Questions Toxicologists Asked About Cosmetic Safety Assessment – COSMETICK Webinar
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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.
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.
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
