Safety Assessments Under Pressure as Documentation Standards Rise
Introduction
The cosmetic product safety report (CPSR), required under Article 10 of Regulation (EC) No 1223/2009, represents the cornerstone of the EU’s science-based regulatory framework for cosmetic products [1]. By May 2024, enforcement authorities across the EU reported increasing scrutiny of CPSR quality, with particular focus on completeness of toxicological data, adequacy of margin of safety calculations, and robustness of exposure assessments [2]. The Scientific Committee on Consumer Safety (SCCS) Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (10th Revision, SCCS/1602/18, with 11th Revision anticipated) established comprehensive methodological standards that many safety assessors struggled to meet, particularly for complex formulations, novel ingredients, and products intended for vulnerable populations [3]. The rising documentation standards reflected the maturation of the EU cosmetic regulatory framework and the accumulation of scientific knowledge regarding ingredient safety, but also created compliance challenges for small and medium-sized enterprises (SMEs) and safety assessors with limited toxicological expertise [4].
Article 10(1) requires that cosmetic products undergo a safety assessment prior to being placed on the market, and Article 10(2) specifies that the safety assessment must be carried out by a person in possession of a diploma or other evidence of formal qualifications in pharmacy, toxicology, medicine, or a similar discipline [5]. The CPSR must follow the structure specified in Annex I of Regulation (EC) No 1223/2009, comprising Part A (Cosmetic Product Safety Information) and Part B (Cosmetic Product Safety Assessment) [6]. Part A must contain comprehensive information on the product’s quantitative and qualitative composition, physicochemical properties, microbiological quality, impurities and contaminants, normal and reasonably foreseeable use, exposure, and toxicological profile of ingredients [7]. Part B must contain an assessment of the safety for human health, considering all information in Part A and concluding whether the product is safe when used under normal or reasonably foreseeable conditions [8].
Regulatory Framework and Legal Analysis
Article 10 of Regulation (EC) No 1223/2009 establishes the safety assessment requirement, stating that “in order to demonstrate that a cosmetic product complies with Article 3, the responsible person shall, prior to placing a cosmetic product on the market, ensure that the cosmetic product has undergone a safety assessment on the basis of the relevant information” [9]. The safety assessment must be part of the Product Information File (PIF) required under Article 11, and must be kept up to date in light of additional relevant information generated subsequent to the product being placed on the market [10].
The SCCS Notes of Guidance (10th Revision, SCCS/1602/18) provide detailed methodological recommendations for conducting safety assessments, covering all toxicological endpoints required under Annex I [11]. These endpoints include: acute toxicity, irritation and corrosivity, skin sensitization, dermal absorption, repeated-dose toxicity, mutagenicity and genotoxicity, carcinogenicity, reproductive toxicity (including effects on fertility and developmental toxicity), toxicokinetics, photo-induced toxicity, and human data [12]. For each endpoint, the Notes of Guidance specify preferred test methods, data quality requirements, and interpretation criteria [13].
Dermal absorption is a critical parameter because it determines systemic exposure and forms the basis for margin of safety (MoS) calculation [14]. The SCCS recommends in vitro dermal absorption studies using validated methods (OECD TG 428) with human or porcine skin, and specifies that the highest dermal absorption value from multiple studies should be used for SED calculation unless scientifically justified otherwise [15]. If in vitro data are not available, default values may be used: 100% for substances <100 Da, 50% for substances 100-500 Da, 10% for substances 500-1,000 Da, and case-by-case assessment for substances >1,000 Da [16].
Systemic exposure dosage (SED) is calculated using the formula: SED (mg/kg bw/day) = (A × C × DAp) / BW, where A is the amount of product applied per day (mg/day), C is the concentration of the ingredient in the product (%), DAp is the dermal absorption percentage, and BW is body weight (kg) [17]. The SCCS provides default values for product application amounts based on product type and application site, ranging from 0.01 g/day for lipstick to 18 g/day for body lotion [18]. For children’s products, lower body weights (10 kg for infants, 25 kg for children) and higher application amounts (relative to body surface area) must be used [19].
Margin of safety (MoS) is calculated as: MoS = NOAEL / SED, where NOAEL is the No Observed Adverse Effect Level from the most sensitive relevant toxicity study [20]. An MoS ≥100 is generally considered acceptable, providing a 10-fold safety factor for interspecies extrapolation and a 10-fold safety factor for intraspecies variability [21]. If the MoS is below 100, the ingredient concentration must be reduced, additional safety data must be generated to support a higher NOAEL, or the product must not be placed on the market [22].
The 11th Revision of the SCCS Notes of Guidance, anticipated in 2024-2025, was expected to introduce additional requirements, including enhanced guidance on mixture toxicity, endocrine disruption assessment, and use of new approach methodologies (NAMs) such as in vitro assays and computational models [23]. The revision also anticipated addressing safety assessment of complex natural extracts, microbiome-modulating ingredients, and products intended for use on compromised skin [24].
