YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==SARIN NERVE GAS== 6 AUTHOR YOSHIDA T TITLE Toxicological reconsideration of organophosphate poisonings-in relation to the possible nerve gas sarin-poisoned disaster happened in Matsumoto-city, Nagano. SOURCE JAPANESE JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH; 40 (6). 1994. 486-497. ABSTRACT BIOSIS COPYRIGHT: BIOL ABS. The present review describes the structure of anticholinesterase organophosphates (OPs), which are worldwidely and predominantly used as insecticides, in relation to the poisonous gas (possibly sarin-poisoned) disaster happened recently in Matsumoto-city, Nagano. As evident from the disaster, many OP compounds have caused the severe toxicity and even death in humans and domestic animals. The toxicity, chemical structures, mechanism of action (cholinesterase inhibition), clinical signs and syndromes, antidotes and treatment, and prophylactics of nerve gases and OPs are described and discussed. The general metabolic fates of OP insecticides are also dealt with in this review. Some OPs including insecticides have been known to cause chronic toxicity, particularly delayed-type neuropathy (organophosphorus ester-induced delayed neuropathy, OPIDN), which is currently understood to be due to the inhibition of nerve toxic esterase or neuropathy target esterase. OPIDN still has the merit of further study and thus I describe here in detail, because it contributes to the long-term morbidity in cases of severe acute, or chronic, exposure to OPs. 10 AUTHOR ANZUETO A AUTHOR DELEMOS RA AUTHOR SEIDENFELD J AUTHOR MOORE G AUTHOR HAMIL H AUTHOR JOHNSON D AUTHOR JENKINSON SG TITLE Acute inhalation toxicity of soman and sarin in baboons. SOURCE FUNDAM APPL TOXICOL; 14 (4). 1990. 676-687. ABSTRACT BIOSIS COPYRIGHT: BIOL ABS. Adult baboons (Papio sp.; 8-12 kg) were anesthetized with sodium pentobarbital (20 mg/kg iv). The animals were instrumented for measurements of mean blood pressure (MBP), pulmonary artery pressure (PAP), ECG, arterial and mixed venous blood gases, lung volumes, lung pressures, and efferent phrenic nerve activity. Bronchoalveolar lavage (BAL) was performed. Studies were done prior to exposure, at intervals during the first 4 h postexposure, and at 4 and 28 days after exposure. Control animals received a sham exposure to 2-propanol (N = 5), Soman (pinacolyl methylphosphonofluoridate) at 13.14 mug/kg (2 group of animals (N = 5), and sarin (isopropyl methylphosphonofluoride) 30 mug/kg (2 of animals (N = 4). Controls showed no change in any parameter either immediately after diluent exposure or during the monitoring period. Soman and sarin produced a decline in MBP and bradyarrhythmias that were reversed with atropine. Apnea occurred in all soman- and sarin-exposed animals within 5 min postexposure, and was associated with absence of phrenic nerve signal. Ventilation was mechanically supported until the animal could maintain normal arterial blood gases during spontaneous breathing. BAL studies revealed an increase in total white cell population and neutrophils at 4 hr in all three groups. There were signs of impaired hemodynamics and persistent lung injury for 4 days that resolved by 28 days after exposure. In conclusion, inhalation of soman and sarin in the baboon is associated with cardiac arrhythmias, development of apnea, and a significant decrease in MBP. Inhalation exposure also resulted in a persistent influx of neutrophils and hypoxemia. 16 AUTHOR Masuda N AUTHOR Takatsu M AUTHOR Morinari H AUTHOR Ozawa T TITLE Sarin poisoning in Tokyo subway SOURCE Lancet; VOL 345 ISS Jun 3 1995, P1446, (REF 2) ABSTRACT IPA COPYRIGHT: ASHP An overview of the signs, symptoms, and treatment of 71 patients admitted to a hospital in Tokyo following an attack in the subway with the nerve gas sarin on March 20, 1995 is presented. Twenty-five of the patients received inpatient treatment. All patients had local symptoms, such as eye pain, cough, tightness in throat, and nausea. On neurological examination, 41 patients showed miosis and 3 ataxia. No other neurological abnormalities were seen, apart from headache. All patients were discharged within 4 days. In 66 patients, both serum and red-blood-cell cholinesterase activity were examined. Serum cholinesterase activity was decreased in 12 patients, and red-cell cholinesterase activity was decreased in 34 patients. Serum cholinesterase activity ranged from 182 to 804 IU/l in these 66 patients and red-cell cholinesterase activity ranged between 0.3 and 2 U. All patients with decreased red-cell cholinesterase activity showed miosis. 