National Toxicology Program

CASRN: 7220-79-3

Formula: C16 H18 N3 S CL.3H20

Synonyms/Common Names:

• C.I. BASIC BLUE 9, TRIHYDRATE
• PHENOTHIAZIN-5-IUM, 3,7-BIS(DIMETHYLAMINO)-,CHLORIDE, TRIHYDRATE

Known Uses:

BLUE DYE USED IN BACTERIOLOGY, PAPER, SURGICAL SKIN MARKING, ANTIHEMOGLOBINEMIC, CYANINE POISONING ANTIDOTE, FORMERLY USED IN HAIR COLORING

Nomination Background

Short-Term Toxicity

• 13-WEEK (Gavage)  (C91005B) Completed 
  • Rats: F344/N; Mice: B6C3F1
  • Dose: R&M: 0, 25, 50, 100, OR 200 MG/KG; 30 SEX/SPECIES/GROUP
• 4-WEEK (Gavage)  (C91005) Completed 
  • Rats: F344/N; Mice: B6C3F1
  • Dose: R&M: 0, 0.125, 0.25, 0.5, 1.0, OR 2.0 MG/KG BODY WT. R: 20/GROUP/SEX; M: 10/GROUP/SEX

Long-Term Carcinogenicity

• 2-YEAR (Gavage)  (C91005C) Report Review 
  • TR-540   (Peer Review 06/12/2006)
    Toxicology and Carcinogenesis Studiies of Methylene Blue Trihydrate (CAS No. 7220-79-3) in F344/N Rats and B6C3F1 Mice (gavage studies)
  • Rats: F344/N; Mice: B6C3F1
  • Carcinogenesis Results
  • Male Rats Some Evidence 
  • Female Rats No Evidence 
  • Male Mice Some Evidence 
  • Female Mice Equivocal Evidence 
  • Dose: R: 0, 5, 25, OR 50 MG/KG; M: 0, 2.5, 12.5, OR 25 MG/KG; 50/SEX/SPECIES

Special Studies

• Toxicokinetic Study (Intravenous; Gavage; Intravenous; Gavage)  (S0660) Completed 
  • Citation: PART OF TWO YEAR TECHNICAL REPORT C91005C
  • M/F Rats: F344/N; M/F Rats: F344/N; M/F Mice: B6C3F1; M/F Mice: B6C3F1
  • Dose: IV: 0.625 mg/ml (rats, 2 ml/kg); 0.125 mg/ml (mice, 4 ml/kg)

Genetic Toxicology

• In Vitro Cytogenetics (CA/SCE)  (563848) Completed 
  • Chromosome Aberation Positive 
  • Sister Chromatid Exchange Positive 
• Micronucleus  (A76244) Completed 
  • Mice: B6C3F1
  • Male Negative 
• Micronucleus  (A77225) Completed 
  • Mice
  • Male Negative 
  • Female Negative 
• Salmonella  (811345) Completed 
  •  Positive 
• Salmonella  (A35880) Completed 
  •  Positive 

Organ Systems Toxicity

• Conventional Teratology (Gavage)  (TER92124) Completed 
  • NTIS No. PB93-219574
    Citation: Final Report on the Developmental Toxicity of Methylene Blue Trihydrate in Sprague-Dawley (CD) Rats
  • Rats: Sprague Dawley
  • Rats Maternal Positive 
  • Rats Fetal Positive 
  • Dose: REP I: 0, 50, 200, 350 MG/KG/DAY REP II: 0, 50, 125, 200 MG/KG/DAY
• GD 6 THROUGH 19 Conventional Teratology (Gavage)  (TER92125) Completed 
  • NTIS No. PB94-207214
    Citation: Final Report on the Developmental Toxicity of Methylene Blue Trihydrate in New Zealand White Rabbits
  • NTIS No. PB94-207503
    Citation: Final Report on the Developmental Toxicity of Methylene Blue Trihydrate in New Zealand White Rabbits
  • F Rabbit: New Zealand White
  • Rabbits Maternal Positive 
  • Rabbits Fetal Positive 
  • Dose: 0, 50, 100, 150 MG/KG/DAY
• GD 6 THROUGH 15 Teratology Pilot Studies (Gavage)  (TRP91018) Completed 
  • F Rats: Sprague Dawley
  • Dose: 0, 50, 100, 200, 400, OR 600 MG/KG
• GD 6 THROUGH 19 Teratology Pilot Studies (Gavage)  (TRP91019) Completed 
  • F Rabbit: New Zealand White
  • Dose: 0, 10, 50, 100, 200, OR 300 MG/KG