2,2',4,4'-テトラヒドロキシベンゾフェノン

Cosmetic ingredients (Benzophenone-2) -> CIR (Cosmetic Ingredient Review)

Uv absorber

Yellow needles

Light yellow powder

In water, 8,821 mg/L at 24.99 °C

In water, <1 g/100 mL at 30 °C

Very soluble in acetone, diethyl ether, ethanol

Ethyl acetate 10, methanol 50, methyl ethyl ketone 22, toluene < 1 (all g/100 ml at 25 °C)

152.3 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID5041306]

152 Ų [M+H]+

This chemical does not meet GHS hazard criteria for 3.3% (13 of 393) of reports.

Warning

H302 (96.4%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P272, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 393 reports by companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

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

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

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. 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.

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. 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 Benzophenone-2 (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: Complete suit protecting against chemicals. 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).

Biomonitoring of human exposure to bisphenol A diglycidyl ethers (BADGEs; resin coating for food cans), p-hydroxybenzoic acid esters (parabens; preservatives), benzophenone-type UV filters (BP-UV filters; sunscreen agents), triclosan (TCS; antimicrobials), and triclocarban (TCC; antimicrobials) has been investigated in western European countries and North America. Nevertheless, little is known about the exposure of Greek populations to these environmental chemicals. In this study, 100 urine samples collected from Athens, Greece, were analyzed by liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination of total concentrations of five derivatives of BADGEs, six parabens and their metabolite (ethyl-protocatechuate), five derivatives of BP-UV filters, TCS, and TCC. Urinary concentrations of BADGEs, parabens, ethyl-protocatechuate, BP-UV filters, TCS and TCC (on a volume basis) ranged 0.3-20.9 (geometric mean: 0.9), 1.6-1010 (24.2), <2-71.0 (2.1), 0.5-1120 (4.4), <0.5-2580 (8.0) and <0.5-1.9 (0.6) ng/mL, respectively. All 19 target chemicals were found in urine, and the highest detection rates were observed for methyl paraben (100%), bisphenol A bis (2,3-dihydroxypropyl) ether (90%), ethyl paraben (87%), 2,4-dihydroxybenzophenone (78%), propyl paraben (72%), and TCS (71%). Estimated daily intakes (EDIurine), calculated on the basis of the measured urinary concentrations, ranged from 0.023 ug/kg bw/day for SumS5BADGEs to 31.4 ug/kg bw/day for SumS6Parabens.

The secondary sex ratio (SSR), defined as the ratio of males to females at birth, has been investigated in relation to endocrine disruptors to search for environmental toxicants perturbing human sex selection. Benzophenone (BP)-type ultraviolet (UV) filters, which are used in sunscreens and personal care products, have been reported to exert estrogenic and anti-androgenic activities. This study aimed to evaluate the association between maternal, paternal, and couple urinary concentrations of BP-type UV filters and the SSR, given the absence of previous investigation. The study cohort comprised 220 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and who had a singleton birth during the follow-up period. Couples' urinary concentrations of five BP-type UV filters (ng/mL) were measured using triple-quadrupole tandem mass spectrometry: 2,4-dihydroxybenzophenone (BP-1), 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), and 4-hydroxybenzophenone (4-OH-BP). Modified Poisson regression models were used to estimate the relative risks (RRs) of a male birth for each BP-type UV filter, after adjusting for potential confounders. When maternal and paternal urinary BP-type UV filter concentrations were modeled jointly, both maternal BP-2 (2nd vs 1st tertile, RR, 0.62, 95% confidence interval [CI], 0.43-0.91) and paternal BP-2 (3rd vs 1st tertile, RR, 0.67, 95% CI, 0.45-0.99; p-trend, 0.04) were significantly associated with an excess of female births. Contrarily, maternal 4-OH-BP was significantly associated with an excess of male births (2nd vs 1st tertile, RR, 1.87, 95% CI, 1.27-2.74; 3rd vs 1st tertile, RR, 1.80, 95% CI, 1.13-2.87; p-trend, 0.02). ...

