Method for improving the actual skin-sensation effect of a combined product

Abstract

A method for predictively evaluating the skin sensitization of a personal care product formulation includes calculating an upper confidence limit at a desired confidence level from a plurality of physical tests for each skin sensitization of the components in the personal care product formulation to define a calculated skin sensitization value for each component, applying at least one safety factor to at least one of the calculated skin sensitization values for the components to define an adjusted skin sensitization value for each component, summing the adjusted skin sensitization values of the components to define the total sensitization of the personal care product formulation, and comparing the total sensitization with a target product sensitization for the personal care product formulation. Such a personal care product formulation does not require further testing and can be applied to the skin by the user. A prediction system and method for 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. Specifically, the present invention relates to a method for predictively evaluating the skin sensitization of personal care product formulations, and a system therefor.

Background Art

[0002] The skin sensitization phenomenon consists of the induction of sensitization and subsequent induction of an allergic reaction in the skin of a human patient or user of a personal care product. The potential for sensitization depends on the bioavailability or absorbability of the chemical substance, as well as the initial and rate-limiting ability of the chemical substance to bind to epidermal proteins and induce a reaction. The human repeat insult patch testing (HRIPT) for finished cosmetic product formulations has been used as part of the skin sensitization evaluation ability. However, such tests are time-consuming because the time for product test results can be at least about 8 weeks or more. Furthermore, if there is a reaction in this product test, testing for each component may be required.

[0003] Considering that finished product formulations are often complex blends of various chemical substances, the skin sensitization risk assessment process may involve consideration of the bioavailability and sensitization ability of the components (component sensitization effect), as well as the influence of the formulation components on the finished product delivery system (matrix effect).

Summary of the Invention

Problems to be Solved by the Invention

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

Means for Solving the Problems

[0005] The present invention relates to a method for developing a product with an improved skin sensitization risk assessment, and a product developed as a result of this method. This method can assess the skin sensitization hazard for the component constituents in the formulated product, and based on these assessments, can identify improvements in the skin sensitization risk assessment safety process. The method of the present invention includes HRIPT test results, but the methodology of the present invention is further based on the binomial distribution of the sample size and the percentage of subjects in the population that develop sensitization under the same or suitable test conditions. Under the same parameters, the statistical probability of detecting the population sensitivity and certainty for a finished cosmetic formulation improves as the HRIPT sample or population size increases.

[0006] A finished cosmetic product formulation generally includes a desired set of ingredients with defined dosages intended to deliver related functions such as stability, microbiology, aesthetics, and / or to deliver specific attributes. Considering that the finished product formulation is a complex blend of various chemicals, the skin sensitization risk assessment process requires consideration of the bioavailability and sensitizing ability of the ingredients (ingredient sensitization effect), as well as the influence of the formulation constituents on the finished product delivery system (matrix effect).

[0007] The method of the present invention provides the actual consumer sensitization threshold for the component chemicals in the finished product formulation with a 95% upper confidence score application, prompting the formulator to move in the direction of designing a finished formulation with improved safety confidence. This method can be used to track and improve the skin sensitization risk assessment performance of product lines, brands, product functions (e.g., shampoo, lotion, essence, facial wash, soup, mask) or product types (e.g., rinse-off, non-rinse-off) through the use of the sensitization threshold of the ingredients and the upper 95% confidence score for the actual consumer use of the finished product formulation. Using measurement criteria derived from the component score tests over time for a common set of ingredients across various formulation types, the formulation sensitization threshold of the upper confidence level for the actual consumer use of the finished product can be predicted, and the overall organizational formulation design changes required to enhance and improve future skin sensitization threshold risk assessment predictions can be identified.

[0008] In one aspect of the present invention, a method for predictively evaluating the skin sensitization of a personal care product formulation containing a plurality of components comprises: calculating an upper confidence limit at a desired confidence level from a plurality of physical tests for the skin sensitization of each component in the personal care product formulation to define a calculated skin sensitization value for each component; applying at least one safety factor to at least one of the calculated skin sensitization values for the components to define an adjusted skin sensitization value for each component; summing the adjusted skin sensitization values of the components to define the total sensitization of the personal care product formulation; comparing the total sensitization with a target product sensitization for the personal care product formulation, wherein if the total sensitization is less than the target product sensitization, the product formulation of the personal care product formulation does not require further testing and is applicable to the skin by the user.

[0009] The skin sensitization of each component can be defined as the percentage of subjects having an allergic reaction to a physical allergy test, such as a human repeated insult test. Thus, a low value of skin sensitization is desired.

[0010] The method may further comprise setting an initial sensitization target for the personal care product formulation and obtaining the skin sensitization of each component from a computer database having a plurality of test results for each component. The initial sensitization target can be about 0.2 percent or less than 0.2 percent, and the target product sensitization can be about 0.1 percent or less than 0.1 percent.

[0011] The method further comprises selecting components used in a plurality of personal care products, such as about 10 or more different personal care products. Further, it is desirable that the selected components have been tested in a plurality of subjects, such as about 2,000 subjects or more.

[0012] In such a large number of test results, the sensitization value is determined at a confidence level of at least 95%. Instead of using the average value at this confidence level, the upper confidence limit is used to provide a more conservative prediction method. The component sensitization value and / or the component upper confidence limit can be adjusted according to the weight composition of the components in the proposed formulation. However, the methods described herein do not require such weight adjustment since typical formulations often contain a large number of proposed components.

[0013] The methods described herein may further include applying a product use factor to the calculated skin sensitization value for a component, and the product use factor may be based on the estimated amount of the product used and the estimated area of product use. For example, the product use factor can be the ratio of the estimated daily usage amount (which can be in grams or milligrams) to the estimated application surface area (which can be in square centimeters or square millimeters).

[0014] The step of applying at least one safety factor may include multiplying at least one calculated skin sensitization value for at least one component by at least one safety factor. The safety factor can be applied or multiplied to a plurality of components including all or substantially all of the components. The safety factor can include (a) a safety factor based on impairment of the skin barrier function, (b) a safety factor based on product delivery that results in skin occlusion, and / or a safety factor based on an occlusive application site, (c) a safety factor based on a preconditioned skin potential having the potential for an activated inflammatory response, and combinations thereof. The order in which the safety factors are applied is not critical, and any order of the safety factors applied can be suitably used. When applied, the safety factor based on impairment of the skin barrier function is about 5 or greater than 5, when applied, the safety factor based on product delivery that results in skin occlusion, and / or the safety factor based on an occlusive application site is about 5 or greater than 5, and when applied, the potential based on the safety factor for a preconditioned skin having the potential for an activated inflammatory response is about 2 or greater than 2.

