In 2021, the "377 incident" sparked widespread concern and debate within the industry, and it was made clear that "377" was intended for skin whitening and could not be used in ordinary cosmetics.

On 1 February 2023, the EU Scientific Committee on Consumer Safety (SCCS) issued its final opinion on the safety of alpha-arbutin and beta-arbutin in cosmetics.

On 17 March 2023, the National Institutes for Food and Drug Control released the "Technical Guidelines for Research on Spot Whitening Cosmetics (Draft for Comments)" and other documents to publicly solicit comments from the community.

Whitening efficacy ingredients always touch the hearts of industry professionals. Today, ZOOP introduce you to the common spot whitening efficacy ingredients and the analysis of risk aspects.

I. Common efficacy ingredients of freckle-removal and whitening cosmetics

Whitening cosmetics can achieve whitening effects by means of physical concealment or by adding whitening agents. For the latter, the mechanism of action mainly includes: inhibition of melanin production, blocking of melanin transit, reduction of melanin and promotion of epidermal melanin shedding, etc. The whitening effect that the product has actually depends on the type and amount of whitening agent added to the product. The ingredients commonly used in blemish whitening cosmetics include physical masking ingredients and whitening agents, and the whitening agents include some botanical ingredients, as shown in Table 1.

Table 1 Commonly used raw materials for freckle-removal and whitening cosmetics

II. Safe dosage of some whitening agents

In China, freckle-removal and whitening cosmetics are classified as special cosmetics and are subject to stricter regulation, one of the reasons being that the risks associated with such cosmetics are higher than those of ordinary cosmetics. The risks of whitening cosmetics are multifaceted. Firstly, whitening products inhibit melanin synthesis, which protects skin cells from UV damage; secondly, the use of inappropriate types and dosages of whitening agents in whitening products can also cause some harm, such as the 2013 Japanese case of azulenol causing white spots and the presence of potential endocrine disrupting properties of kojic acid. Therefore, the safety assessment of whitening agents deserves more attention. Table 2 demonstrates the safe dosage of some whitening agents and the assessment bodies.

Table 2 Safe dosage of some whitening agents

Among other things, the SCCS final opinion states that hydroquinone should be as low as possible in formulations containing α- or β-arbutin and should not be higher than the unavoidable traces in both arbutins; in the latest study submitted by the applicant, the LOQ (limit of quantitation) for hydroquinone is 3 ppm and the LOD (limit of detection) is 1 ppm. The SCCS was not able to derive safe concentration limits for the two arbutin species in cosmetics at this time.

The aforementioned "377" is phenethylresorcinol, a new cosmetic ingredient approved by the former State Food and Drug Administration in 2012, with a use limit of 0.5% and the only approved purpose of use being "skin whitening, inhibiting melanin formation by inhibiting tyrosinase activity". The only approved purpose is to "lighten the skin and inhibit melanin formation by inhibiting the activity of tyrosinase", therefore "377" cannot be used in ordinary cosmetics.

Figure 1 Arbutin

Figure 2 Hydroquinone (hydroquinone)

Figure 3 Phenylethylresorcinol

In terms of chemical structure, arbutin, hydroquinone and phenethylresorcinol all contain a benzol structure, with arbutin and hydroquinone as para-hydroxyl groups and phenethylresorcinol as meso, which may reveal the reason for the whitening effect of all three ingredients. However, hydroquinone is classified as a banned component in cosmetics due to its toxicity and potential side effects. When hydroquinone is used as a prescription medicine, it needs to be used under the supervision of a physician for the treatment of melasma and hyperpigmentation spots.

It can be seen that not all raw materials can be used in cosmetics, even though they have the same spot-lighting and whitening effect, and a rigorous safety assessment is needed to control the risks before the raw materials are used in cosmetics.

III. Some key points of the Technical Guidelines (Draft for Comments)

The guiding principles mentioned in the title refer to the "Technical Guidelines for the Study of Efficacy Raw Materials for Spot Whitening Cosmetics (Draft for Comments)" (hereinafter referred to as the Technical Guidelines) issued by the National Institutes for Food and Drug Control. The following points in the technical guidelines are of interest:

1. clarifies the scope of application of the technical guidelines. Not applicable to raw materials that function by means of physical masking and not applicable to registration declarations for new raw materials for spot whitening;

2. The difference between the mechanism of action of spot whitening ingredients and other ingredients is clarified. The mechanism of action of spot whitening is different from that of sun protection, exfoliation and skin tone brightening.

3. It is clarified that the dosage of spot whitening principle formulations should take into account both safety and effectiveness. There are different requirements for the use of human efficacy evaluation tests or in vitro testing methods respectively; for raw materials that can produce spot whitening effects at very low dosages, the reasons and corresponding risks should be fully analysed, while setting up corresponding quality control measures.

4. Encourage research on specific efficacy ingredients for non-single ingredient spot whitening ingredients such as plant extracts.

5. Research should be conducted on the stability, risk substances and quality control of spot whitening ingredients; adverse reaction monitoring and long-term data accumulation.

6. clarify that the use of the same raw material in different products should comply with the relevant regulatory requirements, comprehensive consideration of the scientific rationality of the use of raw materials.

References

[1] Former State Food and Drug Administration. Announcement of the State Food and Drug Administration on the approval of 4-(1-phenylethyl)-1,3-benzenediol for use as a cosmetic ingredient (No. 71).2012-12-05

[2] SCCS. Safety of alpha-arbutin and beta-arbutin in cosmetic products (Final Opinion). 2023-02-01.

[3]National Medical Products Administration. Rational Understanding and Use of Spot Whitening Cosmetics. 2020-07-15.

[4] National Medical Products Administration. An introduction to whitening cosmetics and whitening agents. 2021-12-16.

[5] National Institutes for Food and Drug Control. Notice of public consultation on "Technical Guidelines for Research on Spot Whitening Cosmetics (Draft for Comments)" and others. 2023-03-17.