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Environmental Toxicology and Pharmacology 26 (2008) 113122

Contents lists available at ScienceDirect

Environmental Toxicology and Pharmacology


journal homepage: www.elsevier.com/locate/etap

Mini-review

Chemical warfare agents


S. Chauhan a , S. Chauhan b, , R. DCruz f , S. Faruqi c , K.K. Singh d , S. Varma e , M. Singh a , V. Karthik e
a

Department of Chemical Engineering, Panjab University, Chandigarh, India


Department of Medicine, Government Medical College and Hospital, Chandigarh 160030, India
c
Department of Respiratory Medicine, Pinderelds General Hospital, Aberford Road, Wakeeld WF1 4DG, UK
d
Department of Neurology, Army Hospital (Research & Referral), New Delhi, India
e
Department of Internal Medicine, Post Graduate Institute of Medical Education & Research, Chandigarh, India
f
City Clinic, MDC, Panchkula 134109, Haryana, India
b

a r t i c l e

i n f o

Article history:
Received 5 August 2007
Received in revised form 6 March 2008
Accepted 11 March 2008
Available online 18 March 2008
Keywords:
Blister agents
Nerve agents
Asphyxiants
Choking agents

a b s t r a c t
Chemical warfare agents (CWAs) are dened as any chemical substance whose toxic properties are utilised
to kill, injure or incapacitate an enemy in warfare and associated military operations. Chemical agents have
been used in war since times immemorial, but their use reached a peak during World War I. During World
War II only the Germans used them in the infamous gas chambers. Since then these have been intermittently used both in war and acts of terrorisms. Many countries have stockpiles of these agents. There
has been a legislative effort worldwide to ban the use of CWAs under the chemical weapons convention
which came into force in 1997. However the manufacture of these agents cannot be completely prohibited as some of them have potential industrial uses. Moreover despite the remedial measures taken so far
and worldwide condemnation, the ease of manufacturing these agents and effectiveness during combat
or small scale terrorist operations still make them a powerful weapon to reckon with. These agents are
classied 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 to immediate injuries caused by chemical agents, some of them are associated with long term morbidities and psychological problems. In this review we will discuss briey about
the historical background, properties, manufacture techniques and industrial uses, mechanism of toxicity,
clinical features of exposure and pharmacological management of casualties caused by chemical agents.
2008 Elsevier B.V. All rights reserved.

Contents
1.
2.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abbreviations: CWA, chemical warfare agent; WWI, rst world war; WWII, second world war; US, United States (of America); CWC, chemical weapons convention;
NATO, North Atlantic Treaty Organisation; SM, sulfur mustard; NM, nitrogen mustard; DNA, de-oxy ribonucleic acid; LD50 , lethal dose in 50%; LCt50 , lethal concentration in
50%; TEPP, tetra-ethyl pyrophosphate; PTSD, post-traumatic stress disorder; FDA, US Food and Drug Administration; 2-PAM Cl, 2-pralidoxime chloride; CK, cyanogen chloride;
HCN, hydrogen cyanide; SA, arsine; PS, chloropicrin; CG, phosgene; ARDS, acute respiratory distress syndrome.
Corresponding author. Tel.: +91 172 2561355; fax: +91 172 2608488.
E-mail address: drsc88@rediffmail.com (S. Chauhan).
1382-6689/$ see front matter 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.etap.2008.03.003

114

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4.

5.

6.

7.
8.
9.

S. Chauhan et al. / Environmental Toxicology and Pharmacology 26 (2008) 113122

2.2.4.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.5.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.
Lewisite (L) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.1.
Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.2.
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.3.
Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.4.
Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.5.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.6.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nerve agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.
Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.
Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.4.
Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.5.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.6.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Asphyxiants/blood agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
Cyanogen chloride (CK) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.1.
Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.2.
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.3.
Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.4.
Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.5.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.6.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.
Hydrogen cyanide (HCN) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.1.
Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.2.
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.3.
Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.4.
Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.5.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.6.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.
Arsine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.1.
Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.2.
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.3.
Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.4.
Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.5.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.6.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Choking/pulmonary damaging agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.
Chlorine (Cl) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.1.
Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.2.
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.3.
Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.4.
Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.5.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.6.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.
Chloropicrin (PS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.1.
Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.2.
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.3.
Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.4.
Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.5.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.6.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.
Phosgene (CG) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.1.
Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.2.
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.3.
Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.4.
Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.5.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.6.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Behavioural agents/incapacitating agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.1.
Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.2.
Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.3.
Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.4.
Mechanism of human toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.5.
Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.6.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Detection of CWAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Destruction of chemical weapons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction

Table 1
Classication of chemical warfare agents

Chemical warfare is the use of the toxic properties of chemical


substances to kill, injure or incapacitate an enemy in warfare and
associated military operations. A chemical substance intended for
such use in military operations is dened as a chemical warfare
agent (CWA). Chemical agents have been used in war since times
immemorial. These have been elaborately described in ancient
Chinese literature. In 600 B.C. Helleborus roots were used successfully by the Athenians to contaminate water supplies during
the siege of Kirrha. Spartans ignited pitch and sulfur to create
toxic fumes during the Peloponnesian War in 429 B.C. Thereafter,
there have been intermittent use of CWAs in battleelds, but their
use reached a peak during World War I (WWI). French were the
rst to use ethylbromoacetate in WWI. It was followed by use
of o-dianisidine chlorosulphonate, chloroacetate, chlorine, phosgene, hydrogen cyanide, chlorine, diphenylchloroarsine, ethyl- and
methyldichloroarsine and sulfur mustard resulting in nearly 10,000
deaths and over a million casualties (Eckert, 1991). CWAs were not
used on the eld during World War II (WWII) due to the fear that the
enemy possessed more deadly CWAs, except for by the Germans
who used them in the infamous gas chambers for mass genocide
of Jews. After WWII, CWAs have been used intermittently both in
war, as in the IraqIran war, and acts of terrorisms as in the Japanese
underground rail station attacks (Okumura et al., 1996). It is estimated that nearly 1,00,000 United States (US) troops may have been
exposed to CWAs during operation Desert Storm. There has been a
legislative effort worldwide to ban the use of CWAs. The chemical
weapons convention (CWC) which came into force in 1997 stated
that all member countries must destroy all chemical weapons over
a 10-year period, with the treaty providing a leveling out principle that ensures possessors destroy their stockpiles at roughly
the same time. More than 170 countries have signed the CWC and
139 have ratied it. The manufacture of some of these agents however cannot be banned because of important industrial uses. These
agents also still remain a threat especially from countries that do
not possess nuclear technology as these are easy to manufacture,
cheap and have devastating effects. Moreover, these can also be
used effectively as weapons of small scale terrorist attacks. North
Atlantic Treaty Organization (NATO) has classied agents of chemical terrorism as blister agents, nerve agents, asphyxiants, choking
agents and incapacitating/behavior altering agents (Table 1). In this
review we will discuss briey about the CWAs. The CWAs are classied and their historical perspective, manufacture, mechanisms of
toxicity, clinical features on exposure and treatment are discussed.
This review is conned to synthetic chemicals only and biological
agents are not discussed.

1. Blister agent
Sulfur mustard
Nitrogen mustard
Lewisite

2. Blister agents
Blister agent or vesicants are a group of chemicals that cause
severe blistering when they come in contact with skin. These may
also have systemic effects if absorbed. These agents are not very
lethal as far as causing death is concerned but can incapacitate the
enemy and overload the already burdened health care services during war time. These include sulfur mustard, nitrogen mustard and
lewisite.
2.1. Sulfur mustards
Sulfur mustards (SMs), commonly known as mustard gas, are
alkylating agents capable of causing short and long term morbidity. Since these had a mustard like odor, these were called
sulfur mustard or mustard gas. They were discovered acciden-

115

2. Nerve gases
G series
Tabun
Sarin
Soman
V series
VE
VX
VG
VM
3. Choking agent
Chlorine
Chloropicrin
Phosgene
4. Asphyxiants
Cyanogen chloride
Hydrogen cyanide
Arsine
5. Behavioral altering agent

tally in 1822. Guthrie in the United Kingdom and Niemann in


Germany synthesized, 2,2-dichlorodiethylsulde, also known as
sulfur mustard (SM) in 1860. In 1917, the German forces used SM
for the rst time in battleeld. It accounted for about 70% of the
million-plus gas related casualties in WWI. Several varieties and
mixtures of SMs have been employed (HD, H, HT, HL, HQ). The
NATO codenamed SM as H which stood for Germans or Hunns. The
letter D in HD indicated that it was a distilled product of SM or
H.
2.1.1. Manufacture
Chemically mustard gas is a -chloro thioether with the formula
C4 H8 Cl2 S. The Germans produced SM using the Meyer process.
This involved reacting ethylene with hypochlorous acid followed
by sodium sulde, forming , -dihydroxy-methyl sulde. Further heating with hydrochloric acid produced SM. In the US, the
Levenstein process was used in which ethylene was reacted with
sulfur monochloride. Another process used in the US involved the
reaction between ethylene oxide and hydrogen sulde to form
bis-(2-hydroxyethyl)-thioether, which on further reaction with
hydrochloric acid forms SM.
Under the CWC the stockpiles of SM are required to be destroyed
by 2007. The various methods for destruction include hightemperature incineration, plasma treatment and electrochemical
reduction, hydrolysis and oxidation and reacting sulfur dissolved
in ethylenediamine with SM (Menger and Elrington, 1990; Ganesan
et al., 2005).
2.1.2. Properties
Sulfur mustard is not a gas but a pale yellow, oily liquid of specic
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 vaporizes in warm dry environments. It is heavier than air with a density
5.6 times that of air. It has an odor of mustard in the impure form
but the pure form is colorless and odorless. It is sparingly soluble
in water and soluble in fat, fat solvents, and other common organic
solvents. It penetrates ordinary clothes easily in the vaporized form.
2.1.3. Uses
It has no industrial use at present.

