Department of Veterans Affairs Victoria A. Cassano, MD, MPH Acting Chief Consultant Environmental Health Strategic Healthcare Group

SARIN GAS PESTICIDES & ANTIDOTES Was I exposed? Was the cure worse?

Pesticides Organochlorines Organochlorines Organophosphates Organophosphates Pyrethrins Pyrethrins Carbamates Carbamates

Pesticides Pesticides are preparations used to control or destroy organisms that interfere with man's agricultural, environmental or amenity requirements Pesticides are preparations used to control or destroy organisms that interfere with man's agricultural, environmental or amenity requirements They are used in the form of liquid preparations, powders or granules They are used in the form of liquid preparations, powders or granules

Pesticides - Organochlorines DDT ( 1,1-bis[p-chlorophy]2,2,2 trichloroethane) DDT ( 1,1-bis[p-chlorophy]2,2,2 trichloroethane) –Acute toxicity in mammals low –Accumulates in environment deposited in lipids of mammals, birds and fish –Carcinogenic –Acute toxicity leading to convulsions only with ingestion –Banned in 1973 DDE DDE –Hepatotoxic Benzene Hexachloride (Lindane) Benzene Hexachloride (Lindane) –? Aplastic anemia Dieldrin, Aldrin, Endrin and Chlordane Dieldrin, Aldrin, Endrin and Chlordane

Pesticides – Carbamates CO 2 NH 3 – Carbamic Acid CO 2 NH 3 – Carbamic Acid No Chlorine No Chlorine No Phosphates No Phosphates Trade name – SEVIN Trade name – SEVIN Anticholinesterase Inhibitor Anticholinesterase Inhibitor Rapidly reversible inhibition Rapidly reversible inhibition

Pesticides - Organophosphates Irriversible anticholinesterase activity Irriversible anticholinesterase activity –Parathion –Malathion –Phosdrin –Dichlorvos –SARIN (CH3)2CHO-PO-CH3-F * Most toxic of the “nerve gases” Most toxic of the “nerve gases”

Pesticides- Acute Effects Organochlorines Nausea Nausea Vomiting Vomiting Restlessness Restlessness Tremor Tremor Apprehension Apprehension Convulsions Convulsions Coma Coma Respiratory Failure Respiratory Failure Death DeathOrganophosphates MILD: Headache, dizziness, weakness, anxiety, miosis, loss of visual acuity MILD: Headache, dizziness, weakness, anxiety, miosis, loss of visual acuity MODERATE: Nausea, salivation, lacrimation, abdominal cramps, vomiting, sweating, slow pulse, muscle tremors MODERATE: Nausea, salivation, lacrimation, abdominal cramps, vomiting, sweating, slow pulse, muscle tremors SEVERE: diarrhea, pinpoint & non-reactive pupils, respiratory difficulty, pulmonary edema, cyanosis, loss of sphincter control, convulsions, coma, death SEVERE: diarrhea, pinpoint & non-reactive pupils, respiratory difficulty, pulmonary edema, cyanosis, loss of sphincter control, convulsions, coma, death

SARIN Most toxic nerve agent (until VX) Most toxic nerve agent (until VX) 1,000 X more toxic than parathion 1,000 X more toxic than parathion LCt 50 : vapor: 100 mg. min/m 3 LCt 50 : vapor: 100 mg. min/m 3 LD 50 : liquid: 1,700 mg (skin) LD 50 : liquid: 1,700 mg (skin)

SARIN Skin exposure: Mild: Mild: –increased sweating at site –Muscular fasciculation at site Moderate: same as above+ Moderate: same as above+ –Nausea, vomiting, diarrhea, generalized weakness Severe: Same as above + Severe: Same as above + –LOC, Convulsions, generalized fasciculations, flaccid paralysis, apnea, generalizes secretions, loss of sphincter control

Was I exposed?

