KR101515189B1 - Method for Evaluating Safety of Cosmetics Based on Primary Irritation Index for Human Skin - Google Patents

Abstract

The present invention relates to method for evaluating the safety of cosmetics based on a primary irritation index for human skin. The method for evaluating the safety of cosmetics comprises: a step (S100) of applying and patching testing cosmetics to the skin of testing target individuals; a step (S200) comparing the results in accordance with the reaction of the skin of the individuals and determining the results into several reaction classes after the removal of the patch; a step (S300) of calculating reactivity (R) on the basis of the compared and determined results; a step (S400) of calculating a Z-score (z) using the calculated reactivity (R); a step (S500) of classifying the degree of irritation of the skin reactions on the basis of the calculated Z-score; a step (S600) of classifying the reactivity (R) corresponding to the effective value of the Z-score in accordance with the degree of irritation of the skin reactions; a step (S700) of re-calculating the Z-score by newly classifying the calculated reactivity in accordance with the formulation of the cosmetics; a step (S800) of determining a case when the re-calculated Z-score is at or lower than one as a safe zone; a step (S900) of setting the range of the reactivity corresponding to the safe zone set by the formulation of the cosmetics; and a step (S1000) of determining the safety of the cosmetics using the reactivity when the reactivity of the testing cosmetics is within the range of the reactivity set by the formulation of the cosmetics. Therefore, the present invention provides an easy, simple, and reliable method for evaluating the safety of cosmetics.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0002] The present invention relates to a method for evaluating safety of a cosmetic according to a primary stimulation evaluation standard for human skin,

The present invention relates to a method for evaluating safety of a cosmetic according to a primary stimulation evaluation standard of human skin.

Cosmetics are applied to all parts of the body (skin, hair, nails, lips and external reproductive organs) or to the teeth and oral mucous membranes for the purpose of maintaining cleanliness and orientation, appearance changes, body trimming, As a substance or preparation, since it is a product that people use for a long period of time, it is most important to secure safety in the human skin to which the cosmetic is applied.

In fact, as the use of cosmetics continues to increase, cases of skin side effects of cosmetics are also increasing, and the side effects are variously reported from mild skin irritation to severe dermatitis.

Therefore, evaluation of the safety of cosmetics is important. Evaluation of the safety of such cosmetics is reported by various methods at the cellular level, the animal level, or the human level. However, the safety evaluation at the cellular level or the animal level The safety evaluation of human skin does not clearly reflect the safety of human skin and there is still controversy in its suitability. Therefore, safety evaluation for cosmetics should be made at human level.

Accordingly, the current human-level cosmetic safety test items include single dose toxicity test, primary skin irritation test, mucous membrane stimulation or other mucosal irritation test, skin sensitization test, phototoxicity and photosensitization test . In addition, methods for examining the stimulation caused when the cosmetic is topically applied to the skin or mucous membranes include a skin irritation test, an intraocular mucosal irritation test, an oral mucosal irritation test, and a phototoxicity test, and an abnormal immune response And a skin sensitization test to search for a skin sensitization test.

Among these tests, Japanese Laid-Open Patent Application No. 2013-178114 discloses a method of culturing a keratinocyte to detect an increase in HSP27 expressed in keratinocytes to determine whether or not cosmetic raw materials or cosmetics have micro stimulation on the skin, However, this method has a drawback in that it takes a lot of time, labor, and cost.

In view of this, among the various methods of evaluating the safety of cosmetics in human-level testing, the human skin patch test is widely used.

When the cosmetic is applied to the skin, the acute primary irritation of the skin caused by the above-mentioned cosmetics shows various degrees of irritation from the light stimulus to the strong stimulus of the skin such as skin erythema, swelling, fever, burning, itching, The primary skin irritation test using the human skin patch used for judging this is to apply a single appropriate concentration of cosmetics to the area of the skin to be evaluated for the primary irritation of the skin, and to open and close the skin for a certain period of time , 24 hours, 48 hours, 72 hours), it is determined by visual observation of the patched area and scoring by an evaluation table which can be appropriately evaluated. Therefore, such a human skin patch test is applied to human skin It is known to be a useful test for checking the skin's primary stimulation of direct contact materials.

