Evaluation of the Skin Irritation and Sensitization Potential of the Cussons Baby Sensicare Skin Range of Products in Healthy Volunteers

Introduction: The Cussons Baby Sensicare Range is a newly developed set of products specially formulated for newborn, sensitive and eczema prone skin. As such, these products need to be tested to evaluate their skin irritation and sensitization potential before use. The products were evaluated with two separate tests. The first test was conducted in a single-center, within-subject comparison using assessor-blind, randomised human skin irritation patch test (48 hour/96 hour exposure) and conducted on healthy adults with sensitive, atopic skin. The second test was conducted in a single-center, controlled (sterile water), within subject using human repeat-insult patch tests (HRIPTs) and conducted on healthy female Indonesian and Asian adult female subjects, with sensitive skin. The sensitization potential of each product was determined from International Contact Dermatitis Research Group (ICDRG) scores at 30 minutes, 24 hours, 48 hours and 72 hours after patch removal. Skin irritation tests show that all products were significantly lower than the positive control sodium lauryl sulphate (SLS) (p < 0.05) but not significantly different to the negative control (sterile water) in terms of irritation scores at the respective time points. HRIPTs results show that Cussons Baby Sensicare Range was non-sensitizing. As such, it can be concluded that the Cussons Baby Sensicare Range tested is well tolerated on skin and has low skin irritation and sensitization potential. Thus, they can be considered hypoallergenic on sensitive skin and suitable for eczema prone skin.


Introduction
Contact sensitization is a process whereby the host (through prior skin exposure) acquires a specific, increase sensitivity (reactivity) to a substance upon subsequent exposure. Whereas reactions may be minimal or absent upon the first contact, the skin responds to subsequent applications in a heightened manner. The reaction may range in severity from a minor annoyance of transient redness and itching, to a severe, widespread and possibly disabling eczematous eruption. It is important that new cosmetic products are tested to evaluate their skin irritation and sensitization potential.
The Cussons Baby Sensicare Range (PZ Cussons, Indonesia) is a new specially developed range of products for newborn, sensitive and eczema prone skin. Baby skin differs from adult skin and requires special care [1] [2]. The products are based on a Triple Protection Complex consisting of avena sativa (oat) extract, olea Europaea (olive) fruit oil and ceramides; ingredients selected for their dermocosmetic properties (moisturization, barrier protection, anti-inflammatory, antioxidant and soothing effects). Oats have been used for a long time to alleviate itching and irritation [3] and avena sativa has been shown to have preventive effects on skin irritation in a SLS model [4]. Olive oil's composition is similar to that of sebum which makes it particularly able to protect the skin [5]. Ceramide 3 has been shown to have a protecting effect against surfactant-induced dermatitis [6]. In order to determine the hypoallergenicity and skin irritation potential of the Cussons Baby Sensicare range of products a human repeat insult patch test (HRIPT) and human skin irritation patch test were conducted in adult volunteers.

Skin Irritation Potential (48/96 h Single Patch Test)
This was a single-centre, within-subject comparison, assessor blinded, randomised study conducted by Alba Science Ltd in 26 healthy volunteers, male and female aged 18 to 70 who had self-assessed sensitive, atopic skin (assessed by completion of a questionnaire).  The application area for the test and control products was the upper, outer arms. A randomised product application schedule was generated for each subject to randomly allocate each product to an application site. The order of products in the patch schedule was randomised to eliminate position and order bias.
Approximately 20 µl of each product and control was applied to the skin under an occlusive patch (Finn Chamber 8 mm). Skin markers marked either end of the Finn Chamber to allow exact relocation to the test areas at subsequent applications. Approximately 23 hours after application the subjects removed their patch and washed the test sites to remove residual test and control material. The test sites were assessed approximately 1 hour later by a trained assessor, following the scoring system detailed in Table 2. After assessment, an identical patch was reapplied to the same area for a further period of approximately 23 hours.
The test and control materials were reapplied to the same sites as before, following assessment. Any test or control material which elicited erythema or dryness with a score of 5 or more was not reapplied. Any test or control material which elicited a palpable response was not reapplied.

