Human Repeated Insult Patch Test Research Articles

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.

Safety Assessment of Pentaerythrityl Tetra-Di-t-Butyl Hydroxyhydrocinnamate as Used in Cosmetics

Pentaerythrityl tetra-di -t-butyl hydroxyhydrocinnamate functions as an antioxidant in cosmetic products and is used at concentrations up to 0.8%. Given the high molecular weight of this ingredient, skin penetration is not likely. The available toxicity data, together with the low ingredient use concentrations, suggest that systemic toxicity would not be likely if percutaneous absorption were to occur. Additionally, the negative human repeated insult patch test data at a concentration of 0.5% were deemed sufficient for evaluating the skin irritation and sensitization potential of pentaerythrityl tetra-di -t-butyl hydroxyhydrocinnamate over the range of use concentrations in cosmetic products. The Cosmetic Ingredient Review Expert Panel concluded that pentaerythrityl tetra-di -t-butyl hydroxyhydrocinnamate is safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Safety Assessment of PEG-150 Pentaerythrityl Tetrastearate as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of polyethylene glycol (PEG)-150 pentaerythrityl tetrastearate, which functions as a viscosity-increasing agent-aqueous in cosmetic products and is being used at concentrations up to 5%. Given the chemical structure (large molecule), skin penetration is not likely. The available toxicity data and the low ingredient use concentrations suggest that systemic toxicity would not be likely even if percutaneous absorption were to occur. Additionally, the negative human repeated insult patch test data on the undiluted ingredient were deemed sufficient for evaluating skin irritation and sensitization potential. The Panel concluded that PEG-150 pentaerythrityl tetrastearate is safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Novel peptide inhibits inflammation by suppressing of protease activated receptor-2

We synthesized and investigated the effects of a novel peptide B, RRFSLLRY as a novel PAR-2 antagonist. Peptide B decreased calcium levels in HaCat cells stimulated with trypsin and PAR-2 activator (SLIGKV) and cytokeratin 14 and PCNA was decreased by peptide B. Peptides B also reduced the expression of inflammatory cytokines such as TNF-α and interleukin-6. Significant increase of oxazolone-induced transepidermal water loss (TEWL) was decreased by the addition of peptide B in hairless mice. These findings suggest that the anti-inflammatory effect of peptide B is due to inhibition of PAR-2 signaling. Skin safety of peptide B was demonstrated by performing MTT assay and human repeated insult patch test. Our findings indicate that peptide B might have potential as an anti-inflammatory agent without irritating skin for use in cosmetics and medical treatment of dermatologic disorders.

1257 Topical application of self-delivering RNAi (sd-rxRNA®) compounds for reduction of hyperpigmentation

There are many dermal hyperpigmentation disorders caused by an over-production of melanin. The enzyme tyrosinase catalyzes the rate-limiting steps in the production of melanin by melanocytes and inhibition of tyrosinase may result in a reduction in pigmentation. We have developed a new class of stable, self-delivering RNAi compounds that incorporate features of RNAi and antisense technology. sd-rxRNAs demonstrate potent activity, stability, and reduced immune stimulation, and are rapidly and efficiently taken up by cells. Tyrosinase-targeting sd-rxRNAs were screened to identify RXI-231, a lead compound to be developed as a cosmetic ingredient for improvement of skin tone. RXI-231 was tested in normal human embryonic melanocytes and MelanoDerm, a 3D reconstituted human epidermal culture model. Treatment with RXI-231 resulted in a reduction in tyrosinase mRNA expression, in vitro dopachrome formation, and melanin content in both models. We have developed a topical gel formulation that enables non-invasive epidermal delivery of our compounds using a proprietary mixture of penetration enhancers that can be used in cosmetic or pharmaceutical formulations. A consumer testing program consisting of 3 studies was carried out. The first 2 studies were human repeat insult patch tests (hRIPT). Results from a 14-day cumulative irritation assay and human maximization test showed that RXI-231 gel did not cause irritation or sensitization to human skin. A third study investigated the potential of RXI-231 to impact a skin melanin content (pigmentation) increase induced by UV in healthy volunteers, as measured by narrow-band reflectance spectroscopy. The spectroscopic results - known to correlate well with skin melanin content - demonstrated that application with RXI-231 containing gel can reduce a change of skin tone triggered by UV exposure, as compared to vehicle control (p < 0.04). Combined with the preclinical data, these clinical results suggest that RXI-231 may impact skin pigmentation induced by UV exposure.

