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Objectives: The suicidal ingestion of a herbicide BASTA[R] containing 20% glufosinate ammonium and 33% anionic surfactant is increasing in Japan. This herbicide is used over 80 countries, including Canada and USA where recombinant plants resistant to glufosinate are cultivated. In 1998, a severe case of BASTA[R] ingestion was recorded in Canada. BASTA[R] produces central nervous system (CNS) signs, such as coma, apnea, and generalized convulsions, with a latent period of 8-38 hours.[1] Though, patients look asymptomatic during the latent period, they deteriorate unexpectedly. If we can predict the severity during the latent period, the treatment will be more safe and effective. Because the CNS signs are considered to be due essentially to glufosinate,[2] we studied the relationship between the serum glufosinate level ([GLF]s) and severe CNS signs. Method: We collected cases of acute BASTA[R] poisoning, referring to MEDLINE and Japana Centra Revuo Medicina, and records of the Japan Poison Information Center. From 1990 to May 1999, we found 74 cases of acute BASTA[R] poisoning where [GLF]s on admission was measured. The severe cases were defined as those who developed at least one of the following signs: coma, apnea, and generalized convulsions that are common and need life-saving respiratory management. Patients who developed none of these signs were defined as non-severe. Results: We obtained 42 severe cases (male 16, female 26; 22-86 year-old), and 32 non-severe cases (male 21, female 11; 20-86 year-old). When [GLF]s on admission was plotted semi-logarithmically related to the time from ingestion, severe cases were located higher than non-severe cases. Above the A-line, connecting 200 ppm at 2 hours and 15 ppm at 8 hours, all cases were severe. Below the B-line, connecting 70 ppm at 2 hours and 5 ppm at 8 hours, all cases were non-severe. Between A-line and B-line, 50% (6/12) were severe cases. Eighty percent of cases were above the A-line or below the B-line. Conclusion: [GLF]s on admission had a close relation to the development of severe CNS signs in acute BASTA[R] poisoning. Measurement of [GLF]s on admission by HPLC, which needs only 2-3 hours[3], may be valuable in the treatment of acute BASTA[R] poisoning. References: [1] Oxford Textbook of Critical Care. Oxford University Press 1999:657-659.[2] Koyami K. Glufosinate and a surfactant: which component produces effects on the central nervous system in acute oral BASTA poisoning? Vet Hum Toxicol 1999;41:341.[3] Bunseki Kagaku 1997; 46:66-74. Koyama K, Hirose Y, Tase C, Kohriyama K, Ohashi N, Goto K, Okuda T, Akuzawa H, Kohda Y, Goto K. Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575 Japan; Japan Poison Information Center, Suita, Osaka, 565-0871 Japan

Objectives: Acute poisoning caused by the suicidal ingestion of the herbicide BASTA[R], containing glufosinate ammonium 20%, is increasing in Japan. Symptoms of this poisoning include coma, apnea, and generalized convulsions etc.[1] These signs are considered to be due to the effects of glufosinate on the central nervous system.[2] At present, human toxicokinetics of glufosinate, essential for evaluating the indication for treatments such as forced diuresis and extracorporeal hemopurification, have not been studied except one case report we previously published.[3] Adding a case we experienced recently, we report here 2 cases of acute oral BASTA[R] poisoning where toxicokinetics of glufosinate were studied. Methods: A 65-year-old male who had ingested about 300 mL of BASTA[R] (case 1),[3] and a 46-year-old female who had ingested about 200 mL of BASTA[R] (case 2) were studied. Treatments consisted of gastric lavage, activated charcoal and cathartics, and fluid infusion without diuretics. Extracorporeal hemopurifications were not conducted. Artificial ventilation was necessary for 5 days and 10 days in case 1 and case 2, respectively. Both patients were discharged without any sequelae. Serum obtained from 2 mL blood, drawn every 3-6 hours during the first 2 days, and daily urine collection sampled for 8 days, were used for measurement of glufosinate concentration by HPLC[4]. The toxicokinetics of glufosinate were analyzed by a 2-compartment model. Based on the previous report[3], the absorbed amount of glufosinate was estimated to be the total amount of glufosinate excreted in urine divided by 0.9, the urinary excretion ratio obtained experimentally. Results: The toxicokinetic parameters calculated were as follows in case 1 and case 2, respectively: AUC = 657.6, 1389.7 (h [micro]g/mL), Vd [Beta] = 1.44, 1.92 (L/kg), [CL.sub.total] = 0.103, 0.144 (L/kg/hr), [t.sub.1/2][Alpha] = 1.84, 1.23 (hr), [t.sub.1/2][Beta] = 9.59, 9.22 (hr). In the initial 24 hours, 97% and 98% of total urinary glufosinate was excreted in urine in case 1 and case 2, respectively. Conclusion: The obtained value of Vd of greater than 1 L/kg indicates that glufosinate distributes in tissues more than in the blood. On the other hand, [CL.sub.total] values were at a similar level to creatinine clearance, and over 95% of total urinary glufosinate was excreted in urine within 24 hours after ingestion. From these characteristics in toxicokinetics of glufosinate, we consider that extracorporeal hemopurification might not be indispensable in the treatment of acute BASTA[R] poisoning. References: [1] Oxford Textbook of Critical Care. Oxford University Press 1999:657-659. [2] Koyami K. Glufosinate and a surfactant: which component produces effects on the central nervous system in acute oral BASTA poisoning? Vet Hum Toxicol 1999;41:341. [3] Hirose Y, Kobayashi M, Koyama K et al. A toxicokinetic analysis in a patient with acute glufosinate poisoning. Hum Exp Toxicol 1999;18: 305-308. [4] Bunseki Kagaku 1997;46:66-74. Koyama K, Hirose Y, Iimori E, Kohriyama K, Tase C, Khoda Y, Goto K. Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575 Japan