Regulation and Safety of Cosmetics: Pre- and Post-Market Considerations for Adverse Events and Environmental Impacts

Abstract

Cosmetic products have been increasingly regulated, particularly in Europe. With the introduction of the cosmetic regulation in 2013, stricter quality standards were implemented, surpassing those set by the 1976 legislation. The primary objective of these regulations is to safeguard consumer safety during the use of cosmetic products. Despite these advancements, certain regulatory gaps remain, indicating the need for more effective measures to enhance human and environmental health protection. Considering the aforementioned, this work aims to provide an overview of the current Cosmetics Regulation, highlighting the weakest cornerstones that represent the missing link keeping the core objective from being achieved. While there is ongoing reliance on historical data from animal studies, efforts are actively underway to replace these methods with new new approach methodologies for risk assessment. Additionally, regulatory authorities continue to improve environmental considerations in the assessment process. These measures, along with enhanced surveillance systems, are gradually addressing existing gaps and contributing to a more robust regulatory framework that balances market access with consumer safety. Legally non-compliant—or perhaps compliant but unknowingly dangerous—products may be used by people who relativize them as inherently safe, leading to adverse events. Whether caused by an underlying disease or purely by the chemical’s toxicity, these may never come to the attention of the authorities as they are generally under-reported, making it unfeasible to implement corrective or preventive measures to address their root cause. To illustrate, non-compliant products that have been detected by the Portuguese authority, INFARMED, I. P., from January 2018 to September 2023 are discussed, which were found to be potentially dangerous to human health and, therefore, withdrawn from the market.

1. Introduction

Cosmetic products result from the inclusion of cosmetic active ingredients in a vehicle that ensures chemical, physical, and microbiological stability to enable cleansing, protection, beautification, and/or odor correction [1]. For the most diverse functions, the growing demand for the category leads to the development and implementation of new technologies, increasingly based on specialized scientific knowledge. It is estimated that the global cosmetics industry market currently exceeds hundreds of billions of dollars [2,3].

Formulation strategies in cosmetology prioritize meeting the new market trends, which lately have included heightened attention to aspects such as skin care, sustainability, social beauty, customizability, and the ongoing commitment to safety, which although not new, remains a fundamental and highlighted aspect [4]. However, the claims made by the products, the marketing strategies, as well as the formulation itself are not always in accordance with what is required by the competent authorities (CA) [5]. The criteria distinguishing cosmetic products that are allowed on the market from those prohibited due to safety or ethical concerns are clearly defined in Regulation (EC) No 1223/2009. For example, the regulation enforces a ban on substances classified as carcinogenic, mutagenic, or reprotoxic (CMR), ensuring these harmful ingredients are not present in cosmetic products. Additionally, the ban on animal testing for both finished products and cosmetic ingredients reflects the EU’s ethical stance on testing methods [1,5]. Products must undergo a thorough safety assessment before being marketed, conducted by a qualified safety assessor to ensure that they do not pose risks to human health [2]. These stringent regulations make the EU´s cosmetic framework one of the most rigorous worldwide, particularly in comparison to North American or Asian regulatory systems.

The European method for the registration of cosmetics on the market, the applicable legislation, and the cosmetovigilance system are primarily aimed at protecting public health against the risks associated with exposure to formulations considered as risks [1]. This regulatory system has significantly evolved since its development and continues to do so through ongoing updates and refinements. Although certain gaps in regulatory enforcement and surveillance remain, particularly in the assessment of adverse events, current measures are being actively improved to address these issues. As part of these, initiatives like the CLP regulation are working toward enhancing the traceability and risk management of hazardous substances. Since the implementation of Regulation (EC) No 1223/2009, regulatory authorities like the Scientific Committee on Consumer Safety (SCCS) have regularly reviewed the safety of ingredients and acted upon emerging risks. For instance, substances such as Butylphenyl Methylpropional (Lilial) and Zinc Pyrithione were banned after SCCS evaluations identified their reproductive toxicity and carcinogenic potential, leading to their removal from cosmetic products in 2021 [6]. Furthermore, the RAPEX platform has proven effective in identifying non-compliant products. From 2018 to 2023, the platform recorded over 150 cases of cosmetics products containing banned or hazardous substances, underscoring the ongoing need for market surveillance and regulatory enforcement [7].

Originally conceived as preparations to enhance personal appearance and hygiene/cleanliness through direct application to the skin, cosmetics have now taken on a new role in dermatology by supporting the management of many skin conditions. With the improved understanding of skin physiology and the development of technological advances in cosmetology science, it is now better known that cosmetics could change the aesthetic appearance and the well-being of the skin. Such category of products can alleviate discomforts caused by dermatological diseases, improve quality of life and self-esteem, and prevent diseases that may ultimately evolve into serious outcomes. Cosmetic formulations are increasingly customized based on consumer profiles, including age, skin type, sensitivity, and specific dermatological conditions. Advances in analytical methods have enabled manufacturers to develop products that cater to the unique needs of consumers, including those with conditions like rosacea, eczema, or mature skin [8]. For example, formulations containing peptides, ceramides, and botanical extracts like niacinamide are commonly used in products targeting specific skin concerns. It is therefore justified that these products should be regulated with some stringency by the CAs to establish the quality criteria and ensure that they will not cause harm to human health if used correctly [9].

In comparison, the United States and Asia have also witnessed significant growth in personalized cosmetics. In the US, advancements in AI-driven skincare diagnostics and customizable formulas have allowed consumers to create bespoke products [10]. In Asia, particularly in South Korea and Japan, customization has been a long-standing trend, with brands offering personalized beauty routines based on skin concerns, climate conditions, and cultural preferences [11]. Despite regional differences, the common goal across these markets is to provide targeted solutions that address individual consumer needs.

2. Literature Review Methodology

2.1. Search Strategy

In this comprehensive review, the search terms included the keywords relevant to this manuscript. Specifically, the keyword “cosmetic” was employed in conjunction with the following index terms: “physicochemical properties”, “vigilance”, “non-animal approaches”, “skin sensitization”, “nanotechnology”, “market products”, “safety assessment”, “adverse reactions”, “environmental hazards”, “regulation”, and “toxicology”. Additionally, keywords were selected based on a review of the literature and tailored to capture a wide range of safety and regulatory issues in cosmetics. Although some older articles were cited, the majority of the search covered articles published between January 2018 and December 2023, with an emphasis on the most recent publications to ensure timeliness and relevance. The electronic databases searched included PubMed, ScienceDirect, Web of Science, Google Scholar, ResearchGate, and Eur-Lex. Other important sources included the official websites of the European Commission and Portuguese regulatory authorities (INFARMED, I.P.), especially for guidelines on registration and cosmetovigilance. Boolean operators “AND”, “OR” or “NOT” were applied to refine the search and cover different combinations of keywords. The inclusion criteria were articles that contained one or more of the relevant keywords and/or index terms in the title or abstract, and preference was given to articles written in English. No geographical limitations were applied, but the primary focus was on the European market, given the nature of the regulatory framework. At least one author reviewed the title and abstract of each manuscript to determine its relevance and decide whether to include it as bibliographic support for this review.

2.2. Material Selection

The references consulted comprised the applicable legislation for the current European regulatory framework for cosmetics, alongside relevant articles which provided background knowledge on the core issue of cosmetovigilance.

Identified through database searching were 249 records. Some of them were excluded due to being outdated, non-relevant, or lacking data related to cosmetic regulations or safety assessments. Screening of the remaining records was conducted by reading the abstracts and full texts, based on the pre-established eligibility criteria. This screening process was used to ensure that only articles addressing key topics such as cosmetic regulations, safety assessments, and adverse reaction reporting were included.

Ultimately, 158 references, corresponding to informative circulars from INFARMED, I.P., laws and guidelines, and peer-reviewed scientific articles, were used for the reviewing process. Of these, 33 studies were excluded because they focused on non-cosmetic industries, lacked relevant safety or regulatory data, or used methodologies that did not meet the required rigor. This approach ensured that the review was based on accurate, up-to-date, and relevant sources.

