chemical warfare agents

M

C

Sa

b

c

d

e

f

C

N5H

1d

Environmental Toxicology and Pharmacology 26 (2008) 113–122

Contents lists available at ScienceDirect

Environmental Toxicology and Pharmacology

journa l homepage: www.e lsev ier .com/ locate /e tap

ini-review

hemical warfare agents

. Chauhan a, S. Chauhan b,∗, R. D’Cruz f, S. Faruqi c, K.K. Singh d, S. Varma e, M. Singh a, V. Karthik e

Department of Chemical Engineering, Panjab University, Chandigarh, IndiaDepartment of Medicine, Government Medical College and Hospital, Chandigarh 160030, IndiaDepartment of Respiratory Medicine, Pinderfields General Hospital, Aberford Road, Wakefield WF1 4DG, UKDepartment of Neurology, Army Hospital (Research & Referral), New Delhi, IndiaDepartment of Internal Medicine, Post Graduate Institute of Medical Education & Research, Chandigarh, India
City Clinic, MDC, Panchkula 134109, Haryana, India
a r t i c l e i n f o

Article history:Received 5 August 2007Received in revised form 6 March 2008Accepted 11 March 2008Available online 18 March 2008

Keywords:Blister agentsNerve agentsAsphyxiantsChoking agents

a b s t r a c t

Chemical warfare agents (CWA’s) are defined as any chemical substance whose toxic properties are utilisedto kill, injure or incapacitate an enemy in warfare and associated military operations. Chemical agents havebeen used in war since times immemorial, but their use reached a peak during World War I. During WorldWar II only the Germans used them in the infamous gas chambers. Since then these have been inter-mittently used both in war and acts of terrorisms. Many countries have stockpiles of these agents. Therehas been a legislative effort worldwide to ban the use of CWA’s under the chemical weapons conventionwhich came into force in 1997. However the manufacture of these agents cannot be completely prohib-ited as some of them have potential industrial uses. Moreover despite the remedial measures taken so farand worldwide condemnation, the ease of manufacturing these agents and effectiveness during combator small scale terrorist operations still make them a powerful weapon to reckon with. These agents areclassified according to mechanism of toxicity in humans into blister agents, nerve agents, asphyxiants,choking agents and incapacitating/behavior altering agents. Some of these agents can be as devastating
as a nuclear bomb. In addition tated with long term morbiditiethe historical background, propclinical features of exposure an
ontents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2. Blister agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2.1. Sulfur mustards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.1.1. Manufacture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.1.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.1.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.1.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.1.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.1.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2.2. Nitrogen mustards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.2.1. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.2.2. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.2.3. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Abbreviations: CWA, chemical warfare agent; WWI, first world war; WWII, seconATO, North Atlantic Treaty Organisation; SM, sulfur mustard; NM, nitrogen mustard; DN0%; TEPP, tetra-ethyl pyrophosphate; PTSD, post-traumatic stress disorder; FDA, US FoodCN, hydrogen cyanide; SA, arsine; PS, chloropicrin; CG, phosgene; ARDS, acute respirato∗ Corresponding author. Tel.: +91 172 2561355; fax: +91 172 2608488.

E-mail address: [email protected] (S. Chauhan).

382-6689/$ – see front matter © 2008 Elsevier B.V. All rights reserved.oi:10.1016/j.etap.2008.03.003

o immediate injuries caused by chemical agents, some of them are associ-s and psychological problems. In this review we will discuss briefly abouterties, manufacture techniques and industrial uses, mechanism of toxicity,d pharmacological management of casualties caused by chemical agents.

© 2008 Elsevier B.V. All rights reserved.

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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115

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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

d world war; US, United States (of America); CWC, chemical weapons convention;A, de-oxy ribonucleic acid; LD50, lethal dose in 50%; LCt50, lethal concentration in

and Drug Administration; 2-PAM Cl, 2-pralidoxime chloride; CK, cyanogen chloride;ry distress syndrome.

http://www.sciencedirect.com/science/journal/13826689

mailto:[email protected]

dx.doi.org/10.1016/j.etap.2008.03.003

114 S. Chauhan et al. / Environmental Toxicology and Pharmacology 26 (2008) 113–122

2.2.4. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1162.2.5. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

2.3. Lewisite (L) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1162.3.1. Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1172.3.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1172.3.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1172.3.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1172.3.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1172.3.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117

3. Nerve agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1173.1. Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1173.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1173.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1173.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1173.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1183.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

4. Asphyxiants/blood agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1184.1. Cyanogen chloride (CK) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

4.1.1. Manufacture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1184.1.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1184.1.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1184.1.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.1.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.1.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

4.2. Hydrogen cyanide (HCN) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.2.1. Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.2.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.2.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.2.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.2.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.2.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

4.3. Arsine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.3.1. Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.3.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.3.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1194.3.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1204.3.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1204.3.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

5. Choking/pulmonary damaging agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.1. Chlorine (Cl) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

5.1.1. Manufacture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.1.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.1.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.1.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.1.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.1.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

5.2. Chloropicrin (PS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.2.1. Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.2.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.2.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.2.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.2.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.2.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

5.3. Phosgene (CG) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1215.3.1. Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1215.3.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1215.3.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1215.3.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1215.3.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1215.3.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

6. Behavioural agents/incapacitating agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1216.1. Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1216.2. Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1216.3. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1216.4. Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1216.5. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1216.6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

7. Detection of CWA’s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1228. Destruction of chemical weapons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1229. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122