However, this skin irritation test was based only on the visual criteria and judgment of the examiner, and the criteria for whether the test was subjective, the reliability of the test was low and the degree of skin reaction was safe in terms of primary skin irritation was not clear. In addition, it was not possible to compare / judge the results with the calculated results in order to show the degree of reaction to each kind of cosmetics,

Therefore, the interpretation of the results of the patch test is becoming very important, and the reliability and convenience of the safety inspection of the cosmetics by the database of the accumulated test results are also continuously demanded .

Accordingly, one embodiment of the present invention discloses at least the following aspects.

[One]. The safety inspection method for cosmetics according to one embodiment of the present invention includes a step (S100) of applying test cosmetics to the skin of a body of each subject, A step S200 of comparing the results of the skin patches after the removal of the patches with various reaction classes according to the skin reactions; A step (S300) of calculating a reaction degree (R) based on the comparison result; Calculating a z-score (z) using the calculated reactivity (R) (S400); Classifying the degree of stimulation of the skin reaction based on the value of the calculated z-score (S500); Among the values of the calculated z-scores (z), a value corresponding to 0? Z? 3 is adopted as a valid value, and a response (R) corresponding to the value of the effective z- (S600); (S700) classifying the calculated reactivity according to the cosmetic formulation and re-classifying the z-score; (S800) setting a case where the value of the re-calculated z-score for each cosmetic formulation is equal to or smaller than 1 as a safe area of cosmetics; (S900) of setting a range of the degree of reactivity as a degree of reactivity having a value corresponding to the safety region set for each cosmetic formulation; (S1000), when the degree of reactivity of the test cosmetics belongs to the range of the degree of reactivity set for each of the formulations of the cosmetics, the test cosmetics are evaluated to be safe only by the degree of reaction.

[2]. [1], wherein said plurality of reaction classes consists of 0, 1, 2, 3, and 4 classes, each of which has little or no effect on skin, In cases of normal erythema, edema, severe erythema, edema and severe erythema with smallpox, it is divided into the following cases.

[3]. The method according to [1], wherein the step of calculating the reactivity (R)

의 방정식을 사용하여 산출되고,

Lt; / RTI > is calculated using the equation < RTI ID =

Wherein G is a rating; n is the number of subjects by grade; M is a maximum rating of 4; And N is the total number of subjects.

의 방정식을 사용하여 산출되어, 화장품의 안전성을 판단하는 기준을 설정하는데 사용되며, 상기 방정식에서 χ는 각각의 화장품에 대한 각각의 반응도를 의미하는 원(raw) 점수이고; μ는 대상의 평균 반응도이고; 그리고 σ는 대상 반응도의 표준 편차이다.[4]. The method according to any one of [1] to [3], wherein the z-score (z)

, And is used to set a criterion for judging the safety of the cosmetic, wherein? In the equation is a raw score representing the degree of reactivity for each cosmetic; μ is the mean response of the subject; And σ is the standard deviation of the target response.

[5]. [4], 0? Z? 3 adopted in the step (S900), 0.0? Z <0.5; 0.5? Z <2.0; 2.0? Z <3.0; And 3.0 ≤ z, respectively. The range of reactivity (R) corresponding to each of the four grades was 0.0 ≤ R <0.87 as hypothesis, 0.87 ≤ R <2.42 as light stimulus, 2.42 ≤ R <3.44 is classified as middle irritation and 3.44 ≤ R is classified as strong irritation.

[6]. The range of response (R) corresponding to the safety zone set for each cosmetic formulation in step S600 is 0.87 to 2.96 for the rib on product group and 1.33 to 1.36 for the tissue off product group in step S600. And 2.82 to 3.98 for the washoff product family.