3. Regulatory Framework for Cosmetics in Europe

Aiming to guarantee safety and quality, the European CA established a set of standardized norms that outlines the threshold of acceptability for cosmetic products to be placed on the market within the European Union. The main requirements and definitions are mentioned in Regulation (EC) No. 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products—also called the Cosmetics Regulation (CR)—which entered into force on 11 July 2013, replacing the obsolete Council Directive 76/768/EC of 27 July 1976 (Figure 1). The primary points of the legislation are the following:

• Cosmetics products are defined as “any substance or mixture intended to be placed in contact with the external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance, protecting them, keeping them in good condition or correcting body odours”.
• Manufacturers are required to conduct a safety assessment for each cosmetic product to predict any potential risks to human health arising from its use. It is required that they maintain a Product Information File (PIF) containing the relevant data consistent with the most recent scientific information available, which must be kept for a period of 10 years after the latest batch of the product has been marketed.
• Manufacturers must comply with the Good Manufacturing Practices (GMP) for cosmetics to ensure the quality, safety, and stability of cosmetic products throughout their production, packaging, storage, and distribution. To demonstrate compliance with GMPs, one way is through ISO 22716:2007 certification.
• Before the product is placed on the market, manufacturers are required to notify the responsible authority. The notification is a charge-free procedure and is submitted via the Cosmetic Product Notification Portal (CPNP). It allows relevant product information to be available electronically to CAs for market surveillance, market analysis, review, and consumer information purposes. Once notified on the portal, there is no need for periodic renewals or additional steps at the national level of any of the European countries. There is no specific timetable for it; it is only specified in the CR that it should be prior to placing the product on the market. If it contains nanomaterials, an additional notification of the full product needs to be sent at least 6 months in advance through the CPNP.
• Products must be traceable within the supply chain.
• Manufacturers and distributors have a responsibility to report adverse events caused by their cosmetic products.
• In line with the prohibition of animal testing, the CR proposes alternative testing methods and encourages their implementation.
• The notion of a responsible person (RP) is developed as the person within the EU who is committed to ensuring compliance with all obligations mentioned in the legislation and acts as a point of contact for the authorities for each product placed on the market.
• The competent authorities undertake market surveillance actions to ensure compliance with the mentioned legislation.
• Annexes to the regulation, usually updated once a year, are as follows:

• Minimum information to be mentioned in the Cosmetic Product Safety Report (CPSR). The CPSR is a part of the PIF written by the qualified person designated as a safety assessor, who will ensure the safety of the product under normal and reasonably foreseeable conditions of use. It is divided into two parts: the relevant information about the cosmetic product (part A) and the conclusion of the safety assessor based on part A (part B).
• Substances that have been prohibited for being considered unsafe for use in cosmetics by the Scientific Committee on Consumer Safety (SCCS).
• Restricted substances, in the sense that they can be included only under conditions set regarding concentration and mandatory labeling.
• List of authorized colorants.
• List of authorized preservatives.
• List of authorized UV filters.
• Labeling requirements: cosmetics should be labeled in a designated form, containing the composition in descending order of concentration and in the International Nomenclature of Cosmetic Ingredients (INCI), the presence of nanomaterials, the batch number, the date of minimum durability and RP contact information.
• Mention and description of the validated approaches to replace animal testing in safety assessments.

4. Safety Evaluation of Cosmetic Ingredients

The European regulatory framework for cosmetic products requires a safety evaluation to be performed prior to its placing on the market. Cosmetic product safety is established by assessing the toxicological profile of each of the ingredients in the formulation, both independently and in combination with the others [12]. The cosmetic formulation, in general, is a compilation of chemical compounds in direct contact with the skin and mucous membranes, which can be absorbed to some extent through the dermis [13]. By controlling which substances are used, their chemical structures, toxicological profiles, and exposure patterns, it is possible to manage the overall safety of cosmetic products circulating in Europe. It is particularly important to consider the long-term picture since these are products used extensively throughout an individual’s lifetime, including those with easily sensitized skin [12].

The Scientific Committee on Consumer Safety (SCCS) is the group responsible for advice on the ingredients listed in the annexes of the CR, on which the assessment is based. The main function of the experts on this committee is to provide technical advice on policies and proposals relating to health and chemical, biological, mechanical, or physical hazards associated with non-food consumer goods or services, such as cosmetic and body care products. The SCCS Notes of Guidance (NoG) for the Testing of Cosmetic Ingredients and their safety evaluation is a document that aims to provide practical support for the safety assessment of cosmetic ingredients in line with scientific requirements in accordance with the requirements of the CR, namely the description of the proper methods for assessing the risk of chemicals and the provision of updated scientific information. It is to be noted that this guide may be subject to revision based on scientific advances in toxicology, validated alternative methods, or changes in legislation, though the timing of revisions is based on the occurrence of significant advancements, and, therefore, it is not fixed [12].

Typically, a safety evaluation procedure comprises the following criteria (Figure 2) [14]:

• Hazard identification: is carried out to identify the intrinsic toxicological properties of the substance. It is based on the results of in vivo studies, in vitro and ex vivo tests, in chemical methodology, in silico methods and read-across, clinical studies, case reports, epidemiological studies, and data from Post-Marketing Surveillance. Intrinsic physical and chemical properties of the substance under consideration are also taken into account.
• Exposure assessment: human exposure is calculated based on the declared functions and uses of a substance as a cosmetic ingredient, the amount present in the respective cosmetic product categories, and their frequency of use. The single-product exposure describes the exposure to a cosmetic ingredient in one product category via one route. The aggregate exposure, in the context of the NoG, is the sum of all relevant single-product exposures so that it describes the exposure from all product categories in which the cosmetic ingredient is used and all relevant exposure routes. Where necessary, exposure of vulnerable consumer groups could be assessed separately (e.g., children, pregnant women, etc.).
• Dose-response assessment: for the relationship between the exposure and the toxic response, a Point of Departure (PoD) is determined. The PoD is defined as the dose-response point that marks the beginning of a low-dose extrapolation (for threshold and non-threshold compounds). In most opinions, a No Observed Adverse Effect Level (NOAEL) has been used as PoD. The SCCS considers that, where usable in vivo data are available, the preferred method for both threshold and non-threshold cosmetic ingredients is to express the dose metric as BenchMark Dose (BMD). Both the European Food Safety Authority (EFSA) and the World Health Organization also recommend using the BMD approach for deriving the PoD as a starting point for human health risk assessment.
• Risk characterization: In risk characterization, the focus in the NoG is on systemic effects. In the case of a threshold effect, the margin of safety (MoS) is mostly calculated from oral toxicity studies, unless robust dermal toxicity data are available.

It is essential to recognize that while these steps are part of the CR, broader environmental assessments of chemical ingredients fall under the REACH legislation.

In addition to these foundational steps, both deterministic and probabilistic approaches are employed to quantify and refine the assessment of risk. The deterministic approach estimates the risk by using point estimates of exposure and toxicity. In this approach, a single or “worst-case” scenario is often assumed, giving a more conservative estimate of the potential risk. In contrast, the probabilistic method accounts for variability and uncertainty in the data, producing a range of possible outcomes. This approach allows for a more nuanced understanding of risk by calculating a distribution of potential exposures, which can be used to determine the likelihood of adverse effects at different exposure levels [15].

Traditional toxicological studies have used animal models to investigate the adverse effects of chemicals on living organisms. Instead of following the ongoing ecological trend, the EU Cosmetics Regulation has pioneered the adoption of alternative and innovative in silico or in vitro methods for chemical risk assessment, known as the new approach methodologies (NAMs), in alignment with REACH regulation (EC) No 1907/2006 [14,16,17,18,19,20]. The CR defines as prohibited, since 2013, the marketing of cosmetic products that have been or contain ingredients tested on animals [1], regardless of the availability of satisfactory alternative resources for the toxicological evaluation of these formulations [21]. The technical difficulties relate mainly to repeated-dose toxicity, reproductive toxicity, and toxicokinetics, for which there are no alternatives yet defined [1,14,16,22]. In the current state of the art, it is not possible to demonstrate the profile of a new cosmetic ingredient—or any other that has not yet been extensively tested on animals—on the endpoints referred to with satisfactory regulatory acceptance. Given that this information is necessary for the assessment of cosmetics, it is imperative to develop improved methods based on non-animal models that will ensure equal or better safety [14,22,23]. The in vitro tests currently accepted by regulatory agencies concern skin sensitization, skin irritation and corrosivity, eye damage, and eye irritation [16,17,19] (Figure 3). There is also a lack of alternative means for performing the required studies of acute toxicity, dermal absorption, sub-chronic toxicity (such as 90-day oral toxicity in rats, NOAEL, repeated use toxicity), DNA damage, phototoxicity and photomutagenicity, human data, reproductive toxicity, and carcinogenicity [12] (Figure 3). If repeated use toxicity data are not included in the submission of a new cosmetic ingredient to the SCCS, it is considered that the risk assessment of the compound in question may be insufficient or incomplete for a full evaluation of safety [12].

