POSSIBLE LONG-TERM HEALTH EFFECTS OF SHORT-TERM EXPOSURE TO CHEMICAL AGENTS -- Copyright -- ACKNOWLEDGEMENTS -- PREFACE -- EXECUTIVE SUMMARY -- ANTICHOLINESTERASE CHEMICALS -- ANTICHOLINERGIC CHEMICALS -- MORTALITY -- MORBIDITY -- Contents -- 1 INTRODUCTION -- HISTORY OF THE EDGEWOOD TESTING PROGRAM -- PROCEDURES USED AT THE EDGEWOOD CHEMICAL TESTING PROGARM -- RECRUITMENT OF VOLUNTEERS -- GUIDELINES FOLLOWED IN THE PROTECTION OF SUBJECTS -- INVESTIGATORS -- SELECTION OF DOSES FOR HUMAN TESTS -- RANGE OF DOSES -- SAFETY MARGIN -- 2 ANTICHOLINESTERASES -- CHEMISTRY OF ANTICHOLINESTERASES -- "REVERSIBLE" INHIBITORS -- ORGANOPHOSPHORUS (OP) INHIBITORS -- ABSORPTION, FATE, AND EXCRETION OF ANTI-CHES -- MECHANISMS OF ACTION -- INHIBITION OF ACETYLCHOLINESTERASE BY ANTICHOLINESTERASES -- REACTIVATION OF ACHE -- AGING OF INHIBITED ACHE -- CHOLINERGIC RECEPTOR AND ACH CHANNEL -- PRESYNAPTIC ACTION -- NERVE MEMBRANE -- CENTRAL NERVOUS SYSTEM -- "NEUROTOXIC" ESTERASE (NTE) -- BIOCHEMICAL AND METABOLIC CHANGES -- OP ALKYLATION -- BIOLOGIC AND CLINICAL EFFECTS -- ACUTE EFFECTS: PHARMACOLOGY -- Eye -- Gastrointestinal Tract -- Actions at Other Autonomic Sites -- Neuromuscular Junction -- Brain -- ACUTE TOXIC EFFECTS -- DELAYED NEUROPATHY (CNS-PNS DISTAL AXONOPATHY) -- Clinical Features -- Neuropathologic Features -- Neuropathic Potency -- LONG-TERM BRAIN DYSFUNCTION -- JUNCTIONAL NEUROMYOPATHY -- OTHER ADVERSE HEALTH EFFECTS -- Mutagenicity -- Carcinogenicity -- Fetal and Teratogenic Effects -- Effects on Male Reproduction -- Cataractogenic Effects -- Hemocoagulation -- IMMEDIATE AND DELAYED EFFECTS IN VOLUNTEERS AFTER SINGLE OR REPEATED EXPOSURE TO ANTI-CHES AT EDGEWOOD -- MORTALITY DATA -- EVALUATION OF THE LIKELIHOOD OF LONG-TERM ADVERSE HEALTH EFFECTS -- BRAIN DYSFUNCTION -- JUNCTIONAL NEUROMYOPATHY AND DELAYED NEUROPATHY -- OTHER ADVERSE HEALTH EFFECTS.

Mutagenicity, Carcinogenicity, and Male Reproductive Effects -- Cataractogenicity -- Blood Changes -- CONCLUSIONS -- REFERENCES -- 3 ANTICHOLINERGICS -- ATROPINE, SCOPOLAMINE, AND RELATED THERAPEUTIC ANTICHOLINERGIC CHEMICALS -- SITES OF ACTION -- PERIPHERAL EFFECTS -- CENTRAL EFFECTS -- POISONING BY BELLADONNA ALKALOIDS -- SYMPTOMS AND SIGNS OF ATROPINE POISONING -- TREATMENT -- MECHANISM OF ACTION -- ABSORPTION, FATE, AND EXCRETION -- PHARMACOLOGICAL PROPERTIES OF SYNTHETIC ATROPINE DERIVATIVES -- ROLE OF DRUG DISPOSITION IN EXPLAINING DIFFERENCES AMONG ANTICHOLINERGIC COMPOUNDS -- ATROPINE -- BZ -- ANIMAL TOXICOLOGY OF ANTICHOLINERGIC COMPOUNDS -- IMMEDIATE EFFECTS -- EA 3443 -- EA 3834 -- LONG-TERM AND DELAYED EFFECTS -- Atropine -- Clidinium (Quartzan) -- Other Data -- HUMAN TOXICOLOGY OF ANTICHOLINERGIC COMPOUNDS -- DOSING CONSIDERATIONS -- Atropine -- Other Anticholinergic Compounds -- USE OF ANTIDOTES -- IMMEDIATE EFFECTS -- Peripheral and Behavioral Effects -- EEG Effects -- BZ Case Reports -- EA 3834 -- Overall Evaluation of Immediate Adverse Effects -- LONG-TERM AND DELAYED EFFECTS -- MORTALITY -- SUMMARY -- CONCLUSIONS -- REFERENCES -- 4 MORTALITY -- METHOD OF ANALYSIS -- RESULTS -- REFERENCE -- APPENDIX A MASTER FILE-ANTICHOLINESTERASE CHEMICALS -- APPENDIX B MASTER FILE-ANTICHOLINERGIC CHEMICALS -- APPENDIX C LIST OF DOCUMENTS SUPPLIED TO ANTICHOLINESTERASE PANEL -- APPENDIX D LIST OF DOCUMENTS SUPPLIED TO ANTICHOLINERGIC PANEL -- APPENDIX E CASE-FILE DATA ON EDGEWOOD SUBJECTS -- SUMMARY OF VOLUNTEER TESTING WITH GB (A1) -- SUMMARY OF VOLUNTEER TESTING WITH VX (A2) -- SUMMARY OF VOLUNTEER TESTING WITH GA (A3) -- SUMMARY OF VOLUNTEER TESTING WITH GD (A5) -- SUMMARY OF VOLUNTEER TESTING WITH DFP (A6) -- SUMMARY OF VOLUNTEER TESTING WITH EA 3148 (A7) -- SUMMARY OF VOLUNTEER TESTING WITH THA (A9), TACRINE.

