Method for improving real-world skin sensitization effects of formulations

Abstract

A method of predictively assessing skin sensitization of a personal care product formulation includes calculating a confidence upper limit at a desired confidence level from a plurality of physical tests for skin sensitization of each of the ingredients in the personal care product formulation to define a calculated skin sensitization value for the respective ingredient; applying at least one safety factor to at least one of the calculated skin sensitization values of the ingredient to define an adjusted skin sensitization value for the respective ingredient; combining the adjusted skin sensitization values of the ingredients to define the total sensitization of the personal care product formulation; and comparing the total sensitization to the target product sensitization of the personal care product formulation. Such personal care product formulations do not require further testing and can be applied to the skin by a user. Predictive systems and methods of preparing personal care products are also disclosed.

Description

Technical Field

[0001] The present invention relates to personal care products and methods for formulating the same. In particular, the present invention relates to methods for predictive assessment of skin sensitization of personal care product formulations and systems for such predictive assessment. Background Art

[0002] The phenomenon of skin sensitization consists of the induction of sensitization and subsequent induction of an allergic reaction on the skin of a human patient or user of a personal care product. The sensitizing potential depends on the bioavailability or absorption of the chemical and the initial and rate-limiting ability of the chemical to bind to epidermal proteins to induce a reaction. Human repeated provocation patch testing (HRIPT) of finished cosmetic formulations has been used as part of the potential for skin sensitization assessment. However, such testing is inherently time consuming, as the time for product testing results may be on the order of at least eight weeks or longer. In addition, if there is a reaction on the product test, ingredient-by-ingredient testing may be required.

[0003] Considering that finished dosage forms are often complex blends of different chemical substances, the risk assessment approach for skin sensitization may involve consideration of the effects of formulation components (matrix effects) on the bioavailability and sensitizing potential of ingredients (ingredient sensitization effects) as well as the finished product delivery system.

[0004] Therefore, due to the complex nature of personal care products, there is a need in the art for improved tools for assessing sensitization potential. Summary of the invention

[0005] The present invention relates to a method for developing products with improved skin sensitization risk assessment impact, and the resulting products developed as a result of the method. The method can assess the skin sensitization hazard of ingredient components in formulated products, and can determine improvements in skin sensitization risk assessment safety methods based on those assessments. The method of the present invention includes HRIPT test results, but the methodology of the present invention is also based on sample size and a binomial distribution of the percentage of subjects in a population who will develop sensitization under the same or appropriate test conditions. The statistical probability of detecting the population sensitivity and reliability of finished cosmetic preparations under the same parameters increases with larger HRIPT sample or population sizes.

[0006] A cosmetic finished formulation typically contains a set of desired ingredients in defined doses that are intended to deliver relevant functions such as stability, microscopicity, aesthetics, and / or to deliver specific attributes. Considering that the finished formulation is a complex blend of different chemical substances, the risk assessment approach for skin sensitization needs to consider the impact of formulation components (matrix effects) on the bioavailability and sensitization potential of the ingredients (ingredient sensitization effects) as well as the finished delivery system.

[0007] The method of the present invention provides real-world consumer sensitization thresholds and 95% confidence upper limit scores for ingredient chemicals in finished formulations, and encourages formulators to move toward designing finished formulations with improved safety confidence. The method can be used to track and improve the skin sensitization risk assessment performance of product lines, brands, product functions (e.g., shampoos, lotions, serums, washes, soups, masks) or product types (e.g., wash-off, leave-on) by using the sensitization thresholds and 95% confidence upper limit scores of ingredients for real-world consumer use of finished formulations. Metrics derived from ingredient score tests of common ingredient groups over time in various formulation types can be used to predict the confidence upper limit of the formulation sensitization threshold used by real-world consumers of finished products, and can determine the full-organization formulation design changes required to strengthen and improve future skin sensitization threshold risk assessment predictions.

[0008] In one aspect of the present invention, a method for predictively evaluating skin sensitization of a personal care product formulation comprising a plurality of ingredients comprises:

[0009] calculating an upper confidence limit at a desired confidence level from multiple physical tests for skin sensitization of each of the ingredients in the personal care product formulation to define a calculated skin sensitization value for the corresponding ingredient;

[0010] applying at least one safety factor to at least one of the calculated skin sensitization values ​​of the ingredients to define an adjusted skin sensitization value for the corresponding ingredient;

[0011] Adding the adjusted skin sensitization values ​​of the ingredients defines the total sensitization of the personal care product formulation; and

[0012] The total sensitization is compared to a target product sensitization for the personal care product formulation, wherein when the total sensitization is less than the target product sensitization, the product formulation for that personal care product formulation does not require further testing and can be applied to the skin by the user.

[0013] Skin sensitization of each of the ingredients can be defined as the percentage of subjects who have an allergic reaction to a physical allergy test (such as a human repeated challenge test). Therefore, a low skin sensitization value is desired.

[0014] The method may also include: setting an initial sensitization target for the personal care product formulation; and obtaining skin sensitization of each of the ingredients from a computer database having a plurality of test results for each ingredient. The initial sensitization target may be about 0.2% or less, and the target product sensitization may be about 0.1% or less.

[0015] The method also includes selecting ingredients that have been used in a variety of personal care products, such as about ten or more than ten different personal care products. In addition, it is desirable that the selected ingredients have been tested on a plurality of subjects, such as about 2,000 subjects or more than 2,000 subjects.

[0016] In the case of such a large number of test results, the sensitization value is determined at a confidence level of at least 95%. An upper confidence limit is used to provide a more conservative prediction method rather than using an average value of the confidence level. The component sensitization value and / or the upper confidence limit of the component can be adjusted for the weight composition of the components in the proposed formulation. However, the methods described herein do not require such weight adjustments because typical formulations generally contain a large amount of the proposed components.

[0017] The methods described herein may also include applying a product use factor to the calculated skin sensitization value of the ingredient; wherein the product use factor may be based on the estimated amount of product to be used and the estimated area of ​​product use. For example, the product use factor may be a ratio of the estimated daily amount (which may be in grams or milligrams) to the estimated application surface area (which may be in square centimeters or square millimeters).

[0018] The step of applying at least one safety factor may include multiplying at least one calculated skin sensitization value of at least one ingredient by at least one safety factor. The safety factor may be applied to or multiplied by a plurality of ingredients, including all or substantially all ingredients. The safety factor may include a safety factor based on: (a) impaired skin barrier function, (b) product delivery and / or occlusive property application site that affects skin occlusion, (c) the potential for pre-conditioned skin to activate an inflammatory response, and combinations thereof. The order of the safety factors applied is not critical, and any order of the safety factors applied may be used appropriately. If applied, the safety factor based on impaired skin barrier function is about 5 or greater than 5; if applied, the safety factor based on product delivery that affects skin occlusion and / or based on occlusive property application site is about 5 or greater than 5; and if applied, the safety factor based on the potential for pre-conditioned skin to activate an inflammatory response is about 2 or greater than 2.

