Our recent experiences with sarin poisoning cases in Japan and pesticide users with references to some selected chemicals.

Attention has been paid to neurobehavioral effects of occupational and environmental exposures to chemicals such as pesticides, heavy metals and organic solvents. The area of research that includes neurobehavioral methods and effects in occupational and environmental health has been called "Occupational and Environmental Neurology and Behavioral Medicine." The methods, by which early changes in neurological, cognitive and behavioral function can be assessed, include neurobehavioral test battery, neurophysiological methods, questionnaires and structured interview, biochemical markers and imaging techniques. The author presents his observations of neurobehavioral and neurophysiological effects in Tokyo subway sarin poisoning cases as well as in pesticide users (tobacco farmers) in Malaysia in relation to Green Tobacco Sickness (GTS). In sarin cases, a variety effects were observed 6-8 months after exposure, suggesting delayed neurological effects. Studies on pesticide users revealed that organophosphorus and dithiocarbamate affected peripheral nerve conduction and postural balance; subjective symptoms related to GTS were also observed, indicating the effects of nicotine absorbed from wet tobacco leaves. In addition, non-neurological effects of pesticides and other chemicals are presented, in relation to genetic polymorphism and oxidative stress.

[1]  Andreas Hald,et al.  Oxidative stress and inflammation in Parkinson's disease: is there a causal link? , 2005, Experimental Neurology.

[2]  T. Kawada,et al.  Elevated frequency of sister chromatid exchanges of lymphocytes in sarin-exposed victims of the Tokyo sarin disaster 3 years after the event. , 2004, Toxicology.

[3]  F. Coppedè,et al.  Oxidative DNA damage in peripheral leukocytes of mild cognitive impairment and AD patients , 2005, Neurobiology of Aging.

[4]  Tomoko Yamaguchi,et al.  Teratogenicity and developmental toxicity of chlorpyrifos. Maternal exposure during organogenesis in mice. , 2005, Reproductive toxicology.

[5]  S. Araki,et al.  Assessment of Urinary Cotinine as a Marker of Nicotine Absorption from Tobacco Leaves: A Study on Tobacco Farmers in Malaysia , 2003, Journal of occupational health.

[6]  I. Ho,et al.  Relationship between the neurotoxicities of Soman, Sarin and Tabun, and acetylcholinesterase inhibition. , 1986, Toxicology letters.

[7]  T. Galloway,et al.  Immunotoxicity of Organophosphorous Pesticides , 2003, Ecotoxicology.

[8]  K. Murata,et al.  Chronic neurobehavioral and central and autonomic nervous system effects of Tokyo subway sarin poisoning , 1998, Journal of Physiology-Paris.

[9]  S. Kuzuhara,et al.  Atypical parkinsonism of Japan: Amyotrophic lateral sclerosis–parkinsonism–dementia complex of the Kii peninsula of Japan (Muro disease): An update , 2005, Movement disorders : official journal of the Movement Disorder Society.

[10]  K. Yokoyama,et al.  Gene-environmental interactions between alcohol-drinking behavior and ALDH2 and CYP2E1 polymorphisms and their impact on micronuclei frequency in human lymphocytes. , 2006, Mutation research.

[11]  A Bhattacharya,et al.  Health status of pesticide applicators: postural stability assessments. , 1993, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[12]  K. Murata,et al.  Chronic neurobehavioral effects of Tokyo subway sarin poisoning in relation to posttraumatic stress disorder. , 1998, Archives of environmental health.

[13]  K. Savolainen,et al.  Second messengers in cholinergic-induced convulsions and neuronal injury. , 1992, Toxicology letters.

[14]  Y. Nishiwaki,et al.  Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack. , 2001, Environmental health perspectives.

[15]  T Okumura,et al.  Report on 640 victims of the Tokyo subway sarin attack. , 1996, Annals of emergency medicine.

[16]  Mohammad Abdollahi,et al.  Pesticides and oxidative stress: a review. , 2004, Medical science monitor : international medical journal of experimental and clinical research.

[17]  Christophe Tzourio,et al.  CYP2D6 polymorphism, pesticide exposure, and Parkinson's disease , 2004, Annals of neurology.

[18]  McLeod Cg,et al.  Acute neuropathology in soman poisoned rats. , 1984 .

[19]  W K Anger,et al.  Worksite behavioral research. Results, sensitive methods, test batteries and the transition from laboratory data to human health. , 1990, Neurotoxicology.

[20]  Y. Nishiwaki,et al.  Effects of Sarin on the Nervous System of Subway Workers Seven Years after the Tokyo Subway Sarin Attack , 2005, Journal of occupational health.

[21]  N. Benowitz Drug therapy. Pharmacologic aspects of cigarette smoking and nicotine addiction. , 1988, The New England journal of medicine.