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S. Chauhan et al. / Environmental Toxicology and Pharmacology 26 (2008) 113122

2.1.4. Mechanism of human toxicity


SMs are alkylating agents. They damage all exposed epithelial surfaces, both in aerosol and liquid form. These effects appear
within 212 h after exposure, depending on the exposure dose. The
exact mechanism of its toxicity is yet to be elucidated. Most authors
believe that it dissolves aqueous media, such as sweat, rapidly
forming extremely reactive cyclic ethylene sulfonium ions. These
reactive ions react with deoxyribonucleic acid (DNA) in rapidly
dividing cells leading to cellular death and inammatory reactions
(Papirmeister et al., 1985). An alternative theory suggests that it
depletes the cell of Glutathione which leads to oxidative damage
and cell death (Gross et al., 1993).

eyes. Chemical pneumonitis, characterized by productive cough,


dyspnea and fever, occurs within 1224 h of inhalation. Infection generally occurs on the third to fth day, signaled by an
increased fever, pulmonary inltrates, and an increase in sputum
production with a change in color. Formation of pseudomembrane necessitates breoptic bronchoscopy. Bronchodilators and
glucocorticoids are of benet for bronchospasm. Bone marrow
suppression beginning on the 3rd day and peaking at 714 days
requires granulocyte colony-stimulating factor, transfusion support
or even bone marrow transplants. Recent research has shown some
benecial effects of vanilloid compounds and N-acetylcysteine in
animal trials.

2.1.5. Clinical features


Exposure to SM results in high morbidity and psychological
impact but low mortality. The mortality rate with sulfur mustard
is estimated to be 25%. The lethal dose of HD to cause death
in 50% of persons exposed (LD50 ) is estimated to be 100 mg/kg
and lethal concentration of vapor/aerosol to cause death in 50% of
exposed persons (LCt50 ) is 15,000 mg min/mm3 (Raber et al., 2001).
Most often exposed surfaces i.e. skin, airways, and eyes suffer the
brunt of the damage. Irritation of the eyes followed by conjunctivitis, photophobia, blepharospasm, pain, and corneal damage, which
can lead to perforation, is seen after exposure of the eyes. Glaucoma may develop later as a result of scarring. Dermatological
manifestations are akin to second degree burns, StevenJohnsons
syndrome or toxic epidermal necrolysis. Contact with skin can
manifest as painful erythema, vesicles or bullae containing a transudative straw colored uid. As the uid is a transudate it does lead
to as much protein loss as would be expected with burns of a similar nature. Inhalation of SM leads to irritation of the nose, epistaxis,
pharyngeal pain, laryngitis, voice changes, cough and dyspnea. Terminally, there may be necrosis of airways with hemorrhagic edema,
pseudomembrane formation and obstruction of the bronchi. Systemic 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 formation and laryngospasm are the major cause of death in the rst
24 h. Secondary bacterial pneumonia may cause mortality between
the third and fth days. Bone marrow suppression which peaks in
721 days is a cause of delayed mortality. Late complications which
do occur after exposure to SM include ulcerative keratitis, chronic
bronchitis, pulmonary brosis, hypo or hyperpigmentation of skin
and psychological problems. In a study involving 500 soldiers who
were exposed to SM during the IranIraq war (19831988) showed
that all of them developed either pulmonary or ocular complications 15 years after the war (Mohammad et al., 2004). Chronic
low grade exposure also results in morbidity (chronic conjunctivitis with impaired vision, nasal polyps, anorexia, vomiting weight
loss, irritability, bladder carcinoma and leukemia).

