BENZOPHENONE 3

Benzophenone-3

cas : 131-57-7

SYNONYM : Oxybenzone, Benzophenone-3; BP3; BENZOPHENONE-3; 2-Hydroxy-4-Methoxy Benzophenone; (2-Hydroxy-4-methoxyphenyl)-phenylmethanone; oxybenzone; 131-57-7; 2-HYDROXY-4-METHOXYBENZOPHENONE; Benzophenone-3; 4-Methoxy-2-hydroxybenzophenone; 2-Benzoyl-5-methoxyphenol; (2-hydroxy-4-methoxyphenyl)(phenyl)methanone; Oxybenzon; Methanone, (2-hydroxy-4-methoxyphenyl)phenyl-; Anuvex; Escalol 567; Chimassorb 90; Uvinul 9; Advastab 45; Cyasorb UV 9; Oxibenzona; Oxybenzonum; Sunscreen UV-15; Syntase 62; Uvistat 24; Usaf cy-9; Uvinul M40; Spectra-sorb UV 9; Benzophenone 3; Ongrostab HMB; Oxybenzonum; Oxibenzona; Oxibenzonum; HMBP; Cyasorb UV 9 Light Absorber; (2-Hydroxy-4-methoxyphenyl)phenylmethanone; UF 3; UV 9; NSC-7778; Benzophenone, 2-hydroxy-4-methoxy-; DuraScreen; (2-HYDROXY-4-METHOXYPHENYL)PHENYL- METHANONE; (2-HYDROXY-4-METHOXYPHENYL)PHENYLMETHANONE; 2-BENZOYL-5-METHOXYPHENOL; 2-HYDROXY-4-METHOXYBENZOPHENONE; 4-METHOXY-2-HYDROXYBENZOPHENONE; ADVASTAB 45; AI3-23644; ANUVEX; B3; BENZOPHENONE; 2-HYDROXY-4-METHOXY-; BENZOPHENONE-3; BRN 1913145; CCRIS 1078; CHIMASSORB 90; CYASORB UV 9; CYASORB UV 9 LIGHT ABSORBER; DURASCREEN; EINECS 205-031-5; ESCALOL 567; HMBP; HSDB 4503; METHANONE; (2-HYDROXY-4-METHOXYPHENYL)PHENYL-; METHANONE; (2HYDROXY4METHOXYPHENYL)PHENYL; MOB; MOD; NCI-C60957; NSC 7778; ONGROSTAB HMB; OXIBENZONA; OXIBENZONUM; OXYBENZON; OXYBENZONE; OXYBENZONE (BENZOPHENONE-3); OXYBENZONE 6; OXYBENZONUM; SOLAQUIN; SPECTRA-SORB UV 9; SUNSCREEN UV-15; SYNTASE 62; UF 3; USAF CY-9; UV 9; UVINUL 9; UVINUL M40; and UVISTAT 24; Photosensitivity, Photoallergy

Chemical Name: 2-Hydroxy-4-Methoxy Benzophenone
INCI Name: BENZOPHENONE-3
EINECS No.: 205-031-5
CAS No.: 131-57-7
Molecular Formula: C14H12O3
Molecular Weight: 228.24

Physical Property 
Appearance:     Pale greenish yellow crystalline powder
Assay:         99.0%min
Melting Point:     62.0-65.0℃
Gardner Color:     4.0 max
Specific Extinction 1%,1cm
(E288nm):     630 min
(E325nm):     410 min
Heavy Metals(Pb): 5ppm max
Burnt Residue: 0.1% max
Loss on drying: 0.2% max

Application 
BP-3 is uv absorber Used in topical sunscreens,moisturizers,shampoos,hair care products,lipstick,lip balms,nail polish,plastic materials,dental composite materials.It is also used as color preserver in paints and varnishes.

Storage
Must be stored in closed containers in dry cool conditions. The shelf life of BP-3 is three years in original, unopened containers.

Benzophenone-3 (BP-3) Factsheet
Benzophenone-3 (BP-3) is a naturally occurring chemical found in some flowering plants. BP-3 absorbs and scatters the sun’s harmful ultraviolet (UV) rays. For this reason, it is produced for use as sunscreen in lotions, conditioners, and cosmetics. BP-3 also is used in plastic products to block and prevent UV rays from altering the plastic and the contents inside.

How People Are Exposed to BP-3
People may be exposed to BP-3 when they apply sunscreen or cosmetic products that contain the chemical to their skin. Once applied, a small amount of BP-3 passes through the skin into the body.

How BP-3 Affects People’s Health
The human health effects from skin exposure to low levels of BP-3 are unknown. Occasionally, wearing products containing BP-3 has resulted in a skin allergy or photo allergy, a skin reaction that occurs with exposure to sunlight. BP-3 has been shown to cause weak hormonal activity in laboratory animals. More research is needed to assess the human health effects of exposure to BP-3.

Levels of BP-3 in the U.S. Population
In the Fourth National Report on Human Exposure to Environmental Chemicals (Fourth Report), CDC scientists measured BP-3 in the urine of 2,517 participants aged six years and older who took part in the National Health and Nutrition Examination Survey (NHANES) during 2003–2004. By measuring BP-3 in urine, scientists can estimate the amount of BP-3 that has entered people’s bodies.

CDC scientists found BP-3 in the urine of nearly all of the people tested, indicating widespread exposure to BP-3 in the U.S. population.

Finding a measurable amount of BP-3 in urine does not imply that levels of BP-3 cause an adverse health effect. Biomonitoring studies on levels of BP-3 provide physicians and public health officials with reference values so they can determine whether people have been exposed to higher levels of BP-3 than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

Oxybenzone or benzophenone-3 or BP-3 (trade names Milestab 9, Eusolex 4360, Escalol 567, KAHSCREEN BZ-3) is an organic compound. It is a pale-yellow solid that is readily soluble in most organic solvents. Oxybenzone belongs to the class of aromatic ketones known as benzophenones. It is a naturally occurring[4] chemical found in various flowering plants[5] as well as being an organic component of many sunscreen lotions. It is also in widespread use in things like plastics, toys, furniture finishes, and more to limit UV degradation.

Structure and electronic structure
Being a conjugated molecule, oxybenzone absorbs light at lower energies than many aromatic molecules. As in related compounds, the hydroxyl group is hydrogen bonded to the ketone.[8] This interaction contributes to oxybenzone's light-absorption properties. At low temperatures, however, it is possible to observe both the phosphorescence and the triplet-triplet absorption spectrum. At 175 K the triplet lifetime is 24 ns. The short lifetime has been attributed to a fast intramolecular hydrogen transfer between the oxygen of the C=O and the OH.

