벤조페논-4

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Wear self contained breathing apparatus for fire fighting if necessary.

Keep container tightly closed in a dry and well-ventilated place. Hygroscopic. Store under inert gas. Keep in a dry place.

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

Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Do not let product enter drains. Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. 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 soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

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).

Handle with gloves. 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.

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).

Agricultural workers are encouraged to use sunscreen to decrease the risk of UV-related skin cancer. Our previous studies have shown certain commercial sunscreens to be penetration enhancers. The focus of this project is to determine whether active ingredients in sunscreen formulations (i.e., the UV absorbing components and insect repellants for the sunscreen/bug repellant combinations) also act as dermal penetration enhancers for herbicides in vitro. The total percentages of 2,4-dichlorophenoxyacetic acid (2,4-D) penetrating through hairless mouse skin in 24 h ranged from 54.9 +/- 4.7 for the no sunscreen control to 86.9 +/- 2.5 for padimate-o. Of the active ingredients tested (7.5% octyl methoxycinnamate, 7% octocrylene, 0.6% oxybenzone, 5% homosalate, 5% octyl salicylate, 8% padimate-o, 10% sulisobenzone, and 9.5% and 19% N,N-diethyl-m-toluamide [DEET]), all but octocrylene led to a significant increase in total 2,4-D penetration as compared to the control (P < 0.05), and only octocrylene and oxybenzone did not significantly decrease the corresponding lag time. Octyl salicylate (P < 0.01) and octyl methoxycinnimate (P < 0.05) significantly increased the 3H2O penetration across mouse skin, indicating physical damage to the stratum corneum. Additional studies demonstrated that the penetration enhancement seen across hairless mouse skin also occurred with human skin. Thus, the active ingredients of sunscreen formulations enhance dermal penetration of the moderately lipophilic herbicide 2,4-D.

Diminish the penetration of ultraviolet (UV) light through the epidermis by absorbing UV radiation within a specific wavelength range. The amount and wavelength of UV radiation absorbed are affected by the molecular structure of the sunscreen agent. /Sunscreen agents, topical/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 67(SRC), determined from a structure estimation method(2), indicates that sulisobenzone is expected to have high mobility in soil(SRC). The estimated pKa values of sulisobenzone are -2.4 and 7.6(3), indicating that this compound will exist almost entirely in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Sulisobenzone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). No relevant data were available to assess the importance of biodegradation in the environment(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 67(SRC), determined from a structure estimation method(2), indicates that sulisobenzone is not expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of -2.4 and 7.6(3) indicate sulisobenzone will exist almost entirely 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(4), an estimated BCF of 3(SRC), from an estimated log Kow of 0.37(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Sulisobenzone is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(5). Sulisobenzone absorbs at wavelengths >290(6) nm and therefore may be susceptible to direct photolysis by sunlight(SRC). Phenols are susceptible to sensitized photolysis in natural waters exposed to sunlight through reaction with hydroxy and peroxy radicals(7); therefore sensitized photolysis may have some importance in the environment(SRC). No relevant data were available to assess the importance of biodegradation in the environment(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sulisobenzone, which has an estimated vapor pressure of 1.3X10-11 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 sulisobenzone may be removed from the air by wet and dry deposition(SRC). Sulisobenzone absorbs at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

