4-(Dimethylamino)benzoic acid 2-ethylhexyl ester

277.4

277.40

244-289-3

DTXSID7029320

Light yellow, mobile liquid|Colorless liquid

2922499990

29.5

5.77 (est)

Liquid

0.995 g/cu cm at 25 deg C

242.5-243.5 °C

325 °C(lit.)

>230 °F

1.514

soluble in alcohol, isopropyl alcohol, mineral oil; practically insoluble in water, glycerin, propylene glycol

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage.

5.1X10-4 mm Hg at 25 deg C (est)

Henry's Law constant: 4.0X10-6 atm-cu m/mole at 25 °C (est)

pKa = 2.9 for N+ (est)

Hydroxyl radical reaction rate constant: 1.3X10-10 cu cm/molecule sec at 25 °C (est)

NONH for all modes of transport

2

36/37/38

26-27-36

Xi

Stable under recommended storage conditions.

P261-P305 + P351 + P338

H315-H319-H335

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.

Strong oxidizing agents, Strong acids

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: Padimate O up to 8 percent is included on this list.

ESFA; The EFSA Journal (2005) 293: 1-15 (2005). The European Food Safety Authority (EFSA) developed a report on the risk to human health from Padimate O, acting as a photoinitiator in inks applied to food packaging materials.[Available from, as of April 21, 2014: http://www.efsa.europa.eu/en/efsajournal/doc/293.pdf]

|Warning|H315 (57.76%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 395 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Wear self contained breathing apparatus for fire fighting if necessary.|Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.

Avoid contact with skin and eyes. Avoid inhalation of vapor or mist. Normal measures for preventive fire protection.|Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.

Derivatives of PABA, benzophenone, cinnamic acid, and salicylate and 2-phenylbenzimidazole-5-sulfonic acid have caused skin irritation including burning, stinging, pruritus, and erythema on rare occasions. /Sunscreens/

Padimate O causes DNA strand breaks of cells under the epidermis _in vitro_. No LD50 value reported.

Hesperetin is one of the flavonoids and possess anti-inflammatory, UV-protecting and antioxidant effects. Permeation issues for topical delivery systems of such effects are occasionally problematic, and in view of the fact that microemulsions are potential carriers for transdermal delivery system, the objective of this study was to design an optimal microemulsion formulation by in vitro permeation study for hesperetin topical dosage form and determine its topical photoprotective effect and skin irritation by in vivo study. The hesperetin-loaded microemulsion showed an enhanced in vitro permeation compared to the aqueous and isopropyl myristate (IPM) suspension dosage form of hesperetin. In comparison, the effect of co-surfactant on the drug permeation capacity, propylene glycol showed highest permeation rate, followed by ethanol, glycerol and polyethylene glycol (PEG 400). Sunscreen agent padimate O, as a transdermal enhancer could increase the permeation rate of hesperetin.|Agricultural workers are encouraged to use sunscreen to decrease the risk of UV-related skin cancer. /The authors'/ 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 hr 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 (3)H2O 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/

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/

No pharmacokinetic data available.

Padimate O's production and use as an ultraviolet absorber in sunscreens and cosmetics(1,2) and as a synergistic agent-photoinitiator for UV-curable inks(3) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2200(SRC), determined from a structure estimation method(2), indicates that Padimate O is expected to have slight mobility in soil(SRC). Volatilization of Padimate O from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Padimate O is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.1X10-4 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 2200(SRC), determined from a structure estimation method(2), indicates that Padimate O is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 4X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 15 and 117 days, respectively(SRC). Volatilization from water surfaces may be attenuated by adsorption to suspended solids and sediment in the water column. According to a classification scheme(4), an estimated BCF of 2960(SRC), from an estimated log Kow of 5.77(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC). A base-catalyzed second-order hydrolysis rate constant of 3.7X10-4 L/mole-sec(SRC) was estimated using a structure estimation method(2); this corresponds to half-lives of 590 and 59 years at pH values of 7 and 8, respectively(2). Padimate O absorbs UV light in the sunlight spectrum(5) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Aromatic amines are susceptible to sensitized photolysis in natural waters exposed to sunlight through reaction with hydroxy and peroxy radicals(6). 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), Padimate O, which has an estimated vapor pressure of 5.1X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist primarily as a vapor in the ambient atmosphere at 25 °C. At temperatures below 10 °C, the model of gas/particle partitioning(1) indicates that Padimate O will exist in both the vapor and particulate phases(SRC). Vapor-phase Padimate O 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 2.9 hours(SRC), calculated from its rate constant of 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase Padimate O may be removed from the air by wet and dry deposition(SRC). Padimate O absorbs UV light in the sunlight spectrum(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of Padimate O with photochemically-produced hydroxyl radicals has been estimated as 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.9 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A base-catalyzed second-order hydrolysis rate constant of 3.7X10-4 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 590 and 59 days at pH values of 7 and 8, respectively(1). Padimate O absorbs UV light in the sunlight spectrum(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Aromatic amines are susceptible to sensitized photolysis in natural waters exposed to sunlight through reaction with hydroxy and peroxy radicals(3).

