2,4-Dihydroxybenzophenon

Needles from hot water

Light-yellow, crystalline solid

Practically insoluble in cold water

Insoluble in water

Easily soluble in alcohol, ether, glacial acetic acid; scarcely soluble in cold benzene

Soluble in ethanol, methanol, methyl ethyl ketone, and ethyl acetate

148.3 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID8022406]

142.36 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

UV: 1119 (Absorption Spectra in the UV and Visible Regions, Academic Press, New York) /Methanone, 2,5-dihydroxyphenyl)phenyl-/

UV: 6-450 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /Benzophenone, 4,4'-dihydroxy/

This chemical does not meet GHS hazard criteria for 5.6% (109 of 1938) of reports.

Warning

H315 (69.3%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (93.6%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H335 (68.8%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract 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 1938 reports by companies from 18 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 109 of 1938 reports by companies.；There are 16 notifications provided by 1829 of 1938 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Chemical: Methanone, (2,4-dihydroxyphenyl)phenyl-

Status: Active Update: 09-05-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/12687

2,4-Dihydroxybenzophenone: Does not have an individual approval but may be used under an appropriate group standard

Incompatible materials: Strong oxidizing agents, strong bases.

Benzophenone-1 reacts with a variety of organic and inorganic compounds. ... An etherification of the 4-hydroxy group of Benzophenone-1 to 4-(beta-aryioxymethyl), 4-(beta-arylethoxymethyl), and 4-[beta-(aryloxymethoxy)ethyl] derivatives /was reported/. In the presence of bromide, phenyl nitrate, or nitric acid, Benzophenone-1 can react to form a number of bromo-and nitrobenzenes. Benzophenone-1 and methyl acrylate can combine to form a product that can polymerize with other compounds to form a photostable polymer. Benzophenone-1 is highly reactive with diphenylpicrylhydrazyl.

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

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

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. 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.

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 vapors, mist or gas. Ensure adequate ventilation. 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 2,4-Dihydroxybenzophenone (6 total), please visit the HSDB record page.

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).

/The study objective was/ to investigate the protective effect of 2,4-dihydroxybenzophenone (BP-1) on acute hepatotoxicity and neurotoxicity induced by cocaine in mice, and its possible mechanism. Male ICR mice were pretreated with BP-1 (100, 200, 400 mg/kg, ig, 4 d), cocaine (75 mg/kg) was injected 30 minutes after BP-1 administration on day 4.Twenty-four hours after the injection of cocaine, the serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed by HITACHI-7170A automatic analyzer. The content of malondialdehyde (MDA) and the content of reduced glutathione (GSH) and oxidized glutathione (GSSG) were examined, and the ratio of GSH/GSSG was calculated, and histopathological analyses were also made. Male ICR mice were pretreated with BP-1(100, 200, 400 mg/kg, ig, 3 d), cocaine (20 mg/kg) was injected 30 minutes after BP-1 administration on day 3.The locomotor activity during 0-180 minutes of mice was recorded individually for each animal immediately after cocaine injection. After the administration of cocaine, compared with corresponding solvent group, the activities of ALT [(1571+/-1161) IU/L vs. (30 +/-16) IU/L, P<0.05], AST [(408 +/- 226) IU/L vs. (101 +/- 12) IU/L, P<0.05] and LDH [(3963 +/- 1431) IU/L vs. (1935 +/- 287) IU/L, P<0.05] were significantly increased; the ratio of GSH/GSSG [(5.11 +/- 0.63) vs. (6.88 +/- 1.13),P<0.05] was decreased and the content of MDA [(1.97 +/- 1.36) umol/g vs. (0.07 +/- 0.06) umol/g, P<0.01] was significantly increased. With the pretreatment of BP-1, compared with cocaine treatment group, the serum ALT [(112 +/- 96 )IU/L, (54 +/- 20) IU/L, (35 +/- 15) IU/L, P<0.05],AST [(130 +/- 33) IU/L,(107 +/- 5) IU/L, (99 +/- 9) IU/L, P<0.05] and LDH [(1 667 +/- 564) IU/L, (1 507 +/- 365) IU/L, (1 249 +/- 349) IU/L, P<0.01] were significantly decreased, the ratios of GSH/GSSG [(7.33 +/- 1.84), (9.28 +/- 0.67), (10.5 +/- 1.20), P<0.05] were increased and the contents

/The study objective was/ to examine the effects of 2,4-dihydroxybenzophenone (BP-1), a benzophenone derivative used as an ultraviolet light absorbent, on acetaminophen (APAP)-induced hepatotoxicity in C57BL/6J mice. Mice were administered orally with BP-1 at doses of 200, 400 and 800 mg/kg body weight respectively every morning for 4 d before a hepatotoxic dose of APAP (350 mg/kg body weight) was given subcutaneously. Twenty four hours after APAP intoxication, the serum enzyme including serum alaine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were measured and liver histopathologic changes were examined. BP-1 administration dramatically reduced serum ALT, AST and LDH levels. Liver histopathological examination showed that BP-1 administration antagonized APAP-induced liver pathological damage in a dose-dependent manner. Further tests showed that APAP-induced hepatic lipid peroxidation was reduced significantly by BP-1 pretreatment, and glutathione depletion was ameliorated obviously. BP-1 can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity, and reduction of oxidative stress might be part of the protection mechanism.

