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CLIMBAZOLE

CLIMBAZOLE; CAS Number: 38083-17-9

Synonym: CLIMBAZOLE; CLİMBAZOLE; KLİMBAZOL; KLIMBAZOL; clımbazole; climbazole; klimbazol; klımbazol; 1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutan-2-one; 1-(4-Chlorophenoxy)-1-(imidazole-1-yl)-3,3-dimethylbutan-2-one; 2-Butanone; 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3; 3-dimethyl-; Climbazole; 38083-17-9; Climbazol; Baypival; Baysan; BAY-E 6975; 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one; Climbazol [INN-Spanish]; Climbazolum [INN-Latin]; 2-Butanone, 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethyl-; EINECS 253-775-4; 1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethylbutan-2-one; BRN 0618020; CHEBI:83719; OWEGWHBOCFMBLP-UHFFFAOYSA-N; NCGC00166153-01; AK161858; 1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutanone; 1-(p-Chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2-butanone; 1-(p-Chlorophenoxy)-3,3-dimethyl-1-(1-imidazolyl)-2-butanone; DSSTox_CID_26555; DSSTox_RID_81715; DSSTox_GSID_46555; AO-295/40848554; Q-100974; Climbazolum; 1-(4-chlorophenoxy)-1-(1-imidazolyl)-3,3-dimethyl-2-butanone; 1-(4-Chlorophenoxy)-1-(1H-imidazolyl)-3,3-dimethyl-2-butanone; 1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethyl-2-butanone; 2-BUTANONE, 1-(p CHLOROPHENOXY)-3,3-DIMETHYL-1-(1-IMIDAZOLYL)-; CAS-38083-17-9; Climbazole [BAN:INN; Climbazole [INN:BAN]; Bay e 6975; CCRIS 8169; MEB 6401; EC 253-775-4; SCHEMBL39729; US9138393, Climbazole; US9144538, Climbazole; 5-23-04-00209; MLS004773943; BAY e-6975; CHEMBL1437764; DTXSID6046555; KS-00000UQD; OWEGWHBOCFMBLP-UHFFFAOYSA-; BDBM181112; HMS2090O13; HMS3652P05; HMS3744O15; Pharmakon1600-01504833; 1-(4-Clorophenoxy)-3,3-dimethyl-1-(imidazole-1-yl)-2-butanone; HY-B1151; MEB-6401; Tox21 112343; Tox21_112343; 1-(4-Chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethyl-2-butanone; AC-272; DL-358; MFCD00055505; NSC759808; s4178; AKOS015895513; Tox21_112343_1; API0026090; CCG-213958; CS-4675; KS-5112; NSC-759808; Climbazole 10 microg/mL in Cyclohexane; NCGC00166153-02; NCGC00166153-03; LS-46662; SC-25381; SMR001550495; AB0012194; AX8020560; DB-049235; FT-0624097; FT-0655760; ST24046357; SW219213-1; Climbazole, PESTANAL(R), analytical standard; K-8328; AB01275501-01; AB01275501_02; AB01275501_03; 083C179; A824009; C-36329; Q629373; SR-05000001501; SR-05000001501-1; BRD-A61676498-001-01-7; Climbazole, United States Pharmacopeia (USP) Reference Standard; 1-(4-chloranylphenoxy)-1-imidazol-1-yl-3,3-dimethyl-butan-2-one; 1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutan-2-one; 1-(4-chlorophenoxy)-3,3-dimethyl-1-(imidazol-1-yl)-butan-2-one; 1-(4-Chlorophenoxy)-3,3-dimethyl-1-(imidazole-1-yl)-2-butanone; InChI=1/C15H17ClN2O2/c1-15(2,3)13(19)14(18-9-8-17-10-18)20-12-6-4-11(16)5-7-12/h4-10,14H,1-3H3

Climbazole

Climbazol saçta oluşan yoğun kepek tedavisi için üretilen şampuanlarda bulunan en etkili mantar öldürücü maddedir. Çünkü kepek ve aşırı kepek sorununa neden olan en önemli faktör mantar olduğu bilinmektedir.

Climbazol Dışındaki Maddeler
Uzun yıllardır kullanılan itrakonazol, ketokonazol gibi diğer mantar öldürücülere karşı mantarlarda direnç gelişmiş ve bu maddelerin etkisi eskiye kıyasla azalmıştır. Mantarlar tarafından tanınmadığı için climbazol etkinlik açısından hepsinin önüne geçmektedir. Avrupa ülkelerinde 2-3 yıldır kullanılan climbazol son dönemde Türkiye`de üretilen şampuanlarda da kullanılmaya başlanmıştır.

