In this article you will learn how cosmetic products are assessed for their safety. Cosmetic product safety takes into consideration the exposure scenario, target audience, relevant toxicological endpoints and toxicological studies.
Regulatory Framework for Cosmetic Safety
Under European Regulation 1223/2009, all cosmetic products must undergo a rigorous safety assessment before market release. Article 10 mandates the preparation of a Cosmetic Product Safety Report (CPSR), as outlined in Annex I. The CPSR is an essential component of the Product Information File (PIF) and serves as a regulatory compliance document for market surveillance. Compliance with these regulations ensures that consumers are protected from potentially harmful ingredients and formulations.
Structure of the Cosmetic Product Safety Report (CPSR)
Part A: Cosmetic Product Safety Information
This section compiles detailed technical and toxicological data, including:
- Formulation Composition: A comprehensive list of ingredients with their INCI names, CAS numbers, and functional roles.
- Physicochemical Properties and Stability: Data on product stability, pH, viscosity, and interactions between ingredients.
- Microbiological Specifications: Includes microbial limits, preservative efficacy testing, and contamination control.
- Impurities and Traces: Identification and permissible levels of impurities, including those from packaging interactions.
- Intended Use and Consumer Exposure: Frequency of application, exposure duration, and target demographic considerations (e.g., infants, sensitive skin populations).
- Toxicological Profile of Ingredients: A risk-based evaluation of each substance’s safety, supported by available toxicological data.
- Undesirable Effects: Compilation of adverse reactions and consumer complaints post-market introduction.
- Additional Safety Data: Human volunteer studies, dermatological testing, and other risk assessments complementing the safety profile.
Part B: Cosmetic Product Safety Assessment
This expert assessment is based on the data in Part A and consists of:
- Final Safety Conclusion: A professional statement on the product’s safety for consumer use.
- Labeling Requirements: Identification of precautionary statements and recommended usage instructions.
- Scientific Justification: Toxicological reasoning supporting the safety determination.
- Assessor’s Credentials: The safety assessor must have a recognized background in toxicology, pharmacology, or medicine and be able to justify their expertise. They must also provide documentation proving their qualifications and relevant experience in cosmetic product safety assessment.
Risk Assessment in Cosmetic Toxicology
Cosmetic safety evaluations are based on risk assessment methodologies that determine the likelihood of harm based on exposure. This process includes:
Hazard vs. Risk Distinction
Hazard: The intrinsic capacity of a substance to cause harm.
Risk: The probability of harm occurring under typical use conditions.
Equation: Risk = Hazard x Exposure
Exposure Considerations
Ingredient concentration within the formulation.
Frequency and duration of application.
Skin contact area and penetration potential.
Likelihood of ingestion or inhalation.
Synergistic Effects
Some substances may enhance the dermal penetration of others, affecting systemic exposure. Examples of these substances include surfactants (SLS, SLES), exfoliants (AHAs, BHAs), chelating agents (EDTA).
Vulnerable Populations
Special considerations must be made for at-risk populations, such as individuals with compromised skin barriers, children, and pregnant women.
Toxicological Data Sources
Reliable safety assessments rely on a variety of data sources, including:
Safety Data Sheets (SDS)
Provides summarized toxicology information from raw material suppliers. This data will likely be taken from the European Chemicals Agency (ECHA), where ingredients are classified based on their posed risk to human health and the environment.
Regulatory Databases
Includes scientific evaluations from organizations like the Cosmetic Ingredient Review (CIR) and European Scientific Committees.
In Vitro Predictive Models
Structure-activity relationship (SAR) and quantitative structure-activity relationship (QSAR) models – collectively referred to as (Q)SARs – are mathematical models that can be used to predict the physicochemical, biological and environmental fate properties of compounds from the knowledge of their chemical structure. QSARs and computer-based modeling help estimate toxicity profiles for novel compounds.
Clinical and Epidemiological Studies
Data derived from population studies and long-term consumer use provide additional insights into ingredient safety over extended periods.
History of Safe Use
When lacking toxicological data to back the safety of a cosmetic ingredient, a history of safe use can be used to add to the weight of toxicological safety – although this cannot be the singular source of toxicological data.
Toxicological Endpoints and Testing
Toxicological Endpoints
To determine ingredient safety, various toxicological endpoints must be assessed:
Acute Toxicity
Evaluates the immediate harmful effects of a single exposure to a substance.
Repeat Dose Toxicity
Examines the long-term effects of repeated exposure over days, weeks, or months.
Skin Irritation and Corrosion
Tests whether a substance causes reversible (irritation) or irreversible (corrosion) damage to the skin.
Eye Irritation and Corrosion
Determines the potential of a substance to cause ocular damage.
Genotoxicity
Investigates whether a substance can damage genetic material, potentially leading to mutations.
Carcinogenicity
Assesses whether a substance increases the risk of cancer development.