ology and Pharmacology 26 (2008) 113–122 115

Table 1Classification of chemical warfare agents

1. Blister agentSulfur mustard

S. Chauhan et al. / Environmental Toxic

1. Introduction

Chemical warfare is the use of the toxic properties of chemicalsubstances to kill, injure or incapacitate an enemy in warfare andassociated military operations. A chemical substance intended forsuch use in military operations is defined as a chemical warfareagent (CWA). Chemical agents have been used in war since timesimmemorial. These have been elaborately described in ancientChinese literature. In 600 B.C. Helleborus roots were used suc-cessfully by the Athenians to contaminate water supplies duringthe siege of Kirrha. Spartans ignited pitch and sulfur to createtoxic fumes during the Peloponnesian War in 429 B.C. Thereafter,there have been intermittent use of CWA’s in battlefields, but theiruse reached a peak during World War I (WWI). French were thefirst to use ethylbromoacetate in WWI. It was followed by useof o-dianisidine chlorosulphonate, chloroacetate, chlorine, phos-gene, hydrogen cyanide, chlorine, diphenylchloroarsine, ethyl- andmethyldichloroarsine and sulfur mustard resulting in nearly 10,000deaths and over a million casualties (Eckert, 1991). CWA’s were notused on the field during World War II (WWII) due to the fear that theenemy possessed more deadly CWA’s, except for by the Germanswho used them in the infamous gas chambers for mass genocideof Jews. After WWII, CWA’s have been used intermittently both inwar, as in the Iraq–Iran war, and acts of terrorisms as in the Japaneseunderground rail station attacks (Okumura et al., 1996). It is esti-mated that nearly 1,00,000 United States (US) troops may have beenexposed to CWA’s during operation Desert Storm. There has been alegislative effort worldwide to ban the use of CWA’s. The chemicalweapons convention (CWC) which came into force in 1997 statedthat all member countries must destroy all chemical weapons overa 10-year period, with the treaty providing a “leveling out prin-ciple” that ensures possessors destroy their stockpiles at roughlythe same time. More than 170 countries have signed the CWC and139 have ratified it. The manufacture of some of these agents how-ever cannot be banned because of important industrial uses. Theseagents also still remain a threat especially from countries that donot possess nuclear technology as these are easy to manufacture,cheap and have devastating effects. Moreover, these can also beused effectively as weapons of small scale terrorist attacks. NorthAtlantic Treaty Organization (NATO) has classified agents of chem-ical terrorism as blister agents, nerve agents, asphyxiants, chokingagents and incapacitating/behavior altering agents (Table 1). In thisreview we will discuss briefly about the CWA’s. The CWA’s are clas-sified and their historical perspective, manufacture, mechanisms of
toxicity, clinical features on exposure and treatment are discussed.This review is confined to synthetic chemicals only and biologicalagents are not discussed.
2. Blister agents

Blister agent or vesicants are a group of chemicals that causesevere blistering when they come in contact with skin. These mayalso have systemic effects if absorbed. These agents are not verylethal as far as causing death is concerned but can incapacitate theenemy and overload the already burdened health care services dur-ing war time. These include sulfur mustard, nitrogen mustard andlewisite.

2.1. Sulfur mustards

Sulfur mustards (SMs), commonly known as mustard gas, arealkylating agents capable of causing short and long term mor-bidity. Since these had a mustard like odor, these were calledsulfur mustard or mustard gas. They were discovered acciden-

Nitrogen mustardLewisite

2. Nerve gasesG series

TabunSarinSoman

V seriesVEVXVGVM

3. Choking agentChlorineChloropicrinPhosgene

4. AsphyxiantsCyanogen chlorideHydrogen cyanideArsine

5. Behavioral altering agent

tally in 1822. Guthrie in the United Kingdom and Niemann inGermany synthesized, 2,2-dichlorodiethylsulfide, also known assulfur mustard (SM) in 1860. In 1917, the German forces used SMfor the first time in battlefield. It accounted for about 70% of themillion-plus gas related casualties in WWI. Several varieties andmixtures of SM’s have been employed (HD, H, HT, HL, HQ). TheNATO codenamed SM as H which stood for Germans or Hunns. Theletter D in HD indicated that it was a distilled product of SM orH.

2.1.1. ManufactureChemically mustard gas is a �-chloro thioether with the formula

C4H8Cl2S. The Germans produced SM using the Meyer process.This involved reacting ethylene with hypochlorous acid followedby sodium sulfide, forming �,�′-dihydroxy-methyl sulfide. Fur-ther heating with hydrochloric acid produced SM. In the US, theLevenstein process was used in which ethylene was reacted withsulfur monochloride. Another process used in the US involved thereaction between ethylene oxide and hydrogen sulfide to form
bis-(2-hydroxyethyl)-thioether, which on further reaction withhydrochloric acid forms SM.
Under the CWC the stockpiles of SM are required to be destroyedby 2007. The various methods for destruction include high-temperature incineration, plasma treatment and electrochemicalreduction, hydrolysis and oxidation and reacting sulfur dissolvedin ethylenediamine with SM (Menger and Elrington, 1990; Ganesanet al., 2005).

2.1.2. PropertiesSulfur mustard is not a gas but a pale yellow, oily liquid of specific

gravity of 1.27 that vaporizes at 25 ◦C and decomposes at 217.5 ◦C.Hence it is a liquid in cold and damp environments and easily vapor-izes in warm dry environments. It is heavier than air with a density5.6 times that of air. It has an odor of mustard in the impure formbut the pure form is colorless and odorless. It is sparingly solublein water and soluble in fat, fat solvents, and other common organicsolvents. It penetrates ordinary clothes easily in the vaporized form.

2.1.3. UsesIt has no industrial use at present.

ology
116 S. Chauhan et al. / Environmental Toxic
2.1.4. Mechanism of human toxicitySM’s are alkylating agents. They damage all exposed epithe-

lial surfaces, both in aerosol and liquid form. These effects appearwithin 2–12 h after exposure, depending on the exposure dose. Theexact mechanism of its toxicity is yet to be elucidated. Most authorsbelieve that it dissolves aqueous media, such as sweat, rapidlyforming extremely reactive cyclic ethylene sulfonium ions. Thesereactive ions react with deoxyribonucleic acid (DNA) in rapidlydividing cells leading to cellular death and inflammatory reactions(Papirmeister et al., 1985). An alternative theory suggests that itdepletes the cell of Glutathione which leads to oxidative damageand cell death (Gross et al., 1993).

