon the Koc values. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 15 and 110 days, respectively. Measured BCF values of 3.4-9.2 suggest bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to Benzophenone 4 (benzophenone-4) may occur through inhalation and dermal contact with this compound at workplaces where Benzophenone 4 (benzophenone-4) is produced or used. Monitoring data indicate that the general population may be exposed to Benzophenone 4 (benzophenone-4) via ingestion of food and dermal and inhalation contact with consumer products or flowers containing Benzophenone 4 (benzophenone-4).
About Benzophenone 4
Benzophenone 4 is registered under the REACH Regulation and is manufactured in and / or imported to the European Economic Area, at ≥ 100 to < 1 000 per annum.
Benzophenone 4 is used by consumers, in articles, by professional workers (widespread uses), in formulation or re-packing, at industrial sites and in manufacturing.
Consumer Uses of Benzophenone-4
Benzophenone 4 is used in the following products: cosmetics and personal care products, washing & cleaning products, leather treatment products and air care products.
Other release to the environment of Benzophenone 4 is likely to occur from: indoor use (e.g. machine wash liquids/detergents, automotive care products, paints and coating or adhesives, fragrances and air fresheners) and outdoor use as processing aid.
Article service life of Benzophenone-4
Other release to the environment of Benzophenone 4 is likely to occur from: outdoor use in long-life materials with high release rate (e.g. tyres, treated wooden products, treated textile and fabric, brake pads in trucks or cars, sanding of buildings (bridges, facades) or vehicles (ships)), outdoor use in long-life materials with low release rate (e.g. metal, wooden and plastic construction and building materials), indoor use in long-life materials with low release rate (e.g. flooring, furniture, toys, construction materials, curtains, foot-wear, leather products, paper and cardboard products, electronic equipment) and indoor use in long-life materials with high release rate (e.g. release from fabrics, textiles during washing, removal of indoor paints). Benzophenone 4 can be found in products with material based on: plastic (e.g. food packaging and storage, toys, mobile phones) and paper used for articles with intense direct dermal (skin) contact during normal use such as personal hygiene articles (e.g. nappies, feminine hygiene products, adult incontinence products, tissues, towels, toilet paper).
Widespread uses by professional workers of Benzophenone-4
Benzophenone 4 is used in the following products: cosmetics and personal care products, washing & cleaning products, air care products, pharmaceuticals and polishes and waxes.
Benzophenone 4 is used in the following areas: health services, agriculture, forestry and fishing and formulation of mixtures and/or re-packaging.
Other release to the environment of Benzophenone 4 is likely to occur from: indoor use (e.g. machine wash liquids/detergents, automotive care products, paints and coating or adhesives, fragrances and air fresheners).
Formulation or re-packing of Benzophenone-4
Benzophenone 4 is used in the following products: cosmetics and personal care products, washing & cleaning products, coating products, laboratory chemicals and paper chemicals and dyes.
Release to the environment of Benzophenone 4 can occur from industrial use: formulation of mixtures.
Uses at industrial sites of Benzophenone-4
Benzophenone 4 is used in the following products: coating products, laboratory chemicals, polishes and waxes, textile treatment products and dyes, washing & cleaning products and cosmetics and personal care products.
Benzophenone 4 is used for the manufacture of: textile, leather or fur and pulp, paper and paper products.
Release to the environment of Benzophenone 4 can occur from industrial use: in processing aids at industrial sites and in the production of articles.
Manufacture of Benzophenone-4
Release to the environment of Benzophenone 4 can occur from industrial use: manufacturing of Benzophenone 4.
General description of Benzophenone-4
Benzophenone 4 is a broad spectrum organic UV filter in sunscreen formulations, known to absorb deleterious UV light.
Application of Benzophenone-4
Refer to the product′s Certificate of Analysis for more information on a suitable instrument technique. Contact Technical Service for further support.
Benzophenone 4 may be used as an analytical reagent for the determination of the analyte in sunscreen formulations by high-performance liquid chromatography with UV spectrophotometric detection.
Benzophenone 4 was detected in 7 out of 44 samples of emissions from a range of commercially available furniture coatings. The concentration of benzophenone 4 in emissions from a UV-cured system was 52 ug/cu m. Average benzophenone 4 emissions from six varnished parquets (flooring) three and 28 days old were 16 and 27 ug/sq m-hr, respectively. Benzophenone may migrate from food packaging where it is used as photo-initiator in UV-cured inks.