Uses
Oxybenzone is used in plastics as an ultraviolet light absorber and stabilizer. It is used, along with other benzophenones, in sunscreens, hair sprays, and cosmetics because they help prevent potential damage from sunlight exposure. It is also found, in concentrations up to 1%, in nail polishes.[10] Oxybenzone can also be used as a photostabilizer for synthetic resins.[10] Benzophenones can leach from food packaging, and are widely used as photo-initiators to activate a chemical that dries ink faster.[11]

As a sunscreen, it provides broad-spectrum ultraviolet coverage, including UVB and short-wave UVA rays. As a photoprotective agent, it has an absorption profile spanning from 270 to 350 nm with absorption peaks at 288 and 350 nm.[12] It is one of the most widely used organic UVA filters in sunscreens today.[12] It is also found in nail polish, fragrances, hairspray, and cosmetics as a photostabilizer. Despite its photoprotective qualities, much controversy surrounds oxybenzone because of its possible hormonal and photoallergenic effects, leading many countries to regulate its use.

Safety
Some debate focuses on the potential of oxybenzone as a contact allergen with a 2001 study finding contact dermatitis "uncommon" for oxybenzone.[13] Due to the advent of PABA-free sunscreens, oxybenzone is now the most common allergen found in sunscreens.[14][15][16][17]

In vivo studies
The incidence of oxybenzone causing photoallergy is extremely uncommon, however, oxybenzone has been associated with rare allergic reactions triggered by sun exposure. In a study of 82 patients with photoallergic contact dermatitis, just over one quarter showed photoallergic reactions to oxybenzone.[18]

In a 2008 study of participants ages 6 and up, oxybenzone was detected in 96.8% of urine samples. Humans can absorb anywhere from 0.4% to 8.7% of oxybenzone after one topical application of sunscreen, as measured in urine excretions. This number can increase after multiple applications over the same period of time.[20] Oxybenzone is particularly penetrative because it is the most lipophilic of the three most common UV filters.[21]

When applied topically, UV filters, such as oxybenzone, are absorbed through the skin, metabolized, and excreted primarily through the urine.[22] The method of biotransformation, the process by which a foreign compound is chemically transformed to form a metabolite, was determined by Okereke and colleagues through oral and dermal administration of oxybenzone to rats. The scientists analyzed blood, urine, feces, and tissue samples and found three metabolites: 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DHMB) and 2,3,4-trihydroxybenzophenone (THB).[23][24] To form DHB the methoxy functional group undergoes O-dealkylation; to form THB the same ring is hydroxylated.[22] Ring B in oxybenzone is hydroxylated to form DHMB.[22]

A study done in 2004 measured the levels of oxybenzone and its metabolites in urine. After topical application to human volunteers, results revealed that up to 1% of the applied dose was found in the urine.[25] The major metabolite detected was DHB and very small amounts of THB were found.[25] By utilizing the Ames test in Salmonella typhimurium strains, DHB was determined to be nonmutagenic.[26] In 2019, the U.S. Food and Drug Administration (FDA) noted in their recommendations for future study that, "While research indicates that some topical drugs can be absorbed into the body through the skin, this does not mean these drugs are unsafe."

Effects on coral
Media reports link oxybenzone in sunscreens to coral bleaching, although some environmental experts dispute the claim.[29] A small number of studies have been released which linked coral damage to oxybenzone exposure.[30][31] A 2015 study published in the Archives of Environmental Contamination and Toxicology led to ban of oxybenxzone containing sunscreen in Palau.[32] However, the purported link between oxybenzone and coral decline is widely discussed within the environmental community since most studies on the subject have been conducted in a lab environment.[33] A 2019 study of UV filters in oceans found far lower concentrations of oxybenzone than previously reported, and lower than known thresholds for environmental toxicity.

A chemical sunscreen agent that absorbs UVB and short UVA rays (280-350nm) with its peak protection at 288 nm. Unlike many other chemical sunscreens, it is highly stable but its UV absorbing abilities are weak so it always has to be combined with other sunscreen agents for proper protection. More often than not, it's used as a photostabilizer rather than a proper sunscreen agent as it can protect formulas nicely from UV damage.
Regarding safety, BP-3 is somewhat controversial. First, its molecules are small (228 Da) and very lipophilic (oil loving) and these properties result in very good absorption. The problem is that you want sunscreens on the top of your skin and not in your bloodstream, so for BP-3 this is a problem. In fact, it absorbs so well that 4 hours after application of a sunscreen product with BP-3, it can be detected in urine. 
Another concern of BP-3 is that it shows some estrogenic activity, though it's probably not relevant when applied topically to the skin. Estrogenic activity was confirmed only in-vitro (in test tubes) and when taken orally by lab animals, and not when used topically as you would normally. In fact, a 2004 follow-up study to examine the estrogenic effect of sunscreens when used topically on the whole body found that "the endogenous levels of reproductive hormones were unaffected" (even though BP-3 could be detected both in plasma and urine, so its absorption is no doubt too good).
If that was not enough, Wikipedia claims that BP-3 is nowadays the most common allergen found in sunscreens, and the always-trustworthy smartskincare writes that "[benzophenones] have been shown in some studies to promote the generation of potentially harmful free radicals".
On the up side, sunscreens are pretty well regulated in several parts of the world, and BP-3 is considered "safe as used" and is an allowed sunscreen agent everywhere. It can be used in concentrations of up to 10% in the EU and up to 6% in the US.
Overall, BP-3 is probably our least favorite sunscreen agent and we prefer sunscreens without it. However, if you find a formula that you love and contains BP-3, we do not think that you should throw it away. A sunscreen with BP-3 is definitely better than no sunscreen. 

Physical Description
2-hydroxy-4-methoxybenzophenone appears as white to off-white or light yellow powder
DryPowder; Liquid
Solid

Color/Form
Colorless crystals
Crystals from isopropanol
White yellowish, cream colored powder
Pale yellow powder

Odor
Weak odor
Almost odorless or faint characteristic

Boiling Point
302 to 320 °F at 5 mm Hg (NTP, 1992)
155 °C at 5.00E+00 mm Hg
Melting Point
151 °F (NTP, 1992)
65.5 °C

Flash Point
100 °C (212 °F) - closed cup

Solubility
less than 1 mg/mL at 68° F (NTP, 1992)
In water, 3.7 mg/L at 25 °C
Density
1.32 at 25 °C

Vapor Pressure
6.62X10-6 mm Hg at 25 °C (est)

Decomposition
When heated to domposition it emits acrid smoke and irritating fumes.