Today, topical application of sunscreens, containing ultraviolet-filters (UV-filters), is preferred protection against adverse effects of ultraviolet radiation. Evidently, use of sunscreens is effective in prevention of sunburns in various models. However, evidence for their protective effects against melanoma skin cancer is less conclusive. Three important observations prompted us to review the animal data and human studies on possible side effects of selected chemical UV-filters in cosmetics. (1) the utilization of sunscreens with UV-filters is increasing worldwide; (2) the incidence of the malignant disorder for which sunscreens should protect, malignant melanoma, is rapidly increasing and (3) an increasing number of experimental studies indicating that several UV-filters might have endocrine disruptive effects. The selected UV-filters we review in this article are benzophenone-3 (BP-3), 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), Homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) and 4-aminobenzoic acid (PABA). The potential adverse effects induced by UV-filters in experimental animals include reproductive/developmental toxicity and disturbance of hypothalamic-pituitary-thyroid axis (HPT). Few human studies have investigated potential side effects of UV-filters, although human exposure is high as UV-filters in sunscreens are rapidly absorbed from the skin. One of the UV-filters, BP-3, has been found in 96% of urine samples in the US and several UV-filters in 85% of Swiss breast milk samples. It seems pertinent to evaluate whether exposure to UV-filters contribute to possible adverse effects on the developing organs of foetuses and children. /Sunscreens/

Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro - in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data ... for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds.

EC50; Species: Danio rerio (Zebra Danio) age 48 hr postfertilization embryo; Conditions: freshwater, semistatic, 28 °C; Concentration: 19.1 uM for 72 hr; Effect: hormones, decreased thyroxine /formulation/

LC50; Species: Danio rerio (Zebra Danio) age 48 hr postfertilization embryo; Conditions: freshwater, semistatic, 28 °C; Concentration: 48 uM for 72 hr /formulation/

LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: freshwater, static, 25 °C; Concentration: 8300 ug/L for 24 hr (95% confidence interval: 8100-8600 ug/L) />99% purity/

LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: freshwater, static, 25 °C; Concentration: 6500 ug/L for 48 hr (95% confidence interval: 6200-6900 ug/L) />99% purity/

For more Ecotoxicity Values (Complete) data for Benzophenone-2 (6 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3200(SRC), determined from a structure estimation method(2), indicates that benzophenone-2 is expected to have slight mobility in soil(SRC). The estimated pKa1 and pKa2 values of benzophenone-2 are 7.1 and 7.9, respectively(3), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the neutral species of benzophenone-2 from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.6X10-16 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Benzophenone-2 is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017)