According to the method of the present invention, the reliability of the safety inspection method of cosmetics can be improved by clearly showing the criteria for skin irritation classification and safety criteria of cosmetics in terms of the primary stimulation of human skin.

1 is a photograph showing a representative grade of a skin reaction by human skin patch test;
2 is a chart showing the distribution of reactivity to a subject of the human skin patch test;
FIG. 3 is a flow chart showing the step of judging the safety in terms of skin primary stimulation for cosmetics according to the results of the patch test.

The present invention is based on the prototype of a prototype product before final sale to the market through a skin patch test conducted on the basis of the CTFA guidelines (Cosmetric, Toiletry, and Fragrance Association Guideline) and MFKM (Modified Frosch & Kligman's Method) The present invention relates to a method for measuring the degree of primary skin irritation of finished cosmetic products and systematically comparing / calculating / determining the measured results to determine whether or not the skin is safe in terms of primary skin irritation for cosmetics.

More particularly, the present invention relates to a cosmetic composition for skin care, which comprises a cosmetic composition, wherein the degree of skin reaction varies depending on the subject, Since the interpretation of the results of the patch test is very important since it is not possible to compare / calculate / judge the result of the response of the skin to the skin, it is possible to apply the formula (1) (Refer to the following equation (2)) based on the value obtained by the above-mentioned method, and finally, a standardized evaluation standard for each formulation of cosmetics is presented to provide reliability and convenience of safety inspection of cosmetics.

In accordance with one embodiment of the present invention, Applicants have found that, in order to provide confidence in the interpretation of the results of a human-level cosmetic patch test and the convenience of cosmetic safety testing, A total of 4,606 kinds of cosmetics were tested for the skin patch test for 12 years until December, and the results were analyzed. From the human skin patch test of the present invention alone, The criteria for safety in terms of primary skin irritation were clearly presented.

The safety inspection method for cosmetics according to one embodiment of the present invention includes a step (S100) of applying test cosmetics to the skin of a body of each subject, A step S200 of comparing the results of the skin patches after the removal of the patches with various reaction classes according to the skin reactions; A step (S300) of calculating a reaction degree (R) based on the comparison result; Calculating a z-score (z) using the calculated reactivity (R) (S400); Classifying the degree of stimulation of the skin reaction based on the value of the calculated z-score (S500); Among the values of the calculated z-scores (z), a value corresponding to 0? Z? 3 is adopted as a valid value, and a response (R) corresponding to the value of the effective z- (S600); (S700) classifying the calculated reactivity according to the cosmetic formulation and re-classifying the z-score; (S800) setting a case where the value of the re-calculated z-score for each cosmetic formulation is equal to or smaller than 1 as a safe area of cosmetics; (S900) of setting a range of the degree of reactivity as a degree of reactivity having a value corresponding to the safety region set for each cosmetic formulation; (S1000) in which the test cosmetics are evaluated as safe even if the degree of reactivity of the test cosmetics is within the range of the degree of reactivity set for each of the formulations of the cosmetics, and these steps are carried out sequentially.

More specific embodiments of the present invention are as described below.

One. Experimental group  selection

Among women who were aged between 18 and 60 years old at the time of the human skin patch test, those who fulfilled the conditions for age were selected according to the selection criteria of the human skin patch test as shown in Table 1 , Experimental group) and exclusion criterion (that is, experimental exclusion group), and the skin patch test was performed for each cosmetic species.

Experimental group and exclusion group for human skin patch test

Experimental group Healthy person without any skin disease between 18 and 60 years old Applicants who voluntarily signed a written consent before he / she fully explained the purpose and contents of the examination prior to the examination Those who are willing to cooperate well with the requirements of the experiment during the test period and to contact them promptly if there are any strange symptoms Applicants who can follow up during the test




