Absorption, Distribution and Excretion
This product does not easily penetrate the skin but can enhance the penetration of other chemicals. The main metabolite of this drug is excreted in the urine as a glucuronide conjugate. In pharmacokinetic studies in rats, p-hydroxybenzoic acid was not detected in urine or feces. Solvents used in sunscreen products can affect the stability of the drug and its binding to the skin; generally, alcohol solvents allow sunscreens to penetrate the epidermis the fastest and deepest. Sunscreens appear to be absorbed by the intact epidermis, but the degree of absorption varies. /Sunscreen/

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Metabolism/Metabolites In rabbits, the main metabolic pathway for benzophenone is reduction to benzyl alcohol. Following oral administration to rats, a small amount (1%) of benzophenone is converted to p-hydroxybenzophenone.

Interactions
This study encourages agricultural workers to use sunscreen to reduce the risk of UV-related skin cancer. Our previous research has shown that some commercially available sunscreens have a penetration-enhancing effect. This project aimed to determine whether the active ingredients in sunscreen formulations (i.e., the UV-absorbing components and insect repellents in sunscreen/insect repellent combinations) can also enhance the skin penetration of herbicides in vitro. Within 24 hours, the total percentage of 2,4-dichlorophenoxyacetic acid (2,4-D) penetrating the skin of hairless mice ranged from 54.9 ± 4.7% in the control group that had never applied sunscreen to 86.9 ± 2.5% in the pardimat-O group. Of the active ingredients tested (7.5% octyl methoxycinnamate, 7% octocrylene, 0.6% oxybenzone, 5% homosalate, 5% octyl salicylate, 8% pardimethicone-O, 10% sulfonylurea benzophenone, and 9.5% and 19% N,N-diethyl-m-toluamide [DEET]), all except octocrylene significantly increased the total permeability of 2,4-D (P < 0.05 compared to the control group), and only octocrylene and oxybenzone did not significantly shorten the corresponding hysteresis time. Octyl salicylate (P < 0.01) and octyl methoxycinnamate (P < 0.05) significantly increased the trihydrate permeability of 2,4-D in mouse skin, indicating that they caused physical damage to the stratum corneum. Further studies showed that the enhanced permeation observed in hairless mouse skin also existed in human skin. Therefore, the active ingredients in sunscreen formulations can enhance the skin penetration of the moderately lipophilic herbicide 2,4-D. This is achieved by absorbing UV radiation within a specific wavelength range, reducing UV penetration into the epidermis. The amount and wavelength of UV radiation absorbed are influenced by the molecular structure of the sunscreen agent. /Sunscreen agent, topical/

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Non-human toxicity values
Oral LD50 in rats: 3530 mg/kg

Sulisobenzone belongs to the benzophenone class of compounds. It has been approved by the U.S. Food and Drug Administration (FDA) at concentrations up to 10%, and by Health Canada at the same concentration. It effectively filters UVA and UVB rays, protecting skin from UV damage. This UV filter, Sulisobenzone (BP-4), is widely used in sunscreens and other personal care products. Benzophenone is an aromatic ketone with pharmaceutical and industrial applications. It is naturally found in fruits such as grapes. Benzophenones can be used as photoinitiators, flavoring agents, UV curing agents, and sometimes as flavoring agents; they are also used in the production of pesticides, agricultural chemicals, and pharmaceuticals, as well as as additives in plastics, coatings, and adhesives. Benzylbenzophenone compounds can be used to delay the photodegradation of cosmetics and plastic surface coatings or extend their shelf life. See also: Octyl methoxycinnamate; Sulfobenzophenone (ingredient); Ensolazole; Sulfobenzophenone (ingredient)... See more...

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Drug Indications
Sunscreens are used to prevent sunburn, actinic keratosis, and premature skin aging, and to reduce the incidence of skin cancer.