Dissociation Constants
pKa = 7.1 

Pharmacology
Oxybenzone is an organic compound used in sunscreens. It is a derivative of benzophenone.
Oxybenzone is a benzophenone derivative used as a sunscreen agent. Oxybenzone absorbs UVB and UVA II rays, resulting in a photochemical excitation and absorption of energy. Upon return to ground state, the absorbed energy results in emission of longer wavelength radiation and decreased skin penetration of radiation which reduces the risk of DNA damage.

MeSH Pharmacological Classification
Sunscreening Agents
Chemical or physical agents that protect the skin from sunburn and erythema by absorbing or blocking ultraviolet radiation. (See all compounds classified as Sunscreening Agents.)

Absorption, Distribution and Excretion
Route of Elimination
In vivo studies show oxybenzone is abosorbed transdermally (through the skin) and is excreted in the urine.
The disposition of Benzophenone-3 in rats dosed orally, intravenously and topically, has been investigated. (14)C-Benzophenone-3 was administered orally at dosages of 3, 28, 293 and 2570 mg/kg, dermally at approximate dosages of 0.2, 0.6, 0.8 and 3.2 mg/kg and intravenously at a dosage of 4.6 mg/kg. The dermal dosage of 0.6 mg/kg involved the use of a sunscreen lotion as vehicle, while the other dermal dosage levels concerned alcoholic solutions of the compound. Through all routes and dosages, Benzophenone-3 appeared to be well-absorbed and urinary secretion clearly showed to be the major route of elimination, followed by the fecal route. Only trace amounts appeared to be measured in tissues after 72 hours.
Benzophenone-3 formed part of a battery of five UV filters for which standard operating procedures for their rapid analysis in various skin layers, were established. Benzophenone-3 was included at 4.9% in a cosmetic formulation (composition not stated) applied at 3 mg/sq cm on fresh dermatomed (+/- 344 um) human skin (6 samples from different donors) put on static diffusion cells. The 3 mL receptor fluid (pH 7.4) was maintained at 32 °C and consisted of 1% bovine serum albumin, 0.9% NaCl, 0.02% KCl and 0.04% gentamycin in distilled water. The transepidermal water loss (TEWL) was recorded at each site with a Tewameter. After an exposure time of 16 hours, the skin was washed and dried with cotton swabs. The receptor fluid was collected and 16 strippings were carried out on the skin surface to determine the stratum corneum (SC) content and subsequently the epidermis was separated from the dermis. Analysis was performed by isocratic RP-HPLC2 with UV detection. Benzophenone-3 quantification led to the following results: Total amount applied 147 ug/sq cm (3 mg cream/sq cm, 4.9% Benzophenone-3); Stratum corneum (SC) 8.5 +/- 3.3 ug/sq cm; Epidermis 0.3 +/- 0.2 ug/sq cm; Dermis 0.4 +/- 0.1 ug/sq cm; Receptor fluid 1.0 +/- 0.4 ug/sq cm; Washing solution 85.7% +/- 4.5%; Recovery 93.4% +/- 3.1%. The results indicate that the SC adsorbed the greatest proportion of the applied amount (5.8%), while about 0.5% was absorbed in the viable skin and 0.7% was analyzed in the receptor fluid. ... They estimate the dermal absorption of Benzophenone-3 in respect to bioavailability after topical application to freshly dermatomed human skin for 16 hours as 1.7 ug/sq cm (1.0 ug/sq cm receptor fluid, 0.4 ug/sq cm dermis, 0.3 ug/sq cm epidermis), corresponding to 1.16% of the applied dose.
The results of a study investigating the urinary content of Benzophenone-3 after topical application to human volunteers can be considered as an indication for low bioavailability. A commercial available sunscreen containing 4% Benzophenone-3 was topically applied in an amount of 40 g to the average body area of 2.0 sq m of each of 11 volunteers and urine samples were collected subsequently during 48 hours. Although the urine is known as the major excretion route for absorbed and bioavailable material, only 0.4% (corresponding a median of 9.8 mg/volunteer) of the applied Benzophenone-3 dose was recovered in the urine within the 48 hours sampling period.
In this study, 32 volunteers were treated with 2 mg/sq cm of a basic cream formulation on a daily basis for 4 days during the first week, followed by the same treatment regime with a sunscreen containing 30% of UV-filters in total (10% 4-Methylbenzylidene Camphor, 10% Benzophenone-3 and 10% Ethylhexyl Methoxycinnamate) during the second week. Blood was collected at several time intervals on the first day of treatment and subsequently on a daily basis. All three compounds were detected in their parent forms both in plasma (Benzophenone-3 up to 300 ng/mL) and urine, showing that there is a substantial skin penetration, dermal uptake and urinary excretion in humans.
For more Absorption, Distribution and Excretion (Complete) data for 2-Hydroxy-4-methoxybenzophenone (22 total), please visit the HSDB record page.

Metabolism/Metabolites
The metabolism and disposition of Benzophenone-3 when administered orally in rats and mice and dermally in the rat at a uniform single dosage of 100 mg/kg bw /were described/. The same metabolites /were/ detected in all cases: 2,4-Dihydroxybenzone (DHB), 2,2'-dihydroxy-4-methoxybenzone (DHMB) and 2,3,4-trihydroxybenzophenone (THB). They have been identified in their free and conjugated (glucuronidated or sulfonated) forms.
Benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) is widely used as sunscreen for protection of human skin and hair from damage by ultraviolet (UV) radiation. In this study, we examined the metabolism of BP-3 by rat and human liver microsomes, and the estrogenic and anti-androgenic activities of the metabolites. When BP-3 was incubated with rat liver microsomes in the presence of NADPH, 2,4,5-trihydroxybenzophenone (2,4,5-triOH BP) and 3-hydroxylated BP-3 (3-OH BP-3) were newly identified as metabolites, together with previously detected metabolites 5-hydroxylated BP-3 (5-OH BP-3), a 4-desmethylated metabolite (2,4-diOH BP) and 2,3,4-trihydroxybenzophenone (2,3,4-triOH BP). In studies with recombinant rat cytochrome P450, 3-OH BP-3 and 2,4,5-triOH BP were mainly formed by CYP1A1. BP-3 was also metabolized by human liver microsomes and CYP isoforms. In estrogen reporter (ER) assays using estrogen-responsive CHO cells, 2,4-diOH BP exhibited stronger estrogenic activity, 2,3,4-triOH BP exhibited similar activity, and 5-OH BP-3, 2,4,5-triOH BP and 3-OH BP-3 showed lower activity as compared to BP-3. Structural requirements for activity were investigated in a series of 14 BP-3 derivatives. When BP-3 was incubated with liver microsomes from untreated rats or phenobarbital-, 3-methylcholanthrene-, or acetone-treated rats in the presence of NADPH, estrogenic activity was increased. However, liver microsomes from dexamethasone-treated rats showed decreased estrogenic activity due to formation of inactive 5-OH BP-3 and reduced formation of active 2,4-diOH BP. Anti-androgenic activity of BP-3 was decreased after incubation with liver microsomes.
This study was performed to investigate the pharmacokinetics of benzophenone-3 (BZ-3) after oral administration at 100 mg/kg bw in male Sprague-Dawley rats. ... Urine and feces analysis indicate that urine was the major route of excretion, followed by feces. Further analysis of urine samples also indicates that conjugation of BZ-3 with glucuronic acid was the major systemic elimination route for the compound.
The disposition of benzophenone-3 (BZ-3) was investigated after dermal administration of 100 mg/kg bw in Sprague-Dawley rats. ... Three metabolites were identified in plasma, 2,4-dihydroxybenzophenone (DHB) and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB) were the major metabolites detected in the plasma, while 2,3,4-trihydroxybenzophenone (THB) was detected in trace amounts. Tissue distribution studies revealed that THB was the major metabolite followed by DHB (both free and conjugated) in all tissues examined. The liver contained the highest amount followed by the kidney, spleen and testes, respectively.