2.2. Nitrogen mustards

2.1.6. Treatment
There is no specic antidote. Supportive treatment remains
the mainstay. Removal of exposed persons by well protected rescuers is of prime importance. Thereafter removal of all clothing
and giving a through bath helps in decontamination. Clothing
removed should be packed in plastic bags. Topical cortisone may
be of benet in erythematous skin lesion. Larger bullae require
unroong with saline irrigation and application of antibiotics (silver sulfadiazine or modied Dakins solution) over denuded areas.
Management of large areas of skin involvement is similar to burns
patient requiring supportive measures but with special regard to
uids as these patients are prone to pulmonary edema. Irrigation, topical antibiotic and steroids are required for exposure to

Nitrogen mustards (NMs) are alkylating agents, like SMs. These


have also been classied under blister agents by NATO and are
nitrogen analogues of SMs. They are commonly known by their military designations i.e. HN-1 (bis(2-chloroethyl) ethylamine), HN-2
(bis(2-chloroethyl) methylamine), and HN-3 ( ). These were produced in 1920s and 1930s as potential CWAs. During WWII, nearly
100 tons of HN-1 was produced by the US and 2000 tons of HN-3
by Germany, but these were never used. HN-1 was originally used
for treatment of warts but later found itself in category of CWAs.
HN-2 and HN-3 were specically produced as CWAs.
2.2.1. Properties
HN-1 (bis(2-chloroethyl) ethylamine) has the chemical formula
C6 H13 Cl2 N It has a faint, shy or musty odor. It is sparingly soluble in water but miscible with acetone and other organic solvents
and decomposes at temperatures greater than 194 C. HN-2(bis(2chloroethyl) methylamine) has the chemical formula C5 H11 Cl2 N. It
has a fruity odor at high concentrations and a soapy odor at low
concentrations. HN-3 (tris(2-chloroethyl) amine) has the chemical
formula C6 H12 Cl3 N. It is odorless when pure but has been reported
to have a bitter almond odor. It is the most stable of the nitrogen
mustards but decomposes at temperatures greater than 256 C. It
has a much lower vapor pressure than HN-1 or HN-2 and is insoluble in water.
2.2.2. Uses
HN-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 SMs (Papirmeister et al., 1985; Gross et al., 1993).
2.2.4. Clinical features
Typically, signs and symptoms of NM exposure do not occur
immediately. The onset of symptoms may be up to several hours
after exposure to the agent. The concentration of the agent exposed
to would determine how soon symptoms occur after contact. These
agents, like SMs, affect the skin, eyes, respiratory tract and gastrointestinal tract. Like SMs, systemic absorption can lead to bone
marrow suppression and central nervous system effects.
2.2.5. Treatment
As no specic antidote exists for NM exposure, management is
supportive and on similar lines as that of SMs.
2.3. Lewisite (L)
This agent is classied as a blistering agent. It was developed as
a potential CWA during WWI, but by the time it was synthesized
the war had ended. During WWII it was found to be less effective

S. Chauhan et al. / Environmental Toxicology and Pharmacology 26 (2008) 113122

as compared to SM and therefore was not stockpiled. It also gets


hydrolysed in humid environment; there by rendering it less effective in operational conditions. Though it has never been used in
warfare, it is classied as a potential CWA.
2.3.1. Manufacture
Synthesis can be carried out by reacting arsenic trichloride with
acetylene in the presence of a hydrochloric acid solution of mercuric
chloride.
2.3.2. Properties
Lewisite chemically is C2 H2 AsCl3 (2-chloroethenyldichloroarsine). It is usually a mixture of the isomers 2-chlorovinylarsonous
dichloride, bis(2-chloroethenyl) arsinous dichloride and tris(2chlorovinyl) arsine. It has a density of 1.89 g/cm3 with melting and
boiling points of 18 and 190 C respectively. It hydrolyses in water
to form hydrochloric acid, and in contact with alkaline solutions
can form poisonous trisodium arsenate.
2.3.3. Uses
It was used initially as antifreeze for mustard gas or to penetrate
protective clothing in special situations by the US. However it was
declared obsolete in 1950s and it has no present industrial use.
2.3.4. Mechanism of human toxicity
It can easily penetrate ordinary clothing and even rubber. It is
a powerful blistering agent and damages the surfaces it comes in
contact with. Since it also contains arsenic, some features of arsenic
toxicity can also develop.
2.3.5. Clinical features
The LD50 of L is estimated to be 30 mg/kg and LCt50 is
100,000 mg min/mm3 for dermatological manifestations (Raber et
al., 2001). Signs and symptoms are similar to other blistering agent.
In addition, refractory hypotension known as Lewisite shock, can
develop in persons exposed to L. Bone marrow suppression is not
a feature of toxicity.
2.3.6. Treatment
Removal of casualties by well protected staff from area of contamination is most important followed by removal of clothing
and a liberal bath. In addition to supportive treatment, a specic antidote British anti-Lewisite (dimercaprol, BAL) is used for
systemic 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 sodium
2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3 dimercaptosuccinic acid (DMSA) and the mono and dialkylesters of DMSA.
All of them are derivatives of BAL. DMPS and DMSA can be given
both intravenous as well as orally and are believed to be possibly
more effective.
3. Nerve agents
These are organophosphorus compounds which inhibit the
enzyme acetylcholinesterase. Cholinesterase inhibitors have been
used in the treatment of human diseases, the control of insect
pests, and more notoriously as CWAs and weapons of terrorism. Commonly known as nerve agents, these are the deadliest
of CWAs. These agents have both chemical names as well as 2letter 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. Historically earliest recorded use of cholinesterase inhibitors was by