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3200(SRC), determined from a structure estimation method(2), indicates that benzophenone-2 is expected to adsorb to suspended solids and sediment(SRC). Volatilization of teh neutral species from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.6X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). The estimated pKa1 and pKa2 values of benzophenone-2 are 7.1 and 7.9, respectively(5) indicate benzophenone-2 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), a BCF of 1.9(7) suggests that bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2017).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), benzophenone-2, which has an estimated vapor pressure of 1.6X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase benzophenone-2 may be removed from the air by wet and dry deposition(SRC). Benzophenone-2 absorbs UV light at wavelengths approximately 350 nm(3) and, therefore, 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: Benzophenone-2 (BP2) is used as UV filter in a personal care products. Benzophenone-2 is commonly used in cosmetic products and food container plastics to filter out ultraviolet light. HUMAN STUDIES: Sensitization against benzophenone-2 has been reported. BP2, may disturb thyroid hormone homeostasis by inhibiting or inactivating thyroid peroxidase, effects that are even more pronounced in the absence of iodide. ANIMAL STUDIES: Benzophenone-2 was estrogenic in vitro and in the rat uterotropic assay. BP2 was shown to bind to the estrogen receptors. Benzophenone-2 was reported to be positive for mutagenicity using Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 with metabolic activation. An in vitro cytogenic assay was used to evaluate the ability of Benzophenone-2 to induce sister chromatid exchange (SCE) and chromosome aberrations (CA) in L5178Y mouse lymphoma cells. Benzophenone-2 does not directly induce significant SCE or CA increases but does, under metabolic activation, induce these changes. Benzophenone-2 induced an increase in mutations at the TK locus in L5178Y mouse lymphoma cells only for highly toxic doses with or without metabolic activation. UV-screens at high doses also may possess immunomodulatory effects some of which resemble those of 17beta-estradiol. ECOTOXICITY STUDIES: BP2 is estrogenic in fish and act as pure- or partial estrogen receptor alpha agonists. Reproductively mature fathead minnows (Pimephales promelas) were exposed to 0.002, 0.1, 1.2, 5.0 and 9.7 mg/L BP-2 for 15 days. Testes of exposed males had much fewer spermatocytes and ovaries of exposed females had much fewer mature and more atretic follicles. Reproduction was negatively affected in a dose-dependent manner with a decrease in egg production at 5.0 mg/L and a complete cessation of spawning activity at 9.7 mg/L BP-2. In other experiment, Xenopus laevis embryos were exposed in flow-through conditions to 0, 1.5, 3.0 or 6.0 mg/L BP-2 until 2 months post-metamorphosis. Concentration-dependent increases in severity of thyroid follicular cell hypertrophy and hyperplasia occurred in larval tadpoles indicating BP-2-induced impacts on the thyroid axis. Additionally, gonads were impacted in all treatments with some genetic males showing both testis and ovary tissues (1.5 mg/L) and 100% of the genetic males in the 3.0 and 6.0 mg/L treatments experiencing complete male-to-female sex reversal. Concentration-dependent vitellogenin induction occurred in both genders with associated accumulations of protein in the livers, kidneys and gonads, which was likely vitellogenin and other estrogen-responsive yolk proteins. BP-2 is a genotoxicant to corals, exhibiting a strong positive relationship between DNA-AP lesions and increasing BP-2 concentrations. BP-2 exposure in the light induced extensive necrosis in both the epidermis and gastro dermis. In contrast, BP-2 exposure in darkness induced autophagy and autophagic cell death.

/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 we investigated 3 commonly used UV filters, 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 we exposed juvenile fathead minnows 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 assessment of UV filters and xenoestrogens.

/AQUATIC SPECIES/ The UV filter benzophenone-2 (BP-2) is largely used in personal care products such as cosmetics and in numerous other materials for UV protection. Like other UV filters, BP-2 has been found to be estrogenic in vitro and in vivo, but potential effects on reproduction of fish are unknown. In this study, we evaluate whether BP-2 affects important reproductive parameters such as fecundity, gametogenesis and secondary sex characteristics. After a pre-exposure period of 19 days, reproductively mature fathead minnows (Pimephales promelas) were exposed to 0.002, 0.1, 1.2, 5.0 and 9.7 mg/L BP-2 for 15 days. BP-2 was accumulated in fish up to 3.1 ug/g body weight. In males, a dose-dependent vitellogenin induction and decrease in the number of nuptial tubercles occurred. Moreover, significant dose-related effects on gonads of male and female fish were observed. At concentrations of 1.2 mg/L and higher, spermatocyte and oocyte development was significantly inhibited in male and female fish, respectively. Testes of exposed males had much fewer spermatocytes and ovaries of exposed females had much fewer mature and more atretic follicles. Reproduction was negatively affected in a dose-dependent manner with a decrease in egg production at 5.0 mg/L and a complete cessation of spawning activity at 9.7 mg/L BP-2. Our findings show significant estrogenic effects of the common UV filter BP-2 on vitellogenin induction, secondary sex characteristics, gonadal development, and reproduction in fish.

