オキシベンゾン

Other Uses -> Sunscreens

UV filter

Cosmetics ingredient -> UV Inhibitor

Cosmetic ingredients (Benzophenone-3) -> CIR (Cosmetic Ingredient Review)

Uv filter; Uv absorber

log Kow = 3.79

3.79

Weak odor

Almost odorless or faint characteristic

Colorless crystals

Crystals from isopropanol

White yellowish, cream colored powder

Pale yellow powder

less than 1 mg/mL at 68 °F (NTP, 1992)

In water, 3.7 mg/L at 25 °C

Readily soluble in most organic solvents; freely soluble in alcohol and toluene; practically insoluble in water

Soluble in carbon tetrachloride

Solubility in various solvents (in percent): ethanol, 6%; acetone, >20%; chloroform, >20%; glycerin,<0.01%; isopropyl stearate, 9%; olive oil, 9%; peanut oil, 9%

1.28e-01 g/L

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

This chemical does not meet GHS hazard criteria for 6% (116 of 1945) of reports.

Warning

H315 (70.2%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 1945 reports by companies from 26 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

Chemical: Methanone, (2-hydroxy-4-methoxyphenyl)phenyl-

Methanone, (2-hydroxy-4-methoxyphenyl)phenyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Methanone, (2-hydroxy-4-methoxyphenyl)phenyl- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 01-02-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/5515

Methanone, (2-hydroxy-4-methoxyphenyl)phenyl-: Does not have an individual approval but may be used under an appropriate group standard

Of 7 sunscreen allergens photo-patch tested in 1990 in 355 Swedish patients, it caused the most positive reactions (15 photocontact and 1 contact); [HSDB] May cause contact dermatitis, urticaria, and irritation; [CAMEO] It is tested in a 3% concentration in petrolatum; It causes both contact and photo-contact allergic reactions; Patients may also be allergic to other benzophenone sunscreens; [Marks, p. 221] An irritant; Effects in high-dose animal studies include effects on liver, kidneys, and reproductive system; Oral LD50 (rat) = 7500 mg/kg; [MSDSonline]

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed over-the-counter drug products, including oxybenzone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Sunscreen active ingredients. The active ingredient of the product consists of any of the following, within the concentration specified for each ingredient, and the finished product provides a minimum SPF value of not less than 2 as measured by the testing procedures established in subpart D of this part: Oxybenzone up to 6 percent is included on this list.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date: September 29, 2006; Reporting date: November 28, 2006.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Methanone, (2-hydroxy-4-methoxyphenyl) phenyl- is included on this list. Effective date: September 29, 2006; Sunset date: November 28, 2006.

Skin Irrit. 2 (70.2%)

Skin sensitization - Category 1

Reproductive toxicity - Category 2

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.

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.

Keep container tightly closed in a dry and well-ventilated place.

Store below 40 °C (104 °F), preferably between 15 and 30 deg. C (59 and 86 deg. F), unless otherwise specified by manufacturer. /Sunscreen agents, topical/

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.

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.

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

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

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid 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.

For more Preventive Measures (Complete) data for 2-Hydroxy-4-methoxybenzophenone (6 total), please visit the HSDB record page.

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

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

2-Hydroxy-4-methoxybenzophenone was detected in 97% of <2500 urine samples collected 2003-2004 from the US population aged 6 years and older, females and non-Hispanic white people had the highest concentrations regardless of age(1). 2-Hydroxy-4-methoxybenzophenone was potentially detected in 76.5% of human milk samples collected in Europe from mothers that had direct exposure to the use of sunscreen products containing the chemical(1). 2-Hydroxy-4-methoxybenzophenone and octyl methoxycinnamate were detected in German human breast milk samples at a concentration range of 16 to 417 ug/kg fat(2).

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)...

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.

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.

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.

For more Interactions (Complete) data for 2-Hydroxy-4-methoxybenzophenone (7 total), please visit the HSDB record page.