117

native tribesmen of Western Africa. They used Calabar bean as


an ordeal poison in witchcraft. An extract of Calabar bean was
later used for various medicinal purposes and the active principle physostigmine was isolated in 1864 (Fraser, 1863). Wurtz
in 1854 synthesized the rst organophosphate compound, tetraethyl pyrophosphate (TEPP). In 1937 Gerhard Schrader developed
the general formula for all organophosphorus compounds and
manufactured GB and GA. This was followed rapidly by development of other agents. It is estimated that Germany manufactured
about 12,000 tons of these nerve agents during WWII. However,
Germany restrained from their use in the battleeld. The nerve
agents GA and GB were rst used on the battleeld by Iraq against
Iran during the rst Persian Gulf war and again against the Kurdish rebels (Dingeman and Jupa, 1987; Barnaby, 1988). In 1995,
the Japanese cult Aum Shinrikyo used GB in terrorist attacks in
Tokyo resulting in 12 deaths (Okumura et al., 1996; Yokoyama et
al., 1996).
3.1. Manufacture
Many nerve gases require chemical technologies similar to those
used for production of agricultural insecticides. VX is produced
by the Transester Process, where phosphorus trichloride is methylated to produce methyl phosphorous dichloride. This compound is
reacted with ethanol to form a diester and then trans-esteried to
produce an intermediate which is then reacted with sulfur to form
VX.
3.2. Properties
All nerve agents are liquid at standard temperature and pressure. Their high volatility makes them a powerful weapon. The term
nerve gas itself is a misnomer. This arises from a misunderstanding as chlorine and phosgene, which were the rst CWAs used in
WWI, were true gases at standard temperature and pressure. Popular accounts tend to refer to subsequently developed CWAs as
poison gas or nerve gas.
GA (ethyl N,N-dimethylphosphoramidocyanidate) is chemically
C5 H11 N2 O2 P and is a colorless to brown liquid, with a faintly
fruity odor. It evaporates twice as fast as mustard gas making it
a powerful CWA. GB (2-(uoro-methyl-phosphoryl)oxypropane)
is chemically C4 H10 FO2 P. It is a clear colorless and odorless liquid and with a boiling point of 158 C, it is one of the most
volatile agents. It evaporates at the same rate as water and 36
times faster than GA. A lethal dose of GB in humans is about
0.5 mg making it 500 times more deadly than cyanide. VX (O-ethylS-[2(diisopropylamino)ethyl]methylphosphonothiolate) is chemically C11 H26 NO2 PS. VX is the least volatile agent with consistency
of motor oil. They can persist in the ground for as long as 24 h. This
persistence and higher lipophilicity make VX 100150 times more
toxic than GB in cases of delayed evacuation.
3.3. Uses
Besides as CWAs, organophosphorus compounds are widely
used as insecticides in agriculture.
3.4. Mechanism of human toxicity
These agents inhibit the enzyme acetylcholinesterase at cholinergic 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 to
be 24.3, 14.3, 5 and 0.14 mg/kg and the LCt50 is 400, 100, 50
and 10 mg min/mm3 respectively (Menger and Elrington, 1990;
Raber et al., 2001). Exposure can be either to vapors or liquid, the
former being more likely in a war scenario. The onset of symptoms from time of exposure generally occurs within minutes if
inhaled but can vary from 30 min to 2 days with liquid exposure. Exposure of a person to nerve agent vapor affects the eye
(miosis) due to papillary muscle contraction described by Tokyo
subway victims as the world going black, causes increase in
secretions from various glands (manifesting as rhinorrhea, salivation, bronchorrhea), contraction of bronchial smooth muscle
resulting in bronchospasm and impaired ventilation of the lungs
leading to hypoxia and death. This is commonly termed as the
patient drowning in his own secretions. Gastrointestinal tract exposure results in abdominal cramping and pain, nausea, vomiting,
and diarrhea. Other organs affected include the heart (increased
or decreased heart rate, hypo or hypertension), exocrine glands
(increased sweating), muscles (fasciculations, twitching and paralysis), and brain (loss of consciousness, seizures, and central apnea).
Death is due to respiratory failure due to a combination of bronchorrhea, bronchospasm, respiratory muscle paralysis and central
apnea. Neuropsychiatric sequelae in non-dose dependant fashion have been described (Murata et al., 1997; McDonough, 2002;
Hatta et al., 1996). This syndrome overlaps with post-traumatic
stress disorder (PTSD) and in some patients it may actually be a
true PTSD. Other delayed manifestations that have been observed
include organophosphorus induced neuropathy (not seen with VX)
and intermediate syndrome. Intermediate syndrome has been well
described in organo phosphate insecticide toxicity. It is characterized by muscular weakness and occurs after apparent recovery
from the acute cholinergic syndrome and reects prolonged action
of acetyl choline on nicotinic receptors. Also a delayed neurobehavioural syndrome has been described in a small proportion
of nerve agent survivors.
Other than nerve agents, cyanides can potentially cause a person
to suddenly fall, lose consciousness and develop seizures. Miosis, a
typical feature of nerve agent toxicity is not seen with cyanide poisoning. Absence of secretions favors cyanide exposure. In cyanide
poisoning a classical cherry red color of the skin is seen. Amongst
laboratory tests a raised anion gap metabolic acidosis is typical of
cyanide poisoning. Cholinesterase levels may not be helpful as the
range is very variable. Sometimes it may be difcult to differentiate between the two and in such a scenario treatment should be
instituted for both.
3.6. Treatment
Acute nerve agent poisoning is treated by decontamination,
respiratory support, and specic antidotes. Decontamination of a
vapor is theoretically not necessary, but vapors can be trapped
in clothes and therefore removal of all clothes and decontamination of skin using copious amount of water or sodium hypochlorite
solution is mandatory. A skin decontamination kit approved by
FDA containing activated charcoal impregnated with ion exchange
resins (Ambergard) is also available. Atropine rapidly reverses
cholinergic overload at muscarinic synapses and is the antidote of
choice. US military personnel are given MARK I kits, which contain 2 mg atropine in an auto injector form for use intramuscularly.
The eld-loading dose is 2, 4, or 6 mg, with retreatment every
510 min until the patients secretions are dry. Oximes reactivate
cholinesterase and restore normal enzyme function (Quinby, 1964).
The US has approved and elded 2-pralidoxime chloride (2-PAM

