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In August 2023, the European Chemicals Agency (ECHA) and the European Food Safety Authority (EFSA) jointly published a landmark guidance document on the impact of water treatment processes on residues of active substances in water abstracted for drinking water production (EFSA Journal, doi: 10.2903/j.efsa.2023.8194). For companies placing biocidal products on the EU market, this guidance is not merely a technical update. Rather, it represents a fundamental shift in how regulatory dossiers must be constructed. Its applicability requirements have been formally agreed and have become mandatory as of 1 April 2026. What the Guidance Covers The 2023 ECHA/EFSA guidance establishes a tiered framework to assess how water treatment processes (such as chlorination, ozonation, or UV treatment, etc.) transform residues of active substances into potentially hazardous compounds known as treatment transformation products (tTPs). This matters because some tTPs, such as nitrosamines, can be significantly more toxic than the parent active substance from which they derive. The guidance applies to both plant protection products (PPPs) and biocidal products, but its implications are especially acute for the biocides sector, where products in areas such as drinking water treatment (Product Type 5), surface disinfection, and water used in food processing directly intersect with the water supply chain. The BPR Regulatory Context Under Regulation (EU) No 528/2012, no active substance may be approved, and no biocidal product may be authorized for market placement, without a rigorous demonstration that it does not pose unacceptable risks to human health, animals, or the environment. This explicitly includes risks arising via drinking water, either from direct use or from residues reaching water abstraction points. The 2023 guidance fills a critical gap that previously existed in BPR compliance. While earlier frameworks addressed disinfection by-products in limited contexts, they did not systematically assess what happens when biocide residues or their environmental metabolites enter a water treatment facility and undergo further chemical transformation. That gap is now closed and its closure has direct consequences for both active substance approval applications and product authorisation dossiers. When Does the Guidance Apply? The Agreed Applicability Rules The question of when exactly this guidance becomes mandatory generated significant debate among EU Member States' Competent Authorities (CAs) for biocidal products, which was formally resolved at the 104th CA meeting in June 2024 (CA-June24-Doc.7.2). The agreed conclusion is as follows: The guidance will NOT apply to: Active substance dossiers currently in the Review Programme. Given that the Review Programme has already been extended to December 2030, applying the new guidance to ongoing review submissions would induce delays to an already stretched schedule. The guidance WILL apply to: All other procedures both active substance approvals/renewals and biocidal product authorisations/renewals for which applications are submitted on or after 1 April 2026. Applications submitted before that date are not subject to the guidance. This approach deliberately aligns with the applicability framework agreed for the ECHA guidance on risks to bees from biocide use, and with the general CA practice on implementing new guidance documents in the biocides area. It also mirrors, in broad terms, the schedule adopted by the PAFF Committee (Standing Committee on Plants, Animals, Food and Feed) for plant protection products though with one important difference: unlike in the PPP area, the CA did not restrict product authorisation applications to only those products whose active substance was already assessed under this guidance. The rationale is that in the biocides sector, active substance approvals do not typically cover all the uses relevant at the product authorisation stage, meaning the guidance retains independent relevance for product-level dossiers regardless of how the AS was evaluated. It is also worth noting that applicants preparing submissions before 1 April 2026 are not prohibited from voluntarily applying the guidance. In fact, doing so proactively can help demonstrate compliance with the existing BPR requirement that residues must not cause unacceptable effects through drinking water. The Four-Step Assessment Framework The guidance introduces a structured, risk-proportionate methodology built around four sequential steps: Step 1 Exposure at the abstraction point: Using Predicted Environmental Concentrations (PEC), applicants must determine whether residue concentrations exceed 0.1 µg/L. If this threshold is breached, a full tTP formation assessment becomes mandatory. Step 2 Identification of treatment transformation products: Applicants must characterise which tTPs form during treatment processes. Any tTP detected above 0.075 µg/L triggers chemical identification and hazard characterisation. Step 3 Toxicity assessment: A tiered toxicological evaluation is applied to identified tTPs, starting with genotoxicity screening (Tier 1) and escalating to targeted experimental testing (Tier 3) where needed. Step 4 Risk characterisation for the consumer: If risk is considered acceptable based on the above, appropriate risk management and monitoring measures are defined. If not, the use may be refused for specific applications or the authorisation rejected entirely. What This Means for Industry For companies holding or seeking BPR-compliant authorisations, the practical implications are significant. Dossiers submitted from 1 April 2026 onwards must incorporate this framework, meaning that toxicological and environmental fate data packages must now extend well beyond the active substance itself to encompass its transformation products under realistic drinking water treatment conditions. Several structural challenges make this transition demanding. First, toxicological data on tTPs is often simply absent, forcing companies to rely on predictive in silico tools such as QSAR modelling and read-across approaches that regulators accept as a starting point but that frequently require subsequent experimental validation. Second, water treatment processes vary considerably across EU Member States, complicating the design of standardised simulation studies. Third, the costs and timelines involved in generating adequate tTP data can be prohibitive, particularly for SMEs. Coordination between active substance manufacturers and downstream biocidal product formulators is also critical. Data on tTPs generated by AS manufacturers must flow effectively to formulators who bear responsibility for full product dossier compliance. Without early, structured communication across the value chain, gaps in data availability will translate directly into delays or refusals at the authorisation stage. Proactive Compliance: Where to Start Companies should treat the April 2026 deadline not as a future concern but as an immediate operational priority. The recommended starting points are: Portfolio review: identify which active substances and product types have exposure pathways to drinking water abstraction areas. PEC screening: conduct preliminary PEC calculations to determine which products trigger the full tTP assessment. Supplier engagement: initiate dialogue with AS suppliers to understand what tTP data is already available and what studies remain outstanding. Data gap analysis: map missing toxicological and analytical data against the tiered requirements of the guidance, and commission studies accordingly. Conclusion The 2023 ECHA/EFSA guidance on water treatment transformation products is a regulatory milestone that reshapes what compliance looks like for the biocides industry. It operationalises existing BPR obligations, that authorised products must not endanger health via drinking water, with a data-driven methodology that leaves little room for ambiguity. For companies placing biocidal products on the EU market, the question is no longer whether to engage with this framework, but how quickly and systematically they can build it into their regulatory strategy. If you are a company looking for support in how to tackle this requirement, please don’t hesitate to contact our regulatory team Author: Barbara DHOOP References: EFSA Journal 2023, doi:10.2903/j.efsa.2023.8194; ECHA Guidance on Biocides Legislation (Vol. V); Regulation (EU) No 528/2012 (BPR); Directive (EU) 2020/2184 (Drinking Water Directive): https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.8194 https://circabc.europa.eu/ui/group/e947a950-8032-4df9-a3f0-f61eefd3d81b/library/0c904047-6742-4f85-9a1f-44d357dbc10f/details

Since 13 December 2024, the European consumer landscape has changed drastically with the application of Regulation (EU) 2023/988, better known by its acronym GPSR (General Product Safety Regulation). Less than a year later, an important milestone completed the framework: on 21 November 2025, application guidelines were published. They provide the long-awaited clarifications on the interpretation of the text and its operational requirements. GPSR: A Universal Safety Net for All Consumer Products The GPSR applies to all non-food consumer products, whether new, second-hand, repaired, or refurbished. Its strength lies in its transversal scope: it applies whenever there is no stricter specific provision in EU harmonization legislation. The goal is simple: no dangerous product should slip through the safety net, whether sold in physical stores or online. General Safety Obligation: Ensuring Safe Products on the Market The GPSR is abased on a general safety obligation: economic operators may only place safe products on the market. A safe product is defined as: "any product which, under normal or reasonably foreseeable conditions of use, including the actual duration of use, does not present any risk or only the minimum risks compatible with the product’s use, considered acceptable and consistent with a high level of protection of the health and safety of consumers." To achieve this, the regulation requires a rigorous methodological approach. Each manufacturer must now carry out an internal risk assessment before placing any product on the market. Risk is defined as "the combination of the probability of an occurrence of a hazard causing harm and the degree of severity of that harm." This assessment must be recorded in technical documentation, proportionate to the product's complexity, and retained for 10 years. Main Product Safety Assessment Criteria Under the GPSR Product characteristics: Design, composition, packaging, and instructions. Consumer categories: Special attention is given to vulnerable consumers (children, elderly, people with disabilities). Misleading appearance: Products mimicking foodstuff or particularly attractive to children (food imitations) are specifically targeted. New technologies: Cybersecurity, machine learning (AI) functions, and software updates are now integral to the safety assessment. Traceability and Notification: New GPSR Obligations for Manufacturers and Importers The GPSR modernizes market surveillance through two key platforms: Safety Gate: The former RAPEX system, renamed, for information exchange between authorities on dangerous products. Safety Business Gateway: A mandatory portal for companies. Any manufacturer or importer aware of a serious accident or a dangerous product on the market must notify through this single access point. For example, in 2025, 2,755 chemical and environmental alerts were reported across various consumer products. European Tools and Guidelines to Comply with the GPSR The GPSR relies on a set of guides and resources provided at the European level. They are a useful starting point to understand requirements and structure a compliance approach, but operational implementation often requires dedicated expertise, particularly when demonstrating and documenting risk levels robustly. SAGA: A First Qualitative Approach To support risk assessment, the Commission provides SAGA (Safety Gate Risk Assessment) via the Safety Gate ecosystem. This tool can provide a qualitative risk analysis which can be used as a first tiered approach (hazard, exposure, severity/probability) with models adapted to different product types. However, this approach alone is often insufficient when precise quantitative risk levels must be justified. Blue Guide and GPSR Guidelines for Businesses For the general implementation framework, operators can rely on the Blue Guide on the application of EU product rules. More specifically, on 21 November 2025, the Commission published dedicated guidelines: On the application of the general product safety regulation (GPSR) by businesses On the practical implementation of the Safety Business Gateway These texts aim to guide and harmonize practices while largely referencing existing EU standards, sector-specific requirements, and risk assessment methodologies already used at the EU level. Focus on Chemical Risks: Aligning With REACH When a product contains chemicals chemical component (substances, emissions, migration, skin contact, etc.), the dedicated risk assessment benefits from approaches consistent with REACH, including hazard characterization, exposure scenarios, risk characterization, and risk management measures. This is precisely the methodological foundation CEHTRA uses daily to produce robust, documented assessments aligned with European expectations, useful in a GPSR compliance approach. Conclusion: Ensure Your Products Comply with the GPSR The GPSR (EU Regulation 2023/988) strengthens consumer product safety in Europe and imposes strict obligations on manufacturers and importers for risk assessment, traceability, and notification. To ensure your products fully comply and protect consumers, it is essential to work with experts. Are you affected by this regulation? To determine whether your company is concerned, take our self-assessment GPSR quiz. You can also contact our team for personalized support and recommendations tailored to your regulatory context. Author: Anna Chelle, Product Safety Specialist Regulatory Sources and References Regulation (EU) 2023/988 (GPSR): https://eur-lex.europa.eu/legal-content/FR/TXT/?uri=CELEX:32023R0988 Product Safety Legislation: https://ec.europa.eu/safety-gate/#/screen/pages/productSafetyLegislation Obligations for Businesses: https://ec.europa.eu/safety-gate/#/screen/pages/obligationsForBusinesses

The draft 24th Adaptation to Technical Progress (ATP) to the CLP Regulation (EC) No 1272/2008 proposes a significant number of new harmonised classifications that could affect chemical substance portfolios across several industrial sectors. Although the proposal has not yet been formally adopted, it already provides valuable regulatory news and scientific insights that companies can use to anticipate potential impacts on their substances and products. According to the current draft, 48 substances would receive new harmonised classifications, while 10 substances are proposed for reclassification. These updates are particularly relevant for companies involved in sectors such as coatings and adhesives, plastics and polymers, cosmetics and fragrances, and water treatment or biocides, where several of the substances included in the draft ATP are commonly used. As a result, manufacturers, importers, and downstream users may need to review the regulatory status of substances in their portfolios and assess implications for mixtures, labelling, and safety data sheets. One of the most notable aspects of the draft ATP is the number of high-concern hazard classes proposed. The draft includes four substances classified as Carcinogenicity Category 1A or 1B (among which [ethane-1,2- diylbis[nitrilobis(methylene)]]tetrakisphosphonic acid, sodium salt , CAS n° 22036-77-7), thirty substances classified as Reproductive Toxicity Category 1A or 1B (among which bisphenol F, CAS n° 620-92-8, sodium bromide, CAS n° 7647-15-6, piperonal, CAS n° 120-57-0) , and four substances classified for Specific Target Organ Toxicity following repeated exposure (STOT RE 1) ( among which sodium bromide, CAS n° 7647-15-6, thymol, CAS n° 89-83-8,  fosthiazate, CAS n° 98886-44-3). In addition, among the proposed reclassifications, two substances would receive a STOT RE 1 classification, one substance would be reclassified for reproductive toxicity, and another would receive a classification as a respiratory sensitiser. It is important to emphasise that the current document is still a draft proposal, and therefore the classifications it contains are not yet final. Discussions within the CARACAL group and the remaining steps of the legislative process could still lead to modifications before the ATP is formally adopted. Once adopted, the usual ATP timeline would apply, beginning with publication in the Official Journal of the European Union, followed by entry into force approximately twenty days later, and a transition period of around 18 months. Even at this early stage, however, the draft ATP provides valuable input for regulatory monitoring and scientific watch activities , allowing companies to anticipate upcoming regulatory changes. Organisations can start by reviewing their substance portfolios to determine whether any of the substances included in the proposal are relevant to their products or supply chains. From there, companies should assess potential downstream impacts, such as changes to mixture classifications, labelling requirements, or safety documentation. In parallel, it is essential to continue monitoring developments, as draft ATPs may evolve before final adoption. Understanding CLP lists: from early signals to binding classifications Monitoring ATP updates requires understanding the different types of CLP-related lists that provide complementary regulatory information at different stages. Draft ATPs (under consultation) provide early visibility on proposed classifications based on RAC scientific opinions and represent forward-looking regulatory intelligence.  The Registry of CLH Intentions enables early identification of substances under evaluation, supporting proactive regulatory watch.  Adopted ATPs (not yet applicable) provide a transition phase before legal enforcement, allowing companies to anticipate compliance actions.  CLP Annex VI contains legally binding harmonised classifications that must be applied by industry. Together, these lists form a continuous regulatory monitoring framework , from early signal detection to legally binding obligations. For many companies, keeping track of developments such as ATP updates, new classifications, and other regulatory initiatives can be challenging, particularly when managing large portfolios of substances across multiple markets. This complexity has led to increased use of regulatory monitoring tools for chemicals and substance tracking solutions . Digital solutions can support organisations in monitoring regulatory lists, tracking toxicological updates, and identifying substances impacted by regulatory changes , enabling earlier and more informed decision-making. The CEHTRA WATCH platform supports companies in: tracking regulatory changes affecting their substances  monitoring toxicological data and scientific updates  identifying portfolio exposure to regulatory developments  By monitoring developments such as the draft 24th ATP and evaluating potential impacts ahead of time, companies can reduce regulatory uncertainty and ensure a smoother transition when new classifications become legally binding. Get in touch with our experts to assess the impact of these regulatory changes on your substance portfolio.

On 13 January 2026, the European Commission’s Joint Research Centre (JRC) published a new report: “JRC technical proposal on EU harmonised waste sorting labels under the packaging and packaging waste regulation”. ( Available here: JRC Publications Repository - JRC technical proposal on EU harmonised waste sorting labels under the packaging and packaging waste regulation ) More than just a design report The document is a technical blueprint to support the European Commission in developing future, harmonised packaging-sorting instructions, so consumers and producers encounter the same logic across Member States and packaging can circulate smoothly within the Single Market.  This timing is important because the Packaging and Packaging Waste Regulation (PPWR) applies from 12 August 2026, and the Commission is expected to use the JRC work as an input when preparing the secondary legislation on labelling. What the JRC report is proposing  At its core, the JRC proposes a harmonised system of consumer-facing labels for packaging and waste receptacles (bins), built to work across Europe’s very different collection and sorting systems.   The key idea is intuitive: matching labels so the label you see on packaging corresponds to what you should look for on the bin (and vice-versa).   The report serves as evidence-based input for the Commission services, especially DG Environment, to support the planned implementation measures of the PPWR (the JRC aims to inform the Commission’s implementing acts mentioned in the PPWR).  Built from behavioural evidence, not “designer taste”  One of the strongest signals in the report summary is the methodology behind it. The JRC says the proposal is grounded in:  extensive desk research  empirical evidence from citizen workshops, surveys, and experiments  expert stakeholder workshops and consultations   That matters, because sorting labels only work if they work in real kitchens, offices, and public spaces under time pressure, in different languages, and with varying levels of recycling knowledge. “Flexible, yet harmonised”: the balancing act  The JRC repeatedly frames the challenge as finding the sweet spot between EU-wide harmonisation and practical flexibility for Member States and real-world packaging constraints.   In practice, that balancing act shows up in three main design questions:  What should the label communicate?  The proposed “conceptual approach” focuses on informing consumers about material composition and providing clear sorting instructions, reinforced through matching labels on bins.   Determining the Appropriate Level of Label Granularity  A single “plastic” label offers simplicity but may be overly broad, especially in systems that differentiate between rigid and flexible plastics or where composite materials create confusion. According to the JRC summary, the proposed approach aims for a level of granularity that defines distinct labels based on both theoretical and practical considerations. External feedback on the JRC work indicates that early prototypes explored a range of material categories and subcategories. For instance, one industry analysis describes an initial prototype with eight material categories, including subcategories like “soft” vs “hard” plastics.  What should the label look like across 27 markets?  The visual approach aims to ensure the label both stands out and is understood across Member States, while allowing enough flexibility to work on-pack and on bins as you can see on the figure below.    However, even before the Commission locks anything in, the labelling conversation is already contentious. Several industry groups have publicly warned that heavy reliance on text and/or colour could recreate fragmentation because text triggers translation needs and can easily drift into national variants.   The JRC summary itself acknowledges the reality: the proposal includes compromises, identifies challenges, and flags future work needs given the complex interplay of regulatory requirements, stakeholder preferences, and practical limitations.  In other words, this is not presented as a final “perfect” answer, but as a structured, research-backed basis for the Commission to build on.  What this means for brands, retailers, and compliance teams  If you put packaged goods on the EU market, this is the moment to treat waste-sorting labels as a system change, not a minor artwork update. A few practical implications stand out:  Data discipline becomes design discipline. If labels need to reflect material composition reliably, internal packaging specifications (and component-level bills of materials) have to be clean, current, and auditable.  Space on-pack will be a constraint. Expect tension between information richness and small-format packaging realities especially if multiple components need instructions.  Consistency across SKUs will matter. Harmonisation is partly about consumer learning: the faster people recognise a label family, the better it performs.  Conclusion and next step  Under the PPWR, 12 August 2026 is a key milestone, as it is the date of general application of the Regulation and the deadline for the Commission to adopt implementing acts specifying harmonised labelling requirements. These implementing acts are adopted in 2026, while the harmonised labelling obligations take effect from 2028.  The bottom line: the JRC has now provided a concrete, evidence-backed proposal. For stakeholders, it’s crucial to begin reviewing the proposed direction now, as once the Commission’s act is adopted, the implementation timeline will accelerate rapidly.  CEHTRA supports you in implementing these regulations. Contact us today to learn more about how we can help you.  References  https://www.europen-packaging.eu/news/joint-industry-statement-on-wsl   JRC Publications Repository - JRC technical proposal on EU harmonised waste sorting labels under the packaging and packaging waste regulation   CEHTRA supports packaging stakeholders in anticipating and complying with the new PPWR requirements, particularly in terms of labeling and waste management. Author: Baptiste REVERDY