The toxicological data obtained when identifying the risk is input into the dose-response assessment, in which the NOAEL is established—it, therefore, currently also highly depends on animal data. The testing will ultimately need to demonstrate the severity of the effects, whether they are adverse or adaptive, reversible or not, and whether or not they are precursors to substances that would cause secondary toxicity. Therefore, the aim is to have the highest dose or level of exposure where no adverse effects associated with the product are observed so that this value is divided by the SED—the MoS is then calculated [14].

One in silico tool often used in risk assessment is the Threshold of Toxicological Concern (TTC), which establishes a threshold exposure value below which there is low risk to human health. Furthermore, for chemicals with limited toxicity data, the TTC is particularly useful and has been endorsed by the SCCS as a valid approach for cosmetic safety evaluations, provided it is applied case-by-case and not for all classes of ingredients [24]. The TTC approach is a risk assessment tool that sets a threshold exposure level for chemicals below which there is a low probability of harm, even in the absence of specific toxicity data. This approach uses data from structurally related compounds to derive thresholds for different chemical classes, and it is applied only when robust toxicological data for a substance is unavailable. It is important to note that TTC should not be used as a standalone tool for risk assessment. It is typically applied alongside other methods, and its applicability maybe limited by certain factors such as chemical class and exposure routes. For example, TTC is considered appropriate for non-carcinogenic, non-genotoxic substances. For instance, the SCCS advises that the TTC should not be applied to substances that are classified as CMR, which require full toxicological assessments [14].

Therefore, this approach was considered scientifically acceptable by the SCCS for cosmetics, but it should not be universally applied to all ingredients, as these should be evaluated on a case-by-case basis [23]. When the TTC approach is not feasible, studies suggest the application of a 10-step read-across (RAX), which consists of using relevant information from analogous substances to predict the properties of a test substance. In other words, a health reference value would be calculated for that substance by adjusting the toxicokinetics of another substance that has animal toxicity data and is similar in chemical structure, physicochemical properties, or biological activity [25]. Both in silico NAMs mentioned remain dependent on animal research data, which represents a barrier to the safety assessment of novel ingredients. Extrapolation of in vitro data to in vivo and variability between species may be at the root of potential mistakes that could escalate to human health impacts [23,25].

Other relevant in silico methods that mathematically relate the similarity between chemical structures and help to predict their toxicity by generating models are quantitative structure–activity relationship (QSAR), structural alerts, pharmacokinetic (PK) and pharmacodynamic (PD) models, and dose- and time-response and uncertainty factors in the predicted toxicity. These models rely on computational tools such as chemical databases containing the existing toxicological information prior to the ban on animal testing, specialized software for generating prediction models, statistical modeling packages, toxicology simulation tools, and visualization tools. Such tools are employed in, generally, five main steps during the models’ development: collection of biological data containing associations between chemical substances and toxicity endpoints, calculation of molecular descriptors of the chemical substances, creation of a predictive model, evaluation of the model’s accuracy, and interpretation of the model (Figure 4) [21].

In this way, it is possible to predict the toxicity and biological effects of a given chemical under study by comparing it with another that is already known, supposing they may exhibit similar biological activity in vivo. These tools, however, do not have standalone regulatory acceptance by the SCCS, although considered to provide a high degree of reliability for some endpoints (i.e., the genotoxic potential for chemicals) [14]. The drawback of this method is that the lack of a structural alert does not mean that the molecule is guaranteed to be non-toxic; it could simply indicate a knowledge discrepancy [22]. In silico methods are only ultimately accepted in conjunction with additional supporting documentation in a case-by-case assessment that requires a weight-of-evidence approach for safety [14].

The cosmetics industry perceives as a marketing opportunity the use of ingredients not mentioned in the annexes, as there is no evidence that they will be unsafe, as opposed to others that have a well-established toxicological profile. If there is any endpoint that cannot be tested, it will be at fault, which does not prevent the safety assessment of the ingredient [22,26]. These ingredients may, however, be unknown allergens and pose a risk [22]. Some ingredients are controversial such as parabens—extensively used and known preservatives—which tend to be replaced by less controversial yet less tested and possibly unknowingly unsafe alternatives [27].

Although animal testing has been banned in the EU since 2013, the development of validated alternative testing methods presents several challenges. For instance, while in vitro assays and in silico models are promising, they often lack the ability to fully replicate complex biological systems and may not account for interactions between multiple ingredients. A significant limitation is the inability to assess chronic exposure effects and long-term toxicity accurately [28]. Moreover, the absence of regulatory acceptance for many alternative methods hinders their widespread implementation in safety evaluations [29]. Examples of methods under consideration include organ-on-a-chip technologies, which mimic human physiology but are still in the early stages of validation [30].

4.1. Carcinogenic, Mutagenic, or Reprotoxic Ingredients and Other Special Concerns

There are ingredients that raise a special concern for human health (notably fragrances, colorants, preservatives, and UV filters) [31], mainly in relation to the potential endocrine disrupting or carcinogenic, mutagenic, and/or reprotoxic (CMR) effect they may have. Article 15 of Regulation (EC) No 1223/2009 establishes that the use in cosmetic products of substances that have been classified as CMR substances of category 1A (confirmed effects), category 1B (claimed effects) or category 2 (suspected effects) in Part 3 of Annex VI to Regulation (EC) No 1272/2008 on the Classification, Labelling and Packaging of substances and mixtures under the CLP regulation is prohibited unless evaluated and found safe by the SCCS [1,32]. This classification is based on the overall exposure an individual will have to the substance—including in cosmetics, chemicals, food, and medicines—and may change over time as new data becomes available [32].

The human exposure to the chemicals in the formulation is calculated by taking into consideration the stated function of the cosmetic product according to the location and extent of application, the standard and reasonably foreseeable route of exposure, and the target population, along with the estimated daily applied amount, considering the quantity applied, frequency of use, and retention factor. Skin corrosion, for example, is a non-expectable property for a cosmetic product, unless it is due to production error or misuse by the consumer. In contrast, an ingredient that has the intrinsic quality of corrosion is not necessarily excluded from being formulated in cosmetics; it will all depend on its final concentration and overall context [1,12].

Except for CMR ingredients, the evaluation of the concern only considers the use in the respective cosmetic product, although the exposure may be increased when considering chemicals present in non-cosmetic products, such as the ones used for cleaning purposes [12]. Another concern to be taken into consideration is the cocktail effect, the synergistic potential between substances that interact when applied simultaneously, and the additive effect, which refers to increased exposure to a particular ingredient because it is present in multiple products, leading to a higher probability of unexpected toxicity [33].

In addition to being classified as potential CMRs, cosmetic ingredients can also be classified as sensitizers or non-sensitizers. The subcategory, which would classify them according to sensitizing potency, is only possible if there is sufficient data for it, which is determined by animal testing—usually by murine local lymph node assay. Currently, there is no single NAM that can provide this information. Multiple methods need to be integrated to assess the mechanisms of toxicity and reflect the ability of the substance to induce allergic contact dermatitis and inflammatory responses [34].