Experiment
Exclusion group Women planning to become pregnant during pregnancy, during lactation, or within six months There are tattoos, scars, burns, etc. on the test site, which interferes with the calculation. If you have a skin disorder that interferes with the purpose of infectious skin disease or other tests If the drug currently being treated affects skin reactions Cosmetics, medicines or those who are irritated or allergic to daily light exposure Those with atopic skin Those taking contraceptives, antihistamines, anti-inflammatory drugs If you have pouch keratosis or skin graft donation Those who have severe irritation or allergies on the adhesive tape If you are participating in another exam at the same time If you have participated in the same previous exam and not more than 4 weeks In addition to the above items, if it is judged by the clinical trial manager that clinical trials are difficult

2. Classification of test cosmetics and amount

When a total of 248 human skin patch tests were conducted for a total of 7,440 Korean female subjects during the last 12 years, the test cosmetics used were 4,606 total, The results were excluded.

The cosmetics used in the human skin patch test were classified into four skin care, makeup care, body care and hair care, as shown in Table 2 below, according to their function and purpose, And finally subdivided into 14 sub-categories according to the product group.

Table 3 shows that 3,121 kinds of skin care products, 1,157 kinds of make-up products, 201 kinds of body care products and 127 kinds of hair care products were tested.

Classification of test cosmetics for human skin patch test Classification use Featured Products Number of products
skin care cleansing Makeup remover 141 Facial Cleaner (Wash-off) 152 Moisturizing &
Special Care toner 473 Lotion & Cream 2,130 Pack & Massage Cream 225

make up
Care
Basic makeup UV Cream 313 foundation 190 Face powder 255
Point Makeup Eyeshadow 177 Eyeliner, mascara 104 Lip product 118 Body Care cleansing SOF & BATH 72 Moisturizing Body Lotion & Cream 129 Hair Care Cleansing & Conditioning Shampoo, Conditioner & Hair Treatment 127 total 4,606

3. Human skin Patch  exam

Each of the cosmetics described above was defined as one subject for a human skin patch test. When cosmetics were applied to each subject, 30 to 33 subjects per each subject were subjected to a patch test for 24 hours and 48 hours , And after removal of the patches, the skin's response was rated and ranked as shown in Table 3 below.

The details are as follows.

The cosmetics used in the patch test are applied as they are provided by the manufacturer, and wash-off products such as cleansing foams and shampoos are diluted to 0.1 to 10% in distilled water, and powder or eye shadow is applied Squalane (negative control) was applied at 1 to 50% dispersion.

20 μl of each of these samples was dropped into an IQ chamber ™, placed on a test site, and fixed with a micropore tape. Thereafter, the patch area was observed at 30 minutes and 24 hours after the removal of the patch, and the presence or absence of the stimulation was calculated as shown in Table 3 below.

Estimation criteria for skin reactions sign Rating reaction - 0   none + One   Some erythema, spots or diffuse patterns ++ 2   Common isomeric erythema +++ 3   Severe erythema with edema ++++ 4   Severe erythema with edema and small bubbles

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a representative photograph showing the degree of skin reaction by human skin patch test. FIG. 1 shows the skin reaction grade after removing the patch after 30 minutes or 24 hours, (+), 2 (++), 3 (+++), and 4 (++++), respectively, as shown in Table 3 above 0 &lt; / RTI &gt; rating, indicating no skin effect at all.

4. Output method

Skin reactivity (R) was calculated for each of the above-mentioned cosmetics based on the human skin patch test results using Equation (1) as described below.

In the above formula representing skin response (R), G is grade; n is the number of subjects by grade; M is a maximum rating of 4; And N is the total number of subjects.

That is, a total of 30 subjects were subjected to a human skin patch test on one cosmetic product. Then, based on Table 3, the skin response of each subject was examined. At the 30 minutes after removal of the patch, There were 26 patients, 1 had skin reaction, 3 had skin reaction, 2 had skin reaction, 1 had skin reaction, 3 had skin reaction, and 4 had skin reaction. If there are 28 skin responders and 2 skin reactors of first grade, the skin reactivity (R) is calculated as 2.92 as follows.