2.1.5. Clinical featuresExposure to SM results in high morbidity and psychological

impact but low mortality. The mortality rate with sulfur mustardis estimated to be 2–5%. The lethal dose of HD to cause deathin 50% of persons exposed (LD50) is estimated to be 100 mg/kgand lethal concentration of vapor/aerosol to cause death in 50% ofexposed persons (LCt50) is 15,000 mg min/mm3 (Raber et al., 2001).Most often exposed surfaces i.e. skin, airways, and eyes suffer thebrunt of the damage. Irritation of the eyes followed by conjunctivi-tis, photophobia, blepharospasm, pain, and corneal damage, whichcan lead to perforation, is seen after exposure of the eyes. Glau-coma may develop later as a result of scarring. Dermatologicalmanifestations are akin to second degree burns, Steven–Johnsonssyndrome or toxic epidermal necrolysis. Contact with skin canmanifest as painful erythema, vesicles or bullae containing a tran-sudative straw colored fluid. As the fluid is a transudate it does leadto as much protein loss as would be expected with burns of a simi-lar nature. Inhalation of SM leads to irritation of the nose, epistaxis,pharyngeal pain, laryngitis, voice changes, cough and dyspnea. Ter-minally, there may be necrosis of airways with hemorrhagic edema,pseudomembrane formation and obstruction of the bronchi. Sys-temic absorption from ingestion affects the gastrointestinal tract(nausea and vomiting lasting up to 24 h), central nervous system(seizures, behavioral abnormalities and psychological problems)and also causes bone marrow suppression. Pseudomembrane for-mation and laryngospasm are the major cause of death in the first24 h. Secondary bacterial pneumonia may cause mortality betweenthe third and fifth days. Bone marrow suppression which peaks in7–21 days is a cause of delayed mortality. Late complications whichdo occur after exposure to SM include ulcerative keratitis, chronicbronchitis, pulmonary fibrosis, hypo or hyperpigmentation of skin
and psychological problems. In a study involving 500 soldiers whowere exposed to SM during the Iran–Iraq war (1983–1988) showedthat all of them developed either pulmonary or ocular complica-tions 15 years after the war (Mohammad et al., 2004). Chroniclow grade exposure also results in morbidity (chronic conjunctivi-tis with impaired vision, nasal polyps, anorexia, vomiting weightloss, irritability, bladder carcinoma and leukemia).
2.1.6. TreatmentThere is no specific antidote. Supportive treatment remains

the mainstay. Removal of exposed persons by well protected res-cuers is of prime importance. Thereafter removal of all clothingand giving a through bath helps in decontamination. Clothingremoved should be packed in plastic bags. Topical cortisone maybe of benefit in erythematous skin lesion. Larger bullae requireunroofing with saline irrigation and application of antibiotics (sil-ver sulfadiazine or modified Dakins solution) over denuded areas.Management of large areas of skin involvement is similar to burnspatient requiring supportive measures but with special regard tofluids as these patients are prone to pulmonary edema. Irriga-tion, topical antibiotic and steroids are required for exposure to

and Pharmacology 26 (2008) 113–122

eyes. Chemical pneumonitis, characterized by productive cough,dyspnea and fever, occurs within 12–24 h of inhalation. Infec-tion generally occurs on the third to fifth day, signaled by anincreased fever, pulmonary infiltrates, and an increase in sputumproduction with a change in color. Formation of pseudomem-brane necessitates fibreoptic bronchoscopy. Bronchodilators andglucocorticoids are of benefit for bronchospasm. Bone marrowsuppression beginning on the 3rd day and peaking at 7–14 daysrequires granulocyte colony-stimulating factor, transfusion supportor even bone marrow transplants. Recent research has shown somebeneficial effects of vanilloid compounds and N-acetylcysteine inanimal trials.

2.2. Nitrogen mustards

Nitrogen mustard’s (NM’s) are alkylating agents, like SM’s. Thesehave also been classified under blister agents by NATO and arenitrogen analogues of SM’s. They are commonly known by their mil-itary designations i.e. HN-1 (bis(2-chloroethyl) ethylamine), HN-2(bis(2-chloroethyl) methylamine), and HN-3 ( ). These were pro-duced in 1920s and 1930s as potential CWA’s. During WWII, nearly100 tons of HN-1 was produced by the US and 2000 tons of HN-3by Germany, but these were never used. HN-1 was originally usedfor treatment of warts but later found itself in category of CWA’s.HN-2 and HN-3 were specifically produced as CWA’s.

2.2.1. PropertiesHN-1 (bis(2-chloroethyl) ethylamine) has the chemical formula

C6H13Cl2N It has a faint, fishy or musty odor. It is sparingly solu-ble in water but miscible with acetone and other organic solventsand decomposes at temperatures greater than 194 ◦C. HN-2(bis(2-chloroethyl) methylamine) has the chemical formula C5H11Cl2N. Ithas a fruity odor at high concentrations and a soapy odor at lowconcentrations. HN-3 (tris(2-chloroethyl) amine) has the chemicalformula C6H12Cl3N. It is odorless when pure but has been reportedto have a bitter almond odor. It is the most stable of the nitrogenmustards but decomposes at temperatures greater than 256 ◦C. Ithas a much lower vapor pressure than HN-1 or HN-2 and is insol-uble in water.

2.2.2. UsesHN-1, 2 and 3 have no utility except as a CWA.

2.2.3. Mechanism of human toxicity
These are alkylating agents and damage the DNA in dividing cells
like the SM’s (Papirmeister et al., 1985; Gross et al., 1993).

2.2.4. Clinical featuresTypically, signs and symptoms of NM exposure do not occur

immediately. The onset of symptoms may be up to several hoursafter exposure to the agent. The concentration of the agent exposedto would determine how soon symptoms occur after contact. Theseagents, like SM’s, affect the skin, eyes, respiratory tract and gas-trointestinal tract. Like SM’s, systemic absorption can lead to bonemarrow suppression and central nervous system effects.

2.2.5. TreatmentAs no specific antidote exists for NM exposure, management is

supportive and on similar lines as that of SM’s.

2.3. Lewisite (L)

This agent is classified as a blistering agent. It was developed asa potential CWA during WWI, but by the time it was synthesizedthe war had ended. During WWII it was found to be less effective

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uid and with a boiling point of 158 C, it is one of the most


as compared to SM and therefore was not stockpiled. It also getshydrolysed in humid environment; there by rendering it less effec-tive in operational conditions. Though it has never been used inwarfare, it is classified as a potential CWA.

2.3.1. ManufactureSynthesis can be carried out by reacting arsenic trichloride with

acetylene in the presence of a hydrochloric acid solution of mercuricchloride.

2.3.2. PropertiesLewisite chemically is C2H2AsCl3 (2-chloroethenyldichloro-

arsine). It is usually a mixture of the isomers 2-chlorovinylarsonousdichloride, bis(2-chloroethenyl) arsinous dichloride and tris(2-chlorovinyl) arsine. It has a density of 1.89 g/cm3 with melting andboiling points of −18 and 190 ◦C respectively. It hydrolyses in waterto form hydrochloric acid, and in contact with alkaline solutionscan form poisonous trisodium arsenate.

