Hyperoside as a UV Photoprotective or Photostimulating Compound-Evaluation of the Effect of UV Radiation with Selected UV-Absorbing Organic Compounds on Skin Cells.

Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective.

Effect of Substituent Groups on the Strength of Intramolecular Hydrogen Bonds in 2,4-Dihydroxybenzophenone UV Absorbers.

2,4-Dihydroxybenzophenone is the most widely used molecule in the benzophenone group of UV absorbers. It is known that the UV absorption ability is dependent on the substituents. Numerous studies have shown that the strength of intramolecular hydrogen bonds is the main factor affecting this type of UV absorber. However, the effect of substituents on the formation and nature of the hydrogen bonds has not been well studied. In this work, the effect of the type of substituent and the substitution position on the absorption intensity of 2,4-dihydroxybenzophenone molecules is verified both experimentally and theoretically. The effect of substituents on the intramolecular hydrogen bonding of 2,4-dihydroxybenzophenone was investigated by DFT calculations. The results indicate that the addition of different substituents leads to various changes in the strength of the hydrogen bonding in 2,4-dihydroxybenzophenone. On the X-substitution site or the Y-substitution site, halogen groups and electron-absorbing groups such as -CN and -NO2 increase the strength of the hydrogen bond, while electron-giving groups such as -N(CH3)2 and -OCH3 decrease the strength of the bond. For the same substituent, the one at the Y site has a higher effect on hydrogen bonding than that at the X site. By NBO analysis, it was found that the substituents would cause charge redistribution of the individual atoms of 2,4-dihydroxybenzophenones, thus affecting the formation and strength of the hydrogen bonds. Moreover, when the substituent is at the Y substitution site, the oxygen atom of the carbonyl group is less able to absorb electrons and more charge is attracted to the oxygen atom of the hydroxyl group, resulting in a larger charge difference between the two oxygen atoms and an increase of bond energy. Finally, a multiple linear regression analysis of the NPA charge number of the atoms involved in the formation of the hydrogen-bonded chelated six-membered ring was performed with the energy of the hydrogen bond and the percentage of influencing factors estimated, which were found to jointly affect the strength of hydrogen bonding. The aim of this study is to provide theoretical guidance for the design of benzophenone-based UV absorbers that absorb UV light of specific wavelength bands.

Impact of ultraviolet-absorbing 2-hydroxy-4-quaternaryammoniumalkoxy benzophenone motif on photodegradation of disulfoton: a case study.

Pesticide deposits post-treatment and before diffusing inside the plants are exposed to sunlight. Many of them degrade into a variety of photoproducts that may be harmful to living beings through accidental ingestion. The addition of ultraviolet light absorbers to the pesticide formulations is an attractive strategy to prevent photodegradation of the pesticides. Water-soluble quaternary ammonium ultraviolet light absorbers (QAUVAs) were synthesized from 2,4-dihydroxy benzophenones (BP-1) and their structures were confirmed by 1H NMR, 13C NMR, UV, and FTIR. A cost-saving approach for the photoprotection of disulfoton insecticide using these QAUVAs is presented. All the four QAUVAs exhibit excellent UV screening effect. The insecticide disulfoton was recovered in much higher amounts (22.27 ~ 25.64% higher than control) when it was irradiated in the presence of QAUVAs in comparison with the amount of recovery of pesticide exposed in absence of them.

Effective degradation of 2,4-dihydroxybenzophenone by zero-valent iron powder (Fe0)-activated persulfate in aqueous solution: Kinetic study, product identification and theoretical calculations.

2,4-Dihydroxybenzophenone (BP-1), a typically known derivative of the benzophenone-type UV filter, has been frequently detected in aqueous environments and poses a potential risk to human health and the entire ecosystem. In this study, an effective advanced oxidation technique using zero-valent iron powder (Fe0)-activated persulfate (PS) was used for the degradation of BP-1. The effects of several experimental parameters, including Fe0 dosages, PS dosages, pH, and common natural water constituents, were systematically investigated. The BP-1 degradation efficiency was enhanced by increasing the Fe0 and PS dosages and decreasing the solution pH. The presence of different concentrations of humic acid (HA) could inhibit BP-1 removal, while the addition of various cations and anions had different effects on the degradation. Moreover, the degradation of BP-1 in five water matrices was also compared, and the removal rates followed the order of ultrapure water > tap water > secondary clarifier effluent > river water > synthetic water. Thirteen oxidation products were identified by liquid chromatography-time-of-flight-mass spectrometry (LC-TOF-MS) analysis, and five possible degradation pathways were proposed. The addition reactions initiated by HO and SO4-, as well as single-electron coupling reactions and ring-closing reactions, were further supported by density functional theory (DFT) calculations. Assessment of toxicity of intermediates of the oxidation of BP-1 suggested decreased toxicity from the parent contaminant. The present work illustrates that BP-1 could be efficiently degraded in the Fe0/PS system, which may provide new insights into the removal of benzophenones in water and wastewater.

