Dry goods! How to prepare the poisoning data of the full version of the safety assessment report of cosmetics?

Release time:

2023-11-14 09:31

In order to implement the Regulations on the Supervision and Administration of Cosmetics and regulate and guide the safety assessment of cosmetics, the State Food and Drug Administration has issued the Technical Guidelines for the Safety Assessment of Cosmetics (2021 Edition) (hereinafter referred to as the "Guidelines"), which will come into force on May 1, 2021. The guidelines stipulate that before May 1, 2024, cosmetics registrants and filers may carry out cosmetics safety assessment and submit product safety assessment materials in accordance with the requirements of the simplified version of the guidelines.

At present, the full version of the safety assessment will be implemented on May 1, 2024. New Anrun Consulting will compare the requirements of the full version of the safety assessment and the simplified version of the safety assessment, and share its views on the preparation of future toxicological data.

In the simplified version of the safety assessment, there are four acceptable component safety assessment data, two of which are not accepted in the full version of the safety assessment.

L "cosmetics safety technical specifications (2015 edition)" in the restricted and permitted raw materials, must meet the requirements of its use

l Assessment conclusions of domestic and foreign authorities (WHO/FAO/CIR/GRAS/SCCS/IFRA), etc.

L the historical use of raw materials in the enterprise (at least three years) of the same use method of product concentration (the full version of the safety assessment will not be adopted)

L the highest historical usage (%) in the catalogue of used cosmetic raw materials (2021 edition) (the full version of safety assessment will not be adopted)

Safety Technical Specification for Cosmetics

In the list of restricted raw materials and the list of permitted raw materials in the "Cosmetic Safety Technical Specification", if some raw materials have specified the limit requirements, the use range and addition amount of the raw materials in cosmetics must meet the requirements without providing additional evidence. For the requirements of some infinite value requirements, the evaluation conclusions of domestic and foreign authoritative organizations should be searched down to meet the requirements of the full version of safety assessment.

Assessment conclusions of domestic and foreign authorities

About cosmetic raw material safety assessment authority, common including WHO/FAO/CIR/GRAS/SCCS/IFRA.

In the commonly used American CIR database, 3325 kinds of raw material related data in the catalogue of used cosmetic raw materials can be found, and nearly 6000 kinds of raw materials can not be retrieved. Among the raw materials reported by CIR, if the corresponding safety limits/restrictions have been given, the safety assessment of cosmetics can be used as evidence of safety assessment; if the safety limits/restrictions have not been given, the assessor can obtain the toxicological data of the raw materials from the assessment report for further assessment.

Safety assessment based on toxicological endpoint data

When the above data for the raw material is not available, further evaluation based on toxicological endpoint information is required. Toxicological endpoint information can be obtained through search, such as ECHA, NICAS and other databases, published papers, etc. The toxicological endpoint information of raw materials listed in Table 1 content guidelines includes local toxicity and systemic toxicity data. Generally speaking, local toxicity data need to be provided, and systemic toxicity data can be provided to repeated dose toxicity.

Table 1 Toxicological endpoints of cosmetic raw materials

Serial Number	Toxicological Endpoints		Remarks
1	local toxicity	Irritant/Corrosive	Eyes, skin
2		skin sensitization
3		skin phototoxicity	When the raw material has ultraviolet absorption, it needs to be provided.
4		skin photoallergy	When the raw material has ultraviolet absorption, it needs to be provided.
5	systemic toxicity	acute toxicity	Peroral/Percutaneous
6		Genotoxicity	Include at least one gene mutation test and one chromosome aberration test
7		repeated dose toxicity	28 days/90 days oral/percutaneous
8		reproductive and developmental toxicity
9		Chronic toxicity/carcinogenicity
10		toxicokinetics
11	Other		Inhalation toxicity test shall be provided when the raw material has inhalation risk