24 AUTHOR Goldstein BD AUTHOR Fincher DR AUTHOR Searle JR TITLE Electrophysiological Changes in the Primary Sensory Neuron Following Subchronic Soman and Sarin: Alterations in Sensory Receptor Function SOURCE Toxicology and Applied Pharmacology, Vol. 91, No. 1, pages 55-64, 29 references, 19871987 ABSTRACT Adult mongrel cats were used to determine whether two organophosphorus agents, soman (96640) (pinacolyl-methylphosphonofluoridate) and sarin (107448) (isopropyl-methylphosphonofluoridate), can produce delayed neurotoxicity, and to study the effects of these agents on the function of peripheral processes of the primary sensory neuron. On the first day after subcutaneous administration of a single high dose (1.0mg/kg) of either soman or sarin, the animals were very weak, with noticeable weight loss. They recovered quickly and never displayed neurological or behavioral signs of delayed neurotoxicity. Animals that received either agent at 5 micrograms per kilogram per day (microg/kg/day) for 5 days or 2.5microg/kg/day for 10 days remained completely healthy, never lost weight, and never displayed any signs of delayed neurotoxicity. From these animals, primary and secondary muscle spindle endings of the soleus nerve and mechanoreceptors of the tibial nerve were isolated, and functional tests were performed. In the 5 day groups given either soman or sarin, the frequency of discharge of primary spindle endings decreased by about one third, but significant changes in the 10 day groups were found only for sarin. Conversely, soman increased the discharge rates of secondary spindle endings in the 5 day groups, and sarin did so in both groups. Discharge rates of slowly adapting type 1 mechanoreceptors were augmented with the 5 day treatment and depressed with the 10 day treatment. The total number of mechanoreceptors per fascicle decreased in both soman and sarin 10 day groups, but there was little change in the 5 day groups. The authors conclude that neither soman nor sarin, administered either in a single large dose or in multiple sublethal doses, can produce classical delayed neurotoxicity, but that functional alterations in cutaneous sensory receptors and proprioceptors do occur following multiple sublethal doses of either agent. 26 AUTHOR RENGSTORFF RH TITLE Accidental exposure to sarin: Vision effects. SOURCE ARCH TOXICOL; 56 (3). 1985. 201-203. ABSTRACT HEEP COPYRIGHT: BIOL ABS. Two men were accidentally exposed to vapors of sarin, a cholinesterase inhibitor and extremely toxic nerve gas. Diagnosis was confirmed by depressed cholinesterase activity, and fixed extremely mitotic pupils. No other signs or symptoms developed and neither man required treatment. Recovery to normal cholinesterase activity was gradual over a 90-day period. Pupillary reflexes were not detectable until 11 days after exposure; the mitotic pupils dilated slowly over a 30 to 45 day period. Eye pain and blurred vision did not occur; visual acuity and amplitude of accommodation were improved for several weeks. Other functions not affected significantly were intraocular pressure, visual fields, color vision, heterophorias and vergences. You are now connected to the HSDB file. 1 - HSDB NAME OF SUBSTANCE SARIN CAS REGISTRY NUMBER 107-44-8 HUMAN TOXICITY EXCERPTS Although GB is also effective by penetration through the skin, the dose required to produce toxic effects by this route is very high, so that a masked person is well protected. [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984. V5 398 (1979)] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Inhalation of G-agent vapor at realizable field concentrations is immediately incapacitating. The symptoms in normal order of appearance are running nose; tightness of chest; dimness of vision and pinpointing of the eye pupils (myosis); difficulty in breathing; drooling and excessive sweating; nausea, vomiting; cramps and involuntary defecation or urination; twitching, jerking, and staggering; and headache, confusion, drowsiness, coma, and convulsion. These symptoms are followed by cessation of breathing and death. /G-agents/ [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984. V5 398 (1979)] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS /G-agents/ are sufficiently potent so that even a brief exposure may be fatal. Death may occur in 1-10 min, or may be delayed for 1-2 hr, depending on the concentration of the