Institutional framework and protection objectives The sanitary safety of drinking water in the EU is primarily based on an increasing synergy between two legislative pillars: Directive (EU) 2020/2184 (Drinking Water Directive), which constitutes a revision of the pre-existing Directive 98/83/EC, and Regulation (EU) No 528/2012 (BPR). Although their scopes differ, they converge towards a common goal: the protection of human health. While the BPR governs the placing on the marketing and use of biocidal products (including drinking water treatment products), the Drinking Water Directive defines quality requirements at the tap through a risk management approach. In this interaction, four categories of actors are involved: Competent authorities and EU agencies : ECHA, EFSA, the European Commission and national authorities, responsible for governance and scientific arbitration. Industry and applicants : manufacturers of active substances (AS), formulators of biocidal products, and economic operators responsible for the compliance of files. Technical operators and suppliers : water suppliers and operators in the food sector ensuring treatment and distribution. Professionals and the general public : building professionals and end consumers, benefiting from safe water. The “dual key” principle The implementation of biocidal solutions in emissions integrated into the water cycle requires two-step validation validation to ensure consumer safety. The first key, defined by the Biocidal Products Regulation (BPR) , corresponds to the Authorization for Placing on the Market (AMM in French). This is the fundamental prerequisite for a biocidal product to be marketed. The BPR evaluates and validates the effectiveness of a disinfectant for a specific use and examines the intrinsic risks associated with this product, both for human health and the environment. The second key is determined by the Drinking Water Directive , which focuses on compliance of water at the tap. This step represents the validation of the performance of the biocidal product under real usage conditions. The objective is to ensure that an authorized biocide never leads to exceeding the water quality standards set. Technical requirements and evolution of chemical quality The guarantee of safe drinking water relies on the strict application of quantified health thresholds, on a rigorous framework for substances used in treatment to prevent any alteration of quality, and the implementation of a dynamic monitoring system to track the evolution of knowledge concerning new pollutants, as presented in various sections of Directive 2020/2184. Defined under article 12 , the use of chemical treatment agents and filtration media is subject to four imperatives: Human health: no direct or indirect compromise of health protection.  Organoleptic quality: maintenance the colour, odour and taste of water.  Microbiological stability: no unintended microbial proliferation.  Minimal contamination: strict limitation of residues to the level necessary for the intended use.  Contamination by by-products must be kept as low as possible. To address emerging pollutants, the directive introduces, in Article 13, an obligation for Member States to monitor water for chemical parameters and substances or compounds of concern identified in a watchlist ( Watch List ), such as PFAS, endocrine disruptors, or microplastics, whose parametric values will be specified in delegated acts by the European Commission. The parametric values used to assess water quality are defined by minimum requirements to be met, presented in Annex I of the directive, and cover microbiological, chemical and indicator parameters. Risk-based approach: from source to tap  The legislation requires a systemic analysis covering the entire supply chain (Article 7): Extraction (Art. 8) : assessment of environmental risks in abstraction areas. Treatment & distribution (Art. 9) : management of risks related to water treatment processes and the network.  Private installations (Art. 10) : monitoring of the internal distribution up to the tap. Joint ECHA/EFSA Guidance (2023) The 2023 joint ECHA/EFSA Guidance aims to harmonize the assessment of active substance (AS) residues and their transformation products in drinking water.  Starting from 1 April 2026 , this guidance became mandatory for all new submissions. It specifically includes consideration of environmental transformation products (eTPs), formed in the environment before entering the plant, and treatment transformation products (tTPs), formed during drinking water treatment processes through methods such as chlorination or ozonation. Some of these products, like nitrosamines, may be more toxic than the parent active substance. This regulatory evolution could have a significant impact on biocide manufacturers, potentially affecting them upstream of the active substance manufacturers, resulting in longer approval timelines for dossiers. Risk assessment methodology and critical alerts The assessment of residues and transformation products from the use of biocides (and plant protection products) is divided into four successive steps: Step 1: exposure assessment at the abstraction point via PEC (Predicted Environmental Concentrations). If PEC > 0.1 µg/L , a full assessment of tTP formation is triggered.  Step 2: detection of transformation products (tTPs) from water treatment process. A concentration > 0.075 µg/L triggers chemical identification and hazard assessment.  Step 3: toxicity assessment of formed products according to a tiered approach, from potential for genotoxicity (Tier 1) to targeted testing (Tier 3).  Step 4: risk characterization of the risk to the consumer . If exposure is acceptable, management and monitoring measures can be defined. Strategic impacts and industrial challenges  With the implementation of this regulatory framework, the biocides industry faces several structural obstacles that complicate its development and adaptation to regulatory requirements, with major strategic implications for the entire value chain. On a scientific and public health front , the lack of toxicological data concerning tTPs is a central challenge. In many cases, no experimental data is available regarding their genotoxicity or general toxicity. This gap forces industry players to rely on predictive approaches such as in silico models (QSAR, read-across). Although these tools provide an initial assessment, they generate significant uncertainties and frequently require subsequent experimental validation, impacting costs and timelines. This situation creates a strategic risk because the lack of robust data can delay or jeopardize authorization procedures. On the technical side , the complexity of evaluations is exacerbated by the lack of standardization of drinking water treatment processes at the European level. While the final water quality is regulated, treatment methods vary significantly depending on local contexts. Therefore, manufacturers must design specific experimental protocols, incorporating numerous parameters (raw water quality, pH, temperature, natural organic matter), making studies difficult to replicate and harmonize. The identification of tTPs is itself a major analytical challenge, requiring advanced technologies and non-targeted approaches capable of detecting compounds at extremely low concentrations. From an economic perspective , the costs associated with treatment simulation studies are considerable, making these analyses difficult for many companies, especially smaller ones, to access. Moreover, the time required to complete these studies is often incompatible with strict regulatory deadlines, creating tensions between legal requirements and operational capabilities within the industry. Coordination between the different actors in the value chain, especially between active substance (AS) manufacturers and biocide formulators, is also a critical issue. It is imperative to establish a smooth and efficient data-sharing process to ensure product compliance and safety throughout their life cycle. This cooperation would allow for better anticipation of risks and faster response to regulatory requirements. Finally, the regulatory consequences in case of uncertainty or identified risk are particularly structuring. In the absence of effective risk mitigation measures (RMM), non-compliance due to the presence of concerning tTPs can lead to the refusal of market authorization. Additionally, even if an active substance is approved, the identification of a toxic tTP in the formulated product may lead to rejection for a specific use. This situation places companies at high commercial risk and forces them to integrate tTP-related challenges early in their development, formulation, and marketing strategies. Strategic recommendations for operators  To ensure safe market access, operators must adopt a rigorous and proactive strategy: Review of product portfolio and associated active substances. To identify products that may pose a problem and implement appropriate solutions. In parallel, a thorough analysis of PECs must be conducted to verify if the critical threshold of 0.1 µg/L is exceeded. This step is crucial to ensure that products meet safety standards and do not present any risks to human health or the environment. Evaluate specific uses of products, particularly those that pose a risk to abstraction areas. Operators should engage in proactive and collaborative dialogue with active substance suppliers to improve availability of data on tTPs. Conclusion  According to the BPR, the conditions for granting authorization include ensuring that the biocidal product itself, or its residues, does not have an unacceptable immediate or delayed effect on human health and the environment, including vulnerable groups, or on animal health, directly or via drinking water, food, animal feed, air, or other indirect effects. The publication of the 2023 Joint Guidance ECHA/EFSA does fill a gap in recommendations for assessing effects via drinking water. However, the deadline of April 1, 2026, represents a breaking point: action must be taken now to anticipate the delays linked to technical studies. Authors : Floriane Demailly & Loris Mistrulli

In January 2026, the European Food Safety Authority (EFSA) Panel on Nutrition, Novel Foods, and Food Allergens (NDA) endorsed a draft opinion on the safety of plant preparations containing berberine. This 195-page document, submitted for public consultation, represents a major step in the regulatory oversight of a widely used isoquinoline alkaloid in dietary supplements aimed at metabolic health (blood glucose, lipids, body weight) across Europe. This article provides a factual and structured reading of the draft, followed by an analysis of areas of uncertainty and levers available to industry stakeholders to actively engage in the regulatory dialogue before the final opinion. Context and Scope of the Assessment The request follows the 2019 opinion by ANSES, which identified concerns related to the consumption of plant-based supplements containing berberine: gastrointestinal disorders, hypoglycemia, hypotension, and drug interactions. The European Commission activated the procedure under Article 8(2) of Regulation (EC) No 1925/2006 and asked EFSA to address two key questions: Is there a link between consumption of the listed preparations and an adverse health effect? Can a safe daily intake be defined for the general population and vulnerable subgroups? The mandate covers thirteen species and specific plant parts: Berberis aquifolium , B. aristata , and B. vulgaris  (root, bark); Chelidonium majus (aerial parts); Coptis japonica , C. teeta , and C. trifolia (rhizomes); Coscinium fenestratum  (root, stem); Hydrastis canadensis (rhizome, root); Jateorhiza palmata  (root); Phellodendron amurense (bark); Thalictrum flavum  (root); and Tinospora sinensis  (root, stem, leaf). The assessment focuses on the preparations in their entirety, not on berberine alone. Three lines of evidence were integrated: data on isolated berberine, data on other protoberberine alkaloids present in these plants, and data specific to each plant preparation. Explicitly excluded are: benefit-risk analyses, medicinal products, and synthetic forms of berberine (covered under the Novel Food Regulation). EFSA Conclusions by Toxicological Endpoint Genotoxicity Berberine (isolated substance) EFSA concludes there is compelling evidence of in vitro genotoxicity for berberine. Gene mutations were observed in the HPRT test on murine cells and in the Ames test (S. typhimurium TA98), only without metabolic activation, suggesting a direct mutagenic potential. Clastogenic and/or aneugenic effects were reported in two in vitro  mammalian micronucleus tests. Identified mechanisms include DNA intercalation, inhibition of topoisomerases I and II, induction of single- and double-strand breaks, and oxidative DNA damage. Berberrubine, the main phase I metabolite, also inhibits topoisomerase II. In vivo  data remain inconclusive: a single mouse study did not confirm these effects, and the Panel emphasizes the need to verify genotoxicity at first-contact sites such as the gastrointestinal tract and liver. Other Protoberberines The Panel considers that other protoberberines present in plant preparations may share this genotoxic potential due to strong structural similarity with berberine. QSAR models predict mutagenicity for berberastine, columbamine, epiberberine, jatrorrhizine, palmatine, stephabine, and several others, while experimental data remain sparse and inconclusive, with only isolated signals for coptisine and palmatine. Chelidonium majus-specific Alkaloids Sanguinarine and chelerythrine, present in C. majus , pose genotoxic concerns independent of berberine, with evidence of chromosomal and DNA damage in vivo  for sanguinarine and QSAR predictions for chelerythrine. These non-protoberberine alkaloids constitute an additional concern. Carcinogenicity EFSA establishes evidence of carcinogenicity in rodents for H. canadensis  rhizome/root preparations. Two Tier 1 studies show an increased incidence of hepatocellular adenomas in male and female rats, with a positive trend in male mice. Consumption of these preparations therefore represents a carcinogenic risk for humans, even though the exact mechanism remains unclear. A genotoxic role of berberine or its metabolites is possible but not confirmed in vivo . For the other twelve evaluated species, no data are available. Hepatotoxicity Berberine (isolated substance) Hepatotoxicity cannot be established based on available studies. Ninety-day rat studies (156 mg/kg/day) and developmental toxicity studies showed no liver damage, with only two isolated cases of transaminase elevation reported in clinical trials. Berberrubine showed signs of hepatotoxicity in a 42-day rat study at 100 mg/kg/day. H. canadensis Tier 1 subchronic studies (90 days) identify the liver as the primary target organ, with rats being the most sensitive species. Increases in liver weight appear at the lowest tested dose (255-260 mg/kg/day), accompanied at higher doses by nearly generalized hepatocellular hypertrophy. These results, consistent with carcinogenicity data, indicate dose-dependent toxicity. EFSA notes that berberine is unlikely responsible, as hepatotoxicity occurs at doses far lower than those used for berberine alone. C. majus (aerial parts) Preparations of aerial parts are associated with 43 human cases of idiosyncratic hepatotoxicity, predominantly presenting with jaundice. Latency ranges from a few weeks to several months, making causality difficult to establish. This type of reaction is unpredictable, does not follow a dose-response relationship, and cannot be reliably reproduced in the laboratory. Developmental and Reproductive Toxicity Berberine showed signs of maternal and fetal toxicity in rats and mice, with a maternal NOAEL of 223 mg/kg/day in rats and a fetal NOAEL of 666 mg/kg/day in mice. These data are Tier 2 quality. For all plant preparations, information is almost nonexistent, and no reproductive toxicity studies are available, representing a critical data gap. Systemic Toxicity (Repeated Doses) No repeated-dose toxicity study compliant with OECD and GLP guidelines is available for berberine alone, preventing the establishment of a regulatory reference point. For most other species, general toxicity profiles are largely unknown. Available studies are Tier 2-3 quality and present limitations such as poorly described test material, a limited number of organs assessed, or incomplete reports. Drug Interactions Berberine inhibits CYP3A4 and possibly CYP2D6 and CYP2C9. H. canadensis  preparations also show inhibition of CYP3A and CYP2D6 and potential effects on intestinal influx transporters (OCTs), with (−)-β-hydrastine contributing significantly. Preparations containing berberine may therefore interact with many drugs, including anticoagulants, statins, antidiabetics, and antiarrhythmics. Gastrointestinal Effects Supplements containing berberine may cause constipation, diarrhea, nausea, or abdominal pain, the most systematically observed signal in clinical trials, at doses of 400-1500 mg/day. Hypoglycemia, Hypotension, Immunotoxicity Contrary to previous concerns, no evidence of hypoglycemia, hypotension, or immunotoxicity was found in available animal or human studies. NDA Panel Conclusion The Panel concludes: “The available data do not allow for the establishment of a safe intake for any of the plant preparations of the species included in the assessment.” This conclusion applies to all thirteen species and plant parts of the mandate. It is based on two determinants: established hazard signals ( in vitro  genotoxicity, H. canadensis  carcinogenicity, idiosyncratic hepatotoxicity of C. majus ) and a massive insufficiency of data for the majority of species. Grey Areas and Industry Levers Although the Panel’s conclusion is strict, a careful reading of the draft reveals an ecosystem of substantial scientific uncertainties, providing real space for dialogue and generation of complementary data. EFSA itself details in Section 6 a structured timeline (Steps 1-4) of information needed to move toward a more differentiated final opinion. Relevance of in vivo genotoxicity signals In vitro  genotoxicity of berberine is central to the Panel’s concern. However, the draft highlights a major methodological tension: berberine has low systemic bioavailability. Intestinal absorption is limited, intestinal metabolism predominates, and actual systemic exposure is low, with circulating forms mainly as phase II metabolites (glucuro- and sulfoconjugates). All genotoxicity evidence is based on in vitro  systems using free berberine at concentrations that may not reflect actual tissue exposure under real use conditions. EFSA explicitly states that negative in vivo  results will only be considered valid if target tissue exposure is demonstrated (toxicokinetic measurements in plasma and tissue homogenates). Robust tissue toxicokinetic data coupled with well-designed in vivo  studies could substantially alter the interpretation of genotoxic risk. Matrix effect: evaluating preparations, not berberine alone One of the draft’s key grey areas concerns the matrix effect of plant preparations. EFSA chose to evaluate whole preparations, not berberine alone. While scientifically justified, this creates complexity: the composition of a plant preparation is not limited to its marker alkaloid. Berberine content varies widely depending on botanical origin, plant part, developmental stage, harvest season, extraction process (solvent, temperature, drug/solvent ratio), and analytical method. Beyond berberine, most co-occurring protoberberines have not been systematically identified and quantified. The unidentified fraction complicates the assessment of mixture genotoxicity. For H. canadensis , the Panel explicitly notes that berberine is likely not responsible for observed hepatotoxicity and carcinogenicity, given the disproportion between equivalent berberine exposure (≈5 mg/kg/day in the hepatotoxic preparation) and doses of berberine alone without effect. Other plant constituents, including (-)-β-hydrastine and canadine, are suggested as potential contributors. In this context, complete and reproducible chemical characterization of preparations (full alkaloid profile, validated methods, botanical traceability) is the first step required by EFSA (Step 1) and a prerequisite for any regulatory argument. Non-transposability of data between species A major difficulty is the lack of data for most species, combined with the temptation to extrapolate from berberine or a better-documented species. The Panel explicitly resists automatic extrapolation, stating that study results for one preparation cannot automatically apply to another, even if berberine content is similar, due to distinct complete alkaloid profiles, differing unknown fractions, and variable component interactions. This is scientifically coherent but implies that each manufacturer wishing to maintain a species in their portfolio must generate or reference data specific to their preparation. Professional associations (such as EHPM, which has already submitted data in response to the data call) represent an important pooling lever. EFSA leaves a small door open: “The extent to which results can be extrapolated from one preparation to another will be evaluated based on the data provided and will be subject to expert judgment.”  Strong arguments on chemical profile comparability could be presented. Read-across for protoberberines Given the absence of experimental data for most protoberberines, the Panel allows for a read-across approach, conditional on applying EFSA SC 2025 guidance. This approach is considered applicable for mutagenicity (given convergent structural alerts and VEGA prediction reliability) but carries high uncertainty for chromosomal effects, due to VEGA model limitations for in vitro  and in vivo  MN. Experimental data on at least one other protoberberine family member (selected based on a worst-case criterion) are required to reduce uncertainty. A structured read-across argument supported by PBPK data (physiologically based pharmacokinetic modeling) and in vitro  MN data for a worst-case alkaloid could significantly reduce the evidence burden for the entire family. Public consultation as a dialogue space With the draft open to public consultation, the window for submitting comments and additional data is a direct lever. Industry stakeholders can: Submit comments on unclear methodological points (inter-preparation extrapolation criteria, exposure threshold for validating in vivo studies, worst-case definition for protoberberine read-across); Provide additional analytical data on the alkaloid profile of their preparations; Contribute to targeted toxicological studies, ideally through consortia via sector associations, for the species best represented in the European market. Conclusion EFSA’s draft opinion on berberine and plants containing it is a rigorous scientific assessment but suffers from considerable data asymmetry between species. While the in vitro  genotoxic signal and critical cases of H. canadensis  and C. majus  are legitimate and serious concerns, the inability to establish a safe intake for all thirteen species reflects more a data gap than unequivocal evidence of hazard. To meet regulatory requirements and support constructive dialogue with authorities, it is essential to provide reliable, well-targeted data, compliant with OECD and GLP standards, and supported by precise chemical characterization of preparations. Within this framework, CEHTRA assists industry by leveraging toxicology expertise to design and conduct rigorous, relevant, and actionable evaluation strategies, enhancing the scientific quality of dossiers and facilitating their assessment. Author: Marie LIAMIN References Draft Scientific Opinion on the safety of plant preparations containing berberine (EFSA-Q-2022-00803). EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA). 29 January 2026.