Toxicological and Safety Science Considerations
The toxicological assessment required for the CPSR integrates data from multiple sources, including in vitro assays, in vivo animal studies, human clinical data, and computational models [25]. The EU’s commitment to replacing, reducing, and refining animal testing (the 3Rs principle) has driven development of alternative methods, but validation and regulatory acceptance of these methods remain ongoing challenges [26]. Regulation (EC) No 1223/2009 Article 18 prohibits the marketing of cosmetic products containing ingredients tested on animals after March 2009 (for most endpoints) and March 2013 (for repeated-dose toxicity, reproductive toxicity, and toxicokinetics), with limited exceptions [27].
In vitro alternatives have been validated and accepted for several endpoints. For skin irritation, the Reconstructed Human Epidermis (RHE) test (OECD TG 439) provides a validated alternative to the Draize rabbit test [28]. For skin sensitization, a battery of in vitro assays—including the Direct Peptide Reactivity Assay (DPRA, OECD TG 442C), KeratinoSens™ (OECD TG 442D), and h-CLAT (OECD TG 442E)—can be integrated using defined approaches to predict sensitization potential [29]. For genotoxicity, the bacterial reverse mutation assay (Ames test, OECD TG 471) and in vitro micronucleus test (OECD TG 487) are well-established alternatives [30].
However, for systemic toxicity endpoints—particularly repeated-dose toxicity, reproductive toxicity, and carcinogenicity—validated in vitro alternatives remain limited [31]. The SCCS accepts read-across from structurally similar substances, quantitative structure-activity relationship (QSAR) predictions, and weight-of-evidence approaches integrating multiple data sources, but emphasizes that these approaches must be scientifically justified and adequately documented [32]. For novel ingredients lacking comprehensive toxicity data, the SCCS may conclude that safety cannot be demonstrated, necessitating generation of additional data or reformulation [33].
Mixture toxicity is an emerging concern, as cosmetic products typically contain 15-50 ingredients, and multiple products may be used concurrently [34]. The SCCS Notes of Guidance acknowledge that “the safety assessor should consider the possibility of combined effects from multiple ingredients,” but provide limited methodological guidance [35]. Concentration addition (assuming ingredients act on the same toxicological pathway) and independent action (assuming ingredients act on different pathways) are theoretical frameworks for mixture assessment, but their practical application to cosmetic formulations remains challenging due to data limitations [36].
Vulnerable populations, including infants, children, pregnant women, and individuals with compromised skin (e.g., atopic dermatitis, psoriasis), require special consideration in safety assessment [37]. The SCCS recommends that products intended for these populations undergo enhanced safety assessment, including use of lower body weights, higher application amounts, and consideration of age-specific toxicokinetics and susceptibility [38]. For products intended for use on compromised skin, enhanced dermal absorption and potential for systemic exposure must be considered [39].
Practical Compliance Guidance
For Responsible Persons, ensuring CPSR quality requires engagement of qualified safety assessors, comprehensive data collection, and systematic documentation. First, the safety assessor must possess appropriate qualifications as specified in Article 10(2), and should have practical experience in cosmetic toxicology and familiarity with SCCS guidance [40]. Many Member States maintain registers of qualified safety assessors, and professional organizations such as the European Society of Cosmetic and Investigative Dermatology (ESCD) provide training and certification programs [41].
Second, comprehensive toxicological data must be obtained for all ingredients, including raw materials, impurities, and potential degradation products [42]. Suppliers should provide detailed safety data sheets (SDS) and toxicological dossiers, including results from relevant toxicity studies, dermal absorption data, and information on impurities and contaminants [43]. For novel ingredients or ingredients lacking comprehensive data, additional testing may be necessary, prioritizing in vitro methods and read-across approaches to minimize animal testing [44].
Third, Part A of the CPSR must be completed with meticulous attention to detail, ensuring that all required information is included and properly documented [45]. The quantitative and qualitative composition must list all ingredients with their INCI names, CAS numbers, and concentrations (as ranges if proprietary information must be protected) [46]. The physicochemical properties must include molecular weight, log P, water solubility, pH, and stability data [47]. The microbiological quality must address preservative efficacy testing (challenge testing) and compliance with microbiological limits [48]. The toxicological profile must summarize available data for each endpoint, citing original studies and SCCS opinions where available [49].
Fourth, Part B must provide a clear, scientifically justified conclusion on product safety [50]. The SED and MoS must be calculated for each ingredient, using the highest dermal absorption value and the most sensitive NOAEL [51]. If the MoS is below 100, the safety assessor must explain why the product is nonetheless safe (e.g., due to conservative assumptions in the calculation) or recommend reformulation [52]. The conclusion must address all relevant exposure scenarios, including use by vulnerable populations if the product is intended for or likely to be used by such populations [53].
