Evaluation of the skin safety of a test product (sunscreen) for primary skin irritation using the skin irritation test (patch test in humans)

INTRODUCTION

Ultraviolet (UV) radiation is a major environmental factor that affects skin health. While essential for vitamin D synthesis, excessive exposure causes acute damage such as sunburn and erythema, and contributes to long-term risks, including photoaging and skin cancer.^[1-3] It has also been recognized as a confirmed carcinogen for humans because of its ability to cause mutations and its nonspecific damaging effects.^[4]

Photoprotection is therefore a cornerstone of preventive dermatology, achieved through behavioral measures (such as wearing protective clothing, seeking shade) and regular use of topical sunscreens. Modern sunscreens are designed to prevent solar erythema and broader UV-induced damage to the skin. Clinical guidelines, including those from the American Academy of Dermatology, recommend daily use of broad-spectrum sunscreens with a sun protection factor ≥30, applied generously and reapplied every 2 h.^[5] Sunscreen products are available in various forms, such as creams, lotions, sprays, and sticks.^[6]

However, real-world adherence is often poor, and product tolerability plays a critical role in its sustained use. Formulations containing harsh filters or allergens may provoke irritation or photoallergic contact dermatitis, especially in sensitive skin populations.^[7,8] Hence, concerns regarding phototoxicity, photoirritation, photoallergenicity, photogenotoxicity, and photocarcinogenicity persist in the evaluation of sunscreen formulations, alongside allergic reactions caused by excipients, perfumes, and preservatives.^[9]

Patch testing is therefore crucial for identifying the responsible irritant or agent, a practice that began with Josef Jadassohn (1863–1936) in 1895, especially Marion B. Sulzberger (1895– 1983), who introduced it to dermatologists in the United States during the 1930s.^[10] Standardized patch testing remains the gold standard for evaluating the primary irritation potential of topical products, providing dermatologists with evidence to guide safe recommendations.^[11] The concept of patch testing involves mimicking a mini-model of allergic contact dermatitis in a clinical environment using allergens dissolved in a vehicle at concentrations that do not irritate.^[12] It assists in verifying contact sensitivity that is suspected based on the clinical history, and it also helps in revealing sensitivities that were previously unrecognized.^[13] Erythema, swelling, and papules, which may occasionally include small vesicles that extend slightly beyond the border of the patch test, are indicative of contact allergy.^[14]

Dermatologists play a critical role in counseling patients about photoprotection, particularly the right selection and usage of sunscreens. The hazards associated with acute and long-term UV-induced damage to the skin can be greatly decreased by increasing awareness and encouraging appropriate sun protection practices.^[15]

Against this background, the present study was conducted to evaluate the skin safety of Venusia Sun Unseen through a human patch test in accordance with the IS 4011:2018 guidelines, including both sensitive and normal skin populations.

MATERIALS AND METHODS

Study design and population

This study was a monocentric, non-randomized, evaluator-blinded, single-application, controlled study conducted at C.L.A.I.M.S. Pvt. Ltd., Mumbai. The investiigational plan are depicted in Figure 1. Twenty-six adults (18–65 years; 13 males, 13 females; 50% with sensitive skin based on the lactic acid sting test) with the Fitzpatrick skin types III–V were enrolled. Participants were required to have healthy skin at the test site and avoid confounding exposures (UV radiation, swimming, sauna, strenuous exercise). Key exclusions included pregnancy, lactation, dermatological conditions, known cosmetic allergies, and chronic systemic illness.

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Figure 1:

The investigational plan.

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RESULTS

Data product assessment criteria

According to the IS 4011: 2018 criteria, Venusia Sun Unseen Sunscreen and 0.9% isotonic saline-negative control with a combined mean score of Erythema/Dryness/Wrinkles + Edema of 0.69 and 0.00, respectively, can be considered nonirritants. Whereas 1% sodium lauryl sulfate (SLS)-positive control with a score of 3.04, was classified as mildly irritant.

The combined mean skin irritation scores of participants, recorded at Visit 3 (48 h), are given in Table 4 and Figure 2.