Absence of human skin irritation and allergenic potential after repeated patch applications of a lamellar moisturizer.

SummaryBackgroundNew cosmetic products should undergo clinical evaluation for skin sensitization potential.ObjectivesTo assess the irritation and sensitization potential of a moisturizer containing lamellar structured lipids after repeated patch application in humans, using human repeated insult patch test methodology.MethodsThis 6‐week, single‐center, open‐label study compared a lamellar moisturizer with negative saline control in human subjects aged 18‐70 years and skin phototype (Fitzpatrick) classification I–IV. During an initial induction phase, semi‐occlusive multi‐test patches were applied to the skin of participants’ backs three times per week for 3 consecutive weeks; clinical assessments were performed per International Contact Dermatitis Research Group criteria. Participants subsequently underwent a challenge phase, where a new patch was applied to a contact‐naïve area of the skin to assess sensitization to the moisturizer.ResultsThe study commenced with 233 voluntary participants, 214 of whom completed the study and underwent the final dermatological assessment. Most participants (232/233; 99.6%) demonstrated negative patch test results. One participant had a positive reaction at the lamellar moisturizer application site, with visible erythema and edema (classified as an adverse event [AE]); however, this reaction was observed 24 hours after a reaction to another product in the patch test panel (a prototype cleanser). Importantly, no skin reactions were detected during the challenge phase. Two participants had AEs of mild contact dermatitis in the area of patch adhesive application during the induction phase. No serious AEs occurred during the study.ConclusionsThese findings suggest that the lamellar moisturizer has low irritant and allergenic potential.

Rice Water: A Traditional Ingredient with Anti-Aging Efficacy

The skin healing benefits of rice have been known for centuries. Rice (Oryza sativa) water is a food processing waste that can potentially be incorporated into cosmetic formulations. However, no scientific evidence supports their role in skincare products. The aim of this project is to design and develop a topical gel formulation containing rice water and to evaluate its biological properties, namely, the anti-aging and antioxidant rice water properties. Rice water was evaluated in terms of physico-chemical composition and in terms of in vitro biological antioxidant activity and elastase inhibitory effect. Rice water was incorporated into a hydrogel and the developed formulation was subjected to pharmacotechnical tests such as pH and viscosity. Biological and sensory effects were evaluated on a panel of 12 volunteers for 28 days. The safety evaluation study was performed on rice water gel, using the Human Repeat Insult Patch test protocol. Rice water presented in vitro biological antioxidant activity and elastase inhibitory effect. The gel formulation containing 96% rice water was biocompatible with the human skin and presented suitable cosmetic properties. Rice water should be thus considered as an anti-aging ingredient to be used as raw material for skincare applications.

Safety assessment of starch-based personal care products: Nanocapsules and pickering emulsions

The safety profile of the ingredients used in topical dosage forms and its evaluation is an issue of utmost importance. A suitable equilibrium between safety and efficacy is crucial before promoting a dermatological product. The aim of this work was to assess the safety and biological effects of starch-based vehicles (St-BV) used in such products. The hazard, exposure and dose-response assessment were used to characterize the risk of each ingredient. The EpiSkin™ assay and human repeat insult patch tests were performed to compare the theoretical safety assessment to in vitro and in vivo data. The efficacy of the St-BV was studied using biophysical measurements in human volunteers during 28 days, showing that all ingredients and their combinations were safe for the consumer. Tissue viability determined using the EpiSkin™ testing reached values between 84.0 ± 5.0% and 98.0 ± 8.6% after application of St-BV, which were considered as non-irritant to the skin. These observations were confirmed by the in vivo studies where the St-BV did not induce any sensitization on the volunteers, being safe for human use. Moreover, St-BV increased skin hydration and microcirculation, emerging as an attractive alternative to chemical raw materials.

