Is Methotrexate safe in cosmetics?
Methotrexate has a safety rating of "MODERATE" in our database. EU status: prohibited. US status: prohibited.
Moderate
Cosmetic Ingredient
Methotrexate
Also known as: MTX, (2S)-2-[[4-[[(2,4-Diaminopteridin-6-yl)methyl]methylamino]benzoyl]amino]pentanedioic acid, CL 14377, Caditrex, EMT 25299 (+15 more)
INCI: METHOTREXATE
Methotrexate (CAS 59-05-2) is a cosmetic cosmetic ingredient functioning as Antimetabolite / cytotoxic agent (pharmaceutical - NOT a cosmetic function). EU Regulation 1223/2009 status: prohibited. Industrial safety data is also available in the chemical safety database. Same-CAS public records also appear in industrial chemical safety and pharmaceutical data.
View industrial chemical safety profile for CAS 59-05-2 →
Auto-generated CPSR Part A draft with source citations
Cross-Vertical Regulatory Divergence
Methotrexate is prohibited in EU cosmetics but has active industrial GHS classifications (H301, H315, H319, H340, H360).
Source: Cosmetics: ingredients.eu_status; Chemicals: ghs_classifications.signal_word/hazard_statement_code
Function
Antimetabolite / cytotoxic agent (pharmaceutical - NOT a cosmetic function)
Safety Rating
MODERATE
Chemistry & Identifiers
IUPAC Name
(2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid
InChIKey
FBOZXECLQNJBKD-ZDUSSCGKSA-N
Regulatory Status
EU EU Status
prohibited
US US Status
prohibited
US Notes
Prohibited - classified as a prescription drug (antineoplastic/immunosuppressant); its presence in any cosmetic product would render it an adulterated/misbranded drug under the FD&C Act
For full compliance data across multiple jurisdictions, use the Substance Compliance tool.
Safety Data
Margin of Safety, dermal absorption, and sensitization profile summaries for Methotrexate.
Calculate MoS for your specific formulation with the MoS Calculator.
IARC Carcinogenicity
International Agency for Research on Cancer (WHO) monograph evaluation.
IARC Group
3
Volume
26, Sup 7
Evaluation Year
1987
EU CosIng Annex Listing
European Commission CosIng database Annex references per Regulation (EC) No 1223/2009.
Annex II — Prohibited
Ref: 6
(EC) 2009/1223
Expanded Jurisdictional Detail
Additional regulatory detail beyond the 7-jurisdiction summary: Saudi SFDA, Korea MFDS, ASEAN ACD, Japan/Korea, Brazil/India, and cross-jurisdictional restriction entries.
SA Saudi SFDA (II - Prohibited)
ASEAN Cosmetic Directive (II)
Ref: 6
BRIN Brazil/India Cosmetics
Brazil: Prohibited
India: Prohibited (GNRAS)
Additional Jurisdictional Restrictions (4)
| Jurisdiction | Status | Max % | Product Type |
|---|---|---|---|
| GCC | banned | - | All cosmetics |
| BR | banned | - | - |
| CA | banned | - | - |
| ASEAN | banned | - | All cosmetic products prohibited |
Expanded Dermal Absorption Data
Cross-database dermal penetration: EPA Dryad physics-based, Roberts Mendeley permeation, and SCCS-aggregated measured values.
Roberts Skin Permeation (Mendeley 2022)
MW: 454.44
Log Kow: -1.85
Log Kp: -3.3615107430453626
Log Jmax: -8.604013946242995
Source: Roberts_Cheruvu_Mendeley_2022
PubChem Annotations
Safety and regulatory annotations from PubChem (NCBI) aggregated sources.
Safety (3)
Carcinogen Classification
3, not classifiable as to its carcinogenicity to humans. (L135)
Source: Toxin and Toxin Target Database (T3DB)
Carcinogen Classification
Methotrexate | Group 3: Not classifiable as to its carcinogenicity to humans | Volume 26: (1981) Some Antineoplastic and Immunosuppressive Agents | Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)
Source: International Agency for Research on Cancer (IARC)
Evidence for Carcinogenicity
Classification of carcinogenicity: 1) evidence in humans: Inadequate data; 2) evidence in animals: Inadequate data. Overall summary evaluation of carcinogenic risk to humans is Group 3: The agent is not classifiable as to its carcinogenicity to humans. /From table/
Source: Hazardous Substances Data Bank (HSDB)
Function Categories & List Membership
Cosmetic/Chemical Function Categories
No specific technical function
Regulatory List Membership (3)
California Proposition 65 (OEHHA)
EU Banned in Cosmetics
EU CosIng Cosmetics Ingredient Database
Expert Verdict
Expert safety assessment and concern-level summary for Methotrexate.
Regulatory Flags
prop65
eu_banned_cosmetics
eu_cosing_listed
Known Synonyms
MTX
(2S)-2-[[4-[[(2,4-Diaminopteridin-6-yl)methyl]methylamino]benzoyl]amino]pentanedioic acid
CL 14377
Caditrex
EMT 25299
Emtexate
Emthexate PF
Emtrexate
Folex
Folex PFS
Folitrax
Merex
Methocip
Methotrexate LPF
Metorex
Mexate
Mexate-AQ
Oncotrex
R 9985
Remtrex
Chemical Function
No specific technical function
Regulatory Lists
Canada; consumer_product; Substances in Products - Canada (4/2014)
pharmaceutical
pharmaceutical
OEHHA Proposition 65 (3/2019)
Canada; pharmaceutical
OEHHA Proposition 65 (1/2023)
banned; Europe; Personal care
Cross-Vertical Safety Context
Same-CAS public records found in pharmaceutical data.
SOURCE
ChEMBL / DrugCentral / FAERS
DB_PHARMA CAS match
Pharmaceutical Data
Same-CAS rows from the pharmaceutical spoke database.
Compound
METHOTREXATE
ChEMBL ID
CHEMBL34259
Max Phase
4
Adverse Event Associations
2431
Frequently Asked Questions
Is Methotrexate allowed in the EU?
Methotrexate EU regulatory status: prohibited. This is based on EU Regulation 1223/2009 and its amendments.
What does Methotrexate do in cosmetics?
Methotrexate functions as: Antimetabolite / cytotoxic agent (pharmaceutical - NOT a cosmetic function). It is classified as a cosmetic ingredient in our database. CAS number: 59-05-2.
Is Methotrexate used outside cosmetics?
Methotrexate also appears in industrial chemical safety and pharmaceutical data. The cross-vertical cards on this page render same-CAS public rows from the matched databases.
Does Methotrexate have different safety status in cosmetics vs industrial chemicals?
Methotrexate is prohibited in EU cosmetics but has active industrial GHS classifications (H301, H315, H319, H340, H360).
Compliance Tools
Check Methotrexate compliance across multiple jurisdictions:
Ingredient Decoder
Paste a full ingredient list for instant analysis
82 Allergen Checker
Check for EU declarable fragrance allergens
Substance Compliance
Check compliance across multiple jurisdictions
MoS Calculator
Calculate Margin of Safety using SCCS methodology
Heavy Metal Limits
Compare limits across jurisdictions
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