Cl). MARK I kits in addition to atropine also contain auto injectors


of 600 mg of 2-PAM Cl. Initial eld loading doses are 600, 1200,
or 1800 mg. The usual recommendation is 1000 mg through slow
intravenous drip over 2030 min, with no more than 2000 mg over
a period of 11.5 h. Nerve agent-induced seizures respond only to
benzodiazepines. Midazolam is the fastest acting and most effective. However under eld conditions, diazepam is equally effective.
It is distributed amongst the forces as 10-mg injectors for intramuscular use (McDonough et al., 1999, 2000).
To counteract rapidly acting agents such as GD, the US military
evaluated the use of pyridostigmine bromide, which was approved
by the FDA, for wartime use. It is to be used only prophylactically
before exposure in a dose of 30 mg every eight hourly and not after
the exposure. It binds reversibly with cholinesterase thereby preventing more deadly GD to bind to the receptors. This gives time for
other antidotes to act which are given after exposure. It was given
to 250,000300,000 American troops in a daily dose of 90 mg for
a maximum of 7 days in the Gulf War, as a pretreatment against
potential Iraqi attacks with the nerve gas Soman (Cerasoli et al.,
2005). However, still uncertainties prevail about its efcacy.
Recently researchers have developed bioscavangers, which are
either a human cholinesterase molecule or an altered human
cholinesterase which would bind and detoxify nerve agent entering a patients circulation so that it would not be able to reach the
tissues. These include plasma-derived butyrylcholinesterase and
recombinant butyrylcholinesterase (Huang et al., 2007). Furthermore for neuroprotection, several drugs including ketamine and
HU-211 have shown promising results in clinical trials.
4. Asphyxiants/blood agents
Asphyxiants are substances that cause tissue hypoxia. These are
classied as either simple or chemical. Simple asphyxiants (e.g.,
methane and nitrogen) physically displace oxygen in inspired air,
resulting in oxygen deciency and hypoxemia. Chemical asphyxiants like cyanides interfere with oxygen transport at cellular level
causing tissue hypoxia, anaerobic metabolism and lactic acidosis. The important chemical asphyxiants used as CWAs include
cyanogen 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 called
it Mauguinite. Two properties made it an effective CWA: Firstly CK
could penetrate the masks of that time. The mask breaking properties of cyanogen chloride lead to its mass production (around
11,000 tons) by the US. Secondly, it was not inammable and therefore did not burn up during the burster charge. After WWII, CK
rapidly fell out of favor being replaced by faster acting nerve agents.
4.1.1. Manufacture
CK is produced as a byproduct when bleach-containing decontaminants are used for decomposition of the nerve agent GA.
4.1.2. Properties
Cyanogen chloride is chemically ClCN. It is a colorless vapor at
normal temperatures with a boiling point of 13.8 C. It has a pungent
biting, pepper-like odor.
4.1.3. Uses
Cyanogen chloride is used in industry for synthesis of herbicides,
ore rening, and as a metal cleaner.