[0019] In another aspect of the present invention, a system for predictive evaluation of skin sensitization of a personal care product formulation comprising a plurality of ingredients is provided. The system may include:

[0020] Computing equipment;

[0021] A memory storing instructions that, when executed by the computing device, cause the computing device to perform operations comprising:

[0022] Calculating an upper confidence limit at a desired confidence level from multiple tests for skin sensitization of each of the ingredients in the personal care product formulation to define a calculated skin sensitization value for the corresponding ingredient;

[0023] applying at least one safety factor to the calculated skin sensitization value of the ingredient to define an adjusted skin sensitization value for the corresponding ingredient;

[0024] Adding the adjusted skin sensitization values ​​of the ingredients defines the total sensitization of the personal care product formulation; and

[0025] The total sensitization is compared to the target product sensitization for the personal care product formulation, wherein when the total sensitization is less than the target product sensitization, the product formulation does not require further testing and can be applied to the skin by the user.

[0026] In another aspect of the present invention, a method of preparing a personal care product may include:

[0027] Selecting various ingredients for use in personal care product formulations;

[0028] calculating an upper confidence limit at a desired confidence level from multiple physical tests for skin sensitization of each of the ingredients in the personal care product formulation to define a calculated skin sensitization value for the corresponding ingredient;

[0029] applying at least one safety factor to at least one of the calculated skin sensitization values ​​of the ingredients to define an adjusted skin sensitization value for the corresponding ingredient;

[0030] Add the adjusted skin sensitization values ​​of the ingredients to define the total sensitization of the personal care product formulation;

[0031] Comparison of total sensitization to target product sensitization for personal care product formulations; and

[0032] If the total sensitization is less than the target product sensitization, the ingredients are mixed to form a personal care product, wherein the product formulation for personal care product formulation does not require further testing and can be applied to the skin by the user.

[0033] These and other aspects, features and advantages of the present invention will become apparent from the following detailed description of illustrative embodiments of the present invention, which is to be read in conjunction with the accompanying drawings, in which corresponding reference numerals or characters indicate corresponding parts throughout the several views of the drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 Flowchart for predictive assessment of skin sensitization of personal care product formulations according to the present invention.

[0035] Figure 2 To present Figure 1 A flowchart with additional details of a portion of a flowchart.

[0036] Figure 3 To present Figure 1 A flowchart of additional details for another portion of the flowchart.

[0037] Figure 4 Schematic illustration of a system for predictive assessment of skin sensitization of personal care product formulations according to the present invention.

[0038] Figure 5 A block diagram of a general purpose computing system. DETAILED DESCRIPTION

[0039] The present invention is a method for predictive assessment of skin sensitization of personal care product formulations. The method is particularly useful because it allows personal care products to be formulated without the need for additional physical (such as HRIPT) testing for skin sensitization.

[0040] Figure 1 Flow chart for predictive evaluation of skin sensitization of personal care product formulations according to the present invention. Figure 1 As shown, the proposed ingredients are first proposed at step 10. The ingredients, types and amounts thereof may be based on the end-use requirements of the finished product, such as but not limited to product functions (e.g., shampoo, lotion, serum, wash, soup, mask), product types (e.g., rinse-off, leave-on), etc.

[0041] At step 20, only ingredients that meet certain threshold conditions are selected. It is desirable to set the threshold conditions so that the predictive evaluation represents real-world experience. For example, it is desirable to select ingredients with a history of physical testing (e.g., HRIPT) in a variety of final human care product formulations and a large number of test subjects. In addition, it is desirable to select only those ingredients that meet sensitization values ​​or standards.

[0042] The multiple final personal care product formulations can be set to any reasonable value, such as ten or more formulations. One reason for selecting multiple finished products is to prevent unexpected adverse effects when preparing different ingredients in different products. A variety of ten or more formulations is non-limiting, and other multiple values ​​can be used. Such other values ​​may include five or more formulations, fifteen or more formulations, twenty or more formulations, fifty or more formulations, etc.

[0043] The number of subjects tested can be set to about 2,000 or more subjects. However, the present invention is not limited thereto. The number of subjects tested can be set to 500 or more subjects; 1,000 or more subjects; 3,000 or more subjects; 5,000 or more subjects; etc. Although there is no upper limit to the number of subjects to be tested, in some aspects, there may be up to about 1,000,000 test subjects, or up to about 500,000 test subjects, or up to about 100,000 test subjects. Such a large number of test subjects provides a good predictive assessment of skin sensitization of personal care product formulations.

[0044] At step 30, for example, if all ingredients do not meet the desired testing threshold, e.g., about ten or more formulations and about 2,000 or more subjects, then reselection of ingredients is recommended because the accuracy of the predictive assessment of skin sensitization may not be as accurate or precise as desired. Since the predictive assessment of skin sensitization is used as an alternative to physical formulation testing, a conservative testing threshold needs to be used. In such cases where the desired testing threshold is not met, a return to Figure 1 Alternatively, the method of the present invention may be configured to select only possible components that meet a desired test threshold.

[0045] Ingredient skin sensitization values ​​can be set so that each ingredient is at or below the skin sensitization standard. Skin sensitization can be defined as the percentage of allergic reactions in a group of subjects, such as:

[0046] (∑Subjects with confirmed allergic reaction ÷∑Subjects who completed patch testing)*(100)

[0047] The frequency of commonly used adverse reactions can be described as follows:

[0048] Very common, such as greater than or equal to (≥) about 10%;

[0049] Common, such as ≥ about 1% and less than (<) about 10%;

[0050] Uncommon, such as ≥ about 0.1% and < about 1%;

[0051] Rare, such as ≥ about 0.01% and < about 0.1%; and

[0052] Very rare, such as < about 0.01%.

[0053] Such characterization of frequencies is non-limiting.

[0054] Ideally, the ingredient sensitization threshold or standard at step 20 is set to a reasonably low value for adverse reaction, such as less than or equal to (≤) about 0.2% for each ingredient. This threshold is non-limiting, and other thresholds may be used. For example, thresholds of ≤ 0.1%, ≤ 0.3%, ≤ 0.4%, ≤ 0.5%, etc. may be used appropriately. In such cases where the desired ingredient sensitization threshold is not met, a return to step 20 is made. Figure 1 Alternatively, the method of the present invention may be configured to select only possible ingredients that meet a desired ingredient sensitization threshold.

[0055] At step 40, setting of further conservative ingredient sensitization thresholds is performed by intentionally applying a 95% ingredient upper confidence limit to the individual skin sensitization value for each ingredient. This 95% upper confidence limit or sensitization score is obtained by using the total number of subjects tested (n) and the total number of subjects with confirmed allergic reactions (a). The 95% upper confidence limit is obtained using the Clopper-Pearson exact confidence interval method. This upper confidence limit is applicable to the population of all possible subjects treated under exaggerated HRIPT patch test conditions. Therefore, numerically, the 95% upper confidence limit value is greater than the mean, thereby providing an additional conservative approach.