An estimated BCF of 2960 was calculated in fish for Padimate O(SRC), using an estimated log Kow of 5.77(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of Padimate O can be estimated to be 2200(SRC). According to a classification scheme(2), this estimated Koc value suggests that Padimate O is expected to have slight mobility in soil.

The Henry's Law constant for Padimate O is estimated as 4X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that Padimate O is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 15 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 117 days(SRC). However, volatilization from water surfaces may be attenuated by adsorption to suspended solids and sediment in the water column. The volatilization half-life from a model pond is about 1400 days when adsorption is considered(3). Padimate O's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to be an important fate process(SRC). Padimate O is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.1X10-4 mm Hg(SRC), determined from a fragment constant method(1).

SURFACE WATER: In surface seawater samples collected from Folly Beach, South Carolina in the summer of 2010, Padimate O was detected at concentrations ranging from <1 to 111 ng/L(1).

Industry reported the results of analytical tests on the occurrence of Padimate O (2-ethylhexyl-4-dimethylaminobenzoate) in a number of food products packaged in cartons printed with UV-cured inks containing Padimate O as a photoinitiator(1); in the milk and soy based products tested, not specifically intended for babies, the level of Padimate O ranged from 27 to 134 ug/L, for pack sizes of 1000 mL; in a chocolate milk sample (200 mL pack size) Padimate O level was 148 ug/L(1); in fruit juices, fruit nectars and drinks indicated as "cloudy" due to the presence of fruit pulp and fibres, the levels of Padimate O ranged from <5 ug/L to 125 ug/L(1).

In a chocolate milk sample (200 mL pack size) Padimate O level was 148 ug/L(1).|Researchers in Europe analyzed samples of human milk for the presence of sunscreens and other chemicals with possible endocrine activity. Mothers were asked about their use of sunscreens and cosmetics that contained sunscreen ingredients (benzophenone 2, benzophenone 3, 3-benzylidene camphor, 4-MBC, OMC, homosalate, octocrylene, and octyl-dimethyl PABA). Responding to questionnaires, 78.8% of the women reported using products that contained sunscreens; 76.5% of human milk samples contained these chemicals. There was a high correlation reported between mothers' use of these chemicals and their concentrations in human milk. The authors concluded that except for lipsticks (the ingestion of which is probably important), their results agree with studies in animals and humans showing dermal absorption of sunscreens. Given that some of these chemicals have endocrine activity in animals, the authors suggested that exposure could be lessened if mothers abstained from using these products during their children's sensitive life stages.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 7,828 workers (7,210 of these were female) were potentially exposed to Padimate O in the US(1). Occupational exposure to Padimate O may occur through dermal contact with this compound at workplaces where Padimate O is produced or used. The general population may be exposed to Padimate O via dermal contact with this compound in consumer products, such as cosmetics and sunscreens, and through ingestion of foods(SRC) where Padimate O has migrated from inks in the food packaging into the food(2).

Indicated as an active UV-B filter to prevent photodamage.

Daily use of a sunscreen with a high SPF (greater than 15) on usually exposed skin is recommended for residents of areas of high ... /solar radiation/ who work outdoors or ... /enjoy/ regular outdoor recreation. Daily use of a sunscreen can reduce the cumulative ... /solar/ exposure that causes actinic keratoses and squamous-cell carcinoma.

