Oxybenzone

Oxybenzone is an organic sunscreen that primarily absorbs the sun's UVB rays. Apart from skin care products, it is also used in shampoos, hair sprays and hair dyes to prevent the fading of artificial hair colour caused by sunlight.

Effects


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments

D

Photoprotection

Moderate

Absorbs in the entire UVB spectrum but only part of the UVA spectrum. Does not protect against UV-induced DNA damage or immunosuppression.

Looking to buy skin care products containing Oxybenzone?

Buy from Amazon.com.

Scientific Research


Caution: Please read wisderm.com's medical disclaimer.

Table of contents:

1. Sources

1.1 In nature

Oxybenzone, also known as benzophenone-3, occurs naturally in flower pigments.[1] It is a UV filter that was first approved by the FDA in the early 1980s.[2]

1.1 In personal care products

Oxybenzone is very commonly used in personal care products. Surveys of 114 and 117 such products collected from the United States and China found it in 81% of the samples analyzed, at concentrations up to 0.148%. The highest levels were in skin lotions (including sunscreen lotions), followed by makeup products. Personal care products collected from the US contained higher concentrations of oxybenzone than those collected from China.[3]

Oxybenzone may also exist in hair care products, as it has the ability to protect against hair damage caused by sunlight and to attenuate the fading of artificial hair colour through UV absorption.[4][5]

1.2 In aquatic environments

Oxybenzone washed from the skin during recreational water activities and bathing can directly or indirectly (through wastewater treatment plant effluents) pollute aquatic environments.[6] It has been detected in Spanish coastal waters[7][8] and river waters,[9] seawater from Italy,[10] river water from Switzerland,[11] surface waters from Japan[12] and recreational waters from Slovenia.[13] It has also been recovered from marine sediment extracts from the Southern California Bight in the US.[14]

Fortunately, oxybenzone can undergo photodegradation by direct photolysis and by reacting with hydroxyl radicals and the triplet states of chromophoric dissolved organic matter, leading to a predicted half-life of several weeks under summertime conditions in Italian surface waters.[15] The white rot fungus Trametes versicolor can also efficiently remove oxybenzone by more than 99% in less than 24 hours.[16]

1.3 In food and water

Oxybenzone present in aquatic environments can end up in tap water as well as bio-accumulate in fish, as has been shown in Spain.[17][18] Oxybenzone has also been used as an ultraviolet stabilizer in plastic surface coatings for food packaging, to prevent photodegradation.[19]

2. Exposure

Human exposure to oxybenzone is prevalent. A 2003-2004 survey of US residents found oxybenzone in 96.8% of the 2,517 urine samples, at a mean concentration of 22.9 µg/L. Females had significantly higher mean concentrations of oxybenzone compared to males, probably because women and girls use more sunscreens and personal care products. Mean concentrations also varied among the different ethnic groups. Non-Hispanic whites appeared to be more highly exposed than Mexican Americans and non-Hispanic blacks, which was thought to be a result of increased sunscreen use among people with lighter skin pigmentation.[20][21] The latter finding was similar to that in a previous study on US girls aged 6-8 years, which found that whites had higher mean concentrations of oxybenzone than Hispanics and blacks.[22] Serum and urine burdens of oxybenzone are also higher in individuals of higher socioeconomic status in the US.[23]

Oxybenzone was also detected in the majority of urine samples from Danish men, women and children,[24][25][26][27] in urine samples from the Belgian population,[28][29] and in both urine and semen samples from Spain.[30] Interestingly, there was no significant difference in oxybenzone concentrations between males and females in Belgium, but Belgian adolescents had significantly higher oxybenzone levels than adults, which could not be reasonably explained. Measured oxybenzone concentrations were markedly lower in Denmark, Belgium and Spain than in the US, which was considered a reflection of the more frequent inclusion of oxybenzone in sunscreen products in North America.[28]

Urinary concentrations of oxybenzone is also lower in children and adults in China than those in the US.[31] Chinese women appear to be more exposed to oxybenzone than Chinese men.[32]

Fetuses may also be exposed to oxybenzone, since urine samples from pregnant women in the US, Puerto Rico, Spain, France and China have been shown to contain oxybenzone.[33][34][35][36][37] In fact, oxybenzone was present at detectable levels in 61% of the amniotic fluid samples analyzed in a study of 97 pregnant women.[38]

3. Skin penetration

Oxybenzone is absorbed into the skin following dermal exposure, as shown by experiments on rat and pig skins.[39][40][41][42][43]

In vitro studies on human epidermal membranes indicate that oxybenzone can pass into and through the skin in significant amounts, more so than other chemical sunscreens like octinoxate, octocrylene, octisalate, avobenzone and padimate O.[44][45] When oxybenzone was applied to the inner forearm of human volunteers, 4% of the dose was found in the stratum corneum after 30 minutes, and nearly 35% was absorbed by the skin after 4 hours under occlusion.[46]

In vivo studies have also confirmed the transdermal absorption of oxybenzone, showing its appearance in human plasma and urine following dermal exposure.[47][48][49][50] A single application led to up to 0.4% to 2% of the applied dose detected in urine,[48][49][50] but repeated whole-body applications can cause accumulation.[51][52]

The effect of UV irradiation on the cutaneous absorption of oxybenzone is inconsistent -- one study found no significant difference between irradiated and un-irradiated skin,[51] another found that simulated solar radiation decreased the diffusion through pig skin but did not affect the total absorbed dose,[53] and a third found that both UVA and UVB enhanced oxybenzone flux and skin uptake.[54]

Although percutaneous absorption of oxybenzone does not seem to increase in intrinsically or extrinsically aged skin,[54] absorption varies depending on the anatomical site and is higher for facial skin compared to the skin of the back.[55] Laser skin resurfacing can increase the skin deposition of oxybenzone by several-fold, as it reduces the barrier function of the skin.[56]

