Ecamsule (Mexoryl SX)
INCI: Terephthalylidene Dicamphor Sulfonic Acid CAS: 92761-26-7 · PubChem CID: 146382 · ChEMBL: CHEMBL3989850 · MW: 562.7 g/mol · Formula: C₂₈H₃₄O₈S₂
Ecamsule (trade name Mexoryl SX; USAN/INN: ecamsule; abbreviated TDSA in regulatory documents) is a water-soluble, photostable organic UV filter that absorbs predominantly in the UVA-II and short-UVA-I range (λmax ≈ 345 nm), providing coverage from approximately 290–380 nm with peak activity around 345 nm. It was developed by L’Oréal R&D and is commercially used as the foundation UVA filter in the Mexoryl family of L’Oréal/La Roche-Posay sunscreen formulations, typically paired with its lipophilic sibling drometrizole-trisiloxane (Mexoryl XL; λmax 303/344 nm, oil-soluble) to achieve complementary UVA coverage, and further extended to 385 nm with the newer mexoryl-400 (MCE) in the Anthelios UVMune 400 line.
Ecamsule’s most clinically distinguishing property is its water solubility — it dissolves in the aqueous phase of sunscreen emulsions, making it compatible with formulations where oil-soluble UVA absorbers (avobenzone, Tinosorb S, Mexoryl XL) cannot provide full coverage. It is photostable at expected in-use concentrations and does not require separate photostabilizers.
This page covers the underlying filter molecule. For the umbrella photoprotection intervention, see uv-protection.
Regulatory status — the critical nuance (product-specific NDA, NOT GRASE)
Ecamsule’s US regulatory status is categorically distinct from both the EU/global approval and from filter-molecules that simply lack US approval. It is FDA-approved, but through a product-specific New Drug Application (NDA) — not via the OTC sunscreen monograph route that would make it Generally Recognized as Safe and Effective (GRASE) for general use.
| Region | Status | Notes |
|---|---|---|
| United States (FDA) | Approved — product-specific NDA, non-GRASE | Approved 2006 via NDA for specific L’Oréal/La Roche-Posay products. Primary NDA: NDA021502 (Anthelios SX SPF 15; L’Oréal USA). Related NDAs: NDA021501 (Capital Soleil SPF 15), NDA021471 (Anthelios 20), NDA022009 (Anthelios 40). Not on the FDA OTC sunscreen monograph (21 CFR Part 352); NOT GRASE for general/free use by other formulators. Only named NDA-holder products may market ecamsule as a sunscreen in the US. |
| EU | Approved; long-standing Annex VI entry | One of the original 28 permitted UV filters in Annex VI of the EU Cosmetics Regulation (1223/2009/EC); authorized at ≤10% in products for skin (much higher ceiling than the newer MCE 3% or TriAsorB 5%). The SCCS has reviewed ecamsule multiple times without generating safety concerns. |
| Australia (TGA) | Permitted | Listed ingredient in TGA-registered sunscreens. |
| Canada (Health Canada) | Permitted | On the Cosmetic Ingredient Hotlist as a permitted sunscreen active. |
| Japan / Asia | Widely permitted | Part of standard broad-spectrum EU-influenced approvals in major Asian markets. |
Why the product-specific-NDA matters in practice:
L’Oréal holds the US NDA. This means:
- Only L’Oréal-designated products (Anthelios SX) may lawfully include ecamsule and be marketed as sunscreens in the US.
- Competing formulators cannot add ecamsule to their products — they would need their own NDA (an entirely new pharmaceutical development program) or petition for inclusion in the OTC monograph.
- The FDA’s broader 2019 proposed rule determined that most organic UV filters, including ecamsule, do not have sufficient safety data to be classified as GRASE Category I under the maximal-use PK threshold test (see § Systemic absorption). Ecamsule’s NDA approval pre-dated this rulemaking; it was not prospectively re-evaluated under the 2019 standard.
- From a consumer perspective: US-market Anthelios SX is available, but it contains ecamsule only at SPF 15 in the original NDA formulation — the broader Anthelios lineup in the US uses GRASE filters only (avobenzone + mineral filters). Importing EU-formulation Anthelios with Mexoryl SX/XL or Mexoryl SX + Mexoryl 400 is the practical route to ecamsule use at SPF 50+ in the US.
This makes ecamsule unique in the UV-filter landscape: it is the only chemical UV filter that is simultaneously (1) FDA-approved via NDA, (2) EU-permitted, and (3) not GRASE for general US use. Contrast with avobenzone (US GRASE) and mexoryl-400 / triasorb (neither GRASE nor NDA-approved in the US).