/AQUATIC SPECIES/ The Larval Amphibian Growth and Development Assay (LAGDA) is a globally harmonized chemical testing guideline developed by the U.S. Environmental Protection Agency in collaboration with Japan's Ministry of Environment to support risk assessment. The assay is employed as a higher tiered approach to evaluate effects of chronic chemical exposure throughout multiple life stages in a model amphibian species, Xenopus laevis. To evaluate the utility of the initial LAGDA design, the assay was performed using a mixed mode of action endocrine disrupting chemical, benzophenone-2 (BP-2). X. laevis embryos were exposed in flow-through conditions to 0, 1.5, 3.0 or 6.0 mg/L BP-2 until 2 months post-metamorphosis. Overt toxicity was evident throughout the exposure period in the 6.0 mg/L treatment due to elevated mortality rates and observed liver and kidney pathologies. Concentration-dependent increases in severity of thyroid follicular cell hypertrophy and hyperplasia occurred in larval tadpoles indicating BP-2-induced impacts on the thyroid axis. Additionally, gonads were impacted in all treatments with some genetic males showing both testis and ovary tissues (1.5 mg/L) and 100% of the genetic males in the 3.0 and 6.0 mg/L treatments experiencing complete male-to-female sex reversal. Concentration-dependent vitellogenin induction occurred in both genders with associated accumulations of protein in the livers, kidneys and gonads, which was likely vitellogenin and other estrogen-responsive yolk proteins. This is the first study that demonstrates the endocrine effects of this mixed mode of action chemical in an amphibian species and demonstrates the utility of the LAGDA design for supporting chemical risk assessment.

/AQUATIC SPECIES/ Benzophenone-2 (BP-2) is an additive to personal-care products and commercial solutions that protects against the damaging effects of ultraviolet light. BP-2 is an "emerging contaminant of concern" that is often released as a pollutant through municipal and boat/ship wastewater discharges and landfill leachates, as well as through residential septic fields and unmanaged cesspits. Although BP-2 may be a contaminant on coral reefs, its environmental toxicity to reefs is unknown. This poses a potential management issue, since BP-2 is a known endocrine disruptor as well as a weak genotoxicant. We examined the effects of BP-2 on the larval form (planula) of the coral, Stylophora pistillata, as well as its toxicity to in vitro coral cells. BP-2 is a photo-toxicant; adverse effects are exacerbated in the light versus in darkness. Whether in darkness or light, BP-2 induced coral planulae to transform from a motile planktonic state to a deformed, sessile condition. Planulae exhibited an increasing rate of coral bleaching in response to increasing concentrations of BP-2. BP-2 is a genotoxicant to corals, exhibiting a strong positive relationship between DNA-AP lesions and increasing BP-2 concentrations. BP-2 exposure in the light induced extensive necrosis in both the epidermis and gastro dermis. In contrast, BP-2 exposure in darkness induced autophagy and autophagic cell death. The LC50 of BP-2 in the light for an 8 and 24 hour exposure was 120 parts per million (ppm) and 165 parts per billion (ppb), respectively. The LC50s for BP-2 in darkness for the same time points were 144 ppm and 548 ppb.

/AQUATIC SPECIES/ The determination of estrogenic activity (EC50) and acute toxicity (LC50) of benzophenones was undertaken, and experimental and predicted estrogenic potency values were compared. The Saccharomyces cerevisiae-based lac-Z reporter assay was used to generate experimental data. Estrogenicity was measured colormetrically as Beta-galactosidase activity. On the basis of the series of rules, Beta-galactosidase activity was predicted correctly for 14 of the 18 benzophenones tested. As predicted, benzophenone, as well as derivatives with a methyl-, chloro-, or nitro-substituent, exhibited no Beta-galactosidase activity. As anticipated, 4-hydroxybenzophenone exhibited weak Beta-galactosidase activity (EC50 value of e-06 M). The 3-hydroxybenzophenone exhibited almost the same activity as the 4-hydroxy derivative, whereas the 2-hydroxy derivative was nonactive. It was observed while replacing the para-hydroxyl group with an amino moiety decreased Beta-galactosidase activity by a half order of magnitude, replacement of the para-hydroxy moiety with a methoxy group negated activity. The nonsymmetrical trihydroxylated benzophenone exhibited activity near to the monohydroxyl derivative. Near symmetrical tri- and symmetrical tetrahydroxylated benzophenones were determined to have greater estrogenic activity (EC50 values of e-07 M) than nonsymmetrical molecules. A comparison of estrogenicity (EC50) with acute toxicity (LC50) reveals a less than a 10-fold difference in activities for weaker estrogenic compounds. However, the more hydrophilic, stronger estrogenic compounds typically exhibit a difference of two to three orders of magnitude between EC50 and LC50 values.