4.2. The Need for a Case-by-Case Study

In recent years, much progress has been made in the development and validation of alternative methods for the testing of chemicals in the context of cosmetic products. Despite these efforts, these tests are currently best defined for risk identification in the context of local toxicity and short-term testing. This means that to obtain quantitative information regarding systemic toxicity, risk potency, or long-term effects, the methodology is still highly dependent on the results of animal testing. Without such data, the systemic NOAEL information is lacking and, consequently, it will be impossible to calculate the MoS, resulting in incomplete safety information [22]. It is to be noted that, in the context of cosmetics, the use of safety data obtained in territories outside the European Union is prohibited, according to the REACH regulation [18].

Therefore, it is not clear from the legislation exactly how to proceed in these cases, which causes severe problems for the safety assessment of new cosmetic products or new cosmetic ingredients. The practical interpretation of the regulation by the SCCS allows for certain exemptions, meaning that cosmetics are not required to have complete information unless there is a need to verify the risks of occupational exposure—in these cases, there is increased potential hazard, as in the example of nail and hair salon workers [35]. The approach suggested by the SCCS is phased but still emphasizes that a thorough, case-by-case assessment of all available data is necessary to have a critical view of the applicability of the alternative methods. This approach involves the integration of different strategies, which implies the need to, besides the individual validation, establish the relationship between them and comprehensively validate the overall study model in order to be accepted by the regulatory organizations and considered effective [19,36].

Although there is no formal data requirement for absorption, distribution, metabolization, and excretion of cosmetic ingredients in most cases, these are relevant for the extrapolation of in vivo and in vitro findings to humans. In the case of systemic exposure via sprays, aerosols, and products that contact the oral mucosa, there are some suggested approaches from the SCCS, but there are currently no formally validated methods available. Currently, a default dermal absorption of 50% is considered for all substances included in the annexes of the CR in the scope of the calculation of the margin of safety [14].

4.3. Environmental Concern

The chemical safety assessment also includes the environmental hazard assessment and the assessment of persistent, bioaccumulative, and toxic (PBT) and very persistent and very bioaccumulative (vPvB) risks [18]. This assessment is not required for cosmetic ingredients in the European Union [12], although some could have an important environmental impact, such as some UV filters [37]. It is important to note that environmental assessments for cosmetic ingredients are not mandated under the CR; instead, they fall under the jurisdiction of REACH legislation.

An important example is benzophenone-3 (also known as oxybenzone), a widely used UV filter in sunscreens and personal care products, which raises significant safety concerns. Compounds of the benzophenone group have bioaccumulation properties and thus can be detectable in aquatic environments and in the organisms of animals higher up the food chain. One possibility that might be overlooked, but should not be dismissed, is human exposure to the substance through ingestion of water or contaminated fish. In addition to the increased exposure to humans, the aquatic ecosystem might also be harmed by inducing adverse effects on animal and vegetal species, and therefore threatening ecological safety. Studies show that oxybenzone concentrations in some popular tourist destinations, such as Hawaii and the Caribbean, have reached levels of up to 4000 times higher than what is considered safe for marine life [38,39,40].

The link between UV filters and coral bleaching and damage to marine life has been increasingly studied and documented. The loss of color in corals is a result of the loss of zooxanthellae (Symbiodinium species.), which are algae that are resident within coral polyps and support marine life—thus, coral bleaching has detrimental impacts throughout the ecosystem [39]. Studies have detected these chemicals in marine environments, particularly near popular tourist destinations, where they contribute to the degradation of coral reefs and marine ecosystems [37]. It is estimated that between 6000 and 14,000 tons of sunscreen are released into coral reef areas each year. A comprehensive review highlighted that these chemicals disrupt the reproductive systems of marine organisms, raising concerns about their long-term ecological impacts [41]. Regulatory actions, such as the impending ban on certain UV filters in several jurisdictions, reflect a growing awareness of their environmental risks and the need for safer alternatives. In 2018, Hawaii became the first U.S. state to ban the sale of sunscreens containing oxybenzone and octinoxate due to their harmful effects on coral reefs. Similar bans were implemented in Palau (2020), Key West, Florida (2021), and Thailand (2021) in a bid to protect vulnerable marine ecosystems [40]. Beyond marine ecosystems, human exposure to these chemicals through ingestion of contaminated water or fish should not be overlooked. The bioaccumulation of benzophenone-3 has been detected in fish and other wildlife, raising concerns about the potential for long-term health effects on both human populations and the broader ecological system [42]. The widespread use of sunscreens, combined with inadequate water treatment to remove these contaminants, poses a significant challenge to ecological safety.

Despite the issue of environmental concerns not being part of the safety assessment of cosmetic products, some initiatives have been conducted by the authorities in favor of sustainability. The Commission Regulation (EU) 2023/2055 of 25 September 2023 was introduced to ban microplastic, non-biodegradable, and insoluble glitter, which pollute the oceans and can be easily ingested by living organisms [43]. This restriction applies to toys, textiles, arts and crafts, cosmetics, and detergents, except the glitter affixed to or trapped in an article. The cosmetic products within this scope that are already placed on the market do not need to be recalled or withdrawn from the market; they can continue to be sold for a longer transitional period—until October 2027 for rinse-off products, October 2029 for leave-on cosmetics and October 2035 for makeup, as long as the latter contains a label indicating they contain microplastics [14].

With regard to environmental concerns, it is also important to note that while the CR addresses the safety of cosmetic products, the environmental impact of cosmetic ingredients is primarily governed by REACH legislation. Reach ensures that all chemical substances, including those used in cosmetics, undergo rigorous assessment for environmental hazards before being marketed in the EU. This distinction is critical, as it highlights the regulatory framework that specifically addresses the ecological implications of chemical substances. The SCCS focuses on evaluating the safety of cosmetic ingredients concerning human health but does not cover the environmental assessments required under REACH [44].

4.4. Nanomaterials

Nanomaterials (NM) are slowly being introduced to the cosmetic market, being internationally defined by the CR as “an insoluble or biopersistent and intentionally manufactured material with one or more external dimensions, or an internal structure, on the scale from 1 to 100 nm” [1,20]. In 2022, the European Commission recommended broadening this definition to include a minimum of 50% of total particles at the nanoscale in the material for it to be classified as a nanomaterial; however, it has not been implemented in the regulation yet [20].

Advances in technology have led various NMs to find applications in cosmetic formulations, including nanoparticules, nanocapsules, and nanoemulsions. Some examples are the encapsulation of fragrances, enabling sustained and controlled release of the aroma [45], and UV filters, due to enhancement of the protective effects of natural sunscreen agents from plant extracts [46] or optical properties of the mineral ones [47,48]. The integration of NMs in cosmetic products represents a significant stride in product innovation due to their interesting characteristics [20,49]:

• Increased surface area: the high surface area to volume ratio allows for better interaction with the skin, leading to better performance of cosmetic active ingredients.
• Optimized penetration/permeation: smaller particles are more likely to reach deeper layers of the skin than larger particles, which is particularly beneficial for delivering cosmetic active ingredients.
• Improved stability, contributing to a longer shelf life.
• Enhanced sensoriality (smoother textures, better spreadability, and overall comfort in the cosmetic application experience).
• Other physical-chemical properties influence skin penetration, such as size, surface charge, hydrophobicity, shape, and chemical structure.

Although appealing from the innovation standpoint, the improved penetration of NM raises questions about their potential toxicity. Some levels of systemic absorption and translocation to the lymphatic and circulatory systems need to be taken into consideration as those factors could result in potential health hazards through mechanisms that are not fully understood. The latter becomes more prevalent when other exposure routes are considered, such as inhalation and ingestion [20,47,48,49,50].

