Octinoxate is commonly used as a UVB filter in cosmetic and skin care products. Because it breaks down when exposed to light, octinoxate needs to be formulated with other UV absorbers or photostabilizers.


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




Absorbs UVB radiation. Though relatively weak, it can be quite effective at a concentration of 10%, the highest authorized in the EU.

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Scientific Research

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Table of contents:

1. Sources

1.1 In personal care products

Octinoxate is an organic compound that can be enzymatically synthesized from p-methoxycinnamic acid and 2-ethyl hexanol.[1] Despite being a relatively weak UVB absorber,[2] it is nevertheless a very popular sunscreen active. It was found in 96 out of 101 (95%) commercial suncare products from South Korea[3] and in 59 out of 116 (51%) personal care products from Switzerland.[4] In a larger study of 4,447 cosmetic products, it was detected in 38.5% of the products, a proportion that was lower than only titanium dioxide (40.1%) and avobenzone (48.7%).[5]

1.2 In the environment

UV filters occur in the aquatic environment through 2 principal sources: direct inputs from recreational activities in the water and indirect wastewater- and river-borne inputs.[6] Octinoxate has been detected in seawater samples from Italy,[7] environmental water samples from Slovenia,[8] Japanese and Swiss rivers and lakes,[9][10][11] as well as in Mediterranean rivers.[6] It appears to accumulate in marine life, having been detected in marine mussels from French coastal regions[12] and in macroinverterbrates and fish from Switzerland.[13] It has even been found in tap water samples from Spain.[14]

In addition, one study found that octinoxate was ubiquitous in samples of indoor dust from private flats, public buildings and vehicle cabins, where it was measured at a maximum concentration of 15 µg/g.[15]

2. Skin penetration

An ideal sunscreen agent should remain localized close to the skin surface without penetrating into the deeper layers of the skin to be safe and effective.[16]

Experiments on animal skin have shown that octinoxate can penetrate through baby mouse skin[17] and dermatomed micro-Yucatan pig skin,[18] but not the skin of the hairless rat.[19]

In vitro experiments using real or reconstituted human skin suggest that octinoxate can penetrate significantly into the skin[18][20] and reach the viable epidermis,[21] but that it does not penetrate across the skin.[19][20] 2 in vivo studies involving daily repeated whole-body topical applications of creams containing 10% octinoxate, 10% oxybenzone and 10% enzacamene have however clearly shown systemic absorption, as evidenced by the detection of octinoxate in the plasma after just the first application.[22][23] Moreover, for the male subjects in both studies the 96-hour median plasma concentrations of octinoxate were higher than the 24-hour concentrations, suggesting that accumulation occurred during the treatment period.[22][23]

The penetration and retention of octinoxate in the skin is formulation-dependent. For instance, the in vitro skin release and permeation of octinoxate from cosmetic emulsions varies with different types of emulsions,[24] different emulsifiers[16][25] and different oil phases.[26][27] Applying octinoxate solubilized in an emulsion gel to the skin also led to higher concentrations of it in the stratum corneum compared to octinoxate solubilized in petrolatum.[28]

Encapsulating octinoxate in liposomes,[29][30][31] lipid microspheres[32] or microparticles,[33] nanoparticles,[34][35][36][37][38] nanocapsules[39][40][41] or nanostructured lipid carriers[42] can diminish its systemic absorption by limiting its release and/or increasing its retention in the outermost skin layers.

On the other hand, nanoemulsions seem to increase the extent of octinoxate penetration and skin deposition compared to nanocapsules or conventional oil-in-water emulsions,[40][43] especially when formulated with sucrose laureate.[44]

Application temperature does not appear to influence the stratum corneum adsorption of octinoxate.[28]

3. Effects on the skin

3.1 Photoprotection

Octinoxate absorbs radiation in the 290-320 nm region of the UV spectrum,[36] with a maximum absorbance at 311 nm.[45] Its sun protection factor (SPF) corresponds to its concentration in the formulation.[46] In vitro and in vivo testing found that a lotion containing 2% octinoxate had an SPF of ~5, which increased to 10 at a concentration of 4.5%, and 15/16 at a concentration of 7.5%.[47] Though considered a weak UVB absorber (an order of magnitude less potent than Padimate O)[2] that must be combined with other UV filters in order to achieve an adequate SPF,[45] when compared to 17 other sun filters at their highest concentrations authorized in the European Union, octinoxate was actually among the most efficacious.[48]

