According to the requirements of the National Medical Products Administration, after May 1, 2024, cosmetic registrants and filers must conduct cosmetic safety assessments in accordance with the requirements of the “Technical Guidelines for Cosmetic Safety Assessment (2021 Edition)” (hereinafter referred to as the “Technical Guidelines”) and submit a complete version of the “Cosmetic Safety Assessment Report”.
In response to this change, Enzyme Products took the lead in launching safety evaluations of all cosmetic raw materials on the market at the end of 2023. Currently, raw materials such as S-Pro-Xylane, Blue Copper Peptide, Ergothioneine, Ectoin, Acetyl Hexapeptide-8, and Snake Venom Peptide can all provide third-party “Cosmetic Raw Material Safety Assessment Reports”. The testing items include acute oral/dermal toxicity tests, repeated skin irritation tests, eye irritation tests, skin phototoxicity tests, skin photoallergy tests, mammalian chromosome aberration tests, bacterial reverse mutation tests, and repeated dose toxicity tests. In addition, human closed patch tests and chicken embryo chorioallantoic membrane tests have been completed.
The raw material safety assessment results show that the raw materials sold for the finished enzyme product have good safety under normal, reasonable and foreseeable use conditions, within the recommended concentration range, and will not cause harm to human health; the risks are controllable.
1. How to use the raw material safety assessment report?
After obtaining the raw material safety assessment reports for each component in the cosmetic product, the professional organization commissioned by the cosmetic registrant/filer assesses the cosmetic raw materials or any potentially hazardous substances according to the risk assessment procedure. This assessment considers factors such as the product’s usage method, application site, dosage, and exposure levels to residues, and includes a safety assessment of the cosmetic product. An example of such an assessment is as follows:
Raw Material X (XXX) : Acute Toxicity: Acute oral toxicity testing showed that this raw material is practically non-toxic. Acute dermal toxicity testing showed that this raw material is slightly toxic. Skin Irritation: According to the toxicological safety data provided by the raw material supplier, this raw material is non-irritating to the skin at a concentration of 50%. Eye Irritation: According to the toxicological safety data provided by the raw material supplier, this raw material is non-irritating to the eyes at a concentration of 50%. Skin Allergic Reaction: This raw material is non-sensitizing. Skin Phototoxicity: This raw material is non-phototoxic. Mutagenicity: No potential for gene mutation or chromosomal aberration. Systemic Toxicity: Based on the hazard characterization, the No Observed Adverse Effect Level (NOAEL) of this raw material is 1000 mg/kg bw/day. The NOAEL of 1000 mg/kg/day from the repeated oral exposure test data was selected to calculate the safety margin. Exposure dose = 7.82 × 1000 × 0.6000 × 1 × 1 / (60 × 100) = 0.782 mg/kg/d. Safety margin MoS = 1000/0.782 = 1279 > 100. The risk of using this raw material in this product is within acceptable limits.
The raw material safety assessment report will be uploaded as an attachment along with the “Cosmetic Safety Assessment Report”.
2. How to conduct a safety assessment of cosmetics?
Cosmetic products are generally considered to be a combination of various raw materials, and the safety of these raw materials is a prerequisite for the safety of cosmetic products. According to the Technical Guidelines, the safety assessment of cosmetic raw materials involves four steps:
Step 1: Hazard Identification. Identify the health hazards posed by the cosmetic ingredients used, such as acute toxicity, skin irritation, eye irritation, and sensitization. Cosmetic ingredients here refer not only to the substances themselves but also to other potentially hazardous substances they may introduce, such as impurities, microorganisms, heavy metals, and solvent residues. Furthermore, the stability of the ingredients during use and whether they will react with other ingredients to produce hazardous substances should also be considered.
Step 2: Dose-Response Relationship Assessment. This step requires clarifying the relationship between the toxic response of the raw material or hazardous substance and the exposure dose based on toxicological test results; that is, at what dose is toxic. Commonly used reference indicators are the No Observed Adverse Effect Level (NOAEL) or the Benchmark Dose (BMD). NOAEL is generally determined through repeated dose toxicity studies (90 days or 28 days) and chronic toxicity studies. Note: The dose here refers to the exposure dose, not the actual usage dose (concentration) in the product. How to convert between the exposure dose and the usage dose (concentration)? This requires an exposure assessment.