Mechanism
Ecamsule is a di-sulfonic acid derivative of camphor — specifically the disodium salt of terephthalylidene dicamphor sulfonic acid. Structurally, two camphor rings are bridged by a terephthalylidene (para-phenylene-bis-methylenyl) linker, with sulfonate groups providing the water solubility that makes Mexoryl SX the aqueous-phase UVA absorber in emulsion systems.
The molecule absorbs UV photons in the UVA-II range (320–340 nm) and short UVA-I (340–380 nm), with a secondary absorption shoulder in UVB. Upon photon absorption the molecule undergoes photoisomerization around the exocyclic double bond — the E/Z isomerization cycle dissipates the absorbed energy non-radiatively as heat and regenerates the ground-state absorber. This intramolecular photoisomerization mechanism is the basis for ecamsule’s photostability: unlike avobenzone (which photodegrades into non-absorbing ring-opened products and generates free radicals), ecamsule cycles between E and Z forms without meaningful net photodegradation under normal in-use solar exposure 1.
Coverage compared to related UVA filters:
| Filter | λmax (nm) | Primary coverage | Photostable? | Water-soluble? |
|---|---|---|---|---|
| Ecamsule (Mexoryl SX) | 345 | UVA-II + short UVA-I | Yes | Yes |
| Drometrizole trisiloxane (Mexoryl XL) | 303, 344 | UVB + UVA-II + short UVA-I | Yes | No (oil) |
| Avobenzone | 357 | UVA-I (360–400 nm peak) | No (requires photostabilizer) | No (oil) |
| mexoryl-400 (MCE) | 385 | Long UVA-I (380–400 nm) | Yes | No (oil) |
| triasorb (PBT) | UVB–HEV | UVB + UVA + HEV 400–450 nm | Yes | No (particulate) |
Ecamsule fills the 320–360 nm UVA-II and short-UVA-I band with high efficiency and photostability. Its aqueous-phase character means it can achieve UVA-II protection in a water-based or combination-emulsion formula without competing for the oil phase that lipophilic filters occupy. The canonical L’Oréal pairing is ecamsule (Mexoryl SX, aqueous) + drometrizole trisiloxane (Mexoryl XL, oil-phase) for combined ~290–380 nm broad UVA coverage — extended to 400 nm by MCE (Mexoryl 400) in the UVMune 400 line.
Aging-relevance of the UVA-II band
The UVA-II (320–340 nm) and short UVA-I (340–370 nm) bands drive:
- Indirect DNA damage: ROS-mediated 8-OHdG, single-strand breaks, and pyrimidine dimer induction (lower efficiency than UVB, but higher ambient irradiance and dermal penetration depth) 1
- Immunosuppression: Langerhans cell migration, contact-hypersensitivity attenuation, p53 induction
- Pigmentation: Persistent pigment darkening (PPD) through oxidative stress and melanocyte stimulation
- MMP induction: UVA-I (340–400 nm) activates AP-1 and NF-κB, driving MMP-1/3/9; the Fisher 1996 mechanism cascade (see uv-protection) is band-agnostic at the AP-1 level
- Polymorphous light eruption (PLE): An immunologically mediated photodermatosis disproportionately triggered by UVA, attenuated by ecamsule-containing formulations in controlled trials 2
Ecamsule filters specifically the band most responsible for photoimmunological responses and ROS-mediated indirect DNA damage, complementing avobenzone’s UVA-I (360–400 nm) peak absorption.
Human evidence
Ecamsule’s clinical evidence base is substantially older and more mechanistically diverse than the newer MCE/TriAsorB evidence bases, but shares the same limitation of sponsor-authored studies (L’Oréal / La Roche-Posay).