Because octinoxate absorbs UVB radiation, it can prevent UVB-induced damage such as the formation of sunburn cells and pyridimine dimers,[49][50][51] thought it does not seem to protect against oxidative DNA lesions.[52]

In mouse models, it was also able to provide partial protection against UV-induced immunosuppression,[53][54] apparently by inhibiting the depletion of Langerhans cells[55] and by directly inactivating epidermal cis-urocanic acid,[56] a known mediator of photoimmunosuppression.[57][58]

Further, octinoxate appears to inhibit UV-induced tumour promotion. When applied before UV irradiation to mice, it afforded effective protection from the overt expression of tumours such as squamous cell carcinomas.[59][60][61] However, it failed to reduce the UV-induced increase in melanoma incidence in mice in another study.[62]

The photoprotective efficacy of octinoxate can be enhanced in several ways. Some plant extracts can intensify the SPF values of octinoxate formulations,[63] and the bioconvertible antioxidants tocopheryl acetate and sodium ascorbyl phosphate can improve photoprotection by converting to vitamin E and vitamin C, which then deactivate reactive oxygen species generated by UV photons.[64] Incorporating octinoxate within certain vehicles can also increase the photoprotection it provides. Liposomes containing octinoxate, for instance, may interact with the cells of the stratum corneum, promoting the retention of octinoxate in this layer and increasing the SPF.[30] Likewise, polymethylmethacrylate (PMMA) microspheres of octinoxate had nearly 4 times the SPF of a similar formulation containing free octinoxate,[65] and octinoxate nanocapsules provided better protection against UV-induced erythema than a conventional gel or emulsion.[66][41] The encapsulation of octinoxate within nanoparticles has also been demonstrated to improve its photoprotection, as evidenced by increased absorbance[67] and higher SPF values.[68][38]

Octinoxate should be combined with a UVA filter like avobenzone or zinc oxide to enable broad-spectrum protection.[69][70] In one study, a SPF 15 sunscreen containing octinoxate and avobenzone was found to reduce UV-induced free radical damage to the skin by 21%.[71]

4. Stability

Octinoxate degrades rapidly upon exposure to light through photoisomerization and photodimerization.[72] When mouse skins were applied with a typical skin coverage of octinoxate in one study, UVB exposure induced approximately 50% photoisomerization, resulting in a 25% loss of octinoxate's UV filtering efficiency.[73]

A recent survey of >300 sunscreen products in the US revealed that 19% contained octinoxate and avobenzone,[74] a combination that is known to lead to the photolysis of both sunscreen agents upon irradiation, with a consequent loss of UV protection.[75][76][77]

Fortunately, other UV absorbers such as octocrylene and Tinosorb S can help stabilize both octinoxate and avobenzone, as can the photostabilizer SolaStay S1.[78][79][80] It is also possible to improve the photostability of octinoxate through nanoencapsulation. Poly(D,L-lactide) nanocapsules and chitosan nanoparticles have been shown to minimize the photoisomerization of octinoxate,[81][34] and poly-epsilon-caprolactone nanocapsules, poly-D,L-lactide-co-glycolide (PLGA) nanocapsules and viscosized nanostructured lipid carriers were also efficient at reducing the extent of light-induced octinoxate degradation.[82][83][37] Still, not all nanodelivery systems are able to influence the photostability of octinoxate.[42][83]

Other ways in which octinoxate can be photostabilized include complexation with β-cyclodextrin,[84] incorporation within solid lipid microspheres[32] and entrapment within the pores of the mesoporous silicate MCM-41 as a particulate carrier.[85] In addition, quercetin has also been proven to photostabilize the combination of octinoxate and avobenzone more effectively and at a lower concentration than octocrylene and other antioxidants (vitamin E, butylated hydroxyanisole) through comparative photodegradation studies.[86]

5. Safety

Octinoxate is approved by the US FDA as a sunscreen active ingredient in cosmetic products up to a concentration of 7.5%.[87] It is also an approved UV filter under the EU Cosmetics Directive, which stipulates a maximum concentration of 10%.[88]

5.1 Effects on skin cells

Octinoxate can delay the cell cycle, cause mitochondrial stress and induce the uptake of hydrophobic cations in cultured human cells.[89] However, the amount of octinoxate that reaches the viable epidermis after topical application is probably too low to cause toxicity to human keratinocytes.[21]