Climbazol Seboreik Dermatit Tedavisinde
Mantar ilaçlarının etkili dozda şampuanlarda kullanılması saçlı deri mantarları, yağlı egzama ve yoğun kepeğin en sık sebebi olan mantarların tedavisinde en yaygın tedavi şeklidir. Gerek yoğun kepekte gerekse yağlı egzama (seboreik dermatit) da % 60-80`ler düzeyinde mantar (malesezia furfur ve pitriazis sporum mantarları) görülmektedir. Bu sebeple bu hastalıklar teşhis edildiğinde mutlaka mantar öldürücü etkiye de sahip şampuanlar önerilir.
Climbazole Yan Etkisi Yoktur
Kepeğe yani mantara etkili ketoral Şampuan, konazol, nizoral şampuan yan etkileri sebebiyle ancak haftada bir iki defa kullanılabilirken climbazol içeren şampuanlar günlük şampuanlar gibi her gün kullanılabilir.

IUPAC name[show]
PubChem CID 37907
ChemSpider 34752
UNII 9N42CW7I54
ChEBI CHEBI:83499
ChEMBL
ChEMBL1437764 ☒
CompTox Dashboard (EPA)
DTXSID6046555 Edit this at Wikidata
ECHA InfoCard 100.048.870 Edit this at Wikidata
Chemical and physical data
Formula C15H17ClN2O2
Molar mass 292.76 g·mol-1
3D model (JSmol)
Interactive image
Chirality Racemic mixture
SMILES[show]
InChI[show]
☒☑ (what is this?) (verify)
Climbazole is a topical antifungal agent commonly used in the treatment of human fungal skin infections such as dandruff[2] and eczema. Climbazole has shown a high in vitro and in vivo efficacy against Malassezia spp. that appear to play an important role in the pathogenesis of dandruff.[2] Its chemical structure and properties are similar to other fungicides such as ketoconazole and miconazole.

Indications and formulations
It is most commonly found as an active ingredient in OTC anti-dandruff and anti-fungal products, including shampoos, lotions and conditioners. It may be accompanied by other active ingredients such as zinc pyrithione or triclosan.

Side effects
May cause localized irritation of the skin with symptoms including redness, rashes and itching.[citation needed]

References
Chemical Properties of Climbazole Archived 2007-11-13 at the Wayback Machine
Wigger-Alberti, W; Kluge, K; Elsner, P (2001). "Clinical effectiveness and tolerance of climbazole containing dandruff shampoo in patients with seborrheic scalp eczema". Praxis. 90 (33): 1346-9. PMID 11534318.
vte
Antifungals (D01 and J02)
Wall/
membrane
Ergosterol
inhibitors
Azoles (lanosterol 14α-
demethylase inhibitors)
Imidazoles
Topical: bifonazole‡ butoconazole chlormidazole‡ clotrimazole# croconazole‡ eberconazole econazole fenticonazole‡ flutrimazole isoconazole ketoconazole luliconazole miconazole# neticonazole‡ omoconazole‡ oxiconazole sertaconazole sulconazole tioconazole
Systemic: ketoconazole
Triazoles
Topical: efinaconazole fluconazole# terconazole
Systemic: fluconazole# hexaconazole‡ fosfluconazole isavuconazole itraconazole posaconazole voriconazole
Unknown: albaconazole‡ ravuconazole†
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Topical: abafungin‡
Polyene antimycotics
(ergosterol binding)
Topical: hamycin‡ natamycin nystatin#
Systemic: amphotericin B#, hamycin‡
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Topical: butenafine
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Intracellular
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thymidylate synthase inhibitors
Systemic: flucytosine#
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Systemic: griseofulvin#
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bromochlorosalicylanilide chlorophetanol chlorphenesin ciclopirox crystal violet dimazole ethylparaben haloprogin‡ polynoxylin potassium iodide# salicylic acid selenium disulfide# sodium thiosulfate# sulbentine taurolidine ticlatone tolciclate tolnaftate tribromometacresol undecylenic acid Whitfield`s ointment#
citronella oil lemon grass lemon myrtle orange oil patchouli tea tree oil PCP: atovaquone dapsone pentamidine
#WHO-EM ‡Withdrawn from market Clinical trials: †Phase III §Never to phase III

Climbazole
Bilindiği gibi yağlı egzama ve yoğun kepekte en önemli sebep saçlı derideki mantarlardır.Climbazol bilinen en etkili mantar öldürücü maddelerden biridir, diğer mantar öldürücülere karşı mantarlarda direnç gelişmiş olması sebebiyle climbazol etkinlik açısından hepsinin önüne geçmektedir.Avrupa ülkelerinde 2-3 yıldır kullanılan climnazol son dönemde Türkiyede üretilen şampuanlarda da kullanılmaktadır.

