Research Article| Volume 249, ISSUE 1, P76-85, November 01, 2006

Sarin experiences in Japan: Acute toxicity and long-term effects


      Two terrorist attacks with the nerve agent Sarin affected citizens in Matsumoto and Tokyo, Japan in 1994 and 1995, killing 19 and injuring more the 6000. Sarin, a very potent organophosphate nerve agent, inhibits acetylcholinesterase (AchE) activity within the central, peripheral, and autonomic nervous systems. Acute and long-term Sarin effects upon humans were well documented in these two events.
      Sarin gas inhalation caused instantaneous death by respiratory arrest in 4 victims in Matsumoto. In Tokyo, two died in station yards and another ten victims died in hospitals within a few hours to 3 months after poisoning.
      Six victims with serum ChE below 20% of the lowest normal were resuscitated from cardiopulmonary arrest (CPA) or coma with generalized convulsion. Five recovered completely and one remained in vegetative state due to anoxic brain damage. EEG abnormalities persisted for up to 5 years.
      Miosis and copious secretions from the respiratory and GI tracts (muscarinic effects) were common in severely to slightly affected victims. Weakness and twitches of muscles (nicotinic effects) appeared in severely affected victims. Neuropathy and ataxia were observed in small number (less than 10%) of victims, which findings disappeared between 3 days and 3 months. Leukocytosis and high serum CK levels were common. Hyperglycemia, ketonuria, low serum triglyceride, hypopotassemia were observed in severely affected victims, which abnormalities were attributed to damage of the adrenal medulla. Oximes, atropine sulphate, diazepam and ample intravenous infusion were effective treatments. Pralidoxime iodide IV reversed cholinesterase and symptoms quickly even if administered 6 h after exposure.
      Post Traumatic Stress Disorder (PTSD) was less than 8% after 5 years. However, psychological symptoms continue in victims of both incidents.
      In summary, both potent toxicity and quick recovery from critical ill conditions were prominent features. Conventional therapies proved effective in Sarin incidents in Japan.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Bright J.E.
        • Inns R.H.
        • Tuckwell N.J.
        • Griffiths G.D.
        • Marrs T.C.
        A histochemical study of changes observed in the mouse diaphragm after organophosphate poisoning.
        Hum Exp Toxicol. 1991; 10: 9-14
        • Burchfiel J.L.
        • Duffy F.H.
        Organophosphate neurotoxicity: chronic effects of Sarin on the electroencephalogram of monkey and man.
        Neurobehav Toxicol Teratol. 1982; 4: 768-778
        • Crowell J.A.
        • Parker R.M.
        • Bucci T.J.
        • Dacre J.C.
        Neuropathy target esterase in hens after Sarin and soman.
        J Biochem Toxicol. 1989; 4: 15-20
        • Duffy F.H.
        • Burchfiel J.L.
        • Bartels P.H.
        • Gaon M.
        • van Sim M.
        Long-term effects of an organophosphate upon the human electroencephalogram.
        Toxicol Appl Pharmacol. 1979; 47: 161-176
        • Goldstein B.D.
        • Fincher D.R.
        • Searle J.R.
        Electrophysiological changes in the primary sensory neuron following subchronic soman and Sarin: iterations in sensory receptor function.
        Toxicol Appl Pharmacol. 1987; 91: 55-64
        • Gupta R.C.
        • Dettbarn W.D.
        Potential of memantine, d-tubocurarine, and atropine in preventing acute myopathy induced by organophosphate nerve agents: soman, Sarin, tabun and VX.
        Neurotoxicology. 1992; 13: 649-661
        • Husain K.
        • Vijayaraghavan R.
        • Pant S.C.
        • Raza S.K.
        • Pandy K.S.
        Delayed neurotoxic effect of Sarin in mice after repeated inhalation exposure.
        J Appl Toxicol. 1993; 13: 143-145
        • Inns R.H.
        • Tuckwell N.J.
        • Bright J.E.
        • Marrs T.C.
        Histochemical demonstration of calcium accumulation in muscle fibers after experimental organophosphate poisoning.
        Hum Exp Toxicol. 1990; 9: 245-250
        • Kadar T.
        • Shapira S.
        • Cohen G.
        • Sahar R.
        • Alkalay D.
        • Raven L.
        Sarin-induced neuropathology in rats.
        Hum Exp Toxicol. 1995; 14: 252-259
        • Kadokura M.
        • Ushijima S.
        • Ogawa Y.
        • Shimizu H.
        • Agata T.
        • Yamamura T.
        Post traumatic stress disorder in victims of an attack with Sarin nerve gas on the Tokyo subway system.
        Rinsho Seishin Igaku. 2000; 29: 677-683
        • Kato T.
        • Hamanaka T.
        Ocular signs and symptoms caused by exposure to Sarin gas.
        Am J Ophthalmol. 1996; 121: 209-210
        • Kawana N.
        • Ishimatsu S.
        • Kanda K.
        Victims of the terrorist Sarin attack on the Tokyo subway system.
        Rinsho Seishin Igaku, Special Issue. 2002; : 139-145
        • Masuda N.
        • Okuda T.
        • Miyazaki S.
        • Takatsu M.
        • Ito K.
        • Kanetaka T.
        • et al.
        Clinical and laboratory data in 71 patients with Sarin poisoning.
        Teishin Igaku. 1995; 47: 387-390
        • Matsumoto Regional Comprehensive Medical Council
        Health emergency control system in Matsumoto city.
        Health Hyg Matsumoto. 2000; 22 ([supplement]): 1-107
        • Morita H.