PABA derivatives reportedly have weak sensitization potential, but the incidence of allergic and photoallergic contact dermatitis associated with their use is increasing. Contamination of PABA derivatives with benzocaine which may cause allergic reactions has been reported. In patients allergic to compounds that are structurally similar to PABA (e.g., ester-type anesthetics, aniline dyes, thiazides, sulfonylurea and paraphenylenediamine drugs), cross-sensitivity to PABA derivatives has been reported occasionally; therefore, sunscreens containing PABA derivatives may be contraindicated in patients with a history of hypersensitivity to these chemicals.|The manufacturers of sunscreen preparations with propellants warn that concentrating and subsequently inhaling the fumes from these preparations may be harmful or fatal. /Propellants/|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/|Little information is available regarding the safety of chronic sunscreen usage, but commercially available physical and chemical sunscreens appear to have a low incidence of adverse effects. Derivatives of PABA, benzophenone, cinnamic acid, and salicylate and 2-phenylbenzimidazole-5-sulfonic acid have caused skin irritation including burning, stinging, pruritus, and erythema on rare occasions. /Sunscreens/|For more Drug Warnings (Complete) data for PADIMATE O (12 total), please visit the HSDB record page.

Padimate O absorbs UV-B rays, which can in turn induce DNA damage in human keratinocytes. While treatment of padimate O suppresses the formation of UV-endonuclease-sensitive sites, there is also an increase in direct strand breaks of DNA in cells.

Chemical or physical agents that protect the skin from sunburn and erythema by absorbing or blocking ultraviolet radiation. (See all compounds classified as Sunscreening Agents.)

Padimate O is capable of human skin penetration.|No pharmacokinetic data available.|... None of the subjects tested showed any sign of skin irritation at the application site. ... In four postmenopausal women (age 54-63 years, weight 67-93 kg) the mean estradiol level 24 hr postapplication over the 9 day study period was 53 pg/mL. This result was significantly greater (p < 0.001) than the baseline value of 13 pg/mL. The mean estradiol/estrone ratio also rose significantly (p < 0.04) from a baseline value of 0.2 up to 0.8.|It appears that sunscreen agents are absorbed by the intact epidermis to varying degrees. /Sunscreens/|Sunscreen skin penetration and safety assessment should be considered together in order to ensure that in vitro cytotoxicity studies examine relevant doses of these organic chemical UV filters to which viable epidermal cells are realistically exposed. In this study, /investigators/ sought to determine whether sufficient topically applied sunscreens penetrated into human viable epidermis to put the local keratinocyte cell populations at risk of toxicity. The penetration and retention of five commonly used sunscreen agents (avobenzone, octinoxate, octocrylene, oxybenzone and padimate O) in human skin was evaluated after application in mineral oil to isolated human epidermal membranes. Sunscreen concentration-human keratinocyte culture response curves were then defined using changes in cell morphology and proliferation (DNA synthesis using radiolabelled thymidine uptake studies) as evidence of sunscreens causing toxicity. Following 24 hr of human epidermal exposure to sunscreens, detectable amounts of all sunscreens were present in the stratum corneum and viable epidermis, with epidermal penetration most evident with oxybenzone. The concentrations of each sunscreen found in human viable epidermis after topical application, adjusting for skin partitioning and binding effects, were at least 5-fold lower, based on levels detected in viable epidermal cells, than those appearing to cause toxicity in cultured human keratinocytes. It is concluded that the human viable epidermal levels of sunscreens are too low to cause any significant toxicity to the underlying human keratinocytes.|Researchers in Europe analyzed samples of human milk for the presence of sunscreens and other chemicals with possible endocrine activity. Mothers were asked about their use of sunscreens and cosmetics that contained sunscreen ingredients (benzophenone 2, benzophenone 3, 3-benzylidene camphor, 4-MBC, OMC, homosalate, octocrylene, and octyl-dimethyl PABA). Responding to questionnaires, 78.8% of the women reported using products that contained sunscreens; 76.5% of human milk samples contained these chemicals. There was a high correlation reported between mothers' use of these chemicals and their concentrations in human milk. The authors concluded that except for lipsticks (the ingestion of which is probably important), their results agree with studies in animals and humans showing dermal absorption of sunscreens. Given that some of these chemicals have endocrine activity in animals, the authors suggested that exposure could be lessened if mothers abstained from using these products during their children's sensitive life stages.|Information on the cutaneous absorption, distribution, and elimination of most topically applied sunscreen agents is limited. Solvents used in sunscreen products affect the stability and binding of the drug to the skin; in general, alcoholic solvents allow for the most rapid and deepest epidermal penetration of sunscreens. It appears that sunscreen agents are absorbed by the intact epidermis to varying degrees. PABA reportedly diffuses into the stratum corneum, reaching maximum concentrations there 2 hours following application, but apparently does not penetrate deeper layers of the skin to a substantial extent. Homosalate's penetration also appears to be limited to the stratum corneum. One study in animals indicated that PABA may penetrate the skin to a greater extent than does padimate A. Although some studies have shown that substantive concentrations of PABA remain on the skin after washing, other studies have failed to confirm this. One study showed that PABA esters were removed from the skin less readily than was PABA or other chemical sunscreens. /PABA/

