Dioxybenzon

Cosmetic ingredients (Benzophenone-8) -> CIR (Cosmetic Ingredient Review)

Uv absorber

Practically insoluble in water

Solubility in g/100 mL at 25 °C: ethanol 21.8; isopropanol 17; propylene glycol6.2; ethylene glycol 3.0; n-hexane 1.5

Freely soluble in alcohol, toluene

338 to 347 °F at 1 mmHg (NTP, 1992)

BP: 172 °C at 1 mm Hg

Hazardous decomposition products formed under fire conditions: Carbon oxides

When heated to decomposition it emits acrid smoke and irritating vapors.

68 °C

MP: 70.6-77.2 °C

2,2'-dihydroxy-4-methoxybenzophenone is a yellow powder. (NTP, 1992)

Dry Powder

This chemical does not meet GHS hazard criteria for 9.8% (5 of 51) of reports.

Warning

H315 (84.3%): Causes skin irritation [Warning Skin corrosion/irritation]

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

Aggregated GHS information provided per 51 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

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

Methanone, (2-hydroxy-4-methoxyphenyl)(2-hydroxyphenyl)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Methanone, (2-hydroxy-4-methoxyphenyl)(2-hydroxyphenyl)- 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: 29-03-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/23375

Methanone, (2-hydroxy-4-methoxyphenyl)(2-hydroxyphenyl)-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

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. Dixoybenzone up to 3% is included on this list.

An alcohol and a ketone. Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides. Ketones are reactive with many acids and bases liberating heat and flammable gases (e.g., H2). The amount of heat may be sufficient to start a fire in the unreacted portion of the ketone. Ketones react with reducing agents such as hydrides, alkali metals, and nitrides to produce flammable gas (H2) and heat. Ketones are incompatible with isocyanates, aldehydes, cyanides, peroxides, and anhydrides. They react violently with aldehydes, HNO3, HNO3 + H2O2, and HClO4.

This compound is not very flammable but any fire involving this compound may produce dangerous vapors. You should evacuate the area. All firefighters should wear full-body protective clothing and use self-contained breathing apparatuses. You should extinguish any fires involving this chemical with a dry chemical, carbon dioxide, foam, or halon extinguisher. (NTP, 1992)

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.

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, 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, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol 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 alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate 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. Contaminated packaging: Dispose of as unused product.

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.

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

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains.

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.

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.

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).

2,2'-Dihydroxy-4-methoxybenzophenone was tested for but not detected (detection limit = 0.10ng/mL) in 34 urine samples from Tunisian women, collected from May to October 2012(1). The compound was detected, not quantified in four of 177 urine samples from the general population in Seoul and Gyeonggi province, Korea; sampling was conducted between July and August, 2014(2).

Amiodarone hydrochloride is currently being investigated in the United States as a cardiac antiarrhythmic agent. Previous reports from Europe indicate that amiodarone occasionally causes a cutaneous photosensitivity reaction that may be associated with a peculiar blue-gray discoloration of the skin. In addition, corneal microdeposits of yellow-brown granules may occur. We report observations on a case of amiodarone photosensitivity and corneal deposits developing in a patient shortly after amiodarone therapy was begun. Symptoms included burning and stinging of the skin, with redness and swelling that developed immediately after sun exposure. Phototesting showed that the photoactivating wavelengths were primarily in the long-wave UV-A spectrum between 350 and 380 nm. Prior application of a 10% dioxybenzone sunscreen greatly reduced the phototest reaction. Four weeks after the patient stopped taking amiodarone, the UV-A sensitivity was still present but diminished, and by ten weeks it had disappeared. During this time, the corneal deposits were reduced in number. All ten patients we have treated so far with amiodarone for cardiac arrhythmias have shown a similar photosensitivity, indicating that this is probably a phototoxic reaction.

Sunscreens are widely utilized due to the adverse effects of ultraviolet (UV) radiation on human health. The safety of their active ingredients as well as that of any modified versions generated during use is thus of concern. Chlorine is used as a chemical disinfectant in swimming pools. Its reactivity suggests sunscreen components might be chlorinated, altering their absorptive and/or cytotoxic properties. To test this hypothesis, the UV-filters oxybenzone, dioxybenzone, and sulisobenzone were reacted with chlorinating agents and their UV spectra analyzed. In all cases, a decrease in UV absorbance was observed. Given that chlorinated compounds can be cytotoxic, the effect of modified UV-filters on cell viability was examined. Chlorinated oxybenzone and dioxybenzone caused significantly more cell death than unchlorinated controls. In contrast, chlorination of sulisobenzone actually reduced cytotoxicity of the parent compound. Exposing a commercially available sunscreen product to chlorine also resulted in decreased UV absorbance, loss of UV protection, and enhanced cytotoxicity. These observations show chlorination of sunscreen active ingredients can dramatically decrease UV absorption and generate derivatives with altered biological properties.