Reproductive and Developmental Toxicity
Evaluates effects on fertility, pregnancy, and fetal development.
Skin Sensitization
Determines whether a substance can cause allergic reactions upon repeated exposure.
Toxicological Testing Strategies
Cosmetic ingredients undergo a variety of toxicological tests to determine their safety profile, including:
Irritation and Sensitization Testing
- Assesses potential skin, eye, and mucosal irritation.
- Replaced animal models with validated in vitro tests following OECD guidelines.
- Skin Sensitization Tests: Local Lymph Node Assay (LLNA) and Direct Peptide Reactivity Assay (OECD TG 442C) assess allergic potential.
Acute Toxicity Testing
- Evaluates the toxic effects of a single exposure via dermal, oral, or inhalation routes.
- Important for accidental ingestion or overexposure risk assessments.
Mutagenicity and Genotoxicity Testing
- Determines whether a substance induces genetic mutations or chromosomal aberrations.
- Uses bacterial reverse mutation assays and mammalian cell culture tests.
Dermal Absorption and Penetration Studies
- Measures the extent of percutaneous absorption and systemic exposure.
- Classified into penetration (stratum corneum absorption), permeation (dermal layer migration), and resorption (vascular entry).
- Evaluates the impact of formulation enhancers, emulsifiers, and active delivery systems on ingredient absorption.
Repeated Dose Toxicity Studies
- Evaluates potential toxic effects following prolonged exposure.
- Conducted if substantial systemic absorption is expected.
- Most cosmetic formulations utilize well-characterized substances with established safety profiles.
- Considers potential cumulative effects from repeated exposure to the same or similar ingredients in multiple products.
Cosmetic Product Safety Determination
Margin of Safety (MoS)
The MoS is a critical indicator in cosmetic safety evaluation. It is calculated as follows:
Mos = NOAEL / SED
A MoS value greater than 100 is generally considered safe, based on regulatory guidelines. This threshold accounts for interspecies variability (factor of 10) and intraspecies variability (factor of 10), ensuring human safety.
No Observed Adverse Effect Level (NOAEL)
NOAEL (No Observed Adverse Effect Level) is the highest dose of a substance at which no harmful effects are observed in toxicological studies. This data is typically derived from repeat-dose toxicity studies conducted on animals or in vitro models. These studies assess the effects of prolonged exposure to a substance over time, identifying the threshold at which adverse effects begin to appear. NOAEL values are often sourced from OECD guideline studies, regulatory toxicology reports, and peer-reviewed toxicological databases. They are essential in determining safe exposure levels for cosmetic ingredients.
Systemic Exposure Dose (SED)
The evaluation of the safety of a cosmetic product is not only based on its intrinsic toxicological properties, but also on the way it will be used. Since cosmetic products cover a wide range of product types, many exposure scenarios can be described, e.g.:
- Soaps are applied in diluted form and, although the area of application may be extensive, the product is rapidly washed off.
- Products used on the lips and mouth will be ingested to some extent.
- Cosmetics used around the eyes and genital regions may come into contact with the conjunctiva or mucosa, respectively, potentially resulting in reactions due to the thin epithelial lining of these areas.
- Body lotions or body creams may be applied over a large surface of the body and the substances, often at appreciable concentrations, may remain in contact with the skin for several hours.
- Sunscreens, due to their extensive skin contact, combined with direct exposure to UV
- radiation for prolonged periods, requires a distinct type of safety evaluation.
- The substances of permanent hair dyes undergo oxidative reactions (e.g. with hydrogen peroxide) on the hair, precursors(s), coupler(s), intermediate(s) and final products come into contact with the skin.
Exposure Scenario
Every specific exposure scenario will be linked to a certain amount of a substance that may
be ingested, inhaled or absorbed through the skin or mucous membranes. Translated into a
daily amount per kg body weight, it is considered the SED of the finished cosmetic product.
It is clear that in-use exposure levels can only be obtained on a case-by-case basis for
cosmetic products, taking into consideration at least the following factors:
- Class of cosmetic product(s) in which the substance may be used,
- Method of application: rubbed-on, sprayed, applied and washed off, etc.,
- Concentration of the substance in the finished cosmetic product,
- Quantity of product used at each application,
- Frequency of application,
- Total area of skin contact,
- Site of contact (e.g. , mucous membrane, sunburnt skin),
- Duration of contact (e.g. , rinse-off products),
- Foreseeable misuse which may increase exposure,
- Consumer target group (e.g. , children, people with “sensitive skin”),
- Quantity likely to enter the body,
- Application on skin areas exposed to sunlight.