Climbazol ve benzerleri ketokonazol, itrakonazol gibi mantar ilaçlarının etkili dozda şampuanlarda kullanılması saçlı deri mantarları, kafada yağlı egzama (seboreik dermatit) ve yoğun kepeğin en sık sebebi olan mantarların tedavisinde en yaygın tedavi şeklidir.Gerek yoğun kepekte gerekse yağlı egzama da % 60 -80 oranında rastlanan mantar (malesezia furfur ) görülmektedir.Bu sebeple yoğun kepek ve seboreik dermatit teşhis edildiğinde mutlaka mantar öldürücü etkiye de sahip şampuanlar önerilir.

Bu gurup mantar ilacı içeren şampuanların en önemli dezavantajı genellikle günlük kullanıma uygun olmamalarıdır.Climbazol şampuanlara konan diğer maddelerle etkileşime girmediği için climbazole içeren şampuanlar günklük kullanıma uygun kaliteli şampuanların içeriğiyle üretilebilmektedir.
Climbazol (Kafada Mantar Öldürücü)
Uzun süre geçmeyen kepek ve kafada kaşıntı problemi yaşıyorsanız mutlaka mantar öldürücü etkili kepek şampuanı kullanmalısınız. Aldığınız şampuan markasının içeriğinde Climbazol olmasına dikkat edin. Peki bu Climbazole nedir, neden bu kadar önemli, hangi şampuan markalarında bulunur? birlikte görelim.


Tüm sağlık sorunları gibi saç hastalıklarında da uygun tedavi yöntemleri geliştirilmiş olup, yeter ki doğru ve bilimsel maddeyi zamanında tercih kullanmasını bilelim. Saç dökülmesinden sonra en fazla görülen problemlerden biri kepek olup, normal ve seboreik dermatit dediğimiz aşırı kepek şeklinde görülmektedir. Her ikisi de saçlı deride ortaya çıkan mantar nedeniyle olmaktadır. Kafada mantar probleminin belirtisi kepek yanı sıra kafada ciddi düzeyde kaşıntı görülmesidir. Kepek ciddi bir hastalık olmayıp, doğru şampuan seçimi ile önlenebilir. Bunun için market şampuanları yerine mantar öldürücü bilimsel madde bulunan medikal şampuanlar tercih etmelisiniz.
Mantar Öldürücü Bilimsel Maddeler
Marketlerde satılan kepek şampuanları sadece hafif kepek problemi ile mücadele etmekte olup, hiç bir zaman kepeğe kesin çözüm olmamaktadır. Çünkü belirli sürelerde artan kafada mantar problemi kepeklenmeye neden olur. Tek çözümü ise Climbazol, Zinc Pyrithion, Ketokonazol, İtrakonazol gibibilimsel maddeler ile mümkündür. Fakat bazı maddelere karşı direnç geliştirmiş olan mantar mikrobu ile mücadelede en etkili madde şuan Climbazole olup, bunun dışında yine diğerlerine göre avantajı günlük kullanıma uygun olmasıdır. Ketokonazol içeren ürünler sık kullanımda saçlı deride alerji, tahriş ve incelmeye neden olurken, Climbazol bunların hiç birini içermez.

Climbazole Nedir?
Son yıllarda kafada mantar problemine karşı geliştirilmiş ve mantar mikrobunun henüz tanımadığı, direnç geliştiremediği maddelerden olup, Avrupa ülkelerinde son 5 yılda en çok tercih edilen mantar öldürücü haline gelmiştir. Genellikle şampuan içerisine eklenen Climbazol tüm kepek ve seboreik dermatit problemini ortadan kaldırırken kepeğe neden olan mantarları öldürerek saçlı deriden temizlemektedir.

Climbazol İçeren Şampuanlar
Avrupa da üretilen kepek şampuanlarında sıkça tercih edilen Climbazole maddesi Ketokonazol`a göre daha pahalı bir madde olması nedeniyle ülkemizde şuan yeteri kadar Climbazol içeren şampuan bulunmaz. Öyleki Hair Pharma tarafından üretilen Seboderm Şampuan dışında hiç bir şekilde Climbazole içeren şampuan bulma imkanınız yoktur.

