CBW

1. CBW CH 339K

2. CBW - An Ancient Tradition

3. Fritz Haber • 1868 – 1934 • 1918 Nobel for synthesis of ammonia (Haber process) • Father of modern chemical warfare (probably has a plaque on his office door in Hell)

4. Haber’s Law • Where • W = Haber Product, also known as lethality index • C = Concentration of the agent in the air • t = time of exposure • The lower the Haber Product, the more lethal the agent • Lower concentration for a longer time will yield the same effects as a larger concentration over a shorter exposure

5. Beginnings • The large-scale use of poison gas in modern warfare originated during WWI in the battle of Ypres, April 22, 1915 • 168 tons of Cl2 were released from cylinders along a 4 mile front • 5700+ cylinders of gas, weighing 90 lbs. each • 6000+ French troops were killed within 10 minutes • Due to the vagaries of wind and the crude delivery method, a fair number of Germans were also killed or wounded • 1.3 million casualties, 91,000 fatalities were attributed to the use of phosgene, chlorine, and mustard gas during the course of the war. • Including my grand uncle Bill

6. Modern Chemical Agents • Early Agents (WW1) • Inhalation (Choking) Agents • Chlorine • Chloropicrin • Phosgene • Vesicants • Mustards • Lewisite • Blood Agents (Metabolic Poisons) • Cyanide Post-WWI Agents • Nerve “gases”

7. Chlorine • Thick greenish vapor • First used by Germans in 1915 • Dispensed from gas cylinders • Caused massive casualties due to total lack of defense

8. Chlorine Effects (Initial) • Burning pain in the throat and eyes, • Sensation of suffocation; • Painin the chest, especially behind the sternum. • Rapid, painful, difficult respiration with coughing • Profuse lachrymation. • Retching and vomiting, • Severe headache • Face violet red, ears and finger nails blue • Respiration often over 40 and sometimes even 80 a minute • Dyspnoea lasts about thirty-six hours, after which it gradually subsides, if death does not occur before. The patient then falls asleep and wakes up feeling much relieved.

9. Chlorine Effects (Pneumonial Stage) • A few hours later acute bronchitis or broncho-pneumonia develops. • Sputum viscid, yellow or greenish, and muco-purulent with occasional streaks of blood. • Respiration shallow and rapid, up to 80 a minute. • Rapid pulse • Fever as high as 104. • Possible delirium. • Pleurisy may occur • Empyema and gangrene of the lung may occur. • Most survive after long recovery

10. Use of Chlorine French cylinder attack on German trenches in Flanders, year unknown. Note dependence on wind direction for successful attack.

11. Chloropicrin • CCl3NO2 • pungent, colorless, oily liquid • oral–nasal irritation, coughing, and vomiting • LC50 = 20,000+ mg-min/m3 (i.e. usually sublethal) • First used by Russians in 1916 in hand grenades • Used as secondary agent to make targets remove their masks to vomit • Used today as a fumigant

12. Phosgene • COCl2 • Colorless gas, smells like new mown hay • BP 8o C • LC50 = 3200 mg-min/m3 • Common industrial chemical • Reacts with amino groups on surface proteins of the lung alveolar cells, cross linking them • Shortness of breath, coughing, tight chest, fluid buildup in lungs causing asphyxia • Can be asymptomatic for up to 24 hours

13. Synthesis • Purified caron monoxide and chlorine gas are passed together through a porous bed of activated carbon • Reactor must e cooled to temps of 50 – 150o C CO + Cl2 → COCl2 (ΔHrxn = −107.6kJ/mol)

14. Sulfur Mustards Bis (beta-chloroethyl) sulfide • Vesicant (blister agent) • Alkylating agent cross-links lipids, proteins, and DNA • Not very volatile (610 mg/l at 20o C) • Strong smell like horseradish or garlic • Persistant agent • LD50 (human) = 20 mg/kg pericutaneous • LC30 (human) = 900 mg-min/m3 by inhalation • Interestingly, the Canadians in 1942 determined that anthrax spores can survive in sulfur mustard

15. Action • Sulfur mustard readily loses Cl- to form a highly reactive cyclic sulphonium ion • This ion reacts with free amino groups on biomolecules – e.g. guanine nucleotides in DNA, lysine residues in proteins • Molecular disruption – particularly of DNA – leads to cell death. • Blistering of skin • Blindness from eye damage • Lung damage and asphyxia due to filling of lungs with fluid

16. Use of Mustard • WW1 – both sides • Second Italo-Abysinnian War 1935-36 (League of Nations fretted and did nothing) • Sino-Japanese War • Iran-Iraq War • American troops exposed to low levels during Gulf War 1

17. Mustard (continued) Iranian victim of Iraqi mustard attack, 1980’s Americans blinded by mustard, France, 1918

18. Production Pre-WWII mustard production plant at Edgewood Arsenal, MD

19. Synthesis • Lommel-Steinkopf method using 2-chloroethanol • Modern method using ethylene oxide

20. Synthesis • Levinstein method using ethylene • Radical addition reaction using vinyl chloride

21. Lewisite • Talked about before as inhibitor of PDH • LC50 = 1300 mg-min/m3 • Severe chemical burns • Inhalation causes a burning pain, sneezing, coughing, vomiting, and pulmonary edema • AFAIK, never used (manufacturing process was being worked out when WW1 ended) • Significant numbers of Chinese were killed in the latter years of the 20th century from accidental exposure to stockpiles left by the Japanese