Fifth, the CPSR must be kept up to date, as required by Article 11(2), which states that “the product information file shall be kept up to date” [54]. If new toxicological data become available (e.g., new SCCS opinions, published studies, post-market surveillance data), the CPSR must be reviewed and updated as necessary [55]. If the updated assessment indicates that the product is no longer safe, Article 4(4) requires the Responsible Person to take corrective action, including withdrawal or recall under Article 25 [56].
Sixth, enforcement authorities increasingly request CPSRs under Article 21, and the quality of the CPSR directly influences enforcement outcomes [57]. A well-documented, scientifically robust CPSR demonstrates compliance and reduces enforcement risk, while a deficient CPSR may result in product withdrawal, fines, or other penalties [58]. The Administrative Cooperation (AdCo) group has developed guidance on CPSR quality assessment, and enforcement authorities use standardized checklists to evaluate completeness and adequacy [59].
Conclusion
The rising documentation standards for cosmetic product safety reports during 2024 reflected the maturation of the EU’s science-based regulatory framework and the accumulation of scientific knowledge regarding ingredient safety. Article 10 of Regulation (EC) No 1223/2009 and the SCCS Notes of Guidance establish comprehensive requirements for safety assessment, covering all relevant toxicological endpoints and requiring rigorous margin of safety calculations. Responsible Persons must engage qualified safety assessors, obtain comprehensive toxicological data, and maintain meticulous documentation to demonstrate compliance. As the SCCS continues to refine methodological guidance and enforcement authorities intensify scrutiny of CPSR quality, the cosmetic industry must invest in safety assessment expertise and infrastructure to meet evolving standards while maintaining the 3Rs principle and advancing alternative testing methods.
References
[1] Regulation (EC) No 1223/2009, Article 10.
[2] European Commission. (2024). AdCo guidance on cosmetic product safety reports. European Commission.
[3] Scientific Committee on Consumer Safety. (2018). SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 10th revision. SCCS/1602/18.
[4] European Commission. (2024). AdCo guidance on cosmetic product safety reports. European Commission.
[5] Regulation (EC) No 1223/2009, Article 10.
[6] Regulation (EC) No 1223/2009, Annex I.
[7] Regulation (EC) No 1223/2009, Annex I, Part A.
[8] Regulation (EC) No 1223/2009, Annex I, Part B.
[9] Regulation (EC) No 1223/2009, Article 10(1).
[10] Regulation (EC) No 1223/2009, Article 11(2).
[11] Scientific Committee on Consumer Safety. (2018). SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 10th revision. SCCS/1602/18.
[12] Scientific Committee on Consumer Safety. (2018). SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 10th revision. SCCS/1602/18.
[13] Scientific Committee on Consumer Safety. (2018). SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 10th revision. SCCS/1602/18.
[14] SCCS. (2018). Notes of Guidance (10th Rev.). SCCS/1602/18. European Commission.
[15] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[16] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[17] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[18] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[19] SCCS. (2018). SCCS/1602/18 — Notes of Guidance (10th Revision).
[20] SCCS. (2018). SCCS/1602/18 — Notes of Guidance (10th Revision).
[21] SCCS. (2018). SCCS/1602/18 — Notes of Guidance (10th Revision).
[22] SCCS. (2018). Notes of Guidance (10th Rev.). SCCS/1602/18. European Commission.
[23] SCCS. (2018). Notes of Guidance (10th Rev.). SCCS/1602/18. European Commission.
[24] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[25] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[26] Regulation (EC) No 1223/2009 on cosmetic products. OJ L 342, 59–209.
[27] Regulation (EC) No 1223/2009 on cosmetic products. OJ L 342, 59–209.
[28] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[29] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[30] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[31] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[32] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[33] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[34] SCCS. (2018). Notes of Guidance (10th Rev.). SCCS/1602/18. European Commission.
[35] SCCS. (2018). Notes of Guidance (10th Rev.). SCCS/1602/18. European Commission.
[36] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[37] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[38] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[39] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[40] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[41] Scientific Committee on Consumer Safety. European Commission. https://health.ec.europa.eu/scientific-committees/scientific-committee-consumer-safety-sccs_en
[42] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[43] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[44] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[45] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[46] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[47] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[48] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[49] Scientific Committee on Consumer Safety. SCCS opinions. European Commission.
[50] Scientific Committee on Consumer Safety. SCCS opinions. European Commission.
[51] Scientific Committee on Consumer Safety. SCCS opinions. European Commission.
[52] SCCS. (2018). SCCS/1602/18 — Notes of Guidance (10th Revision).
[53] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[54] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[55] Scientific Committee on Consumer Safety. SCCS opinions. European Commission.
[56] Regulation (EU) 2019/1020 on market surveillance and compliance of products.
[57] Regulation (EC) No 1223/2009 on cosmetic products; SCCS/1602/18. European Commission.
[58] Administrative Cooperation Group (AdCo) for Cosmetic Products. European Commission.
[59] Administrative Cooperation Group (AdCo) for Cosmetic Products. European Commission.