Percutaneous absorption involves 2 processes, the release of the solute from its vehicle to the skin followed by the permeation of the solute through the skin. Both processes can potentially be modulated by the formulation vehicle through vehicle-solute and vehicle-skin interactions. Vehicle-solute interactions influence the rate and extent of solute release from the vehicle. For example, an oil-in-water emulsion where oxybenzone is likely to exist in the internal phase, should exhibit a slower release rate than a water-in-oil emulsion, where oxybenzone is in the external phase. A vehicle for which oxybenzone has high affinity, such as coconut oil, will also show a slower release.[55] Vehicle-skin interactions on the other hand result in penetration enhancement or retardation. Ethanol, for instance, is thought to enhance penetration by extraction of stratum corneum lipids.[55] Polyethylene glycol 400 has the potential to increase the vehicle-skin partitioning of oxybenzone and therefore its dermal absorption.[57] The inclusion of propylene glycol[58] or thickening agents that increase the viscosity of formulations may also promote the penetration of oxybenzone.[59]

For single phase solvents, it has been reported that oxybenzone penetration can be minimized by choosing vehicles with a vehicle solubility parameter substantially different from the solubility parameter of the membrane.[60] A comparison of 5 different vehicles found that a mixed ethanol:oil-based formulation, which is used for some commercial sunscreen spray formulations, led to significantly higher retention of oxybenzone in the epidermis.[55] Other studies show that oxybenzone is better retained in the upper layers of the skin when formulated in an emulsion gel than when formulated in petrolatum.[61][62]

Encapsulating oxybenzone within solid lipid microspheres or microparticles,[63] nanoparticles,[64][65][66][67][68] and nanocapsules[69] is another viable strategy to decrease the penetration of oxybenzone in the skin and avoid systemic absorption, as is cyclodextrin complexation,[70][71][72] though there are exceptions.[70][73]

Oxybenzone that is systemically absorbed is metabolized by the body[31][74] and conjugated to make it water-soluble before excretion in the urine.[48][75]

3. Effects on the skin

3.1 Photoprotection

Oxybenzone's absorption profile spans from 270 to 350 nm, with absorption peaks at 288 and 350 nm.[2] This encompasses the entire UVB spectrum but only part of the UVA spectrum,[76] which explains why oxybenzone provides relatively weak UVA protection compared to avobenzone.[77][78] In a comparison of 18 sun filters all at the highest concentration allowed by European legislation, oxybenzone also had one of the lowest efficacies.[79]

Alone, oxybenzone can diminish the UV-induced formation of sunburn cells, physical damage to the skin structure[80] and inflammation,[81][82] but it is unable to inhibit thymine dimer formation or immunosupression.[83][84] Combinations of oxybenzone with other UV filters can be effective in preventing DNA damage, inflammation and immunosuppression caused by UV radiation.[85][86][87] However, a sunscreen containing oxybenzone, octinoxate and octisalate could not completely protect the skin against UV-induced oxidative stress parameters such as glutathione depletion and matrix metalloproteinase-9 (MMP-9) secretion,[88] and sunscreens containing octinoxate, padimate O and oxybenzone failed to protect against the UV-induced increase in melanoma incidence in mice.[89]

The photoprotective effect of oxybenzone can be enhanced by the choice of an appropriate vehicle, such as an emulsion-gel that helps retain oxybenzone in the superficial skin layers,[62][61] by encapsulation within nanoparticles or nanocapsules that can scatter or reflect UV radiation,[90][91][92][67][68][93][66][94] by complexation with cyclodextrins,[80][71] by loading onto microspheres, microparticles or liposomes,[95][96][97] by adsorption on a mesoporous silica drug carrier,[98] and by the addition of antioxidants such as vitamin C, vitamin E and melatonin.[99][100]

It is noteworthy that the oxybenzone in some commercial sunscreens may be prone to recrystallization after being applied to the skin, which may interfere with its UV-light absorbing function.[101] Exposing oxybenzone to chlorine, a disinfectant in swimming pools, also leads to the loss of UV protection.[102]

3.2 Prevent photoaging

The major histopathologic change in the dermis of photoaged skin is the accumulation of massive amounts of abnormal elastic tissue, termed solar elastosis. In mice, a SPF 15 sunscreen containing oxybenzone and octinoxate inhibited elastin gene induction by 57% in response to PUVA treatment, an indication of protection against photoaging.[103] It is not clear however whether oxybenzone alone has this effect.

4. Stability

Although it has been proposed that oxybenzone is rapidly photo-oxidized to its semiquinone following UV irradiation,[104][105] this claim contradicted other published stability data[106] and has been contested, with other groups showing that oxybenzone is actually quite photostable.[107][108]

In fact, oxybenzone can stabilize the UVA filter avobenzone,[109] retinol,[110] and the topical corticoid desonide.[111] It does undergo significant photodegradation in the presence of the physical sunscreen titanium dioxide,[112] but its stability can be improved via combination with octocrylene[113] or by encapsulation.[93][92]

5. Safety

Oxybenzone is approved by both the US FDA (up to 6%[114]) and the EU Cosmetics Directive (up to 10%[115]) as an active ingredient in sunscreens.

5.1 Cytotoxicity

Oxybenzone can inhibit cell growth and retarded cell cycle progression in cultured human cells.[116] Chlorinated oxybenzone has also been shown to induce increased cell death.[102] Nevertheless, these in vitro effects may not necessarily be relevant in vivo, as one study has found that the concentration of oxybenzone that penetrates to the viable epidermis of human skin is several times lower than those that cause toxicity in cultured human keratinocytes.[44] There is also evidence to suggest that the cytotoxicity and phototoxicity of oxybenzone can be reduced by nanoencapsulation.[68][73][117]

5.2 Pro-oxidant action

Topically applied oxybenzone leads to an increased production of reactive oxygen species under UV illumination[118] and also appears to decrease the activity of the antioxidant enzyme superoxide dismutase.[119] It has been suggested that the UV photo-oxidation of oxybenzone deactivates thioredoxin reductase, a central component of the thioredoxin system that is an important antioxidant defense.[104][105] Fortunately, its inclusion in cyclodextrin complexes can markedly inhibit the formation of free radicals on exposure to UV light.[120]

5.3 Contact allergy and contact dermatitis

While true photoallergic reactions to sunscreens is considered rare,[121] oxybenzone is among the most common elicitors,[122][123][124] as demonstrated by photopatch testing results from North America,[125][126][127] Europe,[128][129][130][131][132][133][134][135][136][137][138] and the Asia-Pacific.[139][140][141] This may be due to its tendency to react with free amino acids or peptides of the human skin.[142]

