LIP BALM: SUMMARY OF THREE DERMATOLOGICAL STUDIES 5 assessment and reapplication for 3 weeks at 48 h intervals or 72 h intervals over a week- end (±1 d) for a total of eight applications. After the last assessment for cumulative dermal irritation, the sensitization (challenge) phase of the study was initiated. Volunteers completed a 2-week wash out period, and then returned to the clinic for the application of patches with test product and controls to skin areas on the back or forearm that had not been previously occluded. After 48 h, the patches were removed and initial sensitization assessments were recorded. Volunteers returned the following day for their 72-h assessment. Study 2 consisted of two phases of separate assessments for dermal photoirritation and dermal photosensitization. For the assessment of dermal photo irritation, patches with test product and controls were applied to volunteers’ backs after 2 h, the patches were removed and the patch area was irradiated by UVA-emitting equipment at the 10 J/cm2 dose. The volunteers returned after 24 h for a dermal assessment of the patch area. In parallel to the photo irritation phase of the study, the accumulated photosensitization effect was measured. On day 1, patches with test product and controls were applied to a different area of volunteers’ back. During a 12-d period, the procedure included the re- moval of the patches, the UVA irradiation to the area at 4 J/cm2 dose, and the reapplica- tion of the patches on days 2, 4, 5, 8, and 10. On day 12, the patches were removed and irradiation performed. After the last irradiation, volunteers were off product for 2 weeks and then returned for a challenge phase. Two sets of patches containing the same test product and controls were applied to volunteers’ back in areas that had not been previously occluded. Twenty-four hours later, volunteers re- turned for patch removal. One area received UVA irradiation at 4 J/cm2 dose, and the other area received no irradiation. Assessments were performed on both areas 48 h after irradiation. After the last assessment, volunteers had a new dermatological assessment performed to compare the baseline and end of study skin condition. Study 3 was a single-center, noncomparative, blind study, where the product was assessed at the site of use (on the lips) for 28 ± 2 d in volunteers with a clinical diagnosis of sensi- tive skin. Assessments performed by dermatologists were conducted at the beginning and end of the study. The study was conducted in healthy volunteers of both genders between 18 and 60 years of age who met criteria of sensitive facial skin as diagnosed using the stinging test proce- dure (7), as follows: Two different cotton swabs were soaked, one with 10% lactic acid and the other with saline solution, and applied in different areas of the volunteer’s alar groove. Five minutes after the application, the grade for sensation of burning was recorded, according to the following scale: 0 - None, 1 – Little, 2 – Moderate, and 3 – High/Severe. Volunteers re- porting a grade of ≥2 meet the criteria for Sensitive Facial Skin. After confi rmation of sensitive skin diagnosis, the tubes of test product, including in- structions for use (as many times as needed, at least twice daily) and the Diary of Use, were dispensed to the volunteers. Volunteers were provided instructions for the correct completion of the diary (date, number of times the test product was applied and whether there were any sensations of discomfort) and were required to bring the completed diary

JOURNAL OF COSMETIC SCIENCE 6 to their last study visit. The volunteer was instructed to go to the Institute for a medical assessment in case he/she experiences any discomfort during the study period. After 28 d of use, the volunteers returned to the Institute for a new dermatological assess- ment to assess skin integrity and whether or not there had been the formation of ery- thema, edema, desquamation, vesiculation, or other clinical signs and/or symptoms at the site where the product had been applied. A tolerance of ±2 d was allowed for volunteers to return for their fi nal assessment. At the study end, the volunteer answered the Subjective Assessment (redness, itching, swelling, desquamation, small spots, small blisters, marks, and burning) to identify po- tential signs and/or symptoms seen during the study, according to his/her self-perception. RESULTS The studies provided robust data to assess the irritation and sensitization properties of the prototype lip balm. The demographics of the studies are described in Table III. Most subjects were female, with a broad distribution of enrollment for age range of 18–61 years targeted for inclu- sion in studies. Of the 99 subjects who enrolled in the three studies, 92 completed study obligations and provided data for the analyses. There were four subjects lost to follow-up, one subject in Study 1 (did not attend visit three onward and withdrew consent for personal reasons) and three subjects in Study 3 (did not attend the fi nal study visit or respond to efforts to contact them). Thus, these volunteers were discontinued from the studies and their data were not considered (Table IV). There were two subjects who discontinued due to protocol violations (Table IV), both subjects were withdrawn from the respective study for using an anti-infl ammatory drug during the study period. One subject in Study 1 was withdrawn from the study when she presented with erythematous papular lesions in the posterior chest area (eczema) on day 3 (Table IV). According to the medical evaluation, the lesion was classifi ed as moderate and the diagnostic hypothesis as contact eczema probably related to the glue from the adhesive tape (Micropore®). The subject discontinued the use of the test product patch without any new challenge. Treatment with Diprogenta (betamethasone dipropionate 0.64 mg + betamethasone 0.5 mg + gentamicin 1 mg) was administered twice daily for 5 d the subject was subsequently evaluated in 7 d and the Diprogenta treatment was discontinued as the adverse event had resolved with no sequelae. Table III Demographic Data for Subjects that Completed Studies 1–3 Study 1 Study 2 Study 3 Subjects completed 52 30 30 Male 5 3 4 Female 47 27 26 Age range (year) 18–60 21–60 23–60 Median age (year) 39 37 47.5