Enzacamene

Enzacamene ^[1]

Names
IUPAC name (3E)-1,7,7-Trimethyl-3-[(4-methylphenyl)methylene]-2-norbornanone
Other names 4-Methylbenzylidene camphor 3-(4-Methylbenzylidene)bornan-2-one 3-(4-Methylbenzylidene)-dl-camphor
Identifiers
CAS Number	36861-47-9  Y
3D model (JSmol)	Interactive image
Abbreviations	4-MBC
ChemSpider	4939160  Y
ECHA InfoCard	100.048.386
EC Number	253-242-6
PubChem CID	6434217
UNII	8I3XWY40L9  Y
CompTox Dashboard (EPA)	DTXSID201348972 DTXSID8047896, DTXSID201348972
InChI InChI=1S/C18H22O/c1-12-5-7-13(8-6-12)11-14-15-9-10-18(4,16(14)19)17(15,2)3/h5-8,11,15H,9-10H2,1-4H3/b14-11+ Y Key: HEOCBCNFKCOKBX-SDNWHVSQSA-N Y InChI=1/C18H22O/c1-12-5-7-13(8-6-12)11-14-15-9-10-18(4,16(14)19)17(15,2)3/h5-8,11,15H,9-10H2,1-4H3/b14-11+ Key: HEOCBCNFKCOKBX-SDNWHVSQBW
SMILES O=C2\C(=C\c1ccc(cc1)C)C3CCC2(C)C3(C)C
Properties
Chemical formula	C18H22O
Molar mass	254.37 g/mol
Appearance	White crystalline powder
Melting point	66 to 69 °C (151 to 156 °F; 339 to 342 K)
Solubility in water	Insoluble
Hazards
GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H410
Precautionary statements	P273, P391, P501
Pharmacology
Legal status	Banned in Thailand, Palau and Hawaii
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N  verify  (what is  YN ?) Infobox references

Enzacamene (INN; also known as 4-methylbenzylidene camphor or 4-MBC) is an organic camphor derivative that is used in the cosmetic industry for its ability to protect the skin against UV, specifically UV B radiation. As such, it is used in sunscreen lotions and other skincare products claiming a SPF value.

Mechanism

All camphor-derived sunscreens dissipate photon energy by cis-trans isomerisation. However, for enzacamene, the quantum yield for this isomerization is only between 0.13 and 0.3. This low quantum yield means that other photochemical processes are also occurring, which may contribute to its limited photostability compared to other UV filters. ^[2]

Endocrine disruptor

Studies have extensively documented that enzacamene acts as an endocrine disruptor. The scientific evidence demonstrates both estrogenic and thyroid-disrupting effects:

Estrogenic Effects

Multiple peer-reviewed studies have demonstrated that 4-MBC exhibits estrogenic activity through estrogen receptor binding and activation. Mueller et al. (2003) showed that 4-MBC activates both estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in human and rat cells, with preferential binding to ERβ. The compound stimulated estrogen-responsive alkaline phosphatase activity in human endometrial cells and showed measurable transactivation at concentrations above 1 μM. ^[3]

Schlumpf et al. (2004) demonstrated that 4-MBC and the related compound 3-benzylidene camphor displaced estradiol from estrogen receptors, particularly ERβ, with 4-MBC showing an IC₅₀ of 35.3 μM for ERβ binding. The compound stimulated MCF-7 breast cancer cell proliferation with an EC₅₀ of 3.9 μM. ^[4]

Developmental exposure studies by Durrer et al. (2005) found that prenatal and postnatal exposure to 4-MBC in rats altered expression of estrogen target genes including ERα, progesterone receptor, and insulin-like growth factor-I in the uterus. A related study by Maerkel et al. (2007) demonstrated sex- and region-specific alterations in estrogen target gene regulation in the brain following developmental 4-MBC exposure. ^{[5] [6]}

Thyroid Effects

Research has demonstrated that 4-MBC significantly disrupts thyroid function. Wuttke et al. (2006) found that 4-MBC treatment in rats resulted in decreased serum T₄ levels and increased TSH levels, indicating thyroid disruption. The study showed that 4-MBC inhibited T₄ production while stimulating TSH release, effects that were distinct from estradiol treatment. ^[7]

A comprehensive study presented at the European Congress of Endocrinology (2008) demonstrated that 4-MBC causes effects comparable to primary hypothyroidism in rats. At concentrations ≥33 mg/kg, 4-MBC significantly elevated TSH levels while T₄ levels decreased and T₃ levels remained unchanged - a pattern typical of early hypothyroidism. The study found increased thyroid gland weights and altered expression of thyroid-related genes including TSH receptor, sodium-iodide symporter, and thyroid peroxidase. ^[8]

Regulatory Status and Bans

European Union Ban

The European Union has completely banned 4-MBC in all cosmetic products through Commission Regulation (EU) 2024/996, adopted on April 3, 2024. The Scientific Committee on Consumer Safety (SCCS) concluded in their 2022 opinion that there is insufficient data to evaluate potential genotoxicity and sufficient evidence that 4-MBC acts as an endocrine disruptor affecting both thyroid and estrogen systems. ^{[9] [10]}

Implementation timeline:

• May 1, 2025: Products containing 4-MBC cannot be placed on the EU market
• May 1, 2026: Products containing 4-MBC cannot be made available on the EU market

The compound has been moved from Annex VI (permitted UV filters) to Annex II (prohibited substances) as entry 1730.