There are well over a dozen reports in the medical literature describing contact allergies and contact dermatitis to oxybenzone,[143][144][145][146][147][148][149][150][151][152][153][154][155][156][157] including a few cases relating to skin eruptions,[158][159][160] cheilitis[161][162][163] and anaphylaxis.[164][165][166] This is very likely because of its popularity as a sunscreen ingredient, as data from human repeat insult patch tests and photoallergy studies indicate that the mean rate of contact allergy to oxybenzone is just 0.07%.[167]

Encapsulating oxybenzone in zeolite or incorporating it lipid nanoparticles can help overcome its skin irritancy problems.[91][90][168]

5.4 Genotoxicity

Oxybenzone was weakly mutagenic in Salmonella studies and induced sister-chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells in the presence of a metabolic activation system.[1] However, results from a Drosophila somatic mutation and recombination test (SMART) and an in vivo cytogenetic assay in rat bone marrow cells were both negative, supporting the conclusion that oxybenzone is not genotoxic in vivo.[169]

5.5 Reproductive toxicity

Male rodents exposed to oxybenzone orally or dermally sometimes have altered reproductive parameters such as reduced epididymal sperm densities,[1] but not always.[170][171] A case-control study of 877 idiopathic infertile men and 713 fertile controls did not find a relationship between exposure to oxybenzone and idiopathic male infertility.[172]

In Japanese medaka reproduction assays, female Japanese medaka exposed to µg/L levels of oxybenzone had significantly lower hatching success, indicating that oxybenzone can alter reproduction endpoints in fish.[173][174]

Importantly, oxybenzone has been detected in human placental tissue samples,[175] suggesting that prenatal exposure does occur. Higher maternal urinary concentrations of oxybenzone has been linked to decreased birth weight in girls, increased birth weight in boys and increased head circumference at birth.[36][176]

5.6 Potential endocrine disruptor

Oxybenzone exerts uterotrophic effects in rats.[177][178] It has also been shown to induce vitellogenin production[173] and to alter the expression of various endocrine genes in fish.[174][179] There have even been studies demonstrating the endocrine activities of oxybenzone on the insect Chironomus riparius, a reference organism in aquatic toxicology.[180][181]

Specifically, oxybenzone appears to be a partial agonist towards estrogen receptors, and an antagonist towards androgen and progesterone receptors,[182][183][184] though one study in 2005 concluded that oxybenzone was not estrogenic at a concentration of 100 µm.[185]

In addition, there is evidence that oxybenzone or its metabolites stimulate proliferation of human breast cancer cells,[177][186] providing further support of its estrogenic activity. Oxybenzone exposure was not significantly associated with age of menarche in adolescent girls however.[187]

When creams containing 10% each of oxybenzone, octinoxate and 4-methylbenzylidene camphor (4-MBC) were applied to the whole bodies of 15 young men and 17 post-menopausal women, there were no biologically significant effects on thyroid hormone levels, indicating that the concentrations of the sunscreens absorbed were not sufficient to disturb the homeostasis of thyroid hormones in adult humans.[188]

5.7 Alters absorption of herbicides and insect repellents

Oxybenzone can act as a dermal penetration enhancer, with 0.6% oxybenzone significantly increasing the total peentration of a moderately lipophilic herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D).[189] Moreover, oxybenzone and the insect repellent N,N-diethyl-m-toluamide (DEET) show a synergistic permeation enhancement when applied concurrently.[190][191][192][193][194][195][196][197]

Since the simultaneous application of oxybenzone and the insect repellent picaridin has the opposite effect (supression of the transdermal penetration of both compounds), it has been suggested that picaridin would be a better candidate for concurrent use with sunscreen preparations in terms of minimizing percutaneous permeation of the chemicals.[198][199]

