Enzacamene

Identification

Name
Enzacamene
Accession Number
DB11219
Description

Commonly known as 4-methylbenzylidene-camphor (4-MBC), enzacamene is a camphor derivative and an organic chemical UV-B filter. It is used in cosmetic products such as sunscreen to provide skin protection against UV rays. While its effects on the human reproductive system as an endocrine disruptor are being investigated, its use in over-the-counter and cosmetic products is approved by Health Canada. Its tradenames include Eusolex 6300 (Merck) and Parsol 5000 (DSM).

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 254.373
Monoisotopic: 254.167065328
Chemical Formula
C18H22O
Synonyms
  • (+/-)-3-(p-methylbenzylidene)camphor
  • 3-(4-methylbenzylidene)camphor
  • 3-(p-Methylbenzylidene)-DL-camphor
  • 4-MBC
  • 4-methylbenzylidene camphor
  • enzacamène
  • Enzacamene
  • Enzacamene D-L form
  • enzacameno
  • enzacamenum
  • Methyl benzylidene camphor

Pharmacology

Indication

Indicated for use as an active sunscreen agent.

Contraindications & Blackbox Warnings
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Pharmacodynamics

Several studies suggest that enzacamene elicit estrogen-like effects. In prepubertal male rats exposed to enzacamene during embryonic and fetal development, decrease in testicular weight with decreased levels of LH, GnRH, and glutamate were observed; in comparison, there was an increase in LH, GnRH, and aspartate levels in peripubertal rats 2. These findings suggest that high concentrations of enzacamene during embryonic and fetal stage inhibits the testicular axis in male rats during the prepubertal stage and stimulates it during peripubertad stage 2. In a study of zebrafish (Danio rerio) embryo, exposure to enzacamene during early vertebrate development was associated with muscular and neuronal defects that may result in developmental defects, including a reduction in AChE activity, disorganized pattern of slow muscle fibers, and axon pathfinding errors during motor neuron innervation 5. Enzacamene displays a weak binding activity in receptors binding assays using the mammalian estrogen receptor (ER) 4.

Mechanism of action

Enzacamene absorbs UV-B rays. It is proposed that enzacamene exerts estrogen-like activities in the same direction as endogenous estrogens via nonclassical estrogen signaling mechanisms that do not involve gene regulation by the nuclear ER 4. It binds to cytosolic estradiol binding sites of estrogen receptors with low to moderate affinity compared to that of the endogenous agonist. Based on the findings of a study with Xenopus hepatocytes in culture, enzacamene has a potential to induce the ER gene only at higher concentrations (10–100 μmol/L). While enzacamene was not shown to activate estrogen-dependent gene transcription when tested in an ER reporter gene assay in yeast cells, it was demonstrated in Xenopus hepatocytes cultures that activate ER-dependent signaling mechanisms leading to altered gene expression 4. In micromolar concentrations, enzacamene accelerates cell proliferation rate in MCF-7 human breast cancer cells 4.

TargetActionsOrganism
UProgesterone receptor
antagonist
Humans
UAndrogen receptor
antagonist
Humans
UEstrogen receptor betaNot AvailableHumans
UEstrogen receptor alphaNot AvailableHumans
Absorption

The maximum plasma concentration of enzacamene was 16ng/mL in healthy female volunteers following daily whole-body topical application of 2mg/cm^2 of sunscreen formulation at 10% (weight/weight) for four days 1. Blood concentration of enzacamene (4-MBC) and its main metabolite, 3-(4-carboxybenzylidene)camphor, peaked within 10 h after oral administration of enzacamene 6.

Volume of distribution

No pharmacokinetic data available.

Protein binding

No pharmacokinetic data available.

Metabolism

Based on the findings of a rat pharmacokinetic study, it is proposed that absorbed enzacamene following oral administration undergo extensive first-pass hepatic metabolism 6. Following oral administration of enzacamene (4-MBC) in rats, detected metabolites in the plasma and urine were 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. However the blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection following peak concentration 6.

Via hydroxylation mediated by cytochrome P450 system, 3-(4-hydroxymethylbenzylidene)camphor is formed. This metabolite is further oxidized to 3-(4-carboxybenzylidene)camphor via oxidation of alcohol dehydrogenase and aldehyde dehydrogenase, and may be further hydroxylated to form 3-(4-carboxybenzylidene)-6-hydroxycamphor mediated by CYP450 system 6.