[0015] In another aspect of the present invention, a system for predictively evaluating the skin sensitization of a personal care product formulation containing a plurality of components is provided. The system includes a computing device, and a memory storing instructions which, when executed by the computing device, cause the computing device to calculate, from a plurality of tests on the skin sensitization of each of the components in the personal care product formulation, an upper confidence limit at a desired confidence level to define a calculated skin sensitization value for each of the components; apply at least one safety factor to the calculated skin sensitization value for a component to define an adjusted skin sensitization value for each of the components; sum the adjusted skin sensitization values of the components to define the overall sensitization of the personal care product formulation; and compare the overall sensitization with a target product sensitization of the personal care product formulation, wherein the product formulation is capable of being applied to the skin by a user without the need for further testing if the overall sensitization is less than the target product sensitization.

[0016] In yet another aspect of the present invention, a method of preparing a personal care product comprises selecting a plurality of components for use in a personal care product formulation; calculating, from a plurality of physical tests on the skin sensitization of each of the components in the personal care product formulation, an upper confidence limit at a desired confidence level to define a calculated skin sensitization value for each of the components; applying at least one safety factor to at least one of the calculated skin sensitization values for a component to define an adjusted skin sensitization value for each of the components; summing the adjusted skin sensitization values of the components to define the overall sensitization of the personal care product formulation; comparing the overall sensitization with a target product sensitization for the personal care product formulation; and If the overall sensitization is less than the target product sensitization, forming a personal care product may include combining ingredients such that the product formulation of the personal care product formulation is ready for use by the user without further testing and applicable to the skin by the user.

[0017] These and other aspects, features, and advantages of the present invention will become apparent from the following detailed description of its exemplary embodiments, to be construed in conjunction with the accompanying drawings. Corresponding reference numerals or letters indicate corresponding parts throughout several views of the drawings.

Brief Description of the Drawings

[0018]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Modes for Carrying Out the Invention

[0019] The present invention is a method for predictively evaluating the skin sensitization of a personal care product formulation. This method is particularly useful in that it enables the formation of personal care products without the need for additional physical tests for skin sensitization, such as the HRIPT test.

[0020] Figure 1 is a flow chart for predictively evaluating the skin sensitization of a personal care product formulation according to the present invention. As illustrated in Figure 1, the proposed ingredients are first proposed in step 10. The ingredients, their type and amount can be based on the end-use requirements of the final product, such as product function (e.g., shampoo, lotion, beauty essence, facial cleanser, soup, mask), product type (e.g., rinse-off, non-rinse-off), etc., but are not limited thereto.

[0021] In step 20, only the ingredients that meet specific threshold conditions are selected. It is desirable to set the threshold conditions so that the predictive evaluation represents the actual experience. For example, in multiple completed personal care product formulations and across a large number of tested subjects, it may be desirable to select ingredients that have a physical test history (e.g., HRIPT). Further, it may be desirable to select only the ingredients that meet the sensitization value or criteria.

[0022] The multiple completed personal care product formulations can be set to any reasonable value, e.g., 10 or more formulations. One reason for selecting multiple completed products is to protect against unexpected adverse effects since different ingredients are formulated in different products. The 10 or more multiple formulations are non-limiting, and other multiple values can be used. Such other values can include 5 or more formulations, 15 or more formulations, 20 or more formulations, 50 or more formulations, etc.

[0023] The number of subjects to be tested can be set to about 2,000 or more subjects. However, the present invention is not limited thereto. The number of subjects to be 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. There is no upper limit set for the number of subjects to be tested, but in some embodiments, there can be up to about 1,000,000 tested subjects, or up to about 500,000 tested subjects, or up to about 100,000 tested subjects. Such a large number of test subjects provides a good predictive evaluation of skin sensitization for personal care product formulations.

[0024] For example, in step 30, if all components do not meet the desired test threshold, for example, about 10 or more formulations and about 2,000 or more subjects, re-selection of components 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, the use of conservative test thresholds is desirable. If the desired test threshold is not met, return to step 10 of the flowchart of FIG. 1. Alternatively, the method of the present invention may be configured to select only those components that are likely to meet the desired test threshold.

[0025] The component skin sensitization value can be set such that each component is below the skin sensitization criterion. Skin sensitization can be defined as the percentage of allergic reactions for a group of subjects as follows. (Σ Subjects with confirmed allergic reactions ÷ Σ Subjects who completed patch tests) * (100)

[0026] The frequency of adverse reactions typically used can be described as follows. Very frequent, for example, about 10% or more (≧), Frequent, for example, ≧ about 1% and less than about 10% (<), Rare, for example, ≧ about 0.1% and < about 1% Very rare, for example, ≧ about 0.01% and < less than about 0.1%, and Extremely rare, < about 0.01%. Such frequency characterizations are non-limiting.

[0027] Desirably, the component sensitization threshold or criterion in step 20 is set as a reasonably low value of adverse reaction, such as about 0.2% or less (≦) for each component. This threshold is non-limiting and other thresholds may be used. For example, thresholds such as ≦ 0.1%, ≦ 0.3%, ≦ 0.4%, ≦ 0.5% can be preferably used. If the desired component sensitization threshold is not met, return to step 10 of the flowchart of FIG. 1. Alternatively, the method of the present invention may be configured to select only those components that are likely to meet the desired component sensitization threshold.

[0028] In step 40, for each component's individual skin sensitization value, a more conservative component sensitization threshold is set by intentionally using the 95% upper confidence limit. This 95% upper confidence limit or sensitization response score is obtained by using the total number of subjects tested (n) and the total number of subjects in which an allergic reaction was confirmed (a). The upper 95% confidence limit is obtained using the Clopper-Pearson exact confidence interval approach. This upper confidence limit is applied to the entire population of all subjects who may be treated under severe HRIPT patch test conditions. Thus, numerically, the upper 95% confidence limit value is greater than the mean value, thereby providing an additional conservative approach.

[0029] The step of selecting the skin sensitization value in set 40 is described in more detail in FIG. 2. In step 42, the confidence level is set, for example, at 95%. Other confidence levels from about 90% to about 99% can be selected if desired. In step 44, the upper confidence limit of skin sensitization for each component is determined as described above. In step 46, this upper confidence limit is applied as the skin sensitization value for each component.

[0030] Returning to FIG. 1, the upper confidence limit of skin sensitization for each component is further adjusted in step 50 to apply this upper confidence limit to the actual consumer use of the component in the finished product formulation.

