Margin of Safety: How Cosmetic Safety Is Actually Calculated

The Core Formula

The EU's Scientific Committee on Consumer Safety (SCCS) uses a straightforward formula to assess cosmetic ingredient safety:

MoS = NOAEL / SED

If MoS ≥ 100, the ingredient is considered safe

Where:

NOAEL = No Observed Adverse Effect Level (from animal studies, usually oral)
SED = Systemic Exposure Dose (how much actually enters your body from cosmetic use)
100 = Safety factor (10× for interspecies differences × 10× for human variability)

Breaking Down the SED Calculation

The SED is where the real complexity lies. Per SCCS Notes of Guidance (12th Revision, 2023), there are two methods:

Method 1: Percentage-Based (DAp)

SED = E_product × (C/100) × (DAp/100)

E_product = Daily product exposure (mg/kg bw/day)
C = Ingredient concentration (%)
DAp = Dermal absorption percentage (default 50% if unknown)

Method 2: Amount-Based (DAa)

SED = DAa × SSA × f_appl / 60 kg

DAa = Dermal absorption amount (μg/cm²)
SSA = Skin surface area (cm²)
f_appl = Application frequency per day

Real-World Example: Benzophenone-3

Let's walk through how the SCCS assessed oxybenzone (BP-3) using actual data from Rousselle et al. (2022):

BP-3 Safety Assessment

NOAEL: 67.9 mg/kg bw/day (rat developmental study, Nakamura 2015)
Max concentration: 6% in sunscreens
Dermal absorption: 9.9%
Product amount: 18 g/day (whole-body sunscreen)
Body weight: 60 kg

SED = (18,000 mg × 0.06 × 0.099) / 60 kg = 1.78 mg/kg bw/day

MoS = 67.9 / 1.78 = 38

MoS = 38 is below 100, which is why the EU reduced the maximum BP-3 concentration from 6% to 2.2% in body products.

Standard Exposure Values

The SCCS provides default values for daily product exposure (Table 3A in the Notes of Guidance):

Product Type	Daily Amount	mg/kg bw/day
Body lotion	7.82 g	123.2
Face cream	1.54 g	24.1
Hand cream	2.16 g	34.0
Lipstick	0.057 g	0.9
Shampoo	10.46 g	0.3 (rinse-off factor)
Toothpaste	2.75 g	0.5 (limited absorption)

Notice how body lotion has the highest exposure (123.2 mg/kg/day) - this is why retinol limits are stricter for body products (0.05%) than face products (0.3%).

The Dermal Absorption Question

Dermal absorption is often the critical variable. The SCCS accepts data from:

OECD Test Guideline 428: In vitro skin absorption using Franz diffusion cells
Human skin: Preferred, but pig skin is accepted as a surrogate
Default 50%: Used when no data available (conservative assumption)

Example dermal absorption values from the literature:

Ingredient	Dermal Absorption	Source
Retinol	7.7%	Yourick 2008
Benzophenone-3	9.9%	SCCS Opinion
Homosalate	5.3%	Najjar 2022
Benzyl salicylate	9.1%	Ebmeyer 2024
Caffeine	Variable	Bessems 2017

The Next Generation: MOIE

Traditional MoS compares external doses (applied amount vs. NOAEL). But researchers are moving toward Margin of Internal Exposure (MOIE), which compares internal doses:

MOIE = Internal PoD (animal) / Internal Exposure (human)

Uses plasma concentrations instead of applied doses

Why is this better? A 2017 study by Bessems et al. demonstrated that traditional MoS can be non-conservative:

Caffeine dermal scenarios showed traditional MoS = 4
But MOIE values were often <25 (the minimum safe threshold for internal comparisons)
The internal approach accounts for route-specific metabolism that external comparisons miss

PBPK Modeling: The Future

Physiologically-Based Pharmacokinetic (PBPK) modeling is increasingly used to predict internal doses. A 2022 study on homosalate (Najjar et al.) demonstrated:

Homosalate PBPK Results

Rat oral NOAEL: 120 mg/kg/day
Rat AUC at NOAEL: 31,980 ng·h/mL
Human dermal AUC (Day 30): 316 ng·h/mL
MOIE: 31,980 / 316 = ~101

MOIE >25 indicates safety using internal dose comparison

PBPK modeling also allows reducing uncertainty factors. Instead of the default 10× for interspecies toxicokinetics, chemical-specific data can refine this to 2.5× or less - resulting in lower required MoS thresholds.

Aggregate Exposure

For ingredients used in multiple products, the SCCS requires aggregate SED calculation:

SED_aggregate = SED_product1 + SED_product2 + ... + SED_productN

This is why parabens, for example, need aggregate assessment - methylparaben might be safe in one product, but if it's in your face cream, body lotion, shampoo, and deodorant, cumulative exposure matters.

What This Means For You

Key Takeaways

MoS ≥ 100 is the safety threshold - ingredients below this get restricted or banned.
Body products have higher exposure than face products - hence stricter limits for body lotions.
Dermal absorption is usually low - most ingredients don't enter systemic circulation efficiently.
The 100× safety factor is conservative - it accounts for worst-case scenarios and sensitive individuals.
Aggregate exposure matters - using the same ingredient in multiple products adds up.

References

SCCS (2023). Notes of Guidance for the Testing of Cosmetic Ingredients and Their Safety Evaluation (12th Revision). SCCS/1647/22. European Commission.
Bessems JGM, et al. (2017). The margin of internal exposure (MOIE) concept for dermal risk assessment. Toxicology. DOI: 10.1016/j.tox.2017.03.012
Rousselle C, et al. (2022). Using Human Biomonitoring Data to Support Risk Assessment of Cosmetic Ingredients—A Case Study of Benzophenone-3. Toxics. DOI: 10.3390/toxics10020096
Najjar A, et al. (2022). Use of Physiologically-Based Kinetics Modelling to Reliably Predict Internal Concentrations of Homosalate. Frontiers in Pharmacology. DOI: 10.3389/fphar.2021.802514
Ebmeyer J, et al. (2024). Next generation risk assessment: an ab initio case study for benzyl salicylate. Frontiers in Pharmacology. DOI: 10.3389/fphar.2024.1345992