S. Chauhan et al. / Environmental Toxicology and Pharmacology 26 (2008) 113122

4.1.4. Mechanism of human toxicity


Cyanide interferes with aerobic respiration at a cellular level
by forming a reversible complex with the cytochrome oxidase
enzyme system (Singh et al., 1989). This enzyme is responsible for
oxygen utilization and cell respiration. The resultant inhibition of
cytrochrome oxidase enzyme results in inability to utilize oxygen
and accumulation of lactic acid and cell death from tissue anoxia.
An airborne concentration of 270 ppm is immediately fatal.
4.1.5. Clinical features
Onset is usually rapid with deaths occurring in less than
10 min. Inhalation in low concentration causes breathlessness,
headache, dizziness, anxiety, palpitations, mydriasis, blurring of
vision, nausea and drowsiness. Exposure to high concentrations
produces hyperventilation, followed by loss of consciousness, convulsions, xed and dilated pupils. High concentrations result in
death from respiratory and/or cardiac arrest within minutes without any symptoms. Despite hypoxia, there is no cyanosis. Instead
the color of skin turns cherry red (Salkowski and Penney, 1994;
Johnson and Mellors, 1988). Cyanides should be suspected in
areas of mass fatalities, especially when the characteristic symptoms of nerve agent intoxication are absent. Other clues would
be persistent hypotension, metabolic acidosis, normal arterial oxygenation, and excessive venous oxygenation (Johnson and Mellors,
1988).
4.1.6. Treatment
Adequate protection by wearing protective impermeable clothing with breathing apparatus and evacuating staff must be ensured
before rescuers attempt to aid casualties. Skin decontamination should be carried out using a rinse-wipe-rinse technique
with a dilute detergent solution. Besides supportive management,
three specic antidotes are available and include nitrites, dicobalt
edentate and hydroxycobalamine/thiosulfate. Ten milliliters of 3%
sodium nitrite is given intravenously over 520 min. Amyl nitrite
(one 0.2 ml ampoule inhaled over 0.51 min) can be used in case
intravenous access is a problem followed by sodium thiosulfate
which 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 to
cytochrome oxidase and thus preventing the toxicity. Sodium thiosulfate removes cyanide from methhemoglobin by forming sodium
thiocyanate which is removed from the body and methhemoglobin
is converted back to hemoglobin. Dicobalt edetate given in doses
of 300600 mg intravenously over 25 min is equally effective
in cases of severe cyanide poisoning, but its use is limited by
severe cardiovascular side effects (Braitberg and Vanderpyl, 2000).
Hydroxycobalamine/thiosulfate is emerging as the drug of choice
as 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 to
head comparison between the three antidotes, but considering the
safety prole and overall efcacy, hydroxycobalamine is the drug
of choice. In cases of poisoning with cyanides, it is of the utmost
importance that counter measures are immediately introduced. For
this 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. Liquid
hydrocyanic acid was rst produced by Scheele in 1782. In WWI
French forces used this in large quantities but it proved to be less
effective as compared to other CWAs because of its tendency to
rapidly evaporate. However, under the brand name Zyklon-B it was
perhaps most infamously employed by the Nazi regime in mid-20th