LC50; Species: Acartia tonsa (Calanoid Copepod) age 2 weeks; Conditions: saltwater, static, 20 °C; Concentration: 2600 ug/L for 24 hr (95% confidence interval: 2100-3200 ug/L) />99% purity/

LC50; Species: Acartia tonsa (Calanoid Copepod) age 2 weeks; Conditions: saltwater, static, 20 °C; Concentration: 2600 ug/L for 24 hr (95% confidence interval: 1900-3100 ug/L) />99% purity/

LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: freshwater, static, 25 °C; Concentration: 4500 ug/L for 24 hr (95% confidence interval: 4100-4900 ug/L) />99% purity/

LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: freshwater, static, 25 °C; Concentration: 2800 ug/L for 96 hr />99% purity/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1900(SRC), determined from a structure estimation method(2), indicates that 2,4-dihydroxybenzophenone is expected to have low mobility in soil(SRC). The pKa1 and pKa2 values of 2,4-dihydroxybenzophenone are estimated at 7.1 and 8.0(3), respectively, indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb as strongly to soils containing organic carbon and clay relative to their neutral counterparts(4). Volatilization of the neutral species of 2,4-dihydroxybenzophenone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.7X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Additionally, adsorption to soil is expected to attenuate volatilization(SRC). 2,4-Dihydroxybenzophenone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.4X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). A 0% of theoretical BOD using activated sludge in an aqueous screening test(6) suggests 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 1900(SRC), determined from a structure estimation method(2), indicates that 2,4-dihydroxybenzophenone is expected to adsorb to suspended solids and sediment(SRC). Volatilization of the neutral species from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.7X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Additionally, the estimated pKa1 and pKa2 values of 7.1 and 8.0(5), respectively, indicate 2,4-dihydroxybenzophenone will exist partially in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(6), an estimated BCF of 11(SRC), from an estimated log Kow of 2.96(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A 0% of theoretical BOD using activated sludge in an aqueous screening test(7) suggests 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), 2,4-dihydroxybenzophenone, which has an estimated vapor pressure of 1.4X10-7 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 2,4-dihydroxybenzophenone 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(3). Particulate-phase 2,4-dihydroxybenzophenone may be removed from the air by wet and dry deposition(SRC). 2,4-Dihydroxybenzophenone absorbs light in the environmental spectrum, with reported maximum near 292 nm(4) and 323 nm(4,5) and, therefore, is 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: 2,4-Dihydroxybenzophenone (BP1) is a solid. It is used as an ultraviolet light absorber, especially in paints and plastics. HUMAN STUDIES: Benzophenone (BP) derivatives show anti-androgenic activity. Treatment with BP1 (10(-5) - 10(-7) M) promoted proliferation of MCF-7 breast cancer cells by regulating cell cycle-related genes. BP1 may enhance the progression of prostate cancer by regulating cell cycle and metastasis-related genes via androgen receptor signaling pathway. ANIMAL STUDIES: It was minimally irritating when applied to the intact and abraded skin of albino rabbits and slightly to moderately irritating when applied to the eyes of rabbits. BP1 fed to 40 rats at doses of 0-1.9 g/kg for 90 days produced depressed growth and liver and kidney lesions in animals at doses of 0.6 and 1.9 g/kg. BP1 is a weak estrogenic compound based on an ovariectomized rat uterotrophic assay. It was nonmutagenic in Salmonella typhimurium strains TA100, TA98, TA1535, TA1537, and TA1538. ECOTOXICITY STUDIES: BP1 was estrogenic in fish and acted as pure- or partial estrogen receptor alpha agonists.