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Mechanism of Action
The surface coating of benzophenone compounds reduces the amount of ultraviolet radiation absorbed by the skin by limiting the total energy reaching the skin. Topically applied benzophenone sunscreens protect the skin from the harmful effects of ultraviolet radiation by chemically absorbing light energy (photons). In this process, the benzophenone molecule is activated to a higher energy level. When the excited molecule returns to the ground state, the energy is released as heat. The ortho-hydroxyl group is considered a structurally necessary condition for benzophenone to absorb ultraviolet light. This structural arrangement also contributes to the electronic stability of the molecule. Benzophenone absorbs energy across the entire ultraviolet band, but the maximum ultraviolet absorption wavelength of 2-hydroxybenzophenone is between 284 and 287 nanometers. Benzophenone sunscreens, applied topically, protect the skin from the harmful effects of ultraviolet (UV) radiation by chemically absorbing light energy (photons). In this process, the benzophenone molecule is excited to a higher energy level. When the excited molecule returns to its ground state, the energy is released as heat. The ortho-hydroxyl group is considered a structurally necessary condition for benzophenone to absorb UV light. This structural arrangement also contributes to the electronic stability of the molecule. Therefore, a benzophenone surface coating reduces the amount of UV radiation absorbed by the skin by limiting the total energy reaching it. Benzophenone can absorb energy across the entire UV wavelength range, but the maximum absorption wavelength of 2-hydroxybenzophenone is between 284 and 287 nanometers…
By absorbing UV radiation within a specific wavelength range, UV penetration into the epidermis is reduced. The amount and wavelength of UV radiation absorbed are influenced by the molecular structure of the sunscreen agent. /Sunscreen, Topical/
Therapeutic Use
It is recommended that residents living in areas with high solar radiation, those working outdoors, or those who frequently engage in outdoor recreational activities use a sunscreen with a high SPF (greater than 15) daily on normally exposed skin. Daily use of sunscreen can reduce cumulative sun exposure, thereby lowering the risk of actinic keratosis and squamous cell carcinoma. Sunscreen is intended to prevent sunburn. In addition to limiting the time skin is exposed to sunlight, regular use of sunscreen in the sun can help reduce long-term sun damage, such as premature skin aging and skin cancer. /Sunscreen, for external use; included on US product label/

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Drug Warning
Manufacturers of sunscreens using propellants warn that inhaling the fumes produced by these formulations may be harmful or even fatal. /Propellant/
Because the skin absorption characteristics of infants under 6 months of age may differ from those of adults, and their metabolic and excretory pathways are not yet mature, potentially limiting their ability to clear transdermal sunscreens, sunscreen products should only be used on infants under the guidance of a clinician. The skin characteristics of older adults may also differ from those of younger adults, but these characteristics and the special considerations for using sunscreens in this age group are not fully understood. /Sunscreen/
Limited information exists regarding the safety of long-term use of sunscreen, but commercially available physical and chemical sunscreens appear to have a low incidence of adverse reactions. Derivatives of para-aminobenzoic acid (PABA), benzophenone, cinnamic acid, salicylates, and 2-phenylbenzimidazole-5-sulfonic acid can cause skin irritation, including burning, stinging, itching, and erythema, in rare cases. /Sunscreen/
Sunscreen should not be applied to clothing worn on areas not normally exposed to sunlight, such as the torso and buttocks, such as during extended sunbathing. /Sunscreen/
For more complete data on drug warnings for sulphurebenone (11 in total), please visit the HSDB records page.

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Pharmacodynamics
Topically applied benzophenone sunscreens protect the skin from the harmful effects of ultraviolet radiation by chemically absorbing light energy (photons). Proper use of sunscreen helps reduce the risk of sunburn. Sunscreen is primarily used for unintentional sun exposure and can help prevent squamous cell carcinoma of the skin. However, it is currently inconclusive that topical sunscreen can prevent basal cell carcinoma and melanoma. Using sunscreen may prolong the duration of intentional sun exposure, such as sunbathing.

C14H12O6S

308.3065

308.035

4065-45-6

6628-37-1 (mono-hydrochloride salt)

19988

White to off-white solid powder

1.4±0.1 g/cm3

0°C

170 °C

0°C

1.617

0.89

2

6

4

21

462

0

CXVGEDCSTKKODG-UHFFFAOYSA-N

InChI=1S/C14H12O6S/c1-20-12-8-11(15)10(7-13(12)21(17,18)19)14(16)9-5-3-2-4-6-9/h2-8,15H,1H3,(H,17,18,19)

5-benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 100 mg/mL (~324.35 mM)
DMSO : ≥ 34 mg/mL (~110.28 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)