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Annex II Entry 6 15/10/2010

Methotrexate (INN)

Methotrexate (INN) is listed in Annex II as a prohibited substance for cosmetic products placed on the EU market.

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Prohibited substance— Annex II, EU Regulation 1223/2009
Entry: 6

Chemical identity and properties

PubChem 2D chemical structure for CAS 59-05-2
CAS 59-05-2PubChem CID 126941

Methotrexate

Methotrexate is a member of pteridines, a monocarboxylic acid amide and a dicarboxylic acid. It has a role as an antimetabolite, an antineoplastic agent, an immunosuppressive agent, an antirheumatic drug, a dermatologic drug, an EC 1.5.1.3 (dihydrofolate reductase) inhibitor, an abortifacient and a DNA synthesis inhibitor. It is functionally related to a L-glutamic acid. It is a conjugate acid of a methotrexate(1-). — ChEBI

IUPAC name
(2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid
Molecular formula
C20H22N8O5
Molecular weight
454.4 g/mol
Exact mass
454.17131583 Da
XLogP3
-1.8
Topological polar surface area
211.0 Ų
Hydrogen-bond donors
5
Hydrogen-bond acceptors
12
Covalent units
1
Defined stereocentres
1

Also known as

RheumatrexAmethopterinMetatrexanHdmtxLedertrexateMethylaminopterinumMethotrexatumMetotrexato
16 more reported names
AntifolanRasuvoEmtexateL-AmethopterinAmethopterineNSC-740MaxtrexFarmitrexatMedsatrexateMethoblastinMethotextrateMethotrexatBrimexateEmthexatEmthexateFauldexato
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External database identifiers

Retrieved from NIH PubChem on 2026-08-31 by checksum-valid CAS matching. Chemical properties do not replace the regulatory decision on this page.

Record details

Chemical name

Methotrexate (INN)

Regulatory information

Regulation

(EC) 2009/1223

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Key data

CAS
59-05-2
EC
200-413-8
Annex
II
Entry number
6

Inventory links for Methotrexate (INN)

Inventory Restriction reference
Ref 95795

METHOTREXATE

CAS: 59-05-2
EC: 200-413-8 (I)

Direct matches are limited for this record, so nearby entries from Annex II are shown as well.

What Annex II means for Methotrexate (INN)

Methotrexate (INN) is listed as a prohibited substance under Annex II of EU Cosmetics Regulation 1223/2009 and must not be intentionally added. Article 17 separately addresses unintended small quantities that are technically unavoidable under good manufacturing practice and compatible with the Article 3 safety requirement.

Formulators must screen their ingredients and raw materials to ensure none contain this substance. Suppliers should provide documentation confirming absence when requested.

This record is linked to 2 CosIng inventory ingredients for name and identifier cross-reference. The page also surfaces 12 related annex records with overlapping identifiers, annex logic or naming patterns.

Compliance checklist

  • Verify this substance is absent from all raw materials and finished formulations.
  • Request absence confirmation or CoA from raw material suppliers.
  • Document the screening result in the Product Information File (PIF).

Frequently asked questions

Yes. Methotrexate (INN) is listed in Annex II of EU Cosmetics Regulation 1223/2009 and is prohibited as an intentionally added cosmetic ingredient. Article 17 provides a narrow exception for unintended small quantities that are technically unavoidable under good manufacturing practice, provided the product remains safe under Article 3.

CAS 59-05-2 is the unique numerical identifier assigned to Methotrexate (INN) by the Chemical Abstracts Service. In cosmetic compliance work, the CAS number is used to cross-reference the substance across regulatory databases, raw material specifications and safety assessment reports. Multiple EU annex entries may share the same CAS number if the same substance appears under different conditions or in different annexes.

Use the INCI Checker tool on this site to paste your full ingredient list (INCI) and scan it against all Annex II–VI entries. The tool highlights any ingredients that match restricted, prohibited or allergen-flagged records. This is useful for rapid compliance screening of finished product formulas or raw material declarations.
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Source note for Annex II record Methotrexate (INN)

This page summarizes one Annex II record for Methotrexate (INN) from public European Commission cosmetic materials and adds linked inventory or identifier matches when available.

Use this record page to review Annex II conditions for Methotrexate (INN), but confirm any final regulatory decision against the current official annex wording and source files.

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