| Study | Design | n | Key result |
|---|---|---|---|
| Fourtanier 2008 1 | Review of multiple in-vitro + in-vivo clinical studies | Multiple cohorts | Mexoryl SX formulations prevented pigmentation, reduced CPD/pyrimidine dimers + p53 accumulation, suppressed MMP expression, attenuated immunosuppression endpoints, and prevented PLE flares in multiple independent studies summarized |
| DeLeo 2009 2 | Double-blind randomized outdoor trial (PLE prevention) | 144 | SPF40 formula with ecamsule + avobenzone: 56% PLE flare prevention vs formula without ecamsule (p<0.001); 36% vs formula without avobenzone (p=0.02); full dual-UVA formula significantly superior — demonstrates ecamsule’s additive role over UVA-I-only coverage · Published in Cutis, not JAAD (footnote corrected) |
| Matta 2019 3 (FDA) | Maximal-use pharmacokinetic RCT | 24 | Ecamsule Cmax 1.5 ng/mL under maximal-use conditions (2 mg/cm² × 4 applications/day × 4 days); exceeded FDA’s 0.5 ng/mL threshold; see § Systemic absorption |
| Hofer 2019 4 | In-vitro ROS / cell viability in UV-stressed keratinocytes + fibroblasts | Cell culture | Ecamsule showed protective effects vs oxybenzone (pro-oxidative) under combined UV/ROS stress — a mechanistic differentiation from legacy filters; noted as contradictory between filters |
What’s missing from this evidence base:
- No independent (non-L’Oréal) long-term photoaging RCT with biopsy endpoints (CPD, collagen histology, MMP-1 IHC)
- No head-to-head comparison isolating ecamsule vs avobenzone for hard photoaging outcomes in healthy (non-PLE) populations
- Limited evidence at the filter-molecule level vs whole-formulation comparisons (photostabilizer contributions cannot be isolated in most studies)
gap/no-independent-replication · gap/no-biopsy-endpoint
Systemic absorption
The FDA’s 2019 maximal-use pharmacokinetic study 3 found ecamsule plasma Cmax = 1.5 ng/mL — the lowest of the four filters tested (oxybenzone 209.6 ng/mL [spray 1]; avobenzone 1.8–4.3 ng/mL [cream → lotion/spray]; octocrylene 2.9–7.8 ng/mL; ecamsule 1.5 ng/mL [cream only, the ecamsule-containing formulation]). All four exceeded the FDA’s 0.5 ng/mL threshold above which additional safety data is required.
Interpreting this for ecamsule specifically:
- Ecamsule’s 1.5 ng/mL Cmax is ~130-fold lower than oxybenzone and ~3–6x lower than avobenzone and octocrylene under the same maximal-use exposure protocol.
- The 0.5 ng/mL threshold is a regulatory trigger for additional safety studies, not an established harm threshold.
- Ecamsule’s high MW (562.7 g/mol), water solubility (rather than lipid-phase partitioning), and sulfonate groups plausibly limit membrane permeation compared with oil-soluble filters — consistent with the lowest Cmax in the FDA panel.
- No in-vitro endocrine-disrupting activity has been reported for ecamsule in the published literature at concentrations relevant to dermal absorption levels.
- The FDA has not withdrawn or restricted Anthelios SX based on the Matta 2019 data; the study’s implication is that further long-term safety data would be needed before ecamsule could be considered GRASE, not that known harm exists.
Under standard daily use (not maximal-use: ~0.5 mg/cm² face application 1x/day), expected plasma exposure would be substantially lower than the Matta 2019 maximal-use Cmax.
Safety
- Photostability: Ecamsule is photostable in finished formulations and does not photo-degrade under solar UV. No photosensitization cases attributed to photodegradation products.
- Contact sensitization: Low — limited published case reports of contact allergy to ecamsule. No major independent adverse event signal analogous to oxybenzone or avobenzone.
- Aquatic ecotoxicity: Published data on ecamsule’s aquatic persistence are limited relative to the newer triazine filters. Its water solubility may increase aquatic compartment partitioning but ecamsule-specific reef/aquatic-organism ecotoxicology is not as well-characterized as for oxybenzone (known coral toxin) or Fagervold 2025’s TriAsorB sediment-persistence finding. gap/long-term-unknown
- Systemic safety: See § Systemic absorption. No reproductive, carcinogenic, or endocrine harm documented at dermal-absorption levels.
Product availability
| Product | Manufacturer | Region | Ecamsule present? |
|---|---|---|---|
| Anthelios SX SPF 15 | L’Oréal / La Roche-Posay | US (NDA-approved) | Yes — only US-market product with ecamsule |
| Anthelios SPF 50+ (EU/global, non-UVMune 400 line) | L’Oréal / La Roche-Posay | EU / UK / CA / AU | Yes (Mexoryl SX in standard Anthelios stacks) |
| Anthelios UVMune 400 (SPF 50+, 5 SKUs) | L’Oréal / La Roche-Posay | EU / UK / CA / AU | Yes — Mexoryl SX + Mexoryl XL + Mexoryl 400 (MCE) triple-Mexoryl stack |
| Capital Soleil (Vichy) | L’Oréal group | EU | Select SKUs contain Mexoryl SX |
| Non-L’Oréal products | — | Anywhere | No — ecamsule is L’Oréal-proprietary and not available for licensing to other formulators |
US-market Anthelios products with higher SPF (Melt-In Milk SPF 60, Clear Skin SPF 60, Mineral SPF 50, etc.) do not contain ecamsule — they use FDA-GRASE filters only. The Anthelios SX SPF 15 product is the sole NDA-approved US ecamsule product and is limited to SPF 15, which is below the SPF 30 recommended for daily anti-photoaging use by AAD guidelines.