Table 2 Summary endpoints of in vitro alternative methods

Toxicological Endpoints	In vitro alternative methods
acute oral toxicity	OECD 129 uses cytotoxicity tests to predict initial doses in acute oral toxicity tests
Skin Irritation/Corrosivity	In Vitro Skin Irritation of OECD 439: A Recombinant Human Epidermal Model Test
	OECD 430 in vitro skin corrosion: rat transcutaneous electrical resistance test (TER)
	OECD 431 in vitro skin corrosion: a recombinant human epidermal model test
	OECD 435 skin corrosion in vitro membrane barrier test
skin phototoxicity	OECD 432 Neutral Red Uptake Phototoxicity Test Method (3T3)
	OECD 495 Reactive Oxygen Species (ROS) Test
	In Vitro Phototoxicity of OECD 498-Phototoxicity Test of Recombinant Human Epidermal Model
Eye Irritation/Corrosive	OECD 492 Recombinant Human Corneal Model Test (RhCE)
	OECD 491 Short Exposure Test (STE) of Rabbit Corneal Epithelial Cells in Vitro
	OECD 437 Bovine Corneal Permeability and Permeability Test (BCOP)
	OECD 492B SkinEthic™Recombinant Human Corneal Epithelium (HCE) Time-Toxicity Test (TTT)
	OECD 438 Ex Vivo Corn Test (ICE)
	OECD 460 Fluorescein Leakage Test (FL)
	OECD 494 Glass Gel-Eye Irritation Test (EIT)
	OECD 496 In Vitro Macromolecular Test Method (OI)
Skin allergy	OECD 442C Direct Peptide Response Assay (DPRA)
	OECD 442C Amino Acid Derivatization Reaction Assay (ADRA)
	OECD 442C Dynamic Direct Peptide Response Assay (kDPRA)
	OECD 442D ARE-Nrf2 Fluorescent Enzyme Assay (KeratinoSensTM)
	OECD 442D ARE-Nrf2 Fluorescent Enzyme Assay (LuSens)
	OECD 442E Human Cell Line Activation Assay (h-CLAT)
	OECD 442E bone marrow U937 cell line activation assay (U-SensTM)
	OECD 442E Interleukin-8 Reporter Gene Test (IL-8 Luc)
	OECD 442E Genomic Allergen Rapid Detection Test (GARDTM)

Based on the above situation, in response to the full version of the cosmetics safety review, the cosmetics raw materials industry pain points focused on:

ü High cost and long cycle of repeated dose toxicity;

ü The ban on animal testing prevents raw material/cosmetic companies with market needs in the EU and other regions from obtaining systematic toxicity data through animal testing.

In response to point 2, the guideline states that "for non-efficacious ingredients or risk substances for which systematic toxicological data are lacking, reference may be made to the use of Grouping/Read Across". Cross-referencing is to infer the toxicity of the target chemical based on the toxicity characteristics of the analogs, based on the fact that substances with similar chemical structures have the same metabolic pathways and chemical/biological reactivity. The structural similarity is shown 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 component or is classified into the same hazard level, with similar carbon chain length;(3) each chemical substance presents the characteristics of increasing or unchanged in structure (such as carbon chain length), this feature can be obtained by observing the physical and chemical properties of each chemical substance;(4) Due to the similarity of the structure of each chemical substance, it has the same possibility of precursor or degradation product after chemical substance or biological action.

However, it should be noted that the scope of application of cross-reference in the guidelines is limited to non-functional ingredients or risk substances, and cross-reference requirements substances have a clear chemical structure, the scope of use is narrow, can not be applied to the industry generally concerned about plant extracts, fermentation products and other raw materials.

The implementation of the full version of the safety review of cosmetics is a great challenge to cosmetics/raw material enterprises, and there are many doubts in the response of enterprises. We look forward to the regulatory authorities as soon as possible to issue the appropriate implementation/review rules, but also welcome the industry's small partners to discuss.

Cosmetic New Raw Materials Use Purpose Interpretation Series-Antioxidants

Announcement of the State Food and Drug Administration on Issues concerning Encouraging Innovation and Standardizing Management of New Raw Materials for Cosmetics (No. 143 of 2023)

Cosmetic New Raw Materials Use Purpose Interpretation Series-Antioxidants

Announcement of the State Food and Drug Administration on Issues concerning Encouraging Innovation and Standardizing Management of New Raw Materials for Cosmetics (No. 143 of 2023)

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