Is Theophylline safe in cosmetics?
Theophylline has a safety rating of "MODERATE" in our database. EU status: prohibited. US status: permitted. 2 toxicological study endpoint(s) are available in our database.
Theophylline
Also known as: 1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl-, 1H-Purine-2,6-dione, 3,9-dihydro-1,3-dimethyl-, EINECS 200-385-7, Purine-2,6(1H,3H)-dione, 1,3-dimethyl-, Theophylline, anhydrous (+15 more)
INCI: THEOPHYLLINE
Theophylline (CAS 58-55-9) is a cosmetic cosmetic ingredient functioning as Skin conditioning agent (methylxanthine; promotes microcirculation, lipolysis). NOAEL 7.5 mg/kg bw/day (cross-referenced against ToxValDB ECHA IUCLID); EU Regulation 1223/2009 status: prohibited; GHS signal word DANGER. 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 58-55-9 →
Auto-generated CPSR Part A draft with source citations
Cross-Vertical Regulatory Divergence
Theophylline is prohibited in EU cosmetics but has active industrial GHS classifications (H301, H302, H361, H362, H370, H372, H402, H360D).
Source: Cosmetics: ingredients.eu_status; Chemicals: ghs_classifications.signal_word/hazard_statement_code
Function
Skin conditioning agent (methylxanthine; promotes microcirculation, lipolysis)
Safety Rating
MODERATE
Chemistry & Identifiers
IUPAC Name
1,3-dimethyl-7H-purine-2,6-dione
InChIKey
ZFXYFBGIUFBOJW-UHFFFAOYSA-N
Regulatory Status
EU EU Status
prohibited
US US Status
permitted
US Notes
CIR Panel concluded safe in present practices of use and concentration ; permitted in US cosmetics
For full compliance data across multiple jurisdictions, use the Substance Compliance tool.
Safety Data
Margin of Safety, dermal absorption, and sensitization profile summaries for Theophylline.
Calculate MoS for your specific formulation with the MoS Calculator.
Toxicological Studies
2 study endpoints found for Theophylline. NOAEL (No Observed Adverse Effect Level) values are used to calculate the Margin of Safety per SCCS methodology.
| Endpoint | Value | Route | Species | Study Type | Source |
|---|---|---|---|---|---|
| NOAEL | =30 mg/kg bw/day | injection | Rabbit | reproduction developmental | ToxValDB_ECHA_IUCLID |
| NOAEL | =124 mg/kg bw/day | oral | Rat | reproduction developmental | ToxValDB_ECHA_IUCLID |
GHS Hazard Classification
Globally Harmonized System classification per ECHA C&L inventory and ILO/WHO International Chemical Safety Cards.
Signal Word
DANGER
Pictograms
SkullToxicCancerHealth haz
Hazard Statements
Toxic if swallowed May be harmful if inhaled May cause harm to breast-fed children Causes damage to vascular system and kidneys Causes damage to the kidneys through prolonged or repeated exposure
Short-term Exposure Effects
The substance may cause effects on the heart and central nervous system. This may result in cardiac dysrhythmia and convulsions. The effects may be delayed.
Routes of Exposure
The substance can be absorbed into the body in hazardous amounts by ingestion.
Pre-Calculated Safety Assessment
Pre-calculated NOAEL → SED → MoS audit trail for Theophylline across SCCS product categories, with measured dermal absorption where available.
EPA ToxValDB — Toxicity Values
10 toxicity values from EPA ToxValDB (aggregated from CCTE, HPV, ToxRefDB, IRIS, and other regulatory dossiers).
| Endpoint | Value | Species | Route | Duration | Source |
|---|---|---|---|---|---|
| LC50 | >6700 mg/m3 | Rat | inhalation | - | ECHA IUCLID |
| LD50 | >2000 mg/kg | Rat | dermal | acute | ECHA IUCLID |
| LOAEL | =37.5 mg/kg-day | Rat | oral | subchronic | ECHA IUCLID |
| LOAEL | =126 mg/kg-day | Mouse | oral | - | ECHA IUCLID |
| LOAEL | =126 mg/kg-day | Mouse | oral | - | ECHA IUCLID |
| LEL | =75 mg/kg-day | Rat | oral | chronic | ToxRefDB |
| LEL | =125 mg/kg-day | Rat | oral | chronic | ToxRefDB |
| LEL | =75 mg/kg-day | Rat | oral | chronic | ToxRefDB |
| LEL | =37.5 mg/kg-day | Rat | oral | chronic | ToxRefDB |
| LEL | =225 mg/kg-day | Mouse | oral | chronic | ToxRefDB |
IARC Carcinogenicity
International Agency for Research on Cancer (WHO) monograph evaluation.
IARC Group
3
Volume
51
Evaluation Year
1990
EU CLP Annex VI Harmonized Classification
Legally binding harmonized classification per Regulation (EC) No 1272/2008 (CLP) Annex VI.
Signal Word
Danger
Pictograms
Health Hazard
Hazard Class and Category
Repr. 1B
Hazard Statements
- H360D
Inserted via ATP: ATP18
ECHA REACH Registration
European Chemicals Agency REACH dossier and Substances of Very High Concern listing.
Registration Type
Full
Tonnage Band
1 - 10 tonnes
Substance Type
SUBSTANCE; GROUP
SVHC Candidate
No
Hazard classification: Restricted (Annex XVII)
EU CosIng Annex Listing
European Commission CosIng database Annex references per Regulation (EC) No 1223/2009.