Biological Half-Life
This study was performed to investigate the pharmacokinetics of benzophenone-3 (BZ-3) after oral administration at 100 mg/kg bw in male Sprague-Dawley rats. ... The elimination pattern was biphasic with alpha and beta half-lives of elimination of 0.88 and 15.90 hr, respectively.
The disposition of benzophenone-3 (BZ-3) was investigated after dermal administration of 100 mg/kg bw in Sprague-Dawley rats. Blood samples were collected at various intervals and the parent compound and its metabolites were analyzed by HPLC. Absorption was rapid ... The half-life of absorption was 3.45 hr... . Disappearance from the plasma was biphasic with different half-lives (1.3 for alpha phase and 15.05 hr for beta phase)

Mechanism of Action
Oxybenzone absorbs UV-A ultraviolet rays, preventing them from reaching the skin.
Hirschsprung's disease (HSCR) is neonatal intestinal abnormality which derived from the failure of enteric neural crest cells migration to hindgut during embryogenesis from 5 to 12 weeks. Currently, the knowledge of environmental factors contributing to HSCR is still scarce. Benzophenone-3 (BP-3) is one of the most widely used UV filters, and has weak estrogen and strong anti-androgenic effects. In order to examine the effect of maternal BP-3 exposure on development of offspring and explore the potential mechanism, we conducted case and control study and in vitro study. In this work, BP-3 concentrations in maternal urine was detected by ultra-high performance liquid chromatography. Besides, we investigated the cytotoxicity and receptor tyrosine kinase (RET) expression in cells exposed to BP-3. The results showed that maternal BP-3 exposure was associated with offspring's HSCR in the population as well as inhibited migration of 293T and SH-SY5Y cells. What's more, we discovered dose-response relationship between RET expression and BP-3 exposure dose, and miR-218 and some other genes involved in SLIT2/ROBO1-miR-218-RET/PLAG1 pathway were also related to BP-3 exposure. Therefore, we deduced that BP-3 influenced cell migration via SLIT2/ROBO1-miR-218-RET/PLAG1 pathway. Our study firstly revealed the relationship between maternal BP-3 exposure and HSCR as well as its potential mechanism.
Diminish the penetration of ultraviolet (UV) light through the epidermis by absorbing UV radiation within a specific wavelength range. The amount and wavelength of UV radiation absorbed are affected by the molecular structure of the sunscreen agent. /Sunscreen agents, topical/
Radiation is absorbed by chemical sunscreens when the electron energy level of the drug is raised from its ground state to a higher energy level or excited state. Chromophore groups (C=C, C=O, O-N=O) with loosely held electrons are easily excited by radiation. Compounds which have several chromophore groups in optimal positions have high absorbance over a broad range of wavelengths. Chemical sunscreens are usually agents that absorb not less than 85% of UVB radiation (thus preventing burning) but may permit transmission of UVA radiation (thus allowing tanning). Some sunscreens may absorb wavelengths over a range that is slightly wider or narrower than that of UVB. All PABA derivatives absorb wavelengths of approximately 290-320 nm, benzophenone derivatives absorb wavelengths of approximately 250-360 nm, cinnamic acid derivatives absorb wavelengths of 280-320 nm, and salicylate derivatives and other miscellaneous chemical sunscreens absorb wavelengths of about 270-320 nm.
The wavelength to which the skin is maximally sensitive had been accepted for many years to be 296.7 nm; however, recent evidence suggests that the most erythemogenic UVB wavelength may be slightly lower (e.g., somewhere in the range of 292-295 nm). In addition, of the stronger burning wavelengths that reach the earth's surface, most are approximately 310 nm. Therefore, sunscreens that maximally absorb UVB radiation near either of these wavelengths are particularly effective at preventing sunburn. Maximum absorbance occurs at about 290 nm for PABA, at about 295 nm for glyceryl-p-aminobenzoate, and at about 310 nm for the remaining PABA derivatives. Maximum absorbance occurs at 280-290 nm for benzophenone derivatives, at 310 nm for cinnamic acid derivatives with the exception of diethanolamine-p-methoxycinnamate which has its maximum absorbance at 290 nm, and at 300-305 nm for salicylate derivatives and other miscellaneous sunscreens.