2.3.3. UsesIt was used initially as antifreeze for mustard gas or to penetrate

protective clothing in special situations by the US. However it wasdeclared obsolete in 1950s and it has no present industrial use.

2.3.4. Mechanism of human toxicityIt can easily penetrate ordinary clothing and even rubber. It is

a powerful blistering agent and damages the surfaces it comes incontact with. Since it also contains arsenic, some features of arsenictoxicity can also develop.

2.3.5. Clinical featuresThe LD50 of L is estimated to be 30 mg/kg and LCt50 is

100,000 mg min/mm3 for dermatological manifestations (Raber etal., 2001). Signs and symptoms are similar to other blistering agent.In addition, refractory hypotension known as Lewisite shock, candevelop in persons exposed to L. Bone marrow suppression is nota feature of toxicity.

2.3.6. TreatmentRemoval of casualties by well protected staff from area of con-

tamination is most important followed by removal of clothingand a liberal bath. In addition to supportive treatment, a spe-cific antidote British anti-Lewisite (dimercaprol, BAL) is used forsystemic or severe toxicity. It is a chelating agent which has
proved to be very effective and is widely used (Eagle et al., 1946;Oeheme, 1972). Other chelating agents available include sodium2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3 dimercap-tosuccinic acid (DMSA) and the mono and dialkylesters of DMSA.All of them are derivatives of BAL. DMPS and DMSA can be givenboth intravenous as well as orally and are believed to be possiblymore effective.
3. Nerve agents

These are organophosphorus compounds which inhibit theenzyme acetylcholinesterase. Cholinesterase inhibitors have beenused in the treatment of human diseases, the control of insectpests, and more notoriously as CWA’s and weapons of terror-ism. Commonly known as nerve agents, these are the deadliestof CWA’s. These agents have both chemical names as well as 2-letter NATO codes. These are categorized as G series agents: GB(Sarin), GD (Soman), GA (Tabun), GF and V Series agents: VE,VG, VM and VX, the letter “G” representing the country of origin“Germany” and letter “V” possibly denoting “Venomous”. Histor-ically earliest recorded use of cholinesterase inhibitors was by

and Pharmacology 26 (2008) 113–122 117

native tribesmen of Western Africa. They used Calabar bean asan “ordeal poison” in witchcraft. An extract of Calabar bean waslater used for various medicinal purposes and the active princi-ple “physostigmine” was isolated in 1864 (Fraser, 1863). Wurtzin 1854 synthesized the first organophosphate compound, tetra-ethyl pyrophosphate (TEPP). In 1937 Gerhard Schrader developedthe general formula for all organophosphorus compounds andmanufactured GB and GA. This was followed rapidly by develop-ment of other agents. It is estimated that Germany manufacturedabout 12,000 tons of these nerve agents during WWII. However,Germany restrained from their use in the battlefield. The nerveagents GA and GB were first used on the battlefield by Iraq againstIran during the first Persian Gulf war and again against the Kur-dish rebels (Dingeman and Jupa, 1987; Barnaby, 1988). In 1995,the Japanese cult Aum Shinrikyo used GB in terrorist attacks inTokyo resulting in 12 deaths (Okumura et al., 1996; Yokoyama etal., 1996).

3.1. Manufacture

Many nerve gases require chemical technologies similar to thoseused for production of agricultural insecticides. VX is producedby the Transester Process, where phosphorus trichloride is methy-lated to produce methyl phosphorous dichloride. This compound isreacted with ethanol to form a diester and then trans-esterified toproduce an intermediate which is then reacted with sulfur to formVX.

3.2. Properties

All nerve agents are liquid at standard temperature and pres-sure. Their high volatility makes them a powerful weapon. The term“nerve gas” itself is a misnomer. This arises from a misunderstand-ing as chlorine and phosgene, which were the first CWA’s used inWWI, were true gases at standard temperature and pressure. Pop-ular accounts tend to refer to subsequently developed CWA’s as“poison gas” or “nerve gas”.

GA (ethyl N,N-dimethylphosphoramidocyanidate) is chemicallyC5H11N2O2P and is a colorless to brown liquid, with a faintlyfruity odor. It evaporates twice as fast as mustard gas making ita powerful CWA. GB (2-(fluoro-methyl-phosphoryl)oxypropane)is chemically C4H10FO2P. It is a clear colorless and odorless liq-

◦

volatile agents. It evaporates at the same rate as water and 36times faster than GA. A lethal dose of GB in humans is about0.5 mg making it 500 times more deadly than cyanide. VX (O-ethyl-S-[2(diisopropylamino)ethyl]methylphosphonothiolate) is chemi-cally C11H26NO2PS. VX is the least volatile agent with consistencyof motor oil. They can persist in the ground for as long as 24 h. Thispersistence and higher lipophilicity make VX 100–150 times moretoxic than GB in cases of delayed evacuation.

3.3. Uses

Besides as CWA’s, organophosphorus compounds are widelyused as insecticides in agriculture.

3.4. Mechanism of human toxicity

These agents inhibit the enzyme acetylcholinesterase at cholin-ergic synapses, thereby inhibiting degradation of acetylcholine.Accumulation of the released neurotransmitter acetylcholine,causes end-organ overstimulation, recognized as cholinergic crisis.In addition VX can induce acute lung injury.