BACKGROUND: Sunscreen compounds with added benefit of skin cancer prevention have both public and commercial interests. Our earlier study using the Epstein-Barr virus early antigen in vitro assay reported on skin cancer chemoprevention potential of benzophenone sunscreens. We now report the in vivo antitumor activity of two of the benzophenone sunscreens which tested positively in the in vitro assay, octabenzone (UV-1) and dioxybenzone (UV-2), in the two-stage mouse skin carcinogenesis model using (+/-)-(E)-4-methyl-2-[-(E)-hydroxyamino]-5-nitro-6-methoxy-3-hexanamide (NOR-1) as inducer and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) as promoter. MATERIALS AND METHODS: Pathogen-free, female hairless mice of HOS:HR-1 strain, 15 animals per control and test groups, were used. Skin tumors were induced by a single dose of NOR-1 (390 nmol in 100 uL of acetone). One week later, TPA (1.7 nmol in 100 uL of acetone) was applied to skin twice weekly for 20 weeks as tumor a promoter. The test compounds UV-I or UV-2 were administered at 0.0025% to mice through drinking water ad libitum, starting one week prior to and stopping one week after tumor initiation. All animals were examined weekly for the development of skin papillomas. RESULTS: In both UV-1- and UV-2-treated mice, a two-week delay in tumor appearance, and significant inhibition (p<0.001) of tumor incidence (50% and 60%, respectively) and tumor burden (papilloma inhibition/mouse, 50% and 70%, respectively) were observed when compared to the positive control group. UV-2 (dihydroxy derivative) was a more potent inhibitor of skin tumor than UV-1 (monohydroxy derivative), which followed their antioxidant activity ranking. CONCLUSION: The results affirm the skin cancer chemoprevention potential of orally-ingested benzophenone sunscreens in mice and warrant studies in humans to validate synergistic protection achievable by complementation of oral and topical sunscreen usage.

This study aimed to qualify photosafety screening on the basis of photochemical and pharmacokinetic (PK) data on dermally applied chemicals. Six benzophenone derivatives (BZPs) were selected as model compounds, and in vitro photochemical/phototoxic characterization and dermal cassette-dosing PK study were carried out. For comparison, an in vivo phototoxicity test was also conducted. All of the BZPs exhibited strong UVA/UVB absorption with molar extinction coefficients of over 2000 M(-1) x cm(-1), and benzophenone and ketoprofen exhibited significant reactive oxygen species (ROS) generation upon exposure to simulated sunlight (about 2.0 mW/sq cm); however, ROS generation from sulisobenzone and dioxybenzone was negligible. To verify in vitro phototoxicity, a 3T3 neutral red uptake phototoxicity test was carried out, and benzophenone and ketoprofen were categorized to be phototoxic chemicals. The dermal PK parameters of ketoprofen were indicative of the highest dermal distribution of all BZPs tested. On the basis of its in vitro photochemical/phototoxic and PK data, ketoprofen was deduced to be highly phototoxic. The rank of predicted phototoxic risk of BZPs on the basis of the proposed screening strategy was almost in agreement with the results from the in vivo phototoxicity test. The combined use of photochemical and cassette-dosing PK data would provide reliable predictions of phototoxic risk for candidates with high productivity.

The sunscreen protection factor (SPF) is essentially a factor that accounts for all the variables (UV absorption range, maximum absorbance, molar absorptivity, concentration, pH, solvent) that determine the effectiveness of a sunscreen product. SPFs are derived by dividing the minimum dose of sunlight needed to produce erythema (MED) on sunscreen-protected skin by that dose producing the same effect on unprotected skin. The US Food and Drug Administration's (FDA) approved method for determining SPFs relies on a solar simulator. Sunlight generally cannot be used because it is too variable. However, some clinicians believe that use of a solar simulator on a small number of test subjects may not provide an accurate indication of a product's effectiveness. Sunscreens with SPFs of 2 to less than 4 afford only minimum protection against sunburn but permit suntanning; SPFs of 4 to less than 8 allow moderate sunburn protection and UVB exposures of 4-8 times longer than unprotected skin but permit some suntanning; SPFs of 8 to less than 12 provide high sunburn protection and allow UVB exposures of 8-12 times longer than unprotected skin and permit limited suntanning; SPFs of 12 to less than 20 provide very high sunburn protection and UVB exposures of 12-20 times longer than unprotected skin and permit little or no suntanning; and SPFs of 20-30 provide ultra high sunburn protection, offering the most protection and permitting no suntanning. Effective May 21, 2001, the FDA is condensing these categories into 3 broader groups of sunscreen products and has generalized the category designations. Sunscreens with SPFs of 2 to less than 12 afford minimal protection against sunburn and tanning; SPFs of 12 to less than 30 allow moderate sunburn or suntan protection; and SPFs of 30 and above provide high protection against sunburn or tanning. /Sunscreens/