Use and Manufacturing
Overview
IDENTIFICATION: 2-Hydroxy-4-methoxybenzophenone, also known as benzophenone-3, is a yellowish-white, cream-colored powder. It has a very weak odor. It has low solubility in water. It occurs naturally in some plants. USE: Benzophenone-3 is used as an ingredient in sunscreen products, cosmetics and as a UV stabilizer in paints and plastics. EXPOSURE: Workers that use benzophenone-3 may breathe in mists or have direct skin contact. The general population may be exposed by dermal contact when using sun protection products and cosmetics containing this compound. If benzophenone-3 is released to the environment, it will be broken down in air. Benzophenone-3 released to air will also be in or on particles that eventually fall to the ground. It is expected to be broken down by sunlight. It will not move into air from moist soil and water surfaces. It is expected to move slowly through soil. It will not be broken down by microorganisms, and is expected to build up in fish. RISK: Allergic skin reactions have been reported in some people following skin exposure to benzophenone-3. Some benzophenone UV-absorbing chemicals have been found to alter hormone levels, but no effects on hormone levels were observed in humans following repeated whole-body application of a sunscreen containing benzophenone-3. A possible association between use of benzophonone-3 products during pregnancy and premature birth was observed in one study. There is concern that benzophenone UV-absorbing chemicals, which include benzophenone-3, may increase the risk for certain types of cancer (e.g., breast, ovarian, prostate) through disruption of normal endocrine (hormone) function, but data on the potential for benzophenone-3 to cause cancer in humans were not available. Mild skin and eye irritation developed in laboratory animals following direct exposure. Decreased sperm density was observed in laboratory animals following repeated skin application of moderate-to-high doses of benzophenone-3. No other toxic effects were noted with repeat skin application. Decreased growth, anemia, liver and kidney damage, sperm damage, and altered estrous cycling in females were observed in laboratory animals following repeated exposure to high oral doses. The number of pups/litter and pups surviving after birth was significantly decreased in laboratory animals exposed to benzophenone-3 before mating, during pregnancy, and during nursing for 2 generations. No evidence of abortion or birth defects were observed in laboratory animals following exposure to benzophenone-3 during pregnancy only. Some offspring showed abnormal development of the reproductive system at very high dose levels. Data on the potential for benzophenone-3 to cause cancer in laboratory animals were not available. The potential for benzophenone-3 to cause cancer in humans has not been assessed by the U.S. EPA IRIS program, the International Agency for Research on Cancer, or the U.S. National Toxicology Program 14th Report on Carcinogens. (SRC)

Use Classification
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Cosmetics -> Uv absorber; Uv filter

Uses
Adhesive - General adhesives and binding agents for a variety of uses
Air treatment - Air cleaners and anti-odor agents, air purifiers, air conditioners, air filters, general air care products
Apparel care, footwear, detected - Chemicals detected in substances or products (note that these chemicals may be absent from an 'ingredient list' for the product and thus unexpected, but have been detected in product testing studies) 
Beverage, juice - Subcategory of beverage, food for human consumption
Binding - Binding agents, used in paint, sand, etc
Binding, paint - Various types of paint for various uses, modifiers included when more information is known
Building construction - Related to the building or construction process for buildings or boats (includes activities such as plumbing and electrical work, bricklaying, etc)
Building material - Materials used in the building process, such as flooring, insulation, caulk, tile, wood, glass, etc.
Cleaning washing - Related to all forms of cleaning/washing, including cleaning products used in the home, laundry detergents, soaps, de-greasers, spot removers, etc
Construction - General construction (as opposed to those things labeled building_construction
Consumer use - Term applied when the only information the source indicates is 'consumer' or 'consumer product' ; also applied to terms that the source indicates are for consumer use, yet the descriptor term is ambivalent about usage (e.g., cleaning_washing products may be for industrial or consumer use, when the source indicates consumer use, the consumer_use term is also applied) - see appendix for full list of unambiguous consumer related terms plus ambiguous consumer related terms which if indicated are labeled with 'consumer_use
Drug - Drug product, or related to the manufacturing of drugs; modified by veterinary, animal, or pet if indicated by source
Filler - Fillers for paints, textiles, plastics, etc
Food - Food for human consumption, does not include food additives (see food_additive); also includes manufacture of food, facilities related to food (with appropriate modifiers) 
Fragrance - Fragrances or odor agents, can be used in home products (cleaners, laundry products, air fresheners) or similar industrial products; usage indicated when known; more specific modifiers included when known 
Manufacturing, automotive - Generally related to automobiles or their manufacture, used when automotive_care or automotive_component are not applicable (e.g. auto fuel, GPS units), or detailed information is not known 
Manufacturing, chemical - General term used only when the only information known from the source is 'chemical,' typically related to manufacturing of chemicals, or laboratory chemicals 
Manufacturing, electrical - Related to electrical work (such as wiring of a building), electric current insulation materials, or other electrical components
Manufacturing, furniture - Furniture, or the manufacturing of furniture (can include chairs and tables, and more general furniture such as mattresses, patio furniture, etc.)
Manufacturing, personal care - Personal care products, including cosmetics, shampoos, perfumes, soaps, lotions, toothpastes, etc
Manufacturing, plastics - Plastic products, industry for plastics, manufacturing of plastics, plastic additives (modifiers included when known)
Personal care: scalp treatment - Products for treating the scalp, including products dandruff or hair loss
Personal care, cosmetics, face - Personal care products used on the face (includes facial treatments, oil and blemish control, make-up removers, facial cleansers
Personal care, cosmetics, hair_removal, cream - Personal care products, including scouring cream, hand creams, shaving cream, and tanning cream
Personal care, cosmetics, lips - subcategory of personal care and cosmetics, lip care products
Personal care, cosmetics, lotion - Subcategory of personal care and cosmetics, lotions and moisturizers for consumer use
Personal care, cosmetics, nails, detected - Chemicals detected in substances or products (note that these chemicals may be absent from an 'ingredient list' for the product and thus unexpected, but have been detected in product testing studies) 
Personal care, sunscreen - Sunscreen, used on the skin to protect skin from the sun's rays
Pesticide - Substances used for preventing, destroying or mitigating pests
Photographic - Related to photography, film, photographic equipment, photographic laboraties, photochemicals, and developing of photographs
Spray - Suncreens and blocks marketed to children or babies (spray or aerosol formulations specified
Uv stabilizer - Ultraviolet (UV) stabilizers, used in products to protect them from long-term degradation from the effects of UV exposure

For 2-hydroxy-4-methoxybenzophenone (USEPA/OPP Pesticide Code: 000691) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./
Benzophenone-3 (BZ-3) is one of the UV-absorbing agents that has been used in industry and medicine for more than 30 years. Millions of consumers are exposed to benzophenones on a daily basis owing to the widespread use of these compounds in many of the products on the market, such as lipsticks, hair sprays, hair dyes, shampoo and detergent bars and sunscreen lotions. ...
Used in cosmetics and sunscreen products at a maximum concentration at 10% weight/weight. Used as a broad-band UV filter in concentrations of up to 10% in sunscreen products alone or in combination with other UV filters. Beside the usage in sunscreens, it is incorporated in other types of cosmetic products at concentrations ranging between 0.05 - 0.5% for product protection (photoprotection).
Benzophenones-2, -3, -4, -6, -8, and, -9 are used in suntan lotions and hair sprays because they protect the skin and hair from the harmful effects of the sun. These ingredients also photostabilize cosmetic dyes, creams, and lotions. ...Benzophenones-1, -3, and -6 are ... frequently found in nail polishes (in concentrations up to 1%)...