        • Yanagisawa N.
        • Nakajima T.
        • Shimizu M.
        • Hirabayashi H.
        • Okudera H.
        • et al.
        Sarin poisoning of citizens in Matsumoto.
        Lancet. 1995; 346: 290-293
        • Murata K.
        • Araki S.
        • Yokoyama K.
        • Okumura T.
        • Ishimatsu S.
        • Takasu N.
        • et al.
        Asymptomatic sequelae to acute Sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack.
        J Neurol. 1997; 244: 601-606
        • Nakajima T.
        • Ohta S.
        • Fukushima T.
        • Yanagisawa N.
        Sequelae of Sarin toxicity at one and three years after exposure in Matsumoto, Japan.
        J Epidemiol. 1999; 9: 337-343
        • Nakajima T.
        • Ohta S.
        • Morita H.
        • Midorikawa Y.
        • Mimura S.
        • Yanagisawa N.
        Epidemiological study of Sarin poisoning occurred in Matsumoto City, Japan.
        J Epidemiol. 1998; 8: 33-41
        • Nakajima T.
        • Sato S.
        • Morita H.
        • Yanagisawa N.
        Sarin poisoning of a rescue team in the Matsumoto Sarin incident in Japan.
        Occup Environ Med. 1997; 54: 697-701
        • National Police Academy, Police Science Institute
        A report on casualties of the subway Sarin incident.
        Keisatsu Koron (Police Public Opinion). 1999; 54: 37-47
        • Nishiwaki T.
        • Maekawa K.
        • Ogawa Y.
        • Asukai N.
        • Minami M.
        • Omae K.
        • Sarin Health Effects Study Group
        Effects of Sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway Sarin attack.
        Environ Health Perspect. 2001; 109: 1169-1173
        • Nohara M.
        Opthalmological health checks after Sarin exposure.
        in: Matsumoto Regional Comprehensive Medical Council Health Hyg Matsumoto. vol. 22. 2000: 42-51 (Suppl)
        • Nohara M.
        • Segawa K.
        Ocular symptoms due to organophorus gas (Sarin) poisoning in Matsumoto.
        Br J Ophthalmol. 1996; 80: 1023
        • Nozaki H.
        • Hori S.
        • Shinozawa T.
        • Fujishima S.
        • Takuma K.
        • Kimura H.
        • et al.
        Relationship between pupil size and acetylcholinesterase activity in patients exposed to Sarin vapour.
        Intensive Care Med. 1997; 23: 1005-1007
        • Ohbu S.
        • Yamashita A.
        • Takasu N.
        • Yamaguchi T.
        • Murai T.
        • Nakana K.
        • et al.
        Sarin poisoning on Tokyo subway.
        South Med J. 1997; 90: 587-593
        • Ohtani T.
        • Iwanami A.
        • Kasai K.
        • Yamasue H.
        • Kato T.
        • Sakaki T.
        • et al.
        Post traumatic stress disorder symptoms in victims of Tokyo subway attack: a 5 years follow-up study.
        Psychiatry Clin Neurosci. 2004; 58: 624-629
        • Okudera H.
        • Morita H.
        • Iwashita T.
        • Shibata T.
        • Otagiri T.
        • Kobayashi S.
        • et al.
        Unexpected nerve gas exposure in the city of Matsumoto: report of rescue activity in the firs Sarin gas terrorism.
        Am J Emerg Med. 1997; 15: 527-528
        • Okumura T.
        • Suzuki K.
        • Fukuda A.
        • Koyama
        • Takasu N.
        • Ishimatsu S.
        • et al.
        The Tokyo subway Sarin attack: disaster management: Part l. Community emergency response: Part 2. Hospital response: Part 3. National and international responses.
        Acad Emerg Med. 1998; 5: 613-628
        • Okumura T.
        • Takasu N.
        • Ishimatsu S.
        • Miyanoki S.
        • Mitsuhashi A.
        • Kumada K.
        • et al.
        Report on 640 victims of the Tokyo subway Sarin attack.
        Ann Emerg Med. 1996; 28: 129-135
        • Sekijima Y.
        • Morita H.
        • Yanagisawa N.
        Two-year follow-up study of victims of Sarin poisoning in Matsumoto, Japan.
        Ann Intern Med. 1997; 127: 1042
        • Singer A.W.
        • Jaax N.K.
        • Graham J.S.
        • McLeod Jr., C.G.
        Cardiomyopathy in soman and Sarin intoxicated rats.
        Toxicol Lett. 1987; 36: 243-249
        • Suzuki J.
        • Kohno T.
        • Tsukagoshi M.
        • Furihata T.
        • Yamazaki K.
        Eighteen cases exposed to Sarin in Matsumoto, Japan.
        Int Med. 1997; 36: 466-470
      1. Yanagisawa N. Report for Toxic Gas Attack in Matsumoto. Matsumoto Regional Comprehensive Medical Council1995
        • Yokoyama K.
        • Araki S.
        • Murata K.
        • Nishitani M.
        • Okumura T.
        • Ishimatsu S.
        • et al.
        A preliminary study on delayed vestibulo-cerebellar effects of Tokyo subway Sarin poisoning in relation to gender difference: frequency analysis of postural sway.
        J Occup Environ Med. 1998; 40: 17-21
        • Yokoyama K.
        • Ogura T.
        • Kishimoto M.
        • Hinoshita F.
        • Hara S.
        • Yamada A.
        • et al.
        Blood purification for severe Sarin poisoning after the Tokyo subway attack.
        JAMA. 1995; 274: 379