/AQUATIC SPECIES/ Numerous estrogenic compounds are present in aquatic environments, but currently it is not well understood how compounds that differ in maxima and slope of their individual dose-response curves contribute to the overall mixture effect. In order to better understand such interactions ...3 commonly used UV filters /were investigated/, for their estrogenic mixture activity and analyzed their joint effects by using the concentration addition (CA) concept. Thereby, we extended the method of isoboles for analysis of 3 compounds that differ in maxima and slopes of their dose-response curves. ... 3-Benzylidene camphor (3BC), benzophenone-1 (BP1) and benzophenone-2 (BP2) are estrogenic in fish and act as pure- or partial estrogen receptor alpha agonists. First ... juvenile fathead minnows /were exposed/ for 14 days to six concentrations of each UV filter alone to determine vitellogenin (VTG) induction curves, calculate equi-effective mixture concentrations and predict mixture effects. For 3BC, BP1 and BP2 significant VTG-induction occurred at 420, 2668, and 4715 ug/L, respectively. BP2 displayed a full dose-response curve, whereas 3BC and BP1 showed submaximal activity of 70 and 78%, respectively. Second, we exposed fish to 6 equi-effective mixtures (EC-NOEC, EC1, EC5, EC10, EC20, EC30) of these UV filters. Significant VTG-induction occurred at EC5 and higher. Submaximal activity of 67% as compared to the control EE2 (100 ng/L) was reached. The curves for the observed and predicted mixture activity agreed for mixture levels (EC10 to EC30), however, at EC-NOEC, EC1 and EC5, lower activity was observed than predicted by CA. Detailed isobolographic analysis indicate additivity at EC10 to EC30, and antagonism at low levels (EC-NOEC to EC5). Our data show for the first time, that for compounds with differences in maxima and slope, considerably more mixture combinations are additive than previously thought. This should be taken into account for hazard and risk as

/AQUATIC SPECIES/ Benzophenone (BP) derivatives, BP1 (2,4-dihydroxybenzophenone), BP2 (2,2',4,4'-tetrahydroxybenzophenone), BP3 (2-hydroxy-4-methoxybenzophenone), and THB (2,4,4'-trihydroxybenzophenone) are UV-absorbing chemicals widely used in pharmaceutical, cosmetics, and industrial applications, such as topical sunscreens in lotions and hair sprays to protect skin and hair from UV irradiation. Studies on their endocrine disrupting properties have mostly focused on their interaction with human estrogen receptor alpha (hERalpha), and there has been no comprehensive analysis of their potency in a system allowing comparison between hERalpha and hERbeta activities. The objective of this study was to provide a comprehensive ER activation profile of BP derivatives using ER from human and fish origin in a battery of in vitro tests, i.e., competitive binding, reporter gene based assays, vitellogenin (Vtg) induction in isolated rainbow trout hepatocytes, and proliferation based assays. The ability to induce human androgen receptor (hAR)-mediated reporter gene expression was also examined. All BP derivatives tested except BP3 were full hERalpha and hERbeta agonists (BP2>THB>BP1) and displayed a stronger activation of hERbeta compared with hERalpha, the opposite effect to that of estradiol (E2). Unlike E2, BPs were more active in rainbow trout ERalpha (rtERalpha) than in hERalpha assay. All four BP derivatives showed anti-androgenic activity (THB>BP2>BP1>BP3). Overall, the observed anti-androgenic potencies of BP derivatives, together with their proposed greater effect on ERbeta versus ERalpha activation, support further investigation of their role as endocrine disrupters in humans and wildlife.

/AQUATIC SPECIES/ Benzophenone (BP)-type ultraviolet (UV) filters are widely used in cosmetic and sunscreen products and can enter the aquatic environment. Therefore, ...the subchronic toxicity of 2,4-dihydroxybenzophenone (BP1) on the marine calanoid copepod Acartia tonsa /was investigated/ in an early life-stage development study. Since developmental endpoints depend on environmental conditions, a preceding study of A. tonsa development was performed at three temperatures, four salinities, four light:dark regimes, six food densities, and four culture densities. Times elapsed until 50% of the population had reached a copepodite stage (DT(1/2) ) at the different conditions were calculated. The DT(1/2) values decreased from 296 hr at 15 °C to 89 hr at 25 °C and were also affected by salinity (126 hr at 15 per mil and 167 hr at 30 per mil), whereas the light:dark regime and culture density influenced development only to a minor extent. BP1 was found acutely toxic at 2.6 mg/L (48-hr median lethal concentration [LC50]). The toxicity of BP1 on early life-stage development was studied in combinations of three temperatures (15, 20, 25 °C) and three salinities (15, 20, 25 per mil) using five toxicant concentrations between 0.051 and 2 mg/L in each scenario. Concentrations causing 10 and 50% inhibition of development (EC10 and EC50) were determined. Acartia tonsa was most resistant towards BP1 at 20 °C where an EC50 of 1.1 mg/L was found, whereas EC50 values were significantly lower at 15 °C (0.49 mg/L) and 25 °C (0.77 mg/L), respectively. The EC50 also decreased with increasing salinity.