agent. /G-agents/ [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984. V5 398 (1979)] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Neurotoxic effects of sarin are EEG changes. /From table/ [O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume I. Boca Raton, FL: CRC Press, Inc., 1985., p. 129] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Sarin ... an anticholinesterase nerve gas, produces miosis and enhancement of accommodation for near vision. The miosis is generally not long lasting. Impairment of visual performance in dim illumination appears to be related primarily to reduction of the amount of light entering the eye through the reduced area of the pupillary aperture. No significant difference has been found in effect on visual threshold between sarin vapor and physostigmine eyedrops. However, studies on dark adaptation by one group of investigators resulted in findings that could not be explained by degree of miosis, and led to suggestions of disturbance of some mechanism in the central nervous system. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 801] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Sarin is the most toxic of the "nerve gases". It is related to tabun, and both are extremely active cholinesterase inhibitors, much more severe in activity than parathion. The lethal dose for man is estimated to be 0.01 mg/kg. [Zenz, C. Occupational Medicine-Principles and Practical Applications. 2nd ed. St. Louis, MO: Mosby-Yearbook, Inc, 1988., p. 676] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Organophosphorus cmpd can produce dermal irritation but most are weak sensitizers. /Organophosphorus cmpd/ [Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1073] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS A woman at 34 to 35 weeks' gestation presented in acute respiratory distress with cyanosis and tachypnea and bilateral rhonchi and crepitation. Her heart rate was 78 beats/min and her blood pressure 120/80 mm Hg, with a fetal heart rate of 140 beats/min. The mother was salivating markedly and her pupils were reduced to "pinpoint size." An uncorrected metabolic acidosis was diagnosed. Serum and erythrocyte acetylcholinesterase determinations were near zero. Cholinesterase inhibitor poisoning was felt to be the likely cause of disorders. Administration of atropine 2.4 mg iv bolus with infusion of 0.02 mg/kg/hr lead to unacceptable fetal tachycardia. The woman had shown increased cooperativeness and secretion control until the atropine had to be stopped. A cesarean section was performed for delivery of a hypotonic infant with a 1 minute Apgar score of 3. The baby was mechanically ventilated for 2 days and required atropine therapy at 0.1 mg/kg/hr for 8 days. The mother required 8 days of mechanical ventilation and 11 days of atropine therapy. In this case, the infant appeared relatively less poisoned than the mother by a presumed organophosphate exposure. /Organophosphate poisoning/ [Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 430] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Individuals poisoned by nerve agents /including sarin/ display the following symptoms: difficulty in breathing; drooling and excessive sweating; nausea; vomiting, cramps, and involuntary defecation and urination; twitching, jerking, and staggering; headache, confusion, drowsiness, coma, and convulsion; and, when the agent is inhaled, dimness of vision and pinpointing of the eye pupils. However, if exposure has been cutaneous or by ingestion of a nerve agent, the pupils may be normal or, in the presence of severe systemic symptoms, slightly to moderately reduced in size. In this event, the symptoms of nerve agent poisoning other than its effects on the pupils must be relied upon to establish the diagnosis. These nerve agent symptoms are followed by cessation of breathing and death. Symptoms appear much more slowly from skin dosage. Although skin absorption great enough to cause death may occur in 1 to 2 min, death may be delayed for 1 to 2 hr. Respiratory lethal dosages kill in 1 to 10 min, and liquid in the eye kills nearly as rapidly. The number and severity of symptoms are dependent on the quantity and rate of entry of the nerve agent into the body. (Very small skin dosages sometimes cause local sweating and tremors with little other effect.) [Military Chemistry and Chemical Compounds, Departments of the Army and the Air Force; Field Manual 3-9, Air Force Regulation 355-7:3-3-4 (1975)] **PEER REVIEWED**