[0031] Under typical exposure conditions, the dose per unit area of a chemical substance can have an excessive effect on the effectiveness of sensitization. Thus, the methodological prediction model of the present invention uses a dose density adjustment based on the actual consumer use applications for the components and finished product formulations. This approach conservatively allows for the estimated probability of events in the actual use of the component and finished product formulation matrix and improves the safety design of the formulation. An exemplary list of product dose densities is set forth in Table 1 below.

[0032] [Table 1]

[0033] These values are non-limiting and may change over time, for example, to reflect changes in consumer use.

[0034] The actual predicted use or dose density adjustment factor is based on dividing the use per day in grams by the application surface area in cm 2 units. The greater the dose weight or grams, the greater the adjustment factor, while the greater the cm 2 unit application area, the smaller the adjustment factor. For example, a body sunscreen has an adjustment factor of 18 / 17500 or about 0.00103, and an antifungal foot cream has an adjustment factor of 0.2 / 100 or about 0.002. Such adjustment factors are applied to the upper confidence limit of skin sensitization for each component in step 52 of FIG. 3.

[0035] Continuing with FIG. 3, the dose density-adjusted upper confidence limit for skin sensitization can be further adjusted using a safety factor in step 54 of FIG. 3.

[0036] Adjustment of the safety factor is appropriate to conservatively include the formulation matrix skin effect when predicting the probability of real-world events extrapolated from the sum of the experimental patch data of the components. Safety factor adjustment may optionally be based on (a) impairment of the skin barrier function, (b) product delivery resulting in skin occlusion and / or based on the occlusive application site, (c) preconditioned skin potential with the potential for an activated inflammatory response, and combinations thereof. The present invention is not limited to the use of these three safety factors, and other and / or additional safety factors may be suitably used.

[0037] For the inclusion of components that affect the barrier or impairments to the skin barrier function (e.g., the effects of alcohol drying, surfactants, glycols, acid disruptors, penetration enhancers), a safety factor (e.g., "safety factor a") may be applied. The presence and levels of components that are known or suspected to be potentially irritating in the final formulation with the potential to initiate an inflammatory cascade (e.g., barrier disrupting components such as, among others, benzoyl peroxide (acne prevention) and retinol (anti-aging)) can increase the potential for skin sensitization of the finished product for actual consumer use. A safety factor of about 5 may be used. The value of 5 is non-limiting, and any other suitable safety value such as 2, 3, 4, 6, 7, and 8 may be used. The safety factor may be applied across each component or may be applied to select components by multiplying the dose density-adjusted upper confidence limit for skin sensitization 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.

[0038] Another safety factor (e.g., "safety factor b") can be based on systems that are likely to enhance the delivery or transdermal delivery system effect. For example, skin occlusion can increase the water content of the stratum corneum, skin temperature, microbial count, pH, and skin irritation, and thus can affect the penetration of personal care products. Therefore, regardless of whether it is due to enhanced product delivery (occlusive masks, polymer systems, nappies / diapers), or as a result of an occlusive application site such as under the arm or a highly follicular area, in the actual consumer use scenario that results in enhanced penetration, it is important to note that an additional safety factor is incorporated to maintain a conservative upper limit 95% confidence level for the actual consumer exposure to these occlusive scenarios based on the physicochemical properties of the components. Other factors that can affect this safety factor can include polymer systems, oil / water emulsion systems, and masks / clays with occlusive systems. 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 across each component, or can be applied to select components by multiplying the dose density-adjusted upper confidence limit for skin sensitization 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.

[0039] A further safety factor (e.g., "safety factor c") can be obtained based on the pre-stimulated immune skin condition. A potentially activated inflammatory cascade can reverse the potential for skin sensitization, for example, in the case of abraded shaved skin due to mechanical damage or sunburned skin. Inflammation can be directly affected by chemical or mechanical trauma that can increase keratinocyte activity and potentially increase the effect of the sensitization reaction via primary skin irritation. Even if the inflammatory reaction is unrelated to product application, a skin sensitization assessment safety factor can be conservatively applied to the extrapolation of the actual consumer use upper confidence level. A safety factor of about 2 can be used. The value of 2 is non-limiting, and any other suitable safety value such as 3 or 4 can be used. The safety factor can be applied across each component or can be applied to select components by multiplying the dose density-adjusted upper confidence limit for skin sensitization by the safety factor. If no safety factor is applied, a safety factor of 1 is multiplied by the dose density-adjusted upper confidence limit for skin sensitization.

[0040] Values for estimating the probability of skin sensitization can be generated based on the application of safety factors simulating actual use conditions. Several considerations can lead to the application of safety factors to the set of combined components that make up the proposed or final product formulation, as follows. 1) If one or more of the components in the component set are classified as barrier disruptors (BD) (e.g., alcohol drying effects, glycols, acids, and penetration enhancers), for example, a safety factor of 5 can be applied to each component of the formulated component set. 2) If the delivery (DE) type promotes increased biological permeability (e.g., serum polymer systems, or occlusive delivery such as masks, or cases of inclusion of high levels of occlusive components), another safety factor, for example, 5 can be applied. 3) For example, a safety factor of 2 can be applied to pre-stimulated immune skin end use (PEU) conditions, such as post-sunburn use, acne use.

[0041] Table 2 below illustrates the values for sets of formulation components having achieved values based on the application of respective safety factors. Note that the greater the number of safety factors applied, the greater the value of the set of components relative to the number of components. For example, a formulation having 17 components and a safety factor adjustment of PEU (2x) results in a value of 0.0007%, while a formulation having 29 components and the application of safety factors for both PEU (2x) and BD (5x) will have a value of 0.062%. Alternatively, a formulation having 13 components and a safety factor adjustment of 1x will have a value of 0.0008%.

[0042]

Table 2

[0043] Actual data product monitoring of skin events can be used to support the above trends in safety factor application. For example, products corresponding to DE&BD have higher values for observed skin events compared to products containing only DE, only BD, or neither.

[0044] The data in the following table captures actual data for product delivery enhancement systems (DE: present, absent) and may also contain barrier disrupting components (BD: present, absent). For example, products with DE&BD can have an observed percentage value of 0.056%, while products with only BD can have a value of 0.027%.

[0045]

Table 3

[0046] The value of the percentage of users with observed skin events can be calculated based on the number of subjects in which the event was observed / number of sales units = observed % of skin events. The predicted probability can be calculated based on a logistic regression model having terms for delivery enhancer and barrier disruptor, and these values are shown in parentheses.

[0047] Briefly, the adjusted upper confidence limit for the dose density for skin sensitization for the selection or all of the components is multiplied by "safety factor a", "safety factor b", and "safety factor c" to obtain an adjusted skin sensitization value.