Introduction Per- and polyfluoroalkyl substances ( PFAS ) are a large family of anthropogenic chemicals characterised by highly stable carbon–fluorine bonds. Structurally, PFAS typically contain at least one fully fluorinated methyl (CF₃-) or methylene (-CF₂-) carbon atom. Chemically, PFAS can be divided into polymeric and non-polymeric substances . Polymeric PFAS include fluoropolymers, polymeric perfluoropolyethers and side-chain fluorinated polymers, while non-polymeric PFAS include polyfluoroalkyl and perfluoroalkyl substances. Among non-polymeric PFAS, perfluoroalkyl acids (PFAAs) are often further classified by chain length into long-chain, short-chain and ultrashort-chain PFAS. More than 16,000 PFAS substances  have been identified. These chemicals have been widely used in consumer and industrial applications because of their oil- and water-repellent properties , as well as their resistance to heat and chemical degradation. However, PFAS are highly persistent in the environment and may present toxicological concerns. As a result, regulatory authorities worldwide are introducing increasingly stringent restrictions and bans on PFAS uses, including in cosmetic products . PFAS in Cosmetic Products Technical functions in cosmetic formulations In cosmetic products, PFAS may perform several technical functions, including: hair and skin conditioning agents emulsifiers and stabilisers surfactants oil- and water-repellent agents Examples of PFAS substances reported in cosmetic formulations include: polytetrafluoroethylene (PTFE) perfluorononyl dimethicone trifluoroacetyl tripeptide-2 tetradecyl aminobutyroylvalylaminobutyric urea trifluoroacetate perfluorohexylethyl triethoxysilane methyl perfluorobutyl ether methyl perfluoroisobutyl ether PFAS may enter cosmetic products either intentionally as formulation ingredients (this is a rare situation) or unintentionally as impurities or degradation products .   Occurrence of PFAS in cosmetics In the United States, 51 PFAS substances have been identified as intentionally added ingredients across 1,744 cosmetic product formulations . The most frequently affected product categories include: eye shadows eyeliners face powders foundations leave-on face and neck products Together, these categories represent approximately 56% of PFAS-containing cosmetics . In Europe, an analysis conducted by the Swedish Chemicals Agency (KEMI)  in 2021 reported that PFAS were most frequently detected in decorative cosmetics (3.7%). Lower occurrences were identified in: skin care products (0.78%) hair care products (0.65%) toiletries (0.27%) PFAS occurrence in perfumes and fragrances was almost negligible (0.03%). Overall, the market share of PFAS-containing cosmetic products remains relatively limited.   Increasing Global Regulation of PFAS Regulatory scrutiny of PFAS is increasing rapidly worldwide. Under the EU REACH Regulation , Germany, Denmark, the Netherlands, Norway and Sweden submitted a restriction proposal in 2023 targeting approximately 10,000 PFAS substances , including their use in cosmetics. Several countries have already introduced or proposed additional restrictions: United States:  at least eleven states have introduced bans on PFAS in cosmetics New Zealand:  ban on PFAS-containing cosmetics starting January 2028, with full removal by July 2028 Canada:  restrictions on long-chain PFCAs in cosmetics Republic of Korea:  prohibition of approximately 190 PFAS substances as cosmetic ingredients As regulatory pressure increases, many cosmetic manufacturers are already moving away from PFAS use . However, replacing PFAS often requires significant reformulation efforts, as direct drop-in alternatives are rarely available.   Toxicological and Environmental Concerns PFAS and their degradation products are extremely persistent  in the environment. Their removal from surface water, groundwater, soils and sediments is technically complex and often costly. PFAS have been detected in multiple environmental media, including: drinking water sources food crops wildlife remote geographical regions Human biomonitoring studies show that PFAS are widely detected in human populations , indicating widespread exposure.   Exposure to certain PFAS has been associated with several potential human health effects including increased cholesterol levels, effects on the immune system, thyroid hormone disruption, impacts on infant birth weight, and increased risk of certain cancers. Examples of health effects associated with PFAS exposure reported in the ECHA Annex XV restriction report (2023) are summarised below. Figure . Examples of health effects associated with PFAS exposure (ECHA Annex XV Restriction Report, 2023). Exposure Pathways in Cosmetic Products For cosmetic products, dermal exposure is generally the primary route of exposure. However, other exposure routes may occur depending on the type of cosmetic product: inhalation (e.g., powders or sprays) ocular exposure (e.g., eye makeup) incidental ingestion (e.g., lip products) Because cosmetics are frequently used daily, systemic exposure assessment remains a key element of cosmetic safety evaluation .   Toxicological Reference Values and Risk Assessment Several regulatory bodies have proposed approaches to assess PFAS exposure risks. In 2020, the European Food Safety Authority (EFSA)  concluded that immune system effects represent the most critical endpoint for PFAS risk assessment. EFSA established a group tolerable weekly intake (TWI)  of 4.4 ng/kg body weight per week  for combined exposure to four PFAS substances: PFOA PFNA PFHxS PFOS In 2021, the Dutch National Institute for Public Health and the Environment (RIVM)  proposed a risk assessment approach using relative potency factors (RPFs) , allowing exposure to multiple PFAS to be expressed as PFOA-equivalent concentrations. More recently, the U.S. Food and Drug Administration (FDA)  published a safety assessment of the 25 PFAS most frequently used in cosmetic products . The assessment concluded that: perfluorohexylethyl triethoxysilane  may raise safety concerns five PFAS substances (including PTFE and perfluorodecalin) present low safety concern  under intended conditions of use for 19 of the 25 substances , available data were insufficient to conduct a full safety assessment This highlights the importance of toxicological data availability and structured risk assessment methodologies .   PFAS and Cosmetic Safety Assessment The evaluation of PFAS in cosmetic products requires: access to reliable toxicological data exposure assessment identification of appropriate toxicological reference values calculation of the Margin of Safety (MOS)  when applicable These elements are essential for the preparation of the Cosmetic Product Safety Report (CPSR)  required under the European Cosmetic Regulation. Because PFAS data may be incomplete or evolving, toxicologists often rely on a weight-of-evidence approach , combining experimental studies, predictive tools and regulatory assessments.   Conclusion: Preparing for a Changing Regulatory Landscape PFAS have historically provided valuable technical properties in certain cosmetic formulations. However, increasing regulatory scrutiny, environmental persistence concerns and evolving toxicological knowledge are significantly reshaping the regulatory landscape. Cosmetic manufacturers should therefore: review their product portfolios evaluate supply chain disclosures identify potential PFAS ingredients or impurities anticipate reformulation needs Early strategic planning is likely to be more manageable than reactive reformulation once regulatory restrictions enter into force. Companies must also ensure that cosmetic safety assessments remain robust, transparent and well documented , particularly in the context of evolving PFAS regulations.   Toxicological Expertise for PFAS and Cosmetic Ingredients The safety assessment of PFAS and other complex cosmetic ingredients often requires a comprehensive evaluation of toxicological data , including the identification of relevant studies, the selection of appropriate Points of Departure, and the interpretation of regulatory and scientific literature. In many cases, available information may be fragmented across multiple sources, or important toxicological endpoints may require further evaluation through a structured toxicological profile . CEHTRA supports cosmetic manufacturers, ingredient suppliers and regulatory teams by preparing custom toxicological profiles and safety assessments  for cosmetic ingredients and impurities. These evaluations include: identification and analysis of relevant toxicological studies hazard characterisation across key toxicological endpoints selection and justification of Points of Departure support for Margin of Safety calculations documentation supporting Cosmetic Product Safety Reports (CPSR) These expert assessments help ensure that cosmetic ingredients are evaluated using robust and transparent methodologies aligned with current regulatory expectations . Supporting PFAS Safety Assessment with COSMETICK In addition to expert toxicological evaluations, CEHTRA has developed digital tools to support cosmetic safety assessment workflows. CEHTRA supports cosmetic industry companies in product safety evaluation and regulatory compliance  at European and global levels. This digital platform COSMETICK combines a toxicological database  and a cosmetic risk assessment tool , providing access to more than toxicological and ecotoxicological profiles for more than 4,000 substances , including over 100 PFAS substances . By structuring toxicological data and supporting risk assessment workflows, COSMETICK helps toxicologists prepare robust cosmetic safety assessments and CPSR documentation . Get expert support in assessing PFAS in your cosmetic products and ensure full compliance with evolving regulatory requirements. Authors: Clarisse Bavoux & Pramod Kumar References: FDA (2025), Per and Polyfluoroalkyl Substances (PFAS) in Cosmetics: https://www.fda.gov/cosmetics/cosmetic-ingredients/and-polyfluoroalkyl-substances-pfas-cosmetics ECHA – Annex XV restriction: https://echa.europa.eu/fr/registry-of-restriction-intentions/-/dislist/details/0b0236e18663449b RIVM (2021), Mixture exposure to PFAS and relative potency factors https://www.rivm.nl/bibliotheek/rapporten/2018-0070.pdf Swedish Chemicals Agency (KEMI, 2021), PM 9/21: PFASs in Cosmetics EFSA (2020), Risk to human health related to the presence of perfluoroalkyl substances in food https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2020.6223

The role of the PIF in placing products on the market In the European Union, a cosmetic product cannot be placed on the market without a complete file known as the Product Information File (PIF) . This is a legal requirement defined by Regulation (EC) No 1223/2009 . The PIF serves as regulatory proof that your product is safe, compliant, and scientifically substantiated before commercialization. It must be kept up to date and made available to authorities in the event of an inspection. At CEHTRA, we support brands at every stage of PIF preparation and compliance (toxicological assessment, safety report drafting, labeling, etc.) to ensure a smooth and compliant market entry.   What is the PIF? The PIF is a comprehensive technical dossier containing all necessary information about a cosmetic product: product identity, formulation, safety data, scientific evidence, regulatory compliance, etc. It has been mandatory since the implementation of the EU Cosmetic Regulation. It is the reference file demonstrating that all mandatory steps required by European regulation have been carried out before placing the product on the market.   Who is it mandatory for? The PIF is mandatory for every cosmetic product placed on the European Union market. This means that each variant (size, fragrance, specific formulation) must have its own PIF. Responsibility: The Responsible Person (RP) manufacturer, importer, or designated distributor,is legally required to compile and maintain the PIF.     When must it be created? The PIF must be established before placing the cosmetic product on the market. It ensures product safety, supports product efficacy when specific claims are made, and accurately describes the product to link the dossier content with the product available on the market. What does a PIF contain?  The PIF is a structured compilation of elements required by the EU Cosmetic Regulation: a) Detailed product description Trade name and product function Cosmetic category Intended use and target population Product reference number (unique identity linking all dossier data to the product)   b) Cosmetic Product Safety Report (CPSR)  Part A: safety data (ingredients, toxicology, concentrations) Part B: final safety assessment This report must be prepared by a qualified safety assessor and constitutes the scientific core of the dossier. c) Manufacturing information  Production method Compliance with Good Manufacturing Practices (GMP) d) Test data and evidence Results supporting claims (e.g., “moisturizing”, “anti-aging”) e) Animal testing information   List of animal tests conducted by the manufacturer or suppliers on the product or its ingredients, including those performed to meet third-country requirements     Additional CPSR content, the CPSR also includes: Qualitative and quantitative composition of the formula (chemical names, INCI, CAS/EINECS/ELINCS identifiers) Role and function of each substance Stability data Microbiological data   Shelf life and availability  European regulation requires that the PIF be kept for at least 10 years after the last batch has been placed on the market. It must also be made available to competent authorities within 72 hours in case of inspection.   Relationship with CPNP notification The PIF is linked to the product notification in the Cosmetic Product Notification Portal (CPNP), the European notification platform. Information from the PIF is used to complete this notification.   Why is a well-structured PIF essential? An incomplete, insufficient, or outdated PIF can lead to: Regulatory sanctions Temporary or permanent product withdrawal Loss of market trust Customs or international market access issues At CEHTRA, our expertise helps you anticipate these risks and build a robust, scientifically sound PIF.   Best practices for drafting a PIF  To ensure compliance: Use a clear and updateable structure Rely on recognized scientific sources for safety assessments Monitor regulatory changes (e.g., new ingredient restrictions) Update the PIF whenever there is a change in formulation, claims, or labeling Get expert support in preparing your PIF and ensure full compliance of your products with European regulations.

Endocrine disruption, Margin of Safety and toxicological data gaps in cosmetic safety assessment . During our recent COSMETICK webinar on cosmetic safety assessment, held on February 19, 2026, participants raised a number of insightful questions covering toxicological data gaps, Margin of Safety calculation, endocrine disruption, and modern non-animal approaches. These questions reflect many of the challenges currently faced by safety assessors working on cosmetic ingredients and formulations. COSMETICK is a digital platform combining a toxicological database  with a cosmetic risk assessment tool , designed to support cosmetic safety assessment workflows. Endocrine disruption: what data can toxicological databases provide? During the webinar, several participants asked whether endocrine disruption data are included in COSMETICK toxicological profiles. More broadly, toxicological databases play an important role in gathering and structuring scientific data used in cosmetic safety assessment. The regulatory classification of endocrine disruptors under the CLP Regulation is still relatively recent. As of March 2026, Annex VI contains only one substance classified as an endocrine disruptor, and only for environmental effects: propylparaben. However, toxicologists do not rely solely on harmonised classifications. When assessing potential endocrine activity, they review a range of scientific sources, including international databases and screening programmes such as SVHC listings, ED-related databases and initiatives like ToxCast. When building a toxicological profile, COSMETICK therefore screens these sources to identify potential signals. If a substance does not appear in dedicated endocrine disruption lists, this absence is documented. When relevant studies are available, they are summarised and referenced. Galaxolide Toxicological reference values and warnings within COSMETICK Galaxolide identification and CLP Annex VI classification within COSMETICK Importantly, many endocrine-related studies are mechanistic or screening studies and may not follow OECD Test Guidelines. While such studies may not be sufficient on their own to demonstrate endocrine disruption, they contribute to a weight-of-evidence evaluation  combining in silico, in vitro and in vivo data. In practice, endocrine-related data are often incomplete or heterogeneous. Toxicological profiles therefore provide a screening overview , highlighting potential signals and encouraging further evaluation when needed. From toxicological data to Margin of Safety Once the toxicological profile of an ingredient has been established, the next step for the toxicologist is to identify the Point of Departure (PoD)  used in risk assessment. In most cases, this value corresponds to a NOAEL , although a BMDL may also be used when available. Safety view for a formula within COSMETICK In cosmetic safety assessment, the selected PoD should reflect the most relevant adverse effect following repeated systemic exposure . Long-term exposure is particularly important in cosmetics, as some ingredients may be present in products used daily and sometimes across multiple products. For this reason, sub-chronic studies are generally preferred  when selecting the PoD. If such data are not available, a value may be derived from shorter-term studies or from a LOAEL through the application of adjustment factors. The aim is not simply to select the lowest value reported in the literature, but rather the value that best reflects the most relevant toxicological effect. The choice of PoD is often discussed among toxicologists. Applying a consistent methodology is therefore important to ensure that risk assessments remain transparent and reproducible . Once the PoD is defined, safety is evaluated using the Margin of Safety (MOS) , calculated as the ratio between the PoD and the Systemic Exposure Dose (SED) . According to the SCCS Notes of Guidance (2023), a MOS of 100  is generally considered sufficient for cosmetic ingredients. In some cases, additional factors or specific toxicokinetic data may justify adjustments to this value. These calculations ultimately support the preparation of the Cosmetic Product Safety Report (CPSR)  required under the European Cosmetic Regulation. Addressing data gaps in cosmetic safety assessment Data gaps are a common challenge in toxicological evaluation. One reason is that suppliers of cosmetic ingredients may have limited regulatory obligations regarding toxicological studies. In Europe, compliance with the REACH Regulation is required, but some studies are only mandatory at higher annual tonnage levels, such as micronucleus tests, certain reproductive toxicity studies or carcinogenicity studies. Other endpoints are not systematically covered by REACH requirements. For example, endocrine disruption data or phototoxicity studies may be needed for specific regulatory or safety considerations but are not always available. Another frequent gap concerns the identification of no-effect levels for local effects , such as skin irritation or skin sensitization. Yet these data are often important for cosmetic safety assessment. The first step is therefore a comprehensive review of the available toxicological information. When a data gap is confirmed, alternative approaches may be considered before generating new experimental data. These approaches may include in silico models, QSAR predictions or read-across strategies , which can provide useful indications at a screening level. In toxicological profiles, such predictions may help identify whether a missing dataset is likely to represent a low concern or whether it deserves further investigation. When it’s about impurities, safe levels can be identified through the Threshold of Toxicological Concern (TTC) concept. In practice, the final evaluation relies on a weight-of-evidence approach , combining available experimental data and predictive tools. Questions that reflect evolving safety assessment practices The questions raised during the COSMETICK webinar illustrate how cosmetic safety assessment continues to evolve. Toxicologists must not only access reliable toxicological data, but also interpret these data through transparent and reproducible methodologies. Selecting the appropriate Point of Departure, calculating the Margin of Safety and addressing data gaps remain central steps in the evaluation process. In practice, safety assessors increasingly rely on a combination of structured toxicological data, weight-of-evidence approaches and predictive tools. In this context, toxicological databases play an important role by organising scientific information and facilitating its interpretation. By structuring toxicological profiles and highlighting key parameters relevant to risk assessment, such tools can support toxicologists in navigating complex datasets while maintaining a scientifically robust evaluation process. In current regulatory practice, cosmetic safety assessment increasingly relies on structured toxicological databases and digital cosmetic risk assessment tools. Tools such as COSMETICK support toxicologists by providing structured toxicological profiles and facilitating cosmetic risk assessment workflows. Author : Clarisse Bavoux

Endocrine Disruptors: A Growing Need for Rapid Access to Information The identification of endocrine disruptors (EDs) has become a key challenge for many industries. With increasing regulatory requirements and the growing number of substance lists evaluated by authorities, obtaining a clear and rapid overview of a substance’s status has become increasingly complex. For regulatory, toxicology, and R&D teams, several recurring questions arise: Is a substance suspected of having endocrine-disrupting properties? Have competent authorities already evaluated it? Where can the relevant scientific and regulatory documentation be found quickly? How should this information be interpreted with regard to one’s own regulatory obligations? To facilitate access to this information, CEHTRA has developed ED Pedia , a digital tool dedicated to the structured consultation of data related to endocrine disruptors. ED Pedia: Rapid Access to Key Information ED Pedia enables anyone working with a chemical substance to quickly obtain an initial overview of its potential endocrine-disrupting properties. In particular, the tool allows users to: Instantly check whether a substance may present endocrine-disrupting properties Directly access the relevant associated documentation Download a PDF report summarizing the results Request support from CEHTRA experts when interpretation of the data is required ED Pedia does not replace a full scientific assessment, but it provides a structured entry point to guide the analysis .   How Does ED Pedia Work? ED Pedia is based on a search using the CAS number of a substance . The tool queries several lists originating from risk assessment programs that identify substances potentially presenting endocrine-disrupting properties, with different levels of concern. For each substance searched, ED Pedia indicates: Whether the substance is included in the identified lists In which lists it appears The associated level of concern, when available Access to the corresponding documentary sources This approach provides a consolidated overview without requiring manual consultation of multiple sources . Direct Access to Documentation and an Exportable Report For each search, ED Pedia allows users to: Access relevant references and documentation Quickly consult the available information Download a summary PDF report of the results This report can serve as internal documentation  or as a basis for more detailed regulatory analysis. Interpreting the Results: The Importance of Scientific Expertise The information available in ED Pedia is derived from public lists and existing evaluation programs. The results, particularly those originating from assessments by competent authorities, must be interpreted carefully and within their scientific and regulatory context. ED Pedia provides a structured synthesis, but the final interpretation depends on: the applicable regulatory framework the intended use of the substance the level of exposure the specific requirements of the concerned sector When necessary, users may contact CEHTRA experts  to obtain scientific support in interpreting the conclusions drawn from the generated report. A Digital Tool to Save Time During the Screening Phase The objective of ED Pedia is to facilitate the initial screening phase of substances  and improve access to available information. The tool helps to: Centralize information from multiple lists Accelerate documentary research Structure the initial analysis Quickly identify substances requiring further evaluation It therefore represents a practical operational support for teams dealing with endocrine disruption challenges. A Useful Tool for Several Industrial Sectors ED Pedia can be used by any stakeholder handling or assessing chemical substances, including in: the cosmetics industry biocides industrial chemicals food contact materials consumer products It is particularly relevant for: regulatory affairs managers toxicologists R&D teams product safety managers Check the endocrine disruption potential of a substance with ED Pedia or contact our expert Julien Leghait  for any questions regarding result interpretation or for a more in-depth assessment.