Seboderm Şampuan Nedir?
Ülkemizde medikal kepek şampuanı denince genelde klasik hale gelmiş olan Ketokonazol maddesi kullanılmakta olup, Konazol, Ketoral, Nizoral gibi markaların hepsi ana madde olarak %2 Ketokonazol içermektedir. Fakat günlük kulanıma uygun olmayan hatta bazı ülkelerde üretim durdurulan Ketokonazol yerine ilk defa bir firma farklı bir ürün üreterek içerisinde iki farklı mantar öldürücü maddeye yer vermiştir. Seboderm adını verdiği ürün ile milyonlarca müşteriye ulaşan Hair Pharma bu üründe ana madde olarak Climbazole ve Zinc Pyrithion kullanmış olup, aynı zamanda kepek nedeniyle kalite kaybı yaşayan saçların kalitesini geri kazandırmak için Provitamin B5 ile saçlarda kuruluğun önüne geçmek içinde nemlendirici özelliği olan Pentavitin maddesi eklemiştir.
Currently, CLIMBAZOLE (CAS No. 38083-17-9) is allowed in cosmetic products at a maximum concentration of 0.5% in ready for use preparations when it is a preservative. Referring to the final opinion of Europe`s Scientific Committee on Consumer Safety (SCCS),SCCS/1600/18, considering an aggregate exposure scenario, Climbazole is considered as safe for use as a preservative at a maximum concentration of 0.2% in face cream, hair lotion and foot cream, and at 0.5% in rinse-off shampoo. It is also concluded to be safe in rinse-off shampoo as an anti-dandruff agent at a maximum concentration of 2%. In the light of this opinion, there is a potential risk to keeping the current regulatory limit.
Max. Concentration: 2.0% in rinse-off anti-dandruff shampoo
(For purposes other than inhibiting the development of micro-organisms in the product, the purpose has to be apparent from the presentation of the product
Abstract
Dandruff is a common condition, affecting up to half the global population of immunocompetent adults at some time during their lives and it has been highly correlated with the over-expression of the fungus Malassezia spp. Climbazole (CBZ) is used as an antifungal and preservative agent in many marketed formulations for the treatment of dandruff. While the efficacy of CBZ in vitro and in vivo has previously been reported, limited information has been published about the uptake and deposition of CBZ in the skin. Hence, our aim was to investigate the skin permeation of CBZ as well as the influence of various solvents on CBZ skin delivery. Four solvents were selected for the permeability studies of CBZ, namely propylene glycol (PG), octyl salicylate (OSal), Transcutol® P (TC) and polyethylene glycol 200 (PEG). The criteria for selection were based on their wide use as excipients in commercial formulations, their potential to act as skin penetration enhancers and their favourable safety profiles. 1% (w/v) solutions of CBZ were applied under infinite and finite dose conditions using Franz type diffusion cells to human and porcine skin. In line with the topical use of CBZ as an antidandruff agent, comparatively low amounts of CBZ penetrated across the skin barrier (<1% of the applied dose of CBZ). Finite dose studies resulted in a higher extraction of CBZ from human skin compared with infinite dose studies (p < 0.05). CBZ was also taken up to a higher extent in porcine skin (>7-fold) compared with human skin (p < 0.05). Nevertheless, no statistical differences were observed in the amounts that permeated across the different membranes. These preliminary results confirm the potential of simple formulations of CBZ to target the outer layers of the epidermis. The PG and OSal formulations appear to be promising vehicles for CBZ in terms of overall skin extraction and penetration. Future work will expand the range of vehicles studied and explore the reasons underlying the retention of CBZ in the outer layers of the skin.