/AQUATIC SPECIES/ Benzophenone (BP) type UV filters are widely used in many personal care products to protect human from UV irradiation. Despite the estrogenic potencies to fish and the environmental occurrences of BP derivatives in aquatic systems, little information is available regarding their effects on the antioxidant defense system in fish. In this work, the oxidative stress induced in livers of Carassius auratus /goldfish/ was assessed using four biomarkers. The integrated biomarker response (IBR) was applied to assess the overall antioxidant status in fish. Moreover, liver tissues were also studied histologically. The changes in the activities of antioxidant enzymes and glutathione levels suggested that BPs generates oxidative stress in fish. The IBR index revealed that the hepatic oxidative toxicity followed the order BP-1>BP-2>BP-4>BP-3. The histopathological analysis revealed lesions caused by BPs. This investigation provides essential information for assessing the potential ecological risk of BP-type UV filters.

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/]

2,4-Dihydroxybenzophenone was identified in wastewater effluent from a treatment plant in Cilfynydd, UK at a range of <2-41 ug/L; mean 18 ug/L; 69% detection frequency, sampled April 2007-August 2007(1). 2,4-Dihydroxybenzophenone was identified in wastewater effluent at a treatment plant in Coslech, UK at a range of <2-38 ug/L; mean 12 ug/L; 58% detection frequency, sampled from April 2007 to August 2007(1). 2,4-Dihydroxybenzophenone was detected at concentrations of 134-306, 12-32, and <0.3-9 ng/L in influent, final effluent and surface waters, respectively, in the UK(2).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 2,4-dihydroxybenzophenone can be estimated to be 1900(SRC). According to a classification scheme(2), this estimated Koc value suggests that benzophenone-2 is expected to have low mobility in soil. The pKa1 and pKa2 values of 2,4-dihydroxybenzophenone are estimated at 7.1 and 8.0(3), respectively, indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb as strongly to soils containing organic carbon and clay than their neutral counterparts(4). Using wastewater treatment plant sludge with a pH of 6.8, the log Koc of 2,4-dihydroxybenzophenone is 2.4 (Koc = 260)(5).

/PREGNANCY AND HUMAN REPRODUCTION/ Bisphenol A, benzophenone-type UV filters, and phthalates are chemicals in high production and use including in a range of personal care products. Exposure of humans to these chemicals has been shown to affect endocrine function. Although short-lived, widespread exposure may lead to continual opportunity for these chemicals to elicit health effects in humans. The association of these chemicals with incident uterine leiomyoma, an estrogen sensitive disease, is not known. Urinary concentrations of bisphenol A (BPA), five benzophenone-type UV filters (2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2'-dihydroxybenzophenone (2,2'OH-4MeO-BP), 2,2'4,4'-tetrahydroxybenzophenone (2,2'4,4'OH-BP), and 4-hydroxybenzophenone (4OH-BP), and 14 phthalate monoesters were quantified in 495 women who later underwent laparoscopy/laparotomy at 14 clinical sites for the diagnosis of fibroids. Significantly higher geometric mean creatinine-corrected concentrations of BPA, 2,4OH-BP, and 2OH-4MeO-BP were observed in women with than without fibroids [BPA: 2.09 ug/g vs. 1.46 ug/g p=0.004; 2,4OH-BP:11.10 ug/g vs. 6.71 ug/g p=0.01; 2OH-4MeO-BP: 11.31 ug/g vs. 6.10 ug/g p=0.01]. Mono-methyl phthalate levels were significantly lower in women with than without fibroids (1.78 ug/g vs. 2.40 ug/g). However, none of the exposures were associated with a significant odds ratio even when adjusting for relevant covariates. There was a lack of an association between select nonpersistent chemicals and the odds of a fibroid diagnosis.

/PREGNANCY AND HUMAN REPRODUCTION/ /The study objective was/ to assess benzophenone-type ultraviolet (UV) filter concentrations, chemicals used in sunscreen and personal care products, and semen endpoints. ... A total of 413 men provided semen and urine samples, 2005-2009. Five UV filters were quantified (ng/mL) in urine using liquid chromatography-triple quadrupole mass spectrometry: BP-1 (2,4-dihydroxybenzophenone), BP-2 (2,2',4,4'-tetrahydroxybenzophenone), BP-3 (2-hydroxy-4-methoxybenzophenone), BP-8 (2,2'-dihydroxy-4-methoxybenzophenone), and 4-OH-BP (4-hydroxybenzophenone). Using linear regression, beta-coefficients (beta) and 95% confidence intervals (CIs) for each chemical dichotomized at the 75th percentile and Box-Cox transformed semen endpoint were estimated, after adjusting for age, body mass index, cotinine, season, and site. ... BP-2 was associated with diminished sperm concentration (beta = -0.74; 95% CI -1.41, -0.08), straight (beta = -4.57; 95% CI -8.95, -0.18) and linear movement (beta = -3.15; 95% CI -6.01, -0.30), more immature sperm (beta = 0.38; 95% CI 0.15, 0.62), and a decreased percentage of other tail abnormalities (beta = -0.16; 95% CI -0.31, -0.01). BP-8 was associated with decreased hypo-osmotic swelling (beta = -2.57; 95% CI -4.86, -0.29) and higher acrosome area (beta = 1.14; 95% CI 0.01, 2.26). No associations were observed for BP-1, BP-3, or 4OH-BP. The findings suggest that specific UV filters may be associated with some aspects of semen endpoints, but await future corroboration.