LC50; Species: Dugesia japonica (Flatworm); Conditions: freshwater, static; Concentration: 5.3 mg/L for 24 hr (95% confidence interval: 5.1-5.4 mg/L) />99% purity/

LC50; Species: Dugesia japonica (Flatworm); Conditions: freshwater, static; Concentration: 4.4 mg/L for 48 hr (95% confidence interval: 4.2-4.7 mg/L) />99% purity/

LC50; Species: Dugesia japonica (Flatworm); Conditions: freshwater, static; Concentration: 3.6 mg/L for 72 hr (95% confidence interval: 3.4-3.8 mg/L) />99% purity/

LC50; Species: Dugesia japonica (Flatworm); Conditions: freshwater, static; Concentration: 3.3 mg/L for 96 hr (95% confidence interval: 3.1-3.5 mg/L) />99% purity/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1300(SRC), determined from a structure estimation method(2), indicates that 2,2'-dihydroxy-4-methoxybenzophenone is expected to have low mobility in soil(SRC). Volatilization of 2,2'-dihydroxy-4-methoxybenzophenone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.0X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). 2,2'-Dihydroxy-4-methoxybenzophenone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.0X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Utilizing the CO2 Evolution Test, 0% CO2 Evolution was reached in 28 days(3) indicating that biodegradation is not an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1300(SRC), determined from a structure estimation method(2), indicates that 2,2'-dihydroxy-4-methoxybenzophenone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.0X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 40(SRC), from an estimated log Kow of 3.82(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Utilizing the CO2 Evolution Test, 0% CO2 Evolution was reached in 28 days(5) indicating that biodegradation is not an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2,2'-dihydroxy-4-methoxybenzophenone, which has an estimated vapor pressure of 2.0X10-7 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 2,2'-dihydroxy-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 2 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 2,2'-dihydroxy-4-methoxybenzophenone may be removed from the air by wet and dry deposition(SRC). UV light absorbing substances, such as 2,2'-dihydroxy-4-methoxybenzophenone, accepted as a means of protecting skin against UV radiation damage, absorb UV light in the range of 285-400 nm(2) suggesting that this compound may be susceptible to direct photolysis by sunlight(SRC).

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: 2,2'-Dihydroxy-4-methoxybenzophenone (dioxybenzone) is a solid, which is used as a benzophenone sunscreen agent. Many sunscreens contain UVA-absorbing avobenzone or a benzophenone (such as dioxybenzone, oxybenzone, or sulisobenzone), in addition to UVB-absorbing chemical ingredients (some of which also contribute to UVA protection). HUMAN STUDIES: There are no human toxicity studies available. Although it has been suggested that benzophenone derivatives may protect against photosensitivity reactions to photosensitizing drugs (e.g., chlordiazepoxide, chlorpromazine, demeclocycline, hydrochlorothiazide, nalidixic acid, nystatin, sulfisoxazole), most clinicians agree that these sunscreens provide, at most, only limited protection for patients who are sensitive to these drugs. ANIMAL STUDIES: Dioxybenzone was nonmutagenic when assayed directly and was weakly mutagenic with metabolic activation in Salmonella strain TA1537. Dioxybenzone was not mutagenic in vivo in the mouse micronucleus test. In mice, signs of toxicity including decreased activity, piloerection, and exophthalmus were observed at doses of 166-5000 mg/kg. Dioxybenzone given orally delayed skin tumors and inhibited tumor incidence and tumor burden in the two-stage mouse skin carcinogenesis model. ECOTOXICITY STUDIES: Dioxybenzone was more toxic to the two tested coral species than other benzophenone derivatives.

According to the 2016 TSCA Inventory Update Reporting data, 1 reporting facility estimated the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of 2,2'-dihydroxy-4-methoxybenzophenone in the United States is not known or reasonably ascertainable; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).