Climbazole (CBZ) is an imidazole antifungal agent used to manage dandruff in formulations such as shampoos or conditioners and as a preservative (Fig. 1). It has a molecular weight of 292.8 g mol-1 and a reported melting point of 95-97 °C and it acts by inhibiting the synthesis of ergosterol, a major component in fungal plasma membranes (SCCP, 2009). In addition, CBZ has been shown to upregulate keratinocyte differentiation promoting the expression of small-proline-rich proteins in primary keratinocytes (Pople et al., 2014). Bhogal et al. (2014) also reported inhibitory effects of CBZ on hair proteases involved in anchorage of the hair shaft in an in vitro study.
Climbazole, a new antimycotic agent, comparable with ketoconazole, with a powerful action against Pityrosporum ovale
Salicylic Acid, with keratolytic action
Capryloyl Glycine, with sebum regulating and soothing action
Panthenol, with soothing action
It does not contain tar and has a pleasant smell, while its gentle cleansing base creates rich foam and makes hair soft and easy to style.
Make your own anti-dandruff or anti-fungal products.
Easy to add to any lotion or shampoo.
Over 80% cheaper than buying Climbazole shampoo.
Many people use .3% strength with same results as 1.5% strength
Product description
25 grams 99.7% Pure Cosmetic Grade CLIMBAZOLE, Now you can easily make your own anti-dandruff or anti-fungal products for a fraction of the cost! Use your favorite type of lotion or shampoo or just a $2 bottle of cheap stuff from Walmart. Or make your own shampoo, lotion, body wash, or creams from scratch. A 150ml bottle of Hegor 50 has about .75 grams of Climbazole in it and a 150ml bottle of Hegor 150 has about 2.25 grams of Climbazole in it. DO THE MATH!!! You can make your own 150ml bottle of 1% Climbazole shampoo with $2.37 worth of Climbazole. Many people only use .3% strength with same results as 1.5% strength. For a 1% strength you would mix 1 gram of Climbazole with 100 grams or 100 ml of shampoo. Shampoo weighs about 1g per ml. Dissolve Climbazole in a small amount of warm rubbing alcohol and mix thoroughly into shampoo. Search "climbazole" on youtube and you can see just how easy it is to make your own shampoo.
ChEBI Name climbazole
ChEBI ID CHEBI:83499
Definition A racemate composed of equimolar amounts of (R)- and (S)-climbazole. It is a topically applied antifungal agent used to treat human fungal skin infections.
Stars This entity has been manually annotated by the ChEBI Team.
Climbazole is a topical antifungal agent commonly used in the treatment of human fungal skin infections such as dandruff and eczema. Climbazole has shown a high in vitro and in vivo efficacy against Malassezia spp. that appear to play an important role in the pathogenesis of dandruff. Its chemical structure and properties are similar to other fungicides such as ketoconazole and miconazole.
Climbazole is a topical antifungal agent commonly used in the treatment of human fungal skin infections such as dandruff[2] and eczema. Climbazole has shown a high in vitro and in vivo efficacy against Malassezia spp. that appear to play an important role in the pathogenesis of dandruff.[2] Its chemical structure and properties are similar to other fungicides such as ketoconazole and miconazole.
Indications and formulations
It is most commonly found as an active ingredient in OTC anti-dandruff and anti-fungal products, including shampoos, lotions and conditioners. It may be accompanied by other active ingredients such as zinc pyrithione or triclosan.
Side effects
May cause localized irritation of the skin with symptoms including redness, rashes and itching.[citation needed]
3.2 Climbazole
3. Advisory Committee on Chemicals Scheduling (ACCS #19)
3.2. Climbazole
On this page: Referred scheduling proposal | Current scheduling status | Scheduling history | Scheduling application | Australian regulatory information | International regulations | Substance summary | Pre-meeting public submissions | Summary of ACCS advice to the delegate | Delegate`s considerations | Delegate`s interim decision

Referred scheduling proposal
An application was submitted by the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) to amend the current entries for climbazole in Schedules 5 and 6, to restrict its use in cosmetic products except at concentrations below 0.5% in leave-on hair and face cosmetics, and up to 2% for rinse-off hair cosmetics.

Current scheduling status
Climbazole is in Schedule 5 and Schedule 6 of the Poisons Standard as follows:

Schedule 6

CLIMBAZOLE except:

when included in Schedule 5; or
in preparations containing 2 per cent or less of climbazole.
Schedule 5

CLIMBAZOLE in preparations containing 40 per cent or less of climbazole except in preparations containing 2 per cent or less of climbazole.

Climbazole is also listed in Appendix E as follows:

Appendix E, Part 2

CLIMBAZOLE

Standard statement: A [For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once).].

Scheduling history
Climbazole was first considered for scheduling by the Poisons Schedule Committee (PSC) in November 1980. Although the original application specified use as a household and industrial fungicide, at that time the committee decided that the absence of chronic toxicological data warranted restrictions for human use, and that Schedule 4 was appropriate.

In November 1985 the Poisons Schedule Committee (PSC) considered rescheduling climbazole from Schedule 4 to Schedule 5 (for human use), to permit its use in an antidandruff shampoo. However, the committee did not accept this rescheduling application given the lack of chronic toxicological data.