/ENDOCRINE MODULATION/ Epithelial-mesenchymal transition (EMT) is an important process in embryonic development and cancer progression and metastasis. EMT is influenced by 17beta-estradiol (E2), an endogenous estrogen. Benzophenone-1 (2,4-dihydroxybenzophenone, BP-1) and 4-tert-octylphenol (OP) are suspected endocrine disrupting chemicals (EDCs) because they can exhibit estrogenic properties. In this study, we examined whether BP-1 and OP can lead to EMT of BG-1 ovarian cancer cells expressing estrogen receptors (ERs). A wound healing assay and western blot assay were conducted to show the effect of BP-1 and OP on the migration of BG-1 cells and protein expression of EMT-related genes. BP-1 (10(-6) M) and OP (10(-6) M) significantly enhanced the migration capability of BG-1 cells by reducing the wounded area in the cell monolayer relative to the control, similar to E2 (10(-9) M). However, when BG-1 cells were co-treated with ICI 182,780, an ER antagonist, the uncovered area was maintained at the level of the control. N-cadherin, snail, and slug were increased by BP-1 and OP while E-cadherin was reduced compared to the control. However, this effect was also restored by co-treatment with ICI 182,780. Taken together, these results indicate that BP-1 and OP, the potential EDCs, may have the ability to induce ovarian cancer metastasis via regulation of the expression of EMT markers and migration of ER-expressing BG-1 ovarian cancer cells.

/ENDOCRINE MODULATION/ Benzophenone (BP) derivatives, BP1 (2,4-dihydroxybenzophenone), BP2 (2,2',4,4'-tetrahydroxybenzophenone), BP3 (2-hydroxy-4-methoxybenzophenone), and THB (2,4,4'-trihydroxybenzophenone) are UV-absorbing chemicals widely used in pharmaceutical, cosmetics, and industrial applications, such as topical sunscreens in lotions and hair sprays to protect skin and hair from UV irradiation. Studies on their endocrine disrupting properties have mostly focused on their interaction with human estrogen receptor alpha (hERalpha), and there has been no comprehensive analysis of their potency in a system allowing comparison between hERalpha and hERbeta activities. The objective of this study was to provide a comprehensive ER activation profile of BP derivatives using ER from human and fish origin in a battery of in vitro tests, i.e., competitive binding, reporter gene based assays, vitellogenin (Vtg) induction in isolated rainbow trout hepatocytes, and proliferation based assays. The ability to induce human androgen receptor (hAR)-mediated reporter gene expression was also examined. All BP derivatives tested except BP3 were full hERalpha and hERbeta agonists (BP2>THB>BP1) and displayed a stronger activation of hERbeta compared with hERalpha, the opposite effect to that of estradiol (E2). Unlike E2, BPs were more active in rainbow trout ERalpha (rtERalpha) than in hERalpha assay. All four BP derivatives showed anti-androgenic activity (THB>BP2>BP1>BP3). Overall, the observed anti-androgenic potencies of BP derivatives, together with their proposed greater effect on ERbeta versus ERalpha activation, support further investigation of their role as endocrine disrupters in humans and wildlife.

For more Human Toxicity Excerpts (Complete) data for 2,4-Dihydroxybenzophenone (10 total), please visit the HSDB record page.

AEROBIC: 2,4-Dihydroxybenzophenone, present at 100 mg/L, reached 0% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L in a biodegradation in water screening test(1) suggesting that biodegradation is not an important environmental fate process(SRC).

SEDIMENT: Water quality data compiled from the Retrieval (STORET) Data Warehouse and the USGS National Water Information System (NWIS) reports sediment monitoring data for various chemicals but does not include 2,4-dihydroxybenzophenone as of 2017(1).

