The 500 Dalton Rule Database
An exhaustive list of common active ingredients cross-referenced against the physical limits of dermal penetration.
The Physical Limit of Skin
The stratum corneum is designed to keep external matter out. In 2000, Bos and Meinardi published the 500 Dalton rule: molecules larger than 500 Da cannot passively cross the corneal layer. Any ingredient larger than this acts strictly on the surface.
| Molecule | Weight (Da) | Status | Function |
|---|---|---|---|
| Water | 18.01 | Penetrates | Hydration |
| Glycolic Acid | 76.05 | Penetrates | Exfoliation |
| L-Ascorbic Acid | 176.12 | Penetrates | Antioxidant |
| Retinol | 286.45 | Penetrates | Cell Turnover |
| Hyaluronic Acid (LMW) | 20,000 - 50,000 | Surface Only | Humectant |
| Collagen | ~300,000 | Surface Only | Film Former |
| Hyaluronic Acid (HMW) | > 1,000,000 | Surface Only | Film Former |
What This Means for Your Routine
Do not spend $150 on topical collagen serums expecting them to "rebuild your skin matrix." They physically cannot. They are expensive moisturizers.