[0056] exist Figure 2 The step of selecting a skin sensitization value at setting 40 is further described in detail in . At step 42, the confidence level is set to, for example, 95%. If desired, other confidence levels can be selected from about 90% to about 99%. At step 44, an upper confidence limit for skin sensitization of each ingredient is determined as described above. At step 46, the upper confidence limit is used as the skin sensitization value for each ingredient.

[0057] Back to Figure 1 The upper confidence limit for skin sensitization of each ingredient is further adjusted at step 50 to apply the upper confidence limit to actual real-world consumer usage of the ingredient in the finished product adjustment.

[0058] Under typical exposure conditions, the dosage per unit area of ​​a chemical substance can have an overwhelming effect on the effectiveness of sensitization. Therefore, the methodological prediction model of the present invention uses the dosage density adjustment based on the real life consumer use application of ingredients and finished product formulations. The method conservatively allows the estimated probability of events in the real world use of ingredients and finished product formulation matrices, and improves formulation safety design. An exemplary list of product dosage density is described in Table 1 below.

[0059] Table 1

[0060]

[0061]

[0062] These values ​​are non-limiting and may change over time to, for example, reflect changing consumer usage.

[0063] The adjustment factor for expected real-world use or dose density is based on the daily dose (in grams) divided by the applied surface area (in cm 2 Higher dose weights or grams result in higher adjustment factors, however, 2 A higher application area per unit results in a lower adjustment factor. For example, a body sunscreen would have an adjustment factor of 18 / 17500 or about 0.00103, while an antifungal foot cream would have an adjustment factor of 0.2 / 100 or about 0.002. Figure 3 At step 52 in the method, such adjustment factors are applied to the upper confidence limit for skin sensitization of each ingredient.

[0064] continue Figure 3 ,exist Figure 3 At step 54 in , the upper confidence limit of the dose density adjusted skin sensitization may be further adjusted with a safety factor.

[0065] When predicting the probability of real life events extrapolated from the sum of the ingredient empirical patch data, the adjustment of the safety factor is appropriate to conservatively include the formulation matrix skin effect. The safety factor adjustment may be applied based on: (a) impaired skin barrier function, (b) product delivery and / or occlusive properties of the application site that affect skin occlusion, (c) the potential for pre-conditioned skin to activate an inflammatory response, and / or a combination thereof. The present invention is not limited to the use of these three safety factors, and other and / or additional safety factors may be used as appropriate.

[0066] A safety factor (e.g., "safety factor a") may be applied for the inclusion of barrier-affecting ingredients or for compromising the skin barrier function (e.g., alcohol drying effect, surfactants, glycols, acid disruption, penetration enhancers). The presence and content of ingredients known or suspected to be potentially irritating and having the potential to cause an inflammatory cascade in the final formulation (e.g., barrier disruptor ingredients such as benzoyl peroxide (anti-acne) and retinol (anti-aging), etc.) may increase the skin sensitization potential of the finished product for real-world consumer use. A safety factor of about 5 may be used. The value of 5 is non-limiting, and any other suitable safety value may be used, such as 2, 3, 4, 6, 7, and 8. The safety factor may be applied to each ingredient, or applied to select ingredients by multiplying the upper confidence limit of the skin sensitization adjusted by the dose density by the safety factor. If no safety factor is applied, the upper confidence limit of the skin sensitization adjusted by the dose density is multiplied by the safety factor 1.

[0067] Another safety factor (e.g., "safety factor b") may be based on the system or skin delivery penetration system effects that may enhance delivery. For example, occlusion of the skin increases hydration of the stratum corneum, skin temperature, microbial counts, pH, and epidermal irritation, and thus may affect the penetration of personal care products. Therefore, it is important to note that in real-world consumer use scenarios that lead to enhanced penetration, whether it is due to enhanced product delivery (occlusive masks, polymer systems, diapers / diapers) or the occlusive nature of the application site (such as underarm application or high follicle areas), additional safety factors are combined to maintain a conservative upper limit 95% confidence level for real-world consumer exposure of these occlusive scenarios based on the physicochemical properties of the components. Other factors that affect this safety factor may include polymer systems, oil / water emulsion systems, masks / mud masks with occlusive systems, etc. A safety factor of about 5 can be used. The value of 5 is non-limiting, and any other suitable safety value, such as 2, 3, 4, 6, 7, and 8, can be used. The safety factor can be applied to each ingredient, or applied to select ingredients by multiplying the upper confidence limit of skin sensitization adjusted by the dose density by the safety factor. If no safety factor is applied, the dose density adjusted upper confidence limit for skin sensitization is multiplied by a safety factor of 1.

[0068] Other safety factors (e.g., "safety factor c") may be based on sensitized immune skin conditions. Potential activation of the inflammatory cascade, such as in the case of mechanical damage (abrasional shaved skin or sunburned skin), may reverse the skin sensitization potential. Inflammation may be directly affected by chemical or mechanical trauma, which may increase keratinocyte activity and potentially increase the impact of primary skin irritation-mediated sensitization reactions. Conservatively, the skin sensitization assessment safety factor may be applicable to real-world consumers using an upper confidence level extrapolation method, even if the inflammatory response is not related to product application. A safety factor of about 2 may be used. The value 2 is non-limiting, and any other suitable safety value, such as 3 or 4, may be used. The safety factor may be applied to each ingredient, or applied to select ingredients by multiplying the upper confidence limit of the skin sensitization adjusted by the dose density by the safety factor. If no safety factor is applied, the upper confidence limit of the skin sensitization adjusted by the dose density is multiplied by the safety factor 1.

[0069] Numerical values ​​used to estimate the probability of skin sensitization can be generated based on the application of safety factors that simulate real-world use conditions. Several considerations may lead to the application of safety factors to each set of mixed ingredients that make up a proposed formulation or finished formulation, as follows:

[0070] 1) When one or more of the ingredients in the ingredient group is classified as a barrier disruptor ("BD") (examples: alcohol drying effect, glycols, acids, and penetration enhancers), then a safety factor of, for example, 5x may be applied to each ingredient in the formulation ingredient group.

[0071] 2) If the formulation delivery ("DE") type favors increased biopermeability (such as in the case of serum polymer systems, or occlusive delivery, such as masks, or contains high levels of occlusive ingredients), another safety factor of, for example, 5x may be applied.

[0072] 3) In the case of sensitized immune skin end-use ("PEU") conditions (eg, after-sun use, acne use), a safety factor of, for example, 2x may be applied.