Since the sartans crisis in 2018, the detection of nitrosamines has highlighted systemic gaps in identifying contamination pathways across pharmaceutical supply chains. As impurities belonging to the “cohort of concern” following ICH M7 (R2) , nitrosamines present exceptionally high carcinogenic potency. Their mechanism of action relies on metabolic activation leading to the formation of adducts. If these lesions escape cellular repair systems, they can induce irreversible genetic mutations and carcinogenesis. With a TD50 typically below 1.5 mg/kg/day, this extreme toxicity prevents the application of the standard Threshold of Toxicological Concern (TTC) of 1,500 ng/day defined in ICH M7(R2). Acceptable Intake (AI) and carcinogenic potency assessment Patient safety is ensured through the establishment of an Acceptable Intake (AI), calculated for a theoretical excess cancer risk of 1 in 100,000 over a 70-year exposure. For compounds with sufficient data, the AI is derived through linear extrapolation from the most conservative TD50 values obtained in the most sensitive species. For NDSRIs (nitrosamines related to the active substance) lacking in vivo data, the CPCA (Carcinogenic Potency Categorisation Approach) recommended by the EMA is applied. This method classifies nitrosamines into five potency categories based on structural characteristics influencing metabolic activation. Alternatively, a negative Enhanced Ames Test (EAT) can justify the application of a limit of 1,500 ng/day. Sources and formation of nitrosamines   Control of these impurities requires a rigorous strategy. Nitrosamine formation generally results from the combination of amines with nitrosating agents under acidic conditions. Identified sources include: Contaminated or degraded solvents Nitrites present in excipients Risk management strategy Risk management follows three main steps: Proactive assessment Confirmatory testing Implementation of CAPA According to ICH M7, omission of specification may be considered if levels remain consistently ≤10% of the AI. Batch-by-batch control is required when levels are between 30% and 100% of the AI. When multiple nitrosamines are present, summation strategies must ensure that cumulative risk never exceeds the 1:100,000 threshold. Mitigation options Reformulation can be an effective mitigation strategy. The addition of nitrite scavengers or pH adjustment can slow nitrosation reactions. In some cases, these modifications may benefit from simplified procedures and avoid new bioequivalence studies. CEHTRA Expertise At CEHTRA, we mobilise our toxicology expertise and QSAR tools to support partners in the qualification of these impurities. This topic was presented during our latest webinar dedicated to nitrosamines and related regulatory expectations.Follow us to stay informed about upcoming webinars and publications.

Since 12 January 2026 , the European Union has reached a major milestone in the protection of public health and water resources. The transition period provided for under Directive (EU) 2020/2184 (recast Drinking Water Directive) has now ended. From now on, the systematic and harmonised monitoring of per- and polyfluoroalkyl substances (PFAS) is a legal obligation for all Member States.    1. A dual-threshold regulatory framework    The Directive now requires compliance with two distinct limit values, reflecting complementary monitoring objectives:  → “Sum of PFAS” (0.10 μg/L)   This parameter specifically targets 20 individual substances considered of concern. Listed in Annex III of the Directive, they include 10 perfluoroalkyl carboxylic acids (PFCAs) and 10 perfluoroalkyl sulfonic acids (PFSAs), with carbon chain lengths ranging from 4 to 13 atoms. The limit value is set at 100 ng/L for the sum of these compounds.  → “PFAS Total” (0.50 μg/L)   This parameter takes a much broader approach by covering all per- and polyfluoroalkyl substances . The limit value is set at 500 ng/L . The objective is to capture the total organofluorine load, including thousands of molecules not covered by the “Sum of PFAS”.  In accordance with Article 13(7) of the Directive, and following consultations with Member States, technical guidelines (C/2024/4910) have been published to define the analytical methods applicable to these two parameters.    2. Analytical control: requirements for the “Sum of PFAS”    The assessment of compounds under the “Sum of PFAS” relies on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The EN 17892:2024 standard, used as the reference analytical method, recommends two methodological approaches:  Part A (Direct injection): a rapid method in which unfiltered drinking water samples are injected directly into the LC-MS system.  Part B (SPE enrichment): this method involves solid-phase extraction (SPE) to concentrate the sample, providing higher sensitivity and lower quantification limits.    3. The technical challenge of “PFAS Total”    The comprehensive measurement of PFAS represents a major scientific challenge, as no single method can quantify all compounds in this chemically diverse group. Three approximation methods are currently validated by the Commission:  TOP assay (Total Oxidizable Precursors)    This method uses chemical oxidation to convert PFAS precursors into measurable perfluorocarboxylic acids. However, it may lead to underestimation, as some compounds (notably perfluorinated ethers) are not fully oxidised.  EOF-CIC (Extractable Organic Fluorine)    This method measures extractable organic fluorine via combustion and ion chromatography. The result, expressed in ng/L of fluorine, is converted into PFOA-equivalent using a conversion factor of 1.45 (thus, 345 ng/L F corresponds to 500 ng/L PFAS Total).  LC-HRMS (High-resolution mass spectrometry)    This non-targeted approach enables the detection of a much broader range of compounds. However, it remains semi-quantitative and requires a high level of expertise to interpret signals and minimise false positives.    4. The critical case of trifluoroacetic acid (TFA)     TFA is an ultra-short-chain PFAS (2 carbon atoms), characterised by high mobility, persistence, and strong hydrophilicity. It enters the water cycle through the degradation of pesticides, refrigerants, or industrial discharges. In many Member States, concentrations measured in untreated water frequently exceed the 0.50 μg/L threshold, thereby surpassing the parametric value for “PFAS Total”.  To address this issue, the Commission requires a four-step reporting protocol:  Measure [PFAS Total] using an approximation method.  Measure [TFA] specifically using a targeted analytical method compliant with the Directive.  Report three values: [PFAS Total] , [TFA] , and the difference [PFAS Total] – [TFA] .  If the result is negative, the measurement is considered inconclusive.    5. Performance criteria  To ensure measurement reliability, the Directive establishes several analytical requirements at the point of compliance:  Limits of quantification (LOQ)    The overall LOQ must be ≤ 30% of the parametric value , i.e. 30 ng/L for Sum of PFAS. However, the Commission recommends an individual LOQ of ≤ 1.5 ng/L for each of the 20 substances. For “PFAS Total”, the LOQ must be ≤ 150 ng/L.  For the most toxic compounds identified by EFSA (PFHxS, PFOA, PFOS, PFNA), even lower target limits are recommended.  Measurement uncertainty    The Directive sets a maximum expanded uncertainty of 50% at the parametric value level. In practice, European laboratories generally achieve better performance, with uncertainties ranging from 18% to 39% depending on the method used.  Validation of measurements    At ultra-trace levels (ng/L), environmental and laboratory conditions become limiting factors. Member States must ensure that analytical methods used for monitoring and compliance demonstration are validated in accordance with EN ISO/IEC 17025 or an equivalent internationally recognised standard.  Current limitations    Unlike the “Sum of PFAS”, methods for measuring “PFAS Total” are not yet fully harmonised at the European level. Available data on measurement uncertainty and LOQ remain limited, making it difficult to fully assess compliance with regulatory performance criteria for this global parameter.    6. Immediate actions in case of exceedance    The entry into force of these requirements means that any non-compliance must trigger immediate corrective actions to protect public health.  Water managers, under the supervision of national authorities, must:  Inform the public transparently about risks and precautionary measures.  Shut down wells or abstraction points where PFAS levels are excessive.  Implement specific treatment processes (activated carbon, ion exchange resins, or reverse osmosis) to remove contaminants.  Restrict water use if necessary until compliance is restored.    Conclusion  The implementation of these provisions is part of the “Zero Pollution” Action Plan . The new reporting framework now requires systematic transmission of data on exceedances and incidents to the Commission.  Beyond tap-level compliance, a comprehensive approach is required, including risk assessment from the abstraction area onwards. Anticipating pollution sources, combined with mastering complex analytical protocols (particularly for PFAS Total and TFA), is essential for ensuring sustainable and secure water resource management.    Authors: Floriane DEMAILLY & Loris MISTRULLI References:   Directive (EU) 2020/2184: Directive (EU) 2020/2184 of the European Parliament and of the Council of 16 December 2020 on the quality of water intended for human consumption (recast), OJ L 435 , 23.12.2020, pp. 1–62 . Available on : http://data.europa.eu/eli/dir/2020/2184/oj  (accessed on 24/02/2026).  Commission Notice C/2024/4910: Technical guidelines regarding methods of analysis for monitoring of per- and polyfluoroalkyl substances (PFAS) in water intended for human consumption, OJ C, C/2024/4910. Available on : http://data.europa.eu/eli/C/2024/4910/oj (accessed on 24/02/2026).

The recent amendment to the European Cosmetic Regulation significantly expands the list of fragrance allergens that must be declared on the INCI label (Regulation (EU) No 2023/1545 updating certain entries of Annex III of the EU Cosmetic Regulation).  In the original version of Regulation (EC) No 1223/2009, 26 allergens were subject to mandatory labelling. Two of them ,Lyral and Lilial, have since been prohibited. The new regulation adds 57 additional substances , bringing the total number of l abelled allergens to 81 . These include individual molecules as well as botanical extracts and essential oils that may induce skin allergy. Products already on the market containing these substances must be reviewed more closely, both to ensure correct labelling and to clarify potential risks.  The intrinsic risk of skin sensitisation of a product does not automatically change. However, if a substance was not previously identified, it may now need to be considered, particularly if the product claims to be “hypoallergenic” or suitable for “sensitive skin.”  Among the newly concerned substances are widely used cosmetic ingredients such as:  Vanillin   Benzaldehyde   Lavandin oil and extracts (Lavandula Hybrida Oil)   Peppermint oil (Mentha Piperita Oil)   Labelling is required when concentrations exceed:  0.001% in leave-on products   0.01% in rinse-off products   The regulatory deadlines are clearly defined:  Products placed on the market must comply by July 31, 2026   Products already on the market must comply by July 31, 2028   This regulatory development requires companies to conduct a systematic review of fragrance compositions, supplier data, and safety documentation.  However, labelling is only one part of the regulatory obligation.  Beyond Labelling: Annex I Requires a Complete Safety Assessment   Article 10 and Annex I: Mandatory Update of the Cosmetic Product Safety Report (CPSR) Article 10 of Regulation (EC) No 1223/2009 and Annex I require a complete safety assessment based on documented toxicological profiles and the calculation of the Margin of Safety (MOS) for each ingredient. Article 10(1)(c) specifies that the Safety Report (CPSR) must be updated whenever new relevant information becomes available.  A compliant cosmetic safety assessment requires :  The use of documented toxicological profiles   Evaluation of local effects (sensitisation, irritation, phototoxicity) and systemic effects, including identification of relevant concerns (critical warnings)  Calculation of the Systemic Exposure Dose (SED)   Determination of the Margin of Safety (MOS)   Integration of conclusions into the Cosmetic Product Safety Report (CPSR)  Margin of Safety (MOS): The Central Indicator in Cosmetic Risk Assessment The Margin of Safety (MOS) is the core regulatory indicator used to demonstrate ingredient safety within the CPSR framework.  It quantitatively expresses the relationship between hazard (NOAEL or relevant point of departure POD) and actual consumer exposure.  A product may comply with labelling thresholds while still requiring an in-depth evaluation. It is important to note that the 2012 SCCS opinion focused on skin sensitisation and did not address other potential toxicological endpoints.  Regulatory compliance therefore relies on a structured demonstration of the hazard × exposure assessment , not solely on verification of labelling thresholds.  Allergens requiring labeling (underscored) are identified based on their final concentration and the type of product. A margin of safety or margin of exposure is calculated each time it is possible.   Operational Impact: Recalculation of Margins of Safety and Update of the PIF   The transition from 24 to 81 labelled allergens significantly increases operational complexity:  Verification of fragrance compositions and botanical extracts  Recalculation of cumulative concentrations  Verification of the need to add allergens to the ingredient list  Confirmation of exposure scenarios  Reassessment of risks and recalculation of Margins of Safety  Update of the safety assessment through the CPSR and the Product Information File (PIF)   Any modification in concentration or formulation may directly impact the SED and consequently the MOS.  Traceability and reproducibility of calculations therefore become essential.  Toxicological Database and Digital Cosmetic Risk Assessment Tool In this context, the use of a structured toxicological database combined with a digital cosmetic risk assessment tool facilitates:  Harmonised access to toxicological profiles  Consistent calculation of SED and Margin of Safety  Generation of documentation compliant with Annex I  Consideration of the SCCS assessment methods and other international frameworks.  July 2026: A Regulatory Trigger for Systematic Risk Reassessment Therefore, Regulation (EU) No 2023/1545 updates the list of labelled allergens under Annex III of the EU Cosmetic Regulation and requires an update of the regulatory dossier.  The July 2026 deadline should be considered a regulatory trigger to:  To re-examine fragrance compositions and botanical extracts with regard to labelling requirements  To verify the Margins of Safety and confirm warnings or the absence of risk, and to update the CPSR accordingly The expansion of allergen labelling aims to enhance transparency.  However, consumer protection ultimately depends on the robustness of the cosmetic risk assessment and the scientific justification of safety through the Margin of Safety .  In regulatory practice, compliance does not merely consist of updating the INCI list.  It requires a continuously documented, traceable and scientifically substantiated assessment framework. These updates are therefore not simply an administrative revision of the ingredient list; they require regulatory and scientific expertise which, at least for Part B of the CPSR — covering the safety assessment — must be validated by a qualified safety assessor (toxicologist, pharmacist, etc.), as defined in Article 10 of the EU Cosmetic Regulation.  Would you like to ensure the safe assessment of allergens in your cosmetic formulas? Our experts can assist you in identifying allergens, conducting toxicological assessments, and ensuring your products comply with European and international requirements. To learn more about COSMETICK and our approach to cosmetic risk assessment, please contact: Clarisse Bavoux : Toxicologist, Deputy Chief Executive Officer in charge of digital solutions Florian Gautier : Cosmetics Market Leader References : Commission Regulation (EU) 2023/1545 of 26 July 2023 amending Regulation (EC) No 1223/2009 of the European Parliament and of the Council as regards labelling of fragrance allergens in cosmetic products  https://eur-lex.europa.eu/eli/reg/2023/1545/oj/eng   Regulation (EU) (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products https://eur-lex.europa.eu/eli/reg/2009/1223/oj/eng   Scientific Committee on Consumer Safety SCCS, Opinion on Fragrance allergens in cosmetic products. SCCS/1459/11. 27 June 2012 https://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_102.pdf    To comment on LinkedIn : https://www.linkedin.com/feed/update/urn:li:activity:7427743381092544512/

In December 2025, the European Commission published a targeted legislative proposal under its Food and Feed Safety Simplification Omnibus . One of its most relevant elements for the biocides sector is a proposed amendment to Regulation (EU) No 528/2012 (the Biocidal Products Regulation, or BPR), extending certain data protection periods for active substances still undergoing review. This initiative responds to long-standing concerns raised by industry and Member State authorities and has direct implications for companies supporting active substances, data owners, alternative suppliers, and product authorisation applicants. Background: Why This Amendment Was Needed Under the BPR, approval of biocidal active substances requires extensive scientific data demonstrating safety for human health, animal health, and the environment. These data packages are costly to generate and are therefore protected for a defined period to allow data owners to recover their investment. Article 95(5) of the BPR currently provides that data protection for certain existing active substance/product-type combinations expires on 31 December 2025 , regardless of whether the regulatory review has been completed. This “hard stop” was originally intended to balance fair compensation for data owners with increased market access and competition over time. However, the EU review programme for existing biocidal active substances, initiated more than two decades ago, has experienced significant and repeated delays. Completion is now scheduled for 31 December 2030 . Key drivers of these delays include limited resources in Member State authorities, evolving technical guidance, and, critically, the introduction of new scientific criteria for identifying endocrine-disrupting properties in 2018. These criteria triggered the need for additional, often expensive, studies well after original data submissions. As a result, many companies were required to generate new data without the prospect of adequate protection if the original 2025 cut-off remained unchanged. What the Commission Is Proposing The proposal seeks to realign data protection rules with the reality of the extended review programme. In practical terms, it would: Extend data protection until 31 December 2030 for all active substance/product-type combinations that were still under review on 7 June 2018 . Apply the extension to all data within the relevant dossiers , without distinguishing between older and newly generated studies, ensuring administrative simplicity and legal clarity. Introduce a derogation allowing protection to be reinstated even if it temporarily lapsed after 1 January 2026. Allow data owners to claim compensation  from substance or product suppliers that benefited from the absence of protection during the interim period. This results in a maximum protection period of approximately 11–12 years for data generated since 2018, broadly consistent with the standard data protection framework under the BPR. Balancing Innovation and Competition Stakeholder feedback highlighted diverging perspectives. Data owners and industry associations warned that allowing protection to expire amid regulatory delays would create free-rider risks, discourage investment in new studies (including vertebrate testing), and undermine supply security. Some Member State authorities supported extending protection at least for endocrine disruptor-related data. Conversely, alternative suppliers and SME representatives cautioned that prolonged protection could limit competition, increase costs, and complicate data-sharing negotiations. The Commission’s proposal reflects a compromise: it preserves incentives for data generation and regulatory compliance while maintaining the original objective of Article 95(5) to avoid disproportionate or perpetual exclusivity. What This Means for Companies For companies active in the biocides sector, the proposal provides: Greater legal certainty  for data owners who have invested in additional studies during a delayed review process. Continued relevance of letters of access and compensation negotiations  beyond 2025. Reduced risk of immediate, uncompensated data reuse by competitors. A clearer regulatory framework pending the broader evaluation of the BPR announced for 2026–2027. Next Steps The proposal will now be examined by the European Parliament and the Council under the legislative procedure. Until it enters into force, companies should carefully assess their data protection strategies, Article 95 positioning, and contractual arrangements. We will continue to monitor legislative developments closely and provide updates on timelines, implementation details, and strategic implications for substance suppliers and product authorisation holders. If you would like to discuss how this proposal may affect your portfolio or data protection strategy, please contact our regulatory team. Author: Barbara DHOOP Reference: Simplification Omnibus Package Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Regulation (EU) No 528/2012 as regards the extension of certain data protection periods: https://food.ec.europa.eu/document/download/d8c35be0-ecc9-432b-a645-fd363681f5d3_en?filename=horiz_omnibus_reg_com-2025-1020-1-p1.pdf