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Route of elimination

The urine concentration of 4 ng/mL and 4 ng/mL of enzacamene were observed in female and male volunteers, respectively 3. In a rat pharmacokinetic study, most of orally administered enzacamene was recovered in in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor 6. Glucuronides of both metabolites were also detectable in faces 6. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine 6. Enterohepatic circulation of glucuronides derived from the two major 4-MBC metabolites may explain the slow excretion of 4-MBC metabolites with urine and the small percentage of the administered doses recovered in urine 6.

Half-life

The half life of enzacamene (4-MBC) and its main metabolite, 3-(4-carboxybenzylidene)camphor, displayed half-lives of approximately 15 h after reaching peak plasma concentrations after oral administration in rats 6.

Clearance

No pharmacokinetic data available.

Adverse Effects
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Toxicity

Oral LD50 and dermal LD50 in rat are reported to be 10,000 mg/kg 7. Oral TDLO in rat is 7 mg/kg MSDS. Oral and subcutaneous TDLO following continuous administration in rat are 476 mg/kg/4D and 4 mg/kg/2D, respectively MSDS. Cases of overdose have not been reported for enzacamene. Enzacamene is reported to be an endocrine disruptor that alters the reproductive axis.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.

Products

Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Snik Crm 6%CreamTopicalAustria Import West Ltd.1997-09-102003-07-29Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Anthelios L - Ecran Intolerances Solaires SPF 60Enzacamene (5 %) + Avobenzone (3.5 %) + Ecamsule (3.3 %) + Titanium dioxide (4 %)CreamTopicalLaboratoires La Roche Posay Canada1999-03-012009-06-05Canada flag
Anthelios L-lait Ecran Intol.solaire SPF 60Enzacamene (5 %) + Avobenzone (3.5 %) + Ecamsule (3.3 %) + Titanium dioxide (4 %)LotionTopicalCosmair Canada Inc.1996-12-312001-07-27Canada flag
Anthelios S - Ecran Solaire SPF 30Enzacamene (5 %) + Avobenzone (2 %) + Ecamsule (2 %) + Titanium dioxide (4 %)CreamTopicalLaboratoires La Roche Posay Canada1997-05-292010-06-08Canada flag
Anthelios-creme Solaire SPF 10Enzacamene (3 %) + Avobenzone (3 %) + Ecamsule (2 %) + Titanium dioxide (1.7 %)CreamTopicalCosmair Canada Inc.1996-12-311998-08-12Canada flag
Anthelios-ecran Invisible SPF 20Enzacamene (5 %) + Avobenzone (2 %) + Ecamsule (2 %) + Titanium dioxide (2.5 %)CreamTopicalCosmair Canada Inc.1996-12-311998-08-12Canada flag