[0048] Returning to Figure 1, at step 60, a target product sensitization value or threshold is set. Desirably, the target product sensitization is ≦ about 0.1%. This value is non-limiting and other target sensitization values can be used. Desirably, the target product sensitization value (e.g., ≦ about 0.1%) is less than the component sensitization threshold or initial sensitization target (e.g., ≦ about 0.2%).

[0049] The adjusted skin sensitization values for each component from step 50 are summed at step 70 to define the total sensitization or calculated total sensitization for the proposed personal care product formulation. Here, further adjustment is usually not required, but if additional adjustment is required for some reason, they can be suitably applied at this step 70.

[0050] At step 80, if the total sensitization calculated for the proposed personal care product formulation is greater than the target product sensitization, product reformulation may be required. If the total sensitization calculated for the proposed personal care product formulation is less than the target product sensitization, at step 90, the proposed personal care product formulation is applicable to the user's skin, for example, without further physical product testing or, in some cases, with only minimal product testing (such tests having a reduced number of subjects).

[0051] Figure 4 schematically depicts a system 100 for predictively evaluating the skin sensitization of a personal care product formulation containing a plurality of components. System 100 includes a memory storage of physical test results 130. The physical resting results 140 included 1,274 formulations that were tested across 203,640 subjects in an HRIPT test. The formulations had 1,226 common components reused in 99.98% of the subjects tested (203,602 out of 203,640 subjects), and zero showed an allergic reaction. Approximately 0.02% of the subjects tested (38 out of 203,640 subjects) showed some allergic reaction. These values are non-limiting and are provided to illustrate the population and test size. For example, if additional physical results become available, they can be added to the memory storage of physical test results 130.

[0052] When the memory storing instructions 120 is executed by computing device 110, it causes the computing device to perform operations including, but not limited to, the following. Calculating an upper confidence limit at a desired confidence level from a plurality of tests on the skin sensitization of each component in a personal care product formulation to define a calculated skin sensitization value for each component. Applying at least one safety factor to the calculated skin sensitization value for a component to define an adjusted skin sensitization value for the component. Summing the adjusted skin sensitization values of the components to define the overall sensitization of the personal care product formulation, and Comparing the overall sensitization to a target product sensitization for the personal care product formulation.

[0053] The memory storing instructions 120 can include any of the calculations, data manipulations, logical decisions, sequence instructions described herein.

[0054] FIG. 5 is a block diagram of an exemplary embodiment of a general - purpose computer system 200 that shows the system 100 of FIG. 4 in more detail. The computer system 200 can include a set of instructions that, when executed on the computer system 200, cause the computer system 200 to perform any one or more of the methods or computer - based functions disclosed herein, including FIGS. 1 - 4. The computer system 200 or any portion thereof can operate as a stand - alone 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 a computing device 110 and can further be connected to other systems and devices, such as a content provider, via a network.

[0055] The computer system 200 can also be implemented as or incorporated into various devices, such as a personal computer (PC), a tablet PC, a personal digital assistant (PDA), a computing device or mobile device (e.g., a smartphone), a palmtop computer, a laptop computer, a desktop computer, a communication device, a control system, a web appliance, or any other machine capable of (sequentially or otherwise) executing a set of instructions that specify actions to be taken by that machine. Further, although a single computer system 200 is illustrated, the term "system" is also to be construed to include any collection of systems or subsystems that individually or jointly execute a set of instructions or multiple sets of instructions for performing one or more computer functions.

[0056] As illustrated in FIG. 5, computer system 200 may include a processor 202, such as a central processing unit (CPU), a graphics-processing unit (GPU), or both. Further, 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, computer system 200 may further 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). Additionally, computer system 200 may include an input device 212, such as a keyboard, and a cursor control device 214, such as a mouse. Computer system 200 may also include a disk drive (or solid state) unit 216, a signal generation device 222, such as a speaker or a remote control, and a network interface device 208.

[0057] In certain embodiments or aspects, as depicted in FIG. 5, the disk drive (or solid state) unit 216 may include one or more instruction sets 220, such as a computer-readable medium 218 into which software can be embedded. Further, the instructions 220 may embody one or more of the methods or logics described herein. In certain embodiments or aspects, the instructions 220 may be present, in whole or at least in part, within the main memory 204, within 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 a computer-readable medium.

[0058] Dedicated hardware implementations such as application-specific integrated circuits, programmable logic arrays, and other hardware devices can be constructed to implement one or more of the methods described herein. Uses that may include devices and systems of various embodiments or aspects can broadly include various electronic systems and computer systems. One or more embodiments or aspects described herein can implement functions using two or more specifically interconnected hardware modules or devices with associated control and data signals that can be communicated between and through the modules or as part of an application-specific integrated circuit. Accordingly, the system encompasses software, firmware, and hardware implementations.

[0059] The methods described herein can be implemented by a software program tangibly embodied on a processor-readable medium and executable by a processor. Further, in exemplary and non-limiting embodiments or aspects, the implementations can include distributed processing, component / object distributed processing, and parallel processing. Alternatively, virtual computer system processing can be constructed to implement one or more of the methods or functions as described herein.

[0060] It is also contemplated that a computer-readable medium includes instruction 220 or receives and executes instruction 220 in response to a propagated signal so that a device connected to network 224 can communicate voice, video, or data over network 224. Further, instruction 220 can be transmitted or received over network 224 via network interface device 208.

[0061] Although a computer-readable medium is shown as a single medium, the term "computer-readable medium" includes a single medium or multiple media that store one or more sets of instructions, such as a centralized or distributed database, and / or associated caches and servers. The term "computer-readable medium" also includes any medium that can store, encode, or carry a set of instructions to be executed by a processor or that has the capability of causing a computer system to perform any one or more of the methods or operations disclosed herein.

[0062] In certain non-limiting, exemplary embodiments or aspects, the computer-readable medium can include solid-state memory such as a memory card or other package that houses one or more non-volatile read-only memories. Additionally, the computer-readable medium can be random access memory or other volatile, rewritable memory. Further, the computer-readable medium can include magneto-optical or optical media such as a disk or tape or other storage device for capturing carrier signals such as signals communicated via a transmission medium. A digital file attached to an e-mail or other self-contained information archive or set of archives can be considered a distribution medium equivalent to a tangible storage medium. Accordingly, any one or more of a computer-readable medium or distribution medium on which data or instructions can be stored, as well as other equivalents and successor media, are included herein.

[0063] The methods described herein can be implemented as one or more software programs executed on a computer processor. Dedicated hardware implementations, including, but not limited to, application specific integrated circuits, programmable logic arrays, and other hardware devices, can likewise be constructed to implement the methods described herein. Further, alternative software implementations, including, but not limited to, distributed processing or component / object distributed processing, parallel processing, or virtual machine processing, can also be constructed to implement the methods described herein.