In November 1986 the Drugs and Poisons Scheduling Committee (DPSC) considered an amended application to the one received in November 1985 to reschedule climbazole from Schedule 4 to Schedule 5 (for human use) in order to permit its use in an antidandruff shampoo. In its deliberations, the committee noted that climbazole would be incorporated into the proposed Australian Cosmetic Standard at 0.5% or less. The committee agreed to delete the Schedule 4 entry for climbazole and create: a new Schedule 5 entry for preparations containing 40% or less except in preparations containing 2% or less (as in the current Schedule 5 entry); and a new Schedule 6 entry with an exemption for preparations containing 2% or less of climbazole (as in the current Schedule 6 entry).
Climbazole is readily bioavailable following oral exposure and has moderate acute oral toxicity;
Climbazole is not an eye irritant at 0.5% and not a skin irritant at 2%;
Climbazole has been selected as a candidate for the European Union (EU) Community Action Rolling Plan (CoRAP) initiative for further evaluation of reproductive and developmental toxicity;
Climbazole is reported to be used in cosmetic products overseas (as a preservative or antimicrobial agent); in the absence of Australian specific data, this is assumed to be representative of its use in Australia; and
According to the SCCP Opinion (2009), climbazole is `regulated in the Cosmetics Directive as a preservative in Annex [V], with a maximum authorized concentration of 0.5%` and `is used as an anti-dandruff active agent in hair cosmetic preparations up to a maximum concentration of 2.0% in rinse-off products or up to a maximum concentration of 0.5% in leave-on products. In addition, it is used in leave-on face creams up to a maximum concentration of 0.5%`.
he SCCS has concluded (SCCS 2013) that climbazole `may be used as a preservative (or non-preservative) ingredient up to a maximum concentration of 0.5% in leave-on hair and face cosmetics. Its non-preservative use in rinse-off hair cosmetics up to a maximum concentration of 2% was also considered to be safe. Its use in leave-on products other than those mentioned above was, however, not considered safe`. Furthermore, `the non-preservative use of Climbazole either in foot care cosmetics alone at a concentration of up to 0.5% or in combination with either shampoo (at a maximum concentration of 2%) or face cream (at a maximum concentration of up to 0.5%) or with hair lotion (at a maximum concentration of up to 0.5%), does not pose a risk to the health of the consumer. In the case, however, that 3 products, although each safe when used separately, are combined, the combinations of either shampoo, hair lotion and a foot care product or face cream, hair lotion and a foot care product (all containing Climbazole at the maximum requested concentration) cannot be considered safe for the consumer`.
Based on the available data, climbazole has moderate acute oral toxicity and low acute dermal toxicity. No data is available for acute inhalation toxicity.
No in vivo eye irritation studies are available using neat climbazole, however climbazole was not irritating to rabbit eyes at 0.5% concentration. A Chicken Enucleated Eye Test (screening assay) gave negative results for climbazole up to 2% concentration. A Hen`s Egg Test-Chorioallantoic Membrane (HET-CAM) assay showed negative results for neat climbazole; however, this assay detects only strong eye irritants (SCCP 2009).

Climbazole is not expected to be an eye irritant in humans at 2% concentration (SCCP 2009).

Skin sensitisation
Based on the results of a local lymph node assay (LLNA) in CBA/J mice (OECD TG 429), climbazole up to 20% concentration does not have potential to induce skin sensitisation (SCCP 2009).

Climbazole gave negative results for skin sensitisation in two non-guideline studies (Magnusson Kligman Guinea Pig Maximisation test and Buehler test) in female guinea pigs (Bor:DHPW and Hartley). 

Repeat-dose toxicity
Based on the available data in rats and dogs, climbazole is not considered to cause severe effects following repeated oral or inhalation exposure. However, repeated dose oral toxicity studies in rats showed increased liver enzyme activity from doses at or above 15 mg/kg bw/day. No data are available on repeated dose dermal toxicity.

The SCCP report stated that the available studies were conducted between 1975 and 1983, before GLP-regulations were in place. The descriptions were brief and the raw data incomplete. For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90 day oral study with the rat. This No observed effect level (NOEL) was used in the margin of safety (MoS) calculations for the specific use scenarios of climbazole.

The SCCP report calculated the MoS to be 701 for a 60 kg person using an anti-dandruff shampoo containing 2% climbazole, using an in vitro dermal penetration rate of 0.297 µg/cm2 (0.15%) through human skin. This indicates that climbazole at 2% is safe for use in anti-dandruff shampoo (rinse-off products). The MoS for a 60 kg person using hair lotions, face cream and leave-on body lotion (all containing 0.5% climbazole) were calculated to be 189, 425 and 13, respectively, using in vitro dermal penetration rates of 1.10 µg/cm2 (2.23%) or 1.25 µg/cm2 (3.46%) through pig skin. Considering these MoS values, using a leave-on body lotion containing 0.5% climbazole for whole body (area of 18,000 cm2) was not considered safe as the MoS was calculated to be <100. The SCCP concluded that, `To generate an acceptable MoS (≥ 100), the treated surface area for leave-on products containing 0.5% Climbazole should not exceed 2400 cm2.`

Genotoxicity
Based on the results from the available in vitro and in vivo genotoxicity studies, climbazole is not considered to be genotoxic. Some in vitro genotoxicity tests indicated positive results, but all in vivo tests were negative.

Reproduction and developmental toxicity
Based on the available data, climbazole is not considered to cause specific reproductive or developmental toxicity, as effects were only observed secondary to maternal toxicity. However, climbazole is a candidate for the EU CoRAP initiative for further evaluation of reproductive and developmental toxicity.