Industry Uses
Oxidizing/reducing agents stabilizer
Consumer Uses
Air care products

Methods of Manufacturing
Benzoic acid is condensed with resorcinol monomethyl ether by heating in presence of ZnCl2, polyphosphoric acid (103% H3PO4 equivalent), and PCl3.
Benzophenone-3 is prepared by the Friedel-Crafts reaction of benzoyl chloride with 3-hydroxyanisole. The product is then recrystallized from water/methanol and dried.

Impurities
Impurities/accompanying contaminants: Organic solvents: < 0.01% Xylene; Polycyclic aromatic hydrocarbons: < 10 ppb (total); Benzo(a)-pyrene: < 1 ppb; Heavy metals: < 10 ppm.

General Manufacturing Information
Fragrance manufacture
Plastic material and resin manufacturing
A sunscreen with a high molar absorptivity (20,381 at 290 nm), and it absorbs in both the long and short UV spectrum 270 to 350 nm. ... It serves not only to prevent sunburn but also to protect against the photodynamic, photosensitizing, and phototoxic effects of various drugs.
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).

Identification
Analytic Laboratory Methods
A multiresidue method was developed for the simultaneous determination of 31 emerging contaminants (pharmaceutical compounds, hormones, personal care products, biocides, and flame retardants) in aquatic plants. Analytes were extracted by ultrasound-assisted matrix solid-phase dispersion (UA-MSPD) and determined by gas chromatography-mass spectrometry after sylilation, The method was validated for different aquatic plants (Typha angustifolia, Arundo donax, and Lemna minor) and a semiaquatic cultivated plant (Oryza sativa) with good recoveries at concentrations of 100 and 25 ng/g wet weight, ranging from 70 to 120%, and low method detection limits (0.3 to 2.2 ng/g wet weight). A significant difference of the chromatographic response was observed for some compounds in neat solvent versus matrix extracts, and therefore, quantification was carried out using matrix-matched standards in order to overcome this matrix effect. Aquatic plants taken from rivers located at three Spanish regions were analyzed, and the compounds detected were parabens, bisphenol A, benzophenone-3, cyfluthrin, and cypermethrin. The levels found ranged from 6 to 25 ng/g wet weight except for cypermethrin that was detected at 235 ng/g wet weight in O. sativa samples.
A method of dispersive liquid-liquid microextraction (DLLME) combined with online derivatization-gas chromatography-mass spectrometry (GC-MS) was developed for the determination of benzophenone-type ultraviolet (UV) filers (BPs) in environmental aqueous samples. It is found that the online derivatization was superior to the off-line derivatization with its simplicity, high reaction efficiency and less consumption of potential poisonous reagents. The influential factors for online derivatization, including the temperature of the injection port, the splitless time, the proportion of derivatization reagent and sample solution, were initially optimized. In addition, the influential factors for DLLME, including the type of the extractant and dispersing solvent, the proportion of the extractant and the dispersing solvent, the volume of sample solution, the pH and the salt concentration of the sample solution were individually optimized in detail. Under the optimized derivatization and DLLME conditions, the limits of detection for the six BPs, benzophenone, 2,4-dihydroxybenzophenone, oxybenzone, 4- hydroxybenzophenone, octabenzone and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, ranged from 0.011 to 0.15 ug/L. The intra-day and inter-day relative standard deviations varied from 0.7% to 16.6%. The method was applied to the analysis of lake and river water with good recoveries. It is cost effective, reliable, easy to operate, environment-friendly and promising in the real applications.
A solvent-free method for the rapid analysis of six benzophenone-type UV absorbers in water samples is described. The method involves the use of dispersive micro solid-phase extraction (DmSPE) followed by the simultaneous silylation and thermal desorption (SSTD) gas chromatography-mass spectrometry (GC-MS) operating in the selected-ion-storage (SIS) mode. A Plackett-Burman design was used for screening and a central composite design (CCD) for optimizing the significant factors was applied. The optimal experimental conditions involved immersing 1.5 mg of the Oasis HLB adsorbent in a 10 mL portion of water sample. After vigorous shaking for 1 min, the adsorbents were transferred to a micro-vial, and were dried at 122 °C for 3.5 min, after cooling, 2 uL of the BSTFA silylating reagent was added. For SSTD, the injection-port temperature was held at 70 °C for 2.5 min for derivatization, and the temperature was then rapidly increased to 340 °C to allow the thermal desorption of the TMS-derivatives into the GC for 5.7 min. The limits of quantitation (LOQs) were determined to be 1.5-5.0 ng/L. Precision, as indicated by relative standard deviations (RSDs), was equal or less than 11% for both intra- and inter-day analysis. Accuracy, expressed as the mean extraction recovery, was between 87% and 95%. A preliminary analysis of the municipal wastewater treatment plant (MWTP) effluent and river water samples revealed that 2-hydroxy-4-methoxybenzophenone (BP-3) was the most common benzophenone-type UV absorber present. Using a standard addition method, the total concentrations of these compounds ranged from 5.1 to 74.8 ng/L.
A method has been developed for the trace determination of two sunscreen constituents (2-hydroxy-4-methoxybenzophenone and octyldimethyl-p-aminobenzoic acid) in water samples, which are commonly used in commercial formulations. The method employs solid-phase microextraction (SPME) and gas chromatography with flame ionization and mass spectrometric detection. ... The poly(dimethylsiloxane) 100-um and polyacrylate 85-um fiber coatings were found to be the most efficient for the extraction of these compounds from aqueous matrices. ... The recoveries were relatively high, 82-98%, with quantitation limits below 1 ug/L. A comparison between the proposed methods and the conventional multiresidue solid-phase extraction revealed that the proposed technique(s) can be reliably used for sunscreen residue measurement in water samples with satisfactory results.