Nevertheless, it ought to be emphasized that nanotechnology advances have outpaced progress in safety assessment methodologies, resulting in the absence of crucial information for testing NMs. These gaps have raised safety concerns, particularly in products like sunscreens and hair care formulations, where nanomaterials such as titanium dioxide (TiO₂) and zinc oxide (ZnO) are commonly used. While these nanomaterials are employed for their superior UV protection properties, studies have shown that they can penetrate the skin under certain conditions, potentially causing oxidative stress and cellular damage [51]. A case study involving TiO₂ nanoparticles in sunscreen revealed that under conditions of repeated UV exposure, these nanoparticles could induce DNA damage and inflammatory responses in human keratinocytes [52]. Another study on ZnO nanoparticles in hair care products raised concerns about their potential to cause lung inflammation when aerosolized, leading to respiratory issues upon inhalation [53]. These examples illustrate how the lack of validated safety assessment methodologies for nanomaterials in cosmetic products poses a significant risk to both consumer health and long-term safety. The difficulties in establishing the toxicological profile of nanoscaled ingredients justify having specific guidance for its safety assessment, to be interpreted alongside the NoG: Guidance on the Safety Assessment of Nanomaterials in cosmetics, second revision [20]. Although this guidance is a step in the right direction, it still reveals some regulatory issues: out of 220 NAMs identified for safety assessment, 68 were nano-specific and, out of those, only 8 had regulatory acceptance—most of the remainder are still under development. A primary issue is that in vitro testing methods, while widely used, often fall short when applied to nanomaterials. These methods are typically designed to assess chemical toxicity in bulk form, and they may not account for the unique properties of nanomaterials, such as size, shape, surface, charge, and agglomeration. Nanoparticles can interact differently with biological systems compared to their bulk counterparts, leading to uncertainties in predicting their behavior in vivo. For example, current in vitro assays may struggle to simulate how nanoparticles penetrate cells, cross biological barriers or induce long-term chronic toxicity [54]. Another significant gap is the difficulty in assessing biodistribution and biopersistence—where and how long nanomaterials accumulate in different tissues. Standard toxicology tests often fail to account for the ability of nanomaterials to cross the blood-brain barrier or accumulate in the liver, spleen, and kidneys, potentially causing organ damage over time. Moreover, the reactivity of nanoparticles in biological environments can vary, leading to unexpected toxicological responses such as oxidative stress, inflammation, or genotoxicity, which are not easily predicted by traditional in vitro methods [52]. Many toxicological endpoints will thus remain unknown, including, amongst others, repeated-dose toxicity, toxicokinetics, acute toxicity, phototoxicity, and skin corrosion [20,55].

In addition, most commercially available NMs are developed and synthesized without prioritizing safety and ecology. Attention should be paid to their production, processing, conservation, and discharge to reduce the unpredictability of human and environmental toxicity, which is the promise of green methods for the synthesis of NMs [50].

5. Market Surveillance and Cosmetovigilance

Member States (MS) should not deny, prohibit, or restrict the availability of cosmetic products on the market if they are compliant with the requirements of the CR, as mentioned in article 9. The exception to this rule is determined in article 27: the MS may temporarily and immediately withdraw from the market a product believed to be responsible for serious risks to human health, informing the other MS and the European Commission of the reasons thereof [1].

Cosmetics, being classified as consumer-packaged goods (CPGs), deal with a very competitive market and limited shelf space. Moreover, factors such as territorial supply constraints and regulatory barriers play an important role in the fragmentation of the European single market concept, hindering the economic prosperity of stakeholders [56]. Intending to attenuate this impact, the CPGs are regulated by an in-market control system, rather than by pre-market approval procedures. Cosmetic products, therefore, do not undergo a prior rigorous analysis by the authorities to confirm that the minimum quality parameters have been fulfilled [1,22], like those performed for the administrative authorizations issued for medicines [57]. Even in the case of nanomaterials, which require a six-month prenotification, the European Commission’s intent is to assess whether there are specific concerns with that individual ingredient that would discourage the product from being placed on the market, not an in-depth assessment as such.

The current regulatory framework only requires that the RP guarantees compliance with the legislation and that the respective product is notified on the CPNP platform, which raises an issue: there is a margin for potentially health-damaging products to be sold indiscriminately without consumers or the authorities being aware of the threat. Penalties may be issued to the RP if the requirements are not properly met, but there is no guarantee that those are being identified. There is no filter external to the manufacturers that will eliminate non-compliant products; all products will be regularized independently [1,22].

Although the structuring of the standards for the cosmetic regulation has been carried out at a centralized level by the European Medicines Agency (EMA), they are not responsible for their execution and supervision. The checking task is delegated to the MS in which the product is registered. As stated in article 22, the authorities of each European Member State carry out the market surveillance actions they deem appropriate to supervise the finished products already placed on the market, attempting to find possible quality defects [1]. They typically do so through suspicions triggered by consumer complaints, inspection activities to ensure the principles of good manufacturing practices, and laboratory control actions based on adequate samples, but these operations are not harmonized.

The CR states that cosmetic products must not cause harm to human health when used under normal or reasonably foreseeable conditions [1]. As with any pharmaceutical product, however, in spite of their safety and tolerability, they can lead to unexpected, undesirable effects in the short or long term, even if they comply with all the requirements set by the authorities [58,59,60,61]. Regulation (EC) No 765/2008 of the European Parliament and of the Council of 9 July 2008 foresees the need for collaboration between MS, as well as the possibility of enforcement actions in case of non-compliance verified in-market surveillance activities. Serious safety issues regarding the use or misuse of a product require rapid intervention, which may involve withdrawing the product, recalling it, or prohibiting it from being made available on the market. In those situations, it is necessary to have access to a system of rapid exchange of information between Member States and the Commission [62,63].

For medicinal products, a pharmacovigilance system is implemented, backed by three pillars: a national system for reporting suspected adverse reactions and providing information on medicinal products; a system for detecting and analyzing signals; a system for communicating safety information to the public that is considered relevant for risk minimization [58]. Similarly, but far less developed, a cosmetovigilance system for monitoring cosmetic products is available in Europe to ensure public health [59].

RAPEX Platform

Under article 12 of the Directive 2001/95/EC of the European Parliament and of the Council of 3 December 2001—also known as the General Product Safety Directive—there is mention of the Rapid Alert System for dangerous non-food products (RAPEX) for the improvement of market surveillance activities, including the risk assessment, testing of products, exchange of expertise and scientific knowledge, execution of joint surveillance projects and interventions [63], which has proved its effectiveness and efficiency [62]. Essentially, this platform is a tool for rapid communication between member states via a point of contact: in Portugal’s case, it is the General Consumer Directorate rather than INFARMED, I.P., the CA. It thus enables the prompt exchange of information on any measures taken or restrictions on the marketing of products that endanger human health and consumer safety. The main objective of RAPEX is to involve Member States and the European Union actively in the reporting of products posing a serious risk for the consumer and sending additional notifications about the outcome in response to the initial notifications [64]. The platform features notifications for a broad range of products, including, but not limited to, toys, vehicles, batteries, and cosmetics. Accordingly, RAPEX plays a fundamental role in the post-marketing surveillance of cosmetic products: the Cosmetovigilance system.

This cosmetovigilance system, however, has some limitations to overcome. The number of notifications submitted is highly variable depending on the reporting country and is influenced by several factors: in addition to market size and import volumes, historical differences in risk assessment perception and population awareness play an important role [64]. The notifications of adverse events, when carried out by users on their own initiative, are proportional to the degree of knowledge of the population about the detection of the signs of adverse events and awareness of the reporting platforms, which might not be intuitive [65]. Undesirable effects attributable to cosmetics are generally under-reported [59,60] and can include distressing symptoms (Figure 5) [61,66,67,68].

The issue of under-reporting in cosmetovigilance poses significant challenges in ensuring consumer safety. Studies indicate that less than 10% of adverse events related to cosmetic products are reported to regulatory authorities, primarily due to consumer unfamiliarity with reporting systems and a lack of awareness about the potential risks associated with cosmetic use [69]. For example, a survey conducted among consumers showed that 75% of respondents were unaware of the existence of reporting platforms for adverse cosmetic reactions, suggesting a critical gap in public education [59]. Addressing these challenges through targeted public awareness campaigns and improving the accessibility of reporting systems will be essential in enhancing the effectiveness of cosmetovigilance efforts.