EC50; Species: Isochrysis galbana (Haptophyte) exponential growth phase, 7000 cells/mL; Conditions: saltwater, static, 20 °C, pH 8; Concentration: 13.87 ug/L for 72 hr (95% confidence interval: 0-41.69 ug/L); Effect: decreased population growth rate /formulation/

LC50; Species: Acropora cervicornis (Staghorn Coral ) larva; Conditions: saltwater, static, 22 °C; Concentration: 9 ug/L for 4 hr (95% confidence interval: 5.4-14.5 ug/L) /formulation/

EC50; Species: Mytilus galloprovincialis (Mediterranean Mussel) egg; Conditions: saltwater, static, 20 °C; Concentration: 3472.59 ug/L for 48 hr (95% confidence interval: 3359.65-3585.52 ug/L); Effect: decreased normal development /formulation/

LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: fresh, static, 25 °C; Concentration: 2200 ug/L for 24 hr />99% purity/

For more Ecotoxicity Values (Complete) data for 2-Hydroxy-4-methoxybenzophenone (7 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 950(SRC), determined from a structure estimation method(2), indicates that 2-hydroxy-4-methoxybenzophenone is expected to have low mobility in soil(SRC). The estimated pKa of 2-hydroxy-4-methoxybenzophenone is 7.1(3), indicating that this compound will exist partially 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 of the anion from moist soil is not expected because anions do not volatilize(SRC). Volatilization of neutral 2-hydroxy-4-methoxybenzophenone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.5X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(5). 2-Hydroxy-4-methoxybenzophenone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). A 4% of Theoretical BOD using activated sludge in the Japanese MITI test suggests that 2-hydroxy-4-methoxybenzophenone is not readily biodegradable(6). However, microcosm studies using activated sludge and digester sludge found 2-hydroxy-4-methoxybenzophenone biodegradable under both aerobic and anaerobic conditions with half-lives of 4.2-10.7 days(7). Photodegradation of 2-hydroxy-4-methoxybenzophenone may play an environmentally important role in soil given a 15 day half-life full sun in the summer in surface waters(8).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 950(SRC), determined from a structure estimation method(2), indicates that 2-hydroxy-4-methoxybenzophenone is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 7.1(3) indicates 2-hydroxy-4-methoxybenzophenone will exist partially in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces of the anion is not expected to be an important fate process(SRC). Volatilization from water surfaces of neutral 2-hydroxy-4-methoxybenzophenone is not expected(4) based upon an estimated Henry's Law constant of 1.5X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). 2-Hydroxy-4-methoxybenzophenone did not undergo hydrolysis or volatilization in sterile controls incubated at 25 °C for 42 days(6). According to a classification scheme(7), BCFs of 33-160, reported for 2-hydroxy-4-methoxybenzophenone in carp (Cyprinus carpio), exposed over an 10-week period(8), suggest bioconcentration in aquatic organisms is moderate to high. 2-Hydroxy-4-methoxybenzophenone may biodegrade, based on half-lives of 10.7 and 4.2-8.7 days under aerobic and anaerobic conditions, respectively(6). Photodegradation of 2-hydroxy-4-methoxybenzophenone in surface waters could play an environmentally important role given a 15 day half-life full sun in the summer(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2-hydroxy-4-methoxybenzophenone, which has an estimated vapor pressure of 6.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 2-hydroxy-4-methoxybenzophenone is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.9 hours(SRC), calculated from its rate constant of 2.0X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase 2-hydroxy-4-methoxybenzophenone may be removed from the air by wet and dry deposition(SRC). 2-Hydroxy-4-methoxybenzophenone absorbs light at maximum of 287 nm with absorption extending to 400 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight.

ENVIRONMENTAL: 2-Hydroxy-4-methoxybenzophenone was potentially detected in 76.5% of human milk samples collected in Europe from mothers that had direct exposure to the use of sunscreen products containing the chemical(1). 2-Hydroxy-4-methoxybenzophenone and octyl methoxycinnamate were detected in German human breast milk samples at a concentration range of 16 to 417 ug/kg fat(2).

Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org

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.

Oxybenzone absorbs UV-A ultraviolet rays, preventing them from reaching the skin.

/AQUATIC SPECIES/ Benzophenone-3 (BP-3) is a widely used organic UV-filter compound. Despite the frequent occurrence of BP-3 in aquatic environments, little is known about its effect on fish behavior. The aim of this study was to investigate the endocrine disrupting effects of BP-3 in male fighting fish (Betta splendens) with a focus on agonistic behavior. Male fighting fish were exposed to 10, 100, and 1000 ug/L BP-3, as well as a solvent control (0.1% ethanol) and a positive control (100 ng/L 17alpha-ethynylestradiol, EE2), for 28 days. At the beginning and the end of exposure, standard length and body mass of the fish were measured for calculating the condition factor (CF). In addition, spontaneous swimming activity (total distance moved) and agonistic behavior (maximum velocity and duration of opercular display in front of a mirror) were also quantified. At the end of exposure, the fish gonads were sampled for gonadosomatic index (GSI) measurement and histology. After the exposure, CF was significantly decreased in the 1000 ug/L BP-3 groups. Spontaneous swimming activity was not affected. However, maximum velocity was significantly reduced in the EE2 and 1000 ug/L BP-3 treatments; duration of opercular display was significantly decreased in the EE2 and 10 and 1000 ug/L BP-3 treatments. GSI was not significantly different between groups. There was a slight but statistically significant decrease of relative proportion of mature spermatozoa in testicular tissue in the 100 ug/L BP-3 treatment. Collectively, our results demonstrate that BP-3 can disrupt agonistic behavior of male fighting fish, indicating the endocrine disrupting activity of this compound.