Public exposure
Climbazole is reported to be used in cosmetic products overseas as a preservative or antimicrobial agent. In the absence of Australian specific data, this is assumed to be representative of its use in Australia.

 

CAS Number:38083-17-9; Climbazole is a topical antifungal agent commonly used in the treatment of human fungal skin infections such as dandruff and eczema. Climbazole has shown a high in vitro and in vivo 

efficacy against Malassezia spp. that appear to play an important role in the pathogenesis of dandruff. Its chemical structure and properties are similar to other fungicides such as 

ketoconazole and miconazole.

 

Indications and formulations

It is most commonly found as an active ingredient in OTC anti-dandruff and anti-fungal products, including shampoos, lotions and conditioners. It may be accompanied by other active 

ingredients such as zinc pyrithione or triclosan.

 

 

Human skin is a formidable barrier protecting against the entry of foreign substances and preventing excessive water loss from the body (Hadgraft and Lane, 2005, Notman and Anwar, 2013, Proksch et al., 2008). Notwithstanding this, various formulation approaches have been developed to overcome the skin’s inherent resistance to penetration of actives. Topical and transdermal delivery of drugs is also attractive compared with oral or intravenous administration, as first pass metabolism is avoided and patient compliance when using such formulations is generally higher (Zorec et al., 2013). Many diseases require the active to be targeted to the skin itself. This is the case for many antifungals used to treat skin infections, where the oral route would require comparatively high doses of drugs and may result in undesirable systemic effects (Glujoy et al., 2014).

 

Dandruff is a common scalp disorder causing excessive scaling of the scalp and impaired skin barrier function (Hay, 2011). The commensal fungus Malassezia spp is commonly found in the scalp, but excessive proliferation of this organism is highly correlated with the presence of dandruff (DeAngelis et al., 2005). Dandruff is generally treated using medicated shampoos incorporating one or more actives to target different stages of the condition. These shampoos can contain keratolytic agents (salicylic acid, sulfur), regulators of keratinisation (zinc, tar, steroids), antimicrobial agents (selenium sulphide, imidazole antifungals, hydroxypyridones) and naturopathic remedies (tea tree oil) (Piérard et al., 2000, Sanfilippo, 2).

 

Climbazole (CBZ) is an imidazole antifungal agent used to manage dandruff in formulations such as shampoos or conditioners and as a preservative. It has a molecular weight of 292.8 g mol−1 and a reported melting point of 95–97 °C and it acts by inhibiting the synthesis of ergosterol, a major component in fungal plasma membranes (SCCP, 2009). In addition, CBZ has been shown to upregulate keratinocyte differentiation promoting the expression of small-proline-rich proteins in primary keratinocytes (Pople et al., 2014). Bhogal et al. (2014) also reported inhibitory effects of CBZ on hair proteases involved in anchorage of the hair shaft in an in vitro study.

 

 

 

Ideally, formulations of CBZ should target the molecule to the stratum corneum and/or the hair follicles, for local effects on scalp microbiota. The minimum inhibitory concentration (MIC) for CBZ for various species of Malassezia associated with dandruff ranges from 125 to 62.5 µg ml−1 (M. globosa = M. restricta > M. furfur) as reported by Gokulshankar et al. (2011). Lower MICs have been reported by Youn et al. (2016), in the order of 1–2 µg ml−1, showing a higher antifungal efficacy of CBZ compared with piroctone olamine, another antifungal agent used for the treatment of dandruff. Various authors have reported the in vitro activity and associated clinical outcomes of CBZ in the literature (Chen et al., 2015, Schmidt-Rose et al., 2011, Youn et al., 2016). Garrett et al. (2017) also investigated the deposition of CBZ and zinc pyrithione in porcine skin with stimulated Raman scattering microscopy. Higher penetration of CBZ into the hair shaft was observed compared with zinc pyrithione, the latter compound 

being deposited as crystals on the skin surface because of its lower lipid solubility. However, there is still limited information detailing skin delivery or efficiency of CBZ following

 topical application. As the molecule has a comparatively low melting point, low molecular weight and is lipophilic with a predicted log Po/w of 3.76 (SCCP, 2009), these properties

 suggest it is a suitable permeant for delivery to the skin (Hadgraft, 2004).