Scientific References


  1. French JE. NTP Technical Report on Toxicity Studies of 2-Hydroxy-4-methoxybenzophenone Administered Topically and in Dosed Feed to F344/N Rats and B6C3F1 Mice. National Toxicology Program. (1992)
  2. Burnett ME, Wang SQ. Current sunscreen controversies: a critical review. Photodermatol Photoimmunol Photomed. (2011)
  3. Liao C, Kannan K. Widespread occurrence of benzophenone-type UV light filters in personal care products from China and the United States: an assessment of human exposure. Environ Sci Technol. (2014)
  4. Bernhardt P, et. al. UV filters for hair protection. Int J Cosmet Sci. (1993)
  5. Locke B, Jachowicz J. Fading of artificial hair colour and its prevention by photofilters. Int J Cosmet Sci. (2006)
  6. Kim S, Choi K. Occurrences, toxicities, and ecological risks of benzophenone-3, a common component of organic sunscreen products: A mini-review. Environ Int. (2014)
  7. Paredes E, et. al. Ecotoxicological evaluation of four UV filters using marine organisms from different trophic levels Isochrysis galbana, Mytilus galloprovincialis, Paracentrotus lividus, and Siriella armata. Chemosphere. (2014)
  8. Tovar-Sánchez A, et. al. Sunscreen products as emerging pollutants to coastal waters. PLOS ONE. (2013)
  9. Pedrouzo M, et. al. Stir-bar-sorptive extraction and ultra-high-performance liquid chromatography-tandem mass spectrometry for simultaneous analysis of UV filters and antimicrobial agents in water samples. Anal Bioanal Chem. (2010)
  10. Nguyen KT, et. al. Rapid and selective determination of UV filters in seawater by liquid chromatography-tandem mass spectrometry combined with stir bar sorptive extraction. Talanta. (2011)
  11. Fent K, Zenker A, Rapp M. Widespread occurrence of estrogenic UV-filters in aquatic ecosystems in Switzerland. Environ Pollut. (2010)
  12. Kameda Y, Kimura K, Miyazaki M. Occurrence and profiles of organic sun-blocking agents in surface waters and sediments in Japanese rivers and lakes. Environ Pollut. (2011)
  13. Cuderman P, Heath E. Determination of UV filters and antimicrobial agents in environmental water samples. Anal Bioanal Chem. (2007)
  14. Schlenk D, et. al. vivo bioassay-guided fractionation of marine sediment extracts from the Southern California Bight, USA, for estrogenic activity. Environ Toxicol Chem. (2005)
  15. Vione D, et. al. Phototransformation of the sunlight filter benzophenone-3 (2-hydroxy-4-methoxybenzophenone) under conditions relevant to surface waters. Sci Total Environ. (2013)
  16. Gago-Ferrero P, et. al. Evaluation of fungal- and photo-degradation as potential treatments for the removal of sunscreens BP3 and BP1. Sci Total Environ. (2012)
  17. Gago-Ferrero P, Díaz-Cruz MS, Barceló D. Multi-residue method for trace level determination of UV filters in fish based on pressurized liquid extraction and liquid chromatography-quadrupole-linear ion trap-mass spectrometry. J Chromatogr A. (2013)
  18. Díaz-Cruz MS, et. al. Analysis of UV filters in tap water and other clean waters in Spain. Anal Bioanal Chem. (2012)
  19. Suzuki T, et. al. Estrogenic and antiandrogenic activities of 17 benzophenone derivatives used as UV stabilizers and sunscreens. Toxicol Appl Pharmacol. (2005)
  20. Calafat AM, et. al. Concentrations of the sunscreen agent benzophenone-3 in residents of the United States: National Health and Nutrition Examination Survey 2003--2004. Environ Health Perspect. (2008)
  21. Tibbetts J. Shining a light on BP-3 exposure. Environ Health Perspect. (2008)
  22. Wolff MS, et. al. Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls. Environ Health Perspect. (2007)
  23. Tyrrell J, et. al. Associations between socioeconomic status and environmental toxicant concentrations in adults in the USA: NHANES 2001-2010. Environ Int. (2013)
  24. Lassen TH, et. al. Temporal variability in urinary excretion of bisphenol A and seven other phenols in spot, morning, and 24-h urine samples. Environ Res. (2013)
  25. Frederiksen H, et. al. Bisphenol A and other phenols in urine from Danish children and adolescents analyzed by isotope diluted TurboFlow-LC-MS/MS. Int J Hyg Environ Health. (2013)
  26. Frederiksen H, et. al. Urinary excretion of phthalate metabolites, phenols and parabens in rural and urban Danish mother-child pairs. Int J Hyg Environ Health. (2013)
  27. Frederiksen H, et. al. Human urinary excretion of non-persistent environmental chemicals: an overview of Danish data collected between 2006 and 2012. Reproduction. (2014)
  28. Dewalque L, Pirard C, Charlier C. Measurement of urinary biomarkers of parabens, benzophenone-3, and phthalates in a Belgian population. Biomed Res Int. (2014)
  29. Dewalque L, et. al. Simultaneous determination of some phthalate metabolites, parabens and benzophenone-3 in urine by ultra high pressure liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. (2014)
  30. León Z, et. al. Solid-phase extraction liquid chromatography-tandem mass spectrometry analytical method for the determination of 2-hydroxy-4-methoxybenzophenone and its metabolites in both human urine and semen. Anal Bioanal Chem. (2010)
  31. Wang L, Kannan K. Characteristic profiles of benzonphenone-3 and its derivatives in urine of children and adults from the United States and China. Environ Sci Technol. (2013)
  32. Engel LS, et. al. Predictors and variability of repeat measurements of urinary phenols and parabens in a cohort of shanghai women and men. Environ Health Perspect. (2014)
  33. Mortensen ME, et. al. Urinary concentrations of environmental phenols in pregnant women in a pilot study of the National Children's Study. Environ Res. (2014)
  34. Meeker JD, et. al. Distribution, variability, and predictors of urinary concentrations of phenols and parabens among pregnant women in Puerto Rico. Environ Sci Technol. (2013)
  35. Casas L, et. al. Urinary concentrations of phthalates and phenols in a population of Spanish pregnant women and children. Environ Int. (2011)
  36. Philippat C, et. al. Exposure to phthalates and phenols during pregnancy and offspring size at birth. Environ Health Perspect. (2012)
  37. Tang R, et. al. Associations of prenatal exposure to phenols with birth outcomes. Environ Pollut. (2013)
  38. Philippat C, et. al. Prenatal exposure to environmental phenols: concentrations in amniotic fluid and variability in urinary concentrations during pregnancy. Environ Health Perspect. (2013)