Occupational exposure to 2,2'-dihydroxy-4-methoxybenzophenone may occur through inhalation and dermal contact with this compound at workplaces where 2,2'-dihydroxy-4-methoxybenzophenone is produced or used. Use data indicate that the general population may be exposed to 2,2'-dihydroxy-4-methoxybenzophenone via dermal contact with consumer products containing 2,2'-dihydroxy-4-methoxybenzophenone. Limited monitoring data indicate that the general public may be exposed via inhalation of house dust. (SRC)

/AQUATIC SPECIES/ The benzophenone (BP) organic ultraviolet (UV) filters have been measured in seawater at ng/L to ug/L levels, but more data on their effects in non-target marine organisms are needed. Corals can be exposed to BPs due to wastewater discharges and coastal recreational activities. In this study, toxicities and bioaccumulation of BP-1 (2,4-dihydroxybenzophenone), BP-3 (oxybenzone), BP-4 (sulisobenzone) and BP-8 (dioxybenzone) to larvae and adults of two coral species, Pocillopora damicornis and Seriatopora caliendrum, were assessed at concentrations ranging from 0.1-1000 ug/L. BP-1 and BP-8 exposure caused significant settlement failure, bleaching and mortality of S. caliendrum larvae [lowest observed effect concentration (LOEC): >/=10 ug/L] compared to the other BPs, while none of the tested compounds and concentrations affected P. damicornis larvae. Nubbins were more sensitive to BP-3, BP-1 and BP-8 than larvae. Overall, BP-1 and BP-8 were more toxic to the two tested species than BP-3 and BP-4, which matches the relative bioaccumulation potential of the four BPs (BP->BP-1~BP-3>BP-4). A conservative risk assessment using the effect concentrations derived from this study showed that BP-3, BP-1 and BP-8 pose high or medium risk to the health of corals in popular recreational areas of Taiwan and Hong Kong. ...Future ecotoxicological studies of corals should take their sensitivities, life stages and metabolic capacities into consideration.

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 2,2'-dihydroxy-4-methoxybenzophenone is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

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 February 4, 2019: http://actor.epa.gov/dashboard/]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 2,2'-dihydroxy-4-methoxybenzophenone can be estimated to be 1300(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2,2'-dihydroxy-4-methoxybenzophenone is expected to have low mobility in soil(SRC).

/OTHER TOXICITY INFORMATION/ 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/

/OTHER TOXICITY INFORMATION/ 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. /Sunscreens/

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. Dixoybenzone up to 3% is included on this list.

Dioxybenzone is a sunscreen agent and chemical UV filter that absorbs UV-B rays and UV-AII rays to limit their penetration into human skin. In a screening protocol consisting of the _in vitro_ EBV-EA activation assay followed by the _in vivo_ confirmation test in the two-stage mouse skin cancer model utilizing NOR-1 as inducer and TPA as promoter of tumour, dioxybenzone exhibited a significant chemopreventive activity against mouse skin carcinogenesis which correlated with their antioxidant potency. There is some evidence that suggests some benzophenones and their hydroxylated metabolites act as weak estrogens in the environment; however similar effect of dioxybenzone has not been established.

Emitted by the sun, UVA-II rays, which range at 320–400 nm and are not absorbed by the ozone layer, and UVB rays, which range 290–320 nm and are partially absorbed by the ozone layer and exert a damaging effect on human skin, including basal cell carcinoma and melanoma. As a chemical filter, dioxybenzone absorb these rays to prevent their penetration into the skin and attenuate long-term skin damage caused by UV radiation from the sun. In a rat uterine cytosolic estrogen receptor (ER) competitive binding assay, dioxybenzone was not found to be a ER-binder.

No pharmacokinetic data available.

The pharmacokinetics of benzophenone-3 (BZ-3) was studied in rats. Male Sprague-Dawley-rats were administered 0 or 100 mg/kg oxybenzone orally. Blood samples were collected from some rats for up to 20 hours post dosing and analyzed for plasma oxybenzone by high performance liquid chromatography. Urine, feces, and expired air samples were collected for up to 96 hours and analyzed for BZ-3 metabolites. Selected rats were killed 6 hours after dosing to determine the tissue distribution of BZ-3. The kinetic behavior of oxybenzone was investigated by applying the plasma BZ-3 data to standard pharmacokinetic models. The pharmacokinetic behavior of BZ-3 in the blood could be described by a two compartment model, the halflives for distribution and elimination being 0.88 and 15.90 hours, respectively. The absorption halflife was 0.71 hour. The maximum plasma concentration, 25.6 micrograms per milliliter, occurred 3 hours after dosing. The liver had the largest total concentration of BZ-3, 6.47% of the dose, followed by the kidney, spleen, intestines, and heart in that order. BZ-3 was detected in the testes only after acid hydrolysis and in only one of six rats; however, the concentration represented 1.8% of the dose. Approximately 60% of the dose was excreted in the urine and feces over 96 hours. Urine was the predominant route of excretion. Most of the excreted dose consisted of compounds conjugated with macromolecules. Enzyme hydrolysis of the urine samples with beta-glucuronidase showed that most of the excreted dose was conjugated with glucuronic-acid. Identified metabolites included 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, and 2,3,4-trihydroxybenzophenone. The authors conclude that following oral administration, oxybenzone is rapidly absorbed from the gastrointestinal tract and distributed primarily to the liver, kidneys, and testes, indicating that the liver may be the major organ involved in BZ-3 elimination.