Clinical Laboratory Methods
Phthalates, parabens and 2-hydroxy-4-methoxybenzophenone or benzophone-3 are thought to act as endocrine disrupting chemicals, being able to disrupt the endocrine balance and therefore able to lead to some hormonal diseases. Numerous large-scale biomonitoring studies have detected the biomarkers of these compounds in more than 75% of the general population. To assess the exposure to these chemicals, we developed an analytical method based on a Solid Phase Extraction (SPE) prior to ultra high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous measurement of seven phthalate metabolites (monobenzyl phthalate, mono-n-butyl phthalate, mono-iso-butyl phthalate, mono-2-ethylhexyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, mono-2-ethyl-5-oxohexyl phthalate, monoethyl phthalate), four parabens (methyl paraben, ethyl paraben, n-propyl paraben, n-butyl parabens) and benzophenone-3 in human urine. The distinction between unconjugated, glucuro- and sulfoconjugated forms was achieved using different enzymatic hydrolyses. The whole procedure was validated according to the total error approach, and was demonstrated to be linear (regression coefficient ranging from 0.987 to 0.998) and accurate (inter and intra assay precision <17.71%, relative bias <5.87%) in the dosing range of concentrations. The limits of quantification (LOQs) obtained ranged between 0.30 and 1.23 ng/mL depending on the analyte. The reliability of the method was proven in passing successfully the German External Quality Assessment Scheme (G-EQUAS). Moreover, the urine from 25 volunteers were analyzed for the determination of glucuro-, sulfo- and free species separately. Phthalate metabolites, parabens and benzophenone-3 were positively detected in almost all urine samples, with detection rates ranging from 40 to 100%. Levels measured ranged from
This paper reports the development of a reversed-phase high-performance liquid chromatographic assay for quantifying five of the most common sunscreen agents, namely 2-ethylhexyl-p-dimethyl aminobenzoate (Escalol 507), 2-ethylhexyl-p-methoxycinnamate (Parsol MCX); 4-tert.-butyl-4'-methoxydibenzoylmethane (Parsol 1789), 2-hydroxy-4-methoxybenzophenone-3 (oxybenzone) and 2-ethylhexyl-salicylate (octylsalicylate). The assay permits analysis of the sunscreen agents in formulations and in biological fluids, including bovine serum albumin (BSA) solution, a common additive to in vitro skin diffusion cell receptor fluids, as well as human plasma. Separation was achieved using an ODS C154 column with a methanol-water (88:12) mobile phase. The analytes were detected by ultraviolet light absorption at a wavelength of 315 nm. The assay was linear with minimum detectable limits, calculated as greater than 3-times the baseline noise level: for oxybenzone and Escalol 507, 0.05 ug/mL; for Parsol 1789 and Parsol MCX, 0.1 ug/mL; for octylsalicylate, 1 ug/mL. ...
An analytical method for the determination of UV filter substances in fish tissue has been developed and validated using benzophenone-3, 3-(4-methylbenzylidene)-camphor, 2-ethylhexyl-2-cyano-3,3-diphenyl-2-propenoate and 2-ethylhexyl 3-(methoxyphenyl)-2-propenoate as target analytes. The fish fillets were homogenized and extracted by Soxhlet extraction. The extracts were run through a clean-up process including gel permeation chromatography followed by solid-phase extraction. Quantification of the compounds was performed using liquid chromatography with tandem mass spectrometric detection. ... Mean recoveries were in the range 86-108%. The precision is expressed as the relative standard deviation, and in all but one of the cases was 20% or below. The accuracy of the method allows residue analyses to be performed on biological matrices at ng/g levels. ...
A method using isotope dilution on-line solid-phase extraction (SPE) coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) /was developed/ for the determination in urine of nine environmental phenolic compounds: Bisphenol A; 4-tert-octylphenol; o-phenylphenol; 2,4-dichlorophenol; 2,5-dichlorophenol; 2,4,5-trichlorophenol; 2,4,6-trichlorophenol; benzophenone-3 (2-hydroxy-4-metoxybenzophenone); and triclosan (2,4,4'-trichloro-2'-hydroxyphenyl ether). A unique fully automated column-switching system ... was designed to allow for concurrent SPE-HPLC operation with peak focusing. ... The phenols were detected by negative ion-atmospheric pressure chemical ionization-MS/MS. The efficient preconcentration of the phenols by the SPE column, analyte peak focusing by the dilution, and minimal ion suppression in the LC/MS interface by the buffer-free mobile phases resulted in limits of detection as low as 0.1-0.4 ng/mL for most analytes. ...
The purpose of the present study was to develop a reverse-phase high-performance liquid chromatographic (HPLC) assay for quantifying four common sunscreen agents, namely 2-hydroxy-4-methoxybenzophenone, 2-ethylhexyl-p-methoxycinnamate, 2-ethylhexylsalicylate (octylsalicylate) and salicylic acid 3,3,5-trimethcyclohexyl ester (homosalate) in a range of biological matrices. ... Separation was achieved utilizing a Symmetry C(18) column with methanol-water as the mobile phase. The assay permits analysis of the sunscreen agents in biological fluids, including bovine serum albumin (BSA) solution, plasma and urine, and in human epidermis. The assay was linear (r2 > 0.99) with minimum detectable limits of 0.8 ng for oxybenzone, 0.3 ng for octylmethoxycinnamate, and 2 ng for homosalate and octylsalicylate. 

First Aid Measures
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)

Fire Fighting
Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (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.

Cleanup Methods
ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Disposal Methods
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.

Preventive Measures
ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains.
Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection
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.
SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.
SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Nonfire Spill Response
SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a 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 protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

Stability and Reactivity
Air and Water Reactions
Insoluble in water.
Reactive Group
Ethers
Ketones
Phenols and Cresols

Hazardous Reactivities and Incompatibilities
Incompatible materials: Bases, acid chlorides, acid anhydrides, oxidizing agents.

Interactions
Benzophenone-3 (BZ-3; 2-hydroxy-4-methoxybenzophenone, oxybenzone) ... penetrates the skin and can be found in the urine. The amount varies between 0.4% and 2%. This seems to be the main metabolic pathway in rats. ... To investigate the total amount of BZ-3 excreted in the urine after repeated topical whole-body applications of a sunscreen and to see if UV radiation has any effect on the amount excreted... 25 volunteers applied a commercially available sunscreen containing 4% BZ-3 morning and night for 5 days. Their urine was measured during those 5 days and during a further 5 days after the last application. They were divided into groups A (unirradiated) and B. Group B received UV radiation according to skin type: UVA between 400 and 707 J/sq cm, and UVB between 0.46 and 2.0 J/sq cm. BZ-3 in urine was analysed with a high-performance liquid chromatography method. ... The volunteers excreted 1.2-8.7% (mean 3.7%) of the total amount of BZ-3 applied. There was no significant difference between the two groups (P < 0.99, t-test)...

Gonzalez H et al; Br J Dermatol 154 (2): 337-40 (2006)
Hazardous Substances Data Bank (HSDB)
Mutual enhancement of dermal absorption of N,N-diethyl-m-toluamide (DEET) and oxybenzone (OBZ) has been reported recently with DEET and OBZ being active ingredients of insect repellent and sunscreen, respectively. To assess the reported enhancing effect directly, we used human urinary metabolites as biomarkers; besides, we also sought to determine the best way for concurrent use of these two products without extra absorption of either. Four dermal application methods were used: DEET only (S1), OBZ only (S2), DEET on top of OBZ (S3), and OBZ on top of DEET (S4). Among the study methods, there was a significant difference (p=0.013), which was attributed to the difference between S1 and S4, suggesting that applying OBZ over DEET on the skin lead to significantly higher absorption of DEET. Using both products in reverse order, (S3) did not result in extra DEET absorption significantly. As for OBZ permeation, no significant difference was observed among the methods. In summary, the enhancement of DEET absorption is confirmed for OBZ being applied over DEET on the skin; should concurrent use of both be necessary, applying sunscreen (OBZ) first and then insect repellent (DEET) with a 15-min interval is recommended.

