title: Long-term accumulation of diphenylarsinic acid in the central nervous system of cynomolgus monkeys.
abstract: Diphenylarsinic acid (DPAA) is an organic arsenic compound used for the synthesis of chemical weapons. We previously found that the residents of Kamisu city in Ibaraki Prefecture, Japan, were exposed to DPAA through contaminated well water in 2003. Although mounting evidence strongly suggests that their neurological symptoms were caused by DPAA, the dynamics of DPAA distribution and metabolism after ingestion by humans remain to be elucidated. To accurately predict the distribution of DPAA in the human body, we administrated DPAA (1.0 mg/kg/day) to cynomolgus monkeys (n = 28) for 28 days. The whole tissues from these monkeys were collected at 5, 29, 170, and 339 days after the last administration. The concentration of DPAA in these tissues was measured by liquid chromatography-mass spectrometry. We found that DPAA accumulated in the central nervous system tissues for a longer period than in other tissues. This finding would extend our knowledge on the distribution dynamics and metabolism of DPAA in primates, including humans. Furthermore, it may be useful for developing a treatment strategy for patients who are exposed to DPAA.
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan.|Doctoral and Master's Programs in Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, 305-8577, Japan.|Department of Neurobiology, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8577, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan. kazishii@md.tsukuba.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Third Department of Forensic Science, National Research Institute of Police Science, Chiba, 277-0882, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Seto
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hosoya
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, Ibaraki Prefectural University of Health Sciences, Ibaraki, 300-0331, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Pediatrics, Ibaraki Prefectural University of Health Sciences, Ibaraki, 300-0331, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Iwasaki
authors.affiliation: Center for Environmental Measurement and Analysis, National Institute for Environmental Studies, Ibaraki, 305-8506, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tamaoka
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002490:Central Nervous System / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D023421:Models, Animal; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D001152:Arsenicals; C493087:diphenylarsinic acid
keywords: Cerebellum; Cerebrum; LC–MS; Macaca fascicularis; Phenyl arsenic compound; Primate