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/]

Benzophenone-2 was identified in wastewater influent at a treatment plant in Cilfynydd, UK (9-247 ug/L; mean 53 ug/L; 100% detection frequency), and its treated effluent (<13-17 ug/L; mean 4 ug/L; 62% detection frequency), with lower detections 1 km upstream of the plant, in the River Taff, a major river flowing through an urbanized area (<0.5-1 ug/L; mean 0 ug/L; 25% detection frequency). There were no detections 2 km downstream of the plant, and in the receiving waters of the River Taff the concentration was <0.5 ug/L; 0% detection frequency). Samples were collected April 2007-August 2007(1). Benzophenone-2 was identified in wastewater influent at a treatment plant in Coslech, UK (61-403 ug/L; mean 194 ug/L; 100% detection frequency) and in its treated effluent (<13-13 ug/L; mean 4 ug/L; 42% detection frequency). It was detected 3.5 km downstream of the plant and in its receiving waters from the River Ely, a small river flowing through rural areas, at <0.5-26 ug/L; mean 5 ug/L; 40% detection frequency. Benzophenone-2 was not detected in the River Ely, 7 km upstream of the plant (<0.5 ug/L; 0% detection frequency). Samples were collected April 2007-August 2007(1).

Benzophenone-2 was identified in wastewater effluent from a treatment plant in Cilfynydd, UK at a tange of <13-17 ug/L; mean 4 ug/L; 62% detection frequency, sampled April 2007-August 2007(1). Benzophenone-2 was identified in wastewater effluent at a treatment plant in Coslech, UK at a range of <13-13 ug/L; mean 4 ug/L; 42% detection frequency, sampled from April 2007 to August 2007(1).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of benzophenone-2 can be estimated to be 3,200(SRC). According to a classification scheme(2), this estimated Koc value suggests that benzophenone-2 is expected to have slight mobility in soil. Using watewater treatment plant sludge with a pH of 6.8 the log Koc of benzophenone-2 is 3.0 (Koc = 1,000) (3). The estimated pKa1 and pKa2 values of benzophenone-2 are 7.1 and 7.9, respectively(4), indicating that this compound will exist partially in 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(5).

/CASE REPORTS/ Case 1. A 34-year-old woman presented with a recurrent, itching and erythematous plaque on her right cheek. Case 2. A 27-year-old woman reported itching erythema on her fingertips from time to time recently. Inspection revealed dyshidrosiform blisters. Both patients had been using nail varnish and varnish remover. Case 3. A 49-year-old woman had, for about 5 years, repeatedly experienced itching erythema at the perionychium of several fingers on which she had placed artificial nails. Marked edema and erythema was noted. Extensive epicutaneous tests were performed on these patients. They showed sensitization against important allergens in nail varnish (toluolsulfonamide-formaldehyde resin), nail varnish remover (benzophenone-2) and artificial nails (ethylacrylate), respectively. The three patients also showed type IV sensitization against other substances. Epicutaneous tests documented type IV allergies to important constituents of nail varnish, nail varnish remover and artificial nails. Symptoms and skin changes disappeared when these three items were no longer used. Allergies against nail varnish and its remover and against artificial nails should be included in the differential diagnosis of skin allergies, even when patients have additional type IV sensitizations against common allergens. As the causative allergen can be easily avoided, knowledge of the particular problems associated with these allergies is of a great practical significance.

/CASE REPORTS/ Fragrances contain several hundreds of different chemicals, a few major and many minor, which are responsible for the complexity of the odor. Fragrances are a major cause of allergic contact dermatitis. As a diagnostic tool, the current fragrance mix is very useful though not ideal. A 50-year-old woman presented with a pruriginous, erythematous eruption, characterized by papules, vesicles, exudation and crusting over the neck and chest. With the suspicion of fragrance allergy, patch testing was performed. Initially, the only positive reaction observed was with her own eau de toilette named Woman. The TRUE Test fragrance mix patch test was negative. Chemical fractionation of Woman perfume concentrate was combined with a sequenced patch testing procedure and with structure-activity relationship studies. Ingredients supplied by the manufacturer were also included in the study. Benzophenone-2, Lyral, alpha-hexyl cinnamic aldehyde and alpha-damascone were found to be responsible for the patient's contact allergy to the commercial product. These substances contain chemical structural alerts giving them antigenic ability. The common use of new chemicals to manufacture fragrances, and the increased number of patients sensitive to them but with negative fragrance mix reactions, makes it necessary to identify new potential fragrance sensitizers in commercial products.