[0064] The software implementing the disclosed method may optionally be stored on a tangible storage medium, such as a magnetic medium like a disk or a tape, a magneto-optical medium or an optical medium like 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 attached to an e-mail or other self-contained information archive or archive set is considered a distribution medium equivalent to a tangible storage medium. Accordingly, the tangible storage medium or distribution medium recited herein, as well as other equivalents and successor media on which the software implementations herein may be stored, are included herein.

[0065] The features and advantages of the present invention are more fully shown by the following examples, which are provided for illustrative purposes only and should not be construed as limiting the present invention in any way.

[0066] In the following examples, various components were used for evaluation purposes. The following table identifies the various components evaluated in one or more of the examples herein. These components are only some of the components that may be evaluated throughout the present invention and should in no way be construed as limiting the present invention.

[0067] Component:

[0068]

Table 4-1

[0069]

Table 4-2

Example

[0070] A lotion for sunburned skin was formulated using the following ingredients as shown in Table 4 below.

[0071]

Table 5

[0072] All ingredients were used in more than 10 personal care products. The number of tested formulations containing the above ingredients was between 20 and 1,176. All ingredients were tested on more than 2,000 subjects. The total number of subjects tested with formulations containing the above ingredients was between 3,570 and 187,429.

[0073] Component sensitization for each of the components 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 / 15670 (representing a daily dose of 7.82 g for a surface area of 15,670 cm 2 from Table 1 above) was applied to the upper confidence limits of each component. These values are shown in Table 5 below.

[0074]

Table 6

[0075] As used herein, the scientific notation of the form "x.xxE-yy" represents x.xx×10 -yy or x.xx * ×10 -yy Thus, for example, 3.70E-05 represents 0.0000370.

[0076] Furthermore, in this example, the component sensitization values and upper confidence limits for each component were not adjusted according to the weight composition of the components in the proposed formulation. Nevertheless, if desired, these values and limits can be adjusted according to the weight composition of the components in the proposed formulation.

[0077] The sensitization values of the dosage density adjustment components for each ingredient were adjusted as necessary according to the safety factor. In this example, (a) Applicable safety factor: The delivery system was "1". (b) Applicable safety factor: The component that adjusts the skin barrier to enhance biological delivery was "1". (c) Applicable safety factor: The intended use of the pre-stimulated immune skin state was "2". The first applied safety factor was multiplied by the sensitization value of the dosage density adjustment component, then the second applied safety factor was multiplied by the sensitization value adjusted by the first applied safety factor, and then the third applied safety factor was multiplied by the sensitization value adjusted by the second safety factor. The safety factor "1" means that no adjustment was made according to the sensitization value, that is, a specific safety category was not applicable. The safety-adjusted sensitization values are shown below.

[0078]

Table 7

[0079] The order of the categories of the applied safety factors was not important. In fact, the categories of the applied safety factors can be provided in any desired order.

[0080] Then, as shown in Table 7 below, the safety factor-adjusted sensitization values were totaled.

[0081]

Table 8

[0082] The calculated sensitization value of 0.00070 for the proposed formulation was less than the typical product sensitization value or threshold of 0.1, so the proposed formulation is correlated with the actual data and can be applied to the user's skin without testing or with only minimal testing.

Example

[0083] As shown in Table 8 below, a facial moisturizer in the form of a beauty liquid having an anti-aging component was formulated using the following components.

[0084]

Table 9

[0085] All components were used in 10 or more personal care products. The number of tested formulations containing the above components was 23 to 958. All components were tested on 2,000 or more subjects. The total number of subjects tested with formulations containing the above components was 3,448 to 151,896 people.

[0086] The component sensitizations for each of the components are shown in Table 9 below. The upper confidence limit (UCL(p)) at a 95% confidence level was calculated for each component. The dose density factor 1.54 / 565 (representing a daily dose of 1.54 g for a surface area of 565 cm 2 from Table 1 above) was applied to the upper confidence limits of each component. These values are shown in Table 9 below.

[0087]

Table 10

[0088] Furthermore, in this example, the component sensitization values and upper confidence limits for each component were not adjusted according to the weight composition of the components in the proposed formulation. Nevertheless, if desired, these values and limits can be adjusted according to the weight composition of the components in the proposed formulation.

[0089] The dose density adjustment component sensitization value for each component was adjusted according to the safety factor if desired. In this example, (a) the applied safety factor: the delivery system was "5". (b) the applied safety factor: the component that adjusts the skin barrier to enhance biological delivery was "5". (c) the applied safety factor: the intended use of the pre-stimulated immune skin state was "1". The first applied safety factor was multiplied by the dose density adjustment component sensitization value, then the second applied safety factor was multiplied by the sensitization value adjusted by the first applied safety factor, and then the third applied safety factor was multiplied by the sensitization value adjusted by the second safety factor. The safety factor "1" means that no adjustment was made to the sensitization value, i.e., a particular safety category was not applicable. The safety-adjusted sensitization values are shown below.

[0090]

Table 11

[0091] The order of the categories of the applied safety factors was not important. In fact, the categories of the applied safety factors can be provided in any desired order.

[0092] Then, as shown in Table 11 below, the safety factor-adjusted sensitization values were summed.

[0093]

Table 12

[0094] The calculated sensitization value of 0.0467 for the proposed formulation was less than the typical product sensitization value or threshold of 0.1, so the proposed formulation correlated with the actual data and could be applied to the user's skin without testing or with only minimal testing.

Example

[0095] A facial moisturizer with an anti-aging component was formulated using the following components as shown in Table 12 below.

[0096]

Table 13

[0097] All components were used in more than 10 personal care products. The number of tested formulations containing the above components was 23 to 958. All components were tested on more than 2,000 subjects. The total number of subjects tested with formulations containing the above components was 3,448 to 151,895 people.

[0098] Component sensitization for each of the components is shown in Table 13 below. The upper confidence limit (UCL(p)) at the 95% confidence level was calculated for each component. The dose density factor 1.54 / 565 (representing a daily dose of 1.54 g per 565 cm 2 of the use surface area) was applied to the upper confidence limits of each component. These values are shown in Table 13 below.

[0099]

Table 14

[0100] Furthermore, in this example, the component sensitization values and upper confidence limits for each component were not adjusted according to the weight composition of the components in the proposed formulation. Nevertheless, if desired, these values and limits can be adjusted according to the weight composition of the components in the proposed formulation.