No pharmacokinetic data available.

No pharmacokinetic data available.

It is proposed that simultaneous contact of padimate O with keratinocytes can stimulate the diffusion through human epidermis. Upon photoexcitation, padimate O generates singlet oxygen and forms carbon-centred free radicals. While padimate O attenuates simple and repairable, UV-induced cellular damage, it may also increase complex chemical damage that is more difficult to repair by normal cells.|Radiation is absorbed by chemical sunscreens when the electron energy level of the drug is raised from its ground state to a higher energy level or excited state. Chromophore groups (C=C, C=O, O-N=O) with loosely held electrons are easily excited by radiation. Compounds which have several chromophore groups in optimal positions have high absorbance over a broad range of wavelengths. Chemical sunscreens are usually agents that absorb not less than 85% of UVB radiation (thus preventing burning) but may permit transmission of UVA radiation (thus allowing tanning). Some sunscreens may absorb wavelengths over a range that is slightly wider or narrower than that of UVB. All PABA derivatives absorb wavelengths of approximately 290-320 nm, benzophenone derivatives absorb wavelengths of approximately 250-360 nm, cinnamic acid derivatives absorb wavelengths of 280-320 nm, and salicylate derivatives and other miscellaneous chemical sunscreens absorb wavelengths of about 270-320 nm.|The wavelength to which the skin is maximally sensitive had been accepted for many years to be 296.7 nm; however, recent evidence suggests that the most erythemogenic UVB wavelength may be slightly lower (e.g., somewhere in the range of 292-295 nm). In addition, of the stronger burning wavelengths that reach the earth's surface, most are approximately 310 nm. Therefore, sunscreens that maximally absorb UVB radiation near either of these wavelengths are particularly effective at preventing sunburn. Maximum absorbance occurs at about 290 nm for PABA, at about 295 nm for glyceryl-p-aminobenzoate, and at about 310 nm for the remaining PABA derivatives. Maximum absorbance occurs at 280-290 nm for benzophenone derivatives, at 310 nm for cinnamic acid derivatives with the exception of diethanolamine-p-methoxycinnamate which has its maximum absorbance at 290 nm, and at 300-305 nm for salicylate derivatives and other miscellaneous sunscreens. /Sunscreens/|... The photomutagenic sunscreen Padimate-O attacks DNA on illumination with simulated sunlight, producing strand breaks and lesions that are labile to N,N'-dimethylethylenediamine but few, if any, cyclobutane dimers or other direct photoproducts. The damage can be completely suppressed by the free radical quenchers Tris, ethanol, mannitol and dimethylsulfoxide, which is commonly used as a solvent in conventional photomutagenicity assays.|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/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ENDOCRINE MODULATION/ The in vitro and in vivo estrogenicity of 5 UV B-filters, benzophenone-3 (Bp-3), homosalate (HMS), 4-methyl-benzylidene camphor (4-MBC), octyl-methoxycinnamate (OMC) and octyl-dimethyl-PABA (OD-PABA) and 1 UVA-filter, butyl-methoxydibenzoylmethane (B-MDM) were studied. A general screening assay (E-screen) with a human breast cancer cell line, MCF-7 cells, was carried out. A positive test was based upon the binding of the test compound with the estrogen receptor leading to cell proliferation. As a positive control, 17 b -estradiol, was used and it was, as expected, positive in the assay. The 5 UV-B filters were found to be positive in the assay and caused cell proliferation. The UV-A filter gave a negative result. EC 50 values for 17 b -estradiol, Bp-3, 4-MBC, OMC, OD-PABA and HMS were found to be 1.22 pM, 3.73 uM, 3.02 uM, 2.37 uM, 2.63 uM and 1.56 uM, respectively. The results were supported by the expression of the estrogen-dependent pS 2 protein and by an inhibition of effects with the anti-estrogen ICI 182,780.The potency of the positive control is in the order of picomoles; the in vitro potency of the UV-filters tested lays in the range of uM, which means a difference of 1 million units. The in vitro potency of the UV-filters