Table 4: Combined mean skin irritation scores of participants (recorded at visit 3 [48 h]).

Products	Sample size	Mean score (A)	Mean score (O)	Mean score (A+O)	Irritancy assessment
Venusia Sun Unseen Sunscreen	26	0.50	0.19	0.69	Non-irritant
0.9% Isotonic saline-negative control	26	0.00	0.00	0.00	-
1% Sodium lauryl sulfate- positive control	26	2.00	1.04	3.04	-

A: Erythema/Dryness/Wrinkles, O: Edema, A+O: Erythema/Dryness/Wrinkles+Edema

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Figure 2:

Combined mean skin irritation scores (erythema + edema) of Venusia Sun Unseen, positive control (1% sodium lauryl sulfate), and negative control (0.9% isotonic saline) at 48 h. A: *Erythema/Dryness/Wrinkles, O: Edema, A + O: Erythema/Dryness/Wrinkles + Edema.

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DISCUSSION

This study demonstrated that Venusia Sun Unseen Sunscreen exhibited a non-irritant profile, with a combined mean irritation score of 0.69 at 48 h, well below the IS 4011: 2018 Methods of Test for safety evaluation of cosmetics (Third Revision) threshold of 2.0. In contrast, the positive control (1% SLS) produced meaningful irritation (3.04), whereas saline produced no reaction, validating the sensitivity and specificity of the assay. The results were clinically meaningful, and these findings confirm that the sunscreen is well tolerated across both normal and sensitive skin populations. Participants who had any local reactions were assessed after 1 week to confirm recovery from reactions.

Sunscreen adherence is often compromised by perceived or actual irritation. By demonstrating tolerability under occlusive patch test conditions, Venusia Sun Unseen Sunscreen provides dermatologists with evidence-based reassurance for recommending daily use. This may enhance long-term compliance with photoprotection, which is a critical factor in preventing photoaging, pigmentary disorders, and UV-induced skin cancers. The formulation of this test product combines various ingredients, such as Vitamin C, Vitamin E, Vitamin F, Octinoxate, Octocrylene, Octisalate, Uvinul A Plus, and Tinosorb S.

Vitamin C functions as a cofactor for the proline and lysine hydroxylases that anchor the tertiary structure of collagen molecules. In addition, it also encourages collagen gene expression.^[16] Due to its antioxidant properties, Vitamin E is widely incorporated into topical formulations of skin creams. The reactive oxygen species (ROS) have demonstrated the capacity to modify the production of skin collagen and glycosaminoglycans.^[17] Essential fatty acids have also been referred to as Vitamin F.^[18] Rich in omega-3 polyunsaturated fatty acids, fish oil is often seen to improve inflammatory conditions such as rheumatoid arthritis and psoriasis, along with a possibility of reduction in sensitivity of erythema due to UVB in human beings.^[19] Hence, the addition of Vitamin C, Vitamin E, and Vitamin F to this test product provides skin benefits.

Octinoxate and octocrylene are among the cinnamic acid derivatives that are categorized as UV filters and are permitted to be used in cosmetic products, only at maximum levels and concentrations that may differ between nations. These compounds absorb UV light predominantly in the UVB area, covering wavelengths in the 280–320 nm range for octinoxate and 290–360 nm for octocrylene. UV filters from this group are characterized by weak water solubility and are desirable in waterproof applications.^[20] Octisalate or octyl salicylate is used to increase the UV-B protection in a sunscreen. Salicylates are typically used in conjunction with other UV filters since they are weak UV-B absorbers.^[21] Uvinul A plus exhibits the greatest amount of absorption at 354 nm and thus primarily gives protection against UVA radiation (315-380 nm). In comparison to several other UV filters, Uvinul A plus is photostable as well.^[22] Tinosorb S is a broadband UV filter that delivers protection and safety from direct and indirect UV-induced DNA damage by absorbing solar UV and lowering ROS production in the skin.^[23]