[0101] The dose density adjustment component sensitization value for each component was adjusted according to the safety factor, if desired. In this example, (a) Applied safety factor: The delivery system was "5". (b) Applied safety factor: The component that adjusts the skin barrier to enhance biodelivery was "5". (c) Applied safety factor: The intended use of the pre-stimulated immune skin state was "1". The first applied safety factor was multiplied by the dose density adjustment component sensitization value, then the second applied safety factor was multiplied by the sensitization value adjusted by the first applied safety factor, and then the third applied safety factor was multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment was made to the sensitization value, i.e., no specific safety category was applicable. The safety-adjusted sensitization values are shown below.

[0102]

Table 15

[0103] The order of the categories of applied safety factors was not important. In fact, the categories of applied safety factors can be provided in any desired order.

[0104] Then, as shown in Table 15 below, the safety factor-adjusted sensitization values were summed.

[0105]

Table 16

[0106] The calculated sensitization value of 0.0441 for the proposed formulation was less than the typical product sensitization value or threshold of 0.1, so the proposed formulation is correlated with the actual data and can be applied to the user's skin without testing or with minimal testing.

Example

[0107] A facial moisturizer with an anti-aging component was formulated using the following components as shown in Table 16 below.

[0108]

Table 17

[0109] All components were used in more than 10 personal care products. The number of tested formulations containing the above components was 12 to 1,176. All components were tested on more than 2,000 subjects. The total number of subjects tested with formulations containing the above components was 2,000 to 187,429 people.

[0110] Component sensitization for each of the components is shown in Table 17 below. The upper confidence limit (UCL(p)) at the 95% confidence level was calculated for each component. The dose density factor 1.54 / 565 (representing a daily dose of 1.54 g per 565 cm 2 of the used surface area) was applied to the upper confidence limits of each component. These values are shown in Table 17 below.

[0111]

Table 18

[0112] Furthermore, in this example, the component sensitization values and upper confidence limits for each component were not adjusted according to the weight composition of the components in the proposed formulation. Nevertheless, if desired, these values and limits can be adjusted according to the weight composition of the components in the proposed formulation.

[0113] The dosimetric adjustment component sensitization values for each component were adjusted according to the safety factor, if desired. In this example, (a) the applied safety factor: the delivery system was "1". (b) the applied safety factor: the component that modulates the skin barrier to enhance biodelivery was "5". (c) the applied safety factor: the intended use of the pre-stimulated immune skin state was "1". The first applied safety factor was multiplied by the dosimetric adjustment component sensitization value, then the second applied safety factor was multiplied by the sensitization value adjusted by the first applied safety factor, and then the third applied safety factor was multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment was made to the sensitization value, i.e., a particular safety category was not applicable. The safety-adjusted sensitization values are shown below.

[0114]

Table 19

[0115] The order of the categories of applied safety factors was not important. In fact, the categories of applied safety factors can be provided in any desired order.

[0116] Then, as shown in Table 19 below, the safety factor-adjusted sensitization values were summed.

[0117]

Table 20

[0118] The calculated sensitization value of 0.0265 for the proposed formulation was less than the typical product sensitization value or threshold of 0.1, so the proposed formulation correlates with actual data and can be applied to the user's skin without testing or with minimal testing.

Example

[0119] Anti-acne that is not washed away was formulated using the following components as shown in Table 20 below.

[0120]

Table 21

[0121] All components were used in more than 10 personal care products. The number of tested formulations containing the above components was 16 - 1,176. All components were tested on more than 2,000 subjects. The total number of subjects tested with formulations containing the above components was 2,519 - 187,429 people.

[0122] Component sensitization for each of the components is shown in Table 21 below. The upper confidence limit (UCL(p)) at a 95% confidence level was calculated for each component. The dose density factor 1.54 / 565 (representing a daily dose of 1.54 g per 565 cm 2 of the used surface area) was applied to the upper confidence limits of each component. These values are shown in Table 21 below.

[0123]

Table 22

[0124] Furthermore, in this example, the component sensitization values and upper confidence limits for each component were not adjusted according to the weight composition of the components in the proposed formulation. Nevertheless, if desired, these values and limits can be adjusted according to the weight composition of the components in the proposed formulation.

[0125] The dose density adjustment component sensitization values for each component were adjusted according to the safety factor if desired. In this example, (a) the applied safety factor: the delivery system was "1". (b) the applied safety factor: the component that adjusts the skin barrier to enhance biodelivery was "5". (c) the applied safety factor: the intended use of the pre-stimulated immune skin state was "2". The first applied safety factor was multiplied by the dose density adjustment component sensitization value, then the second applied safety factor was multiplied by the sensitization value adjusted by the first applied safety factor, and then the third applied safety factor was multiplied by the sensitization value adjusted by the second safety factor. The safety factor "1" means that no adjustment was made to the sensitization value, i.e., a particular safety category was not applicable. The safety-adjusted sensitization values are shown below.

[0126]

Table 23

[0127] The order of the categories of the applied safety factors was not important. In fact, the categories of the applied safety factors can be provided in any desired order.

[0128] Then, as shown in Table 23 below, the safety factor-adjusted sensitization values were summed.

[0129]

Table 24

[0130] The calculated sensitization value of 0.0616 for the proposed formulation was less than the typical product sensitization value or threshold of 0.1, so the proposed formulation is correlated with the actual data and can be applied to the user's skin without testing or with minimal testing.

Example

[0131] A baby detergent (6 months) was formulated using the following components as shown in Table 24 below.

[0132]

Table 25

[0133] All components were used in more than 10 personal care products. The number of tested formulations containing the above components was 16 - 1,176. All components were tested on more than 2,000 subjects. The total number of subjects tested with formulations containing the above components was 2,160 - 187,429 people.

[0134] Component sensitization for 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 a daily dose of 5.98 g for a surface area of 3,500 cm 2 used) was applied to the upper confidence limit of each component. These values are shown in Table 25 below.

[0135]

Table 26

[0136] Furthermore, in this example, the component sensitization values and upper confidence limits for each component were not adjusted according to the weight composition of the components in the proposed formulation. Nevertheless, if desired, these values and limits can be adjusted according to the weight composition of the components in the proposed formulation.

[0137] The dose density adjustment component sensitization values for each component were adjusted according to the safety factor if desired. In this example, (a) the applicable safety factor: the delivery system was "1". (b) the applicable safety factor: the component that adjusts the skin barrier to enhance biodelivery was "1". (c) the applicable safety factor: the intended use of the pre-stimulated immune skin state was "1". The first applied safety factor was multiplied by the dose density adjustment component sensitization value, then the second applied safety factor was multiplied by the sensitization value adjusted by the first applied safety factor, and then the third applied safety factor was multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment was made to the sensitization value, i.e., no specific safety category was applicable. The safety-adjusted sensitization values are shown below.