[0073] Table 2 below illustrates the numerical values ​​of the formulation ingredient groups and the numerical values ​​obtained based on the corresponding safety factor application. It should be noted that when more safety factors are applied, the numerical value of the ingredient group relative to the number of ingredients is larger. For example, a formulation with 17 ingredients and a safety factor adjustment for PEU (2x) results in a value of 0.0007%, whereas a formulation with 29 ingredients and a safety factor application for both PEU (2x) and BD (5x) may have a value of 0.062%. Alternatively, a formulation with 13 ingredients and a safety factor adjustment of 1x may have a value of 0.0008%.

[0074] Table 2

[0075]

[0076]

[0077] Real world data product monitoring of skin events can be used to support the trend of applying the above safety factors. For example, a product that is DE and BD will have a higher value for observed skin events compared to a product that contains only DE or BD or neither.

[0078] The data in the table below captures real world data for product delivery enhancer systems (DE: yes, no) that may also contain a barrier disruptor ingredient (BD: yes, no). For example, a product with DE and BD may have a percent observed value of 0.056%, whereas a product with only BD may have a value of 0.027%.

[0079] Table 3

[0080]

[0081] The percentage of users with observed skin events can be calculated based on the number of subjects observed with events / number of units sold = % of observed skin events. The predicted probabilities can be calculated based on a logistic regression model with terms for delivery enhancers and barrier disruptors, and these values ​​are shown in parentheses.

[0082] In summary, the upper confidence limit for the dose density adjusted skin sensitization of selected or all ingredients may be multiplied by "safety factor a" and "safety factor b" and "safety factor c" to obtain an adjusted skin sensitization value.

[0083] Back to Figure 1 , a target product allergenicity value or threshold is set at step 60. Ideally, the target product allergenicity is ≤ about 0.1%. This value is non-limiting, and other target allergenicity values ​​may be used. Ideally, the target product allergenicity value (e.g., ≤ about 0.1%) is less than the ingredient allergenicity threshold or initial allergenicity target (e.g., ≤ about 0.2%).

[0084] The adjusted skin sensitization values ​​for each ingredient from step 50 are summed to define the total sensitization or calculated total sensitization for the proposed personal care product formulation in step 70. Further adjustments are generally not required at this point, but if additional adjustments are necessary for some reason, they may be appropriately applied at this step 70.

[0085] If the calculated total sensitization of the proposed personal care product formulation is greater than the target product sensitization, product reformulation may be necessary at step 80. If the calculated total sensitization of the proposed personal care product formulation is less than the target product sensitization, then at step 90, the proposed personal care product formulation can be applied to the user's skin without, for example, further physical product testing or perhaps only minimal product testing, such testing being conducted with a reduced number of subjects.

[0086] Figure 4 A system 100 for predictive evaluation of skin sensitization of a personal care product formulation containing multiple ingredients is schematically depicted. The system 100 includes a memory storage of physical test results 130. The physical test results 140 include 1,274 formulations tested on 203,640 subjects in the HRIPT test. The formulation reuses 1,226 common components, of which 99.98% of the test subjects (203,602 of the 203,640 subjects) showed zero confirmed allergic reactions. About 0.02% of the test subjects (38 of the 203,640 subjects) showed some allergic reactions. These values ​​are non-limiting and are used to illustrate populations and test amounts. For example, when additional physical results become available, they can be added to the memory storage of physical test results 130.

[0087] The memory stores instructions 120 that, when executed by the computing device 110, cause the computing device to perform operations including, but not limited to, the following operations:

[0088] Calculating an upper confidence limit at a desired confidence level from multiple tests for skin sensitization of each of the ingredients in the personal care product formulation to define a calculated skin sensitization value for the corresponding ingredient;

[0089] applying at least one safety factor to the calculated skin sensitization value of the ingredient to define an adjusted skin sensitization value for the corresponding ingredient;

[0090] Adding the adjusted skin sensitization values ​​of the ingredients defines the total sensitization of the personal care product formulation; and

[0091] The total sensitization was compared to the target product sensitization of the personal care product formulations.

[0092] The memory storing instructions 120 may include any of the computations, data manipulations, logic decisions, sequence instructions described herein.

[0093] Figure 5 is a block diagram of an exemplary embodiment of a general purpose computer system 200, which further details Figure 4 The computer system 200 may include a set of instructions that can be executed to cause the computer system 200 to perform the present invention (including Figures 1 to 4 ) or any one or more of the methods or computer-based functions disclosed in the present invention. The computer system 200 or any portion thereof can operate as a standalone device or can be connected to other computer systems or peripheral devices, for example, using a network or other connection. For example, the computer system 200 can be the computing device 110 and can also be connected to other systems and devices, such as content providers, via a network.

[0094] The computer system 200 may also be implemented as or incorporated into a variety of devices, such as a personal computer (PC), a tablet PC, a personal digital assistant (PDA), a computing device or mobile device (e.g., a smart phone), a palmtop computer, a laptop computer, a desktop computer, a communication device, a control system, a web device, or any other machine capable of executing a set of instructions (sequentially or otherwise) that specify actions to be taken by the machine. In addition, although a single computer system 200 is illustrated, the term "system" should also be considered to include any collection of systems or subsystems that individually or jointly execute one or more sets of instructions to perform one or more computer functions.

[0095] like Figure 5As illustrated, the computer system 200 may include a processor 202, such as a central processing unit (CPU), a graphics processing unit (GPU), or both. In addition, the computer system 200 may include a main memory 204 and a static memory 206 that can communicate with each other via a bus 226. As shown, the computer system 200 may also include a video display unit 210, such as a liquid crystal display (LCD), an organic light emitting diode (OLED), a flat panel display, a solid-state display, or a cathode ray tube (CRT). In addition, the computer system 200 may include an input device 212, such as a keyboard, and a cursor control device 214, such as a mouse. The computer system 200 may also include a disk drive (or solid-state) unit 216, a signal generating device 222 such as a speaker or a remote controller, and a network interface device 208.

[0096] In one specific embodiment or aspect, Figure 5 , the disk drive (or solid state) unit 216 may include a computer readable medium 218 in which one or more instruction sets 220, such as software, may be embedded. In addition, the instructions 220 may embody one or more of the methods or logic as described herein. In one specific embodiment or aspect, the instructions 220 may reside completely or at least partially within the main memory 204, the static memory 206, and / or within the processor 202 during execution by the computer system 200. The main memory 204 and the processor 202 may also include computer readable media.

[0097] Dedicated hardware implementations such as application specific integrated circuits, programmable logic arrays, and other hardware devices may be configured to implement one or more of the methods described herein. Applications that may include the devices and systems of various embodiments or aspects may broadly include various electronic and computer systems. One or more embodiments or aspects described herein may use two or more specific interconnected hardware modules or devices to implement functions, wherein related control and data signals may be transmitted between and through these modules, or communicated as part of an application specific integrated circuit. Therefore, the present system includes software, firmware, and hardware implementations.