  39. el Dareer SM, et. al. Disposition of 2-hydroxy-4-methoxybenzophenone in rats dosed orally, intravenously, or topically. J Toxicol Environ Health. (1986)
  40. Okereke CS, Abdel-Rhaman MS, Friedman MA. Disposition of benzophenone-3 after dermal administration in male rats. Toxicol Lett. (1994)
  41. Gupta VK, Zatz JL, Rerek M. Percutaneous absorption of sunscreens through micro-yucatan pig skin in vitro. Pharm Res. (1999)
  42. Fernandez C, et. al. LC analysis of benzophenone-3 in pigskin and in saline solution: application to determination of in vitro skin penetration. J Pharm Biomed Anal. (2000)
  43. Padula C, Campana N, Santi P. Simultaneous determination of benzophenone-3, retinol and retinyl acetate in pig ear skin layers by high-performance liquid chromatography. Biomed Chromatogr. (2008)
  44. Hayden CG, et. al. Sunscreen penetration of human skin and related keratinocyte toxicity after topical application. Skin Pharmacol Physiol. (2005)
  45. Jiang R, et. al. Absorption of sunscreens across human skin: an evaluation of commercial products for children and adults. Br J Clin Pharmacol. (1999)
  46. Fernandez C, et. al. Benzophenone-3: rapid prediction and evaluation using non-invasive methods of in vivo human penetration. J Pharm Biomed Anal. (2002)
  47. Hayden CG, Roberts MS, Benson HA. Systemic absorption of sunscreen after topical application. Lancet. (1997)
  48. Gustavsson Gonzalez H, Farbrot A, Larkö O. Percutaneous absorption of benzophenone-3, a common component of topical sunscreens. Clin Exp Dermatol. (2002)
  49. Sarveiya V, Risk S, Benson HA. Liquid chromatographic assay for common sunscreen agents: application to in vivo assessment of skin penetration and systemic absorption in human volunteers. J Chromatogr B Analyt Technol Biomed Life Sci. (2004)
  50. Janjua NR, et. al. Systemic absorption of the sunscreens benzophenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzylidene) camphor after whole-body topical application and reproductive hormone levels in humans. J Invest Dermatol. (2004)
  51. Gonzalez H, et. al. Percutaneous absorption of the sunscreen benzophenone-3 after repeated whole-body applications, with and without ultraviolet irradiation. Br J Dermatol. (2006)
  52. Janjua NR, et. al. Sunscreens in human plasma and urine after repeated whole-body topical application. J Eur Acad Dermatol Venereol. (2008)
  53. Duracher L, et. al. Irradiation of skin and contrasting effects on absorption of hydrophilic and lipophilic compounds. Photochem Photobiol. (2009)
  54. Hung CF, et. al. The risk of hydroquinone and sunscreen over-absorption via photodamaged skin is not greater in senescent skin as compared to young skin: Nude mouse as an animal model. Int J Pharm. (2014)
  55. Benson HA, et. al. Influence of anatomical site and topical formulation on skin penetration of sunscreens. Ther Clin Risk Manag. (2005)
  56. Lee WR, et. al. Erbium:YAG laser resurfacing increases skin permeability and the risk of excessive absorption of antibiotics and sunscreens: the influence of skin recovery on drug absorption. Toxicol Lett. (2012)
  57. Mbah CJ. The effect of glycerol, propylene glycol and polyethylene glycol 400 on the partition coefficient of benzophenone-3 (oxybenzone). Pharmazie. (2007)
  58. Fernandez C, et. al. LC analysis of benzophenone-3: II application to determination of 'in vitro' and 'in vivo' skin penetration from solvents, coarse and submicron emulsions. J Pharm Biomed Anal. (2000)
  59. Cross SE, et. al. Can increasing the viscosity of formulations be used to reduce the human skin penetration of the sunscreen oxybenzone? J Invest Dermatol. (2001)
  60. Jiang R, et. al. In vitro human epidermal and polyethylene membrane penetration and retention of the sunscreen benzophenone-3 from a range of solvents. Pharm Res. (1998)
  61. Treffel P, Gabard B. Skin penetration and sun protection factor of ultra-violet filters from two vehicles. Pharm Res. (1996)
  62. Chatelain E, Gabard B, Surber C. Skin penetration and sun protection factor of five UV filters: effect of the vehicle. Skin Pharmacol Appl Skin Physiol. (2003)
  63. Mestres JP, et. al. Benzophenone-3 entrapped in solid lipid microspheres: formulation and in vitro skin evaluation. Int J Pharm. (2010)
  64. Wissing SA, Müller RH. Solid lipid nanoparticles as carrier for sunscreens: in vitro release and in vivo skin penetration. J Control Release. (2002)
  65. Luppi B, et. al. Polymeric nanoparticles composed of fatty acids and polyvinylalcohol for topical application of sunscreens. J Pharm Pharmacol. (2004)
  66. Gulbake A, et. al. Solid lipid nanoparticles bearing oxybenzone: in-vitro and in-vivo evaluation. J Microencapsul. (2010)
  67. do Nascimento DF, et. al. Characterization and evaluation of poly(epsilon-caprolactone) nanoparticles containing 2-ethylhexyl-p-methoxycinnamate, octocrylene, and benzophenone-3 in anti-solar preparations. J Nanosci Nanotechnol. (2012)
  68. Marcato PD, et. al. Nanostructured polymer and lipid carriers for sunscreen. Biological effects and skin permeation. J Nanosci Nanotechnol. (2011)
  69. Siqueira NM, et. al. Innovative sunscreen formulation based on benzophenone-3-loaded chitosan-coated polymeric nanocapsules. Skin Pharmacol Physiol. (2011)
  70. Felton LA, Wiley CJ, Godwin DA. Influence of hydroxypropyl-beta-cyclodextrin on the transdermal permeation and skin accumulation of oxybenzone. Drug Dev Ind Pharm. (2002)
  71. Berbicz F, et. al. Use of photoacoustic spectroscopy in the characterization of inclusion complexes of benzophenone-3-hydroxypropyl-β-cyclodextrin and ex vivo evaluation of the percutaneous penetration of sunscreen. Eur J Pharm Biopharm. (2011)
  72. Shokri J, et. al. The effect of Beta-cyclodextrin on percutaneous absorption of commonly used Eusolex® sunscreens. Drug Res (Stuttg). (2013)
  73. Teixeira Z, et. al. Retinyl palmitate polymeric nanocapsules as carriers of bioactives. J Colloid Interface Sci. (2012)
  74. Kamikyouden N, et. al. 2,5-Dihydroxy-4-methoxybenzophenone: a novel major in vitro metabolite of benzophenone-3 formed by rat and human liver microsomes. Xenobiotica. (2013)