Moreover, even when users identify an adverse reaction, they often intuitively discontinue the use of the product without going through any adverse effect reporting procedure. Several factors contribute to this under-reporting. One key issue is the lack of awareness among consumers about the existence of formal reporting systems such as RAPEX. Many consumers are unaware that they can or should report adverse reactions from cosmetic products to regulatory authorities [59]. Additionally, the complexity of the reporting process can discourage users from filing reports. Procedures often require detailed information, such as batch numbers, ingredient lists, or medical information, which consumers may find overwhelming or difficult to obtain [60]. This gap in reporting means that RAPEX is unable to operate at its full potential, as its core function is to bring unexpected negative outcomes of cosmetic products to light and facilitate appropriate actions, such as analyzing the cause or restricting the marketing of the product. Without sufficient consumer reports, adverse effects may go unnoticed, delaying corrective actions. To address this issue, simplifying the reporting process could improve consumer participation. A more intuitive and mobile-friendly platform that integrates features such as automatic product scanning via barcodes, simplified symptom descriptions, and the ability to upload images could make reporting easier and more accessible. Additionally, raising public awareness through targeted campaigns, particularly on social media, would help educate consumers about the importance of reporting adverse effects. By increasing both the ease of reporting and consumer awareness, RAPEX could more effectively fulfill its role in ensuring the safety of cosmetic products. When appropriate, corrective measures and the dissemination of information should be undertaken to reduce the likelihood of the recurrence of a serious undesirable effect, aiming at the protection of the health and safety of cosmetics users [1].

6. Revision of the Safety Information for Cosmetic Ingredients

For a substance characterized as CMR in category 1A or 1B to be formulated as a cosmetic ingredient, it must be considered safe following a safety assessment performed by the SCCS [32]. This safety opinion is not permanent and may be subject to modification as new scientific evidence is made available to the public, while the market will need to adapt to the new guidelines.

6.1. From Widely Available to Prohibited

Butylphenyl methylpropional, also known as Lilial, is a substance that was very commonly used as an intense floral fragrance in cosmetics, regulated by Annex III of the CR, i.e., it was part of the list of ingredients that could be incorporated if it complied with the concentration limits and labeling requirements [1]. Although it was one of the most frequently found fragrances in cosmetic products, this ingredient already had a well-known sensitizing potential and was listed as a contact allergen by the SCCS [70,71]. New studies showed, however, signs of possible reproductive toxicity and endocrine disruptive effects [71]. Acute toxicity studies via various routes of administration (oral, dermal, intraperitoneal, and inhalation), have shown signs of systemic toxicity in rats, mice, and rabbits, including by inhalation exposure. Irritation of the skin, eyes, and respiratory mucosa of the animals studied was also reported as a consequence of exposure to Lilial. Aspects such as mutagenicity and carcinogenicity could not be conclusively assessed; however, adverse effects on the reproductive system of rats were consistently reported in repeated-dose toxicity studies and in reproductive toxicity studies. These studies were submitted to the SCCS, which gave an unfavorable opinion on the ingredient [6]. Moreover, this ingredient was not only used in cosmetic products: it was also occurring in household cleaning products, which may result in a higher aggregate exposure than initially anticipated, resulting in a higher likelihood of toxicity reactions [33,72]. While Lilial was once considered safe in individual products, it is now banned, as it is prevalent for the same consumer to use several formulations containing it simultaneously [72]. Its prohibition due to being classified as toxic to reproduction (CMR 1B) therefore means its deletion from Annex III of the CR and inclusion in Annex II, relating to prohibited substances [1,73]. The outcome, on a practical note, was the immediate suspension of the marketing of these cosmetics. Any entities that still provide them should not market them, and any consumers who still own these products should not use them [6,73]. The ban on such substances has had a significant impact on the cosmetics industry, particularly in terms of reformulation and innovation. Companies are required to reformulate products to exclude the banned ingredients while maintaining the efficacy and safety of the product. This often necessitates the search for alternative ingredients that can perform similar functions without posing risks to human health. This new scientific information was based on numerous animal tests [6], which are now banned for cosmetic purposes [1]. Data on acute toxicity, referring to the side effects observed after dermal, oral, or inhalation exposure to one or multiple doses of the substance [32], are not mandatory for the safety assessment, as there are no NAMs for such an evaluation [12]. The need for a reconsideration of the hazard of Lilial could be a consequence of the lack of prior studies being performed. For instance, in the case of ingredients like Lilial, which was widely used as a fragrance component but was later banned due to its reprotoxic properties, the industry quickly shifted toward using safer, nature-identical fragrances or synthetic alternatives with fewer safety concerns [6]. The ban on Lilial and similar compounds has also spurred innovation, particularly in the development of green chemistry solutions and the use of more biodegradable ingredients. In some cases, the move toward plant-based and bioengineered ingredients has become a trend, aligning with consumer demand for safer and more sustainable products. These regulatory changes have not only encouraged safer formulations but have also driven the industry to adopt more transparent labeling and sustainability practices, thereby strengthening consumer trust in cosmetic products.

As with Lilial, products containing zinc pyrithione were banned from being marketed after the ingredient was classified as CMR 1B by the SCCS. Previously, zinc pyrithione was often formulated as a preservative in rinse-off products, being regulated by Annex V of the CR, and as an anti-dandruff active ingredient in rinse-off hair products, being regulated by Annex III. The SCCS opinion for this ingredient resulted in the same outcome, but for a different reason: it was not demonstrated that safer alternatives did not exist, and therefore, the alternatives should be prioritized [73]. It is, however, relevant to critically consider the safety of these substitutes, as there are few advantages to public health if they are considered safer solely because they are less extensively tested. Zinc Pyrithione is well studied, being discovered in the late 1950s as an effective antifungal agent for the relief of the discomfort caused by the overgrowth of the scalp fungus in the context of dandruff and seborrheic dermatitis [74].

Regulation (EC) No. 1223/2009 continues to evolve, with regular amendments ensuring that new safety data is incorporated. While instances of non-compliance are still observed, ongoing market surveillance and enforcement actions by regulatory authorities like the Portuguese Government agency, INFARMED, I.P., are actively addressing these issues and removing unsafe products from the market. As an example, the Portuguese Government agency, INFARMED, I. P., carried out market surveillance actions in the year following the ban on the use of buthylphenyl methylpropional and zinc pyrithione (2022), which detected many irregularities. Attempting to alert the population and reduce potential harm, the authority issued circulars to bring this situation to light, stating that these were products considered unsafe by the SCCS. Similarly, other examples of products identified as non-compliant following market surveillance actions are listed in

Table 1. Examples of INFARMED, I. P. alerts regarding cosmetic products following market surveillance actions in the last 5 years (2018–2023).