R = [{(0 rating x 26 people) + (1 rating x 3 people) + (2 stars x 1 person) + (3 stars x 0 people) 28) + (1 class x 2 persons) + (2 classes x 0 persons) + (3 classes x 0 persons) + (4 classes x 0 persons)} / {4 x 30} 2.92

Thus, the reactivity for each of 4,606 cosmetics was calculated, Among the 4,606 cosmetics, there were no specific skin reactions in 70% of 4,606 subjects, and only skin reaction was found in 1,339 (29.07%) subjects. The highest maximal response was 14.60, Was 0.00, and the average of the reactivity was 0.36 and the standard deviation was 1.028 (see Table 4 and FIG. 2).

Calculation of the calculated reactivity after the human skin patch test on 4,606 subjects Number of objects Reactivity at least maximum Average Standard Deviation 4,606 0.00 14.60 0.36 1.028

FIG. 2 is a graph showing the distribution of the reactivity to a human skin patch test subject, wherein the horizontal axis is the number of objects and the vertical axis is the reactivity.

In addition, the reactivity calculated according to each subject was converted into a z-score using the mean and the standard deviation, and after normalization, the relative skin reactivity was compared with each subject, and the stability was judged. The reactivity was normalized by converting using the z-score as shown in the following formula (2), which enables direct comparison in terms of measurement units when analyzing the results of the test (see Table 5 below).

In Equation (2),? Is a raw score indicating the degree of each reaction for each cosmetic product; μ is the mean response of the subject; And σ is the standard deviation of the target response. For example, if the raw score is 1.4 and the values of the mean value and the standard deviation are 0.36 and 1.028, respectively, as shown in Table 4, z-score (z) = (1.40-0.36) / 1.028 = 1.01.

Thus, when all the responses of 4,606 were confirmed and applied to the z-score, the z-score was classified into four stages of low stimulus, light stimulus, middle stimulus and strong stimulus , And the z-score obtained by the formula (2) is 0.0? Z < 0.5 as the hypotonic, 0.5? Z <2.0 as the light stimulus, 2.0? Z <3.0 as the middle stimulus, and 3.0? Z And the skin response (R) corresponding to each of the classified z-scores is shown as a classification criterion of the primary stimulus as shown in Table 6 below.

This classification criterion is useful for judging the degree of skin irritation in the aspect of primary stimulus for human skin in the field of cosmetics.

Classification and standardization of reaction by z-score for total number of cosmetic products for test (4606 cases) object
amount Reactivity z-score reaction
Classification

Generally, when standardizing the original score and setting the reference, the z score is classified based on the integer value of the z score. However, when the z score is 0, 50% of the total 4,606 cases are classified. 15.866% when z score is 1; 2.275% when z score is 2; the range of the z-score judged to be valid in the range of z-score-0.35 to 13.85 as shown in Table 5 is set to be 0.0 to 3.0, and the range of z- As shown in Table 6, it is easy to make the judgment for the safety check by subdividing by 0.5, and the range of the response corresponding to the range of the z score is shown in Table 6 below.

Criteria for judging major human stimuli for cosmetics by human skin patch test Scope of z-score Range of responsiveness result 0.0 < z &lt; 0.5 0.00? R <0.87 Low stimulus 0.5? Z < 2.0 0.87? R <2.42 Light stimulus 2.0? Z <3.0 2.42? R <3.44 Moderate irritation 3.0? Z 3.44? R River stimulation

However, this is a criterion for judging only the degree of stimulation to the skin without considering the formulation characteristics of the cosmetic product, and it is insufficient to judge whether the skin is safe according to the cosmetic preparation. Therefore, as another aspect, it has become necessary to calculate the z-score according to each formulation in order to set the safe region, taking into account the formulation of cosmetics. This is a representative mixture of cosmetics with one or more chemical components, all of which can act as a source of irritation to the skin, but the degree of skin irritation can vary depending on the content of the ingredient or the degree of exposure. For example, in the case of shampoos with a high percentage of surfactants such as Sodium Lauryl Sulfate (SLS), skin irritation by the human skin patch test can be classified as a strong irritation, but the actual contact time with the skin is only 1 Minute to 2 minutes. Since the skin is immediately rinsed with water, the skin irritation is lowered, and it can be said that it is safe in terms of the skin primary stimulus.