Annex II — Prohibited
Ref: 1710
(EU) 2023/1490
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: A1137
Additional Jurisdictional Restrictions (2)
| Jurisdiction | Status | Max % | Product Type |
|---|---|---|---|
| CA | banned | - | - |
| ASEAN | banned | - | All cosmetic products prohibited |
Additional Ingredient Properties
1 property record from structured ingredient metadata.
skin_suitability
{"oily_skin": "acceptable", "dry_skin": "acceptable", "sensitive_skin": "acceptable", "combination_skin": "acceptable", "normal_skin": "acceptable", "acne_prone": "acceptable", "rosacea": "acceptable", "eczema": "acceptable", "hyperpigmentation": "acceptable", "aging_mature": "acceptable", "dehydrated": "acceptable", "skin_benefit_primary": "drainage", "skin_benefit_secondary": "circulation", "mec…
PubChem Annotations
Safety and regulatory annotations from PubChem (NCBI) aggregated sources.
Safety (6)
Carcinogen Classification
3, not classifiable as to its carcinogenicity to humans. (L135)
Source: Toxin and Toxin Target Database (T3DB)
Carcinogen Classification
Theophylline | Group 3: Not classifiable as to its carcinogenicity to humans | Volume 51: (1991) Coffee, Tea, Mate, Methylxanthines and Methylglyoxal
Source: International Agency for Research on Cancer (IARC)
Carcinogen Classification
Theophylline | TR-473: Toxicology and Carcinogenesis Studies of Theophylline in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies) (1998 ) | 12/11/96 | No Evidence | No Evidence | No Evidence | No Evidence | Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of theophylline in male or female F344/N rats administered 7.5, 25, or 75 mg/kg.
Source: NTP Technical Reports
Evidence for Carcinogenicity
Evaluation: There is inadequate evidence for the carcinogenicity in humans of theophylline. There is inadequate evidence for the carcinogenicity in experimental animals of theophylline. Overall evaluation: Theophylline is not classifiable as to its carcinogenicity to humans (Group 3).
Source: Hazardous Substances Data Bank (HSDB)
Endocrine Disruptors
Potential endocrine disrupting compound
Source: NORMAN Suspect List Exchange
Function Categories & List Membership
Cosmetic/Chemical Function Categories
Humectant
Pharmaceutical
Softener and conditioner
Expert Verdict
Expert safety assessment and concern-level summary for Theophylline.
Regulatory Flags
endocrine_disruptor
NOAEL Studies Summary
View details ->Public NOAEL study rows linked to Theophylline by CAS number or substance name.
Studies
8
Lowest NOAEL
30 mg/kg bw/day
Highest NOAEL
124 mg/kg bw/day
ToxValDB_ECHA_IUCLID
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip
Known Synonyms
1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl-
1H-Purine-2,6-dione, 3,9-dihydro-1,3-dimethyl-
EINECS 200-385-7
Purine-2,6(1H,3H)-dione, 1,3-dimethyl-
Theophylline, anhydrous
Xanthine, 1,3-dimethyl-
Theodur
UNII-0I55128JYK
1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
1,3-dimethyl-7H-purine-2,6-dione
Acet-theocin
Aerolate III
Aerolate SR
Aminophylline
Aquaphyllin
Asbron
Asmax
Austyn
Bronkodyl SR
Choledyl SA
Chemical Function
Humectant
Softener and conditioner
Pharmaceutical
Regulatory Lists
active_ingredient; Australia
active_ingredient; animal_products; Europe; pharmaceutical; residue
Europe; pharmaceutical
detected; Europe; surface_water; wastewater
detected; MN Chemical Screening; pharmaceutical; surface_water
detected; MN Chemical Screening; surface_water
detected; MN Chemical Screening; pharmaceutical; surface_water
detected; MN Chemical Screening; surface_water
Canada; pharmaceutical
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
THEOPHYLLINE ANHYDROUS
ChEMBL ID
CHEMBL190
Max Phase
4
Adverse Event Associations
728
Frequently Asked Questions
Is Theophylline allowed in the EU?
Theophylline EU regulatory status: prohibited. This is based on EU Regulation 1223/2009 and its amendments.
What does Theophylline do in cosmetics?
Theophylline functions as: Skin conditioning agent (methylxanthine; promotes microcirculation, lipolysis). It is classified as a cosmetic ingredient in our database. CAS number: 58-55-9.
What is the NOAEL for Theophylline?
The NOAEL (No Observed Adverse Effect Level) for Theophylline is =30 mg/kg bw/day based on a reproduction developmental study via injection route in Rabbit. A total of 2 study endpoints are available. Source: ToxValDB_ECHA_IUCLID.
Is Theophylline classified as hazardous under GHS?
Theophylline carries a GHS signal word of "DANGER". Hazard statements: Toxic if swallowed May be harmful if inhaled May cause harm to breast-fed children Causes damage to vascular system and kidneys Causes damage to the kidneys through prolonged or repeated exposure. This classification is based on the ILO/WHO International Chemical Safety Card and ECHA C&L inventory data. Note: GHS classification applies to the pure substance — at cosmetic use concentrations, hazard thresholds may not be met.
Is Theophylline used outside cosmetics?
Theophylline 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 Theophylline have different safety status in cosmetics vs industrial chemicals?
Theophylline is prohibited in EU cosmetics but has active industrial GHS classifications (H301, H302, H361, H362, H370, H372, H402, H360D).
Compliance Tools
Check Theophylline compliance across multiple jurisdictions:
Ingredient Decoder
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82 Allergen Checker
Check for EU declarable fragrance allergens
Substance Compliance
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MoS Calculator
Calculate Margin of Safety using SCCS methodology
Heavy Metal Limits
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