Cynara scolymus L.: A promising Mediterranean extract for topical anti-aging prevention

Cynara scolymus L. (CS), usually known as globe artichoke, is a Mediterranean plant with antioxidant properties due to its content of polyphenols, including caffeoylquinic and dicaffeoylquinic acids. The use of bioactive ingredients or phytochemicals extracted from plant tissues in cosmetics is increasing, thus artichoke extract due to its promising constituents can be incorporated in topical formulations. The aim of this study was the chemical characterization of different CS extracts in order to investigate the antioxidant and the sun protection potential in topical formulations. Aqueous extracts were analyzed by HPLC to quantify target compounds, such as cynarin, chlorogenic acid and cynaroside. Antioxidant activity by DPPH assay and ROS scavenging activity in HaCaT cells, as well as cytotoxicity assays and sun protection factor were assessed. The results showed that CS extract and CSC fraction, one of the purified fractions, were rich in polyphenols and presented antioxidant and photoprotective activity. Then, both fractions were incorporated in two topical formulations: O/W emulsion and hydrogel. Physicochemical characterization, microbiological control, cytotoxicity assays and ROS scavenging activity in HaCaT cells were performed to ensure the quality, safety and efficacy of the products developed. In vivo studies, Human Repeat Insult Patch Testing and an assay to determine their antioxidant capacity, were also performed. Besides the excellent antioxidant and photoprotective activity, the final formulations proved to be also suitable and safe for topical use.

Characterization of Portuguese Thymbra capitata, Thymus caespititius and Myrtus communis essential oils in topical formulations

AbstractAs the personal care industry evolves, formulators are seeking innovative solutions for their formulations' needs, and for ingredients that can offer multiple functions within formulations. Considering that essential oils (EOs) may present a wide spectrum of biological activities, the composition, antimicrobial and antioxidant activity of Portuguese Thymbra capitata, Thymus caespititius and Myrtus communis EOs were assessed in order to evaluate them as preservatives and antioxidants in topical emulsions. The in vivo safety application of some emulsions was also tested. T. capitata EO was mainly constituted by carvacrol (73%), whereas α‐terpineol (27%), p‐cymene (14%) and carvacrol (10%) dominated Th. caespititius EO, and 1,8‐cineole (37%) was dominant in M. communis EO. The minimum inhibitory concentration of T. capitata, Th. caespititius and M. communis EOs was 0.4 μg/mL against C. albicans and ranged between 0.4 and 30.7 μg/mL against A. brasiliensis. Gram‐positive bacteria were more susceptible to each EO than Gram‐negative bacteria. T. capitata EO showed significantly higher antioxidant activity than Th. caespititius and M. communis EOs. EOs incorporated in emulsions showed preservative activity against all microorganisms tested and T. capitata EO emulsions showed powerful reactive oxygen species (ROS) scavenging effects. A safety evaluation study was performed with 0.10% and 0.01% T. capitata EO emulsions according to the Human Repeat Insult Patch Test (HRIPT). All emulsions were considered safe for topical application. T. capitata, Th. caespititius and M. communis significantly improved the microbiological quality of the prepared emulsions and may constitute a powerful alternative to the current preservatives and antioxidants for use in topical formulations.