/AQUATIC SPECIES/ Due to the concern about the negative effects of exposure to sunlight, combinations of UV filters like 4-Methylbenzylidene-camphor (4-MBC), Benzophenone-3 (BP-3), Benzophenone-4 (BP-4) and 2-Ethylhexyl-4-methoxycinnamate (EHMC) are being introduced in all kind of cosmetic formulas. These chemicals are acquiring a concerning status due to their increasingly common use and the potential risk for the environment. The aim of this study is to assess the behaviour of these compounds in seawater, the toxicity to marine organisms from three trophic levels including autotrophs (Isochrysis galbana), herbivores (Mytilus galloprovincialis and Paracentrotus lividus) and carnivores (Siriella armata), and set a preliminary assessment of potential ecological risk of UV filters in coastal ecosystems. In general, EC50 results show that both EHMC and 4-MBC are the most toxic for our test species, followed by BP-3 and finally BP-4. The most affected species by the presence of these UV filters are the microalgae I. galbana, which showed toxicity thresholds in the range of ug/L units, followed by S. armata>P. Lividus>M. galloprovincialis. The UV filter concentrations measured in the sampled beach water were in the range of tens or even hundreds of ng/L. The resulting risk quotients showed appreciable environmental risk in coastal environments for BP-3 and 4-MBC.

/AQUATIC SPECIES/ Benzophenone-3 (BP-3) has been widely used in sunscreens and cosmetics to protect human skin from the harmful effects of UV irradiation. While BP-3 has been frequently detected in surface waters, sediments and biota, only limited information is available on its in vivo toxicity, particularly in fish. In the present study the endocrine disrupting capacity of BP-3 and its underlying mechanisms were investigated using Japanese medaka (Oryzias latipes). Adult Japanese medaka pairs (F0) were exposed to 0, 4.7, 8.4, 26, or 90 ug/L (or 0, 15, 50, 150, or 500 ug/L of BP-3 based on nominal concentration) for 14 d and its effects on sex steroid hormones, and transcription of various associated genes were determined. Following additional 14 days of exposure, the F1 eggs reproduced were counted and were further exposed to 0, 5.4, 12, or 30 ug/L of BP-3 (or 0, 15, 50, or 150 ug/L based on nominal concentrations) until 30 days after hatching. Chemical analysis of the exposed media confirmed transformation of BP-3 to benzophenone-1 (BP-1), a more potent estrogen agonist. After 14 days of the adult fish exposure, plasma concentrations of testosterone (T) significantly increased in male fish. The 17beta-estradiol (E2) to T (E2/T) ratio showed significant decreases in both male and female fish. Overall down-regulation of gonadal steroidogenic genes such as star, cyp11a, cyp17, hsd3b, hsd17b3, and cyp19a was also observed. After 28 days of exposure, the daily average egg reproduction per female was significantly reduced at 26 ug/L of BP-3. However, hatchability of F1 eggs was not affected by continuous exposure. After continued exposure until 30 dph, juvenile fish showed concentration-dependent decrease of condition factor, but mortality was not affected. Our observation clearly indicates that endocrine balance and reproduction performance in fish could be affected by ug/L level exposure to BP-3. Consequences of longer term exposure over multi-generations warrant further investigation.

/AQUATIC SPECIES/ Personal care products have been detected in superficial waters, representing an environmental risk to the biota. Some studies indicated that 3-benzophenone (3BP) alters hormones, inducing vitellogenesis and having adverse effects on fish reproduction. Other studies have reported generation of free radicals and changes in antioxidant enzymes. Therefore, the aim of the present study was to test acute exposure to 3BP at concentrations within and beyond that found environmentally to provide important toxicological information regarding this chemical. We evaluated the effect of 3BP on vitellogenin 1 (VTG1) gene expression and the transcription of the enzymes catalase (CAT), superoxide dismutase (SOD) or glutathione peroxidase (GPx), which are involved in cellular redox balance. Zebrafish eluthero-embryos (168 hpf) were exposed to 1,10, 100, 1000 ug/L 3BP, in addition to a negative control and a 0.1% ethanol control for 48 hr. The results of our study indicated a positive significant correlation between exposure concentrations and VTG1 expression (r=0.986, p=0.0028) but only 1000 ug/L 3BP produced a significant increase from control. Acute exposure showed no significant differences in transcription levels of CAT, SOD or GPx at the tested conditions. Nevertheless, a trend toward increase in GPx expression was observed as a positive significant correlation (r=0.928, p=0.017) was noted.