/AQUATIC SPECIES/ In this work, /the authors/ evaluate whether in vitro systems are good predictors for in vivo estrogenic activity in fish. /Investigators/ focus on UV filters being used in sunscreens and in UV stabilization of materials. First, /investigators/ determined the estrogenic activity of 23 UV filters and one UV filter metabolite employing a recombinant yeast carrying the estrogen receptor of rainbow trout (rtERalpha) and made comparisons with yeast carrying the human hERalpha for receptor specificity. Benzophenone-1 (BP1), benzophenone-2 (BP2), 4,4-dihydroxybenzophenone, 4-hydroxybenzophenone, 2,4,4-trihydroxy-benzophenone, and phenylsalicylate showed full dose-response curves with maximal responses of 81-115%, whereas 3-benzylidene camphor (3BC), octylsalicylate, benzylsalicylate, benzophenone-3, and benzophenone-4 displayed lower maximal responses of 15-74%. Whereas the activity of 17beta-estradiol was lower in the rtERalpha than the hERalpha assay, the activities of UV filters were similar or relatively higher in rtERalpha, indicating different relative binding activities of both ER. Subsequently, /investigators/ analyzed whether the in vitro estrogenicity of eight UV filters is also displayed in vivo in fathead minnows by the induction potential of vitellogenin after 14 days of aqueous exposure. Of the three active compounds in vivo, 3BC induced vitellogenin at lower concentrations (435 ug/L) than BP1 (4919 ug/L) and BP2 (8783 ug/L). The study shows, for the first time, estrogenic activities of UV filters in fish both in vitro and in vivo. Thus /investigators/ propose that receptor-based assays should be used for in vitro screening prior to in vivo testing, leading to environmental risk assessments based on combined, complementary, and appropriate species-related assays for hormonal activity.

/AQUATIC SPECIES/ ... Here /the authors/ report on acute and chronic effects of UV-filters 3-(4-methylbenzylidene-camphor) (4MBC), 2-ethyl-hexyl-4-trimethoxycinnamate (EHMC), benzophenone-3 (BP3) and benzophenone-4 (BP4) on Daphnia magna. The acute toxicity increased with log Pow of the compound. The LC50 values (48 hr) of 4MBC, EHMC, BP3 and BP4 were 0.56, 0.29, 1.9 and 50 mg/L, respectively. A tentative preliminary environmental risk assessment (ERA) based on a limited set of data indicates that individual UV-filters should undergo further ecotoxicological analysis, as an environmental risk cannot be ruled out. Consequently new data on the environmental occurrence and the effects of UV-filters are needed for a more accurate ERA. When regarded as a mixture occurring in surface waters they may pose a risk for sensitive aquatic organisms.

/AQUATIC SPECIES/ ...In this study, /investigators/ evaluate the effects of benzophenone-4 (BP-4) in eleuthero-embryos and in the liver, testis and brain of adult male fish on the transcriptional level by focusing on target genes involved in hormonal pathways to provide a more complete toxicological profile of this important UV-absorber. Eleuthero-embryos and males of zebrafish were exposed up to 3 days after hatching and for 14 days, respectively, to BP-4 concentrations between 30 and 3000 ug/L. In eleuthero-embryos transcripts of vtg1, vtg3, esr1, esr2b, hsd17beta3, cyp19b cyp19a, hhex and pax8 were induced at 3000 ug/L BP-4, which points to a low estrogenic activity and interference with early thyroid development, respectively. In adult males BP-4 displayed multiple effects on gene expression in different tissues. In the liver vtg1, vtg3, esr1 and esr2b were down-regulated, while in the brain, vtg1, vtg3 and cyp19b transcripts were up-regulated. In conclusion, the transcription profile revealed that BP-4 interferes with the expression of genes involved in hormonal pathways and steroidogenesis. The effects of BP-4 differ in life stages and adult tissues and point to an estrogenic activity in eleuthero-embryos and adult brain, and an antiestrogenic activity in the liver. The results indicate that BP-4 interferes with the sex hormone system of fish, which is important for the risk assessment of this UV-absorber.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of sulisobenzone can be estimated to be 67(SRC). According to a classification scheme(2), this estimated Koc value suggests that sulisobenzone is expected to have high mobility in soil. The estimated pKa values of sulisobenzone are -2.4 and 7.6(3), indicating that this compound will exist 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).