Echinacea purpurea-derived alkylamides exhibit potent anti-inflammatory effects and alleviate clinical symptoms of atopic eczema

BackgroundAtopic eczema (AE) is a chronic inflammatory and pruritic skin disease. There is still an unmet need for topical anti-inflammatory and anti-pruritic substances exhibiting an excellent safety profile. The endocannabinoid system is known to regulate various aspects of cutaneous barrier and immune functions, thus targeting it may be a valid approach for alleviating the symptoms of AE. ObjectiveTo assess the putative efficacy of Echinacea purpurea-derived alkylamides (Ec. extract) activating cannabinoid (CB)-2 receptors in exerting anti-inflammatory effects and alleviating symptoms of AE. MethodsIn vitro anti-inflammatory efficiency was investigated by monitoring the effects of Ec. extract on poly-(I:C)-induced pro-inflammatory cytokine expression (Q-PCR) and release (ELISA) of HaCaT keratinocytes. Irritancy and sensitization potential (assessed by Human Repeat Insult Patch Test; Clinical trial 1); clinical efficiency in alleviating symptoms of AE (Clinical trial 2) as well as effects on human skin structure and lipid content (Clinical trial 3 followed by transmission electron microscopy and HPTLC) were investigated in randomized double blind clinical trials. ResultsEc. extract significantly reduced mRNA expression as well as release of poly-(I:C)-induced pro-inflammatory cytokines (IL-6 and IL-8) in keratinocytes. Thus, not surprisingly, the well-tolerated (Clinical trial 1) Ec. extract-based cream reduced local SCORAD statistically significantly, not only compared to baseline, but also compared to the comparator (Clinical trial 2). Of great importance, besides the in vitro anti-inflammatory effects, administration of the Ec. extract-based cream also resulted in significantly higher levels of overall epidermal lipids, ceramide EOS (ω-esterified fatty acid+sphingosine sphingoid base), and cholesterol at Day 15 compared to baseline as well as significantly greater numbers of intercellular lipid lamellae in the intercellular space (Clinical trial 3). ConclusionThe investigated Ec. extract shows great potential in alleviating cutaneous symptoms of AE, and by exerting remarkable anti-inflammatory actions and restoring the epidermal lipid barrier, it will be very likely a well-tolerated, powerful novel ingredient for the adjuvant therapy of AE.

Skin Sensitization QMM for HRIPT NOEL Data: Aldehyde Schiff-Base Domain.

The general chemistry principles underlying skin sensitization for Schiff base (SB) electrophiles may be used to develop a quantitative mechanistic model (QMM), based on reactivity supplemented with a hydrophobicity parameter for some but not all structures within the SB reaction domain. For aliphatic Schiff base electrophiles, the log of the no observed effect level (NOEL) values (pNOEL) from the human repeated insult patch test (HRIPT) can be calculated by the reactivity parameter summation of sigma star values (Σσ*) and a hydrophobicity parameter (logP). Specifically, the QMM, pNOEL = 2.34(±0.33) Σσ* + 0.19(±0.07) logP - 2.62(±0.22), n = 19, R2 = 0.77, R2(adj) = 0.74, s = 0.20, F = 27, was developed. Not all parts of the Schiff base domain are modeled with one equation. Particularly, predicting aromatic aldehydes and ketones appears to require a separate equation. Interestingly, the same physical organic chemical properties originally applied to modeling the local lymph node assay potency of Schiff base electrophiles apply to human potency as represented by the HRIPT.

Dermal safety assessment of Arm & Hammer laundry products formulated for sensitive skin