Context within the Mexoryl family
L’Oréal’s “Mexoryl” branded filters comprise three distinct molecules at different stages of regulatory clearance:
| Filter | Solubility | λmax | Regulatory range | Status |
|---|---|---|---|---|
| Mexoryl SX (ecamsule, this page) | Water-soluble | ~345 nm | EU ≤10%; US NDA only | Oldest; paired with Mexoryl XL for full UVA-II + short-UVA-I coverage |
| Mexoryl XL (drometrizole-trisiloxane) | Oil-soluble | 303, 344 nm | EU-approved; not GRASE | UVB-range + UVA-II supplementary; photostable siloxane scaffold |
| Mexoryl 400 (mexoryl-400, MCE) | Oil-soluble | ~385 nm | EU ≤3%; not GRASE | Newest; fills 380–400 nm ultra-long UVA-I gap; see separate page |
In the top-tier EU Anthelios UVMune 400 formulation, all three Mexoryl filters are co-formulated alongside avobenzone and Tinosorb S, providing continuous absorption from ~290 nm (UVB onset) through 400 nm (upper limit of UVA-I).
Recency literature search note (R25)
Recency search (R25) was performed on 2026-06-09. Queries: ecamsule OR "Mexoryl SX" OR "terephthalylidene dicamphor sulfonic", mindate 2021 to 2026 (5-year window); plus ecamsule AND (meta-analysis[pt] OR randomized+controlled+trial[pt] OR systematic+review[pt]), mindate 2019–2026.
Results: 9 total recent publications. No recent ecamsule-specific RCTs or meta-analyses on photoaging endpoints were identified. High-priority triaged papers:
- Turner & Torgerson 2025 (PMID 40778531) 5 — regulatory analysis arguing US sunscreen reform would allow ecamsule and other modern filters; contextual, not efficacy data. Consistent with training-era knowledge.
- Matta 2019 (PMID 31058986, RCT) — the most important RCT in the literature; ecamsule Cmax 1.5 ng/mL under maximal-use conditions. Already the canonical PK anchor.
- Wang 2024 (lignin/ecamsule nanoparticles, PMID 39542311) — formulation chemistry paper; no aging endpoint.
- Remaining hits: off-topic (membrane filtration, Crohn’s disease drug repurposing) or formulation/ecotoxicology.
No recent paper contradicts the training-era evidence base. The literature remains thin — ecamsule has few recent primary-efficacy publications because it has been part of the standard Mexoryl stack for 20+ years and is no longer an investigational compound. Evidence gaps are structural (no independent, no biopsy endpoints) not contradicted.
Evidence gaps and limitations
-
No independent-replication long-term photoaging RCT with biopsy histology (collagen, MMP-1). The DeLeo 2009 PLE-endpoint trial is the best human evidence but PLE prevention is a different endpoint from photoaging retardation in healthy skin. gap/no-independent-replication
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Ecamsule contribution vs whole-formulation is difficult to isolate because all clinical studies compared full Mexoryl SX-containing formulas to matched formulas missing only ecamsule (or only avobenzone). The filter-molecule contribution per se is not directly tested in isolation.
-
Long-term systemic safety data gap: Matta 2019 demonstrated plasma absorption; no follow-up chronic-exposure safety study has been published. gap/long-term-unknown
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US regulatory stasis: Ecamsule is FDA-approved only via a product-specific NDA for one SPF 15 product. Without GRASE status, ecamsule cannot be freely incorporated into US sunscreen formulations, constraining consumer access in the highest-UV-protection formulations. gap/regulatory-gap
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Drometrizole trisiloxane (Mexoryl XL) page: Now seeded as drometrizole-trisiloxane. The canonical Mexoryl SX + Mexoryl XL co-formulation strategy is now cross-documented on both pages.
