title: Determination of the LD50 of acridine orange via intravenous administration in mice in preparation for clinical application to cancer therapy.
abstract: OBJECTIVE
  We undertook studies to determine the lethal dose 50 (LD50) of acridine orange (AO) using mice in order to confirm the safety of intravenous administration of AO.
  
  
  METHODS
  We used 40 mice and AO was administered once intravenously. General behavior and mortality were continuously observed for 14 days. At the end of the experiment, all animals were sacrificed for subsequent studies.
  
  
  RESULTS
  The LD50 for AO in male and female mice was determined to be 32 mg/kg and 36 mg/kg, respectively. Histopathological abnormalities were observed in only one mouse which died three days after the administration of AO. The other nine mice which died immediately after the administration of AO had no pathological findings in major organs.
  
  
  CONCLUSIONS
  The clinical use of AO can be kept at 1.0 mg/kg or below and, therefore, intravenous administration of AO might be safe for use as cancer therapy.
authors: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan tomoki66@clin.medic.mie-u.ac.jp.
authors: Tomoki
authors: T
authors: Nakamura
authors: Department of Orthopaedic Surgery, Kujyo Hospital, Kyoto, Japan.
authors: Katsuyuki
authors: K
authors: Kusuzaki
authors: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors: Takao
authors: T
authors: Matsubara
authors: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors: Akihiko
authors: A
authors: Matsumine
authors: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors: Kunihiro
authors: K
authors: Asanuma
authors: Department of Orthopaedic Surgery, Ise Municipal General Hospital, Ise, Japan.
authors: Haruhiko
authors: H
authors: Satonaka
authors: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors: Atsumasa
authors: A
authors: Uchida
authors: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors: Akihiro
authors: A
authors: Sudo
mesh_terms: D000165:Acridine Orange / Q000008:administration & dosage / Q000494:pharmacology*; D061605:Administration, Intravenous; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009153:Mutagens / Q000008:administration & dosage / Q000494:pharmacology*; D023382:Toxicity Tests, Acute
chemical_list: D005456:Fluorescent Dyes; D009153:Mutagens; D000165:Acridine Orange
keywords: Acridine orange; LD50; acute toxicity