[0098] The methods described herein may be implemented by a software program tangibly embodied in a processor-readable medium and may be executed by a processor. In addition, in exemplary, non-limiting embodiments or aspects, implementations may include distributed processing, component / object distributed processing, and parallel processing. Alternatively, a virtual computer system process may be configured to implement one or more of the methods or functions as described herein.

[0099] It is also contemplated that the computer-readable medium includes instructions 220 or receives and executes instructions 220 in response to a propagated signal so that devices connected to network 224 can communicate voice, video, or data over network 224. Instructions 220 may also be transmitted or received over network 224 via network interface device 208.

[0100] Although the computer-readable medium is illustrated as a single medium, the term "computer-readable medium" includes a single medium or multiple media (such as a centralized or distributed database and / or associated caches and servers) that store one or more sets of instructions. The term "computer-readable medium" should also include any medium that can store, encode, or carry a set of instructions for execution by a processor and cause a computer system to perform any one or more of the methods or operations disclosed herein.

[0101] In a specific non-limiting exemplary embodiment or aspect, the computer-readable medium may include a solid-state memory, such as a memory card or other kits that accommodate one or more non-volatile read-only memories. In addition, the computer-readable medium may be a random access memory or other volatile rewritable memory. In addition, the computer-readable medium may include a magneto-optical medium or an optical medium, such as a disk or a tape or other storage device, to capture a carrier signal, such as a signal transmitted by a transmission medium. The digital file attachment of an e-mail or other self-contained information archive or archive set may be considered to be a distributed medium equivalent to a tangible storage medium. Therefore, this article includes any one or more of a computer-readable medium or a distributed medium in which data or instructions can be stored, as well as other equivalents and successor media.

[0102] The methods described herein may be implemented as one or more software programs running on a computer processor. Special hardware implementations, including but not limited to application specific integrated circuits, programmable logic arrays, and other hardware devices may also be configured to implement the methods described herein. In addition, alternative software implementations, including but not limited to distributed processing or component / object distributed processing, parallel processing, or virtual machine processing may also be configured to implement the methods described herein.

[0103] The software implementing the disclosed methods may optionally be stored on a tangible storage medium, such as: a magnetic medium, such as a disk or tape; a magneto-optical medium or an optical medium, such as a disk; or a solid-state medium, such as a memory card or other package containing one or more read-only (non-volatile) memories, random access memories, or other rewritable (volatile) memories. The software may also utilize signals containing computer instructions. A digital file attachment to an e-mail or other self-contained information archive or set of archives is considered a distributed medium equivalent to a tangible storage medium. Therefore, this document includes tangible storage media or distributed media as listed herein and other equivalents and successor media in which the software implementation of this document may be stored.

[0104] The features and advantages of the present invention are more fully illustrated by the following examples, which are provided for the purpose of illustration and are not to be construed as limiting the present invention in any manner.

[0105] In the following examples, various ingredients are used for evaluation purposes. The following table identifies various ingredients evaluated in one or more of the examples herein. These ingredients are only some of the ingredients that can be evaluated by the present invention and should not be construed as limiting the present invention in any way.

[0106] Element :

[0107]

[0108]

[0109]

[0110] Example 1

[0111] As shown in Table 4 below, an after-sun lotion was formulated with the following ingredients:

[0112] Table 4

[0113] Proposed after-sun lotion formulation composition Ingredient No. Skin Conditioners A1 Emulsifier A2 Antioxidants A3 Skin Conditioners A4 Antioxidants A5 Masking Agent A6 Emulsifier A7 Fragrance A8 Emollients A9 Emollients A10 Wetting agent A11 preservative A12 vehicle A13 Antioxidants A14 Emollients A15 pH Adjusters A16 Tackifier A17

[0114] All ingredients were used in ten or more personal care products. The number of tested formulations containing the above ingredients varied from 20 to 1,176. All ingredients were tested on 2,000 or more subjects. The total number of subjects tested with formulations containing the above ingredients varied from 3,570 to 187,429.

[0115] The component sensitization of each component is shown in Table 5 below. The upper confidence limit (UCL(p)) at the 95% confidence level was calculated for each component. The dose density factor 7.82 / 1 5670 (representing the dose at 1 5,670 cm from Table 1 above) was added. 2 Using a daily dose of 7.82 g on surface area) an upper confidence limit was applied to each ingredient. These values ​​are shown in Table 5 below.

[0116] Table 5

[0117]

[0118] As used herein, scientific notation in the format "x.xxE-yy" means x.xx10 -yy or x.xx*10 -yy . So, for example, 3.70E-05 means 0.0000370.

[0119] In addition, in this example, the ingredient sensitization value and upper confidence limit for each ingredient are not adjusted for the weight composition of the ingredients in the proposed formulation. However, if necessary, these values ​​and ranges can be adjusted for the weight composition of the ingredients in the proposed formulation.

[0120] The dose density adjusted ingredient sensitization value for each ingredient can be adjusted for the safety factor as needed. In this example, the safety factor for (a) application: delivery system is "1"; the safety factor for (b) application: ingredients that modulate the skin barrier to enhance biological delivery is "1"; and the safety factor for (c) application: intended use for sensitizing immune skin conditions is "2". The safety factor for the first application is multiplied by the dose density adjusted ingredient sensitization value, and then the safety factor for the second application is multiplied by the sensitization value adjusted by the safety factor of the first application; and then the safety factor for the third application is multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment is made to the sensitization value, that is, the specific safety category does not apply. The safety-adjusted sensitization values ​​are shown below.

[0121] Table 6

[0122]

[0123] The order in which the applied safety factors are categorized is not critical. In fact, the categories of applied safety factors may be provided in any desired order.

[0124] The safety factor adjusted sensitization values ​​were then added as shown in Table 7 below.

[0125] Table 7

[0126]

[0127]

[0128] Since the calculated sensitization value of 0.00070 for the proposed formulation is less than the typical product sensitization value or threshold of 0.1, the proposed formulation can be applied to the user's skin without testing or with only minimal testing because it correlates with real-world data.

[0129] Example 2

[0130] A facial moisturizer in the form of a serum with anti-aging ingredients was formulated with the following ingredients as shown in Table 8 below:

[0131] Table 8

[0132] Proposed facial moisturizer (serum-anti-aging ingredient) formula composition Ingredient No. Antioxidants B1 Emulsifier B2 Emollients B3 Antioxidants B4 Emollients B5 Fragrance B6 Emollients B7 Antioxidants B8 Antioxidants B9 Emollients B10 Emulsifier B1 1 Anti-aging B12

[0133] All ingredients were used in ten or more personal care products. The number of tested formulations containing the above ingredients varied from 23 to 958. All ingredients were tested on 2,000 or more subjects. The total number of subjects tested with formulations containing the above ingredients varied from 3,448 to 151,896.