Wastewater-based epidemiology to assess human exposure to personal care and household products - A review of biomarkers, analytical methods, and applications.

Humans are nowadays exposed to numerous chemicals in our day-to-day life, including parabens, UV filters, phosphorous flame retardants/plasticizers, bisphenols, phthalates and alternative plasticizers, which can have different adverse effects to human health. Estimating human's exposure to these potentially harmful substances is, therefore, of paramount importance. Human biomonitoring (HBM) is the existing approach to assess exposure to environmental contaminants, which relies on the analysis of specific human biomarkers (parent compounds and/or their metabolic products) in biological matrices from individuals. The main drawback is its implementation, which involves complex cohort studies. A novel approach, wastewater-based epidemiology (WBE), involves estimating exposure from the analysis of biomarkers in sewage (a pooled urine and feces sample of an entire population). One of the key challenges of WBE is the selection of biomarkers which are specific to human metabolism, excreted in sufficient amounts, and stable in sewage. So far, literature data on potential biomarkers for estimating exposure to these chemicals are scattered over numerous pharmacokinetic and HBM studies. Hence, this review provides a list of potential biomarkers of exposure to more than 30 widely used chemicals and report on their urinary excretion rates. Furthermore, the potential and challenges of WBE in this particular field is discussed through the review of pioneer WBE studies, which for the first time explored applicability of this novel approach to assess human exposure to environmental contaminants. In the future, WBE could be potentially applied as an "early warning system", which could promptly identify communities with the highest exposure to environmental contaminants.

Formation of novel disinfection by-products chlorinated benzoquinone, phenyl benzoquinones and polycyclic aromatic hydrocarbons during chlorination treatment on UV filter 2,4-dihydroxybenzophenone in swimming pool water.

2,4-Dihydroxybenzophenone (BP-1) is an important component and metabolite of benzophenone-type (BPs) UV filters, it is widely used in commercial products and frequently detected in environmental media and organism samples. The transformation characteristics and genotoxicity changes of BP-1 during chlorination disinfection process were explored. Nineteen transformation products were separated and tentatively identified, eleven of which were not previously reported. Most importantly, nine novel by-products including one chlorobenzoquinone, four phenyl benzoquinones, and four polycyclic aromatic hydrocarbons were formed during BP-1 chlorination. Plausible transformation pathways for BP-1 during chlorination treatment were proposed, in which chlorination substitution, Baeyer-Villiger oxidation, hydrolysis, and CC coupling reactions were involved. The CC coupling reaction is firstly observed in chlorination disinfection system. Higher pH values and chlorine doses would be a benefit for BP-1 transformation. The genotoxicity of the reaction mixture increased significantly with increasing chlorine dose under acid and neutral conditions due to the formation of benzoquinones and polycyclic aromatic hydrocarbons. It was noted that BP-1 and its chlorinated products were found in swimming pool water samples. This work inferred that BP-1 and its analogs are transformed during the chlorination disinfection process and may cause potential ecological and health risks.

Disparate effects of DOM extracted from coastal seawaters and freshwaters on photodegradation of 2,4-Dihydroxybenzophenone.

Dissolved organic matter (DOM) plays an important role in degradation of organic pollutants by photochemically-produced reactive intermediates (RIs), such as excited triplet-states of DOM (3DOM*), singlet oxygen (1O2) and hydroxyl radical (·OH). However, it is not clear whether DOM extracted from coastal seawaters (CS-DOM) and DOM derived from freshwaters (FW-DOM) exhibit similar effects on photodegradation of organic micropollutants. Herein, 2,4-dihydroxybenzophenone (BP-1) was adopted as a model compound to probe the effects of different DOM on photodegradation kinetics of organic micropollutants. Results show that the CS-DOM promotes the photodegradation of BP-1 mainly via the pathway involving 3DOM*; while 3DOM*, 1O2 and ·OH are responsible for BP-1 photodegradation in the presence of the FW-DOM. Compared with the FW-DOM, the CS-DOM undergoes more photobleaching, and contains less aromatic C=C and C=O functional groups. Although 3DOM* formation quantum yields for the CS-DOM are relatively higher than those for the FW-DOM, the CS-DOM has lower rates of light absorption, leading to lower steady-state RI concentrations for the CS-DOM. BP-1 photodegradation in the presence of the CS-DOM is faster than in the presence of the FW-DOM, due to higher second-order reaction rate constants between BP-1 and CS-3DOM* and fewer antioxidants contained in the CS-DOM.

Simultaneous determination of cosmetics ingredients in nail products by fast gas chromatography with tandem mass spectrometry.

