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Evaluation of skin irritation and skin sensitization potential of Venusia CeraPlus cream using human repeat insult patch test
*Corresponding author: Biswajit Aich, Department of Medical Affairs, Dr Reddys Laboratories Ltd, Hyderabad, Telangana, India. biswajitaich@drreddys.com
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Received: ,
Accepted: ,
How to cite this article: Aich B, Kumbhar P, Sanghavi A, Muchhala S, Katare S, Kotak B. Evaluation of skin irritation and skin sensitization potential of Venusia CeraPlus cream using human repeat insult patch test. CosmoDerma. 2025;5:12. doi: 10.25259/CSDM_180_2024
Abstract
Objectives:
This study evaluated the safety of Venusia CeraPlus Moisturizing Cream using the human repeat insult patch test (HRIPT).
Materials and Methods:
A single-center, non-randomized, double-blinded, observational study was conducted from February 12 to March 27, 2024. 211 participants (aged 18–65, Fitzpatrick skin types III–V) completed the study. The HRIPT protocol included induction, rest, and challenge phases. Skin reactions were assessed using the Draize scale during induction and the International Contact Dermatitis Research Group scale during the challenge phase.
Results:
The study demonstrated favorable results for Venusia CeraPlus moisturizing cream. During the induction phase, the product showed a mean cumulative irritation score of 0.37, which was well below the non-irritant threshold of 2. In the challenge phase, no participants exhibited strong positive reactions (++) at any time point. No adverse events were reported by any of the participants.
Conclusion:
Venusia CeraPlus moisturizing cream demonstrated non-irritant properties after nine repeat applications and was found to be hypoallergenic in the study population.
Keywords
Allergic contact dermatitis
Human repeat insult patch test
Moisturizer
Skin Irritation
INTRODUCTION
The widespread use of moisturizers among young individuals is evident, with over 75% of the global youth population incorporating them into their daily routines.[1] This trend reflects the growing emphasis on skin health and hydration. Numerous studies highlight the important role of moisturizers in maintaining skin moisture, enhancing the skin’s barrier function, and protecting against environmental stressors.[2] Moisturizers are also commonly used to manage conditions such as xerosis and atopic dermatitis.[3] However, while their benefits are well documented, research warns of potential risks with excessive use, such as increased susceptibility to food allergies.[4] This highlights the importance of mindful application and understanding individual skin needs.
Patch testing is a key method for assessing the potential of products to cause irritation or allergic reactions by applying a suspected allergen to the skin under occlusion and observing reactions. It effectively distinguishes between allergic and irritant contact dermatitis, proving valuable in diagnosing persistent skin conditions and cutaneous adverse drug reactions. Studies highlight its utility in identifying specific allergens, such as fragrance mixtures, and its sensitivity can be enhanced with protocol modifications, especially for non-irritating products like feminine hygiene items. However, caution is needed due to the risk of false positives, particularly with rinse-off products.
Considering the critical role moisturizers play in skin health, it is imperative to evaluate the safety and efficacy of new formulations. Our study focuses on the Venusia CeraPlus Cream, specifically assessing its potential for skin irritation and sensitization using the human repeat insult patch test (HRIPT).
MATERIALS AND METHODS
This was a single-center, non-randomized, double-blinded, observational study to assess the skin irritation and skin sensitization potential of Venusia CeraPlus moisturizing cream using the HRIPT technique. The study was carried out under the supervision of the principal investigator/dermatologist. The study was conducted from February 12, 2024, to March 27, 2024. The study protocol was approved by an Independent Ethics Committee (ECR/245/lndt/MH/2015/RR-22). The study was conducted in compliance with the Declaration of Helsinki, Good Clinical Practices, and ICMR guidelines concerning medical research in humans. Potential risks and benefits were explained to the participants, and informed consent was obtained from all participants before entry into the study.
Study population
Participants were recruited from the dermatology outpatient department following a thorough screening by the principal investigator. To ensure the inclusion of individuals with normal, healthy skin, a comprehensive dermatological examination was performed. The test area (upper back) was assessed for any conditions such as dermatitis, eczema, scars, or infections that might influence the study results. For participants with sensitive skin, the lactic acid sting test [Appendix A] was used to confirm sensitivity without the presence of active dermatological conditions. The study population consists of 200 complete cases, as determined by the sample size guidelines outlined in IS 4011:2018 (Third Revision, July 2018).
Inclusion criteria
Men and women aged 18–65 years with apparently healthy skin on the test area and Fitzpatrick skin types III–V.