/ENDOCRINE MODULATION/ Endocrine disrupting chemicals (EDCs), either plant constituents or contaminants deriving from industrial products, may interfere with the thyroid hormone (TH) axis. Here, we examined whether selected EDCs inhibit the key reactions of TH biosynthesis catalyzed by thyroid peroxidase (TPO). We used a novel in vitro assay based on human recombinant TPO (hrTPO) stably transfected into the human follicular thyroid carcinoma cell line FTC-238. F21388 (synthetic flavonoid), bisphenol A (building block for polycarbonates), and the UV filter benzophenone 2 (BP2) inhibited hrTPO. BP2 is contained in numerous cosmetics of daily use and may be in regular contact with human skin. Half-maximal inhibition in the guaiacol assay occurred at 450 nmol/liter BP2, a concentration 20- and 200-fold lower than those required in case of the TPO-inhibiting antithyroid drugs methimazole and propylthiouracil, respectively. BP2 at 300 nmol/liter combined with the TPO substrate H(2)O(2) (10 umol/L) inactivated hrTPO; this was, however, prevented by micromolar amounts of iodide. BP2 did not inhibit iodide uptake into FRTL-5 cells. In BP2-treated rats (333 and 1000 mg/kg body weight), serum total T(4) was significantly decreased and serum thyrotropin was significantly increased. TPO activities in the thyroids of treated animals were unchanged, a finding also described for methimazole and propylthiouracil. Thus, EDCs, most potently BP2, may disturb TH homeostasis by inhibiting or inactivating TPO, effects that are even more pronounced in the absence of iodide. This new challenge for endocrine regulation must be considered in the context of a still prevailing iodide deficiency in many parts of the world.

Benzophenone-2's production and use in cosmetics and personal care products(1), as a masking and UV absorber(2) and in plastic, paint and automotive care products(3) may result in its release to the environment through various waste streams(SRC).

An average BCF of 1.9 was calculated in fish for benzophenone-2, using fathead minnows (Pimephales promelas) which were exposed over 15-day period to 0.01-3.1 ug/g body weight(1). According to a classification scheme(2), this BCF suggests that bioconcentration in aquatic organisms is low(SRC).

Zebrafish embryo assays are increasingly used in the toxicological assessment of endocrine disruptors. Among other advantages, these models are 3R-compliant and are fit for screening purposes. Biotransformation processes are well-recognized as a critical factor influencing toxic response, but major gaps of knowledge exist regarding the characterization of functional metabolic capacities expressed in zebrafish. Comparative metabolic studies between embryos and adults are even scarcer. Using (3)H-labeled chemicals, we examined the fate of two estrogenic emerging contaminants, benzophenone-2 (BP2) and bisphenol S (BPS), in 4-day embryos and adult zebrafish. BPS and BP2 were exclusively metabolized through phase II pathways, with no major qualitative difference between larvae and adults except the occurrence of a BP2-di-glucuronide in adults. Quantitatively, the biotransformation of both molecules was more extensive in adults. For BPS, glucuronidation was the predominant pathway in adults and larvae. For BP2, glucuronidation was the major pathway in larvae, but sulfation predominated in adults, with ca. 40% conversion of parent BP2 and an extensive release of several conjugates into water. Further larvae/adults quantitative differences were demonstrated for both molecules, with higher residue concentrations measured in larvae. The study contributes novel data regarding the metabolism of BPS and BP2 in a fish model and shows that phase II conjugation pathways are already functional in 4 days post-fertilization old zebrafish. Comparative analysis of BP2 and BPS metabolic profiles in zebrafish larvae and adults further supports the use of zebrafish embryo as a relevant model in which toxicity and estrogenic activity can be assessed, while taking into account the absorption and fate of tested substances.