[0134] The ingredient sensitization of each of the ingredients is shown in Table 9 below. The upper confidence limit (UCL(p)) at the 95% confidence level was calculated for each ingredient. The dose density factor 1.54 / 565 (representing the dose at 565 cm from Table 1 above) was added. 2 An upper confidence limit was applied to each ingredient using a daily dose of 1.54 g on surface area. These values ​​are shown in Table 9 below.

[0135] Table 9

[0136]

[0137] In addition, in this example, the ingredient sensitization value and upper confidence limit for each ingredient are not adjusted for the weight composition of the ingredients in the proposed formulation. However, if necessary, these values ​​and ranges can be adjusted for the weight composition of the ingredients in the proposed formulation.

[0138] If necessary, the dose density adjusted ingredient sensitization value for each ingredient can be adjusted for the safety factor. In this example, the safety factor for (a) application: delivery system is "5"; the safety factor for (b) application: ingredients that modulate the skin barrier to enhance biological delivery is "5"; and the safety factor for (c) application: intended use for sensitization to immune skin conditions is "1". The safety factor for the first application is multiplied by the dose density adjusted ingredient sensitization value, and then the safety factor for the second application is multiplied by the sensitization value adjusted by the safety factor of the first application; and then the safety factor for the third application is multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment has been made to the sensitization value, that is, the particular safety category does not apply. The safety-adjusted sensitization values ​​are shown below.

[0139] Table 10

[0140]

[0141] The order in which the applied safety factors are categorized is not critical. In fact, the categories of applied safety factors may be provided in any desired order.

[0142] The safety factor adjusted sensitization values ​​were then added as shown in Table 11 below.

[0143] Table 11

[0144] Ingredient No. Real-world sensitization values ​​for ingredients adjusted for intended application and safety factors B1 2.65E-03 B2 6.08E-03 B3 2.75E-03 B4 1.15E-03 B5 3.24E-03 B6 1.36E-03 B7 4.47E-03 B8 2.71E-03 B9 2.39E-03 B10 5.54E-03 B11 3.53E-03 B12 1.08E-02 sum: 0.0467

[0145] Since the calculated sensitization value of 0.0467 for the proposed formulation is less than the typical product sensitization value or threshold of 0.1, the proposed formulation can be applied to the user's skin without testing or with only minimal testing because it correlates with real-world data.

[0146] Example 3

[0147] A facial moisturizer with anti-aging ingredients was formulated with the following ingredients as shown in Table 12 below:

[0148] Table 12

[0149] Facial Moisturizer (Anti-Aging Ingredients) Formula Ingredients Ingredient No. Emulsifier C1 Emollients C2 Antioxidants C3 Emollients C4 Fragrance C5 Emollients C6 Antioxidants C7 Antioxidants C8 Emollients C9 Emulsifier C10 Anti-aging C1 1

[0150] All ingredients were used in ten or more personal care products. The number of tested formulations containing the above ingredients varied from 23 to 958. All ingredients were tested on 2,000 or more subjects. The total number of subjects tested with formulations containing the above ingredients varied from 3,448 to 151,895.

[0151] The ingredient sensitization of each of the ingredients is shown in Table 13 below. The upper confidence limit (UCL(p)) at a 95% confidence level was calculated for each ingredient. The dose density factor 1.54 / 565 (representing a daily dose of 1.54 g on a 565 cm2 surface area of ​​use from Table 1 above) was applied to the upper confidence limit of each ingredient. These values ​​are shown in Table 13 below.

[0152] Table 13

[0153]

[0154]

[0155] In addition, in this example, the ingredient sensitization value and upper confidence limit for each ingredient are not adjusted for the weight composition of the ingredients in the proposed formulation. However, if necessary, these values ​​and ranges can be adjusted for the weight composition of the ingredients in the proposed formulation.

[0156] If necessary, the dose density adjusted ingredient sensitization value for each ingredient can be adjusted for the safety factor. In this example, the safety factor for (a) application: delivery system is "5"; the safety factor for (b) application: ingredients that modulate the skin barrier to enhance biological delivery is "5"; and the safety factor for (c) application: intended use for sensitization to immune skin conditions is "1". The safety factor for the first application is multiplied by the dose density adjusted ingredient sensitization value, and then the safety factor for the second application is multiplied by the sensitization value adjusted by the safety factor of the first application; and then the safety factor for the third application is multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment has been made to the sensitization value, that is, the particular safety category does not apply. The safety-adjusted sensitization values ​​are shown below.

[0157] Table 14

[0158]

[0159] The order in which the applied safety factors are categorized is not critical. In fact, the categories of applied safety factors may be provided in any desired order.

[0160] The sensitization values ​​adjusted by the safety factor were then added together as shown in Table 1 5 below.

[0161] . Table 1 5

[0162] Ingredient No. Real-world sensitization values ​​for ingredients adjusted for intended application and safety factors C1 6.08E-03 C2 2.75E-03 C3 1.15E-03 C4 3.24E-03 C5 1.36E-03 C6 4.47E-03 C7 2.71E-03 C8 2.39E-03 C9 5.54E-03 C10 3.53E-03 C1 1 1.08E-02 sum: 0.0441

[0163] Since the calculated sensitization value of 0.0441 for the proposed formulation is less than the typical product sensitization value or threshold of 0.1, the proposed formulation can be applied to the user's skin without testing or with only minimal testing because it correlates with real-world data.

[0164] Example 4

[0165] A facial moisturizer with anti-aging ingredients was formulated with the following ingredients as shown in Table 16 below:

[0166] Table 16

[0167]

[0168]

[0169] All ingredients were used in ten or more personal care products. The number of tested formulations containing the above ingredients varied from 12 to 1,176. All ingredients were tested on 2,000 or more subjects. The total number of subjects tested with formulations containing the above ingredients varied from 2,000 to 187,429.

[0170] The ingredient sensitization of each of the ingredients is shown in Table 17 below. The upper confidence limit (UCL(p)) at a 95% confidence level was calculated for each ingredient. The dose density factor 1.54 / 565 (representing a daily dose of 1.54 g on a 565 cm2 surface area of ​​use from Table 1 above) was applied to the upper confidence limit of each ingredient. These values ​​are shown in Table 17 below.

[0171] Table 17

[0172]

[0173]

[0174] In addition, in this example, the ingredient sensitization value and upper confidence limit for each ingredient are not adjusted for the weight composition of the ingredients in the proposed formulation. However, if necessary, these values ​​and ranges can be adjusted for the weight composition of the ingredients in the proposed formulation.