  75. Ye X, et. al. Quantification of urinary conjugates of bisphenol A, 2,5-dichlorophenol, and 2-hydroxy-4-methoxybenzophenone in humans by online solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. (2005)
  76. Chew S, DeLeo VA, Harber LC. An animal model for evaluation of topical photoprotection against ultraviolet A (320-380 nm) radiation. J Invest Dermatol. (1987)
  77. Kaidbey K, Gange RW. Comparison of methods for assessing photoprotection against ultraviolet A in vivo. J Am Acad Dermatol. (1987)
  78. Kaidbey KH, Barnes A. Determination of UVA protection factors by means of immediate pigment darkening in normal skin. J Am Acad Dermatol. (1991)
  79. Couteau C, et. al. Study of the efficacy of 18 sun filters authorized in European Union tested in vitro. Pharmazie. (2007)
  80. Felton LA, Wiley CJ, Godwin DA. Influence of cyclodextrin complexation on the in vivo photoprotective effects of oxybenzone. Drug Dev Ind Pharm. (2004)
  81. Couteau C, et. al. UV filters, ingredients with a recognized anti-inflammatory effect. PLOS ONE. (2012)
  82. Couteau C, et. al. The effect of ultraviolet radiation on the anti-inflammatory effect of filters. Int J Pharm. (2013)
  83. McVean M, Liebler DC. Prevention of DNA photodamage by vitamin E compounds and sunscreens: roles of ultraviolet absorbance and cellular uptake. Mol Carcinog. (1999)
  84. Fisher MS, Menter JM, Willis I. Ultraviolet radiation-induced suppression of contact hypersensitivity in relation to padimate O and oxybenzone. J Invest Dermatol. (1989)
  85. Wolf P, Yarosh DB, Kripke ML. Effects of sunscreens and a DNA excision repair enzyme on ultraviolet radiation-induced inflammation, immune suppression, and cyclobutane pyrimidine dimer formation in mice. J Invest Dermatol. (1993)
  86. Whitmore SE, Morison WL. Prevention of UVB-induced immunosuppression in humans by a high sun protection factor sunscreen. Arch Dermatol. (1995)
  87. Wolf P, Donawho CK, Kripke ML. Analysis of the protective effect of different sunscreens on ultraviolet radiation-induced local and systemic suppression of contact hypersensitivity and inflammatory responses in mice. J Invest Dermatol. (1993)
  88. Vilela FM, et. al. Sunscreen protection against ultraviolet-induced oxidative stress: evaluation of reduced glutathione levels, metalloproteinase secretion, and myeloperoxidase activity. Pharmazie. (2013)
  89. Wolf P, Donawho CK, Kripke ML. Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice. J Natl Cancer Inst. (1994)
  90. Sanad RA, et. al. Preparation and characterization of oxybenzone-loaded solid lipid nanoparticles (SLNs) with enhanced safety and sunscreening efficacy: SPF and UVA-PF. Drug Discov Ther. (2010)
  91. Sanad RA, et. al. Formulation of a novel oxybenzone-loaded nanostructured lipid carriers (NLCs). AAPS PharmSciTech. (2010)
  92. Wu PS, et. al. Effects of the novel poly(methyl methacrylate) (PMMA)-encapsulated organic ultraviolet (UV) filters on the UV absorbance and in vitro sun protection factor (SPF). J Photochem Photobiol B. (2014)
  93. Paese K, et. al. Semisolid formulation containing a nanoencapsulated sunscreen: effectiveness, in vitro photostability and immune response. J Biomed Nanotechnol. (2009)
  94. Wissing S, Müller R. The development of an improved carrier system for sunscreen formulations based on crystalline lipid nanoparticles. Int J Pharm. (2002)
  95. Martins RM, et. al. Skin penetration and photoprotection of topical formulations containing benzophenone-3 solid lipid microparticles prepared by the solvent-free spray-congealing technique. J Microencapsul. (2014)
  96. Patel M, et. al. Preparation and characterization of oxybenzone-loaded gelatin microspheres for enhancement of sunscreening efficacy. Drug Deliv. (2006)
  97. Severino P, et. al. Elastic liposomes containing benzophenone-3 for sun protection factor enhancement. Pharm Dev Technol. (2012)
  98. Li CC, et. al. Mesoporous silica aerogel as a drug carrier for the enhancement of the sunscreen ability of benzophenone-3. Colloids Surf B Biointerfaces. (2014)
  99. Darr D, et. al. Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants. Acta Derm Venereol. (1996)
  100. Sierra AF, et. al. In vivo and in vitro evaluation of the use of a newly developed melatonin loaded emulsion combined with UV filters as a protective agent against skin irradiation. J Dermatol Sci. (2013)
  101. Toskić-Radojici MD, et. al. Recrystallization in different sunscreen formulations after cutaneous application. J Cosmet Dermatol. (2004)
  102. Sherwood VF, et. al. Altered UV absorbance and cytotoxicity of chlorinated sunscreen agents. Cutan Ocul Toxicol. (2012)
  103. Takeuchi T, Uitto J, Bernstein EF. A novel in vivo model for evaluating agents that protect against ultraviolet A-induced photoaging. J Invest Dermatol. (1998)
  104. Sundaram C, Köster W, Schallreuter KU. The effect of UV radiation and sun blockers on free radical defence in human and guinea pig epidermis. Arch Dermatol Res. (1990)
  105. Schallreuter KU, et. al. Oxybenzone oxidation following solar irradiation of skin: photoprotection versus antioxidant inactivation. J Invest Dermatol. (1996)
  106. Roscher NM, et. al. Photodecomposition of several compounds commonly used as sunscreen agents. J Photochem Photobiol A. (1994)
  107. Rapp C, Heinsohn G, Hintze U. Raman spectroscopic studies showing the UV stability of oxybenzone. J Invest Dermatol. (1998)
  108. Santoro E. On photo-stability of oxybenzone. J Invest Dermatol. (1998)
  109. Bonda CA. Research pathways to photostable sunscreens. Cosmet Toil. (2008)
  110. Young AM, Gregoriadis G. Photolysis of retinol in liposomes and its protection with tocopherol and oxybenzone. Photochem Photobiol. (1996)
  111. Rosa P, et. al. Investigation of the Stabilizing Effects of Antioxidants and Benzophenone-3 on Desonide Photostability. AAPS PharmSciTech. (2014)
  112. Serpone N, et. al. An in vitro systematic spectroscopic examination of the photostabilities of a random set of commercial sunscreen lotions and their chemical UVB/UVA active agents. Photochem Photobiol Sci. (2002)
  113. Gaspar LR, Maia Campos PM. Evaluation of the photostability of different UV filter combinations in a sunscreen. Int J Pharm. (2006)
  114. US Food and Drug Administration. CFR - Code of Federal Regulations Title 21, Part 352, Subpart B, Section 352.10. Code of Federal Regulations. (2013)