Yiin LM et al; Environ Sci Pollut Res Int 22 (9): 7062-70 (2015)
Hazardous Substances Data Bank (HSDB)
Organic ultraviolet (UV) filters are used in a wide variety of products, including cosmetics, to prevent damage from UV light in tissues and industrial materials. Their extensive use has raised concerns about potential adverse effects in human health and aquatic ecosystems that accumulate these pollutants. To increase sun radiation protection, UV filters are commonly used in mixtures. Here, we studied the toxicity of binary mixtures of 4-methylbenzylidene camphor (4MBC), octyl-methoxycinnamate (OMC), and benzophenone-3 (BP-3), by evaluating the larval mortality of Chironomus riparius. Also molecular endpoints have been analyzed, including alterations in the expression levels of a gene related with the endocrine system (EcR, ecdysone receptor) and a gene related with the stress response (hsp70, heat shock protein 70). The results showed that the mortality caused by binary mixtures was similar to that observed for each compound alone; however, some differences in LC50 were observed between groups. Gene expression analysis showed that EcR mRNA levels increased in the presence of 0.1 mg/L 4MBC but returned to normal levels after exposure to mixtures of 4MBC with 0.1, 1, and 10 mg/L of BP-3 or OMC. In contrast, the hsp70 mRNA levels increased after exposure to the combinations tested of 4MBC and BP-3 or OMC mixtures. These data suggest that 4MBC, BP-3, and OMC may have antagonist effects on EcR gene transcription and a synergistic effect on hsp70 gene activation. This is the first experimental study to show the complex patterned effects of UV filter mixtures on invertebrates. The data suggest that the interactions within these chemicals mixtures are complex and show diverse effects on various endpoints.

Ozaez I et al; Sci Total Environ 556: 154-62 (2016)
Hazardous Substances Data Bank (HSDB)
For the last years, the increase of the number of skin cancer cases led to a growing awareness of the need of skin protection against ultraviolet (UV) radiations. Chemical UV filters are widely used in sunscreen formulations as benzophenone-3 (BP-3), a usually used broad spectrum chemical UV filter that has been shown to exercise undesirable effects after topical application. Innovative sunscreen formulations are thus necessary to provide more safety to users. Lipid carriers seem to be a good alternative to formulate chemical UV filters reducing their skin penetration while maintaining good photo-protective abilities. The aim of this work was to compare percutaneous absorption and cutaneous bioavailability of BP-3 loaded into solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), nanostructured polymeric lipid carriers (NPLC) and nanocapsules (NC). Particle size, zeta potential and in vitro sun protection factor (SPF) of nanoparticle suspensions were also investigated. Results showed that polymeric lipid carriers, comprising NPLC and NC, significantly reduced BP-3 skin permeation while exhibiting the highest SPF. This study confirms the interesting potential of NPLC and NC to formulate chemical UV filters.

Gilbert E et al; Int J Pharm 504 (1-2): 48-58 (2016)
Hazardous Substances Data Bank (HSDB)
For more Interactions (Complete) data for 2-Hydroxy-4-methoxybenzophenone (7 total), please visit the HSDB record page.

Toxicity Summary
IDENTIFICATION AND USE: 2-Hydroxy-4-methoxybenzophenone (Benzophenone-3; BP-3) forms crystals or powder. It is used as an ultraviolet light absorber and stabilizer, especially in plastics and paints. It is also used as a broad-band UV filter in concentrations of up to 10% in sunscreen products alone or in combination with other UV filters. It serves not only to prevent sunburn but also to protect against the photodynamic, photosensitizing, and phototoxic effects of various drugs. HUMAN STUDIES: Photosensitivity to the UV-blocking agent benzophenone-3 has been reported. ANIMAL STUDIES: Benzophenone-3 was not a skin sensitizer in mice. Mice received benzophenone-3 in concentrations of 0; 3,125; 6,250; 12,500; 25,000 and 50,000 ppm in the diet for 13 weeks. The following effects were noted: 554 mg/kg bw/day: no adverse effects noted. 1,246 mg/kg bw/day: increased liver weight. 2,860 mg/kg bw/day: increased liver weight. 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes. 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cytoplasmic vacuolization of hepatocytes; decreased sperm density and increased abnormal sperm in males; increased estrous cycle length in females. In developmental studies in rats, the following effects were noted: 204 mg/kg bw/day: no deviations among the reproductive parameters studied. 828 mg/kg bw/day: no deviations among the reproductive parameters studied. 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females: prolonged cycle length. Benzophenone-3 is an endocrine-disrupting chemical based on in vivo and in vitro testing. Benzophenone-3 did not induce gene mutations in a Salmonella typhimurium photomutagenicity test. In Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 benzophenone-3 was nonmutagenic with and without microsomal activation. ECOTOXICITY STUDIES: Benzophenone-3 can disrupt agonistic behavior of male fighting fish, indicating the endocrine disrupting activity of this compound.

Ecological Information
Environmental Fate/Exposure Summary
2-Hydroxy-4-methoxybenzophenone's production and use as an ingredient in sunscreen products, cosmetics and as an ultraviolet light absorber and stabilizer in plastics and paints may result in its release to the environment through various waste streams. 2-Hydroxy-4-methoxybenzophenone has been reported to occur naturally in some flowering plants. If released to air, an estimated vapor pressure of 6.6X10-6 mm Hg at 25 °C indicates 2-hydroxy-4-methoxybenzophenone will exist in both the vapor and particulate phases. Vapor-phase 2-hydroxy-4-methoxybenzophenone 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 1.9 hours. Particulate-phase 2-hydroxy-4-methoxybenzophenone will be removed from the atmosphere by wet and dry deposition. 2-Hydroxy-4-methoxybenzophenone absorbs light at maximum of 287 nm with absorption extending to 400 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, 2-hydroxy-4-methoxybenzophenone is expected to have low mobility based upon an estimated Koc of 950. The estimated pKa of 2-hydroxy-4-methoxybenzophenone is 7.1, indicating that this compound will exist partially in anion form in the environment and anions generally d