Step 3, Exposure Assessment: This involves determining the exposure level by assessing the site, concentration, frequency, and duration of exposure of cosmetic ingredients and/or hazardous substances to the human body. Different cosmetics expose to different sites. While general skincare products expose to the skin, rinse-off or spray products may expose to mucous membranes or be inhaled. Face creams are generally used on the face, while body lotions are used all over the body; the exposure area differs, and therefore the corresponding exposure amount also differs (the former is approximately one-fifth of the latter). The duration of leave-on application differs from that of post-use rinsing. The frequency of exposure differs between intermittent and daily use. Considering these factors, a quantitative relationship between exposure dose and concentration can be established. The maximum safe concentration of the ingredient in the cosmetic can be calculated by defining the safe exposure dose of the ingredient.
Step 4: Risk Characterization: This describes the likelihood and extent of harm to human health caused by cosmetic ingredients and/or hazardous substances. How is the safe exposure dose of an ingredient determined? A common method is to calculate the Margin of Safety (MoS). Generally, when MoS ≥ 100, it can be considered safe. Based on the NOAEL (Normally Absorbable Exposure Scale), the maximum safe exposure dose can be determined, and then the maximum usable concentration can be calculated.
3. The Challenges of the Full Version of the Security Assessment
Currently, the industry term “complete safety assessment” refers to the “Cosmetic Safety Assessment Report (Complete Version)” submitted to the State Drug Administration’s information service platform during the cosmetic registration/filing process. Therefore, the terms “complete version” and “simplified version” refer to the safety assessment report for cosmetic products. The term “complete safety assessment” does not apply to cosmetic ingredients. Compared to the safety assessment report currently submitted by cosmetic registrants/filers (i.e., the “simplified safety assessment”), the complete safety assessment includes preservative challenge reports, product physicochemical properties and stability testing reports, and product compatibility testing reports with packaging materials. It cannot use “the highest usage amount of ingredients listed in the used ingredient catalog” or “the company’s historical usage concentration” as evidence for the safety assessment of each ingredient in the formula.
When historical usage data cannot be used to determine the safety margin, cosmetic companies need authoritative third-party testing institutions to provide product safety assessment data, or to have raw material suppliers provide comprehensive safety assessment reports for the raw materials to help determine the safety of the added raw materials in terms of product series and concentration.
Although the Technical Specifications clearly state that assessment conclusions published by internationally authoritative cosmetic safety assessment agencies can be adopted, only about 30% of the 8,972 raw materials included in the Catalogue of Used Cosmetic Raw Materials have clear usage scopes and safety conclusions. In particular, for raw materials of plant and fermentation origin, less than 15% have clear assessment conclusions.
4. Should we wait and see or take proactive measures?
The safety evaluation of raw materials involves numerous toxicological tests, representing a significant investment for raw material suppliers. The choice between waiting and observing or taking proactive measures is a dilemma faced by all cosmetic raw material suppliers. For this issue, Enzyme Products offers a simple and direct approach. Based on the team’s over 20 years of experience in the peptide drug field, they have accumulated extensive experience interacting with regulatory authorities in product research and development, production, quality management, and registration applications. They possess a deep understanding and insight into the regulatory logic and system of the cosmetic industry since the promulgation of the “Cosmetics Supervision and Management Regulations.” Furthermore, Enzyme Products’ experience in independently applying for new cosmetic raw material status and its product portfolio across different fields (biopharmaceuticals, nutrition and health) enable the company to confidently handle raw material safety evaluations.
Our enzyme products focus on biomolecules such as peptides, proteins, sugars, and nucleic acids, which inherently possess advantages such as high safety and activity. The company has established a product-centric service system, providing clients with a range of professional support services including quality control, application research, and efficacy evaluation. We firmly believe that safety is the primary characteristic of cosmetics, and that implementing comprehensive safety assessments is essential for the industry’s high-quality development. Based on multidisciplinary technical resources and multi-field research experience, we actively improve the safety assessment of our entire product line, providing clients with end-to-end professional support and striving to become their most reliable partner.
Important Notice: The information published on this public account is for academic research reference only and does not constitute any investment advice or commercial opinion. No one may copy, reproduce, or quote the content of this article without written consent; otherwise, we reserve the right to pursue legal action. The information described herein is derived from research results on finished enzyme products or based on publicly published literature or information. This public account makes no guarantee or promise regarding its accuracy or completeness. Readers should exercise independent judgment when using the information published on this public account and should not rely solely on the information for their personal judgment. Furthermore, readers should be aware of the potential risks associated with using this information and bear the corresponding responsibility themselves.