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3.5. Clinical features

The LD50 of GA, GB, GD and VX in humans is estimated tobe 24.3, 14.3, 5 and 0.14 mg/kg and the LCt50 is 400, 100, 50and 10 mg min/mm3 respectively (Menger and Elrington, 1990;Raber et al., 2001). Exposure can be either to vapors or liquid, theformer being more likely in a war scenario. The onset of symp-toms from time of exposure generally occurs within minutes ifinhaled but can vary from 30 min to 2 days with liquid expo-sure. Exposure of a person to nerve agent vapor affects the eye(miosis) due to papillary muscle contraction described by Tokyosubway victims as “the world going black”, causes increase insecretions from various glands (manifesting as rhinorrhea, sali-vation, bronchorrhea), contraction of bronchial smooth muscleresulting in bronchospasm and impaired ventilation of the lungsleading to hypoxia and death. This is commonly termed as thepatient drowning in his own secretions. Gastrointestinal tract expo-sure results in abdominal cramping and pain, nausea, vomiting,and diarrhea. Other organs affected include the heart (increasedor decreased heart rate, hypo or hypertension), exocrine glands(increased sweating), muscles (fasciculation’s, twitching and paral-ysis), and brain (loss of consciousness, seizures, and central apnea).Death is due to respiratory failure due to a combination of bron-chorrhea, bronchospasm, respiratory muscle paralysis and centralapnea. Neuropsychiatric sequelae in non-dose dependant fash-ion have been described (Murata et al., 1997; McDonough, 2002;Hatta et al., 1996). This syndrome overlaps with post-traumaticstress disorder (PTSD) and in some patients it may actually be atrue PTSD. Other delayed manifestations that have been observedinclude organophosphorus induced neuropathy (not seen with VX)and intermediate syndrome. Intermediate syndrome has been welldescribed in organo phosphate insecticide toxicity. It is charac-terized by muscular weakness and occurs after apparent recoveryfrom the acute cholinergic syndrome and reflects prolonged actionof acetyl choline on nicotinic receptors. Also a delayed neuro-behavioural syndrome has been described in a small proportionof nerve agent survivors.

Other than nerve agents, cyanides can potentially cause a personto suddenly fall, lose consciousness and develop seizures. Miosis, atypical feature of nerve agent toxicity is not seen with cyanide poi-soning. Absence of secretions favors cyanide exposure. In cyanidepoisoning a classical “cherry red” color of the skin is seen. Amongstlaboratory tests a raised anion gap metabolic acidosis is typical ofcyanide poisoning. Cholinesterase levels may not be helpful as the
range is very variable. Sometimes it may be difficult to differenti-ate between the two and in such a scenario treatment should beinstituted for both.
3.6. Treatment

Acute nerve agent poisoning is treated by decontamination,respiratory support, and specific antidotes. Decontamination of avapor is theoretically not necessary, but vapors can be trappedin clothes and therefore removal of all clothes and decontamina-tion of skin using copious amount of water or sodium hypochloritesolution is mandatory. A skin decontamination kit approved byFDA containing activated charcoal impregnated with ion exchangeresins (Ambergard) is also available. Atropine rapidly reversescholinergic overload at muscarinic synapses and is the antidote ofchoice. US military personnel are given MARK I kits, which con-tain 2 mg atropine in an auto injector form for use intramuscularly.The field-loading dose is 2, 4, or 6 mg, with retreatment every5–10 min until the patient’s secretions are dry. Oximes reactivatecholinesterase and restore normal enzyme function (Quinby, 1964).The US has approved and fielded 2-pralidoxime chloride (2-PAM


Cl). MARK I kits in addition to atropine also contain auto injectorsof 600 mg of 2-PAM Cl. Initial field loading doses are 600, 1200,or 1800 mg. The usual recommendation is 1000 mg through slowintravenous drip over 20–30 min, with no more than 2000 mg overa period of 1–1.5 h. Nerve agent-induced seizures respond only tobenzodiazepines. Midazolam is the fastest acting and most effec-tive. However under field conditions, diazepam is equally effective.It is distributed amongst the forces as 10-mg injectors for intramus-cular use (McDonough et al., 1999, 2000).

To counteract rapidly acting agents such as GD, the US militaryevaluated the use of pyridostigmine bromide, which was approvedby the FDA, for wartime use. It is to be used only prophylacticallybefore exposure in a dose of 30 mg every eight hourly and not afterthe exposure. It binds reversibly with cholinesterase thereby pre-venting more deadly GD to bind to the receptors. This gives time forother antidotes to act which are given after exposure. It was givento 250,000–300,000 American troops in a daily dose of 90 mg fora maximum of 7 days in the Gulf War, as a “pretreatment” againstpotential Iraqi attacks with the nerve gas Soman (Cerasoli et al.,2005). However, still uncertainties prevail about its efficacy.

Recently researchers have developed bioscavangers, which areeither a human cholinesterase molecule or an altered humancholinesterase which would bind and detoxify nerve agent enter-ing a patient’s circulation so that it would not be able to reach thetissues. These include plasma-derived butyrylcholinesterase andrecombinant butyrylcholinesterase (Huang et al., 2007). Further-more for neuroprotection, several drugs including ketamine andHU-211 have shown promising results in clinical trials.

4. Asphyxiants/blood agents

Asphyxiants are substances that cause tissue hypoxia. These areclassified as either simple or chemical. Simple asphyxiants (e.g.,methane and nitrogen) physically displace oxygen in inspired air,resulting in oxygen deficiency and hypoxemia. Chemical asphyxi-ants like cyanides interfere with oxygen transport at cellular levelcausing tissue hypoxia, anaerobic metabolism and lactic acido-sis. The important chemical asphyxiants used as CWA’s includecyanogen chloride (CK), hydrogen cyanide (HCN), arsine (SA).

4.1. Cyanogen chloride (CK)

Cyanogen chloride, also known as chlorine cyanide, chlorocyan,
or cyanochloride was used during WWI by the French, who calledit Mauguinite. Two properties made it an effective CWA: Firstly CKcould penetrate the masks of that time. The “mask breaking” prop-erties of cyanogen chloride lead to its mass production (around11,000 tons) by the US. Secondly, it was not inflammable and there-fore did not burn up during the “burster” charge. After WWII, CKrapidly fell out of favor being replaced by faster acting nerve agents.
4.1.1. ManufactureCK is produced as a byproduct when bleach-containing decon-

taminants are used for decomposition of the nerve agent GA.

4.1.2. PropertiesCyanogen chloride is chemically ClCN. It is a colorless vapor at

normal temperatures with a boiling point of 13.8 ◦C. It has a pungentbiting, pepper-like odor.

4.1.3. UsesCyanogen chloride is used in industry for synthesis of herbicides,

ore refining, and as a metal cleaner.

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4.1.4. Mechanism of human toxicityCyanide interferes with aerobic respiration at a cellular level

by forming a reversible complex with the cytochrome oxidaseenzyme system (Singh et al., 1989). This enzyme is responsible foroxygen utilization and cell respiration. The resultant inhibition ofcytrochrome oxidase enzyme results in inability to utilize oxygenand accumulation of lactic acid and cell death from tissue anoxia.An airborne concentration of 270 ppm is immediately fatal.