Metabolism of the ultraviolet absorber benzophenone-3 (BZ3) by Sprague-Dawley-rats was studied. Rats were fed 100 mg/kg BZ3 by gavage and blood, tissue, urine, and fecal samples were examined at various time points. BZ3 and its metabolites were identified in plasma as soon as 5 minutes after administration. 2,4-Dihydroxybenzophenone (DHB), 2,2'-dihydroxy-4-methoxybenzophenone, and 2,3,4-trihydroxybenzophenone were detected in the blood after 30 minutes. DHB was the major metabolite found in tissue, urine, and fecal samples. The parent compound and metabolites appeared bound to macromolecules or in conjugated forms in plasma, as free compounds and conjugates in tissues, and extensively conjugated in feces and urine. The primary route of elimination was urinary and O-dealkylation was found to be the major metabolic pathway.

The metabolism and fate of benzophenone-3 (BZ-3) was studied in male Sprague-Dawley-rats and male B6C3F1-mice after oral administration of 100mg/kg body weight. Blood samples were collected at 5 minutes to 20 hours after administration. For a tissue distribution study, tissue samples were obtained 6 hours after administration of the BZ-3. For urinary and fecal excretion studies, mice and rats were placed in glass metabolism cages for 96 hours after administration of BZ-3. In rats, BZ-3 exhibited a biphasic elimination in plasma with alpha and beta elimination half lives of 0.9 and 15.9 hours, as compared to a single phase elimination half life of 1.8 hours in mice. Absorption was faster and peak plasma concentrations were reached faster in mice than rats. In the tissues studied, accumulation of the parent compound was highest in the liver, with higher amounts in the rat than mouse. 2,4-Dihydroxybenzophenone (DHB) was the major metabolite in the tissues, with higher amounts detected in the rat than the mouse. In rats, the urine was the major route of excretion of BZ-3 and DHB. In mice, elimination was divided between the urine and feces, with 2,3,4-trihydroxybenzophenone (THB) as the primary metabolite. Trace amounts of 2,2'-dihydroxy-4-methoxybenzophenone (DHMB) were found in the urine and feces of both species. The peak excretion in the urine of both the parent compound and DHB was earlier in rats than in mice. Most of the excretion of the BZ-3 and DHB in the feces was complete within 24 hours for both species, although the total fecal excretion for the parent compound was almost double in mice than rats, and for DHB was significantly less in mice than rats. The authors postulate that variations in the absorption rates, distribution patterns, and metabolism of BZ-3 in rats and mice may be related to species specific quantitative and qualitative differences in enzyme activities.

Dioxybenzone is a derivative of benzophenone. In monkeys, percutaneous absorption of benzophenone was observed. Other derivatives of benzophenone are capable of crossing the skin via direct penetration through the intercellular laminae of the stratum corneum (SC) or by passive diffusion by high-concentration gradient into the systemic circulation, where they are transported to different tissues including liver and brain.

No pharmacokinetic data available.

No pharmacokinetic data available.

No pharmacokinetic data available.

Information on the cutaneous absorption, distribution, and elimination of most topically applied sunscreen agents is limited. Solvents used in sunscreen products affect the stability and binding of the drug to the skin; in general, alcoholic solvents allow for the most rapid and deepest epidermal penetration of sunscreens. It appears that sunscreen agents are absorbed by the intact epidermis to varying degrees. /Sunscreens/

CIR ingredient: Benzophenone-8

Broad-spectrum sunscreens often contain a number of chemical ingredients that absorb UVA and UVB radiation. Many sunscreens contain UVA-absorbing avobenzone or a benzophenone (such as dioxybenzone, oxybenzone, or sulisobenzone), in addition to UVB-absorbing chemical ingredients (some of which also contribute to UVA protection).

Cosmetic Ultraviolet Absorber: benzophenone-8. /From table/

MEDICATION

2023: <50,000 lb

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)(2-hydroxyphenyl)-:

Plastics Material and Resin Manufacturing

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