/HUMAN EXPOSURE STUDIES/ ...To determine the frequency of irritant reactions to 19 organic sunscreen filters in current use. Ninety-four healthy volunteers were photopatch tested using the European consensus methodology to three different concentrations (2%, 5%, and 10%) of 19 organic sunscreen filters at the Photobiology Unit in Dundee, UK. Of the 94 subjects recruited, 80 were analyzed after withdrawals and exclusions. Of the 19 organic sunscreen filters studied, only 2 compounds led to irritant reactions in > or =5% subjects. Five per cent and 10% benzophenone-4 led to irritant reactions in four and six subjects, respectively. Five per cent methylene bis-benzotriazolyl tetramethylbutylphenol led to irritant reactions in six subjects, but unlike benzophenone-4, this was not in a dose-dependent fashion. When performing photopatch testing according to the European consensus methodology with these 19 organic sunscreen filters, a 10% concentration is suitable for all filters, except benzophenone-4, which should be tested at a concentration of 2%.

/HUMAN EXPOSURE STUDIES/ Cosmetic products containing Benzophenones-2, -3, or -4 (0.l%-3.5%) were tested for phototoxicity in humans. In each study, the test material was applied under occlusion to the subject's skin for 24 hours. Sites were then scored, exposed to UV radiation, and then scored daily for up to seven days. Nonirradiated/treated and nontreated/irradiated controls were frequently used. Products containing Benzophenones-2, -3, and -4 were nonphototoxic in all studies; however, a number of subjects experienced slight irritation (usually a 1+ response) to the test material.

/HUMAN EXPOSURE STUDIES/ /Investigators/ tested the potential irritancy of Benzophenone-4 on six adult white humans. Patches containing 1% or 10% Benzophenone-4 in alcohol were applied to the subjects for 24 hours, after which time the patches were removed, the sites scored, and fresh patches applied. This procedure was repeated every other day, three days per week for seven weeks, until a total of 21 patches had been made. The mean cumulative irritation scores for 1% and 10% solutions were 8.6 and 53.1, respectively (maximum score = 84). The latter value is indicative of a primary irritant.

/HUMAN EXPOSURE STUDIES/ Benzophenones-4 and -11 were tested for potential skin irritation in separate single insult patch tests. Each ingredient was applied at concentrations of 16, 8, and 4% in DMP /dimethyl phthalate/ and in petrolatum to the skin of each of 14 subjects. At a concentration of 16% in either base, Benzophenones-4 and -11 were irritating to four and two subjects, respectively. Neither ingredient was irritating at concentrations of 4% or 8% in either vehicle.

For more Human Toxicity Excerpts (Complete) data for SULISOBENZONE (8 total), please visit the HSDB record page.

An estimated BCF of 3 was calculated for sulisobenzone(SRC), using an estimated log Kow of 0.37(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The estimated pKa values of -2.4 and 7.6(1) indicate sulisobenzone will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces is not expected to be an important fate process. Sulisobenzone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-11 mm Hg(SRC), determined from a fragment constant method(2).

/LABORATORY ANIMALS: Acute Exposure/ A number of studies have determined the potential irritancy of Benzophenones to the eyes of rabbits. The test material (0.1 mL or 0.1 g) was instilled into one eye of each rabbit; the other eye served as an untreated control. Eyes were examined and scored for irritation daily for a period of three to ten days. Some test procedures included washing of the treated eyes with water four seconds after instillation of the test material. Results of eye irritation tests revealed that most Benzophenones at concentrations of 5%-100% were nonirritating when instilled into the eyes of rabbits. Benzophenones-1, -2, and -4 were slightly to moderately irritating at 100% concentration; however, ... Benzophenone-4 was irritating at concentrations of 8 and 16% in DMP /dimethyl phthalate/ or petrolatum, it was nonirritating when tested as a 5% solution in water.