4.1.5. Clinical featuresOnset is usually rapid with deaths occurring in less than

10 min. Inhalation in low concentration causes breathlessness,headache, dizziness, anxiety, palpitations, mydriasis, blurring ofvision, nausea and drowsiness. Exposure to high concentrationsproduces hyperventilation, followed by loss of consciousness, con-vulsions, fixed and dilated pupils. High concentrations result indeath from respiratory and/or cardiac arrest within minutes with-out any symptoms. Despite hypoxia, there is no cyanosis. Insteadthe color of skin turns cherry red (Salkowski and Penney, 1994;Johnson and Mellors, 1988). Cyanides should be suspected inareas of mass fatalities, especially when the characteristic symp-toms of nerve agent intoxication are absent. Other clues wouldbe persistent hypotension, metabolic acidosis, normal arterial oxy-genation, and excessive venous oxygenation (Johnson and Mellors,1988).

4.1.6. TreatmentAdequate protection by wearing protective impermeable cloth-

ing with breathing apparatus and evacuating staff must be ensuredbefore rescuers attempt to aid casualties. Skin decontamina-tion should be carried out using a “rinse-wipe-rinse” techniquewith a dilute detergent solution. Besides supportive management,three specific antidotes are available and include nitrites, dicobaltedentate and hydroxycobalamine/thiosulfate. Ten milliliters of 3%sodium nitrite is given intravenously over 5–20 min. Amyl nitrite(one 0.2 ml ampoule inhaled over 0.5–1 min) can be used in caseintravenous access is a problem followed by sodium thiosulfatewhich is given as 25 ml of a 50% solution intravenous over 10 min(Kulig, 1991). Nitrites convert hemoglobin to methhemoglobin.Methhemoglobin binds to cyanides more avidly as compared tocytochrome oxidase and thus preventing the toxicity. Sodium thio-sulfate removes cyanide from methhemoglobin by forming sodiumthiocyanate which is removed from the body and methhemoglobinis converted back to hemoglobin. Dicobalt edetate given in doses
of 300–600 mg intravenously over 2–5 min is equally effectivein cases of severe cyanide poisoning, but its use is limited bysevere cardiovascular side effects (Braitberg and Vanderpyl, 2000).Hydroxycobalamine/thiosulfate is emerging as the drug of choiceas it has minimal adverse effects (Mushett et al., 1952; Borron et al.,2007). It has been recently approved by the FDA. There is no head tohead comparison between the three antidotes, but considering thesafety profile and overall efficacy, hydroxycobalamine is the drugof choice. In cases of poisoning with cyanides, it is of the utmostimportance that counter measures are immediately introduced. Forthis reason, a medical antidote (PAPP, para-aminopropiophenone)for use as a pretreatment is under evaluation (Steven et al., 1992).
4.2. Hydrogen cyanide (HCN)

HCN is also known as hydrocyanic acid or prussic acid. Liquidhydrocyanic acid was first produced by Scheele in 1782. In WWIFrench forces used this in large quantities but it proved to be lesseffective as compared to other CWA’s because of its tendency torapidly evaporate. However, under the brand name Zyklon-B it wasperhaps most infamously employed by the Nazi regime in mid-20th


century as a method of mass extermination and again in 1980s inthe Iran–Iraq war against the Kurds. It is highly toxic and in suffi-cient concentrations it rapidly leads to death.

4.2.1. ManufactureHCN can be produced by reaction of ammonia and methane in

the presence of oxygen at about 1200 ◦C over a platinum catalyst orin absence of oxygen by heating formamide. Small amounts of HCNcan be produced in a laboratory by the addition of acids to cyanidesalts of alkali metals.

4.2.2. PropertiesIt is a colorless or pale blue, highly volatile liquid that boils

slightly above room temperature at 25.70 ◦C. High volatility proba-bly makes HCN difficult to use in warfare since there are problemsin achieving sufficiently high concentrations outdoors. HCN has afaint, bitter, almond-like odor.

4.2.3. UsesHCN is a precursor to many chemical compounds ranging from

polymers to plastics. It is used in the pharmaceutical industry andalso for fumigation of ships and buildings.

4.2.4. Mechanism of human toxicityIs same as that of CK.

4.2.5. Clinical featuresThe most important route of poisoning is through inhalation,

though they can be absorbed through the skin also. Signs andsymptoms are similar to those seen after exposure to CK. Lethalconcentration of HCN is 270 ppm for 6–8 min, 181 ppm for 10 minand 135 ppm for 30 min.

4.2.6. TreatmentIs on the same lines as for CK.

4.3. Arsine

Arsine (arsenic hydride, arsenic trihydride, arseniuretted hydro-gen, arsenous hydride, hydrogen arsenide) is the most toxic formof arsenic. During the WWII it was extensively studied as a CWA,but its low toxicity prevented it from being used in war. How-ever, it still remains a potential threat of small scale terrorist
attacks and is included in the NATO’s list of CWA’s. Althougharsine itself has not been used as a CWA, several arsine-derivedorganoarsenic compounds have been developed and used asCWAs, including lewisite (beta-chlorovinyldichloroarsine), adam-site (diphenylaminearsine), Clark I (diphenylchlorarsine), and ClarkII (diphenylcyanoarsine).
4.3.1. ManufactureIt is prepared by the reaction of arsenic chloride (AsCl3) with

NaBH4 and also by reaction of Zn3As2 with hydrogen ion.

4.3.2. PropertiesThe gas is colorless, almost odorless, and 2.5 times denser than

air. It is highly inflammable. It is shipped as a liquefied compressedgas. It is soluble in water (200 ml/l) and in many organic solventsas well. This compound is generally regarded as stable.

4.3.3. UsesArsine may be released in metal refining processes. It is used

as a doping agent in microelectronics and is also used in the man-ufacturing of organic chemicals and lead storage batteries. It has

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applications in the semiconductor industry, and is used in the syn-thesis of organoarsenic compounds.

4.3.4. Mechanism of human toxicityInhaled arsine gas causes rapid destruction of red blood cells

leading to hypoxia and renal failure. Mechanism is believed to benonspecific disruption of ion gradients, leading to cell membraneinstability and lysis of red blood cells (Graham et al., 1946; Pullen-James and Woods, 2006).