SUMMARY OF VOLUNTEER TESTING WITH PHYSOSTIGMINE (A10) -- SUMMARY OF VOLUNTEER TESTING WITH PROSTIGMINE (A11) -- SUMMARY OF VOLUNTEER TESTING WITH HEXAFLUORENIUM (MYLAXINR) (A12) -- SUMMARY OF VOLUNTEER TESTING WITH MALATHION (A14) -- SUMMARY OF VOLUNTEER TESTING WITH METHACHOLINE (A20) -- SUMMARY OF VOLUNTEER TESTING WITH URECHOLINE (A21) -- APPENDIX F EXCERPTS FROM BZ DATA -- CONTENTS -- APPENDIX G SUMMARY OF ACUTE-AND CHRONIC-TOXICITY DATA IN VARIOUS MAMMALS WITH THE ANTICHOLINERGIC TEST AGENTS (DITRAN,… -- TOXICITY -- BLOOD (RATS) -- HISTOPATHOLOGY -- OTHER DRUGS -- CONCLUSION -- APPENDIX H EVALUATION OF DATA FROM SHORT-TERM GENETIC TESTING OF ANTICHOLINERGIC CHEMICALS -- 3-QUINUCLIDINYL BENZILATE -- SCOPOLAMINE -- ATROPINE -- CONCLUSIONS -- REFERENCES -- APPENDIX I DIGEST REPORT-ANTICHOLINERGIC CHEMICALS -- INTRODUCTION -- APPENDIX I DIGEST REPORT ANTICHOLINERGIC CHEMICALS -- INTRODUCTION -- ESTERS OF TROPIC ACID -- STUDIES IN ANIMALS -- HUMAN DATA FROM THE GENERAL LITERATURE -- HUMAN DATA FROM EDGEWOOD ARSENAL -- SUMMARY -- ESTERS OF BENZILIC ACID -- STUDIES IN ANIMALS -- 3-QUINUCLIDINYL BENZILATE (BZ, EA 2277) -- DIETHYLAMINOETHYL BENZILATE -- EFFECTS ON MAN -- SUMMARY -- ESTERS OF PHENYLCYCLOPENTYLGLYCOLIC ACID -- N-METHYL-4-PIPERIDINYL-(PHENYLCYCLOPENTYL)-GLYCOLATE (EA 3443) -- DITRAN (CS 4297) -- 3-QUINUCLIDINYL-(PHENYLCYCLOPENTYL)-GLYCOLATE (EA 3167) -- L-2-ALPHA-TROPINYL-L-(PHENYLCYCLOPENTYL)-GLYCOLATE (226,086) -- 2-METHYL-3-QUINUCLIDINYL-(PHENYLCYCLOPENTYL)-GLYCOLATE (301,060) -- ESTERS OF PHENYLISOPROPYLGLYCOLIC ACID -- N-METHYL-4-PIPERIDINYL-(PHENYLISOPROPYL)-GLYCOLATE (EA 3834) -- 4-(1-METHYL-1,2,3,6-TETRAHYDROPYRIDINYL)-PHENYLISOPROPYLGLYCOLATE (302,668) -- ESTERS OF 1-PROPYNYLCYCLOPENTYLGLYCOLIC ACID -- N-METHYL-4-PIPERIDYL-(PHENYLCYCLOBUTYL)-GLYCOLATE (EA 3580) -- MISCELLANEOUS ESTERS -- 302,282 -- 302,537 -- WIN2299.

NONESTER ANTICHOLINERGIC COMPOUNDS -- BENZETIMIDE -- MEPIPERPHENIDOL -- "TAB" MIXTURE -- DISCUSSION -- REFERENCES -- APPENDIX J ANTICHOLINERGIC DRUGS AND THE EEG -- LITERATURE REVIEW -- MILITARY DATA -- Conclusions -- REFERENCES -- APPENDIX K BIOCHEMICAL ASPECTS OF ANTICHOLINERGIC CHEMICALS -- CONCLUSION -- REFERENCES -- APPENDIX L STRUCTURE-ACTIVITY RELATIONS OF THE CENTRALLY ACTIVE ANTICHOLINERGIC AGENTS -- STEREOSPECIFICITY -- COMPARISON OF ANIMAL AND HUMAN DATA WITH VARIOUS ANTICHOLINERGIC DRUGS -- SITES OF ANTICHOLINERGIC ACTION IN BRAIN -- COMPETITION BETWEEN BEHAVIORAL POTENCY AND RECEPTOR AFFINITY -- REFERENCES.