At least 50 participants with sensitive skin, as determined by the lactic acid sting test were included.
Participants agreed to avoid water contact (such as swimming), excessive sweating activities (like exercise and sauna), and intense ultraviolet exposure on the test site during the study.
In addition, they should be able to read and write in English, Hindi, or the local language and possess valid proof of identity and age.
Exclusion criteria
Pregnancy, lactation, scars, tattoos, excessive terminal hair on the test area, previous hypersensitivity to cosmetic products, chronic illnesses that may influence the study outcome, current or recent (within one month) medical treatments that may interfere with the study, and participation in other clinical trials.
Study intervention and follow-up
The test product, Venusia CeraPlus Moisturizing Cream (Batch No. EOCMC0123–22; contains purified water, propylene glycol, glycerin, emulsifying wax, cyclomethicone, and a blend of natural butter and aloe), and negative control of 0.9% isotonic saline solution (Batch No. 82RL404101) were applied occlusively to the backs of healthy participants.
The study was conducted in three main phases: Induction, rest, and challenge. The induction phase, lasting three weeks, consisted of nine cycles of patch application and removal. On day 1 (Visit 1), patches containing either 0.04 g of the cream or 0.04 mL of saline solution on filter paper were applied occlusively to the participants’ backs. These patches were removed the following day (Visit 2), and on the 3rd day (Visit 3), the patch areas were graded and scored before new patches were applied. This cycle was repeated throughout the induction phase, with patch removals occurring on alternate visits (4, 6, 9, 11, 13, 16, 18, and 20) and grading, scoring, and new patch applications on the subsequent visits (5, 7, 10, 12, 14, 17, and 19). The final grading and scoring of the induction phase took place on Visit 21.
Following the induction phase, participants entered a 14-day rest period. This break applied to both Batch I and Batch II of the study. After the rest period, the challenge phase began. On Visit 22, patches were applied to naïve sites adjacent to the original induction sites. These patches were removed after 24 h on Visit 23. Scoring was then conducted at 48 h (Visit 24), 72 h (Visit 25), and 96 h (Visit 26) post-application to assess any delayed reactions.
Throughout the entire study, clinical research associates, who were trained by the Principal Investigator, were responsible for weighing and applying the products. They also provided crucial support by counseling participants on how to follow the protocol procedures during their site visits. Safety measurements were consistently assessed according to a predetermined schedule outlined [Appendix B, Tables S1 and S2].
The study concluded with a follow-up phase. Participants who showed any reactions during the challenge phase were followed up after one week. This follow-up was crucial to confirm their recovery and ensure that all reactions had completely subsided.
Scoring criteria
In the induction phase, scoring of the test area was done using the Draize scale, which evaluates erythema/dryness/wrinkles and edema on separate 0–4 scales.[5] In the Challenge Phase, reactions were scored using the international Contact Dermatitis Research Group scale, which uses symbols to denote reaction severity from no reaction (-) to extremely positive (+++)[6] [Appendix B, Tables S3 and S4].
Evaluation
Data from participants were analyzed for both the induction phase and the challenge phase.
RESULTS
Out of 220 participants recruited for the study, 211 successfully completed both the induction and challenge phases, resulting in 9 dropouts. The specific participant numbers and reasons for these dropouts were documented, ensuring that any factors influencing their withdrawal were noted [Table 1].
| Participant number | Reason for Dropout | Participant number | Reason for Dropout |
|---|---|---|---|
| Batch I | Batch II | ||
| A56 | Lost to follow up | Z100 | Lost to follow-up |
| A72 | Lost to follow-up | Z108 | Lost to follow-up |
| A73 | Lost to follow-up | Z111 | Lost to follow-up |
| A80 | Lost to follow-up | Z115 | Lost to follow-up |
| Z129 | Lost to follow-up | ||
Participant demographics
211 completed the study (19 males and 192 females). The mean age was 37.09 years (range: 18–63 years). 59 participants had sensitive skin, whereas 152 had normal skin [Table 2].
| Total number of cases (n) | 211 |
|---|---|
| Age (years) | |
| Mean | 37.09 |
| SD | 10.01 |
| Range | 18–63 years |
| Gender | |
| Males | 19 |
| Females | 192 |
| Skin | |
| Sensitive Skin | 59 |
| Normal Skin | 152 |
SD: Standard deviation
Product assessment criteria
During the induction phase, Venusia CeraPlus moisturizing cream demonstrated a mean cumulative irritation score of 0.37, which fell below the threshold of 2, indicating it was non-irritant. The negative control (0.9% isotonic saline) had a lower mean cumulative score of 0.06 [Table 3]. In the challenge phase, none of the participants showed any strong positive reactions (++) at any time point for the test product. The negative control showed a similar trend of decreasing reactions over time, with 204, 209, and 210 participants showing no reactions at 48, 72, and 96 h respectively, and the number of doubtful reactions decreasing from 7 to 1 over the same period [Table 4].