Context: The prevalence of sensitive skin among the general population in industrialized countries is reported to be over 50%. Sensitive skin subjects often report significant reactions to contact with cosmetics, soaps and other consumer products.Objective: This paper describes the overall skin compatibility and mildness program for a newly developed, lightly fragranced, colorant free laundry product (i.e. Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent), specially formulated for individuals with sensitive skin. The skin mildness of the product was compared to Arm & Hammer™ Free & Clear liquid laundry detergent with no fragrance or colorant, and an established history of safe use by sensitive skin consumers.Materials and methods: The test material was a liquid laundry product with a light scent formulated for sensitive skin consumers (Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent). The product was compared to commercially marketed products for sensitive skin with a history of skin safety in the marketplace, including: a very similar product formulation (Arm & Hammer™ Free & Clear with no fragrance), and several selected competitors’ products. Studies were conducted among individuals with self-assessed sensitive skin (based on a questionnaire) using standard protocols for the Human Repeat Insult Patch Test (HRIPT), 10-Day Cumulative Irritation, the Wrist Band Wear test, and the Safety In-Use testing. Responses in all protocols were evaluated by visual scoring of potential dermatologic reactions, and recording any sensory effects at the time of the examination. In addition, sensory effects collected from panelists’ daily diaries were also evaluated.Results: The HRIPT confirmed that neither the fragrance alone, nor the product formulation with fragrance, induced contact sensitization in sensitive skin subjects. The 10-Day cumulative irritation study conducted using sensitive skin subjects showed highly favorable skin compatibility, and the test product was comparable to the control product (Arm & Hammer Free & Clear) and other nonirritant controls. In the Wrist Band Wear test, exposure to laundered fabrics under exaggerated conditions gave similar results for the test and control products, with no objective signs of skin irritation, and no self-reported persistent adverse sensory effects. Very mild, transient and isolated sensory effects were noted in daily diaries by a small proportion of subjects, and were similar for the test and control products. The Safety In-Use tests evaluated 4-week exposure to product and laundered fabrics under realistic use conditions. There were no clinically objective signs of skin irritation, and reports of transitory, mild sensory effects were minimal and similar for the test and controls.Discussion and conclusion: A comprehensive skin safety program on a lightly scented sensitive skin laundry formulation (i.e. Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent) conducted among panels of self-assessed sensitive skin subjects demonstrated that the presence of a light fragrance did not adversely impact skin compatibility in any of the testing protocols when the product was compared to a similar product with no fragrance. The lightly fragranced product demonstrated overall skin compatibility and mildness when tested in a self-assessed sensitive skin population, and compared favorably to currently marketed sensitive skin products.

Melatonin-based pickering emulsion for skin's photoprotection

Context: Based on its antioxidant activity, melatonin was recently found to have a protection effect against photocarcinogenesis.Objective: This work aimed to develop an innovative sunscreen formulation based on the Pickering emulsions concept, stabilized by physical UV filters, modified starch and natural oils associated to melatonin as a key strategy for prevention against UV-induced skin damage.Materials and methods: For this purpose, melatonin was incorporated in Pickering emulsions that were characterized using physicochemical, in vitro and in vivo testing. Physicochemical studies included physical and chemical stability by a thorough pharmaceutical control. The possible protective effects of melatonin against UV-induced cell damage in HaCaT cell lines were investigated in vitro. The safety assessment and the in vivo biological properties of the final formulations, including Human Repeat Insult Patch Test and sunscreen water resistance tests were also evaluated.Results and discussion: These studies demonstrated that melatonin sunscreen Pickering emulsion was beneficial and presented a powerful protection against UVB-induced damage in HaCat cells, including inhibition of apoptosis. The inclusion of zinc oxide, titanium dioxide, green coffee oil and starch ensured a high SPF (50+) against UVA and UVB.Conclusion: The combination of melatonin, multifunctional solid particles and green coffee oil, contributed to achieve a stable, effective and innovative sunscreen with a meaningful synergistic protection against oxidative stress.