/LABORATORY ANIMALS: Acute Exposure/ An occlusive patch containing 0.5 mL or 0.5 mg of the test ingredient was applied to the intact and abraded skin of albino rabbits. Patches remained in place for 24 hours and were then removed and scored for irritation according to the Draize method. Sites were again scored 24 hours after patch removal. ... Benzophenones-1, -4, and -6 were minimally irritating (PII = 0.25-0.50) when applied as 16% solutions in dimethyl phthalate (DMP). However, these ingredients were nonirritating at 8% in DMP and at 16% in petrolatum.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ...A 16-day cumulative test in rabbits /was used/ to study the irritation potential of Benzophenone-4. An alcohol solution containing either 10% or 1% Benzophenone-4 was applied uncovered to the depilated backs of six New Zealand albino rabbits. Twenty-four hours later the sites were scored for irritation, and the solution was reapplied. This procedure was repeated every other day for five weeks, until a total of 16 applications of Benzophenone-4 had been made. The average cumulative irritation score was then calculated (maximum score = 64); applications of Benzophenone-4 (10%) and Benzophenone-4(1%) produced scores of 3.6 and 0.3, respectively.

/GENOTOXICITY/ The Ames Salmonella/Mammalian-Microsomal Assay was used to test Benzophenones-1, -2, -3, -4, -6, -8, -9, and -11 for mutagenicity. Salmonella typhimurium strains TA98, TAl00, TA1535, TA1537, and TA1538 were used; all tests were performed in the presence and absence of Aroclor-induced rat liver microsomal S-9 cell fraction to observe the mutagenic effect of each compound following metabolic activation. Preliminary cytotoxicity studies determined the dose range of each compound to be used. All Benzophenones were nonmutagenic when assayed directly. All but three Benzophenones (-2, -6, and -8) were nonmutagenic with metabolic activation.

Because the absorptive characteristics of skin of children younger than 6 months of age may differ from those of adults and because the immaturity of metabolic and excretory pathways of these children may limit their ability to eliminate any percutaneously absorbed sunscreen agent, sunscreen products should be used in children younger than 6 months of age only as directed by a clinician. It is possible that the characteristics of geriatric skin also differ from those of skin in younger adults, but these characteristics and the need for special considerations regarding use of sunscreen preparations in this age group are poorly understood. /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: Sulisobenzone up to 10 percent is included on this list.

CIR ingredient: Benzophenone-4

Used as ultraviolet absorber for leather and textiles, and ultraviolet screen for humans; Also used in cosmetics and shampoos; [Merck Index]

Leather Tanning and Processing [Category: Industry]

Ultraviolet absorber for leather and textile fibers; in cosmetics and shampoos.

Used as an ultraviolet absorber in US cosmetics at concentrations of 5-10%

Benzophenones-2, -3, -4, -6, -8, and -9 are used in suntan lotions and hair sprays because they protect the skin and hair from the harmful effects of the sun. These ingredients also photostabilize cosmetic dyes, creams, and lotion's.

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.[Table#7083]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Benzenesulfonic acid, 5-benzoyl-4-hydroxy-2-methoxy-. Aggregated National Production Volume: < 500,000 pounds.

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Benzenesulfonic acid, 5-benzoyl-4-hydroxy-2-methoxy-. National Production Volume: Withheld.

Benzophenone-4 is prepared via sulfonation of Benzophenone-3. The product is purified by precipitation from aqueous HCl, isolated by centrifugation, washed with acidic water, and dried.

Preparation: A.J. Cofrancesco, United Kingdom 1136525 (1968 to GAF)

Cosmetics product ingredient: Benzophenone-4

Information on 125 consumer products that contain Benzophenone-4 in the following categories is provided:

Benzenesulfonic acid, 5-benzoyl-4-hydroxy-2-methoxy-: ACTIVE

The FDA Panel on Review of Topical Analgesics has proposed that Benzophenones-3, -4, and -8 are safe and effective as active ingredients in sunscreens for over-the-counter (OTC) use at the following concentrations: Benzophenone-3, 2%-6%; Benzophenone-4, 5%-10%; and Benzophenone-8, 3%. The Panel proposed these concentration limits on a combined safety and efficacy basis (a concentration limit may reflect maximum efficacy and not necessarily an indication of toxicity at a higher concentration).

Sunscreens are available in a variety of dosage forms and formulations. ... Because these formulations frequently change and the manufacturers often are reluctant to reveal specific ingredients in their formulations, a listing of commercially available sunscreens is not included in this monograph. /Sunscreens/