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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

United Kingdom

In May 2025, the UK Scientific Advisory Group on Chemical Safety (SAG-CS) published Opinion 18: 4-Methylbenzylidene Camphor as a UV Filter in Cosmetic Products, concluding that 4-MBC cannot be considered safe for use in cosmetic products at any concentration due to concerns about endocrine-disrupting properties and genotoxicity.[11]

On 15 January 2026, the UK Government laid before Parliament the Cosmetic Products Regulation (EC) No 1223/2009 (Restriction of Chemical Substances) (Amendment and Transitional Provisions) Regulations 2026 (SI 2026/23), adding 4-MBC to Annex II of the UK Cosmetics Regulation as a fully prohibited substance. From 15 July 2026, products containing 4-MBC can no longer be placed on the Great Britain market; products already on the market may continue to be sold until 14 January 2027.[12] Northern Ireland continues to follow EU cosmetics legislation under the Windsor Framework. The UK notified the World Trade Organization of the draft regulation on 31 October 2025 under notification G/TBT/N/GBR/107.

China

On 12 January 2026, China’s National Medical Products Administration (NMPA) issued Announcement No. 6 of 2026, incorporating revised standards into the Cosmetic Safety Technical Standards (STSC 2015). 4-MBC was removed from the list of permitted UV filters and added to the list of prohibited substances, aligning China’s regulatory position with the EU ban. Prior to this update, 4-MBC had been permitted in Chinese cosmetics at a maximum concentration of 4%.[13]

Denmark

In 2001, following the publication of a Swiss study raising concerns about the endocrine-disrupting properties of 4-MBC, the Danish Environmental Protection Agency (Miljostyrelsen) applied the precautionary principle and proposed a voluntary warning label for all sunscreens containing 4-MBC, advising that they should not be used on children under the age of 12.[14] Danish retailers subsequently reached a mutual agreement to discontinue the sale of all sunscreen products containing 4-MBC. Although this was not a formal legislative ban, 4-MBC has been effectively absent from the Danish market since the early 2000s.

In 2013, the Danish Centre on Endocrine Disruptors (CeHoS), funded by the Danish EPA, published a comprehensive assessment confirming that 4-MBC demonstrated endocrine disrupting properties in both in vitro and in vivo studies, with effects on the estrogenic and thyroid hormone systems.[15] The Danish EPA further published Survey and health assessment of UV filters (Survey No. 142, 2015), which confirmed that 4-MBC was no longer found in cosmetic products on the Danish market, though biomonitoring data continued to detect its metabolites in the Danish population.[16]

Other countries

  • United States: Not approved by the FDA as a sunscreen active ingredient.[17]
  • Japan: Not permitted.
  • Palau: Banned nationwide under the Responsible Tourism Education Act of 2018 (RPPL #10-30), effective 1 January 2020, as one of ten reef-toxic sunscreen chemicals. Banned products are confiscated upon entry.[18]
  • Thailand: Banned in all national parks since August 2021 by the Department of National Parks, Wildlife and Plant Conservation, as one of four chemicals harmful to coral reefs. Violators face fines of up to 100,000 Baht.[19]

Still Permitted

  • Canada: Permitted at concentrations up to 4%.
  • Australia: Still permitted in therapeutic sunscreens.

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

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. ^ a b “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.
  12. ^ “The Cosmetic Products Regulation (EC) No 1223/2009 (Restriction of Chemical Substances) (Amendment and Transitional Provisions) Regulations 2026”. legislation.gov.uk. UK Government.
  13. ^ “Announcement No. 6 of 2026: Updates to the Cosmetic Safety Technical Standards”. National Medical Products Administration. People’s Republic of China. 12 January 2026.
  14. ^ “Sunscreen”. Danish Environmental Protection Agency.
  15. ^ “Assessment of the endocrine disrupting potential of UV filters” (PDF). Danish Centre on Endocrine Disruptors. 28 February 2013.
  16. ^ “Survey and health assessment of UV filters” (PDF). Danish Environmental Protection Agency. 2015. ISBN 978-87-93352-82-7.
  17. ^ “Sunscreen Drug Products for Over-the-Counter Human Use”. Federal Register.
  18. ^ “Sunscreen Regulations 2020” (PDF). Republic of Palau.
  19. ^ “Make sure your sunscreen is not on the banned list in Thailand”. Tourism Authority of Thailand. 30 August 2021.