Assessing the dermal compatibility of a new female incontinence product line

Context: We have developed a line of products designed to better meet the overall needs of women suffering from urinary incontinence. The products are more discrete and contain a unique odor neutralizing technology (ONT).Objective: This paper describes the overall skin compatibility program for this product line in which the new products were compared to negative controls and/or commercially marketed reference products with an established history of safe use.Materials and methods: Test products consisted of several product forms (light pads/pantiliners, moderate pads, briefs and taped diapers) with ONT and having various degrees of protection. Studies were conducted using standard protocols for 4-day and 21-day cumulative irritation, the Human Repeat Insult Patch Test (HRIPT), and the Behind-the-Knee (BTK) test for mechanical and chemical irritation. In one 4-day irritation study and one HRIPT, test subjects consisted of individuals with self-assessed sensitive skin. In addition, one 4-day study was conducted using normal skin sites, and sites compromised by tape stripping. Nonirritant controls were physiologic saline and/or current, commercially marketed incontinence products. All responses were evaluated by visual scoring of erythema. In addition, in the BTK, transepidermal water loss (TEWL) and adverse sensory effects collected from panelists’ daily diaries were also evaluated.Results and discussion: Two 4-day cumulative irritation studies and one 21-day study demonstrated that a wide range of product forms (liners, light and moderate pads, briefs and adult diapers) produced skin reactions similar to the nonirritant controls. The 4-day study conducted using sensitive skin subjects showed good skin compatibility, and the test products were comparable to the nonirritant controls. In the 4-day study with both normal and compromised skin sites, test products produced mean erythema scores similar to the nonirritant controls. Three HRIPT separate studies confirm that the products do not induce contact sensitization, including one study conducted on individuals with self-assessed sensitive skin. In the BTK, test and control products produced similar irritation, as assessed by erythema, TEWL and sensory effects.Conclusion: The results from the patch tests and mechanical irritation test demonstrate good skin compatibility of the new line of products with the unique ONT. In addition, the forms of the product (i.e. liner, pad or brief), were equally compatible with skin.

Safety assessment of a novel active ingredient, acetyl aspartic acid, according to the EU Cosmetics Regulation and the Scientific Committee on Consumer Safety guidelines.

Acetyl aspartic acid (A-A-A) was proposed as a new novel active ingredient for use in cosmetics. The safety of A-A-A was assessed by following an in-house-developed 'New Ingredient Testing Strategy', which was designed in accordance with the Scientific Committee on Consumer Safety (SCCS) notes of guidance and the requirements of Annex I of the EU Cosmetics Regulation. The aim of the project was to determine whether A-A-A was safe for use in cosmetics and to determine a maximum permitted safe level in the formulations. A literature review was conducted, consulting over 40 different information sources. This highlighted a number of gaps which required testing data. A-A-A was tested for phototoxicity according to OECD test guideline 432, skin irritation according to OECD test guideline 439 and eye irritation according to OECD test guideline 437. Dermal absorption of A-A-A was measured according to OECD test guideline 428 and was used to calculate the margin of safety (MoS). Finally, A-A-A was tested in a human repeat insult patch test (HRIPT) and a 14-day in-use tolerance study. A-A-A was non-phototoxic and was non-irritating to skin and eyes in in vitro testing. Dermal absorption was calculated to be 5%. The MoS for A-A-A was 351, at a level of 5%, for all cosmetic product types, indicating no systemic safety toxicity concern. A-A-A at 5% under occlusive patch on a panel of 50 adult volunteers induced no skin irritation or allergic reaction in the HRIPT study. Finally, repeated application of A-A-A to the periocular area, twice per day for 14 days, in 21 female volunteers, demonstrated that 1% A-A-A was well tolerated following dermatological and ophthalmological assessment in a cosmetic formulation. A-A-A was assessed as safe by the cosmetic safety assessor for use in cosmetics at a level of 5% in all cosmetic product types, in line with the requirements of the EU Cosmetics Regulation and in accordance with the SCCS notes of guidance.

N-nicotinoyl tyramine, a novel niacinamide derivative, inhibits melanogenesis by suppressing MITF gene expression

We synthesized and investigated the inhibitory effects of a novel niacinamide derivative, N-nicotinoyltyramine (NNT) on melanogenesis. NNT inhibited melanin production in B16F10 murine melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH), in human melanocyte and in three-dimensional cultured human skin model. NNT did not affect the catalytic activity of tyrosinase, but acted as an inhibitor of microphthalmia-associated transcription factor (MITF) and tyrosinase expressions in B16F10 cells. These findings suggest that the hypopigmentary effect of NNT results from the down-regulation of MITF and subsequently of tyrosinase, although NNT did not directly inhibit tyrosinase activity. In addition, safety of NNT was verified through performing neural stem cell morphology assay and Human repeated insult patch test as whitening agent. Our findings indicate that NNT may be a potential and non-skin irritant whitening agent for use in cosmetics and in the medical treatment of pigmentary disorders.