When judging the safety of cosmetics on skin through the human skin patch test, it is necessary to apply different z-score judgment criteria according to the kind of each cosmetic product, actual use method, and use part.

Therefore, safety was evaluated in terms of primary skin irritation for cosmetics according to the type of cosmetics, based on the case where the z-score is 1.

For safety evaluation based on the formulation of cosmetics, cosmetics are divided into products such as leave on, tissue off, and wash off according to the method of use. As shown in Table 7 below, the rib-on product refers to a product (e.g., body lotion or the like) that does not need to be removed after use of the product, and the tissue-off product is removed (E.g., massage cream), and the wash-off product refers to a product (e.g., shampoo, etc.) to be washed after use of the product.

Based on the major product lines shown in Table 7 below, the rib-on products included toner, lotion & cream, foundation, sunscreen, lipstick, body lotion & cream, powder (face powder and eye shadow), eyeliner & mascara, Off products include facial cleansing creams, packs and massage creams, and wash-offs include facial cleansing foam, soap & bath, shampoo and conditioner.

As a result, we could classify 3,889 subjects for rib-on, 366 for tissue off, and 351 for wash-off, and the response of each cosmetic object was converted into z-score When the value is within the range of z score smaller than 1, it is judged to be safe in terms of primary skin irritation for each cosmetic product, and the response at this time is set as a safe area.

Therefore, in the case of the rib-on product group, the safety range of the safety region is 0.87 to 2.96, which is considered to be safe, 1.33 to 1.36 in the tissue off product group, and 2.82 to 3.98 in the wash off product group See Table 6).

Safety limit of cosmetics' response to main human stimulus calculated based on cosmetic formulation
Product Categories by Cosmetic Formulation z-score ≤ 1.00 Safety zone
Reactivity amount Average Standard
Deviation


Rib-on toner 0.87  473 0.28 0.587 Lotion & Cream 1.12  2,130 0.29 0.830 foundation 0.97  313 0.25 0.714 UV Cream 0.83  190 0.25 0.583 Lip product 0.98  118 0.22 0.759 Body Lotion & Cream 0.94  129 0.22 0.718 Face Powder, Eye Shadow 1.02  432 0.23 0.790 Eyeliner, mascara 2.96  104 0.78 2.184 Tissue-off Makeup remover 1.36  141 0.39 0.966 Pack & Massage Cream 1.33  225 0.33 0.993
Wash-off Facial Cleanser 3.20  152 1.09 2.107 SOF & BATH 3.98  72 1.36 2.620 Shampoo, Conditioner & Hair Treatment 2.82 127 1.26 1.563

Thus, in Table 7, the rib-on product group showed that all products except lotion & cream had safety at a relatively low safety level. However, despite the fact that lotion & cream is a product used on the face, the safety area is determined to be higher than other categories, as the number of subjects used in the human skin patch test shows that the most various formulations are developed using the most various raw materials It is thought that it includes products.

Although the eyeliner and mascara showed a moderate irritation level of 2.96 on the occlusion pellet, the film former used to improve the function of the product due to the nature of the product, It is highly likely that there is a difference from the degree of stimulation in actual use conditions.

Therefore, an open or half-open patch test may be performed on this type of product, and an alternative may be to compare and evaluate existing products that have been identified to be safe under the same test conditions, with 50% squalane (negative control ) Or powdered as it was, showed a similar degree of reactivity to the rib-on product line.

In the washoff / tissue off product line, where the type of surfactant is different or the ratio is high, the overall safety value of the product is expected as high as expected. However, due to the nature of the washoff / tissue off product, It is considered that the possibility of irritation to the skin is not high under actual use conditions. In the washoff / tissue off product line, the dilution concentration in the human skin patch test has a large effect on the reaction, so selection of the appropriate dilution concentration and comparison with the control group are very important to accurately evaluate the product safety.