[0175] If necessary, the dose density adjusted ingredient sensitization value for each ingredient can be adjusted for the safety factor. In this example, the safety factor for (a) application: delivery system is "1"; (b) the safety factor for application: ingredients that modulate the skin barrier to enhance biological delivery is "5"; and (c) the safety factor for application: intended use for sensitization immune skin conditions is "1". The safety factor for the first application is multiplied by the dose density adjusted ingredient sensitization value, and then the safety factor for the second application is multiplied by the sensitization value adjusted by the safety factor of the first application; and then the safety factor for the third application is multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment has been made to the sensitization value, that is, the particular safety category does not apply. The safety-adjusted sensitization values ​​are shown below.

[0176] Table 18

[0177]

[0178]

[0179] The order in which the applied safety factors are categorized is not critical. In fact, the categories of applied safety factors may be provided in any desired order.

[0180] The safety factor adjusted sensitization values ​​were then added as shown in Table 19 below.

[0181] Table 19

[0182]

[0183]

[0184] Since the calculated sensitization value of 0.0265 for the proposed formulation is less than the typical product sensitization value or threshold of 0.1, the proposed formulation can be applied to the user's skin without testing or with only minimal testing because it correlates with real-world data.

[0185] Example 5

[0186] As shown in Table 20 below, a leave-on anti-acne agent is formulated with the following ingredients:

[0187] Table 20

[0188]

[0189]

[0190] All ingredients were used in ten or more personal care products. The number of tested formulations containing the above ingredients varied from 16 to 1,176. All ingredients were tested on 2,000 or more subjects. The total number of subjects tested with formulations containing the above ingredients varied from 2,519 to 187,429.

[0191] The ingredient sensitization of each of the ingredients is shown in Table 21 below. The upper confidence limit (UCL(p)) at a 95% confidence level was calculated for each ingredient. The dose density factor 1.54 / 565 (representing a daily dose of 1.54 g on a 565 cm2 surface area of ​​use from Table 1 above) was applied to the upper confidence limit of each ingredient. These values ​​are shown in Table 21 below.

[0192] Table 21

[0193]

[0194]

[0195] In addition, in this example, the ingredient sensitization value and upper confidence limit for each ingredient are not adjusted for the weight composition of the ingredients in the proposed formulation. However, if necessary, these values ​​and ranges can be adjusted for the weight composition of the ingredients in the proposed formulation.

[0196] If necessary, the dose density adjusted ingredient sensitization value for each ingredient can be adjusted for the safety factor. In this example, the safety factor for (a) application: delivery system is "1"; the safety factor for (b) application: ingredients that modulate the skin barrier to enhance biological delivery is "5"; and the safety factor for (c) application: intended use for sensitization to immune skin conditions is "2". The safety factor for the first application is multiplied by the dose density adjusted ingredient sensitization value, and then the safety factor for the second application is multiplied by the sensitization value adjusted by the safety factor of the first application; and then the safety factor for the third application is multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment is made to the sensitization value, that is, the particular safety category does not apply. The safety-adjusted sensitization values ​​are shown below.

[0197] Table 22

[0198]

[0199] The order in which the applied safety factors are categorized is not critical. In fact, the categories of applied safety factors may be provided in any desired order.

[0200] The safety factor adjusted sensitization values ​​were then added as shown in Table 23 below.

[0201] Table 23

[0202]

[0203]

[0204] Since the calculated sensitization value of 0.0616 for the proposed formulation is less than the typical product sensitization value or threshold of 0.1, the proposed formulation can be applied to the user's skin without testing or with only minimal testing because it correlates with real-world data.

[0205] Example 6

[0206] As shown in Table 24 below, prepare a baby wash (6 months) (free type) using the following ingredients:

[0207] Table 24

[0208]

[0209]

[0210] All ingredients were used in ten or more personal care products. The number of tested formulations containing the above ingredients varied from 16 to 1,176. All ingredients were tested on 2,000 or more subjects. The total number of subjects tested with formulations containing the above ingredients varied from 2,160 to 187,429.

[0211] The component sensitization of each of the components is shown in Table 25 below. The upper confidence limit (UCL(p)) at the 95% confidence level was calculated for each component. The dose density factor 5.98 / 3500 (representing the dose at 3,500 cm from Table 1 above) was added. 2 Using a daily dose of 5.98 g on surface area) an upper confidence limit was applied to each ingredient. These values ​​are shown in Table 25 below.

[0212] Table 25

[0213]

[0214] In addition, in this example, the ingredient sensitization value and upper confidence limit for each ingredient are not adjusted for the weight composition of the ingredients in the proposed formulation. However, if necessary, these values ​​and ranges can be adjusted for the weight composition of the ingredients in the proposed formulation.

[0215] If necessary, the dose density adjusted ingredient sensitization value for each ingredient can be adjusted for the safety factor. In this example, the safety factor for (a) application: delivery system is "1"; the safety factor for (b) application: ingredients that modulate the skin barrier to enhance biological delivery is "1"; and the safety factor for (c) application: intended use for sensitizing immune skin conditions is "1". The safety factor for the first application is multiplied by the dose density adjusted ingredient sensitization value, and then the safety factor for the second application is multiplied by the sensitization value adjusted by the safety factor of the first application; and then the safety factor for the third application is multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment has been made to the sensitization value, that is, the particular safety category does not apply. The safety-adjusted sensitization values ​​are shown below.

[0216] Table 26

[0217]

[0218] The order in which the applied safety factors are categorized is not critical. In fact, the categories of applied safety factors may be provided in any desired order.

[0219] The safety factor adjusted sensitization values ​​were then added as shown in Table 27 below.

[0220] Table 27

[0221]

[0222]

[0223] Since the calculated sensitization value of 0.000804 for the proposed formulation is less than the typical product sensitization value or threshold of 0.1, the proposed formulation can be applied to the user's skin without testing or with only minimal testing because it correlates with real-world data.

[0224] Comparative Example 7

[0225] A facial mask with anti-acne agents was formulated with the following ingredients as shown in Table 28 below:

[0226] Table 28

[0227] Proposed anti-acne mask formula composition Ingredient No. Occlusive absorbents G1 Occlusive absorbents G2 preservative G3 Sunscreen G4 Fragrance G5 Coolant G6 Wetting agent G7 vehicle G8 Buffer G9 pH Adjusters G10 pH Adjusters G11 Chelating agents G12 Tackifier G13 Surfactants G14 Anti-acne agents G15

[0228] The number of tested formulations containing the above ingredients varied from 12 to 1,176. The total number of subjects tested with formulations containing the above ingredients varied from 2,006 to 187,429.

[0229] The ingredient sensitization of each of the ingredients is shown in Table 29 below. The upper confidence limit (UCL(p)) at a 95% confidence level was calculated for each ingredient. The dose density factor 1.54 / 565 (representing a daily dose of 1.54 g on a 565 cm2 surface area of ​​use from Table 1 above) was applied to the upper confidence limit of each ingredient. These results are shown in Table 29 below.