[0138]

Table 27

[0139] The order of the categories of the applied safety factors was not important. In fact, the categories of the applied safety factors can be provided in any desired order.

[0140] Then, as shown in Table 27 below, the safety factor-adjusted sensitization values were summed.

[0141]

Table 28

[0142] The calculated sensitization value of 0.000804 for the proposed formulation was less than the typical product sensitization value or threshold of 0.1, so the proposed formulation is correlated with the actual data and can be applied to the user's skin without testing or with minimal testing. Comparative Example 7

[0143] A facial mask with an anti-acne agent was formulated using the following components as shown in Table 28 below.

[0144]

Table 29

[0145] The number of tested formulations containing the above components was 12 to 1,176. The total number of subjects tested with formulations containing the above components was 2,006 to 187,429 people.

[0146] Component sensitization for each of the components is shown in Table 29 below. The upper confidence limit (UCL(p)) at the 95% confidence level was calculated for each component. The dose density factor 1.54 / 565 (representing a daily dose of 1.54 g per 565 cm 2 of the use surface area) was applied to the upper confidence limits of each component. These values are shown in Table 29 below.

[0147]

Table 30

[0148] Furthermore, in this example, the component sensitization values and upper confidence limits for each component were not adjusted according to the weight composition of the components in the proposed formulation. Nevertheless, if desired, these values and limits can be adjusted according to the weight composition of the components in the proposed formulation.

[0149] The sensitization values of the dosage density adjustment components for each ingredient were adjusted according to the safety factor if desired. In this example, (a) applicable safety factor: the delivery system was "5". (b) applicable safety factor: the component that adjusts the skin barrier to enhance biological delivery was "5". (c) applicable safety factor: the intended use of the pre-stimulated immune skin state was "2". The first applied safety factor was multiplied by the sensitization value of the dosage density adjustment component, then the second applied safety factor was multiplied by the sensitization value adjusted by the first applied safety factor, and then the third applied safety factor was multiplied by the sensitization value adjusted by the second safety factor. A safety factor of "1" means that no adjustment was made to the sensitization value, i.e., no specific safety category was applicable. The safety-adjusted sensitization values are shown below.

[0150]

Table 31

[0151] The order of the categories of the applied safety factors was not important. In fact, the categories of the applied safety factors can be provided in any desired order.

[0152] Then, as shown in Table 31 below, the safety factor-adjusted sensitization values were summed.

[0153]

Table 32

[0154] The calculated sensitization value of 0.422 for the proposed formulation was above the typical product sensitization value or threshold of 0.1. The proposed formulation is likely to require product sensitization testing. Alternatively, reformulation may also be considered.

[0155] Although various embodiments and aspects of the present invention are specifically illustrated and / or described herein, it will be understood that modifications and variations of the present invention can be made by those skilled in the art without departing from the spirit and intended scope of the present invention. Further, any of the embodiments or aspects of the present invention described in the claims or the specification can be used with each other without limitation.

[0156] 〔Embodiment〕 (1) A method for predictively evaluating the skin sensitization of a personal care product formulation containing a plurality of components, the method comprising: Calculating an upper confidence limit at a desired confidence level from a plurality of physical tests on the skin sensitization of each of the components in the personal care product formulation to define a calculated skin sensitization value for each of the components; Applying at least one safety factor to at least one of the calculated skin sensitization values for the component to define an adjusted skin sensitization value for each of the components; Summing the adjusted skin sensitization values of the components to define the total sensitization of the personal care product formulation; Comparing the total sensitization with a target product sensitization for the personal care product formulation, wherein if the total sensitization is less than the target product sensitization, the product formulation of the personal care product formulation does not require further testing and can be applied to the skin by the user. (2) The method according to embodiment 1, wherein the skin sensitization of each of the components is defined as the percentage of subjects having an allergic reaction to a physical allergy test. (3) The method according to embodiment 2, wherein the physical allergy test is a human repeat insult test. (4) Setting an initial sensitization target for the personal care product formulation; The method according to any one of embodiments 1 to 3, further comprising obtaining the skin sensitization of each of the components from a computer database having a plurality of test results for each of the components. (5) The method according to embodiment 4, wherein the initial sensitization target is about 0.2 percent or less than 0.2 percent.

[0157] (6) The method according to any one of embodiments 1 to 5, wherein the target product sensitization is about 0.1 percent or less than 0.1 percent. (7) The method according to any one of embodiments 1 to 6, further comprising selecting the components that have been used in a plurality of personal care products. (8) The method according to any one of embodiments 1 to 7, wherein the step of selecting the components further comprises selecting components that have been used in about 10 or more different personal care products. (9) The method according to any one of embodiments 1 to 8, further comprising selecting the components that have been tested on a plurality of subjects. (10) The method according to embodiment 9, wherein the plurality of subjects is about 2,000 subjects or more than 2,000 subjects.

[0158] (11) The method according to any one of embodiments 1 to 10, wherein the desired confidence level is at least 95%. (12) The method according to any one of embodiments 1 to 11, wherein the plurality of physical tests includes tests on about 10 or more different personal care products and tests on about 2,000 subjects or more than 2,000 subjects. (13) The method according to any one of embodiments 1 to 12, further comprising applying a product use factor to the calculated skin sensitization value for the component, wherein the product use factor is based on the estimated amount of the product used and the estimated area of product use. (14) The method according to embodiment 13, wherein the product use factor is the ratio of the estimated daily usage amount in grams to the estimated application surface area in square centimeters. (15) The step of applying the at least one safety factor includes multiplying the at least one calculated skin sensitization value for at least one of the components by the at least one safety factor, the method according to any one of embodiments 1 to 14.