ABIM 2025: a key event for European biocontrol The Annual Biocontrol Industry Meeting (ABIM) was held in Basel (Switzerland) from 20 to 22 October 2025, bringing together more than 2,000 international participants, including industrial stakeholders, scientific institutes, authorities, professional associations and consulting companies. Co-organised by the Research Institute of Organic Agriculture (FiBL) and the International Biocontrol Manufacturers Association (IBMA), ABIM has become the leading European forum dedicated to biocontrol products, biostimulants and regulatory innovations related to natural substances. The role of IBMA IBMA brings together biocontrol manufacturers and advocates for key regulatory developments to: accelerate the evaluation of alternatives to conventional products; introduce new definitions and regulatory requirements; integrate emerging technologies; strengthen the training of competent authorities. Biocontrol, biostimulants, natural substances: clarifying the concepts To support a rapidly growing sector, it is essential to clearly distinguish between regulatory categories. What is biocontrol? Biocontrol products fall under Regulation (EU) No 1107/2009 on plant protection products. They encompass several families: Microorganisms: bacteria, fungi, viruses, etc. Macro-organisms: insects, mites, nematodes used as biological control agents. Natural substances: of plant, animal or mineral origin. Semiochemicals: including pheromones and inter-species communication substances (e.g. allomones). Their mode of action is generally targeted, non-toxic and compatible with objectives to reduce the use of conventional pesticides. What are biostimulants? Biostimulants are regulated at EU level under Regulation (EU) 2019/1009 on fertilising products , or under national regulations. They do not act against pests or pathogens , but instead improve plant resilience to abiotic stresses (water stress, heat, salinity, cold, etc.) and optimise nutrient use efficiency. Two main categories exist: Microbial biostimulants Non-microbial biostimulants What are natural substances used for plant health? These are components derived from nature, including: Animal origin: sheep fat, fish oil, etc. Mineral origin: talc, sulphur, copper, clay, etc. Plant origin : algae, rapeseed, sunflower, orange, etc. New technologies , such as proteins and peptides . Products usable in organic farming: what does the regulation say? Organic production is governed by Regulation (EU) 2018/848, which defines: authorised agricultural practices; categories of natural substances that may be used, including fertilisers, biostimulants and plant protection products. A two-step authorisation process For a plant protection product to be usable in organic farming, the following steps must be completed: Approval of the active substance at EU level → Regulation (EU) No 1107/2009 → Inclusion in the list under Regulation (EU) 2021/1165 Authorisation of the product at national level → Regulation (EU) No 1107/2009 → Certification under organic labels (AB, Bio Suisse, EU Organic, etc.) Key trends observed at ABIM 2025 Regulatory acceleration Discussions highlighted: simplification of dossiers for natural and low-risk substances; modernisation of the regulatory framework; the urgent need to reduce evaluation timelines. Artificial intelligence and biocontrol Several presentations explored the role of AI in: toxicological modelling; digital risk prediction tools; optimisation of formulation strategies. Technical workshops Three major topics attracted particular interest: Semiochemicals: application methods and analytical challenges; Natural substances: classification, safety and identification; Proteins and peptides: emerging approaches in biocontrol. CEHTRA’s participation: expertise, visibility and new opportunities CEHTRA within IBMA CEHTRA acts as an associate member for natural substances and semiochemicals, actively contributing to proposals aimed at improving the regulatory framework, based on extensive field experience. CEHTRA at ABIM 2025 This year, CEHTRA was represented by Steffie Segelle, Raquel Gonzalez de la Huebra and Estelle Beltran, with: a dedicated booth; three scientific posters: endocrine disruption (ED) screening for biocontrol substances (including the Simply Predict offering); comparison between REACH and the Fertilising Products Regulation; comparison between low-risk substances and basic substances. These posters highlighted CEHTRA’s internal expertise in toxicology, regulatory assessment, natural substances, predictive AI and EU compliance. Meetings and outlook Meetings with biocontrol clients across the sector. New collaboration prospects in the areas of: biostimulants; endocrine disruptor screening; training programmes. Presence of major consulting firms and CROs, making ABIM a key moment to track market trends. Why is biocontrol accelerating? The CEHTRA perspective Regulatory developments, pressure to reduce conventional pesticide use and growing interest in natural solutions are creating a favourable environment for innovation. CEHTRA supports this transition by providing: comprehensive regulatory support; optimised dossier strategies; advanced digital solutions (CEHTRAWATCH, Simply Predict); dedicated training programmes. Conclusion: ABIM 2025 confirms the central role of biocontrol in European agriculture ABIM 2025 highlighted a fast-evolving sector, driven by: rapid scientific innovation; complex regulatory requirements; an increasing need for specialised support. Thanks to its recognised expertise, CEHTRA continues to play a key role in guiding biocontrol, biostimulant and natural substance manufacturers through a rapidly changing regulatory landscape. Are you developing a biocontrol product, a natural substance or a biostimulant?

Safety of cosmetic ingredients: a legal and ethical requirement The use of any new cosmetic ingredient must be safe. That is a legal obligation according to Article 3 of the European Cosmetic Regulation and in other cosmetic-related laws and standards throughout the world, but also a moral one, as it would be unethical to place on the market a substance that is toxic, or whose toxicity is unknown and for which safe exposure cannot be demonstrated. Cosmetic safety assessment without animal testing In Europe first, since 2009 -and in more parts of the world each year- animal testing is no longer authorised to demonstrate the safe use of cosmetic ingredients. Many toxicological endpoints must be assessed to demonstrate the safe use of an ingredient: some of them have been assessed in vitro for decades, like mutagenicity, for which the Ames test was first described in the 1970s.Others have been greatly improved in vitro since the enforcement of the European Cosmetics Regulation, such as skin sensitization, for which dozens of in vitro and in chemico models have been proposed since 2009, and several now have an OECD-dedicated guideline (DPRA, U-SENS, GARDskin assay, etc.). The challenge of systemic toxicity endpoints But some endpoints are complex to summarize into a simple in vitro assay, like those related to systemic toxicity (i.e. toxicity that impacts organs not directly exposed to substance, like internal organs). Systemic toxicity includes general toxicity, which can affect organs; carcinogenicity, the induction of cancer by chemicals; and developmental and reproductive toxicity (DART), i.e. toxicity that impact reproductive function or toxicity to the developing foetus. The latter is particularly complex to study, because embryonic and foetal developmental is a long process, starting with a single cell and evolving into a million-cell organism, and it includes many intermediate steps with different sensitivities to chemicals at various doses. The AOP concept Therefore, to simplify DART assessment, the first step consists in identifying a Molecular Initiating Event (MIE), i.e. how a chemical may interact with cellular receptors or enzymes. An MIE leads to a Key Event (KE): a change induced by this chemical interaction between the target and the xenobiotic (i.e. the studied chemical substance -from the Greek "ξένος", xenos, "foreign"). A Key Event then leads to an Adverse Outcome (AO), i.e. a "visible" effect, such as a malformation or reduced fertility in the context of DART. The combination of an MIE, KE, and AO defines an Adverse Outcome Pathway (AOP). Integrated Testing Strategies (ITS) Hence, assays that target a specific AOP may be developed, making DART testing easier to transpose in vitro using simplified models. On the other hand, that also means that several assays, screening several AOPs, are needed to get an overview of the adverse potential of a xenobiotic. Moreover, as any assay always has pitfalls and limitations, combining them reduces the risk of inconclusive results. That is the solution proposed by Burbank et al (2023), which consists in an integrated testing strategy, based on a set of three assays that each show satisfactory predictive capacity, but perform even better when combined, in what is called a "2 out of 3" approach: two tests leading to the same conclusion (positive or negative) determine the overall outcome for the tested substance. The third test is performed if the first two do not show the same conclusion, or to confirm the existing result. If such an ITS leads to a positive conclusion (i.e. that the substance may induce developmental adverse effects), further investigations can subsequently be performed to assess the potential risk, such as PBPK modelling to refine exposure assessment or additional tests to better understand the substance's mode of action. In vitro assays targeting specific AOP steps Several in vitro tests exist, most of them focusing on one specific step of one AOP, like the ER and AR transactivation tests, which evaluate the binding of test substances with Estrogen and Androgen Receptor. This is a typical example of MIE/KE-based assay: the test substance interacts with receptors, and this interaction is directly observed via the expression of genes associated with these receptors (the luciferase gene in most case). Other assays such as those developed by ReproTracker focus on Adverse Outcomes: in a nutshell, morphological changes of exposed cells are observed, and abnormal changes are concluded as positive for teratogenicity potential. However, the main results of ReproTracker assays are the measurement of molecular biomarkers related to cells differentiation. So the main step is the identification of key event, adverse outcome observation is a secondary result. In silico approaches and computational prediction Tests based neither on animal nor in vitro also exist: they are in silico methods, based on computational models. The OECD QSAR Toolbox provide different, free models either based on structure-activity relationship, predicting the effect of a chemical based on its chemical formula and design, or based on its analogy with other known chemicals. These expert models provide various predictivity and are often better at detecting toxic chemicals than detecting non-toxic chemicals, as more data exist, more articles are published, about the toxicity of chemicals than about their non-toxicity ! The development of artificial intelligence and neural networks make those models always more predictive (e.g. Lee et al, 2025), but we can expect a 'glass ceiling', as the predictivity of such models is based on accumulated in vivo data, which will not be infinite. At CEHTRA, our scientific approach builds on these advanced silico methods to develop a robust toxicological profile for each ingredient in our Cosmetick database: toxicological profiling by our toxicologists includes a routine screening with such QSAR tools to provide the highest level of knowledge on each substance. These tests were developed to address the great complexity of embryo and foetus development. To a certain extent though, some assays can still be performed on whole organisms: indeed, the use of animal embryos is still authorised, even in the EU, for the safety assessment of cosmetic ingredients. European directive 2010/63, on the protection of animals used for scientific purposes, applies to "live non-human vertebrate animals, including independently feeding larval forms" and is the legal basis to define "animal testing", even though it is not referenced in the European Cosmetics Regulation. Therefore, it is generally considered that tests performed on embryos, are acceptable for cosmetic ingredient assessment. Moreover, these models have the advantage to be based on complete organisms, authorizing the direct observation of malformations, combined with controlled exposure conditions and great knowledge of the models, as some vertebrate species embryos (e.g. zebrafish), have been reference models in embryology for decades. Ethical issues and possible future regulatory changes However, some groups, associations, NGOs, and governments have raised ethical concerns on this use of animal embryo models, and an update of European regulations might soon forbid the use of such models, and any animal-based ones (vertebrate or not) for cosmetic testings. Until then, assays such as the Zebrasfish Embryotoxicity Test or even the Frog Embryo Teratogenicity assay on Xenopus are authorised and provide quite predictive results regarding teratogenicity assessment (e.g. Leconte & Mouche, 2013). Conclusion In conclusion, a significant number of tests are now available to assess some of DART endpoints. A specific set of these performed under appropriate conditions can produce good predictive results. Like many tests, however, most of these results are hazard-based, i.e. they provide a qualitative response (positive or negative), and not a quantitative one that can support the establishment of a reference value. Whether you need assistance in monitoring such assays, performing in silico analyses with our experts from Simply Predict , or designing an assessment strategy, do not hesitate to reach out to Cehtra for DART-related topics! Author : Florian Gautier References: Burbank et al, 2025. New Approach Methodologies for evaluating Developmental And Reproductive Toxicity potential: review on state of the art, applicability for cosmetic related ingredients and coverage of developmental stages. NAM Journal 1. 100055 Leconte & Mouche, 2013. Frog embryo teratogenesis assay on Xenopus and predictivity compared with in vivo mammalian studies. Methods Mol Biol 947:403-421 Lee et al, 2025. Recent advances in AI-based toxicity prediction for drug discovery. F ront Chem . 13:1632046

On 26 November 2025 , the European Parliament and the Council adopted Regulation (EU) 2025/2509 , a major update that repeals Directive 2009/48/EC  to raise toy safety standards  across the European Union. The regulation defines a toy  as any product designed for play by children under 14 , even if that function is not exclusive. Children  are a particularly vulnerable group, and ensuring their protection from physical and chemical risks  is crucial. This regulation aims not only to safeguard young consumers but also to harmonize toy safety rules across EU Member States , including the online marketplace . Chemical Safety of Toys: Ban on Harmful Substances One of the major advances of this regulation concerns chemical safety. Generic bans now apply to the most dangerous substances: carcinogenic, mutagenic, or toxic for reproduction (CMR) substances, as well as endocrine disruptors and respiratory and skin sensitizers. The regulation also introduces: A strict ban on the intentional use of PFAS (per- and polyfluoroalkyl substances) and certain bisphenols, to protect the developing hormonal system of young children. A list of substances subject to specific limit values , such as heavy metals, nitrosamines, and allergenic fragrance substances. The European Chemicals Agency (ECHA) plays a central role in assessing these risks and managing potential exemptions, which are only granted if no safe alternative exists. Responsibilities of Manufacturers, Importers, and Distributors under EU Toy Safety Regulation 2025/2509 The regulation clarifies the obligations of each operator: Manufacturer Responsibilities Conduct a full safety assessment Prepare technical documentation Create a digital passport containing compliance and safety information Importer Responsibilities Ensure the manufacturer has fulfilled their obligations before placing the product on the EU market Responsibilities of Distributors and Online Marketplace Providers Act diligently and ensure safety warnings are clearly visible, even during remote purchases Immediately inform authorities via the Safety Business Gateway portal and take corrective actions, such as withdrawing or recalling the toy, in case of a dangerous product Safety Gate Alerts 2025: Chemical Hazards in Toys As an example in 2025: 326 chemical alerts were recorded on 261 toys , concerning hazardous chemical substances now mostly covered by the new Regulation. Methodologies for Assessing Children’s Exposure to Chemicals in Toys Methodologies for assessing children’s chemical exposure have evolved over the years: Timeline of Methodologies 2002:  Information sheet on children’s toys – Assessing consumer risks (RIVM report 612810012/2002) 2008:  Chemicals in toys – General methodology for assessing chemical safety of toys – Focus on elements (RIVM report 320003001/2008) 2003-2024:  European Commission guidance on toy safety to help supply chain actors comply with the Directive 2016:  ANSES study on children under 3 years using plastic toys 2024:  OECD study on methodologies for estimating children’s exposure to toys These publications gradually build a solid methodological framework for risk assessment, particularly regarding chemical safety. CEHTRA aligns with this approach: these methodologies structure our evaluations, and we support actors in transforming these references into product compliance evidence. CEHTRA: Your Partner for Securing Toy Safety Regulation (EU) 2025/2509 represents a major step forward for toy safety in Europe, strengthening the protection of children and clarifying the responsibilities of all supply chain actors. Faced with these new requirements, it is essential to rely on solid regulatory expertise to ensure product compliance and protect young consumers. At CEHTRA, we support manufacturers, importers, and distributors in risk assessment, technical documentation, and regulatory compliance. Discover our solutions and approach on our Expertise page, and contact us via our contact form to discuss your projects and secure your toys today. Author : Anna Chelle ,  Product Safety Specialist Sources and Regulatory References: Regulation (EU) 2025/2509 (Toy Safety Directive): https://eur-lex.europa.eu/legal-content/FR/ALL/?uri=CELEX:32025R2509 Toy safety guidelines: https://single-market-economy.ec.europa.eu/sectors/toys/toy-safety/guidance_en Safety Gate Alerts: https://ec.europa.eu/safety-gate-alerts/screen/search?resetSearch=true

COSMETICK is a toxicological and ecotoxicological profile database, combined with a digital cosmetic risk assessment tool. It is designed to support toxicologists and safety assessors in the preparation of Cosmetic Product Safety Reports (CPSR), as well as in the safety assessment of ingredients, impurities, raw materials and fragrance compounds or fragrance concentrates.  COSMETICK enables the structuring, documentation and use of reliable toxicological data, and their direct application in cosmetic risk assessments compliant with European and international regulatory requirements.  COSMETICK: a database, a risk assessment tool… or both?  Having access to a structured toxicological profile database has become essential for the organisation of any safety assessor’s work. To meet the needs of CEHTRA’s own safety assessors, toxicological profiles were originally structured and written to be directly used in safety assessments. In parallel, and because risk assessment is a core requirement for safety assessors, COSMETICK was designed with CEHTRA toxicologists as a digital tool supporting cosmetic risk assessment for finished products and raw materials .    COSMETICK in numbers: a structured toxicological knowledge base  As of the end of December 2025, the COSMETICK database included:  toxicological profiles for 3,400 ingredients,  800 impurities,  500 fragrance substances,  and 1,900 ecotoxicological profiles.  The 3,400 raw materials included are either documented by CEHTRA for its users or entered directly and confidentially by the users themselves.  Each toxicological profile results from a rigorous and standardised process involving data collection, selection of relevant studies, and synthesis of results for all endpoints required for cosmetic risk assessment. Results are described for nine toxicological endpoints : skin and eye irritation, skin sensitisation, phototoxicity, acute toxicity, sub-chronic or chronic toxicity, reproductive toxicity, endocrine disruption, and carcinogenicity. Dermal and oral absorption data are also documented. Data gaps are clearly identified and visualised through colour-coded icons.  The data are derived from numerous recognised scientific sources (SCCS, CIR, ECHA opinions, EFSA, US EPA, etc.), as well as from peer-reviewed scientific literature and in silico approaches . All sources are precisely referenced.  Ecotoxicity is documented in accordance with REACH and CLP/GHS requirements , including PBT/vPvB assessment . It covers biodegradability (OECD, BIOWIN), bioaccumulation (BCF, log Kow), and acute and chronic aquatic toxicity (algae, daphnia, fish), complemented by recognised QSAR models (ECOSAR). The analysis follows a weight-of-evidence approach integrating measured data and literature.  Profiles are continuously updated based on several criteria:  regulatory and toxicological developments,  human health concerns identified during user safety assessments,  and frequency of profile use.  Successive versions are retained for each profile, with documented comparisons between versions, ensuring traceability of updates and methodological consistency . For risk assessment purposes, cosmetic product types and exposure scenarios can be selected from predefined categories in line with standard safety assessment practices.    Developed by toxicologists, used in production at CEHTRA   COSMETICK was initially developed as an internal tool at CEHTRA for the preparation of Cosmetic Product Safety Reports from 2018 onwards. Designed by and for toxicologists , it was made available online in 2021 under a licensing model:  COSMETICK BASIC , providing access to the toxicological profile database,  COSMETICK ADVANCED , providing full access to the database and to cosmetic risk assessment functionalities.  The coexistence of the internal CEHTRA tool and the online user version ensures that users benefit from all improvements identified by CEHTRA toxicologists for their own daily practice. These improvements stem from practical needs (export formats, colour-coded user-friendly displays, formula duplication) as well as methodological developments (reverse calculation for raw materials, QRA2, results by IFRA categories). As a result, users can be confident that their cosmetic risk assessments incorporate the most up-to-date scientific and methodological approaches that digital automation can support. Data personalisation further ensures that each assessment remains specific to the company’s choices and practices.    What does a toxicological profile look like in COSMETICK?  A toxicological profile in COSMETICK includes full substance identification (INCI name, synonyms, CAS number), relevant toxicological data, toxicological reference values , colour-coded warnings , and a structured scientific summary.  For each endpoint, the profile summarises study results, identifies critical effects, and provides the toxicological reference values used for risk characterisation: LOAEL, NOAEL, NESIL, and non-effect, irritant or sensitising concentrations . The selected Point of Departure (PoD) is justified. Missing data are explicitly identified to help the safety assessor define appropriate follow-up actions.    Warnings and signals of concern  Colour-coded warnings allow rapid visualisation of critical toxicological concerns and data gaps. They provide a key decision-support tool, enabling the safety assessor to quickly identify potential issues related to a substance, raw material or formulation before assessing the actual risk based on concentration and intended use. Ecotoxicological profiles are also ranked according to increasing levels of concern.    Example: a preservative  Phenoxyethanol (CAS No. 122-99-6) is authorised as a cosmetic preservative under the European Cosmetic Regulation, up to a maximum concentration of 1% . Based on CEHTRA’s experience over the past four years, it is the most frequently used preservative .  Phenoxyethanol has a broad antimicrobial spectrum, effective against Gram-negative bacteria (e.g. Pseudomonas aeruginosa ), Gram-positive bacteria ( Staphylococcus aureus ), and yeasts ( Candida albicans ). Its activity is attributed to inhibition of microbial DNA/RNA synthesis and increased cell membrane permeability.  In 2016, the SCCS evaluated systemic effects and concluded that phenoxyethanol is not classified as reprotoxic and is only a rare skin sensitiser , considering it one of the best-tolerated preservatives. Systemic toxic effects were observed only at oral or dermal exposures approximately 200-fold higher than consumer exposure levels from cosmetics. Consequently, the SCCS concluded that phenoxyethanol is safe for all consumers, including children of all ages, when used up to 1%.  Although its irritant properties are well established, it remains well tolerated at authorised levels, without inducing skin irritation or sensitisation. Some rare discomfort reactions (stinging, tightness) may occur, particularly in cases of co-exposure with other irritants. This illustrates the importance of the safety assessor’s expertise, which goes beyond bibliographic data to evaluate safety under realistic conditions of use, such as daily facial application. While such discomfort does not represent a major health risk, it is typically undesirable for both consumers and brands.  Phenoxyethanol is classified as STOT SE 3 (H335: May cause respiratory irritation) under CLP Regulation No. 1272/2008. Very rare cases of allergy have been reported and must be assessed case-by-case depending on population, skin type and product type.  The substance is neither phototoxic nor genotoxic and shows low acute toxicity. Systemic toxicity is characterised by a sub-chronic study identifying a NOAEL of 500 mg/kg bw/day (357 mg/kg bw/day for daily administration), which adequately protects against reproductive effects observed at higher doses (SCCS, 2016; Api et al., 2025).  Available receptor binding studies do not suggest endocrine activity. Nevertheless, attention remains warranted pending conclusions from ECHA, which included phenoxyethanol in its Endocrine Disruptor Assessment programme under the Biocidal Products Regulation (assessment ongoing as of 21 August 2025).    From ingredient to finished product: risk assessment in practice  Example 1: cosmetic product with a risk of skin sensitization   The product assessed is a facial sunscreen used daily. It contains the colourant CI 77288. Several cases of allergy have been reported in the literature for various chromium(III) oxides, as highlighted by CORAP in 2022. In the absence of specific skin sensitisation characterisation, and particularly of quantitative data, the risk of sensitisation at 0.1% cannot be excluded. The risk is considered likely, leading to an unfavourable safety conclusion.  Example 2: cosmetic product with insufficient MOS  In a product intended for infants, caprylyl glycol is used at 0.5%. The associated Margin of Safety is insufficient, indicating a probable risk of systemic toxicity. The NOAEL is derived from a sub-chronic OECD 408 study. At higher doses, developmental effects may occur and are currently under regulatory scrutiny, potentially leading to harmonised reprotoxic classification (ECHA ARN on 1,2-ethanediols and their carbonates, 2021). Thus, although the Margin of Safety based on a robust toxicological reference value is insufficient, additional concerns are flagged by the “Reprotoxicity” and “Irritation” warnings . At the assessed concentration, irritation is not expected, and lower exposure levels would be considered safe and can be readily calculated.    COSMETICK and international regulatory requirements  COSMETICK toxicological profiles are prepared in accordance with Annex I of the European Cosmetic Regulation (EC) No. 1223/2009 and SCCS recommendations for CPSR preparation. This methodology reflects principles widely recognised at the international level. For example, China’s CSAR regulation requires documented safety justification based on comprehensive toxicological profiles covering all relevant endpoints. Similarly, the US Modernization of Cosmetics Regulation Act (MoCRA) requires safety substantiation based on reliable and relevant toxicological data for each ingredient. COSMETICK fully aligns with this international approach to cosmetic risk assessment .    Licences and access to COSMETICK   R&D and toxicology teams may limit their needs to consultation of toxicological profiles, available through COSMETICK BASIC . More comprehensive needs — including finished product risk assessment, raw material use evaluation or fragrance concentrate assessment — are addressed through COSMETICK ADVANCED .  Confidential raw materials can be integrated, and users may also include their own toxicological data to personalise reference values.    References  SCCS, Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation , 12th revision  Regulation (EC) No 1223/2009  China Cosmetic Supervision and Administration Regulation (CSAR), NMPA  US FDA – Modernization of Cosmetics Regulation Act of 2022 (MoCRA)     COSMETICK: an established reference for digital cosmetic risk assessment   COSMETICK is a reference digital tool for cosmetic risk assessment, combining a structured toxicological and ecotoxicological database, a robust scientific methodology and decision-support functionalities. It is designed to sustainably support toxicologists, safety assessors and R&D teams in an ever-evolving regulatory landscape.  Discover how COSMETICK integrates with the regulatory requirements of the cosmetics market. Contact our toxicology experts to discuss your cosmetic risk assessment needs. Author: Clarisse BAVOUX