  115. European Commission. List of UV filters allowed in cosmetic products. Cosmetics Directive. (2011)
  116. Xu C, Parsons PG. Cell cycle delay, mitochondrial stress and uptake of hydrophobic cations induced by sunscreens in cultured human cells. Photochem Photobiol. (1999)
  117. Huang X, et. al. UV and dark-triggered repetitive release and encapsulation of benzophenone-3 from biocompatible ZnO nanoparticles potential for skin protection. Nanoscale. (2013)
  118. Hanson KM, Gratton E, Bardeen CJ. Sunscreen enhancement of UV-induced reactive oxygen species in the skin. Free Radic Biol Med. (2006)
  119. Vilela FM, et. al. Effect of ultraviolet filters on skin superoxide dismutase activity in hairless mice after a single dose of ultraviolet radiation. Eur J Pharm Biopharm. (2012)
  120. Molinari A, et. al. Influence of complexation with cyclodextrins on photo-induced free radical production by the common sunscreen agents octyl-dimethylaminobenzoate and octyl-methoxycinnamate. Pharmazie. (2006)
  121. Shaw T, et. al. True photoallergy to sunscreens is rare despite popular belief. Dermatitis. (2010)
  122. Haylett AK, et. al. Sunscreen photopatch testing: a series of 157 children. Br J Dermatol. (2014)
  123. Beleznay K, de Gannes G, Kalia S. Analysis of the prevalence of allergic contact dermatitis to sunscreen: a cohort study. J Cutan Med Surg. (2014)
  124. Spiewak R. The frequency and causes of photoallergic contact dermatitis among dermatology outpatients. Acta Dermatovenerol Croat. (2013)
  125. Greenspoon J, et. al. Allergic and photoallergic contact dermatitis: a 10-year experience. Dermatitis. (2013)
  126. Warshaw EM, et. al. Patch test reactions associated with sunscreen products and the importance of testing to an expanded series: retrospective analysis of North American Contact Dermatitis Group data, 2001 to 2010. Dermatitis. (2013)
  127. DeLeo VA, Suarez SM, Maso MJ. Photoallergic contact dermatitis. Results of photopatch testing in New York, 1985 to 1990. Arch Dermatol. (1992)
  128. European Multicentre Photopatch Test Study (EMCPPTS) Taskforce. A European multicentre photopatch test study. Br J Dermatol. (2012)
  129. Bryden AM, et. al. Photopatch testing of 1155 patients: results of the U.K. multicentre photopatch study group. Br J Dermatol. (2006)
  130. Darvay A, et. al. Photoallergic contact dermatitis is uncommon. Br J Dermatol. (2001)
  131. Schauder S, Ippen H. Contact and photocontact sensitivity to sunscreens. Review of a 15-year experience and of the literature. Contact Dermatitis. (1997)
  132. Szczurko C, et. al. Photocontact allergy to oxybenzone: ten years of experience. Photodermatol Photoimmunol Photomed. (1994)
  133. Journe F, et. al. Sunscreen sensitization: a 5-year study. Acta Derm Venereol. (1999)
  134. Trevisi P, et. al. Sunscreen sensitization: a three-year study. Dermatology. (1994)
  135. Berne B, Ros AM. 7 years experience of photopatch testing with sunscreen allergens in Sweden. Contact Dermatitis. (1998)
  136. Cardoso JC, et. al. Photopatch testing with an extended series of photoallergens: a 5-year study. Contact Dermatitis. (2009)
  137. Katsarou A, et. al. Photoallergic contact dermatitis: the 15-year experience of a tertiary reference center in a sunny Mediterranean city. Int J Immunopathol Pharmacol. (2008)
  138. Rodríguez E, et. al. Causal agents of photoallergic contact dermatitis diagnosed in the national institute of dermatology of Colombia. Photodermatol Photoimmunol Photomed. (2006)
  139. Chuah SY, et. al. Photopatch testing in Asians: a 5-year experience in Singapore. Photodermatol Photoimmunol Photomed. (2013)
  140. Ang P, Ng SK, Goh CL. Sunscreen allergy in Singapore. Am J Contact Dermat. (1998)
  141. Cook N, Freeman S. Report of 19 cases of photoallergic contact dermatitis to sunscreens seen at the Skin and Cancer Foundation. Australas J Dermatol. (2001)
  142. Stiefel C, Schwack W. Rapid screening method to study the reactivity of UV filter substances towards skin proteins by high-performance thin-layer chromatography. Int J Cosmet Sci. (2013)
  143. Beach RA, Pratt MD. Chronic actinic dermatitis: clinical cases, diagnostic workup, and therapeutic management. J Cutan Med Surg. (2009)
  144. Langan SM, Collins P. Photocontact allergy to oxybenzone and contact allergy to lignocaine and prilocaine. Contact Dermatitis. (2006)
  145. Kiec-Swierczynska M, Krecisz B, Swierczynska-Machura D. Photoallergic and allergic reaction to 2-hydroxy-4-methoxybenzophenone (sunscreen) and allergy to cetyl alcohol in cosmetic cream. Contact Dermatitis. (2005)
  146. Landers M, Law S, Storrs FJ. Contact urticaria, allergic contact dermatitis, and photoallergic contact dermatitis from oxybenzone. Am J Contact Dermat. (2003)
  147. Nedorost ST. Facial erythema as a result of benzophenone allergy. J Am Acad Dermatol. (2003)
  148. Cook N, Freeman S. Photosensitive dermatitis due to sunscreen allergy in a child. Australas J Dermatol. (2002)
  149. Schmidt T, Ring J, Abeck D. Photoallergic contact dermatitis due to combined UVB (4-methylbenzylidene camphor/octyl methoxycinnamate) and UVA (benzophenone-3/butyl methoxydibenzoylmethane) absorber sensitization. Dermatology. (1998)
  150. Silva R, Almeida LM, Brandão FM. Photoallergy to oxybenzone in cosmetic creams. Contact Dermatitis. (1995)
  151. Collins P, Ferguson J. Photoallergic contact dermatitis to oxybenzone. Br J Dermatol. (1994)
  152. Lenique P, et. al. Contact and photocontact allergy to oxybenzone. Contact Dermatitis. (1992)
  153. Torres V, Correia T. Contact and photocontact allergy to oxybenzone and mexenone. Contact Dermatitis. (1991)
  154. Peluso AM, Bardazzi F, Tosti A. Photocontact dermatitis due to Eusolex 4360. Contact Dermatitis. (1991)
  155. Knobler E, et. al. Photoallergy to benzophenone. Arch Dermatol. (1989)
  156. Thune P. Contact and photocontact allergy to sunscreens. Photodermatol. (1984)
  157. Hölzle E, Plewig G. Photoallergic contact dermatitis by benzophenone containing sunscreening preparations. Hautarzt. (1982)
  158. Green C, Norris PG, Hawk JL. Photoallergic contact dermatitis from oxybenzone aggravating polymorphic light eruption. Contact Dermatitis. (1991)
  159. Bilsland D, Ferguson J. Contact allergy to sunscreen chemicals in photosensitivity dermatitis/actinic reticuloid syndrome (PD/AR) and polymorphic light eruption (PLE). Contact Dermatitis. (1993)
