What does the restriction note for METHOTREXATE mean?

The restriction field for METHOTREXATE reads: II/6. This is the restriction note from the CosIng inventory. For authoritative conditions and limits, always refer to the linked annex entries.

What other records share CAS 59-05-2?

CAS 59-05-2 may appear across multiple EU annex records. The CAS lookup page shows all Annex II–VI entries sharing this identifier, useful for identifying cross-annex regulatory status of the same chemical substance.

How do I check if my formula contains METHOTREXATE?

Use the INCI Checker to screen a full ingredient list across selected markets, or use the substance market comparison to review this identity across all supported market datasets.

InventoryRef 9579527/04/2018

METHOTREXATE

L-Glutamic acid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-

METHOTREXATE is linked to 1 EU annex record on this page. Inventory note: II/6.

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Regulatory evidence by market

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Market	Evidence status	Records	Source language
European Union	Evidence linked Prohibited entry found Open this evidence	1	English and EU languages
Great Britain	Evidence linked Prohibited Open this evidence	1	English
Canada	Evidence linked Prohibited Open this evidence	1	English and French
New Zealand	Evidence linked Prohibited Open this evidence	1	English
ASEAN	Evidence linked Prohibited Open this evidence	1	English and national languages
China	Evidence linked Prohibited Open this evidence	1	Chinese with selected English material
Japan	Source mapped Official source mapped; ingredient rule not imported	0	Japanese; official English translation available
South Korea	Evidence linked Prohibited Open this evidence	1	Korean with some English names
United States	Source mapped Official source mapped; ingredient rule not imported	0	English
Australia	Source mapped Official source mapped; ingredient rule not imported	0	English
Brazil	Evidence linked Prohibited Open this evidence	1	Portuguese with INCI crosswalks
India	Evidence linked Prohibited Open this evidence	1	English and Hindi
Saudi Arabia	Evidence linked Prohibited Open this evidence	1	Arabic and English

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 Å²
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

Open full PubChem record PubChem annotations 3D structure image

External database identifiers

ChEBI:CHEBI:44185
ChEMBL:CHEMBL34259
EPA DTXSID:DTXSID4020822
PubMed:32020584
PubMed:30415610
PubMed:29268019
PubMed:28117352
PubMed:27379764
PubMed:27210722
PubMed:24284432
PubMed:23895801
PubMed:22968027
PubMed:22702814
PubMed:22639782
PubMed:22587841

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

Inventory details for METHOTREXATE

INCI name

METHOTREXATE

Description

L-Glutamic acid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-

Record provenance

Inventory reference: 95795
Imported identity: METHOTREXATE
Source update: 27/04/2018

European Commission CosIng source notes

Annex records for METHOTREXATE

Annex II Restriction reference

Entry 6

Methotrexate (INN)

CAS: 59-05-2

EC: 200-413-8

Key data

CAS

59-05-2

200-413-8 (I)

Restriction

II/6

Function

NOT REPORTED: No function currently reported.

Ingredients with overlapping formulation functions

METHACRYLOYLOXYETHYL ISOCYANATENOT REPORTED

METHACRYLOYLOXYETHYL PHOSPHORYLCHOLINENOT REPORTED

METHACRYLOYLOXYETHYLTRIMONIUM CHLORIDENOT REPORTED

METHACRYLOYLOXYPROPYL DIMETHICONENOT REPORTED

METHOXY PEG-11NOT REPORTED

METHOXY PEG-125 AMINENOT REPORTED

METHOXY PEG-144NOT REPORTED

METHOXY PEG-15 METHACRYLATENOT REPORTED

Additional official and scientific sources

11 external databases to check this identity in

Each link searches that source for this identity. What each source is, and its legal weight

ECHA CHEM / Information on chemicals PubChem PUG REST EU Safety Gate cosmetic product alerts ECHA CHEM US EPA CompTox Cosmetic Ingredient Review safety assessments FDA Global Substance Registration System ILO/WHO International Chemical Safety Cards Japan NITE-CHRIP NIOSH Pocket Guide to Chemical Hazards OECD eChemPortal

How METHOTREXATE appears in the CosIng inventory

The CosIng inventory lists METHOTREXATE as a cosmetic ingredient and this page links it to 1 annex record. The inventory entry captures names and identifiers, while the annex record shows where the substance is prohibited, restricted or positively listed in EU cosmetics law.

METHOTREXATE is also tagged with 1 cosmetic function in the official data. Function labels describe intended use, but they do not replace regulatory review of linked annex records before formulation or labelling work.

Frequently asked questions

METHOTREXATE appears in the EU CosIng inventory and has linked annex records. Check the annex records above for applicable restrictions, concentration limits and conditions of use. Annex II listing means prohibited; Annex III means restricted; Annexes IV, V and VI mean permitted under specified conditions.

The restriction field for METHOTREXATE reads: "II/6". This is the restriction note recorded in the CosIng inventory for this ingredient. For authoritative conditions and limits, always refer to the linked annex entries above.

According to the EU CosIng inventory, METHOTREXATE carries the following function designation(s):

NOT REPORTED

CAS 59-05-2 may appear across multiple EU annex records. Viewing the CAS lookup page shows all Annex II–VI entries sharing this identifier, which is useful for identifying cross-annex regulatory status of the same chemical substance.

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Source note for METHOTREXATE

This page combines the CosIng inventory entry for METHOTREXATE with 1 linked Annex II–VI record from the local dataset built from public European Commission cosmetic ingredient materials.

Use this inventory page to research METHOTREXATE and compare linked records, but verify restrictions and legal status against the current official source text and law before making regulatory decisions.

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Tools & next steps

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