[0230] Table 29

[0231]

[0232] In addition, in this example, the ingredient sensitization value and upper confidence limit for each ingredient are not adjusted for the weight composition of the ingredients in the proposed formulation. However, if necessary, these values ​​and ranges can be adjusted for the weight composition of the ingredients in the proposed formulation.

[0233] If necessary, the dose density adjusted ingredient sensitization value for each ingredient can be adjusted for the safety factor. In this example, the safety factor for (a) application: delivery system is "5"; the safety factor for (b) application: ingredients that modulate the skin barrier to enhance biological delivery is "5"; and the safety factor for (c) application: intended use for sensitization to immune skin conditions is "2". The safety factor for the first application is multiplied by the dose density adjusted ingredient sensitization value, and then the safety factor for the second application is multiplied by the sensitization value adjusted by the safety factor of the first application; and then the safety factor for the third application is multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment is made to the sensitization value, that is, the particular safety category does not apply. The safety-adjusted sensitization values ​​are shown below.

[0234] Table 30

[0235]

[0236] The order in which the applied safety factors are categorized is not critical. In fact, the categories of applied safety factors may be provided in any desired order.

[0237] The safety factor adjusted sensitization values ​​were then added as shown in Table 31 below.

[0238] Table 31

[0239]

[0240]

[0241] The calculated sensitization value of the proposed formulation, 0.422, is greater than the typical product sensitization value or threshold of 0.1. The proposed formulation may require product sensitization testing. Alternatively, reformulation may also be considered.

[0242] Although various embodiments and aspects of the present invention are specifically illustrated and / or described herein, it should be understood that those skilled in the art can implement modifications and variations of the present invention without departing from the spirit and intended scope of the present invention. In addition, any of the embodiments or aspects of the present invention described in the claims or specification may be used in one embodiment or another embodiment without limitation.

Claims

1. A method for predictively evaluating skin sensitization of a personal care product formulation comprising a plurality of ingredients, the method comprising: calculating an upper confidence limit at a desired confidence level from multiple physical tests of skin sensitization for each of the ingredients in the personal care product formulation to define a calculated skin sensitization value for the corresponding ingredient; applying at least one safety factor to at least one of the calculated skin sensitization values ​​of the ingredients to define an adjusted skin sensitization value for the corresponding ingredient; adding the adjusted skin sensitization values ​​of the ingredients to define the total sensitization of the personal care product formulation; as well as The total sensitization is compared to a target product sensitization for the personal care product formulation, wherein when the total sensitization is less than the target product sensitization, the product formulation for the personal care product formulation requires no further testing and can be applied to the skin by a user.

2. The method of claim 1, wherein skin sensitization of each of the ingredients is defined as the percentage of subjects having an allergic reaction to a physical allergy test.

3. The method of claim 2, wherein the physical allergy test is a human repeated challenge test.

4. The method according to any one of the preceding claims, further comprising: setting an initial sensitization target for the personal care product formulation; as well as Skin sensitization for each of the ingredients was obtained from a computer database having multiple test results for each ingredient.

5. The method of claim 4, wherein the initial sensitization target is about 0.2% or less.

6. The method of any one of the preceding claims, wherein the target product sensitization is about 0.1% or less.

7. The method of any preceding claim, further comprising selecting an ingredient that has been used in a plurality of personal care products.

8. The method of any one of the preceding claims, wherein the step of selecting an ingredient further comprises selecting an ingredient that has been used in about ten or more different personal care products.

9. The method of any one of the preceding claims, further comprising selecting an ingredient that has been tested on multiple subjects.

10. The method of claim 9, wherein the plurality of subjects is about 2,000 subjects or more than 2,000 subjects.

11. A method according to any one of the preceding claims, wherein the desired confidence level is at least 95%.

12. The method of any of the preceding claims, wherein the plurality of physical tests comprises testing of about ten or more different personal care products and testing of about 2,000 or more subjects.

13. The method of any one of the preceding claims, further comprising applying a product usage factor to the calculated skin sensitization value of the ingredient; wherein the product usage factor is based on an estimated amount of product to be used and an estimated area of ​​product use.

14. The method of claim 13, wherein the product use factor is the ratio of the estimated daily usage in grams to the estimated application surface area in square centimeters.

15. The method according to any one of the preceding claims, wherein the step of applying at least one safety factor comprises multiplying the at least one calculated skin sensitization value of at least one of the ingredients by the at least one safety factor.

16. The method of any one of the preceding claims, wherein the step of applying the at least one safety factor comprises multiplying the adjusted skin sensitization value of each of the ingredients by the at least safety factor.

17. The method of claim 15 or 16, wherein the at least one safety factor has a value greater than one.

18. The method of any of the preceding claims, wherein the at least one safety factor is selected from safety factors selected from factors based on: (a) impaired skin barrier function, (b) product delivery and / or occlusive properties of the application site that affect skin occlusion, (c) the potential for pre-conditioning sensitized immune skin with the potential to activate an inflammatory response, and combinations thereof.

19. The method according to claim 18, wherein: If applied, the safety factor based on impaired skin barrier function is about 5 or greater than 5, the safety factor based on product delivery affecting skin occlusion and / or based on the occlusive nature of the application site is about 5 or greater than 5, and the safety factor based on the potential for pre-conditioned sensitized immune skin with the potential to activate an inflammatory response is about 2 or greater than 2.

20. A system for predictive evaluation of skin sensitization of a personal care product formulation comprising a plurality of ingredients, the system comprising: Computing equipment; a memory storing instructions that, when executed by the computing device, cause the computing device to perform operations comprising: calculating an upper confidence limit at a desired confidence level from multiple tests for skin sensitization of each of the ingredients in the personal care product formulation to define a calculated skin sensitization value for the corresponding ingredient; applying at least one safety factor to the calculated skin sensitization value of the ingredient to define an adjusted skin sensitization value for the corresponding ingredient; adding the adjusted skin sensitization values ​​of the ingredients to define the total sensitization of the personal care product formulation; and The total sensitization is compared to a target product sensitization for the personal care product formulation, wherein when the total sensitization is less than the target product sensitization, the product formulation requires no further testing and can be applied to the skin by the user.

21. A method of preparing a personal care product, the method comprising: Selecting various ingredients for use in personal care product formulations; calculating an upper confidence limit at a desired confidence level from multiple physical tests for skin sensitization of each of the ingredients in the personal care product formulation to define a calculated skin sensitization value for the corresponding ingredient; applying at least one safety factor to at least one of the calculated skin sensitization values ​​of the ingredients to define an adjusted skin sensitization value for the corresponding ingredient; adding the adjusted skin sensitization values ​​of the ingredients to define the total sensitization of the personal care product formulation; comparing the total sensitization to a target product sensitization of the personal care product formulation; as well as If the total sensitization is less than the target product sensitization, the ingredients are mixed to form the personal care product, wherein the product formulation for the personal care product formulation requires no further testing and can be applied to the skin by a user.

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