Anthelios-lait Ecran Invisible SPF 20Enzacamene (5 %) + Avobenzone (2 %) + Ecamsule (2 %) + Titanium dioxide (2.5 %)LotionTopicalCosmair Canada Inc.1996-12-311998-08-12Canada flag
Anthelios-stick Ecran SPF 30Enzacamene (6 %) + Avobenzone (3 %)StickTopicalCosmair Canada Inc.1996-06-271999-03-16Canada flag
Antherpos-ceralip Solaire SPF 50Enzacamene (6 %) + Avobenzone (2 %) + Ecamsule (1 %) + Titanium dioxide (4 %)CreamTopicalLaboratoires La Roche Posay Canada1996-12-312008-07-23Canada flag
Autobronzant Creme Fps 15Enzacamene (4 %) + Avobenzone (2 %) + Ecamsule (1 %) + Octocrylene (10 %)CreamTopicalOmbrelle Canada2001-03-312005-07-22Canada flag
Autobronzant SPF 7Enzacamene (4 %) + Avobenzone (2 %) + Ecamsule (0.7 %)GelTopicalVichy Canada1999-04-202002-08-01Canada flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Conju Princess UV Sun BlockEnzacamene (0.05 mL/1mL) + Avobenzone (0.03 mL/1mL) + Octinoxate (0.075 mL/1mL) + Titanium dioxide (0.0249 mL/1mL) + Zinc oxide (0.01 mL/1mL)CreamTopicalConju Inc2010-12-18Not applicableUS flag
Conju Princess UV Sun BlockEnzacamene (0.05 mL/1mL) + Avobenzone (0.03 mL/1mL) + Octinoxate (0.075 mL/1mL) + Titanium dioxide (0.0249 mL/1mL) + Zinc oxide (0.01 mL/1mL)CreamTopicalConju Inc2010-12-18Not applicableUS flag
Laser Block 100 sunblockEnzacamene (0.03 mL/1mL) + Amiloxate (0.02 mL/1mL) + Avobenzone (0.005 mL/1mL) + Octinoxate (0.07 mL/1mL) + Titanium dioxide (0.02 mL/1mL) + Zinc oxide (0.05 mL/1mL)CreamTopicalUniversal Cosmetic Co., Ltd2010-08-04Not applicableUS flag
MediSpa Sunblock sunblockEnzacamene (0.03 mL/1mL) + Avobenzone (0.005 mL/1mL) + Octinoxate (0.07 mL/1mL) + Zinc oxide (0.05 mL/1mL)CreamTopicalUniversal Cosmetic Co., Ltd2010-08-04Not applicableUS flag
MediSpa SunSpray sunblockEnzacamene (0.05 mL/1mL) + Octinoxate (0.075 mL/1mL) + Octocrylene (0.01 mL/1mL)SprayTopicalUniversal Cosmetic Co., Ltd2010-08-06Not applicableUS flag
Outback 2-in-1 Insect Repellent and Protective SunscreenEnzacamene (13 mg/1mL) + Octinoxate (90 mg/1mL) + Zinc oxide (80 mg/1mL)CreamTopicalElmore Oil Company Pty Ltd2012-07-01Not applicableUS flag
Secret Key Natural Cc Cushion Spf50 Pa / 02 Natural CcEnzacamene (3 g/100g) + Octinoxate (7 g/100g) + Octisalate (3 g/100g) + Titanium dioxide (12 g/100g)LiquidTopicalZenpia2015-07-052016-08-01US flag
Secret Key Natural Cc Cushion Spf50 Plus / 01 Light CcEnzacamene (3 g/100g) + Octinoxate (7 g/100g) + Octisalate (3 g/100g) + Titanium dioxide (12 g/100g)LiquidTopicalZenpia2015-07-052018-12-19US flag
Secret Key Natural Cc Cushion Spf50 Plus / 02 Natural CcEnzacamene (3 g/100g) + Octinoxate (7 g/100g) + Octisalate (3 g/100g) + Titanium dioxide (12 g/100g)LiquidTopicalZenpia2015-07-052018-12-19US flag