Chemical: Methanone, (2,4-dihydroxyphenyl)phenyl-

Status: Active Update: 09-05-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/12687

2,4-Dihydroxybenzophenone: Does not have an individual approval but may be used under an appropriate group standard

Epithelial-mesenchymal transition (EMT) is an important process in embryonic development and cancer progression and metastasis. EMT is influenced by 17beta-estradiol (E2), an endogenous estrogen. Benzophenone-1 (2,4-dihydroxybenzophenone, BP-1) and 4-tert-octylphenol (OP) are suspected endocrine disrupting chemicals (EDCs) because they can exhibit estrogenic properties. In this study, we examined whether BP-1 and OP can lead to EMT of BG-1 ovarian cancer cells expressing estrogen receptors (ERs). A wound healing assay and western blot assay were conducted to show the effect of BP-1 and OP on the migration of BG-1 cells and protein expression of EMT-related genes. BP-1 (10(-6) M) and OP (10(-6) M) significantly enhanced the migration capability of BG-1 cells by reducing the wounded area in the cell monolayer relative to the control, similar to E2 (10(-9) M). However, when BG-1 cells were co-treated with ICI 182,780, an ER antagonist, the uncovered area was maintained at the level of the control. N-cadherin, snail, and slug were increased by BP-1 and OP while E-cadherin was reduced compared to the control. However, this effect was also restored by co-treatment with ICI 182,780. Taken together, these results indicate that BP-1 and OP, the potential EDCs, may have the ability to induce ovarian cancer metastasis via regulation of the expression of EMT markers and migration of ER-expressing BG-1 ovarian cancer cells.

2,4-Dihydroxybenzophenone (benzophenone-1; BP-1) is an UV stabilizer primarily used to prevent polymer degradation and deterioration in quality due to UV irradiation. Recently, BP-1 has been reported to bioaccumulate in human bodies by absorption through the skin and has the potential to induce health problems including endocrine disruption. In the present study, we examined the xenoestrogenic effect of BP-1 on BG-1 human ovarian cancer cells expressing estrogen receptors (ERs) and relevant xenografted animal models in comparison with 17-beta estradiol (E2). In in vitro cell viability assay, BP-1 (10(-8)-10(-5)M) significantly increased BG-1 cell growth the way E2 did. The mechanism underlying the BG-1 cell proliferation was proved to be related with the up-regulation of cyclin D1, a cell cycle progressor, by E2 or BP-1. Both BP-1 and E2 induced cell growth and up-regulation of cyclin D1 were reversed by co-treatment with ICI 182,780, an ER antagonist, suggesting that BP-1 may mediate the cancer cell proliferation via an ER-dependent pathway like E2. On the other hand, the expression of p21, a regulator of cell cycle progression at G1 phase, was not altered by BP-1 though it was down-regulated by E2. In xenograft mouse models transplanted with BG-1 cells, BP-1 or E2 treatment significantly increased the tumor mass formation compared to a vehicle (corn oil) within 8 weeks. In histopathological analysis, the tumor sections of E2 or BP-1 group displayed extensive cell formations with high density and disordered arrangement, which were supported by the increased number of BrdUrd positive nuclei and the over-expression of cyclin D1 protein. Taken together, these results suggest that BP-1 is an endocrine disrupting chemical (EDC) that exerts xenoestrogenic effects by stimulating the proliferation of BG-1 ovarian cancer via ER signaling pathway associated with cell cycle as did E2.

Prostate cancer (PCa) is a global health concern in human males. Recently, it has been known that endocrine-disrupting chemicals (EDCs) may act as an exogenous factor to enhance cancer progression. Triclosan (TCS) and 2,4-dihydroxybenzophenone (BP-1) were reported to bioaccumulate in human bodies through the skin absorption. However, there has been insufficient evidence on the findings that the intervention of EDCs may promote the cancer progression in PCa. In the present study, to verify the risk of TCS and BP-1 to a PCa progression, cancer cell proliferation and migration were investigated in LNCaP PCa cells. TCS and BP-1 increased LNCaP cell proliferative activity and migration as did dihydrotestosterone (DHT). This phenomenon was reversed by the treatment with bicalutamide, a well known androgen receptor (AR) antagonist, suggesting that TCS and BP-1 acted as a xenoandrogen in LNCaP cells via AR signaling pathway by mimicking the action of DHT. A Western blot assay was performed to identify the alterations in the translational levels of cell growth- and metastasis-related markers, i.e., c-fos, cyclin E, p21, and cathepsin D genes. The expressions of genes related with G1/S transition of cell cycle and metastasis were increased by DHT, TCS, and BP-1, while the expression of p21 protein responsible for cell cycle arrest was reduced by DHT, TCS, and BP-1. Taken together, these results indicated that TCS and BP-1 may enhance the progression of PCa by regulating cell cycle and metastasis-related genes via AR signaling pathway.

