Organophosphates and their impact on the global environment.

Serious intoxications and incidences due to misuse of organophosphorus insecticides (OP) have been reported for over three decades. In this meeting I am talking about the following three topics. (1) Epidemiological studies on the use of OP in Japan, Taiwan and Thailand. The National Research Institute of Police Science (NRIPS) in Japan has published the annual report of the epidemiological studies on the criminal and suicide events. The numbers of the incidence of pesticides are approximately 22%-30% of the total incidences, during 1991 and 1996. The incidence of pesticides has been gradually reduced for past six years. This seems to be influenced by the decrease of the incidences of paraquat having extremely high toxicity. According to the epidemiological data in the National Poison Center in Taiwan, unlike the prevalence of drug poisoning exposures in most western countries, pesticides poisoning exposures are numerous in Taiwan. The number of pesticide intoxication cases is 6,872 out of 23,436 of total case numbers of various intoxications during the 1985 and 1997. The fatality rate is much higher in Taiwan than in most western countries, with 5.65% of all poisoning exposures resulted in death. Paraquot is the leading cause of death in Taiwan. The ratio of death to total OP intoxication cases is 11.5% including accidental exposure and suicide. According to the report of the Division of Epidemiology, Ministry of Public Health, Thailand during the 1990-1995, the overall morbidity due to poisoning was 30 per 100,000 population with 300 deaths per year. The morbidity rate of reported pesticide poisoning in the whole country was 10 per 100,000 population. (2) Sarin victims in Tokyo. On March 20, 1995, a terrorist attack using sarin (isopropylmethylphosphonofluoridate) occurred on the Tokyo subway. Many people inhaled the sarin gas and collapsed in the train. Eventually, 12 people died and over 5,000 were injured. The results of the forensic studies showed that methylphosphonic acid, the hydrolysis product of sarin, bound to AChE in the cerebellums of the victims was separated and identified using GCMS. (3) A sensitive and rapid biomarker of OP-poisoning. Beta-glucuronidase (beta-G) is loosely bound to egasyn which is one of carboxylesterase isozymes in the liver microsomes. The oxon formed from OP in the liver microsomes is covalently bound to egasyn and causes the cleavage of the egasyn-glucuronidase complex, leading to the release of beta-G into the blood. In fact, plasma beta-G activities is a much more sensitive and rapid biomarker than the blood cholinesterase inhibition. In conclusion, OPs cause serious toxicity in both acute and chronic exposures. The epidemiological data in Taiwan and Thailand show that paraquat intoxication cause the most serious irreversible damage in the patients. In 1995, terrorists attack using sarin which is one of the most toxic OP, on the Tokyo subway, and 12 people died. This is an example of the acute intoxication of OP and some people have been still in hospitalized. Recently, the present authors have reported that the plasma beta-G activity is a novel biomarker of OP intoxication. The plasma beta-G is rapidly and significantly increased after OP exposure, and this is a much more sensitive to OP intoxication than ChE inhibition.