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
8I3XWY40L9
CAS number
36861-47-9
InChI Key
HEOCBCNFKCOKBX-SDNWHVSQSA-N
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+
IUPAC Name
(3E)-1,7,7-trimethyl-3-[(4-methylphenyl)methylidene]bicyclo[2.2.1]heptan-2-one
SMILES
CC1=CC=C(\C=C2/C3CCC(C)(C2=O)C3(C)C)C=C1

References

General References
  1. Latha MS, Martis J, Shobha V, Sham Shinde R, Bangera S, Krishnankutty B, Bellary S, Varughese S, Rao P, Naveen Kumar BR: Sunscreening agents: a review. J Clin Aesthet Dermatol. 2013 Jan;6(1):16-26. [PubMed:23320122]
  2. Carou ME, Szwarcfarb B, Deguiz ML, Reynoso R, Carbone S, Moguilevsky JA, Scacchi P, Ponzo OJ: Impact of 4-methylbenzylidene-camphor (4-MBC) during embryonic and fetal development in the neuroendocrine regulation of testicular axis in prepubertal and peripubertal male rats. Exp Clin Endocrinol Diabetes. 2009 Oct;117(9):449-54. [PubMed:19885997]
  3. Janjua NR, Kongshoj B, Andersson AM, Wulf HC: Sunscreens in human plasma and urine after repeated whole-body topical application. J Eur Acad Dermatol Venereol. 2008 Apr;22(4):456-61. doi: 10.1111/j.1468-3083.2007.02492.x. Epub 2008 Jan 23. [PubMed:18221342]
  4. Klann A, Levy G, Lutz I, Muller C, Kloas W, Hildebrandt JP: Estrogen-like effects of ultraviolet screen 3-(4-methylbenzylidene)-camphor (Eusolex 6300) on cell proliferation and gene induction in mammalian and amphibian cells. Environ Res. 2005 Mar;97(3):274-81. doi: 10.1016/j.envres.2004.07.004. [PubMed:15589235]
  5. Li VW, Tsui MP, Chen X, Hui MN, Jin L, Lam RH, Yu RM, Murphy MB, Cheng J, Lam PK, Cheng SH: Effects of 4-methylbenzylidene camphor (4-MBC) on neuronal and muscular development in zebrafish (Danio rerio) embryos. Environ Sci Pollut Res Int. 2016 May;23(9):8275-85. doi: 10.1007/s11356-016-6180-9. Epub 2016 Feb 18. [PubMed:26888529]
  6. Volkel W, Colnot T, Schauer UM, Broschard TH, Dekant W: Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats after oral administration. Toxicol Appl Pharmacol. 2006 Oct 15;216(2):331-8. doi: 10.1016/j.taap.2006.05.012. Epub 2006 May 23. [PubMed:16806338]
  7. OPINION ON 4-Methylbenzylidene camphor (4-MBC) - European Union [File]
PubChem Compound
7019255
PubChem Substance
347827944
ChemSpider
4939160
BindingDB
50103609
RxNav
1311507
ChEBI
135937
ChEMBL
CHEMBL2104261
Wikipedia
Enzacamene
AHFS Codes
  • 84:80.00 — Sunscreen Agents
MSDS
Download (26.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
StickTopical
EmulsionTopical
GelTopical
SprayTopical
LotionTopical
CreamTopical
LiquidTopical
CreamTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)66-69European Commission SCCP: Opinion on 4-methylbenzylidene camphor (4-MBC)
water solubilityPoorly solubleEuropean Commission SCCP: Opinion on 4-methylbenzylidene camphor (4-MBC)
logP5.14European Commission SCCP: Opinion on 4-methylbenzylidene camphor (4-MBC)
Predicted Properties
PropertyValueSource
Water Solubility0.0051 mg/mLALOGPS
logP5.09ALOGPS
logP5.12ChemAxon
logS-4.7ALOGPS
pKa (Strongest Basic)-5.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area17.07 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity79.68 m3·mol-1ChemAxon
Polarizability30.58 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Schreurs RH, Sonneveld E, Jansen JH, Seinen W, van der Burg B: Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays. Toxicol Sci. 2005 Feb;83(2):264-72. Epub 2004 Nov 10. [PubMed:15537743]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Schreurs RH, Sonneveld E, Jansen JH, Seinen W, van der Burg B: Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays. Toxicol Sci. 2005 Feb;83(2):264-72. Epub 2004 Nov 10. [PubMed:15537743]
  2. Jimenez-Diaz I, Molina-Molina JM, Zafra-Gomez A, Ballesteros O, Navalon A, Real M, Saenz JM, Fernandez MF, Olea N: Simultaneous determination of the UV-filters benzyl salicylate, phenyl salicylate, octyl salicylate, homosalate, 3-(4-methylbenzylidene) camphor and 3-benzylidene camphor in human placental tissue by LC-MS/MS. Assessment of their in vitro endocrine activity. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Oct 1;936:80-7. doi: 10.1016/j.jchromb.2013.08.006. Epub 2013 Aug 8. [PubMed:24004914]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. Matsumoto H, Adachi S, Suzuki Y: [Estrogenic activity of ultraviolet absorbers and the related compounds]. Yakugaku Zasshi. 2005 Aug;125(8):643-52. [PubMed:16079615]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Matsumoto H, Adachi S, Suzuki Y: [Estrogenic activity of ultraviolet absorbers and the related compounds]. Yakugaku Zasshi. 2005 Aug;125(8):643-52. [PubMed:16079615]
  2. Jimenez-Diaz I, Molina-Molina JM, Zafra-Gomez A, Ballesteros O, Navalon A, Real M, Saenz JM, Fernandez MF, Olea N: Simultaneous determination of the UV-filters benzyl salicylate, phenyl salicylate, octyl salicylate, homosalate, 3-(4-methylbenzylidene) camphor and 3-benzylidene camphor in human placental tissue by LC-MS/MS. Assessment of their in vitro endocrine activity. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Oct 1;936:80-7. doi: 10.1016/j.jchromb.2013.08.006. Epub 2013 Aug 8. [PubMed:24004914]

Drug created on December 03, 2015 09:51 / Updated on October 26, 2020 22:41

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