Informative Circular N.º	Date (DD/MM/YYYY)	Title	Alert	Reference
091/CD/100.20.200	08/09/2023	Suspension of marketing and withdrawal from the national market of all batches of cosmetic product.	Unexpected adverse reaction (temporary axillary inflammation)	[75]
083/CD/100.20.200	17/08/2023	Immediate suspension of marketing and withdrawal from the national market of all batches of cosmetic products.	Contains prohibited ingredient (cannabidiol)	[76]
035/CD/100.20.200	27/04/2023	Immediate suspension of marketing and withdrawal from the market of all batches of cosmetic product.	Misclassification as a cosmetic product and ingredient concentration above the threshold (methyl salicylate)	[77]
008/CD/100.20.200	19/01/2023	Immediate suspension of the commercialization and withdrawal from the national market of cosmetic products that have in their composition the ingredient butylphenyl methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[78]
131/CD/100.20.200	11/11/2022	Immediate suspension of marketing and withdrawal from the national market of all batches of all cosmetic products.	Non-compliance with the Regulation	[79]
108/CD/100.20.200	15/09/2022	Immediate suspension of the commercialization and withdrawal from the national market of lots of cosmetic products that have in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[80]
096/CD/100.20.200	16/08/2022	Immediate suspension of marketing and withdrawal from the national market of cosmetic products that have in the list of ingredients and/or in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[81]
088/CD/100.20.200	01/08/2022	Immediate suspension of the commercialization and withdrawal from the national market of cosmetic products that have in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[82]
082/CD/100.20.200	15/07/2022	Immediate suspension of the commercialization and withdrawal from the national market of cosmetic products that have in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[83]
084/CD/100.20.200	15/07/2022	Immediate suspension of marketing and withdrawal from the national market of cosmetic that have in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[84]
081/CD/100.20.200	15/07/2022	Immediate suspension of marketing and withdrawal from the national market of cosmetic products which have in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[85]
074/CD/100.20.200	01/07/2022	Immediate suspension of the commercialization and withdrawal from the national market of cosmetic products that have in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[86]
066/CD/100.20.200	22/06/2022	Immediate suspension of the commercialization and withdrawal from the national market of cosmetic products that have in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[87]
050/CD/100.20.200	17/05/2022	Immediate suspension of marketing and withdrawal from the national market of cosmetic products that have in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[88]
049/CD/100.20.200	17/05/2022	Immediate suspension of marketing and withdrawal from the national market of cosmetic products which contain in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[89]
048/CD/100.20.200	17/05/2022	Immediate suspension of marketing and withdrawal from the national market of cosmetic products which contain in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[90]
044/CD/100.20.200	11/05/2022	Immediate suspension of marketing and withdrawal from the national market of cosmetic products that contain in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[91]
042/CD/100.20.200	04/05/2022	Immediate suspension of marketing and withdrawal from the national market of cosmetic products that contain in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[92]
041/CD/100.20.200	04/05/2022	Immediate suspension of the marketing and withdrawal from the national market of cosmetic products that contain in their composition the ingredient Butylphenyl Methylpropional.	Contains prohibited ingredient (butylphenyl methylpropional)	[93]
025/CD/550.20.001	23/02/2021	RAPEX Alert *.	Need for corrective measures aimed at reducing the risk of ingestion	[94]
177/CD/550.20.001	19/11/2020	Voluntary withdrawal of cosmetic product.	Misclassification as a cosmetic product	[95]
035/CD/550.20.001	31/01/2020	Withdrawal from the market of the cosmetic product.	Contains prohibited ingredient (mercury)	[96]
034/CD/550.20.001	31/01/2020	Withdrawal from the market of the cosmetic product.	Contains prohibited ingrediente (mercury)	[97]
033/CD/550.20.001	31/01/2020	Withdrawal from the market of the cosmetic product.	Contains prohibited ingredient (mercury)	[98]
160/CD/550.20.001	23/10/2019	Voluntary recall of sunscreen.	Inconsistencies in SPF analysis	[99]
146/CD/550.20.001	03/10/2019	Voluntary recall of cosmetic products.	Microbial contamination leading to risk of infection	[100]
141/CD/550.20.001	12/09/2019	Immediate suspension of marketing and withdrawal from the market of cosmetic product.	Contains prohibited ingredient (triclosan)	[101]
068/CD/550.20.001	01/04/2019	Withdrawal from the market.	Contains prohibited ingredients (butylparaben, Solvent Yellow 172, CI 45161, CI 45174, CI 74260)	[102]
063/CD/550.20.001	15/03/2019	Withdrawal from the market.	Contains undeclared allergen ingredients (fragrances)	[103]
032/CD/100.20.200	08/02/2019	Herbal medicines wrongly classified as cosmetics.	Misclassification as a cosmetic product	[104]
163/CD/550.20.001	23/11/2018	Withdrawal from the market of batches of cosmetic product.	Contains prohibited ingredients (methylchloroisothiazolinone, methylisothiazolinone)	[105]
160/CD/550.20.001	14/11/2018	Withdrawal of cosmetic product.	Misclassification as a cosmetic product	[106]
152/CD/550.20.001	19/10/2018	Withdrawal of the cosmetic products.	Contains prohibited ingredient (methylisothiazolinone)	[107]
151/CD/550.20.001	19/10/2018	Withdrawal of cosmetic product.	Contains undeclared allergen ingredients (phenoxyethanol, benzoic acid) and false claim	[108]
140/CD/550.20.001	26/09/2018	Withdrawal of cosmetic product.	Contains undeclared allergen ingredients (phenoxyethanol, preservatives)	[109]
139/CD/550.20.001	26/09/2018	Withdrawal of brand cosmetics.	Contains prohibited ingredients (methylchloroisothiazolinone, methylisothiazolinone)	[110]
132/CD/550.20.001	14/09/2018	Withdrawal of brand cosmetics.	Contains prohibited ingredients (colorants)	[111]
130/CD/550.20.001	14/09/2018	Withdrawal of brand cosmetics.	Contains prohibited ingredients (colorants)	[112]
094/CD/550.20.001	26/06/2018	Withdrawal of the cosmetic product.	Non-compliance with the Regulation (labeling)	[113]
057/CD/550.20.001	05/04/2018	Withdrawal of cosmetic product.	Contains prohibited ingredient (methylisothiazolinone)	[114]
030/CD/550.20.001	15/02/2018	Voluntary recall of cosmetic products.	Non-compliance with the Regulation (good manufacturing practices, safety evaluation, CPNP notification)	[115]
029/CD/550.20.001	15/02/2018	Withdrawal of cosmetic product.	Contains prohibited ingredients (sodium borate, boric acid)	[116]

* No withdrawal from the market required.

, comprising cases reported by INFARMED, I.P. between January 2018 and September 2023. These products have fortunately been identified and have been recalled to meet the requirements of the authorities; however, it is unclear whether all irregularities have been spotted. The majority of those that were recalled featured formulations containing banned or undeclared allergen ingredients and misclassification as a cosmetic product.

Based on the data provided in Table 1, a clear trend emerges regarding the types of cosmetics products most frequently withdrawn from the market. Products containing banned substances such as Lilial and CMR-classified ingredients are the most commonly flagged, highlighting ongoing challenges in product compliance with EU safety regulations. In addition, issues related to improper labeling and undisclosed allergens continue to pose risks to consumer safety. To address these challenges, stricter market surveillance, improved ingredient transparency, and enhanced cosmetovigilance practices should be adopted across all Member States. These measures could significantly reduce the prevalence of non-compliant products and improve consumer protection.

6.2. Specific Cases of Permitted Although Restricted Substances

Annex III of the CR specifies substances that are permitted in cosmetic formulations under strict conditions [1]. These requirements, updated regularly, reflect ongoing efforts to minimize risks while maintaining product efficacy. Regulatory authorities continue to review these substances in light of new scientific evidence, ensuring that adverse events are minimized through improved monitoring and enforcement mechanisms [33].

Methyl salicylate (methyl 2-hydroxybenzoate) is a fragrance that, since it is found in multiple cosmetic and cleaning products, can lead to toxicity reactions from aggregate exposure. This ingredient, which was already known to be a skin sensitizer and eye irritant [117] but not previously mentioned in the regulation, was considered CMR 2 by the SCCS in 2021 [73,118,119]. This considers the information available on salicylic acid, since methyl salicylate is its metabolite and is significantly absorbed through dermal application, to an extent dependent on the carrier of the product. Such exposure could cause harm to human health through the endocrine disruption and reproductive toxicity potential of salicylic acid [118]. It was then established by the SCCS that the chemical would be safe for use in cosmetic formulations as a preservative at a maximum concentration of 0.5%. For non-preservative uses, the maximum concentrations are 3.0% for cosmetic rinse-off hair products and 2.0% for other product types except for body lotion, eye shadow, mascara, eyeliner, lipstick, and roll-on deodorant applications limited to salicylic concentrations of up to 0.5%. Therefore, exposure to salicylic acid remains low, and it is generally believed that there would be no important risks [118,119].

Another example of safe substances with restrictions is UV filters; however, these are not regulated by Annex III. The allowed UV filters are described in Annex VI of the CR [1]. Benzophenone-3 is a UV-absorbing chemical widely present in non-mineral sunscreens and is generally accepted by the public. Exposure to this compound, however, raises concerns over its endocrine disruptive potential and CMR, particularly due to evidence of high systemic absorption [39,40,120]. These concerns, as well as dose-dependent neurotoxicity, have been demonstrated through several studies, with the toxic impact varying depending on the substituents of the benzophenone chemical structure [39]. A systematic review involving older studies had, however, shown that current evidence does not strongly support a causal relationship between systemic Benzophenone-3 level and adverse health outcomes in humans [40], not to exclude the environmental harm [38,39,40]. The SCCS reassessment of the safety of Benzophenone-3 has determined in 2021 that its formulation in cosmetic products is safe, but only at a lower concentration than previously approved. This restriction was established after concluding that there was a potential risk to human health from the use of this substance at the previously approved concentrations [120,121]. The SCCS, in its assessment, does not address environmental aspects [121], which could possibly change the perspective on the safety and restrictions to be imposed on this ingredient. Given the frequency of application required for the prevention of skin cancer [122,123,124], it is assumed that exposure to the ingredients of sunscreens will be substantial, so it is appropriate that an extensive analysis of their safety is conducted, preferably with caution.