is thus importantly lower than the one observed for 17 b -estradiol. Probably a lot of industrial chemicals would show some in vitro estrogenic effects when this type of comparisons is taken seriously. It should be emphasized here that in vitro assays can only demonstrate whether UV-filters bind on the estrogen receptor or not, but they do not provide evidence whether the compounds have estrogenic activity or not. In vitro assays are therefore screening tests useful in setting priorities for further in vivo testing. ...Claiming that 5 UV-filters have estrogenic properties based on an in vitro test is premature. The in vitro ranking for the UV-filters going from Bp3, 4-MBC, OMC, OD-PABA to HMS, did not correspond with the in vivo results. Indeed, in the latter test 4-MBC was most active, followed by OMC and Bp-3. The most active UV-filter in vitro displayed only a weak activity in vivo. In addition OD-PABA and HMS were found to be inactive. Only precise toxicokinetic data can link the in vitro and in vivo data, a conclusion that was also reached by the authors.|/GENOTOXICITY/ ... applying an SPF-15 sunscreen which contains Padimate-O to human skin followed by exposure to only 5 minimum erythemal doses (MED) of sunlight could, while suppressing the formation of UV-endonuclease-senitive sites (ESS), increase /DNA/ strand breaks in cells under the epidermis by at least 75-fold compared to exposure to 1 MED in the absence of sunscreen.|/ALTERNATIVE and IN VITRO TESTS/ Sunscreen skin penetration and safety assessment should be considered together in order to ensure that in vitro cytotoxicity studies examine relevant doses of these organic chemical UV filters to which viable epidermal cells are realistically exposed. In this study, /investigators/ sought to determine whether sufficient topically applied sunscreens penetrated into human viable epidermis to put the local keratinocyte cell populations at risk of toxicity. The penetration and retention of five commonly used sunscreen agents (avobenzone, octinoxate, octocrylene, oxybenzone and padimate O) in human skin was evaluated after application in mineral oil to isolated human epidermal membranes. Sunscreen concentration-human keratinocyte culture response curves were then defined using changes in cell morphology and proliferation (DNA synthesis using radiolabelled thymidine uptake studies) as evidence of sunscreens causing toxicity. Following 24 hr of human epidermal exposure to sunscreens, detectable amounts of all sunscreens were present in the stratum corneum and viable epidermis, with epidermal penetration most evident with oxybenzone. The concentrations of each sunscreen found in human viable epidermis after topical application, adjusting for skin partitioning and binding effects, were at least 5-fold lower, based on levels detected in viable epidermal cells, than those appearing to cause toxicity in cultured human keratinocytes. It is concluded that the human viable epidermal levels of sunscreens are too low to cause any significant toxicity to the underlying human keratinocytes.|/OTHER TOXICITY INFORMATION/ Topical use of sunscreens reduces the risk for sunburn in humans. Sunscreens probably prevent squamous-cell carcinoma of the skin when used mainly during unintentional sun exposure. No conclusion can be drawn about the cancer-preventive activity of topical use of sunscreens against basal-cell carcinoma and cutaneous melanoma. Use of sunscreens can extend the duration of intentional sun exposure, such as sunbathing. Such an extension may increase the risk for cutaneous melanoma. /Sunscreens/|/OTHER TOXICITY INFORMATION/ The manufacturers of sunscreen preparations with propellants warn that concentrating and subsequently inhaling the fumes from these preparations may be harmful or fatal. /Propellants/

2-ethylhexyl 4-(dimethylamino)benzoate

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.

Adhesive manufacturing|Benzoic acid, 4-(dimethylamino)-, 2-ethylhexyl ester: ACTIVE|The drug is the 2-ethylhexyl ester of p-(dimethylamino) benzoic acid, occurs as a clear to yellow, oily liquid having a faint aromatic odor and is insoluble in water and soluble in alcohol.

Cosmetics -> Uv absorber; Uv filter