[0159] (16) The step of applying the at least one safety factor includes multiplying the adjusted skin sensitization value for each of the components by the at least one safety factor, the method according to any one of embodiments 1 to 15. (17) The at least one safety factor has a value greater than 1, the method according to embodiment 15 or 16. (18) The at least one safety factor is selected from the group consisting of (a) a factor based on damage to the skin barrier function, (b) a factor based on product delivery resulting in skin occlusion, and / or a factor based on an occlusive application site, (c) a factor based on the potential of a preconditioned and primed immune skin with the potential for an activated inflammatory response, and combinations thereof, the method according to any one of embodiments 1 to 17. (19) When applied, the safety factor based on damage to the skin barrier function is about 5 or greater than 5, the safety factor based on product delivery resulting in skin occlusion, and / or the safety factor based on the occlusive application site is about 5 or greater than 5, and the safety factor based on the potential of a preconditioned and primed immune skin with the potential for an activated inflammatory response is about 2 or greater than 2, the method according to embodiment 18. (20) A system for predictively evaluating the skin sensitization of a personal care product formulation comprising a plurality of components, the system comprising a computing device, and a memory storing instructions, which when executed by the computing device cause the computing device to To define the calculated skin sensitization value for each component, calculate the upper confidence limit at a desired confidence level from a plurality of tests on the skin sensitization of each of the components in the personal care product formulation, To define the adjusted skin sensitization value for each of the respective components, apply at least one safety factor to the calculated skin sensitization value for the component, To define the total sensitization of the personal care product formulation, sum the adjusted skin sensitization values of the components, Comparing the total sensitization with the target product sensitization of the personal care product formulation, wherein the product formulation does not require further testing and is applicable to the skin by the user if the total sensitization is less than the target product sensitization, a system for performing the comparison.

[0160] (21) A method for preparing a personal care product, comprising: Selecting a plurality of components for use in a personal care product formulation, To define the calculated skin sensitization value for each of the respective components, calculate the upper confidence limit at a desired confidence level from a plurality of physical tests on the skin sensitization of each of the components in the personal care product formulation, To define the adjusted skin sensitization value for each of the respective components, apply at least one safety factor to at least one of the calculated skin sensitization values for the component, To define the total sensitization of the personal care product formulation, sum the adjusted skin sensitization values of the components, Comparing the total sensitization with the target product sensitization for the personal care product formulation, If the total sensitization is less than the target product sensitization, combining the components to form the personal care product, wherein the product formulation of the personal care product formulation does not require further testing and is applicable to the skin by the user, a method comprising combining.

Claims

1. A system for predictively evaluating the skin sensitization of a personal care product formulation containing a plurality of ingredients, said system comprising a computing device, a memory for storing instructions, which when executed by the computing device cause the computing device to calculate, from a plurality of tests on the skin sensitization of each of the ingredients in the personal care product formulation, an upper confidence limit at a desired confidence level to define a calculated skin sensitization value for each ingredient; apply at least one safety factor to the calculated skin sensitization value for each ingredient to define an adjusted skin sensitization value for each ingredient; sum the adjusted skin sensitization values of the ingredients to define the total sensitization of the personal care product formulation; compare the total sensitization with a target product sensitization of the personal care product formulation, the product formulation being suitable for application to the skin by the user without further testing if the total sensitization is less than the target product sensitization.

2. A method of preparing a personal care product, comprising selecting a plurality of ingredients for use in a personal care product formulation; calculating, from a plurality of physical tests on the skin sensitization of each of the ingredients in the personal care product formulation, an upper confidence limit at a desired confidence level to define a calculated skin sensitization value for each ingredient; applying at least one safety factor to at least one of the calculated skin sensitization values for each ingredient to define an adjusted skin sensitization value for each ingredient; summing the adjusted skin sensitization values of the ingredients to define the total sensitization of the personal care product formulation; comparing the total sensitization with a target product sensitization for the personal care product formulation; combining the ingredients to form the personal care product if the total sensitization is less than the target product sensitization, the product formulation being suitable for application to the skin by the user without further testing.

3. A method for predictively evaluating the skin sensitization of a personal care product formulation containing a plurality of components, the method comprising: Calculating an upper confidence limit at a desired confidence level from a plurality of physical tests for the skin sensitization of each of the components in the personal care product formulation to define a calculated skin sensitization value for each of the components; Applying at least one safety factor to at least one of the calculated skin sensitization values for the components to define an adjusted skin sensitization value for each of the components; Summing the adjusted skin sensitization values of the components to define the total sensitization of the personal care product formulation; Comparing the total sensitization with a target product sensitization for the personal care product formulation, wherein if the total sensitization is less than the target product sensitization, the product formulation of the personal care product formulation does not require further testing and is applicable to the skin by the user.

4. The method according to claim 3, wherein each of the skin sensitizations of the components is defined as a percentage of subjects having an allergic reaction to a physical allergy test.

5. The method according to claim 4, wherein the physical allergy test is a human repeat insult test.

6. Setting an initial sensitization target for the personal care product formulation; The method according to claim 3, further comprising obtaining the skin sensitization of each of the components from a computer database having a plurality of test results for each component.

7. The method according to claim 6, wherein the initial sensitization target is about 0.2 percent or less than 0.2 percent.

8. The method according to claim 3, wherein the target product sensitization is about 0.1 percent or less than 0.1 percent.

9. The method according to claim 3, further comprising selecting the components that have been used in a plurality of personal care products.

10. The method according to claim 3, wherein the step of selecting the components further comprises selecting components that have been used in about 10 or more different personal care products.

11. The method according to claim 3, further comprising selecting the components that have been tested on a plurality of subjects.

12. The method according to claim 11, wherein the plurality of subjects are about 2,000 subjects or more than 2,000 subjects.

13. The method according to claim 3, wherein the desired confidence level is at least 95%.

14. The method according to claim 3, wherein the plurality of physical tests include tests on about 10 or more different personal care products and tests on about 2,000 subjects or more than 2,000 subjects.

15. The method according to claim 3, further comprising applying a product usage factor to the calculated skin sensitization value for the component, wherein the product usage factor is based on the estimated amount of the product used and the estimated area of product use.

16. The method according to claim 15, wherein the product usage factor is the ratio of the estimated daily usage amount in grams to the estimated application surface area in square centimeters.

17. The method according to claim 3, wherein the step of applying the at least one safety factor includes multiplying the at least one calculated skin sensitization value for at least one of the components by the at least one safety factor.

18. The method according to claim 3, wherein the step of applying the at least one safety factor includes multiplying the adjusted skin sensitization value for each of the components by the at least one safety factor.

19. The method according to claim 17 or 18, wherein the at least one safety factor has a value greater than 1.

20. The method according to claim 3, wherein the at least one safety factor is selected from the group consisting of (a) a factor based on damage to the skin barrier function, (b) a factor based on product delivery resulting in skin occlusion, and / or a factor based on an occlusive application site, (c) a factor based on the potential of a preconditioned and primed immune skin having the potential for an activated inflammatory response, and combinations thereof.

21. The method according to claim 20, wherein when applied, the safety factor based on damage to the skin barrier function is about 5 or greater, the safety factor based on product delivery resulting in skin occlusion, and / or the safety factor based on the occlusive application site is about 5 or greater, and the safety factor based on the potential of a preconditioned and primed immune skin having the potential for an activated inflammatory response is about 2 or greater.

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