1. What are the main local and systemic toxicity tests for cosmetic safety assessment?

Answer: Local toxicity:
(1) Skin and/or eye irritation/corrosiveness;
(2) Skin sensitization (skin allergy);
(3) Skin phototoxicity;
(4) Skin photoallergic reactions.
System toxicity:
(1) Acute toxicity (acute oral and/or percutaneous);
(2) Genetic toxicity;
(3) Repeated dose toxicity;
(4) Reproductive developmental toxicity;
(5) Chronic toxicity/carcinogenicity;
(6) Toxicokinetics, etc.
2. What types of evidence can be used to evaluate the safety of ingredients and/or risk substances in the simplified version of cosmetic safety assessment report?
Answer: According to the "Guidelines for the Safety Assessment of Cosmetics" (2021 Edition), at least one type of evidence should be selected for evaluation in the following order to determine its safety:
(1) The use of restricted components, permitted preservatives, permitted sunscreen agents, permitted colorants, permitted raw materials in the list of permitted hair dye and risk substances with limited requirements in the Technical Specifications for the Safety of Cosmetics shall meet the requirements of the Technical Specifications.
(2) The published safety limits or conclusions of domestic and foreign authorities, such as the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO, The International Flavor Association (IFRA) has issued standards for spice raw materials. If there are restrictions (such as irritant requirements), based on the historical use concentration of the raw materials, toxicological testing of the product or raw materials, or clinical testing results in humans, their limits or conclusions can be used if they meet their restrictions; If there is only a conclusion of systemic toxicity assessment, combined with the historical use concentration of raw materials, toxicological test results of products or raw materials, or human clinical test results, after evaluating the local toxicity such as product irritation, the limit or conclusion can be used.
(3) The concentration of raw materials in products with the same usage method that have been listed in our company for at least 3 years (i.e. the historical usage concentration of our company) is used as evidence for evaluation. In principle, the concentration of raw materials used in product formulas with the same usage site and method should not be higher than the historical usage concentration of the raw materials in our company. If it is higher than the historical usage concentration, a safety assessment should be conducted in accordance with this guideline to prove its safety; The historical usage concentration of raw materials can be mutually referenced, and products with high exposure and long exposure time can be used for evaluation of products with low exposure and short exposure time. However, it is necessary to fully analyze and explain its rationality from the target population, usage site, and usage method.
The proof documents that should be provided for the historical usage concentration of our company include: 1) Domestic special products and imported products: registered or recorded formula (which must be consistent with the formula submitted at the time of application), product registration certificate or record proof, and product listing proof documents; 2) Domestic ordinary products: production records, process sheets, ingredient lists with raw material content or calculable raw material content, filing vouchers, and product listing proof documents; 3) Description of adverse reaction monitoring; 4) Other supporting documents.
(4) When none of the above three types of evidence can be evaluated, the highest historical usage of raw materials announced by the cosmetics regulatory authority can provide a reference for evaluation. The concentration of raw materials used in the product should not be higher than the highest historical usage of raw materials published by the cosmetics regulatory department.
For raw materials and/or hazardous substances that cannot use any of the above types of evidence, their safety should be evaluated and demonstrated in accordance with the evaluation procedures required by this guideline.
3. Cosmetic safety assessment cannot use simplified reports for any type of evidence of raw materials. How can the safety of raw materials or risk substances be evaluated?
Answer: (1) For raw materials that cannot be used for all four types of evidence in question 2 above, a complete evaluation is required. The complete evaluation of raw materials should be carried out in accordance with the 4. Risk assessment procedure and 6.1. Safety assessment principles specified in the "Guidelines", and an explanation should be given whether the application risk of the raw material in the product is within an acceptable range.
(2) Toxicological Threshold of Concern (TTC) method: if the chemical structure of the raw material is clear, and does not contain raw materials or risk substances with serious mutagenic structure, the content is low and systematic toxicological research data are lacking, the TTC method can be referred to for evaluation, but this method is not applicable to metals or metal compounds, strong carcinogen (such as aflatoxins, nitroso compounds, benzidine and hydrazine) Proteins, steroids, high molecular weight compounds, highly bioaccumulative substances, radioactive chemicals, and mixtures with unknown chemical structures. The classification of TTC structure can be assisted by software such as OECD Toolbox and Toxtree to select the corresponding TTC exposure limit.
(3) For non functional components or risk substances lacking systematic toxicological research data, evaluation can be referred to using grouping/Read Across. The referenced chemical has a similar chemical structure, metabolic pathway, and chemical/biological reactivity to the raw material or risk substance. The structural similarity is manifested in: 1) each chemical substance has the same functional group (such as aldehydes, epoxides, esters, special metal ions); 2) Each chemical substance has the same composition or is classified as the same hazard level, and has similar carbon chain lengths; 3) Each chemical substance exhibits an increasing or constant characteristic in structure (such as carbon chain length), which can be obtained by observing the physicochemical properties of each chemical substance; 4) Due to their structural similarity, each chemical substance has the same precursor or degradation product potential through chemical or biological interactions. When using cross reference methods, similarities in chemical structure, physicochemical properties, and metabolism can be achieved using software such as OECD Toolbox.
4. Under what circumstances are raw materials exempt from conducting systemic toxicity assessments?
Answer: The safety limits and conclusions published by authoritative institutions such as the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), such as daily allowable intake (ADI), daily tolerable dose (TDI), reference dose (RfD), generally considered safe substances (GRAS), raw materials with a long history of consumption, etc., as well as extracts from edible parts, do not involve biochemical or chemical reactions in the extraction process After analyzing the relevant data of raw materials that have not changed their original food composition structure, relevant conclusions can be adopted in accordance with relevant national regulations.
What are the commonly used databases for cosmetic safety assessment?
Answer: (1) The cosmetic ingredient safety assessment database established by the American Cosmetic Ingredient Assessment Committee
(2) European Commission database on cosmetic ingredients
(3) European Chemicals Administration database
(4) Food Additives Related Database under WHO
(5) Health and Environmental Toxicology Database of Food Related Substances Assessed by FFSA
(6) The US Food and Drug Administration generally considers safe substance databases

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Source: Guangzhou Market Supervision Administration