4.3.5. Clinical featuresIt has delayed onset of action with a latent period up to 24 h.

The symptoms are due to rapid destruction of red blood cells(hemolysis). These include abdominal pain, hematuria (red urine),and jaundice. Nonspecific symptoms like fever, chills, confusion,dizziness, vomiting and cramping may be present. Discoloration ofconjunctivae (red, orange, brown, or brassy) and jaundice is seen.In severe cases patient may be passing red or cola colored urineand may develop acute renal failure or acute respiratory distresssyndrome (Pullen-James and Woods, 2006).

4.3.6. TreatmentProperly protected personnel should remove the victim from

continued exposure to arsine. There is no specific antidote. Victimsshould be administered high flow oxygen. Exchange transfusionshould be used in cases of severe hemolysis. Forced alkaline diure-sis may prevent development of renal failure. In patients withestablished renal failure, hemodialysis should be instituted (Pullen-James and Woods, 2006).

5. Choking/pulmonary damaging agents

Lung toxicants are the general class of gases that are toxic to thehuman lung when inhaled, resulting in an inflammatory response.This manifests as pulmonary edema, reduced pulmonary compli-ance and altered gas exchange. The CWA’s under this categoryinclude chlorine, chloropicrin (PS), phosgene (CG) and diphosge-nenitrogen oxides.

5.1. Chlorine (Cl)

Chlorine in gaseous form is poisonous. Chlorine was discoveredin 1774 by the Swedish chemist Carl Wilhelm Scheele. Chlorine wasgiven its current name in 1810. Faced with a shortage of ammuni-
tion, Germany used chlorine as a CWA during WWI without muchsuccess, but this opened the path for large scale manufacture ofCWA’s both by Germany and the allies. However at present it acommon chemical agent of considerable commercial use.
5.1.1. ManufactureIt can be manufactured by a number of processes. Deacon pro-

cess involves the direct oxidation of hydrogen chloride with oxygenor air at 400 ◦C to form chlorine using CuCl2 as a catalyst. Dueto the extremely corrosive reaction mixture, industrial use of thismethod was difficult. Chlorine is now manufactured by electrolysisof a sodium chloride solution (brine). The production of chlorineresults in the byproducts caustic soda (sodium hydroxide, NaOH)and hydrogen gas (H2). These two products, as well as chlorine arehighly reactive. There are three industrial methods for the extrac-tion of chlorine by electrolysis namely mercury cell electrolysis,diaphragm cell electrolysis and membrane cell electrolysis.

5.1.2. PropertiesChlorine gas is pressurized and cooled so that it can be stored

in the liquid form. When liquid chlorine is released, it quickly turns


into a gas with yellow–green color and with an irritating odor. It isheavier than air, there by tending to accumulate in low lying areas.

5.1.3. UsesChlorine is most commonly used as a bleaching agent in the

paper and cloth industry. It is also used to make pesticides, rubberand solvents. Amongst the household uses it is used as a disinfec-tant in drinking water and in the swimming pool. It is also used totreat industrial waste and sewage.

5.1.4. Mechanism of human toxicityWhen chlorine gas comes into contact with moist tissues such

as the eyes, throat, and lungs, hydrochloric and hypochlorous acidis produced. Hypochlorous acid degenerates into hydrochloric acidand nascent oxygen. Both hydrochloric acid and nascent oxygendamages the lung tissue resulting in an inflammatory response thatdamages the alveolar-capillary membrane of the human lung. Thismanifests as pulmonary edema, reduced pulmonary compliance,and altered gas exchange.

5.1.5. Clinical featuresThese depend upon site of exposure and concentration of gas.

Immediately after exposure patients complains of chest tightness,burning sensation in the nose, throat and eyes, redness and blisterson the skin similar to frostbite. Breathlessness and acute lung injury(ARDS) occurs within 2–4 h of exposure (Da and Blanc, 1993).

5.1.6. TreatmentRemoving the causalities from the site by well protected per-

sonnel. There is no specific antidote. Measures include removal ofall clothing and providing supportive medical care.

5.2. Chloropicrin (PS)

PS vapor is highly poisonous when inhaled. It was used in WWIas a CWA with different names. It was called PS by the British, Aqui-nite by the French, and Klop (green cross) by the Germans. AfterWWII, its use as CWA is obsolete.

5.2.1. ManufacturePS is prepared by the reaction of picric acid with calcium

hypochlorite or by the addition of nitrogen to chlorinated hydro-carbons or by chlorinating nitromethane.

5.2.2. PropertiesChloropicrin (tri-chloro(nitro)methane) is chemically CCl3NO2.

It is an oily, colorless and a faintly yellow liquid which decomposesat 112 ◦C to yield phosgene and nitrosyl chloride. It is more toxicthan chlorine but less than phosgene.

5.2.3. UsesIndustrial uses include organic synthesis, in fumigants, in

fungicides and insecticides, and for the extermination of rats.Chloropicrin is also used for fumigation and to sterilize soil andseed.

5.2.4. Mechanism of human toxicityIs the same as that of chlorine.

5.2.5. Clinical featuresThree periods of trichlornitromethane intoxication have been

described which are irritation, latent (average 2–5 h) and develop-ment of pulmonary edema (Asauliuk, 1990). However if inhaled inhigh concentrations, the latent period may not be present. Someauthors have also described low grade rhabdomyolysis associated

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with its inhalation (Prudhomme et al., 1999). Because of its relativeinertness and the small size of its molecule, chloropicrin penetratesgas mask filters causing vomiting. This makes the victim removethe gas mask. For this reason, it is often mixed with other chemicalweapons.

5.2.6. TreatmentIs along the same lines as following exposure to chlorine.

5.3. Phosgene (CG)

CG was first synthesized by Davy in 1812. It was developed intoa CWA by Haber. Since it was more lethal than chlorine, it was usedby Germany in 1915 during WWI resulting in 1069 casualties and120 deaths. Subsequently allied forces also used it. It accounted for85% of war causalities during WWI. Besides being a CWA, CG hasextensive industrial uses. Nearly 1 ton is produced annually by theUS alone.

5.3.1. ManufactureCG is not a natural compound. It is manufactured industrially by

passing purified carbon monoxide and chlorine gas through a bedof catalyst (porous carbon) at temperatures between 50 and 150 ◦C.Above 200 ◦C, phosgene decomposes back into carbon monoxideand chlorine. Also chloroform upon ultraviolet radiation in the pres-ence of oxygen slowly converts into phosgene via a radical reaction.It is also produced as a byproduct during thermal decompositionof chlorinated hydrocarbons.