[22]  R. S. Ahmed,et al.  Pesticide-Induced Oxidative Stress : Perspective and Trends , 2001, Reviews on environmental health.

[23]  Claudia Bolognesi,et al.  Genotoxicity of pesticides: a review of human biomonitoring studies. , 2003, Mutation research.

[24]  T Okumura,et al.  The Tokyo subway sarin attack--lessons learned. , 2005, Toxicology and applied pharmacology.

[25]  S. Gehlbach,et al.  Green-Tobacco Sickness: An Illness of Tobacco Harvesters , 1974 .

[26]  M. Gerber,et al.  Interaction between genetic polymorphism of cytochrome P450-1B1 and environmental pollutants in breast cancer risk , 2004, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[27]  J A Lewis,et al.  Chronic neurological sequelae of acute organophosphate pesticide poisoning. , 1988, Archives of environmental health.

[28]  D. Eaton,et al.  Effect of styrene oxide on rat brain glutathione. , 1991, Neurotoxicology.

[29]  H. Yamasue,et al.  Activation of the prefrontal cortex to trauma-related stimuli measured by near-infrared spectroscopy in posttraumatic stress disorder due to terrorism. , 2003, Psychophysiology.

[30]  A. Usmani,et al.  Pesticide metabolism in humans, including polymorphisms. , 2005, Scandinavian journal of work, environment & health.

[31]  M. Fenech,et al.  Measurement of micronuclei in lymphocytes. , 1985, Mutation research.

[32]  Hidetaka Yamamoto,et al.  Effects of Prednisolone and Complex of Vitamin B1, B2, B6 and B12 on Organophosphorus Compound‐Induced Delayed Neurotoxicity , 2004, Journal of occupational health.

[33]  Nobumasa Kato,et al.  Serum cholesterol, uric acid and cholinesterase in victims of the Tokyo subway sarin poisoning: A relation with post-traumatic stress disorder , 2002, Neuroscience Research.

[34]  Tetsu Okumura,et al.  Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack , 1997, Journal of Neurology.

[35]  T. Yamauchi,et al.  Micronucleus formation in 3-day mouse embryos associated with maternal exposure to chlorpyrifos during the early preimplantation period. , 2003, Reproductive toxicology.

[36]  M. Sanchez,et al.  Chromosome and DNA damage analysis in individuals occupationally exposed to pesticides with relation to genetic polymorphism for CYP 1A1 gene in Ecuador. , 2004, Mutation research.

[37]  F. Duffy,et al.  Long-term effects of an organophosphate upon the human electroencephalogram. , 1979, Toxicology and applied pharmacology.

[38]  K. Schuh,et al.  Nicotine nasal spray and vapor inhaler: abuse liability assessment , 1997, Psychopharmacology.

[39]  R. McConnell,et al.  Chronic central nervous system effects of acute organophosphate pesticide intoxication , 1991, The Lancet.

[40]  J. Graham,et al.  Cardiomyopathy in Soman and Sarin intoxicated rats. , 1987, Toxicology letters.

[41]  J. Ito,et al.  Experimental vestibular pharmacology: a minireview with special reference to neuroactive substances and antivertigo drugs. , 1984, Acta oto-laryngologica. Supplementum.

[42]  Antonio F. Hernández,et al.  Changes in erythrocyte enzymes in humans long-term exposed to pesticides: influence of several markers of individual susceptibility. , 2005, Toxicology letters.

[43]  S. Araki,et al.  Effects of pesticides on the peripheral and central nervous system in tobacco farmers in Malaysia: studies on peripheral nerve conduction, brain-evoked potentials and computerized posturography. , 2005, Industrial health.

[44]  L. Costa Biochemical and molecular neurotoxicology: relevance to biomarker development, neurotoxicity testing and risk assessment. , 1998, Toxicology letters.

[45]  W. Markesbery The role of oxidative stress in Alzheimer disease. , 1999, Archives of neurology.

[46]  G. Lemercier,et al.  Histological and histochemical changes in the central nervous system of the rat poisoned by an irreversible anticholinesterase organophosphorus compound , 2004, Acta Neuropathologica.

[47]  A. Tsatsakis,et al.  A tetranucleotide repeat polymorphism in the CYP19 gene and breast cancer susceptibility in a Greek population exposed and not exposed to pesticides. , 2004, Toxicology letters.

[48]  A. Bittner,et al.  Chronic low-level mercury exposure, BDNF polymorphism, and associations with self-reported symptoms and mood. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[49]  Tsuyoshi Araki,et al.  Association between lower P300 amplitude and smaller anterior cingulate cortex volume in patients with posttraumatic stress disorder: a study of victims of Tokyo subway sarin attack , 2005, NeuroImage.