In 2025, CEHTRA continued its mission to support industrial companies, institutions and regulated stakeholders in a context marked by increasing regulatory complexity and growing challenges related to the protection of human health and the environment. This year was a structuring one for the group, with the launch of new digital tools, the evolution of long-standing services, the strengthening of our expertise and the development of strategic collaborations. CEHTRAWATCH: a global, expert regulatory monitoring platform One of the key highlights of 2025 was the launch of CEHTRAWATCH, a digital solution dedicated to international regulatory monitoring. CEHTRAWATCH enables users to: scan, track and receive alerts on more than 100 regulatory and toxicological lists, cover over 40 countries, receive personalised alerts based on substances or topics of interest, benefit from continuous updates validated by CEHTRA experts. Designed as a decision-support tool, CEHTRAWATCH helps companies save time, anticipate regulatory risks and work with reliable, structured information, while maintaining access to human expertise. RASafe: from Industrial Hygiene to a global Risk Assessment approach Historically focused on supporting chemical industry players through its Industrial Hygiene activity, CEHTRA evolved this offering in 2025 into a transversal service: Risk Assessment & Safety (RASafe). This transformation is based on a clear observation: chemical risk assessment , and particularly exposure assessment , remains a frequently underestimated pillar of regulatory compliance processes. A structured approach built on three complementary pillars RASafe is now organised around three core areas: Toxicological assessment: Hazard identification, data analysis and derivation of relevant reference values. Exposure modelling and estimation: Assessment of occupational and consumer exposure using recognised methodologies and tools. Regulatory support and training: Audits, preparation of technical documents (CSR, SDS…), and training on risk assessment tools and regulatory compliance, particularly under REACH. A transversal mission Through RASafe, CEHTRA supports industrial companies, public bodies and consultants in better understanding, assessing and managing chemical risks, with a central objective: protecting human health and the environment.   CEHTRA blog and webinars: making regulation more accessible The year 2025 also marked the launch of the CEHTRA blog, designed as a space for sharing knowledge and educational resources. Each week, new articles are published to: decode regulatory news, explain key texts and obligations, help stakeholders navigate the regulatory landscape. In parallel, several webinars were organised to provide practical insights into current regulatory topics and to encourage direct exchanges with our experts.   Acquisition of Prosacon: strengthening and expanding group expertise In 2025, CEHTRA continued its development with the acquisition of Prosacon, expanding the group’s scope of expertise and strengthening its ability to address increasingly transversal regulatory challenges. This acquisition is part of a strategy of controlled growth, aligned with the concrete needs of our clients.   Flex+: agile outsourcing of expert resources The launch of Flex+ responds to a need identified in the field: enabling companies to quickly outsource expert resources, while ensuring high-quality deliverables and regulatory compliance. Flex+ offers a flexible approach, adapted to operational constraints and regulatory challenges faced by organisations.   together Alliance: collectively addressing ethanol-related challenges in biocides In response to complex regulatory issues related to ethanol in biocidal products, CEHTRA launched the Together Alliance in 2025. This initiative is based on the belief that certain regulatory challenges require a collaborative approach, encouraging knowledge sharing and the development of joint solutions.   Digital and artificial intelligence: supporting human expertise During the CEHTRA 2025 General Meeting, all group entities came together to work on issues related to digital transformation and artificial intelligence. The objective is clear: to explore how digital tools and AI can support experts’ daily work, improve process efficiency and enhance the quality of support provided — without ever replacing human expertise. 2025: a structuring year in support of regulatory compliance The year 2025 was marked by the commitment of our teams, the trust of our clients and close collaboration with our partners.Each project carried out this year helped strengthen our ability to support regulated stakeholders facing ever-higher requirements in terms of regulatory compliance, chemical risk management and regulatory monitoring. CEHTRA enters 2026 with the same ambition: to offer useful tools, rigorous expertise and operational support, closely aligned with real-world challenges.

Understanding the regulatory and industrial challenges associated with this substance subject to authorisation Introduction Ethylenediamine (EDA, CAS 107-15-3) is a chemical compound widely used as an intermediate in many industrial processes, such as chemical synthesis, resin manufacturing, chelating agents, and additives for lubricating oils. However, due to its hazardous properties, in particular its classification as a respiratory and skin sensitiser, EDA has been identified as a Substance of Very High Concern (SVHC). At this stage, it is included in the 11th Recommendation List for a possible inclusion in Annex XIV of the REACH Regulation. As a reminder, intermediate uses are exempt from REACH authorisation. A future inclusion in Annex XIV would therefore apply only to non-intermediate uses. This overview aims to explain why EDA is concerned by the REACH authorisation process, which stakeholders could be impacted, and how CEHTRA supports its clients throughout this strategic process. Why is Ethylenediamine subject to authorisation? EDA presents several critical hazards, in particular: Respiratory sensitisation (Skin Sens. 1, Resp. Sens. 1), with a high risk of severe allergic reactions, even at low exposure levels. These properties led to its identification as a Substance of Very High Concern (SVHC). When a substance is included in Annex XIV of REACH, its use becomes prohibited after a sunset date, unless an authorisation is granted for a specific use. The objectives of REACH authorisation applied to EDA are to: control health risks linked to exposure, particularly in occupational settings, encourage companies to identify safer alternatives, allow only those uses for which no technically or economically viable alternative is available. Who is concerned? The following stakeholders would be directly concerned by authorisation: Industrial users of EDA for non-intermediate uses, in particular: formulation of resins, adhesives, coatings or inks, manufacture of finished products containing EDA, certain applications in lubricants, additives or treatment products, Importers placing this substance on the market for a specific use. Companies along the value chain when they rely on a product containing EDA. As for any Annex XIV substance, authorisation is linked to the use, not to the substance itself. A company may be authorised for one use, but not for another. When should an authorisation be requested? To date, Ethylenediamine (EDA) has not yet been formally included in Annex XIV of REACH. It is currently listed in the 11th Recommendation List, meaning that a future inclusion is being considered, potentially by 2026. As a result, the key regulatory dates, namely the Latest Application Date (LAD) and the Sunset Date, are not yet defined. They will only be set once a potential inclusion in Annex XIV is confirmed. Once these dates are published, the application must be submitted before the Latest Application Date (LAD). Submitting the application before the LAD would then allow: continued use of EDA after the Sunset Date, while the ECHA and the European Commission finalise their assessment, maintenance of industrial continuity without interruption. Once granted, the authorisation allows the use to continue under strictly controlled conditions. As a reminder, the full REACH authorisation procedure is described in detail in our dedicated article. For any questions or to assess your situation regarding Ethylenediamine, our experts are at your disposal.

In recent years, few regulatory topics have attracted as much attention as endocrine disruptors, chemicals capable of interfering with hormone systems in humans and wildlife. Their potential effects on development, reproduction, and environmental health have prompted increasingly rigorous scrutiny across the globe. Within the European Union, two major legislative frameworks govern how such substances are assessed: Regulation (EC) No 1107/2009 for plant protection products (PPPs) and Regulation (EU) No 528/2012 for biocidal products (BPs). In 2018, the EU implemented a harmonised set of scientific criteria for determining whether a substance exhibits endocrine-disrupting (ED) properties. Now, after several years of applying these criteria, the European Commission has evaluated the experience gained, what worked, what stalled, and what still needs to change. The findings illuminate both the scientific complexity behind ED assessments and the administrative challenges facing regulators and industry alike. This article breaks down the key insights from this extensive review.   Why the EU Updated Its Approach When the PPP and BPR regulations were originally adopted, they included interim criteria for ED identification, with a clear requirement for the Commission to develop more scientifically robust standards. These updated criteria came into force in mid- and late-2018, shaping all ongoing and future assessments of active substances. To support implementation, the European Chemicals Agency (ECHA) and the European Food Safety Authority (EFSA) jointly developed comprehensive guidance explaining how to evaluate ED properties. This guidance became the backbone of the regulatory process, but it also introduced substantial new workloads for both applicants and evaluators.   What Has Happened Since the New Criteria Came into Effect? 1. Plant Protection Products (PPP) As of January 2025, endocrine disruptor assessments had been completed for 104 active substances used in plant protection. Key outcomes: 9 substances were identified as endocrine disruptors , either for human health, non-target organisms, or both. Interestingly, ED properties were not  the sole or decisive reason for their non-approval or non-renewal, other safety concerns also played major roles. 95 substances were concluded not to have ED properties  and therefore remained approved or were renewed. 259 substances are still under assessment , illustrating how resource-intensive ED evaluations have become. Delays have been a major challenge. Many renewal procedures already in progress when the new criteria took effect had to be paused so EFSA could request additional data, a process that could take up to 30 months. Once submitted, these data needed to be reviewed first by Rapporteur Member States and then through EFSA’s peer-review system, creating delays that often exceeded three years overall. A significant bottleneck has been the shortage of experts trained to evaluate complex toxicological and ecological endocrine data. Another issue: the limited availability of certified laboratories capable of performing the highly specialised studies required. Some applicants have challenged ED conclusions in court (most notably the case of mancozeb) but so far, no ruling has overturned the adequacy of the ED assessments themselves.   2. Biocidal Products (BP) For biocides, the pace and complexity of ED assessments have likewise influenced regulatory timelines, particularly the EU’s long-running review programme for “existing” active substances (those on the market before 2000). As of early 2025: Eight substances have been identified as endocrine disruptors  for both human health and the environment. Some were not approved due to ED concerns; others were approved using derogations where no suitable alternatives exist. Seventeen substances were concluded not to have ED properties . Twenty-nine substances could not be conclusively assessed , either because data were insufficient or because parallel concerns made a full ED conclusion unnecessary at the time. ED assessments are ongoing for 169 substances , with 25 older substances awaiting evaluation during their renewal phase. Like PPPs, biocidal ED assessments have faced shortages of experts and laboratory capacity. Some Member States adopted a stepwise approach, requesting limited data first, then additional tests, which unintentionally prolonged evaluations. Competent Authorities have since agreed that when in vivo studies are clearly needed, they should be requested upfront to avoid unnecessary delays. The cumulative burden has been significant enough that the EU extended the biocides review programme until 31 December 2030 , highlighting the scale of the task ahead.   Shared Challenges Across Both Sectors Across PPPs and BPs, several consistent issues have emerged: 1. Limited Scientific Expertise ED assessment is among the most complex areas of modern toxicology. Member States continue to face shortages of skilled experts in endocrinology, ecotoxicology, and evidence synthesis. 2. Insufficient Laboratory Capacity Many ED-relevant studies require specialised test facilities, yet the number of certified labs capable of conducting these tests remains limited. This creates bottlenecks for applicants needing to generate new data. 3. Heavy Data Requirements ED evaluations require extensive literature searches and reviews, including mechanistic, in vivo, and ecological data. Processing this volume of information significantly increases assessment time. 4. Ongoing Legal and Technical Interpretation Questions Some applicants contest ED conclusions, while others question when exactly additional data should be considered sufficient. Though the core criteria remain robust, procedural uncertainties persist.   Do the Current ED Criteria Still Hold Up? Despite operational challenges, the Commission’s assessment confirms that the scientific ED criteria remain valid , scientifically sound, and fit for purpose. They allow for consistent identification of substances with endocrine-disrupting properties, ensuring a high level of protection for human health and the environment. What is clear, however, is that implementation, not the scientific basis, is the limiting factor . Building expertise, expanding laboratory capacity, and streamlining data requests will be crucial steps in meeting future regulatory deadlines.   Looking Ahead The EU’s experience with ED criteria underscores a broader truth: robust scientific regulation is essential, but it must be matched with strong operational capacity. As Member States and EU agencies continue to refine processes and invest in scientific expertise, the assessment of endocrine disruptors should become more efficient without sacrificing rigor. For researchers, industry, and policymakers, this review offers a roadmap of where attention is needed most. And for the public, it reaffirms the EU’s commitment to grounding chemical safety decisions in the best available science; while constantly scrutinising how that science is put into practice. If your organisation is navigating the challenges of ED assessments under PPP or BPR, our CEHTRA experts can support you with strategic, regulatory, and scientific guidance tailored to your substances and timelines. Reference: For further details, please refer to the European Commission guidance document: https://health.ec.europa.eu/document/download/841bf3d9-33ab-4d4d-9fd2-22d99a9b492c_en?filename=endocrine_application-criteria_assessment_en.pdf

Directive (EU) 2020/2184 establishes a harmonised framework intended to ensure the safety of materials and products that come into contact with water intended for human consumption. To achieve this objective, it introduces a central mechanism: the EUropean Positive Lists (EUPL) . These lists now constitute the single reference for determining which substances may be used in drinking water installations, whether pipes, storage tanks, treatment equipment or any other component of the network. The scope of the EUPL is defined in particular under Article 11(2)(b) and Annex V of the Drinking Water Directive (DWD).   The EUPL: Definition, Role and Scope The EUPL are unique reference lists that group together the substances, compositions or constituents considered safe for use in contact with drinking water. Their function is essential, as they make it possible to exclude any material likely to alter drinking water quality or present a health risk for consumers. Article 10 of the directive indeed requires that only materials, meaning solids, semi-solids, or liquids used for the manufacturing of a product (an item intended to be placed on the market and coming into contact with water intended for human consumption), listed on these registers may be used in installations. This requirement ensures full harmonisation at the European level and ends the differences in practices that previously existed between Member States.   Categories of Materials Covered The EUPL, presented in Commission Implementing Decision (EU) 2024/367, cover four major families of materials: Organic materials  including polymers, resins and monomers used in their manufacture. Cementitious materials , such as mortars or other cement-based components used notably in reservoirs or hydraulic structures. Metallic materials , including authorised alloys such as copper or stainless steel. Enamels, ceramics and other inorganic materials , which are included for applications requiring coated surfaces or specific components. For some of these materials, particularly organic and cementitious ones, the evaluation is based on the calculation of the MTCtap (Maximum Tolerable Concentration at the Tap). This threshold represents the maximum acceptable concentration at the point of use, defined either from ECHA opinions or limits set by the European Commission.   The Inclusion Process The inclusion of a substance in an EUPL is based on a strictly regulated scientific procedure involving a thorough risk assessment, taking into account the potential migration from the material into drinking water under the most unfavourable conditions of use. Conformity tests are then carried out to verify the material’s safety, particularly its impact on organoleptic properties and the microbiological balance of water. When all criteria are deemed satisfactory, the substance may be included in the positive list, following the opinion of ECHA’s Risk Assessment Committee (RAC).   Regulatory Framework and Implementing Decisions The evaluation procedure is defined by Delegated Regulation (EU) 2024/369 , which sets out the information requirements and the modalities for ECHA’s assessment. In parallel, implementing acts establish the test methods used to verify the conformity of substances or compositions. The application rules of Directive (EU) 2020/2184, notably the establishment of the lists and the testing requirements, are detailed in the following implementing decisions, all dated 23 January 2024: Commission Implementing Decision (EU) 2024/367 : Establishes the European positive lists of starting substances, compositions and constituents authorised for use in manufacturing materials or products that come into contact with water intended for human consumption. This document contains the European Positive List. Commission Implementing Decision (EU) 2024/365 : Lays down the application rules of the Directive regarding methodologies for testing and accepting starting substances, compositions and constituents for inclusion in the European positive lists. Commission Implementing Decision (EU) 2024/368 : Its annexes specify that certain cementitious constituents and certain starting substances may be used without being listed in the European Positive List. This exemption depends on their level of migration and/or hazard. Consequently, information (and potentially testing) on these aspects must be obtained to determine whether the substance must be included in the EUPL.   Dynamic Lists Regularly Updated The EUPL are not static. They are subject to periodic review to take account of scientific developments, new toxicological data or technological innovations. The first lists currently include 2,042 starting substances, compositions and constituents. Each listed substance must be reassessed at least every fifteen years. The initial European lists will be drawn up from existing national lists, then reviewed by ECHA to ensure compliance with European requirements. Each entry is associated with an expiration date defined according to the characteristics of the substance and the quality of the initial evaluation. The current deadlines extend to 31 December 2028, 2031, 2034 and 2037 . To remain listed, a renewal or re-evaluation request must be submitted 18 months before the expiration date . Regulatory Procedure: From Notification of Intention to Complete Submission The evaluation process begins with a Notification of Intention (NoI)  submitted via the IUCLID platform. This notification identifies the substance concerned, the associated material category and the type of application (new inclusion, withdrawal or re-evaluation of an already listed substance). The texts provide that NoIs may be submitted from 31 December 2025 . The corresponding complete dossiers must then be submitted within twelve months, meaning that the first inclusion or renewal applications may begin as of 31 December 2026 .   Strategic Importance for Public Health and Sector Stakeholders For operators in the sector, the Directive requires constant vigilance in the selection of materials and the verification of their compliance. They must ensure that the products used are listed, anticipate upcoming revisions, and communicate clearly with users regarding the guarantees offered by this regulatory framework.   Conclusion The European Positive Lists are among the most structuring instruments of Directive (EU) 2020/2184. They ensure a high level of health protection by precisely defining which substances are authorised in drinking water installations. Their implementation is based on robust scientific assessment, regular updates and active cooperation between authorities, manufacturers and operators. For more information, please visit the ECHA website ( DWD processes – ECHA ) or contact us.   References: Directive (EU) 2020/2184: Directive (EU) 2020/2184 of the European Parliament and of the Council of 16 December 2020 on the quality of water intended for human consumption (recast), OJ L 435 , 23.12.2020, pp. 1–62 . Available on: http://data.europa.eu/eli/dir/2020/2184/oj  (accessed on 01/12/2025). Commission Implementing Decision (EU) 2024/367:  Commission Implementing Decision (EU) 2024/367 of 23 January 2024 laying down rules for the application of Directive (EU) 2020/2184, OJ L 2024/367, 23.04.2024. Available at: http://data.europa.eu/eli/dec_impl/2024/367/oj (accessed on 01/12/2025). ECHA : European Chemicals Agency, Drinking water directive  [online]. Available on: https://echa.europa.eu/water  (accessed on 01/12/2025) .