7. Final Remarks

The regulatory framework for cosmetic products, while not as stringent as pharmaceutical regulations, has undergone significant improvements through initiatives such as the CR and the CLP regulations. The CPNP notification system, which facilitates product market entry, is a key component of ensuring compliance. Ongoing efforts are being made to enhance both pre-market evaluation processes and post-market surveillance to address gaps in the detection of non-compliant products. While pre-market safety assessments are based on scientifically validated methods, the reliance on NAMs is part of a broader strategy to replace banned animal testing. Although challenges remain in the full implementation of these methods, authorities are actively working to refine them, ensuring higher safety standards and reducing reliance on animal data. The current focus is on improving marketing surveillance and enhancing the reporting and analysis of adverse events. Continuous developments in regulatory frameworks aim to close existing gaps, ensuring that both consumers and the environment are better protected. Consequently, non-compliance can remain undetected for a time sufficiently long to the point of causing unpredictable effects on consumers that could have been avoided. If more samples of more products were tested and inspected, more non-compliant products would be detected, and more interventions, either preventive or corrective measures, would be conducted.

Assuming that a product fully complies with the requirements imposed by the CR, it cannot be guaranteed that it will be completely safe for consumers. The safety assessment, even if performed precisely as defined by the SCCS, may lack toxicological information. The replacement of animal testing by NAMs was implemented before it was well enough developed to have regulatory acceptance on all endpoints. Instead, multiple assays need to be analyzed together, and evaluated on a case-by-case basis, to reach a conclusion about the safety of the ingredient. Also, it may not be possible to disclose the full information, as some criteria are still dependent on the data obtained from animal studies.

In light of this lack of rigor, there is scope for many adverse events to occur with a sizable percentage of users. These adverse events, however, are under-reported to the responsible authorities, making it easier for them to remain unidentified for longer and not bring to the surface the consequences of regulatory shortcomings. Furthermore, there is only a provision for reporting serious events, keeping alive the possibility that non-serious events will perhaps never be analyzed. In a way, the lack of regulatory rigidity in the cosmetics industry, together with the absence of perception of the seriousness of the problem, end up nurturing a cyclical relationship that does not do justice to the importance and social impact that cosmetics have in sustaining people’s health and well-being.

The main regulatory shortcomings identified in the pre-marketing and post-marketing period that compromise the compliance of cosmetic products on the market are summarized in Figure 6.

Even though the legislation envisages ways of safeguarding the consumers, what can be seen in practice is somewhat different. In addition to the issues that are not covered by the regulation, some aspects do not operate to their full potential, putting CAs even further away from achieving the end goal of consumer protection (summarized in

Table 2. Demonstration of regulatory discrepancies, comparing what is foreseen in the European regulation and what occurs in practice.

Expectation	Reality
The RP holds a record of the CSR and the PIF demonstrating the product is safe by conducting a proper safety assessment.	Non-compliance with this requirement is unlikely to be detected.
Only products that are safe under normal and reasonably foreseeable conditions of use are present on the market.	Possible intentional overlooking by authorities to avoid harming industries or sales.
Guidelines issued by the SCCS to guide the testing of cosmetic ingredients and their safety evaluation.	There is a need for the SCCS to also provide a practical interpretation of the guidelines, as it is hardly feasible to comply with all the proposed requirements.
Market surveillance actions undertaken by the regulatory authority of the MS to detect non-compliant products.	The non-standardized approach to market surveillance renders it ineffective.
For ethical and ecological reasons, the testing of cosmetic products and ingredients on animals is banned, being replaced by NAMs.	NAMs have regulatory acceptance on a limited number of endpoints and are not available for all risk assessment criteria. Safety information, especially involving new cosmetic ingredients, often remains incomplete.
Risk assessment is based on the concept of safe dose, establishing an ideal MoS.	The wider the knowledge gap, the more inaccurate the MoS calculation gets.
The SCCS regularly updates the safety information of cosmetic ingredients.	The SCCS re-evaluation has no defined periodicity and often involves animal studies.
The cosmetovigilance system is designed to protect the health of cosmetic product users by monitoring adverse events that may occur post-marketing.	Adverse events are under-reported, keeping the cosmetic surveillance system from working at its most optimal efficiency.
Cosmetic technology is constantly evolving to improve the performance of formulations.	The industry’s progress is limited, especially when concerning test methodologies for nanomaterials and new cosmetic ingredients.

).

8. Future Prospects

Conscious of the limitations of the current regulatory framework, the authorities intend to update the legislation applicable to cosmetic products. Although not confirmed, some of the possibilities of change include improvements to the risk management system (Next Generation Risk Assessment (NGRA)), adopting a generic approach for the systematic and automatic ban of hazardous ingredients, attention to the legibility and digitalization of product labeling information, a new definition of nanomaterials, and consideration of the combined effects of exposure to chemicals from different sources. The draft of this version, called Targeted Revision of the Cosmetic Products Regulation, is under discussion, and no date has been set for its implementation, although it is believed to be in 2024.

Conversely, the latest version (12th) of the NoG for the Testing of Cosmetic Ingredients and their Safety Evaluation was adopted at the plenary session of 26 October 2023. This guideline has been updated with emphasis on NAMs—new methodologies introduced for the testing of acute inhalation, skin irritation, eye irritation, and genotoxicity, along with the extension of in silico prediction possibilities. Attention is also given to the NGRA, as the risk assessment of cosmetics and their ingredients is shifting toward a strategic combination of NAM and new technologies with historical animal data, if available, to come to a weight of evidence (WoE)-based decision-making approach [14]. Due to the improvements introduced in this new revision, it is envisaged that the next generation of cosmetic products will be superior in terms of safety, or, at the very least, will have the means to do so. It is worth noting, however, that this guideline is not a checklist, and, therefore, will not be compulsory until it is fully implemented in the new regulation. Chances are that the compliant products currently on the market still adhere to the previous versions of the document mentioned.

Finally, the regulatory landscape for cosmetics in Europe presents a complex interplay between consumer safety and environmental protection. Although the cosmetic regulation establishes stringent safety requirements, gaps remain in enforcement and the application of alternative testing methods. Environmental assessments, governed primarily by REACH legislation, underscore the importance of a comprehensive approach to chemical safety. Future efforts must focus on bridging these regulatory gaps to ensure the safety and sustainability of cosmetic products.

9. Conclusions

Given the function and area of application, the intrinsic risks of exposure are indeed considerably lower for cosmetic products than for pharmaceuticals but still are not to be dismissed. They are chemical substances formulated into a product to come into contact with the skin and mucous membranes in potentially vulnerable and injured states, so they could have a systemic impact. The inclusion of prohibited substances in the formulation, misclassification of a product as cosmetic, and overall non-compliance, as the examples presented in Annex 1, can be hazardous to human health and, therefore, deserve careful attention. It is possible that some dermatological adverse events associated with cosmetic products could have been avoided if authorities were more stringent in their implementation and monitoring of the regulation and through efforts to address the safety assessment shortcomings, especially covering all toxicological endpoints, and improve the cosmetovigilance system. The introduction of non-compliant cosmetic products onto the market generates a cycle of events resulting from the failure to detect quality defects associated with these products, which can, therefore, cause adverse events and/or signs of toxicity in the consumer. As long as the shortcomings in the regulations are not corrected, this cycle will be constant and will generate more non-compliant products, more undetected quality defects, and more adverse events and/or signs of toxicity for the end user (Figure 7).

Cooperation in dealing with these challenges will, in addition to safeguarding public health, lead to the development of more cosmetic technology, allowing new cosmetic ingredients and nanoformulations to be explored.