The test product is also avobenzone-free, oxybenzone-free, alcohol-free and paraben-free. UV filters, especially avobenzone, tend to lead to various forms of irritant dermatitis.^[24] Among sunscreens, oxybenzone is the most frequent cause of contact dermatitis.^[25] A study, conducted by Onyango et al. (2023), of avobenzone and five additional organic filters (octisalate, homosalate, octocrylene, oxybenzone, octinoxate), utilizing the ToxCast/Tox21 database revealed all except oxybenzone to have reduced intrinsic biological activity and a reduced risk of toxicity, including endocrine disruption in humans.^[26] Regular use of cosmetics containing parabens can also impose harmful effects on the human body.^[27]

In addition, it was seen that in a study conducted by Warshaw et al. (2021), positive patch test reactions to Vitamin E (tocopherol) were relatively low.^[28] Octisalate has a good safety profile.^[24] A retrospective study conducted by Wilson et al.^[29] was conducted to test the dermal safety of sunscreens with UV filters. Octocrylene and octisalate were also included in this study. The results and analysis of the human repeat irritation patch test supported the safety profile of these ingredients by showing no to minimal risks of cutaneous irritation, sensitization, photo-allergy, and photo-irritation.^[29]

Our findings align with existing reports showing that syndet-based and irritant-free formulations have lower cumulative irritancy than traditional surfactant-containing products.^[30-32] The robust irritant response to 1% SLS in studies further support its role as a benchmark control in patch testing and underscores the relative safety of Venusia Sun Unseen Sunscreen.^[30-32] Importantly, the inclusion of participants with sensitive skin strengthens the generalizability of these results to populations most at risk of sunscreen intolerance.

The safety and tolerability findings of this clinical trial address a critical gap between dermatological evidence and real-world sun protection practice. By demonstrating minimal irritation while excluding avobenzone and oxybenzone, two recognized contact sensitizers and allergens, this test product formulation directly tackles barriers to consistent sunscreen use, such as sensory dissatisfaction and fear of adverse reactions.^[8,33] From a consumer perspective, daily application of a well-tolerated sunscreen formulation enables consistent access to all the benefits, including prevention of photoaging, dyspigmentation, protection against photocarcinogenesis, and DNA damage.^[9] Randhawa et al. (2016) conducted a prospective study to demonstrate the benefits of daily use of facial broad-spectrum sunscreen over 52 weeks.^[34] At the end of the study duration, the results showed there were signs of significant improvement in all photoaging parameters. By the end of the trial, the most significantly improved parameters were skin texture, clarity, and discrete and mottled pigmentation.^[34] A randomized clinical trial conducted by Alvares et al. (2022) demonstrated that actinic keratoses in the forearms were reduced or resolved in 38.7% of those who used sunscreen regularly.^[35] An additional benefit was observed when sunscreen was combined with topical antioxidant formulations.^[35] Hence, daily application of our test product will be beneficial in promoting long-term adherence to photoprotective practices, as its favorable tolerability and safety reduce common barriers to regular use. Consistent daily application reinforces preventive dermatologic recommendations, facilitating their translation into sustainable real-world behavior, which is essential for achieving cumulative photoprotective benefits and clinically meaningful long-term outcomes. Furthermore, for individuals having sensitive skin or any inflammatory conditions, or adverse events to conventional sunscreens, this test product with its non-irritant profile becomes a viable pathway to sustained photoprotection, addressing a significant unmet clinical need. By bridging the gap between tolerability and efficacy, the formulation of this test product supports the translation of theoretical photoprotection awareness into sustained behavioral change.

Overall, the findings of this study favor the safety and suitability of Venusia Sun Unseen Sunscreen for regular and daily application, due to its minimal risk of irritation, and thus justify a clear practical application in routine dermatological care. By ensuring tolerability, this formulation enhances patient comfort and long-term adherence.

CONCLUSION

Venusia Sun Unseen Sunscreen was well-tolerated and classified as a non-irritant under standardized patch test conditions for both sensitive and normal skin types. These findings support the dermatological safety and suitability of this sunscreen for daily photoprotection, particularly in individuals prone to skin sensitivity. Future studies should evaluate repeated application, long-term use, and phototoxicity to further strengthen the evidence for its widespread clinical and consumer use.