A rapid and sensitive gas chromatography with tandem mass spectrometry (GC-MS/MS) method has been developed and validated to quantitatively determine cosmetic ingredients, such as toluene, N-methylpyrrolidone, 2,4-dihydroxybenzophenone (benzophenone-1, BP-1), and diethylene glycol dimethacrylate, in nail products. In this procedure, test portions were extracted with acetone, followed by vortexing, sonication, centrifugation, and filtration. During the extraction procedure, BP-1 was derivatized making it amenable to GC-MS analysis, using N,O-​bis(trimethylsilyl)​trifluoroacetamide. The four ingredients were quantified by GC-MS/MS in an electron ionization mode. Four corresponding stable isotopically labeled analogues were selected as internal standards, which were added at the beginning of the sample preparation to correct for recoveries and matrix effects. The validated method was used to screen 34 commercial nail products for these four cosmetic ingredients. The most common ingredients detected in the nail products were toluene and BP-1. Toluene was detected in 26 products and ranged from 1.36 to 173,000µg/g. BP-1 ranged from 18.3 to 2,370µg/g in 10 products.

A novel dispersive solid-phase extraction method using metal-organic framework MIL-101 as the adsorbent for the analysis of benzophenones in toner.

Metal-organic frameworks (MOFs) have been paid widespread attention in the field of adsorption and separation materials due to its porosity, large specific surface area, unsaturated metal-ligand sites and structural diversity. In this study, the green powder MIL-101 was synthesized and used for the extraction of benzophenone, 2,4-dihydroxybenzophenone and 2-hydroxy-4-methoxy-benzophenone from toner samples for the first time. The synthesized MIL-101 was characterized by X-ray diffraction, scanning electron microscopy, thermogravimetry and nitrogen adsorption porosimetry. The MIL-101 was applied as the dispersive solid phase extraction (DSPE) adsorbent for the extraction and preconcentration of benzophenone, 2,4-dihydroxybenzophenone and 2-hydroxy-4-methoxy-benzophenone from toner samples. The extraction conditions were investigated. Under the optimized conditions, a DSPE-HPLC method for the determination of benzophenone, 2,4-dihydroxybenzophenone and 2-hydroxy-4-methoxy-benzophenone was developed. The method yielded a linear calibration curve in the concentration ranges from 4.0 to 3500 µg L(-1) for the three analytes in toner samples with regression coefficients (r(2)) of 0.9992, 0.9999 and 0.9990, respectively. Limits of detection were 1.2, 1.2 and 0.9 µg L(-1), respectively. Both the intra-day and inter-day precisions (RSDs) were <10%.

Widespread occurrence of bisphenol A diglycidyl ethers, p-hydroxybenzoic acid esters (parabens), benzophenone type-UV filters, triclosan, and triclocarban in human urine from Athens, Greece.

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 µg/kg bw/day for Σ5BADGEs to 31.4 µg/kg bw/day for Σ6Parabens.

Protective effects of 2,4-dihydroxybenzophenone against acetaminophen-induced hepatotoxicity in mice.

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

Solid-phase extraction and reverse-phase HPLC: application to study the urinary excretion pattern of benzophenone-3 and its metabolite 2,4-dihydroxybenzophenone in human urine.

BACKGROUND: Benzophenone-3 (BZ-3) is a common ultraviolet (UV) absorbing compound in sunscreens. It is the most bioavailable species of all UV-absorbing compounds after topical application and can be found in plasma and urine. OBJECTIVES: The aim of this study was to develop a reverse-phase high performance liquid chromatography (HPLC) method for determining the amounts BZ-3 and its metabolite 2,4-dihydroxybenzophenone (DHB) in human urine. The method had to be suitable for handling a large number of samples. It also had to be rapid and simple, but still sensitive, accurate and reproducible. The assay was applied to study the urinary excretion pattern after repeated whole-body applications of a commercial sunscreen, containing 4% BZ-3, to 25 healthy volunteers. METHODS: Each sample was analyzed with regard to both conjugated/non-conjugated BZ-3 and conjugated/non-conjugated DHB, since both BZ-3 and DHB are extensively conjugated in the body. Solid-phase extraction (SPE) with C8 columns was followed by reverse-phase HPLC. For separation a Genesis C18 column was used with an acethonitrile-water mobile phase and the UV-detector was set at 287 nm. RESULTS: The assay was linear r(2) > 0.99, with detection limits for BZ-3 and DHB of 0.01 micromol L(-1) and 0.16 micromol L(-1) respectively. Relative standard deviation (RSD) was less than 10% for BZ-3 and less than 13% for DHB. The excretion pattern varied among the human volunteers; we discerned different patterns among the individuals. CONCLUSIONS: The reverse-phase HPLC assay and extraction procedures developed are suitable for use when a large number of samples need to be analyzed and the method fulfilled our objectives. The differences in excretion pattern may be due to differences in enzyme activity but further studies, especially about genetic polymorphism, need to be performed to verify this finding.