Other Jurisdictions

Prohibited countries

• United States: Not approved by the FDA
• Japan: Not permitted
• Denmark: Banned since 2001 following environmental concerns

Still Permitted

• Canada: permitted at concentrations up to 4%
• Australia: Still permitted in therapeutic sunscreens
• United Kingdom: SAG-CS concluded in 2025 that 4-MBC cannot be considered safe for use in cosmetic products due to endocrine disruption and genotoxicity concerns. ^[11]

Safety Concerns

The SCCS has identified multiple safety concerns:

• Insufficient genotoxicity data to exclude mutagenic potential ^[10]
• Endocrine disruption affecting thyroid and estrogen systems
• Systemic absorption through skin with detection in plasma and urine

See also

• Xenoestrogen
• Endocrine disruptor

References

1. 3-(4-METHYLBENZYLIDEN)CAMPHOR at chemicalland21.com
2. Sun Protection in Man. Chapter 26: Cantrell, Ann; McGarvey, David J.; Truscott, T. George. Photochemical and photophysical properties of sunscreens.
3. Mueller, Stefan O.; Kling, Margret; Arifin Firzani, Poppy; Mecky, Astrid; Duranti, Eric; Shields-Botella, Jacqueline; Delansorne, Remi; Broschard, Thomas; Kramer, Peter-Jürgen (2003-04-30). "Activation of estrogen receptor alpha and ERbeta by 4-methylbenzylidene-camphor in human and rat cells: comparison with phyto- and xenoestrogens". Toxicology Letters. 142 (1–2): 89–101. doi:10.1016/s0378-4274(03)00016-x. ISSN   0378-4274. PMID   12765243.
4. Schlumpf, Margret; Jarry, Hubert; Wuttke, Wolfgang; Ma, Risheng; Lichtensteiger, Walter (2004-07-01). "Estrogenic activity and estrogen receptor beta binding of the UV filter 3-benzylidene camphor. Comparison with 4-methylbenzylidene camphor". Toxicology. 199 (2–3): 109–120. Bibcode:2004Toxgy.199..109S. doi:10.1016/j.tox.2004.02.015. ISSN   0300-483X. PMID   15147785.
5. Durrer, Stefan; Maerkel, Kirsten; Schlumpf, Margret; Lichtensteiger, Walter (2005-05-01). "Estrogen Target Gene Regulation and Coactivator Expression in Rat Uterus after Developmental Exposure to the Ultraviolet Filter 4-Methylbenzylidene Camphor". Endocrinology. 146 (5): 2130–2139. doi:10.1210/en.2004-1272. ISSN   0013-7227. PMID   15705771.
6. Maerkel, Kirsten; Durrer, Stefan; Henseler, Manuel; Schlumpf, Margret; Lichtensteiger, Walter (2007-01-15). "Sexually dimorphic gene regulation in brain as a target for endocrine disrupters: developmental exposure of rats to 4-methylbenzylidene camphor". Toxicology and Applied Pharmacology. 218 (2): 152–165. Bibcode:2007ToxAP.218..152M. doi:10.1016/j.taap.2006.10.026. ISSN   0041-008X. PMID   17188730.
7. Seidlová-Wuttke, Dana; Christoffel, Julie; Rimoldi, Guillermo; Jarry, Hubertus; Wuttke, Wolfgang (2006-07-01). "Comparison of effects of estradiol with those of octylmethoxycinnamate and 4-methylbenzylidene camphor on fat tissue, lipids and pituitary hormones". Toxicology and Applied Pharmacology. 214 (1): 1–7. Bibcode:2006ToxAP.214....1S. doi:10.1016/j.taap.2005.11.002. ISSN   0041-008X. PMID   16368123.
8. Gotthardt, Inka; Schmutzler, Cornelia; Petra, Kirschmeyer; Wolfgang, Wuttke; Hubertus, Jarry; Josef, Kohrle (2008-05-01). "The UV absorber 4-methylbenzylidene-camphor (4-MBC) causes effects comparable to primary hypothyroidism". Endocrine Abstracts. 16. ISSN   1470-3947.
9. "4-Methylbenzylidene camphor (4-MBC) - European Commission". health.ec.europa.eu. Retrieved 2025-08-05.
10. "Scientific Committee on Consumer Safety (SCCS). "Opinion on 4-Methylbenzylidene camphor (4-MBC)"" (PDF). Publications Office of the European Union. 29 April 2022.
11. "Opinion 18: 4-Methylbenzylidene Camphor as a UV Filter in Cosmetic Products" (PDF). Department for Business and Trade. UK Government. 22 May 2025.