SED calculations
The following calculations take into account the dermal exposure of the cosmetic product ingredients under consideration. Dependent on whether the dermal absorption is reported in µg/cm² or as a percentage of the substance applied, different exposure parameters must be known in order to calculate the actual SED:
Dermal Absorption Reported in µg/cm²
SED = DAₐ (µg/cm²)) × 10⁻³mg/µg × SSA (cm²) × F (day⁻¹) / 60 kg
With:
- SED (mg/kg bw/d) = Systemic Exposure Dose
- DAₐ (µg/cm²) = Dermal Absorption reported as amount/cm², resulting from an assay under in-use mimicking conditions¹
- SSA (cm²) = Skin Surface Area expected to be treated with the finished cosmetic product
- F (day⁻¹) = Frequency of application of the finished product (F ≥ 1)
- 60 kg = default human body weight
Area and Frequency of Application Data
Product Type | Surface Area (cm²) | Parameters | Frequency of Application |
Shower gel | 17500 | Total body area | 1.43/day |
Hand wash soap | 860 | Area hands | 10/day |
Bath oil, salts etc. | 16340 | Area body Area hands | 1/day |
Shampoo | 1440 | Area hands ½ Area head | 1/day |
Hair conditioner | 1440 | Area hands ½ Area head | 0.28/day |
Hair styling products | 1010 | ½ Area hands ½ Area head | 1.14/day |
Semi-permanent hair dyes | 580 | ½ Area head | 1/week (20 min) |
Oxidative/permanent hair dyes | 580 | ½ Area head | 1/month (30 min) |
Body lotion | 15670 | Area body Area head Female | 2.28/day |
Face cream | 565 | ½ Area head Female | 2.14/day |
Hand cream | 860 | Area hands | 2/day |
Liquid foundation | 565 | ½ Area head Female | 1/day |
Makeup remover | 565 | ½ Area head Female | 1/day |
Eyeshadow | 24 | – | – |
Mascara | 1.6 | – | – |
Eyeliner | 3.2 | – | – |
Lipstick | 4.8 | – | – |
Deodorant (spray & non-spray) | 200 | Axillae | 2/day |
Eua de Toilette | 200 | – | 1/day |
Parfum | 100 | – | 1/day |
Shaving cream | 305 | ¼ Area head Male | 1/day |
Aftershave | 305 | ¼ Area head Male | 1/day |
Sunscreen | 17500 | Total body area | 2/day |
Dermal Absorption Reported in %
SED = A (mg/kg bw/d) X C (%) /100 X DAₚ (%) /100
With:
- SED (mg/kg bw/d) = Systemic Exposure Dose
- A (mg/kg bw/d) = Estimated daily exposure to a cosmetic product per kg body weight, based upon the amount applied and the frequency of application.
- C (%) = the Concentration of the substance under the study in the finished cosmetic product on the application site.
- DAₚ (%) = Dermal Absorption expressed as a percentage of the test dose assume to be applied in real-life conditions.
Relative Exposure Daily Exposure Data
Product Type | Estimated Daily Amount Applied | Relative Amount Applied (mg/kg bw/d) | Retention Factor | Calculated Daily Exposure (g/d) | Calculated Relative Daily Exposure (mg/kg bw/d) |
Shower gel | 18.67 g | 279.20 | 0.01 | 0.19 | 2.79 |
Hand wash soap | 20.00 g | – | 0.01 | 0.20 | 3.33 |
Hair care | |||||
Shampoo | 10.46 g | 150.49 | 0.01 | 0.11 | 1.51 |
Hair conditioner | 3.92 g | – | 0.01 | 0.04 | 0.60 |
Hair styling products | 4.00 g | 57.40 | 0.1 | 0.40 | 5.74 |
Semi-permanent hair dyes (and lotions) | 35 ml (per application) | – | 0.1 | – | – |
Oxidative/permanent hair dyes | 100 ml (per application) | – | 0.1 | – | – |
Body lotion | 7.82 g | 123.20 | 1.0 | 7.82 | 123.20 |
Face cream | 1.54 g | 24.14 | 1.0 | 1.54 | 24.14 |
Hand cream | 2.16 g | 32.70 | 1.0 | 2.16 | 32.70 |
Liquid foundation | 0.51 g | 7.90 | 1.0 | 0.51 | 7.90 |
Make-up remover | 5.00 g | – | 0.1 | 0.50 | 8.33 |
Eye shadow | 0.02 g | – | 1.0 | 0.02 | 0.33 |
Mascara | 0.025 g | – | 1.0 | 0.025 | 0.42 |
Eyeliner | 0.005 g | – | 1.0 | 0.005 | 0.08 |
Lipstick, lip salve | 0.057 g | 0.90 | 1.0 | 0.057 | 0.90 |
Deodorant non-spray | 1.50 g | 22.08 | 1.0 | 1.50 | 22.08 |
Deodorant aerosol spray (ethanol-based) | 1.43 g | 20.63 | 1.0 | 1.43 | 20.63 |
Deodorant spray | 0.69 g | 10.00 | 1.0 | 0.69 | 10.00 |