[50]  I. Kanazawa,et al.  Distal sensory axonopathy after sarin intoxication , 1998, Neurology.

[51]  M Fenech,et al.  The cytokinesis-block micronucleus technique and its application to genotoxicity studies in human populations. , 1993, Environmental health perspectives.

[52]  F. Macciardi,et al.  Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene–environment interactions , 2005, Molecular Psychiatry.

[53]  S. Shima,et al.  Validity of the Japanese version of the GHQ among antenatal clinic attendants , 1989, Psychological Medicine.

[54]  P. Sutker,et al.  Cognitive deficits and psychopathology among former prisoners of war and combat veterans of the Korean conflict. , 1991, The American journal of psychiatry.

[55]  P. Palozza,et al.  DNA damage and apoptosis induction by the pesticide Mancozeb in rat cells: involvement of the oxidative mechanism. , 2006, Toxicology and applied pharmacology.

[56]  K. Murata,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. , 1998, Journal of occupational and environmental medicine.

[57]  K Steenland,et al.  Chronic neurological sequelae to organophosphate pesticide poisoning. , 1994, American journal of public health.

[58]  M. Abou‐Donia,et al.  Organophosphorus Ester-Induced Chronic Neurotoxicity , 2003, Archives of environmental health.

[59]  P. Oteiza,et al.  Metals in neurodegeneration: involvement of oxidants and oxidant-sensitive transcription factors. , 2004, Molecular aspects of medicine.

[60]  X. Zhou,et al.  Polymorphism of metabolic genes and susceptibility to occupational chronic manganism , 2002, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[61]  H. Yamasue,et al.  Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[62]  L. Migliore,et al.  Oxidative damage and cytogenetic analysis in leukocytes of Parkinson’s disease patients , 2002, Neurology.

[63]  H. Yamasue,et al.  Hypoactivation of the prefrontal cortex during verbal fluency test in PTSD: a near-infrared spectroscopy study , 2003, Psychiatry Research: Neuroimaging.

[64]  A. Silver Cholinesterases of the central nervous system with special reference to the cerebellum. , 1967, International review of neurobiology.

[65]  L. Zhong,et al.  Oxidative DNA Damage in Relation to Neurotoxicity in the Brain of Mice Exposed to Arsenic at Environmentally Relevant Levels , 2005, Journal of occupational health.

[66]  G. Geiss,et al.  Role of paraoxonase (PON1) status in pesticide sensitivity: genetic and temporal determinants. , 2005, Neurotoxicology.

[67]  Yi-ping Fu,et al.  Pesticide exposure on southwestern Taiwanese with MnSOD and NQO1 polymorphisms is associated with increased risk of Parkinson's disease. , 2007, Clinica chimica acta; international journal of clinical chemistry.

[68]  G. Edwards Ivermectin: does P-glycoprotein play a role in neurotoxicity? , 2003, Filaria journal.

[69]  S. Bondy,et al.  Ethanol toxicity and oxidative stress. , 1992, Toxicology letters.

[70]  H. Checkoway,et al.  Risk of Brain Tumors in Children and Susceptibility to Organophosphorus Insecticides: The Potential Role of Paraoxonase (PON1) , 2005, Environmental health perspectives.

[71]  J. Adams,et al.  Free radical induction in the brain and liver by products of toluene catabolism. , 1993, Biochemical pharmacology.

[72]  D. Eaton Biotransformation enzyme polymorphism and pesticide susceptibility. , 2000, Neurotoxicology.

[73]  H. Waldron Prevention of neurotoxic illness in working populations , 1988 .

[74]  K. Murata,et al.  Auditory event-related potential (P300) in relation to peripheral nerve conduction in workers exposed to lead, zinc, and copper: effects of lead on cognitive function and central nervous system. , 1992, American journal of industrial medicine.

[75]  Michael J. Aminoff,et al.  Electrodiagnosis in Clinical Neurology , 1980 .

[76]  R. Weizenecker,et al.  Tobacco cropper's sickness. , 1970, The Journal of the Florida Medical Association.

[77]  M. Cullen,et al.  Clinical Occupational Medicine , 1986 .

[78]  K. Murata,et al.  Determination of evoked potentials in occupational and environmental medicine: a review. , 1993, Environmental research.

[79]  W. Markesbery,et al.  Oxidative Alterations in Alzheimer's Disease , 1999, Brain pathology.

[80]  F H Duffy,et al.  Persistent effects of sarin and dieldrin upon the primate electroencephalogram. , 1976, Toxicology and applied pharmacology.

[81]  S. Arlinger,et al.  Visual evoked potentials: relation to adult speechreading and cognitive function. , 1989, Journal of speech and hearing research.

[82]  Barry L. Johnson,et al.  Advances in neurobehavioral toxicology : applications in environmental and occupational health , 1990 .