5.3.2. PropertiesIt is stored as a liquid under low temperatures and pressures

with a boiling point of 8.2 ◦C. Therefore at room temperatures CG isa poisonous gas. It forms a colorless or a white to pale yellow cloudwith a pleasant odor of newly mown hay but at higher concentra-tions it gives an offensive odor. It is 3.5 times heavier than air andtends to accumulate in low lying areas.

5.3.3. UsesSince WWII, CG has found extensive industrial uses. It is widely

used in chemical industries such as pharmaceuticals, dyes, pesti-cides and polyurethane for foam rubber products.

5.3.4. Mechanism of human toxicity
Is same as that of chlorine.
5.3.5. Clinical featuresFollowing exposure, coughing, burning sensation in the throat

and eyes, choking and breathlessness develops. This is followed bya symptom free period which varies from 2 to 48 h followed byacute lung injury (Nelson, 2002). Acute lung injury is precipitatedby exercise as was frequently reported in the WWI. In persons whoremain asymptomatic and whose lungs appear clear on chest filmsobtained 8 h after exposure acute lung injury is unlikely to develop.

5.3.6. TreatmentRemoving the casualties from the site by well protected person-

nel. Removal of clothing and liberal bath in soap water helps todecontaminate. Exposure to CG may cause acute lung injury as lateas 48 h. There is no antidote. Treatment is symptomatic and sup-portive. The role of steroids is not proven (Diller, 1985). Exposedpeople should be observed for up to 48 h. If the patient survives formore than 48 h, the prognosis is excellent (Evison et al., 2002). Inexperimental studies, N-acetylcysteine and Ibuprofen has shownpromising results in phosgene induced lung injury.


6. Behavioural agents/incapacitating agents

Following WWII, the US military investigated a wide rangeof possible nonlethal, psychobehavioural chemical incapacitat-ing agents. These included lysergic acid diethylamide (LSD-25),ketamine, fentanyl, carfentanil and several glycolate anticholiner-gics. The only agent classified as CWA is 3-quinuclidinyl benzilate,an anticholinergic compound. It is codenamed as BZ by NATO. Itis alleged that BZ was stockpiled by Iraq in large quantities, codenamed Agent 15. It is also believed that BZ was the chemical war-fare agent used to subdue terrorists in Moscow on 26 October 2002,though the exact nature of the gas still remains unknown. It isestimated that out of 127 deaths, BZ was responsible for 123 deaths.

6.1. Manufacture

It is manufactured by reacting methyl benzilate with 3-quinuclidinol in an inert anhydrous aliphatic hydrocarbon solventin the presence of 7–15 mol% of metallic sodium based on themethyl benzilate.

6.2. Properties

BZ is odorless gas. It can persist for three to four weeks in moistair. It is extremely persistent in soil and water and on most surfaces.

6.3. Uses

There are no known uses except as CWA.

6.4. Mechanism of human toxicity

BZ is a competitive inhibitor of the neurotransmitter acetyl-choline. The organs primarily affected are those innervated byparasympathetic nerves. These include the central nervous system,eye, heart, respiratory system, skin, gastrointestinal tract, and uri-nary bladder. Sweat glands though innervated by the sympatheticnervous system, are also affected.

6.5. Clinical features

The LCt50 is estimated to be around 3800–40,000 mg min/m3.It affects the central and peripheral nervous system. The central
effects include restlessness, hallucinations, confusion, agitation,tremor, ataxia, stupor, and coma. In the periphery it affects the eye(dilatation of pupil causing photophobia and impairment of nearvision), increase in heart rate, nausea, vomiting, flushing, drynessof skin, mouth and throat, urinary retention and hyperthermia.
The clinical course is divided into four phases:

Phase 1: (0–4 h after exposure), characterized by parasympatheticblockade and mild CNS effectsPhase 2: (4–20 h after exposure), characterized by stupor withataxia and hyperthermiaPhase 3: (20–96 h after exposure), in which overt delirium is seenbut often fluctuates from moment to moment.Phase 4: characterized by paranoia, deep sleep, reawakening,crawling or climbing automatisms, and eventual reorientation

6.6. Treatment

No specific antidote has been found to reverse the action of QNBdefinitively. Physostigmine, a cholinergic agent, has not been foundto be very efficacious in BZ poisoning. Supportive care remains the

ology
best therapy. However, if the exposed patient is markedly agitated,benzodiazepines can be administered.

7. Detection of CWA’s

As a countermeasure against CWA use, detection and identifica-tion are very important. The detection of CWA’s can be difficultas they are frequently rapidly degraded and hence difficult todetect. It may be useful to look for their metabolites and degra-dation products. Any system developed should be accurate withlow false positive and negative alarms, especially in the context ofa complex battlefield environment. Detection equipment such asgas detection tubes and ion mobility spectrometers are used foron-site detection. Common techniques used for detection includeatmospheric pressure and chemical ionization (APCI) and flamephotometric detection. There are several commercially availablealarm units which are known by their acronyms and include GID3,RAID1, M90, CHASE and AP2CV.

8. Destruction of chemical weapons

Under the CWC, the stockpiles of all CWAs are to be destroyed.This poses a great challenge including the high cost of destruction,safety of the staff involved as well as of the neighboring popu-lation and environmental, legal and political factors. Previouslythe most common disposal methods for CWA’s were land burial,sea dumping, detonation and open-pit burning. All these methodsposed great threat to the environment as well as to the health ofunsuspecting population residing in the vicinity. At present, twotechnologies are adopted for destroying CWA’s: incineration andchemical degradation. Under the incineration process, CWA’s aretaken to the demilitarization facility, where the chemical agentis removed from the munitions or bulk containers by automatedequipment. This puts the workers at the demilitarization plant ata very low risk of exposure. Chemical degradation is done usingchemicals, namely alkalis and oxidants, which reduce and oftennegate the toxicity of chemical agents.

9. Conclusion

The use of CWA’s still remains a potential threat despite the
CWC prohibiting their use. They are relatively easy to manufacturewith a potential to cause significant morbidity and mortality. Theseagents can, and have been effectively used in warfare in small scaleoperations and terrorist attacks. Knowledge about these agents isvery important to plan a response in an emergency. If timely pro-tective action is taken and exposed persons treated immediately,the mortality and morbidity can be considerably reduced. Interna-tional treaties such as the CWC should help to control proliferationof chemical weapons along with the safe destruction of existingones.
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