Skin Sensitization Potential (Human Repeat Insult Patch Test, HRIPTs)
One hundred (100)  Phase before the Challenge Phase when subjects were patched again for 24 hours to a previously untreated skin site. An overview of the product application in the RIPTs is provided in Table 3. Thirty minutes after removal of each patch and prior to the next patch application during the Induction Phase, erythema, oedema, dryness and presence of vesicles were assessed and recorded by a Dermatologist according to the criteria detailed in Table 4. The Mean Cumulative Irritation Index (MCII) across the study population was calculated from these scores using the following formula: The irritating potential of each product during the Induction Phase was then classified according to MCII as detailed in Table 5. hours, 48 hours and 72 hours after patch removal ( Table 6). The sensitization potential of each product was determined from these scores.

Skin Irritation Potential
Twenty-nine subjects with self-assessed sensitive, atopic skin were recruited for the study and 27 subjects were screened. Of these, 26 subjects participated in and completed the study (10 males and 16 females). The mean age of study participants was 39.4 years (range 19 -63 years). The total means of irritation scores (erythema and dryness) are presented in Table 7. All products were significantly lower than the positive control (p < 0.05). The products were not significantly different from the negative control in terms of irritation scores at the respective time points. There were no adverse events reported during the study. All test products were well tolerated during the study.

HRIPT
One hundred and forty-five (145) subjects were evaluated with the 1% closed patch test with SLS. From these subjects one hundred and eleven (111) subjects were selected to enter the study, having confirmed sensitive skin. There were seven (7) dropouts and one hundred and four (104) subjects completed the study. The average age of study participants was 34.8 years (range 18 -53 years). The Cussons Baby Sensicare Gentle Hair and Body Wash was found to be slightly irritating during the Induction Phase of the RIPT (MCII = 0.183) and non-sensitizing (reaction was only very slight erythema in 23/104 subjects with no persist oedema or infiltration reactions noted). The Cussons Baby Sensicare 24 hours Daily Moisturizing Lotion was found to be very slightly irritating during the Induction Phase of the RIPT (MCII = 0.097) and non-sensitizing (reaction was only very slight erythema in 18/104 subjects with no persist oedema or infiltration reactions noted). The Cussons Baby Sensicare Intensive Soothing Cream was found to be very slightly irritating during the Induction Phase of the RIPT (MCII = 0.078) and non-sensitizing (reaction was only very slight erythema in 12/104 subjects with no persist oedema or infiltration reactions noted). Results are summarised in Table 8.

Discussion
The Skin Irritation Patch Test (48 h/96 h Exposure) in a panel of healthy subjects who have self-assessed sensitive, atopic skin is used to assess the primary skin irritation potential of Cussons Baby Sensicare products when applied cutaneously to subjects. The aim of this study was to substantiate the claims of "Dermatologically Tested and Approved", "Suitable for Sensitive Skin", "Suitable for Eczema Prone Skin" and "Paediatrician Approved" for each test material.
Assessments were confirmed by a dermatologist and Paediatrician.
The test products were well tolerated during the study, producing low levels of All test products can claim "Dermatologically Tested and Approved", "Suitable for Sensitive Skin", "Suitable for Eczema Prone Skin" and "Paediatrician Approved".
The human repeat insult patch test (HRIPT) is a standard cosmetic industry approach to testing a formulation's irritation and sensitization potential. The method used in this study was based on the Shelanski-Shelanski test method [7].
The induction phase evaluates the irritation potential of a product and the challenge phase (Phase II also known as the Elicitation Phase) evaluates the sensitization potential. A response during the challenge phase is normally an allergic one. The HRIPT evaluated the irritation after application of the products 15 times over a three week period. Irritation potential was also assessed in the cumulative skin patch test following 2 or 4 consecutive 23-hour patch application with assessment of reactions approximately 1 hour after each patch removal. The There were no sensitization reactions in the HRIPT.

Conclusion
In conclusion, the Cussons Baby Sensicare range of products can be considered as low irritation potential and hypoallergenic on sensitive skin and suitable for eczema prone skin.