 

Climbazole

 

38083-17-9

 

Climbazol

 

Baypival

 

Baysan

 

BAY-E 6975

 

1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one

 

Climbazol [INN-Spanish]

 

Climbazolum [INN-Latin]

 

2-Butanone, 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethyl-

 

1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethylbutan-2-one

 

EINECS 253-775-4

 

BRN 0618020

 

CHEBI:83719

 

1-(4-Clorophenoxy)-3,3-dimethyl-1-(imidazole-1-yl)-2-butanone

 

NCGC00166153-01

 

AK161858

 

1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutanone

 

1-(p-Chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2-butanone

 

1-(p-Chlorophenoxy)-3,3-dimethyl-1-(1-imidazolyl)-2-butanone

 

1-(4-Chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethyl-2-butanone

 

DSSTox_CID_26555

 

DSSTox_RID_81715

 

DSSTox_GSID_46555

 

AO-295/40848554

 

Q-100974

 

Climbazolum

 

1-(4-chlorophenoxy)-1-(1-imidazolyl)-3,3-dimethyl-2-butanone

 

1-(4-Chlorophenoxy)-1-(1H-imidazolyl)-3,3-dimethyl-2-butanone

 

1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethyl-2-butanone

 

1-(4-Chlorophenoxy)-3,3-dimethyl-1-(imidazole-1-yl)-2-butanone

 

2-BUTANONE, 1-(p-CHLOROPHENOXY)-3,3-DIMETHYL-1-(1-IMIDAZOLYL)-

 

CAS-38083-17-9

 

Climbazole [BAN:INN]

 

Climbazole [INN:BAN]

 

Bay e 6975

 

CCRIS 8169

 

MEB 6401

 

EC 253-775-4

 

SCHEMBL39729

 

US9138393, Climbazole

 

US9144538, Climbazole

 

5-23-04-00209 (Beilstein Handbook Reference)

 

MLS004773943

 

BAY e-6975

 

CHEMBL1437764

 

DTXSID6046555

 

KS-00000UQD

 

OWEGWHBOCFMBLP-UHFFFAOYSA-

 

BDBM181112

 

HMS2090O13

 

HMS3652P05

 

HMS3744O15

 

Pharmakon1600-01504833

 

HY-B1151

 

MEB-6401

 

Tox21 112343

 

Tox21_112343

 

AC-272

 

DL-358

 

MFCD00055505

 

NSC759808

 

s4178

 

AKOS015895513

 

Tox21_112343_1

 

API0026090

 

CCG-213958

 

CS-4675

 

DB15580

 

KS-5112

 

NSC-759808

 

Climbazole 10 microg/mL in Cyclohexane

 

NCGC00166153-02

 

NCGC00166153-03

 

LS-46662

 

SC-25381

 

SMR001550495

 

AB0012194

 

AX8020560

 

DB-049235

 

FT-0624097

 

FT-0655760

 

FT-0665095

 

NS00008150

 

SW219213-1

 

Climbazole, PESTANAL(R), analytical standard

 

K-8328

 

AB01275501-01

 

AB01275501_02

 

AB01275501_03

 

083C179

 

A824009

 

C-36329

 

Q629373

 

SR-05000001501

 

SR-05000001501-1

 

BRD-A61676498-001-01-7

 

Climbazole, United States Pharmacopeia (USP) Reference Standard

 

1-(4-chloranylphenoxy)-1-imidazol-1-yl-3,3-dimethyl-butan-2-one

 

1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutan-2-one

 

1-(4-chlorophenoxy)-3,3-dimethyl-1-(imidazol-1-yl)-butan-2-one

 

2-Butanone, 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethyl-;CLIMBAZOLE;climbazole

 

 

1-(4-Chlorophenoxy)-1-(1H-imidazolyl)-3,3-dimethyl-2-butanone

Other

1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutan-2-one

Cosmetic Products Regulation, Annex III - Restricted Substances, Cosmetic Products Regulation, Annex V - Allowed Preservatives

1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutanone

Other

1-(p-Chlorophenoxy)-3,3-dimethyl-1-(1-imidazolyl)-2-butanone

Other

2-Butanone, 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethyl-

Other

2-Butanone, 1-(p-chlorophenoxy)-3,3-dimethyl-1-(1-imidazolyl)-

Other

BAY-E 6975

Other

Baypival

Other

Baysan

Other

Climbazol

Other

Climbazole

EC Inventory, Substance Evaluation - CoRAP, Pre-Registration process, Other

Climbazolum

Other

MEB 6401

Other

IUPAC names

(R,S)-1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethylbutan-2-one

C&L Inventory

(RS)-1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethylbutan-2-one

C&L Inventory

1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethyl-2-butanone

C&L Inventory

1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one

C&L Inventory, Registration dossier, Other

1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethylbutan-2-one

C&L Inventory, Other

1-(4-chlorophenoxy)-3,3-dimethyl-1-(imidazole-1-yl)-2-butanone

C&L Inventory

Crinipan AD

Registration dossier

Trade names

CLIMBAZOLE CRUDE

Registration dossier

Crinipan® AD

Registration dossier

Crinipan® USP

Registration dossier

Other identifiers 

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