If you're a cosmetics manufacturer looking to sell your products in the European Union, it's important to understand the requirements for a Cosmetic Product Safety Report (CPSR). A CPSR ensures that your product is safe for consumers and helps to protect public health. Contact a qualified person, such as a toxicologist, to help you prepare a CPSR and ensure that your product complies with the Cosmetics Regulation (EC) No 1223/2009. Don't risk fines or legal consequences - prioritize the safety of your customers with a thorough CPSR. What is a CPSR? A Cosmetic Product Safety Report (CPSR) is a document that presents the conclusion on the safety of a cosmetic product and the rationale used by the safety assessor. The report is required in the European Union under the Cosmetics Regulation (EC) No 1223/2009. The purpose of the CPSR is to consider the expected use, list the useful information, from literature or obtained on the product, and quantify any potential risk, if identified, to demonstrate that it can be used without any risk. What does a CPSR include? A CPSR typically includes the following information: Part A: gathering information on the presentation of the product, its indications, its expected stability, compatibility with the pack, efficient preservation, information on traces, and tolerance results. Part B: presenting the conclusion, any warning if needed, the rationale to conclude on the different risks induced by the product, and the signature of the qualified safety assessor. An important part of the Safety Report is generally included in Annexes: the toxicological profiles, which must be provided for all ingredients. Who prepares a CPSR? A CPSR must be prepared by a qualified person, a safety assessor, such as a toxicologist, who has the necessary diplomas and expertise to assess the safety of cosmetic products. The qualified person may be employed by the cosmetic product manufacturer or by a third-party company that specializes in safety assessments. At CEHTRA, several of our toxicologist can sign the CPSR. Why is a CPSR important and what does CEHTRA recommends? A CPSR is important because it ensures that cosmetic products are safe for use by consumers. By identifying potential risks associated with the use of a cosmetic product, the CPSR helps to prevent harm to consumers and to protect public health. CEHTRA recommends a 1rst step before writing this report, in a pre-assessment, before starting any study. In addition, a CPSR is required by law in the European Union. Failure to comply with the requirements of the Cosmetics Regulation (EC) No 1223/2009 can result in fines and other legal consequences. Overall, the CPSR is a crucial component of ensuring the safety of cosmetic products on the market. Get expert support in preparing your CPSR and ensure your products are fully compliant with EU regulations.

Understanding REACH Authorisation: A Control Mechanism for the Most Hazardous Substances Introduction The REACH Regulation (EC No 1907/2006) aims to ensure a high level of protection for human health and the environment from the risks posed by chemical substances. Among its four main pillars, Registration, Evaluation, Authorisation and Restriction, the Authorisation process is often the most complex for non-specialists to understand. Yet it plays a critical role in managing the most hazardous substances on the European market. This article explains what REACH Authorisation is, why it exists, who is affected, how an Authorisation dossier is built, and how we support our clients throughout the process. ation est d’expliquer ce qu’est l’autorisation REACH, pourquoi elle existe, qui est concerné, et comment se constitue un dossier d’autorisation et enfin comment nous accompagnons nos clients. Why is Authorisation required? Certain chemical substances present severe hazards: carcinogenic, mutagenic, or toxic to reproduction (CMR); persistent, bioaccumulative and toxic (PBT); or endocrine disruptors. These substances are identified as Substances of Very High Concern (SVHCs) . Once an SVHC is added to Annex XIV of REACH  (the “Authorisation List”), its use is prohibited after a specified sunset date , unless a specific Authorisation is granted for defined uses. The REACH Authorisation process therefore aims to: Control risks associated with the use of these substances. Encourage substitution with safer alternatives. Allow continued use when no technically or economically feasible alternative is available. Who is concerned? The following companies may require an Authorisation: Users of a substance listed in Annex XIV. Importers or suppliers placing the substance on the market for a specific use. It is essential to note that Authorisation is use-specific , not substance-specific: a company may apply for Authorisation for one defined use, even if other uses of the same substance are banned. When should an Authorisation be submitted? It is strongly recommended to submit the application before the Latest Application Date (LAD)  for each substance. If the authorities take longer to assess the dossier, the applicant may continue using the substance beyond the sunset date while awaiting the decision. Once granted, the Authorisation allows continued use of the substance beyond the sunset date under the conditions specified. Steps of the Authorisation Process: The Authorisation workflow includes: Identification of the substance as an SVHC. Inclusion in Annex XIV. Preparation and submission of the Authorisation dossier. Evaluation by ECHA (Risk Assessment Committee – RAC, and Socio-economic Analysis Committee – SEAC). Final decision by the European Commission. Building a REACH Authorisation Dossier A REACH Authorisation dossier is a highly technical and regulatory submission. It must demonstrate that risks are adequately controlled (for threshold substances) or minimised as far as possible (for non-threshold substances such as CMRs), and that no suitable alternatives exist. The dossier includes: Justification for the Application The applicant must explain why Authorisation is needed by defining: The precise uses of the substance, including technical context, operational constraints, and sector-specific details. The quantities involved. Chemical Safety Report (CSR) This report assesses human health and/or environmental risks associated with the use of the substance. It includes: Exposure scenarios describing risk management measures and operational conditions. Risk characterisation comparing exposure levels with “safe” limits (usually derived by RAC experts). Analysis of Alternatives The applicant must demonstrate: That alternatives have been investigated. Why they are not technically or economically viable. That alternatives would reduce risks to humans and/or the environment. It is now strongly recommended to include a Substitution Plan , describing timelines, milestones, organisational structure, and reporting mechanisms related to the future switch to alternatives. Socio-economic Analysis (SEA) This analysis generally compares: The societal benefits (not only company benefits) of continuing to use the substance,vs. The human health/environmental costs of discontinuing its use. Submission and Follow-up The dossier is submitted via ECHA’s portal. Fees apply depending on company size. The evaluation period is not legally fixed and may range from 18 months to 3 years based on our experience. Once Authorisation is granted, companies must: Comply with the conditions described in their dossier, plus any additional conditions set by EU authorities. Prepare a review report  when the Authorisation expires (typically after 4, 7, or 12 years), justifying why substitution could not be completed within the initial timeframe. Key Points for Non-Experts REACH Authorisation is not automatic  and must be justified. It concerns the most hazardous substances . The dossier is highly technical and often requires collaboration across the supply chain. How CEHTRA Supports You At CEHTRA, our experts assist clients with all stages of the Authorisation process: Definition of the use(s) Project management Preparation of all dossier components: CSR, Analysis of Alternatives, Substitution Plan, SEA Dossier submission Defence and responses to ECHA committees Our clients have consistently obtained the full durations requested, even for complex cases. Our experts are also active members of NeRSAP  (Network of Experts in Socio-economic Analysis and Analysis of Alternatives under REACH), ensuring they remain aligned with regulatory expectations and can engage informally with authorities when needed. Finally, these dossiers are complex and time-consuming. From experience, drafting all components typically requires 6 to 15 months , depending on team availability. For any additional questions, feel free to contact our experts.

What is an endocrine disruptor? In the European Union, an endocrine disruptor is defined as a substance that interferes with the hormonal system and may have harmful effects on humans and wildlife. These substances can be of synthetic or natural origin and may impact reproduction, growth, and development. In Europe, endocrine disruptors are assessed under various regulations, particularly those related to pesticides and biocides. The EFSA and l’ ECHA , as well as the l’ OCDE , have published guidance to help identify these substances. The criteria for identifying a substance as an endocrine disruptor are as follows: Endocrine activity : the substance must have endocrine activity. Adverse health effect : it must cause a harmful effect on health. Plausible biological link : there must be a plausible biological link between the endocrine activity and the adverse effect. Regulatory framework: Key milestones  2018 : assessing endocrine disruption potential became mandatory for plant protection products and biocides. April 20, 2023 : entry into force of new classifications under the CLP regulation, introducing the following categories: ED HH  (endocrine disruption for human health), Categories 1 and 2 ED ENV  (endocrine disruption for the environment), Categories 1 and 2 Upcoming or pending regulations:   Update of the Cosmetics Regulation to include the evaluation of endocrine disruptors. Upcoming REACH revisions: identification of endocrine disruptors starting at the lowest tonnage band (from 1 tonne/year). How CEHTRA can support you? In this demanding regulatory context, CEHTRA offers solid expertise and tailored services to support companies in the evaluation of endocrine disruptors.   Key services provided: Critical review of existing data: Review of available regulatory data Targeted bibliographic research and analysis Generation of new, specific data when needed: Tailored testing strategies (in vitro, in vivo) In silico screening (predictive modeling) Monitoring of specific ED-related studies Data compilation in line with the regulatory context: Robust synthesis of studies EFSA table and identification of levels of evidence Determination of classification according to CLP criteria Detailed reports for specific substances or formulations Expert statements (position papers) on ED potential for humans and/or the environment Added value: In silico screening by QSAR experts Use of digital tools to optimize analysis and related costs Tailored services for various sectors (biocides, cosmetics, plant protection products, chemicals, etc.) An experienced in-house team of ecotoxicologists and toxicologists Digital tools ED Pedia : CEHTRA also offers ED Pedia, an interactive tool that allows you to: Instantly check, via CAS number, whether a substance is likely to be an endocrine disruptor Access relevant documentation Download a PDF report of the results Request a CEHTRA expert’s opinion if needed ED Pedia relies on official substance evaluation lists to determine the level of concern regarding a substance’s ED potential. Anticipating regulatory changes Regulation is evolving rapidly: new CLP classifications have already been introduced, and further regulatory changes regarding cosmetics and REACH are expected in the coming months. CEHTRA helps you anticipate and adapt to these developments to ensure your products remain compliant while minimizing risks. Contact Julien Leghait , Head of the Endocrine Disruptors Service , or visit the dedicated page for more information.

The Directive (EU) 2020/2184, adopted on December 16, 2020, marks a pivotal change in the management of drinking water across EU. It replaces the 1998 directive (directive 98/83/EC) and aims to ensure universal access to safe and high-quality drinking water while enhancing transparency, monitoring, and risk management. This regulatory text has significant implications for water suppliers, industries manufacturing materials in contact with drinking water, as well as all stakeholders across the sector. In this article, we will explore the key objectives, new requirements, and essential details of this directive to help you understand its impact on water management practices. We will also provide a brief introduction to the positive lists, which we will explore in detail in a next article. The revision of the Drinking Water Directive (DWD) is part of the European Union's strong commitment to protecting public health and the environment by ensuring access to clean and safe drinking water. Originally adopted in 1998 and thoroughly revised in December 2020, the Directive was updated to reflect scientific advances and address emerging pollutants such as endocrine disruptors and microplastics. This revision was also a direct response to the "Right2Water" European Citizens' Initiative, emphasizing citizens' right to access high-quality drinking water. The revised DWD (Directive (EU) 2020/2184) entered into force on January 12, 2021, requiring Member States to transpose its provisions into national legislation by January 2023. Its overarching goal is to ensure that all EU citizens benefit from some of the highest drinking water standards in the world, while promoting sustainable water management and enhancing consumer confidence in tap water.   1. Key Objectives of revised DWD The main objective of this directive is to protect public health while improving the quality of drinking water across the European Union. To achieve this, the directive sets several specific goals: Public Health Protection : Drinking water must be free from chemical and microbiological contaminants that could harm health. Improved Access to Drinking Water : The directive aims to ensure universal access to safe and affordable drinking water. Enhanced Monitoring : It establishes stricter monitoring of water quality and mechanisms for risk assessment. Sustainable Water Management : The directive includes measures to protect water resources against the impacts of climate change and other environmental pressures.   2. New Drinking Water Quality Parameters and the Watch List Mechanism The revised DWD represents a substantial evolution in the EU regulatory framework for drinking water, introducing updated quality parameters and a watch list mechanism to ensure a high level of health protection in light of emerging environmental challenges. In accordance with Article 5 , Member States are required to adopt and comply with the parametric values established in Annex I , which encompass microbiological, chemical, and indicator parameters. This revision integrates the most recent scientific findings and recommendations of the World Health Organization (WHO) , leading to the inclusion of new chemical substances such as Bisphenol A, PFAS (Total and Sum) and Chlorate. These additions reflect growing concerns about endocrine disruptors , pharmaceutical residues , microplastics , and other persistent organic pollutants , thereby reinforcing the long-term safety of drinking water across the European Union. Complementing these static standards, the Directive introduces a dynamic watch list mechanism , established under Article 13 . This tool is used to proactively monitor emerging substances of concern that are not yet subject to mandatory regulatory limits but may pose a risk to human health. The European Commission is mandated to establish and periodically update this list based on scientific evidence and data provided by Member States. The first version of the watch list includes, among others, 17-β-estradiol and nonylphenol, both recognized as endocrine-disrupting chemicals.   3. Risk-Based Approach and Supply System Management The directive strengthens water quality monitoring and requires a complete risk-based approach to water safety  (Article 7). This approach is implemented in line with the Water Safety Plan (WSP) approach developed by the World Health Organization (WHO). Member States must ensure the implementation of this comprehensive risk-based approach. WSPs are proactive risk assessment and risk management approaches  recognized as the most reliable way to manage drinking-water supplies for public health protection. This approach is built on a preventive safety planning approach  and relies on the multiple-barrier approach. The EU risk framework requires three components of assessment: catchment risk (Article 8), supply system risk (Article 9), and domestic distribution system risk (Article 10). Specifically, WSPs, applied through this framework, include: Risk Identification: Water suppliers carrying out the risk assessment of the supply system  must identify the hazards (biological, chemical, physical, or radiological agents) and hazardous events in the supply system. This assessment must take into consideration risks stemming from climate change, leakages and leaking pipes. The identification also covers specific pollutants relevant for the catchment areas. Risk Assessment, Validation, and Management: Once risks are identified, specific strategies must be implemented to mitigate them. This involves systematically determining the risk score  (product of likelihood and severity) and risk level. For existing measures, this requires validating the effectiveness of existing control measures  in controlling the hazardous event. Based on the outcome, control measures  are defined and implemented for the prevention and mitigation of risks identified in the supply system. This also involves implementing a supply-specific operational monitoring program  (article 13) to ensure control measures function as intended. Emergency Procedures and Corrective Actions : The WSP framework includes developing Emergency Response Plans (ERPs) for serious situations that require immediate, extensive action for which there is no standard operating procedure. In the event of non-compliance with parametric values that constitute a potential danger to human health, immediate remedial action (article 14) must be taken, including prohibiting or restricting the water supply.   This approach not only ensures immediate protection but also contributes to the long-term resilience of drinking water supply systems.   4. Materials in Contact with Drinking Water (Articles 10 and 11) A significant innovation introduced by the directive concerns materials in contact with drinking water. To prevent harmful substances from leaching into drinking water, the directive sets minimum requirements for these materials and establishes a harmonized framework across the EU. On April 23, 2024, the European Commission published a comprehensive set of legal acts in the Official Journal of the European Union, including three implementing decisions (EU 2024/365, EU 2024/367, EU 2024/368) and three delegated regulations (EU 2024/369, EU 2024/370, EU 2024/371). These new measures introduce: A Positive List  of authorized starting substances, compositions, and constituents used in materials that encounter drinking water. Testing Methodologies  and harmonized European Positive Lists to ensure consistent safety evaluations. A Procedure for Adding New Substances  to the Positive List (Regulation (EU) 2024/369). Conformity Assessment Procedures and rules for designating assessment bodies (Regulation (EU) 2024/370). Harmonized Specifications for Product Marking , ensuring transparency and traceability (Regulation (EU) 2024/371). These regulations, which came into force on May 15, 2024, will generally apply from December 31, 2026 . They cover materials used in new installations for water abstraction, treatment, storage, and distribution, as well as those used in repair works. Through these measures, the EU has established a unified, science-based approach to ensuring the safety and quality of drinking water from source to tap, further strengthening public health protection and supporting the free movement of compliant materials and products across the internal market.   5. Consumer Information Access A crucial aspect of this directive is transparency. Consumers must be regularly informed about the quality of the water they consume. The results of water quality analyses should be easily accessible and understandable, such as through mobile apps or water bills. Additionally, water suppliers must inform consumers about corrective measures in the event of contamination, potential health risks, and actions taken to ensure water quality. This transparency aims to build consumer trust in tap water, encouraging its use over bottled water.   Conclusion Directive (EU) 2020/2184 represents a major advancement in ensuring high-quality drinking water across the European Union. It imposes new safety standards, strengthens water quality monitoring, and introduces strict requirements for materials used in drinking water infrastructures. Furthermore, it adopts a risk-based approach in line with the Water Safety Plans (WSPs) , supporting proactive risk management. The emphasis on transparency and consumer trust in tap water is also key. In a future article, we will explore in greater detail the European Positive Lists (EUPL) , which play a crucial role in regulating materials in contact with drinking water. Stay tuned! Bibliography Directive (EU) 2020/2184: Directive (EU) 2020/2184 of the European Parliament and of the Council of 16 December 2020 on the quality of water intended for human consumption (recast), OJ L 435 , 23.12.2020, pp. 1–62 . Available on: http://data.europa.eu/eli/dir/2020/2184/oj  (accessed on 19/11/2025). Water safety plan manual : World Health Organization, Water safety plan manual: step-by-step risk management for drinking-water suppliers [online], second edition, 2023, ISBN 978-92-4-006769-1. Available on: https://www.who.int/publications/i/item/9789240067691 (accessed on 19/11/2025).