| Product | Mean cumulative scores n=211 |
|---|---|
| Venusia CeraPlus Moisturizing Cream | 0.37 |
| 0.9% Isotonic saline solution | 0.06 |
n: Total number of cases
| 48 h (n=211) | 72 h (n=211) | 96 h (n=211) | |
|---|---|---|---|
| 0.9% Isotonic saline solution | 204 participants did not react (-) 7 participants had doubtful reactions (?) None of the participants had any weak or strong positive reactions. |
209 participants did not react (-) 2 participants had doubtful reactions (?). None of the participants had any weak or strong positive reactions. |
210 participants did not react (-). 1 participant had a doubtful reaction (?). None of the participants had any weak or strong positive reactions. |
| Venusia CeraPlus Moisturizing Cream | 185 participants did not react (-) 25 participants had doubtful reactions (?) 1 participant had a weak positive reaction (+) None of the participants had any strong positive reactions. |
198 participants did not react (-) 13 participants had doubtful reactions (?) None of the participants had any weak or strong positive reactions. |
209 participants did not react (-) 2 participants had doubtful reactions (?). None of the participants had any weak or strong positive reactions. |
n: Total number of cases.
Adverse events
No adverse events were reported during the study.
DISCUSSION
The HRIPT for Venusia CeraPlus moisturizing cream in our study population showed non-irritant after nine repeat applications and was hypoallergenic.
In this study, we employed the HRIPT, which is widely regarded as the most reliable method for obtaining definitive human data on skin reactions. Studies demonstrate its sensitivity, with repeated exposure to irritants such as sodium lauryl sulfate leading to heightened skin reactions.[7,8] The HRIPT has also been useful in comparing barrier creams, showing significant differences in irritation levels.[9] Standardized protocols ensure reliable results across various settings, and the 4-h patch test has emerged as a reliable alternative to animal testing.[10]
The findings from this study demonstrated that Venusia CeraPlus moisturizing cream did not elicit any adverse events when tested using the HRIPT. These results are consistent with previous research. A similar study on Venusia Max lotion (poly alkyl methacrylate free), where HRIPT similarly revealed no irritant or allergenic reactions.[1] A related study by Nisbet also evaluated the safety of a lamellar moisturizer, comparing it to a saline control.[11] Out of 233 participants, 214 completed the study, and 99.6% of participants had negative patch test results, further supporting the minimal allergenic risk associated with moisturizers.
Limitations
Limitations of the study include a relatively small sample size and the study being conducted at a single center, which may limit the generalizability of the findings. In addition, the exclusion of individuals with varying degrees of sensitivity could affect the results, and the reliance on subjective scoring systems may introduce variability in assessment outcomes.
CONCLUSION
The findings from this study indicate that Venusia CeraPlus moisturizing cream is a safe and well-tolerated option for individuals with sensitive skin, demonstrating low irritation and sensitization potential. The absence of adverse events and the high percentage of participants exhibiting no reactions highlight its suitability for this demographic. Future research should consider larger, multicenter trials to further validate these results and explore long-term effects, thereby enhancing the understanding of the product’s efficacy in diverse populations.
Acknowledgments
We want to express our sincere appreciation to QREC Clinical Research LLP for supporting us with medical writing and submission in the journal and to individuals, whose contributions have greatly improved the quality of this research.
Ethical approval
Institutional Review Board (IRB) approval was obtained by Claims Independent EC for the study (ECR/245/Indt/MH/2015/RR-22), along with the clinical trial registration number CTRI/2024/02/062234.
Declaration of participant consent
The authors certify that they have obtained all appropriate participant consent.
Conflicts of interest
All authors, Dr. Biswajit Aich, Preeti Kumbhar, Dr. Snehal Muchhala, Dr. Arti Sanghavi, Dr. Sagar Katare, and Dr. Bhavesh Kotak are employees of Dr. Reddy ’s Laboratories Ltd.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship
This research was funded by Dr Reddy’s Laboratories Limited, Ameerpet, Hyderabad, Telangana, India.
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