Thus, it can be seen that the value of the responsiveness of the tissue-off product to the safety zone is 1.33 to 1.36, which is greater than the value of the safety of the rib-on product, i.e., 1, and 2.82 to 3.98 for the wash- off product.

The present invention is based on analyzing the skin patch test results of more than 4,000 cosmetics distributed over the past 12 years in Korea and over 7,000 general female subjects, And z scores were applied so that the calculated responses for various types of cosmetics could be compared and standardized. Therefore, safety classification criteria and safety criteria for highly reliable cosmetic primary stimuli were presented, According to the present invention, the method for inspecting the safety of cosmetics is easy and simple.

Claims (6)

A method for inspecting the safety of a cosmetic product according to a primary stimulation evaluation standard of human skin,
(S100) applying the test cosmetics to the skin of the body of each individual subject and then applying them;
A step S200 of comparing the results of the skin patches after the removal of the patches with various reaction classes according to the skin reactions;
A step (S300) of calculating a reaction degree (R) based on the comparison result;
Calculating a z-score (z) using the calculated reactivity (R) (S400);
Classifying the degree of stimulation of the skin reaction based on the value of the calculated z-score (S500);
Among the values of the calculated z-scores (z), a value corresponding to 0? Z? 3 is adopted as a valid value, and a response (R) corresponding to the value of the effective z- (S600);
(S700) classifying the calculated reactivity according to the cosmetic formulation and re-classifying the z-score;
(S800) setting a case where the value of the re-calculated z-score for each cosmetic formulation is equal to or smaller than 1 as a safe area of cosmetics;
(S900) of setting a range of the degree of reactivity as a degree of reactivity having a value corresponding to the safety region set for each cosmetic formulation; And
(S1000) that the test cosmetic is evaluated as safe even if the degree of reactivity of the test cosmetic product is within the range of the degree of reactivity set for each of the formulations of the cosmetic product. method of inspection. The method according to claim 1,
The various classes of reactions consist of 0, 1, 2, 3, and 4 grades, each of which has no effect on the skin at all, some erythema, spots, or dispersed aspect, A method for inspecting the safety of cosmetics according to the criteria for primary stimulation of human skin, in which erythema isomorphous, severe erythema with edema, and severe erythema with edema are observed. The method according to claim 1,
The step of calculating the reactivity (R)

Lt; / RTI &gt; is calculated using the equation &lt; RTI ID =
Wherein G is a rating; n is the number of subjects by grade; M is a maximum rating of 4; And N is the number of total subjects, according to the criteria for evaluating the primary stimulation of human skin. 4. The method according to any one of claims 1 to 3,
The z-score (z)

, And is used to set a criterion for judging the safety of the cosmetic, wherein? In the equation is a raw score representing the degree of reactivity for each cosmetic; μ is the mean response of the subject; And σ is the standard deviation of the target response, based on the primary stimulation evaluation criteria of the human skin. The method of claim 4,
0 < / = z < / = 3 adopted in the step (S900) 0.5? Z &lt;2.0; 2.0? Z &lt;3.0; And 3.0 ≤ z, respectively. The range of reactivity (R) corresponding to each of the four grades was 0.0 ≤ R <0.87 as hypothesis, 0.87 ≤ R <2.42 as light stimulus, 2.42 The method of inspecting the safety of a cosmetic according to a primary stimulation evaluation standard of the human skin, wherein the case where ≤R <3.44 is a middle stimulus and the case where 3.44 ≤ R is classified as a strong stimulus is classified as a criterion of primary stimulation. The method of claim 4,
The range of the response R corresponding to the safety zone set for each cosmetic formulation in the step S600 is 0.87 to 2.96 for the rib on product group, 1.33 to 1.36 for the tissue off product group, Of 2.82 ~ 3.98, according to the evaluation criteria of the primary stimulation of human skin.

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