  160. Zhang XM, et. al. Erythema-multiforme-like eruption following photoallergic contact dermatitis from oxybenzone. Contact Dermatitis. (1998)
  161. Aguirre A, et. al. Allergic contact cheilitis from a lipstick containing oxybenzone. Contact Dermatitis. (1992)
  162. Schram SE, Glesne LA, Warshaw EM. Allergic contact cheilitis from benzophenone-3 in lip balm and fragrance/flavorings. Dermatitis. (2007)
  163. Veysey EC, Orton DI. Photoallergic contact cheilitis due to oxybenzone found in a lip cosmetic. Contact Dermatitis. (2006)
  164. Spijker GT, et. al. Anaphylaxis caused by topical application of a sunscreen containing benzophenone-3. Contact Dermatitis. (2008)
  165. Emonet S, et. al. Anaphylaxis to oxybenzone, a frequent constituent of sunscreens. J Allergy Clin Immunol. (2001)
  166. Yesudian PD, King CM. Severe contact urticaria and anaphylaxis from benzophenone-3(2-hydroxy 4-methoxy benzophenone). Contact Dermatitis. (2002)
  167. Agin PP, et. al. Rates of allergic sensitization and irritation to oxybenzone-containing sunscreen products: a quantitative meta-analysis of 64 exaggerated use studies. Photodermatol Photoimmunol Photomed. (2008)
  168. Chrétien MN, Heafey E, Scaiano JC. Reducing adverse effects from UV sunscreens by zeolite encapsulation: comparison of oxybenzone in solution and in zeolites. Photochem Photobiol. (2010)
  169. Robison SH, et. al. Assessment of the in vivo genotoxicity of 2-hydroxy 4-methoxybenzophenone. Environ Mol Mutagen. (1994)
  170. No authors listed. Reproductive toxicology. 2-Hydroxy-4-methoxybenzophenone. Environ Health Perspect. (1997)
  171. Daston GP. Assessment of the reproductive toxic potential of dermally applied 2-hydroxy-4-methoxybenzophenone to male B6C3F1 mice. Fundam Appl Toxicol. (1993)
  172. Chen M, et. al. Association of exposure to phenols and idiopathic male infertility. J Hazard Mater. (2013)
  173. Coronado M, et. al. Estrogenic activity and reproductive effects of the UV-filter oxybenzone (2-hydroxy-4-methoxyphenyl-methanone) in fish. Aquat Toxicol. (2008)
  174. Kim S, et. al. Effects of benzophenone-3 exposure on endocrine disruption and reproduction of Japanese medaka (Oryzias latipes)-A two generation exposure study. Aquat Toxicol. (2014)
  175. Vela-Soria F, et. al. Determination of benzophenones in human placental tissue samples by liquid chromatography-tandem mass spectrometry. Talanta. (2011)
  176. Wolff MS, et. al. Prenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect. (2008)
  177. Schlumpf M, et. al. In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect. (2001)
  178. Schlecht C, et. al. Effects of estradiol, benzophenone-2 and benzophenone-3 on the expression pattern of the estrogen receptors (ER) alpha and beta, the estrogen receptor-related receptor 1 (ERR1) and the aryl hydrocarbon receptor (AhR) in adult ovariectomized rats. Toxicology. (2004)
  179. Blüthgen N, Zucchi S, Fent K. Effects of the UV filter benzophenone-3 (oxybenzone) at low concentrations in zebrafish (Danio rerio). Toxicol Appl Pharmacol. (2012)
  180. Ozáez I, Martínez-Guitarte JL, Morcillo G. Effects of in vivo exposure to UV filters (4-MBC, OMC, BP-3, 4-HB, OC, OD-PABA) on endocrine signaling genes in the insect Chironomus riparius. Sci Total Environ. (2013)
  181. Ozáez I, Martínez-Guitarte JL, Morcillo G. The UV filter benzophenone 3 (BP-3) activates hormonal genes mimicking the action of ecdysone and alters embryo development in the insect Chironomus riparius (Diptera). Environ Pollut. (2014)
  182. Schreurs RH, et. al. Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays. Toxicol Sci. (2005)
  183. Kunz PY, Galicia HF, Fent K. Comparison of in vitro and in vivo estrogenic activity of UV filters in fish. Toxicol Sci. (2006)
  184. Ma R, et. al. UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci. (2003)
  185. Gomez E, et. al. Estrogenic activity of cosmetic components in reporter cell lines: parabens, UV screens, and musks. J Toxicol Environ Health A. (2005)
  186. Nakagawa Y, Suzuki T. Metabolism of 2-hydroxy-4-methoxybenzophenone in isolated rat hepatocytes and xenoestrogenic effects of its metabolites on MCF-7 human breast cancer cells. Chem Biol Interact. (2002)
  187. Buttke DE, Sircar K, Martin C. Exposures to endocrine-disrupting chemicals and age of menarche in adolescent girls in NHANES (2003-2008). Environ Health Perspect. (2012)
  188. Janjua NR, et. al. Sunscreens and thyroid function in humans after short-term whole-body topical application: a single-blinded study. Br J Dermatol. (2007)
  189. Pont AR, Charron AR, Brand RM. Active ingredients in sunscreens act as topical penetration enhancers for the herbicide 2,4-dichlorophenoxyacetic acid. Toxicol Appl Pharmacol. (2004)
  190. Gu X, et. al. In-vitro permeation of the insect repellent N,N-diethyl-m-toluamide (DEET) and the sunscreen oxybenzone. J Pharm Pharmacol. (2004)
  191. Gu X, et. al. In vitro evaluation of concurrent use of commercially available insect repellent and sunscreen preparations. Br J Dermatol. (2005)
  192. Wang T, Kasichayanula S, Gu X. In vitro permeation of repellent DEET and sunscreen oxybenzone across three artificial membranes. Int J Pharm. (2006)
  193. Wang T, Gu X. In vitro percutaneous permeation of the repellent DEET and the sunscreen oxybenzone across human skin. J Pharm Pharm Sci. (2007)
  194. Kasichayanula S, et. al. Percutaneous characterization of the insect repellent DEET and the sunscreen oxybenzone from topical skin application. Toxicol Appl Pharmacol. (2007)
  195. Fediuk DJ, et. al. Tissue deposition of the insect repellent DEET and the sunscreen oxybenzone from repeated topical skin applications in rats. Int J Toxicol. (2010)
  196. Fediuk DJ, et. al. Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats. Biopharm Drug Dispos. (2011)
  197. Fediuk DJ, et. al. Metabolic disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and skin administration in rats. Int J Toxicol. (2012)
  198. Gu X, Chen T. In vitro permeation characterization of repellent picaridin and sunscreen oxybenzone. Pharm Dev Technol. (2009)
  199. Chen T, et. al. Percutaneous permeation comparison of repellents picaridin and DEET in concurrent use with sunscreen oxybenzone from commercially available preparations. Pharmazie. (2010)