The metabolism and cytotoxicity of 2-hydroxy-4-methoxybenzophenone (HMB) in isolated rat hepatocytes and the xenoestrogenic activity of HMB and its metabolites in MCF-7 human breast cancer cells and an estrogen receptor competitive binding assay have been studied, respectively. The incubation of hepatocytes with HMB caused a concentration- and time-dependent decrease in cell viability, accompanied by loss of intracellular ATP and adenine nucleotide pools. HMB at a low-toxic level (0.25 mM) in the hepatocyte suspensions was converted enzymatically to 2,4-dihydroxybenzophenone (DHB) and a hydroxylated intermediate, which was tentatively identified as an isomer of 2,2prime prime or minute-dihydroxy-4-methoxybenzophenone (DHMB) as determined by mass spectroscopy coupled with HPLC. Furthermore, the parent compound and both intermediates were rapidly conjugated to glucuronides, whereas free unconjugated DHMB and 2,3,4-trihydroxybenzophenone (THB) were identified as trace intermediates. In another experiment, DHB and THB displaced competitively 17beta-estradiol bound to the recombinant human estrogen receptor alpha in a concentration-dependent manner: IC(50) of diethylstilbestrol and bisphenol A, which are known xenoestorogenic compounds, and DHB and THB was approximately 1 x 10(-8), 1 x 10(-5), 5 x 10(-5) and 5 x 10(-4) M, respectively. Further, DHB at concentrations from 10(-8) to 10(-6) M caused a concentration-dependent proliferation of MCF-7 cells. DHMB and THB at 10(-7) and 10(-6) M also elicited a slight increase in cell numbers, whereas HMB at concentrations from 10(-9) to 10(-4) M did not affect the cell proliferation. Based on the relative IC50 for the competitive binding and the proliferative effect on MCF-7 cells, it follows that in estrogenic potency, DHB>THB>DHMB. These results indicate that some hydroxylated intermediates such as DHB rather than the parent compound act as a xenoestrogen via biotransformation.

Sunscreens containing UV filters are recommended to reduce damage caused by solar UV radiation. Recently, benzophenone (BP)-type UV filters have become widely used as UV stabilizers in skin-moisturizing products and sunscreen lotions; however, very little information is available regarding the potential harmful effects of prolonged exposure to these compounds. Therefore, we investigated the toxicokinetics and metabolism of BP-type UV filters in rats using gas chromatography-mass spectrometry (GC-MS). To examine the metabolism of BP-type UV filters, we analyzed the parent compounds BP and 2-hydroxy-4-methoxybenzophenone (HMB). In rats, BP was mainly converted to benzhydrol (BH) and 4-hydroxybenzophenone (HBP) (i.e., type A UV filters). In contrast, HMB was converted into at least three intermediates, including 2,4-dihydroxybenzophenone (DHB), which was formed via o-demethylation and subsequently converted into 2,3,4-trihydroxybenzophenone (THB), and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB), which formed via the aromatic hydroxylation of HMB (i.e., type B UV filters). Next, the toxicokinetic curve for BP showed a peak concentration (Cmax) of 2.06+/-0.46 ug/mL at approximately 4h after BP administration. After a single oral dose of HMB, the Cmax of HMB reached 21.21+/-11.61 ug/mL within 3 hr (Tmax), and then declined rapidly compared to the kinetic curve of BP. The concentration of these metabolites in rat blood decreased much more slowly over time compared to the parent compounds. Thus, our results indicate that such metabolites might have more significant adverse effects than the parent compounds over the long term.

Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, BZ-3) is a UV absorber that is used extensively in medicine, cosmetics and industry as a sunscreen and color fastener. Exposure to the chemical is through the dermal and oral route. Bioavailability of the chemical absorbed through the skin is different from that seen through the oral route. The disposition of BZ-3 was investigated after dermal administration of 100 mg/kg body weight (body wt.) 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 as the parent compound and its metabolites were detected in plasma 5 min post-administration. The half-life (t1/2) of absorption was 3.45 hr corresponding to an absorption rate constant of 0.2 hr-1. Peak plasma concentration of 35 +/- 4.5 ug/mL (mean +/- standard error of the mean, S.E.) was attained at 2.5 hr post-administration. Disappearance from the plasma was biphasic with different half-lives (1.3 for alpha phase and 15.05 hr for beta phase), the area under the plasma concentration versus time curve was 211.1 +/- 38.2 ug/mL/hr (mean +/- S.E). There was also extensive binding of BZ-3 and its metabolites to plasma proteins. 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.

When benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) was incubated with liver microsomes of untreated rats in the presence of NADPH, the 5-hydroxylated metabolite, 2,5-dihydroxy-4-methoxybenzophenone (5-OH-BP-3), was formed as a major novel metabolite of BP-3. The 4-desmethylated metabolite, 2,4-dihydroxybenzophenone (2,4-diOH-BP), previously reported as the major in vivo metabolite of BP-3, was also detected. However, the amount of 5-OH-BP-3 formed in vitro was about the same as that of 2,4-diOH-BP. The oxidase activity affording 5-OH-BP-3 was inhibited by SKF 525-A and ketoconazole, and partly by quinidine and sulfaphenazole. The oxidase activity affording 2,4-diOH-BP was inhibited by SKF 525-A, ketoconazole and alpha-naphthoflavone, and partly by sulfaphenazole. The oxidase activity affording 5-OH-BP-3 was enhanced in liver microsomes of dexamethasone-, phenobarbital- and 3-methylcholanthrene-treated rats. The activity affording 2,4-diOH-BP was enhanced in liver microsomes of 3-methylcholanthrene- and phenobarbital-treated rats. When examined recombinant rat cytochrome P450 isoforms catalyzing the metabolism of BP-3, 5-hydroxylation was catalyzed by P450 3A2, 1A1, 2B1, 2C6 and 2D1, while 4-desmethylation was catalyzed by P450 2C6 and 1A1.

Benzophenone-3 [2-hydroxy-4-methoxybenzophenone (HMB), oxybenzone, Spectra-Sorb UV-9 light absorber] is used in many cosmetics and sunscreens as a UV absorber. This study was conducted to investigate the metabolism of HMB (100 mg/kg body weight administered orally). 2,4-Dihydroxybenzophenone (DHB), 2,2'-dihydroxy-4-methoxybenzophenone (DHMB), and 2,3,4-trihydroxy-benzophenone (THB) metabolites were identified as free and conjugated forms by HPLC analysis. HMB was rapidly absorbed, metabolized, and detected in plasma (as free and protein bound) at 5 min postadministration. The parent compound and metabolites (free and conjugated) were detected at 6 hr in most tissues. DHB was present in most tissues with the highest concentration in the liver. DHMB was only detected as the conjugated form in liver, spleen, and heart. Trace amounts of THB were also detected in biological samples. Urine was the primary route, whereas feces was the secondary route of elimination of HMB and its metabolites. This study revealed O-dealkylation as the major pathway of HMB metabolism.

Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, BZ-3) is a UV absorber that is used extensively in medicine, cosmetics and industry as a sunscreen and color fastener. Exposure to the chemical is through the dermal and oral route. Bioavailability of the chemical absorbed through the skin is different from that seen through the oral route. The disposition of BZ-3 was investigated after dermal administration of 100 mg/kg body weight (body wt.) 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 as the parent compound and its metabolites were detected in plasma 5 min post-administration. The half-life (t1/2) of absorption was 3.45 hr corresponding to an absorption rate constant of 0.2 hr-1. Peak plasma concentration of 35 +/- 4.5 ug/mL (mean +/- standard error of the mean, S.E.) was attained at 2.5 hr post-administration. Disappearance from the plasma was biphasic with different half-lives (1.3 for alpha phase and 15.05 hr for beta phase), the area under the plasma concentration versus time curve was 211.1 +/- 38.2 ug/mL/hr (mean +/- S.E). There was also extensive binding of BZ-3 and its metabolites to plasma proteins. 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.

CIR ingredient: Benzophenone-1

Used as an ultraviolet absorber in polymers, sunscreening agent, and ultraviolet stabilizer for polymers; [HSDB] Used as an ultraviolet light absorber in paints; [Merck Index]

Painting (Pigments, Binders, and Biocides) [Category: Paint]；Plastic Composites Manufacturing [Category: Industry]

Ultraviolet light absorber, especially in paints and plastics.

Ultraviolet absorber in polymers

Used as sunscreening agent. /SRP: Former use/

(1979) No Data

(1981) No Data

(1979) No Data

(1981) 3.75X10+5 GRAMS (PRINCPL CUSTMS DISTS)

(1977) AT LEAST 4.54X10+7 GRAMS

(1981) No Data

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Methanone, (2,4-dihydroxyphenyl)phenyl-. National Production Volume: 31,680 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, (2,4-dihydroxyphenyl)phenyl-:；Table: National Aggregate Production Volume (pounds) [Table#5461]

2,4-Dihydroxybenzophenone ... is formed in 90% yield by the uncatalyzed reaction of benzotrichloride with resorcinol in hydroxylic solvents or in benzene containing methanol or ethanol.

Three methods of Benzophenone-1 preparation from resorcinol are reported. Stephen and Zilberman and Rybakova prepared Benzophenone-1 from the Hoesch reaction of resorcinol and either a substituted imido chloride (to form an imido-ester intermediate) or a corresponding aromatic nitrile and a metal halide catalyst. Shaw and Mehta described the condensation of benzamide with resorcinol in the presence of phosphorous oxychloride and zinc chloride to Benzophenone-1. Additionally, Benzophenone-1 can be prepared in low yield by the Fries rearrangement from phenyl-2-methoxy-benzoate.

Fragrance Ingredients

Cosmetics -> Uv absorber