For more Ecotoxicity Excerpts (Complete) data for 2-Hydroxy-4-methoxybenzophenone (10 total), please visit the HSDB record page.

2-Hydroxy-4-methoxybenzophenone has been reported to occur naturally in some flowering plants(1). Benzophenone (isomer unspicifed) was reported in the leaf of white cabbage (Brassica oleraceae var. capitata L; Brassicaceae) and at 56 ppm in the flower of Merrifll flowers (Telosma coradata; Asclepiadaceae)(2).

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.

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

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for 2-hydroxy-4-methoxybenzophenone is available.[Available from, as of July 6, 2017: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

Gray water (any washwater that has been used in the home, except water from toilets) collected from 32 homes in the Netherlands contained an average 2-hydroxy-4-methoxybenzophenone concentration of 1.0 ug/L with a range of 0.3-4.9 ug/L(1). Influent and effluent samples collected 2002-2003 from 11 wastewater treatment plants in Switzerland contained 2-hydroxy-4-methoxybenzophenone at 0.7-7.8 and <0.01-0.7 ug/L, respectively(2). 2-Hydroxy-4-methoxybenzophenone was detected in 42% of influent samples from Galicia, Spain at <0.090 ug/L, it was not detected in effluent samples(3). Influent and effluent samples collected from wastewater treatment plants in the UK contained 2-hydroxy-4-methoxybenzophenone at 638-1195 and 22-231 ng/L, respectively(4). 2-Hydroxy-4-methoxybenzophenone was detected in influent and effluent wastewater treatment plant samples collected from six countries from 1996 to 2016 at 7-3,975,000 and 1-2,196,000 ng/L, respectively(5).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 2-hydroxy-4-methoxybenzophenone can be estimated to be 950(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2-hydroxy-4-methoxybenzophenone is expected to have low mobility in soil. The pKa of 2-hydroxy-4-methoxybenzophenone is estimated as 7.1(3), indicating that this compound will exist partially 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).

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed over-the-counter drug products, including oxybenzone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Sunscreen active ingredients. The active ingredient of the product consists of any of the following, within the concentration specified for each ingredient, and the finished product provides a minimum SPF value of not less than 2 as measured by the testing procedures established in subpart D of this part: Oxybenzone up to 6 percent is included on this list.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date: September 29, 2006; Reporting date: November 28, 2006.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Methanone, (2-hydroxy-4-methoxyphenyl) phenyl- is included on this list. Effective date: September 29, 2006; Sunset date: November 28, 2006.

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. /Sunscreens/

... 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) ... .

...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.

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.

Route of Elimination: In vivo studies show oxybenzone is abosorbed transdermally (through the skin) and is excreted in the urine.

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.

CIR ingredient: Benzophenone-3

Used as an ultraviolet light absorber and stabilizer (especially in plastics), photostabilizer for synthetic resins, and topical sunscreen agent; [HSDB]

Plastic Composites Manufacturing [Category: Industry]

Sunscreening Agents.

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./

An ultraviolet light absorber and stabilizer, especially in plastics and paints.

2023: <25,000 lb

Methanone, (2-hydroxy-4-methoxyphenyl)phenyl- is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR ) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.[Table#4982]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Methanone, (2-hydroxy-4-methoxyphenyl)phenyl-. Aggregated National Production Volume: < 500,000 pounds.

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Methanone, (2-hydroxy-4-methoxyphenyl)phenyl-. National Production Volume: 100,000 - 500,000 lb/yr.

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Methanone, (2-hydroxy-4-methoxyphenyl)phenyl-:

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.

Cosmetics product ingredient: Benzophenone-3

Information on 77 consumer products that contain Benzophenone-3 (Oxybenzone) in the following categories is provided:

Fragrance Ingredients

Cosmetics -> Uv filter; Uv absorber

Plastics Material and Resin Manufacturing

Methanone, (2-hydroxy-4-methoxyphenyl)phenyl-: ACTIVE

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).