Twelve derivatives of benzophenone (BP1-BP12) are widely used as UV-screens to protect industrial products from light induced damage. There is growing public concern about industrially produced chemicals that might interfere with hormonal signaling pathways, thus having potential adverse effects on human health. The derivative 2,2',4,4'-tetrahydroxybenzophenone (BP2) which is used in cosmetic products and in packaging materials, was previously shown to be an estrogenic endocrine active chemical (EAC). While the metabolization of BP3 has been analyzed in vivo, according to our knowledge little is known about the pharmacokinetics of BP2. Therefore we performed a dose-response experiment with 5 dosages of BP2 /10, 33, 100, 333 or 1000 mg/kg body weight/ which was applied per gavage to adult ovariectomized (ovx) rats for 5 days. Serum samples were analyzed via HPLC. Metabolites were further identified by Helix pomatia glucuronidase treatment and subsequent ion-trap-mass spectrometry. Additionally we analyzed the time dependent metabolization and excretion of BP2 in a kinetic study. The parent compound BP2 is metabolized to glucuronide - and sulfate-conjugates. In the serum maximum levels of BP2, BP2-glucuronide and BP2-sulfate were observed already 30 min after BP2 application while highest concentrations of BP2 and its metabolites in urine were measured 120 min after treatment. It is suggested that this biotransformation occurs via a first-pass effect in the gut wall or the liver. Despite this rapid metabolization and excretion, the amount of unconjugated BP2 was sufficient to induce a dose dependent estrogenic effect in the uterotrophic assay.

Benzophenone-2 (BP2) is widely used as a UV screen in both industrial products and cosmetic formulations, where it is frequently found associated with fragrance compounds, such as isoeugenol and coumarin. BP2 is now recognized as an endocrine disruptor, but to date, no information has been reported on its fate in humans. The intrinsic clearance (Clint) and metabolic interactions of BP2 were explored using cryopreserved human hepatocytes in primary cultures. In vitro kinetic experiments were performed to estimate the Michaelis-Menten parameters. The substrate depletion method demonstrated that isoeugenol was cleared more rapidly than BP2 or coumarin (Clint = 259, 94.7 and 0.40 uL/min/10(6) cells respectively). This vitro model was also used to study the metabolic interactions between BP2 and isoeugenol and coumarin. Coumarin exerted no effects on either isoeugenol or BP2 metabolism, because of its independent metabolic pathway (CYP2A6). Isoeugenol appeared to be a potent competitive substrate inhibitor of BP2 metabolism, equivalent to the specific UGT1A1 substrate: estradiol. Despite the fact that inhibition of UGT by xenobiotics is not usually considered to be a major concern, the involvement of UGT1A1 in BP2 metabolism may have pharmacokinetic and pharmacological consequences, due to the its polymorphisms in humans and its pure estrogenic effect.

Several human and fish bioassays have been designed to characterize the toxicity and the estrogenic activity of chemicals. However, their biotransformation capability (bioactivation/detoxification processes) is rarely reported, although this can influence the estrogenic potency of test compounds. The fate of two estrogenic chemicals, the UV filter benzophenone-2 (BP2) and the bisphenol A substitute bisphenol S (BPS) was deciphered in eight human and zebrafish in vitro cell models, encompassing hepatic and mammary cellular contexts. BP2 and BPS were metabolized into a variety of gluco- and sulfo-conjugated metabolites. Similar patterns of BP2 and BPS biotransformation were observed among zebrafish models (primary hepatocytes, ZFL and ZELH-zfER cell lines). Interestingly, metabolic patterns in zebrafish models and in the human hepatic cell line HepaRG shared many similarities, while biotransformation rates in cell lines widely used for estrogenicity testing (MELN and T47D-KBLuc) were quantitatively low and qualitatively different. This study provides new data on the comparative metabolism of BP2 and BPS in human and fish cellular models that will help characterize their metabolic capabilities, and underlines the relevance of using in vitro zebrafish-based bioassays when screening for endocrine disrupting chemicals.

CIR ingredient: Benzophenone-2

Additives such as benzophenone-2 are commonly used in cosmetic products and food container plastics to filter out ultraviolet light...

Cosmetics product ingredient: Benzophenone-2

Information on 73 consumer products that contain Benzophenone-2 in the following categories is provided:

Fragrance Ingredients

Cosmetics -> Uv absorber