title: A safety study on single intravenous dose of tetrachloro-diphenyl glycoluril [iodogen] dissolved in dimethyl sulphoxide (DMSO).
abstract: 1. Iodogen (tetrachloro-diphenyl glycoluril) dissolved in DMSO (dimethyl sulphoxide) appears indispensable in radioiodination of hypericin for a new anticancer strategy. We studied the safety of intravenously administered iodogen/DMSO in mice (n = 132). 2. Median lethal dose (LD50) of iodogen/DMSO was determined with doses of 40.0, 50.0, 55.0, 60.0, 65.0 and 70.0 mg/kg. Next, toxicity of iodogen/DMSO at 30.0 mg/kg was evaluated using saline and DMSO as controls. Changes in behaviour, body weight and serum biochemistry were evaluated. Histopathology of lungs, heart, liver and kidney was performed. 3. LD50 values of iodogen/DMSO were 59.5 mg/kg (95% confidence limits (CI): 54.1-65.4 mg/kg) and 61.0 mg/kg (95%CI: 56.2-66.2 mg/kg) for female and male mice, respectively. Similar to that of control groups, no animal deaths were encountered after iodogen/DMSO administration at 30.0 mg/kg. Body weights over 24 h were not altered in all groups, but significantly higher in iodogen/DMSO and DMSO groups (p < 0.05) 14 d post-injection. Blood urea nitrogen and alkaline phosphatase increased (p < 0.05) in iodogen/DMSO group without clinical symptoms. No pathologies were found by gross and microscopic inspection. 4. A single dose of iodogen/DMSO up to 30.0 mg/kg, over 3000 times the dose in potential human applications, appears safe, with an LD50 doubling that dose in mice.
authors.affiliation: Department of Imaging & Pathology, Biomedical Sciences Group, KU Leuven, Leuven, Belgium.
authors.forename: Marlein Miranda
authors.initials: MM
authors.lastname: Cona
authors.forename: Junjie
authors.initials: J
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Feng
authors.forename: Yeranddy Aguiar
authors.initials: YA
authors.lastname: Alpizar
authors.forename: Florent
authors.initials: F
authors.lastname: Vanstapel
authors.forename: Karel
authors.initials: K
authors.lastname: Talavera
authors.forename: Peter
authors.initials: P
authors.lastname: de Witte
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
authors.forename: Ziping
authors.initials: Z
authors.lastname: Sun
authors.forename: Raymond
authors.initials: R
authors.lastname: Oyen
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009928:Organ Specificity / Q000187:drug effects; D010084:Oxidation-Reduction; D012995:Solubility; D016019:Survival Analysis; D014508:Urea / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D007457:Iodine Radioisotopes; C012385:1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril; D014508:Urea; D004121:Dimethyl Sulfoxide