Cross-organism extrapolation
Not applicable — UV filtration is a physical/chemical process, not a biological pathway dependent on species-specific biology.
| Dimension | Status |
|---|---|
| Pathway conserved in humans? | Yes — UV → CPD/8-OHdG/AP-1/MMP cascade is human-validated (Fisher 1996) |
| Phenotype conserved in humans? | Yes — photoaging is a human endpoint; PLE prevention directly measured |
| Replicated in humans? | Partial — PLE endpoints replicated; hard photoaging biopsy endpoints not independently replicated |
Cross-references
- uv-protection — parent intervention page (UV protection as anti-photoaging strategy; Cmax table including ecamsule 1.5 ng/mL)
- mexoryl-400 — newer Mexoryl family member (λmax 385 nm; ultra-long UVA-I gap-fill); comparison table above
- triasorb — competing ultra-long UVA-I + HEV filter (Pierre Fabre/Avène); comparison table on that page
- drometrizole-trisiloxane — Mexoryl XL (oil-soluble partner filter; no wiki page yet — implicit stub)
- bemotrizinol — Tinosorb S; broad-spectrum EU filter; EU/Asia approved, not US GRASE
- bisoctrizole — Tinosorb M; particulate hybrid; EU/Asia approved, not US GRASE
- iscotrizinol — HDT / Uvasorb HEB; EU approved
- tinosorb-a2b — Tinosorb A2B; EU recently approved
- genomic-instability — UV-induced CPD/6-4PP/8-OHdG DNA damage burden
- loss-of-proteostasis — UV-MMP cascade degrading dermal collagen/elastin
- chronic-inflammation — UV-NF-κB cytokine induction; immunosuppression
- skin-aging — primary photoaging endpoint
Footnotes
Footnotes
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doi:10.1111/j.1600-0781.2008.00365.x · Fourtanier A, Moyal D, Seité S · Photodermatol Photoimmunol Photomed 2008;24(4):164–174 · review · Multiple L’Oréal-authored in-vitro + in-vivo cohorts · Mexoryl SX formulations: dose-dependent pigmentation prevention; reduced pyrimidine dimer + p53 accumulation; attenuated immunosuppression; reduced MMP expression; prevented PLE flares · photoisomerization-based photostability mechanism described · COI: L’Oréal-authored review · gap/no-fulltext-access ↩ ↩2 ↩3
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PMID:19326695 · DeLeo VA, Clark S, Fowler J, Poncet M, Loesche C, Soto P · Cutis 2009;83(2):95–103 · rct (double-blind, randomized outdoor) · n=144 · SPF40 with ecamsule+avobenzone vs formula minus ecamsule vs formula minus avobenzone · 56% PLE flare prevention vs ecamsule-deprived comparator (p<0.001); 36% vs avobenzone-deprived comparator (p=0.02); full dual-UVA formula significantly superior · Note: doi:10.1016/j.jaad.2008.11.032 is a conference abstract in JAAD 60(3):AB2 (2009 AAD meeting poster); the peer-reviewed full paper is in Cutis (PMID 19326695); Crossref does not list a separate DOI for the Cutis paper · COI: L’Oréal-sponsored · gap/no-fulltext-access ↩ ↩2
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doi:10.1001/jama.2019.5586 · Matta MK, Zusterzeel R, Pilli NR, et al. (FDA Office of Clinical Pharmacology) · JAMA 2019;321(21):2082–2091 · rct (open-label maximal-use PK) · n=24 healthy adults · 2 mg/cm² × 4 applications/day × 4 days across 75% BSA · ecamsule Cmax 1.5 ng/mL (cream); oxybenzone 194.9–209.6 ng/mL; avobenzone 1.8–4.3 ng/mL (cream 1.8 ng/mL → sprays up to 4.3 ng/mL); octocrylene 2.9–7.8 ng/mL; all 4 exceeded 0.5 ng/mL regulatory threshold within 4 hr · 0.5 ng/mL is a regulatory trigger, NOT an established harm level · PMID:31058986 ↩ ↩2
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doi:10.14573/altex.1808201 · Hofer S, Stonig M, Wally V, et al. · ALTEX 2019 · in-vitro · UV-stressed keratinocytes + fibroblasts · ecamsule showed protective vs oxybenzone (pro-oxidative) and menthyl anthranilate under combined UV/ROS stress; “remarkable differences in mode of action” between filters · mechanistic differentiation study; no in-vivo endpoints · open access (gold OA) ↩
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PMID 40778531 · Turner CW, Torgerson L · Photodermatol Photoimmunol Photomed 2025;41(5) · review/regulatory analysis · US sunscreen regulatory framework lags behind EU; newer filters (bemotrizinol, drometrizole trisiloxane) provide broader protection but lack FDA GRASE; OTC Monograph Order Request process proposed as reform pathway · contextual; no new efficacy data for ecamsule · no declared COI ↩