Potential US Troop Exposure Khamisiyah – March 1991 Khamisiyah – March 1991 –Destruction of enemy munitions in Occupied areas of Iraq –US 37 th and 307 th engineering Battalions –Sarin and cyclosarin –Detectors did not go off, sensitive only to lethal or near lethal concentrations –UNSCOM confirmed presence of nerve agents in October 1991 –Modeling indicates that noticible effects might have been seen within 25km of the demolition site –Approximately 20,000 troops were within 50 miles None reported acute effects in DOD mailed questionnaire None reported acute effects in DOD mailed questionnaire Al Muthanna Al Muthanna Muhammadiyat Muhammadiyat

Potential US Troop Exposure First noticeable effects First noticeable effects –Ct : 1mg-min/m 3 –Watery eyes, runny nose, sweating, twitching, General population level General population level –Ct : mg-min/m 3 –“General population including children and older people can remain for 72 hours with no effects” (i.e. acute effects) 99,000 troops may have been exposed between these two levels. 99,000 troops may have been exposed between these two levels.

Pyridostygmine Bromide (PB) Peripherally Acting Carbamate Compound Peripherally Acting Carbamate Compound Penetrates poorly into the CNS Penetrates poorly into the CNS Used in the therapy of neurological disorders where inhibition of synaptic AChE is clinically beneficial. Used in the therapy of neurological disorders where inhibition of synaptic AChE is clinically beneficial. In large doses it mimics the peripheral effects of organophosphate nerve agents In large doses it mimics the peripheral effects of organophosphate nerve agents Does not allow the irreversible nerve agents to bind to Acetylcholinesterase Does not allow the irreversible nerve agents to bind to Acetylcholinesterase PB + atropine + 2-PAM chloride showed greater protection than atropine + 2- PAM CL alone PB + atropine + 2-PAM chloride showed greater protection than atropine + 2- PAM CL alone It is an essential pretreatment adjunct for nerve agent threats; with target inhibition of AChE of 20 to 40%. (30 mg dose). It is an essential pretreatment adjunct for nerve agent threats; with target inhibition of AChE of 20 to 40%. (30 mg dose). US forces were instructed to use PB only when a nerve agent attack was assessed to be imminent. US forces were instructed to use PB only when a nerve agent attack was assessed to be imminent.

DEET N, N, Diethyl-meta-toluimide N, N, Diethyl-meta-toluimide –Is an insect repellant, not a pesticide –Developed by the Army in 1946 –Released to general public in 1957 –EPA Assessment Used by 1/3 of the population Used by 1/3 of the population Normal usage is not considered hazardous to the general public Normal usage is not considered hazardous to the general public Long term exposure is not expected* Long term exposure is not expected* This differs with how DEET was/is used by soldiers in SW Asia This differs with how DEET was/is used by soldiers in SW Asia

Is the cure worse?

from Dulce and Decorum ~ Lt Wilfred Owen, 1918 Gas! Gas! Quick, boys ---- An ecstasy of fumbling, Fitting the clumsy helmets just in time; But someone still was yelling out and stumbling And flound’ring like a man in fire or lime… Dim, through the misty panes and thick green light, As under a green sea, I saw him drowning. In all my dreams, before my helpless sight, He plunges at me, guttering, choking, drowning.

Summary The primary purpose of the military is to maintain National security and The primary purpose of the military is to maintain National security and When directed by Congress and the Commander In Chief to prosecute a War When directed by Congress and the Commander In Chief to prosecute a War The primary purpose of the medical departments of the military in time of war is to maintain the fighting force The primary purpose of the medical departments of the military in time of war is to maintain the fighting force While more precautions can, should and are being taken, the readiness and strength of the fighting force can never be subordinated to the potential for long term sequelae of combat. While more precautions can, should and are being taken, the readiness and strength of the fighting force can never be subordinated to the potential for long term sequelae of combat. It is the Department of Veteran’s Affairs’ mission to care for those who have born the burden of our wars. It is the Department of Veteran’s Affairs’ mission to care for those who have born the burden of our wars. We will continue to elucidate the health outcomes in our combat Veterans and strive to find ways to treat them effectively. We will continue to elucidate the health outcomes in our combat Veterans and strive to find ways to treat them effectively.

Thank you! Questions???