22. Cyanide (HCN or salt thereof) • By inhalation or skin adsorption • LC50 = 3000 mg-min/m3 • First used by Austria in 1915 • Used by Iraq against both Iran and Iraqi Kurds • More commonly used for assassinations, murders, and executions (not easy to disseminate on battlefield) • Used by KGB to assassinate Stepan Bandera, Ukranian resistance leader, in Germany in 1959

23. Nerve Agents • We talked about these with respect to enzyme inhibitors • Organophosphates first developed by IG Farben in 1936 • Extensively produced by Germans but never used in WWII • Russians in Afghanistan (?), Iraq versus Iran and versus Kurds • Tokyo subway attacks of 1995 by AumShinrikyo

24. Irreversible Inhibition at the NM Junction

25. Nerve Gases Sarin Tabun Soman VX Symptoms: Contraction of pupils, profuse salivation, convulsions, involuntary urination and defecation and eventual death by asphyxiation as control is lost over respiratory muscles.

26. Action of Nerve Agents

27. Common Nerve Agents

28. Toxicity of Nerve Agents

29. Use of nerve agents • Iraq produced (admitted values) • 3.9 tons of VX • 795 tons of Sarin • 210 tons of Tabun • In addition to 2850 tons of good old mustard. • Sarin and Tabun were loaded into bombs and ballistic missile warheads.

30. Synthesis

31. Synthesis (cont.) Alternative syntheses for sarin (GB) Top: binary synthesis (components used in inary munitions) Bottom: Di-di process using methyl phosphonyldifluoride and methyl phosphonyl dichloride

32. Production US GB (Sarin) Production Plant, Rocky Mountain Arsenal, CO (now closed)

33. Delivery BLU-80B Bigeye Binary Chemical Munition Could deliver 180 lbs. VX

34. Delivery (cont.) Honest John rocket warhead containing M139 bomblets, each with about 1.5 lbs of Sarin

35. Binary munitions • Binary munitions contain reactants which produce active agent on mixing • Can e shipped and stored with only one (or no) components present • Final filling at staging are before use • Greater safety in storage and transport

36. Delivery (cont.) • M687 Binary 155mm Projectile • Forward chamber contains methyl phosphonyldifluoride • Rear contains mixture of isopropyl alcohol and isopropyl amine • Munition is shipped / stored with rear compartment empty for safe handling – filled for final use • Separation between chambers id broken upon firing, creating agent “on the fly.”

37. Delivery (cont.) • M23 Chemical Land Mine • Last units were destroyed in 2008 • Charged with 10.5 lbs VX

38. Nerve Gas Antidotes Atropine sulfate from Atropa belladonna (left) competes with acetylcholine for the receptor binding site Blocks ACH and offsets the effects of the nerve agent

39. Pralidoxime Hydrochloride(Pyridine Aldoxime Methyl Chloride) Usually given along with atropine Reversibly binds to the enzyme acetylcholinesterase, competing with organophosphate binding. Doesn’t inhibit acetylcholinesterase – reactivator.

40. 2-PAM Action

41. Antidote Delivery • US Mark 1 anti-nerve agent kit containing (top to bottom) atropine autoinjector, 2-PAM autoinjector, and the carrying case. The two autoinjectors are held together by a safety clip which prevents accidental discharge

42. Chemical Agents - Persistence Classification of agents as “persisting,” “transitional,” or “volatile” based on dispersal times. Wind conditions, rainfall, and cloudiness will also impact persistence Persistent agents are best used for area denial; volatile agents if attacking troops are to follow through.

43. Biochemical Weapons • Split the difference between Chemical and Biological • Mostly Protein toxins

45. Amount of toxin needed to lethally expose humans in a 100 km2 (38 mile2)area. (from Spertzel RO, Wannemacher RW, Patrick WC, Linden CD, Franz DR. Technical Ramifications of Inclusion of Toxins in the Chemical Weapons Convention (CWC). Alexandria, Va: Defense Nuclear Agency; 1992: 18. DNA Technical Report 92-116.)

47. LCt50 for Selected Aerosols

48. Botulinum Toxin • Clostridium botulinum is a spore-forming, anaerobic bacterium found worldwide in soil. • Mix of 7 related toxins • LD50 = 1 ng/kg subq, 3 ng/kg inhaled • Bind to receptor on nerve cell • Taken in by receptor-mediated endocytosis • Prevents release of acetylcholine at synaptic cleft • Death by flaccid paralysis, respiratory failure • 6000 liters of concentrate were produced at Al Hakkam in 1990 • Delivery by warhead or from underwing spray tanks • High terrorist potential but technically difficult to produce • High lethality, low persistence

50. Ricin and related toxins • We’ve discussed extensively • US and England produced and tested a ricin bomb in WWII, but never used. • Inhalation causes death through lung damage rather than the organ failure seen in internal exposures • Diffuse necrotizing pneumonia • Not as toxic as botulinum, but easy to produce in large quantities