5.2 Production of reactive oxygen species

A 4-hour illumination of a solution containing octinoxate with simulated sunlight was found to generate carbon-centered free radicals in one study.[90] Another study showed that if octinoxate penetrates into the nucleated layers of the skin, it can increase the levels of reactive oxygen species in the skin over that naturally produced by epidermal chromophores under UV illumination.[91] Further, a cream gel formulation containing octinoxate, oxybenzone and octisalate significantly decreased the activity of superoxide dismutase, an important antioxidant defense in the skin, in irradiated mice, indicating that they may have formed degradation producted under UV radiation that either inhibited the enzyme or generated reactive species in the skin.[92]

Complexation of octinoxate with β-cyclodextrin appears to markedly inhibit the formation of free radicals it generates under UV exposure however, minimizing its photosensitizing potential.[90]

5.3 Possible genotoxicity

Octinoxate appeared to be mutagenic in a Salmonella/microsome assay, and seemingly increased the frequency of sex-linked recessive lethal alleles in the fruit fly Drosophila melanogaster. However, it is possible that these findings may be invalid, as many samples were obtained from several sources and the results were batch-related, implicating the presence of a trace contaminant.[93]

A more recent study confirmed that octinoxate is not photogenotoxic, finding no increase in DNA damage in mouse lymphoma cells following irradiation.[94]

5.4 Reproductive toxicity

In a reproductive toxicity study on rats, octinoxate was continuously administered in the diet through 2 successive generations at doses up to 100 mg/kg body weight/day. This had no adverse effects on estrous cycles, mating behavior, conception, parturition, lactation and weaning, sperm and follicle parameters or the macropathology and histopathology of the sexual organs. The highest dose did however reduce parental food consumption and body weight, increase liver weights, produce hepatic cytoplasmic eosinophilia and erosion/ulceration of glandular stomach mucosa, and lead to a slightly decreased implantation rate in dams from both generations. In addition, pups from both generations had reduced lactation weight gain, reduced organ weights and delayed sexual maturation landmarks.[95]

5.5 Enhanced herbicide absorption

Octinoxate at approved concentrations in sunscreens can enhance the dermal penetration of the herbicide 2,4-dichlorophenoxyacetic acid,[96] which is exacerbated with the consumption of alcohol.[97] This suggests that it may pose a risk to agricultural workers; however, limiting excessive alcohol consumption is more important than limiting the use of sunscreens for individuals with potential herbicide exposure, since the consequences of UV-induced skin cancer are far more serious than the risks associated with increased exposure to herbicides.[97]

5.6 Photoallergic contact dermatitis

Although the incidence of allergic contact dermatitis to sunscreens in considered low, there are several reports in the medical literature of reactions towards octinoxate.[98][99][100][101][102] In 2014, a study published in the British Journal of Dermatology identified octinoxate as one of 2 most common UV filters responsible for positive photopatch reactions in an analysis of 157 children.[103] This may be due to the carbonyl groups of octinoxate reacting with peptides or free amino acids of the human skin.[104]

5.7 Developmental effects

Significantly, perinatal exposure to octinoxate led to effects on the reproductive, auditory and neurological development of rat offspring. Female offspring had decreased motor activity levels, while male offspring had reduced prostate and testis weights, lower sperm counts and testosterone levels, but improved spatial learning abilities.[105]

5.8 Potential endocrine disruptor

Octinoxate can increase the uterine weights of rats when administered by the oral route, but only at high doses. One study found no detectable effect at doses up to 333 mg/kg/day,[106] while another showed that the median effective dose was 934 mg/kg/day.[107] A third study on rodents indicated that octinoxate has very mild estrogenic effects in the uterus and vagina, but not in the bone.[108]

Additional evidence that octinoxate is a endocrine active chemical comes from studies investigating the effects of octinoxate on the hypothalamic-pituitary thyroid axis, which demonstrate that it changes the serum levels of several hormones, alters the expression of some hormone receptors, and affects the release of neurotransmitters from the hypothalamus.[109][110][111][112]

Octinoxate has also shown that it can affect the expression of endocrine-related genes in the insect Chironomum riparius, and in various species of fish.[113][114][115][116] Moreover, it acted as a partial agonist in a human breast cancer cell line, stimulating the cells' proliferation though not to the maximal level observed with estradiol.[107]

When a cream formulation containing 10% octinoxate + 10% oxybenzone + 10% enzacamene was topically applied to 32 human volunteers for 1 week, the sunscreens did not appear to have any influence on the levels of endogenous reproductive hormones in either the men or the women enrolled in the study, despite being systematically absorbed.[22] A similar study observed statistically significant differences in the levels of some thyroid hormones, but these were too minor to be biologically significant.[117]

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