The sensitization potential of sunscreen after ablative fractional skin resurfacing using modified human repeated insult patch test

Background: Ablative fractional skin resurfacing has become popular and proven to be useful in treating scars, photoaging and wrinkles. Although post-inflammatory hyperpigmentation (PIH) is the most common complication especially in dark-skinned patients like Asian. Several modalities have been used to overcome the PIH. Objective: To determine the sensitization potential of sunscreen applied immediately after ablative fractional skin resurfacing. Material and methods: Sixty volunteers were recruited. Of these 30 subjects were from previous ablative fractional skin resurfacing study who applied broad-spectrum sunscreen containing anti-inflammatory agent starting on the first day after resurfacing and another 30 non-resurfacing subjects had applied the same sunscreen on the intact skin. All subjects were patch/photopatch tested for sensitization study by using modified human repeated insult patch test (HRIPT). Results: There were significantly higher sensitization rate of UV-filter, octocrylene and the sunscreen in resurfacing group than in non-resurfacing group. Conclusion: Early application of sunscreen after ablative fractional skin resurfacing has increased the incidence of sensitization potential of sunscreen. The sunscreen is recommended to start using from D3 after fractional ablative skin resurfacing to ensure the complete recovery of skin barrier and minimize the risk of sensitization.

Correlation between experimental human and murine skin sensitization induction thresholds

Quantitative risk assessment for skin sensitization is directed towards the determination of levels of exposure to known sensitizing substances that will avoid the induction of contact allergy in humans. A key component of this work is the predictive identification of relative skin sensitizing potency, achieved normally by the measurement of the threshold (the “EC3” value) in the local lymph node assay (LLNA). In an extended series of studies, the accuracy of this murine induction threshold as the predictor of the absence of a sensitizing effect has been verified by conduct of a human repeated insult patch test (HRIPT). Murine and human thresholds for a diverse set of 57 fragrance chemicals spanning approximately four orders of magnitude variation in potency have been compared. The results confirm that there is a useful correlation, with the LLNA EC3 value helping particularly to identify stronger sensitizers. Good correlation (with half an order of magnitude) was seen with three-quarters of the dataset. The analysis also helps to identify potential outlier types of (fragrance) chemistry, exemplified by hexyl and benzyl salicylates (an over-prediction) and trans-2-hexenal (an under-prediction).

Risk Assessment of residual monomer migrating from acrylic polymers and causing Allergic Contact Dermatitis during normal handling and use

Acrylic, Poly Methyl Methacrylate (PMMA) based polymers are found in many industrial, professional and consumer products and are of low toxicity, but do contain very low levels of residual monomers and process chemicals that can leach out during handling and use. Methyl Methacrylate, the principle monomer is of low toxicity, but is a recognized weak skin sensitizer. The risk of induction of contact allergy in consumers was determined using a method based upon the Exposure-based Quantitative Risk Assessment approach developed for fragrance ingredients. The No Expected Sensitization Induction Level (NESIL) was based on the threshold to induction of sensitization (EC3) in the Local Lymph Node Assay (LLNA) since no Human Repeat Insult Patch Test (HRIPT) data were available. Categorical estimation of Consumer Exposure Level was substituted with a worst case assumption based upon the quantitative determination of MMA monomer migration into simulants. Application of default and Chemical-Specific Adjustment Factors results in a Risk Characterization Ratio (RCR) of 10,000 and a high Margin of Safety for induction of Allergic Contact Dermatitis (ACD) in consumers handling polymers under conservative exposure conditions. Although there are no data available to derive a RCR for elicitation of ACD it is likely to be lower than that for induction.