Octocrylene is a widely used ultraviolet (UV) filter in cosmetic products, particularly sunscreens, designed to absorb UVB and part of the UVA spectrum, thereby protecting the skin against the harmful effects of sunlight. Currently, octocrylene is authorised in cosmetic products at a maximum concentration of 9% in accordance with Annex VI of the European Cosmetics Regulation [1]. However, due to increasing environmental concerns, and following a proposal from the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), the European Chemicals Agency (ECHA) launched in 2025 a public consultation concerning a potential restriction on the use of octocrylene in finished cosmetic products. This proposed restriction aims to prohibit octocrylene in cosmetic products at concentrations equal to or greater than 0.001% [2]. The public consultation will open on 24 September 2025  and close on 24 March 2026 . Early comments are encouraged before 23 January 2026 , to allow the Committees to consider feedback during their initial discussions. The final decision on this proposed restriction is expected in 2027, following the opinions of ECHA’s scientific committees and the European Commission [2].   1. Rationale for the Restriction The primary objective of this restriction is to mitigate environmental risks arising from the widespread accumulation of octocrylene in aquatic environments. Although octocrylene is an effective UV filter for skin protection, it poses an environmental hazard due to its persistence and toxicity, particularly in aquatic ecosystems. Indeed, octocrylene is poorly biodegradable and may accumulate in the biological tissues of aquatic organisms [1] .   2. Hazard Characterisation The hazard profile of octocrylene is evaluated based on its ecotoxicological properties, including toxicity, persistence, and bioaccumulation potential. • Persistence and limited biodegradability: Octocrylene is concluded to be persistent (P)  and very persistent (vP)  due to its low biodegradability, according to standard OECD 301 biodegradation tests. It displays high lipophilicity (log Kₒw > 6) and an aromatic structure, both indicators of potential bioaccumulation in biological tissues.Although environmental monitoring data suggest in situ accumulation in living organisms, in vivo fish studies  indicate that octocrylene is neither bioaccumulative (B) nor very bioaccumulative (vB)  under the bioaccumulation criteria of Annex XIII of REACH. Consequently, octocrylene is not classified as very persistent and very bioaccumulative (vPvB)  [1]. • Aquatic toxicity: Octocrylene exhibits high chronic toxicity to aquatic organisms. Tests on Daphnia magna  established a NOEC (No Observed Effect Concentration)  of 2.66 µg/L  for reproduction, indicating significant toxicity even at low concentrations. From this, a PNEC (Predicted No Effect Concentration)  of 0.266 µg/L  for freshwater can be derived [1] .   3. Risk Characterisation The environmental risk assessment combines both the hazard profile of octocrylene and the actual exposure conditions in aquatic environments. The risk is expressed as the ratio between the Predicted Environmental Concentration (PEC) and the Predicted No Effect Concentration (PNEC).   Risk Characterisation Ratios (RCR): The RCRs—comparing PEC to PNEC—are used to assess risk under various exposure scenarios. RCR values exceed 1 in most cases. In the scenario related to emissions during bathing in freshwater lakes (ES 12), RCR values are calculated at 744 for freshwater and 7443 for freshwater sediments.For marine coastal waters, the RCR is 109 for water and 1108 for sediments. These values indicate that actual concentrations of octocrylene in the environment far exceed the PNEC of 0.266 µg/L, suggesting an unacceptable environmental risk [1,2]. Emission and dissemination pathways: The main emission routes of octocrylene into the environment include: Direct release during swimming , where up to 50% of the applied amount may be washed off into the water [2]; Indirect release via domestic wastewater , leading to the dissemination of octocrylene into agricultural soils and watercourses, thereby increasing aquatic contamination [1,2]. Such widespread and persistent emissions contribute significantly to aquatic pollution and heighten environmental risk.   4. Proposed Restriction The restriction proposal under public consultation aims to ban the use of octocrylene in finished cosmetic products at concentrations ≥ 0.001% . This measure seeks to reduce emissions of the substance into the environment, mainly by limiting its use in cosmetics, which constitute the primary source of exposure [1,2] .   5. Scientific and Industrial Implications Key strengths of the restriction: Protection of aquatic ecosystems:  Octocrylene is toxic to many aquatic organisms even at low concentrations. Restricting its use would help preserve aquatic ecosystem integrity [1] . Availability of substitutes:  Several next-generation UV filters with more favourable environmental profiles are available as potential alternatives to octocrylene in cosmetic formulations. Precautionary principle:  Reducing exposure to this substance aligns with the REACH Regulation’s objectives to minimise exposure to persistent and toxic chemicals [1] . Limitations and uncertainties: Bioaccumulation uncertainty:  Although persistent, the bioaccumulation potential of octocrylene in aquatic organisms remains insufficiently characterised [1] . Ecological substitutes:  While alternative UV filters exist, their environmental profiles have not yet been fully validated, which may hinder their immediate implementation   [2] .   6. Conclusion Assessments by France and ECHA conclude that the widespread use of octocrylene represents an unacceptable environmental risk under REACH criteria. The key hazard elements, chronic toxicity, persistence, and wide diffusion, justify a preventive regulatory action.The proposed restriction, setting a threshold of 0.001%, represents a strong regulatory measure to protect aquatic ecosystems, while granting industry sufficient time to adapt. Octocrylene exemplifies the balance between environmental protection and human health safety. The European Commission’s final decision will need to ensure a transition towards safe, efficient, and sustainable cosmetic products.   References French Agency for Food, Environmental and Occupational Health & Safety (ANSES). Regulatory Management Option Analysis (RMOA) on Octocrylene.  Report for public consultation, March 2023. Available on the official ANSES website. (2023) European Chemicals Agency (ECHA). Annex XV Restriction Report: Proposal to restrict Octocrylene (CAS 6197-30-4).  Consultation launched on 24 September 2025, closing on 24 March 2026. Accessible via the ECHA website. (2025) To access the full toxicological and ecotoxicological profiles of this substance in COSMETICK To learn more about CEHTRA’s expertise in cosmetics and ingredient safety

The unexpected appearance of N-nitrosamine impurities in medicines marked a major regulatory turning point. These compounds, already known to occur in the environment and food, compelled the global pharmaceutical industry to re-evaluate its manufacturing processes. In response, an unprecedented level of international coordination emerged among major regulatory agencies, including the FDA (United States), EMA (Europe), Anvisa (Brazil), and Health Canada, aiming to assess the extent of the issue and establish mitigation strategies. This event had a profound impact on the reassessment of manufacturing processes, enforcing increased vigilance and stricter controls at all stages of pharmaceutical production—from raw materials to finished products. Toxicological Profile of N-Nitrosamines Structure and Mechanism of Action N-nitrosamines are characterized by a nitroso (-N=O) functional group bound to an amine (>NR₂). Their toxicity relies on a crucial bioactivation mechanism that begins with α-hydroxylation, primarily catalyzed by cytochrome P450 (CYP 450) enzymes. This step leads to the formation of unstable intermediates that subsequently generate reactive diazonium ions. These ions are highly electrophilic and can interact with DNA, causing irreversible genetic damage. Mutagenic and Carcinogenic Properties Due to their ability to alter DNA, N-nitrosamines are classified as mutagenic and genotoxic agents. Their properties also make them potent carcinogens. Extensive studies have shown that 82% of 228 tested nitrosamines were carcinogenic in vivo, underlining their hazardous nature. This high prevalence of carcinogenicity justifies the stringent regulatory measures implemented and the need to minimize their presence in pharmaceutical products. The 2018 Crisis and Its Expansion The N-nitrosamine crisis emerged in 2018, following the unexpected detection of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in sartan drugs—commonly used for the treatment of hypertension and heart failure. This initial discovery quickly led to a broader investigation, revealing a more systemic issue. Contamination was subsequently identified in other widely prescribed medicines, including ranitidine (an H2 receptor antagonist), nizatidine (another antiulcer drug), and metformin (used to treat type 2 diabetes). The detection of these impurities resulted in large-scale product recalls worldwide, exposing the systemic nature of the problem and highlighting the need for a comprehensive reassessment of manufacturing and quality control processes within the pharmaceutical industry Sources of N-Nitrosamine Contamination Contamination of pharmaceuticals with N-nitrosamines can arise from multiple sources and complex mechanisms throughout the drug lifecycle. Understanding these origins is essential to prevent and mitigate their formation: Formation during synthesis:  Reaction between nitrites and secondary or tertiary amines (or their precursors) under acidic or high-temperature conditions. Reagents or intermediates may themselves be contaminated. Contaminated solvents:  Certain solvents such as Dimethylformamide (DMF) or N-Methyl-2-pyrrolidone (NMP) may degrade into amines or nitrites, leading to N-nitrosamine formation. Recycled materials:  Use of recycled solvents or reagents, if insufficiently purified, can introduce N-nitrosamines or their precursors. Azide degradation:  Azides used in specific syntheses may degrade in the presence of nitrites to form N-nitrosamines. Excipients:  Some excipients may contain tertiary amines (e.g., crospovidone, povidone) or be contaminated with nitrites, promoting in situ formation of N-nitrosamines in the finished product. Active substance degradation:  The active ingredient itself can degrade to generate amines or other precursors of N-nitrosamines. Packaging materials:  Primary packaging materials (e.g., certain plastic films or labels) may release amines or nitrites that react with the drug product. Storage conditions:  Elevated temperature and humidity during storage can accelerate component degradation and N-nitrosamine formation over time. Regulatory Framework and Mitigation Strategies Given the complexity and scale of the N-nitrosamine issue, regulatory agencies have established a structured three-step approach for the pharmaceutical industry: Risk Assessment: The first step involves identifying potential risks of N-nitrosamine formation or contamination across the entire product portfolio. This requires a detailed analysis of synthesis pathways, raw materials, excipients, solvents, and manufacturing and storage conditions. Manufacturers must demonstrate that they have thoroughly evaluated and characterized these risks. Confirmatory Testing: Following risk assessment, robust analytical testing is required to confirm the presence or absence of N-nitrosamines. High-sensitivity methods, such as liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), are preferred for their precision and ability to detect trace levels of these impurities. Control and Mitigation: If N-nitrosamines are detected, or a significant risk is identified, control and mitigation strategies must be implemented. These may include modifications to synthesis routes, use of alternative raw materials, optimization of storage conditions, or the establishment of strict impurity limits. Dedicated working groups, such as the NISG (Nitrosamine Impurities Steering Group)  and the NITWG (Nitrosamine Impurities Working Group) , have been created to coordinate actions and share best practices globally. Acceptable Intakes of N-Nitrosamines To protect public health, regulatory authorities have defined Acceptable Intake (AI)  limits for N-nitrosamines. The underlying principle is to ensure that the additional lifetime cancer risk remains below 1 in 100,000. Specific AI limits have been established for the most common N-nitrosamines: NDMA (N-nitrosodimethylamine):  96 ng/day NDEA (N-nitrosodiethylamine):  26.5 ng/day For newly identified nitrosamines lacking compound-specific toxicological data, the Carcinogenic Potency Categorization Approach (CPCA)  is applied. This approach classifies nitrosamines into carcinogenic potency categories (PC 1 to PC 5), each associated with corresponding AI limits. In addition, the Less-Than-Lifetime (LTL)  concept allows temporary adjustment of exposure limits for shorter treatment durations, acknowledging that cumulative risk is lower over limited periods. Need assistance ensuring regulatory compliance for your pharmaceutical products?

When a company develops a new ingredient, whether it is a concentrated plant extract, a biotech-derived ferment, a processed algae or a “functional” mushroom, one recurring question always arises: is a Novel Food procedure required before marketing the ingredient within the EU?   This question often emerges when the project is already well advanced: the formulation is nearly finalized, the marketing identity is ready, the first commercial discussions have started… and suddenly, regulatory uncertainty arises. This can cause a serious slowdown, or even block market entry, if the question has not been addressed early on.  The reality is that innovation does not take place solely in the laboratory or through marketing arguments. An essential part of success lies in the regulatory qualification of the ingredient , particularly regarding its possible classification as a Novel Food  under the criteria defined by the European Union.    What “Novel Food” Really Means  The term Novel Food  does not imply a risk or a restriction. It refers to a regulatory concept : a Novel Food is simply a food or ingredient that was not consumed to a significant degree before 15 May 1997  by the European population, or that results from an innovative process  altering its composition or bioavailability.  Since safety cannot be justified through long-term, significant consumption, it must instead be demonstrated through toxicological safety studies .  Therefore, Novel Food status is not a judgment of immediate safety , but rather an invitation to demonstrate safety  in an official dossier, evaluated by EFSA and validated at the European level. Being classified as Novel Food does not mean “impossible to market”, but rather “requires prior authorization”.    A Quick Test to Know if Your Ingredient Falls Within the Novel Food Scope  Here are a few simple points of attention. If several of these statements apply to your ingredient, a Novel Food status analysis is likely necessary.  Your ingredient has not been the subject of documented consumption in Europe before 1997.   You use an innovative process that modifies the concentration, structure, or metabolites of the raw material.   The ingredient is fermented using a strain or a technique that is not part of Europe’s food tradition.   The source comes from a species rarely consumed in the EU (specific microalga, medicinal mushroom, microorganism, cell culture, etc.).   The final chemical profile is no longer comparable to the traditional raw material.  If you identify with one or more  of these cases, a regulatory screening  is recommended before any commercial communication or product launch.    Common, and Often Underestimated, Situations  Many companies believe they fall outside the scope of the Novel Food Regulation because the ingredient exists naturally or is consumed in other parts of the world. However, the reality is quite different.  example, while curcuminoids extracted from Curcuma longa  root  and standardized to 95% curcumin are authorized in Europe for use in food supplements, curcumin itself  is considered a Novel Food.    Regulatory Solutions to Confirm the Status of Your Ingredient  The Novel Food Regulation allows, in cases where an ingredient’s status is unclear, to consult the competent authorities  through a formal consultation procedure  designed to officially determine the status of an ingredient.  This procedure gives an EU Member State the responsibility, based on data provided by the applicant, to decide on the ingredient’s classification. It is an optional procedure , with both advantages and disadvantages  that should be carefully assessed before submission.    What Changes When an Ingredient Is a Novel Food  When an ingredient is considered a Novel Food, the regulatory approach changes. It is no longer simply a matter of verifying compliance with a positive list, but of providing scientific evidence of safety  for European consumers under realistic conditions of use (dose, formulation, target population, cumulative exposure, etc.).  The evaluation covers:  The exact composition, including impurities, possible nanoparticles, solvents, or residues  Technical specifications (natural variability, stability)  Manufacturing processes  Dietary exposure of different population groups  Available toxicological data  The ability to demonstrate absence of risk under intended conditions of use    The Importance of Anticipation  The earlier the status is assessed, the more secure the time-to-market  will be. Conversely, discovering a potential Novel Food issue once formulations are finalized and commercial partners are engaged can lead to multi-year delays,  time needed to compile a dossier, conduct or gather the required studies, submit to the competent authorities, and wait for their evaluation.  This is why more and more companies are integrating a Novel Food regulatory screening  early in the development phase, even before finalizing the product positioning.    CEHTRA, Supporting You to Decide Quickly and Wisely  At CEHTRA , we support project leaders, manufacturers, and start-ups during this critical qualification phase. The goal is not only to prepare a dossier later, but to help you make the right decisions quickly :  Verify whether the ingredient falls under the scope of the Novel Food Regulation  Identify the elements to be documented (consumption history, equivalence, composition, etc.)  Build a realistic and progressive safety assessment strategy  Develop a clear, well-argued, and robust dossier in case of official submission  Our approach aims to secure your innovation without unnecessary obstacles .    In Conclusion  Determining whether an ingredient is a Novel Food is not a mere administrative formality, it is a strategic step  that defines commercial feasibility, cost anticipation, and credibility with partners.  The earlier the verification is carried out, the smoother, more controlled, and transparent the innovation path will be, both internally and with investors, clients, and distributors.  To discuss your specific case or request a Novel Food status assessment, you can contact Marie Liamin , Food Products Market Manager at CEHTRA .

The identification of endocrine disruptors (EDs) has become a major public health and environmental concern worldwide. EDs are chemical substances capable of interfering with the hormonal system, leading to adverse effects on both humans and wildlife. Monitoring and assessing these substances is essential to protect human health, particularly among vulnerable populations such as pregnant women, children, and wild species. To this end, the U.S. Environmental Protection Agency (EPA) has developed ToxCast , a comprehensive database compiling in vitro  biological activity data for hundreds of chemicals, enabling the analysis of their potential endocrine-disrupting effects. What is the ToxCast Database? ToxCast  (short for Toxicity Forecaster ) is a flagship EPA program designed to evaluate the toxicological potential of chemicals. Using a suite of high-throughput in vitro screening (HTS)  assays, ToxCast examines the bioactivity of thousands of chemicals across multiple biological targets. These in vitro  assays measure biological responses, including hormonal activity, on specific receptors, enzymes, and cellular processes involved in endocrine regulation. The main goal of ToxCast is to provide detailed data on chemical substances to predict their potential to interfere with biological systems, particularly endocrine systems in humans and animals. With data on more than 10,000 chemicals , ToxCast has become an invaluable resource for researchers and regulators seeking to identify endocrine disruptors. One of the key advantages of ToxCast lies in its non-animal testing approach , reducing reliance on traditional animal studies. This aligns with the European Union’s “One Health” strategy , Directive 2010/63/EU, and the EU roadmap toward phasing out animal testing, by promoting the use of alternative methods such as in vitro  assays and computational approaches in toxicity assessment. What Does This Update Include? The latest version of the ToxCast database, invitrodb v4.3 , introduces several critical improvements, many of which directly enhance its usefulness in endocrine disruptor evaluation. 1. Enhanced Data Analysis The updated ToxCast release introduces new analytical features that improve the accuracy and reliability of in vitro  screening data interpretation. These enhancements allow researchers to better understand biological effects on hormone receptors and other key mechanisms underlying endocrine function. Improved analytical tools now integrate additional parameters, making it easier to compare data across substances. For example, chemical effects on hormonal receptors can be assessed faster and more precisely, allowing for early detection of substances potentially disrupting endocrine pathways . 2. Updated Software Tools The software tools used to process ToxCast data have also been upgraded. Widely used R packages , such as tcpl and tcplFit2, have been enhanced to provide improved data handling, smoother workflow management, and more advanced visualization capabilities. The tcplFit2 package, for instance, now offers more accurate dose–response curve fitting , enabling more reliable estimation of effect concentrations. This is essential for assessing risks associated with low-dose exposures to EDs, which are frequently encountered in real-world environmental settings. 3. Expanded Chemical Coverage The update also expands ToxCast’s chemical coverage, now encompassing over 10,000 evaluated substances . This broader dataset supports a more comprehensive toxicological assessment, including for lesser-known or emerging substances that may pose endocrine-related risks. CEHTRA’s Digital Tool: Supporting ED Identification One of the major advances in applying ToxCast data is CEHTRA’s digital tool , designed to facilitate rapid access and interpretation of information from the ToxCast database. 1. Instant Substance Check Through a CAS number search , CEHTRA’s tool allows instant verification of a chemical’s regulatory status and its inclusion in lists of potential or confirmed endocrine disruptors. By entering a single CAS number, users can access detailed information about a substance’s status, potential toxicity, and regulatory evaluation history. This feature represents a significant time-saver , offering quick and reliable access to critical regulatory and toxicological data. 2. Integrated ToxCast Data Analysis Beyond regulatory status, the CEHTRA tool also enables direct analysis of ToxCast data  for the queried substances. It streamlines the exploration of in vitro  high-throughput screening results to assess bioactivity on endocrine-relevant biological targets. In just a few clicks, users can visualize the full spectrum of a substance’s biological effects on hormone receptors, enzymes, and related cellular pathways. By simplifying the use of complex datasets, CEHTRA’s tool empowers users to draw scientifically robust conclusions on endocrine activity , supporting both regulatory assessments and research efforts. This functionality is particularly valuable for ED studies, where data heterogeneity often poses analytical challenges. Conclusion The latest ToxCast database update  marks a major step forward in the evaluation of endocrine disruptors. With expanded chemical coverage, improved analytical methods, and enhanced data management, this update provides a stronger foundation for assessing the potential hazards of chemical substances. CEHTRA’s digital tool complements this progress by offering an intuitive platform to access and analyze ToxCast data efficiently. Together, these innovations enable faster, more reliable identification of endocrine-disrupting substances, strengthening the capacity of regulatory and industrial stakeholders to protect public health and the environment . Need expert support for your endocrine disruptor assessments?