119

century as a method of mass extermination and again in 1980s in


the IranIraq war against the Kurds. It is highly toxic and in sufcient concentrations it rapidly leads to death.
4.2.1. Manufacture
HCN can be produced by reaction of ammonia and methane in
the presence of oxygen at about 1200 C over a platinum catalyst or
in absence of oxygen by heating formamide. Small amounts of HCN
can be produced in a laboratory by the addition of acids to cyanide
salts of alkali metals.
4.2.2. Properties
It is a colorless or pale blue, highly volatile liquid that boils
slightly above room temperature at 25.70 C. High volatility probably makes HCN difcult to use in warfare since there are problems
in achieving sufciently high concentrations outdoors. HCN has a
faint, bitter, almond-like odor.
4.2.3. Uses
HCN is a precursor to many chemical compounds ranging from
polymers to plastics. It is used in the pharmaceutical industry and
also for fumigation of ships and buildings.
4.2.4. Mechanism of human toxicity
Is same as that of CK.
4.2.5. Clinical features
The most important route of poisoning is through inhalation,
though they can be absorbed through the skin also. Signs and
symptoms are similar to those seen after exposure to CK. Lethal
concentration of HCN is 270 ppm for 68 min, 181 ppm for 10 min
and 135 ppm for 30 min.
4.2.6. Treatment
Is on the same lines as for CK.
4.3. Arsine
Arsine (arsenic hydride, arsenic trihydride, arseniuretted hydrogen, arsenous hydride, hydrogen arsenide) is the most toxic form
of arsenic. During the WWII it was extensively studied as a CWA,
but its low toxicity prevented it from being used in war. However, it still remains a potential threat of small scale terrorist
attacks and is included in the NATOs list of CWAs. Although
arsine itself has not been used as a CWA, several arsine-derived
organoarsenic compounds have been developed and used as
CWAs, including lewisite (beta-chlorovinyldichloroarsine), adamsite (diphenylaminearsine), Clark I (diphenylchlorarsine), and Clark
II (diphenylcyanoarsine).
4.3.1. Manufacture
It is prepared by the reaction of arsenic chloride (AsCl3 ) with
NaBH4 and also by reaction of Zn3 As2 with hydrogen ion.
4.3.2. Properties
The gas is colorless, almost odorless, and 2.5 times denser than
air. It is highly inammable. It is shipped as a liqueed compressed
gas. It is soluble in water (200 ml/l) and in many organic solvents
as well. This compound is generally regarded as stable.
4.3.3. Uses
Arsine may be released in metal rening processes. It is used
as a doping agent in microelectronics and is also used in the manufacturing of organic chemicals and lead storage batteries. It has

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applications in the semiconductor industry, and is used in the synthesis of organoarsenic compounds.

into a gas with yellowgreen color and with an irritating odor. It is


heavier than air, there by tending to accumulate in low lying areas.

4.3.4. Mechanism of human toxicity


Inhaled arsine gas causes rapid destruction of red blood cells
leading to hypoxia and renal failure. Mechanism is believed to be
nonspecic disruption of ion gradients, leading to cell membrane
instability and lysis of red blood cells (Graham et al., 1946; PullenJames and Woods, 2006).

5.1.3. Uses
Chlorine is most commonly used as a bleaching agent in the
paper and cloth industry. It is also used to make pesticides, rubber
and solvents. Amongst the household uses it is used as a disinfectant in drinking water and in the swimming pool. It is also used to
treat industrial waste and sewage.

4.3.5. Clinical features


It 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. Nonspecic symptoms like fever, chills, confusion,
dizziness, vomiting and cramping may be present. Discoloration of
conjunctivae (red, orange, brown, or brassy) and jaundice is seen.
In severe cases patient may be passing red or cola colored urine
and may develop acute renal failure or acute respiratory distress
syndrome (Pullen-James and Woods, 2006).

5.1.4. Mechanism of human toxicity


When chlorine gas comes into contact with moist tissues such
as the eyes, throat, and lungs, hydrochloric and hypochlorous acid
is produced. Hypochlorous acid degenerates into hydrochloric acid
and nascent oxygen. Both hydrochloric acid and nascent oxygen
damages the lung tissue resulting in an inammatory response that
damages the alveolar-capillary membrane of the human lung. This
manifests as pulmonary edema, reduced pulmonary compliance,
and altered gas exchange.

4.3.6. Treatment
Properly protected personnel should remove the victim from
continued exposure to arsine. There is no specic antidote. Victims
should be administered high ow oxygen. Exchange transfusion
should be used in cases of severe hemolysis. Forced alkaline diuresis may prevent development of renal failure. In patients with
established renal failure, hemodialysis should be instituted (PullenJames and Woods, 2006).
5. Choking/pulmonary damaging agents

5.1.5. Clinical features


These 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 blisters
on the skin similar to frostbite. Breathlessness and acute lung injury
(ARDS) occurs within 24 h of exposure (Da and Blanc, 1993).
5.1.6. Treatment
Removing the causalities from the site by well protected personnel. There is no specic antidote. Measures include removal of
all clothing and providing supportive medical care.

Lung toxicants are the general class of gases that are toxic to the
human lung when inhaled, resulting in an inammatory response.
This manifests as pulmonary edema, reduced pulmonary compliance and altered gas exchange. The CWAs under this category
include chlorine, chloropicrin (PS), phosgene (CG) and diphosgenenitrogen oxides.

5.2. Chloropicrin (PS)

5.1. Chlorine (Cl)

5.2.1. Manufacture
PS is prepared by the reaction of picric acid with calcium
hypochlorite or by the addition of nitrogen to chlorinated hydrocarbons or by chlorinating nitromethane.

Chlorine in gaseous form is poisonous. Chlorine was discovered


in 1774 by the Swedish chemist Carl Wilhelm Scheele. Chlorine was
given its current name in 1810. Faced with a shortage of ammunition, Germany used chlorine as a CWA during WWI without much
success, but this opened the path for large scale manufacture of
CWAs both by Germany and the allies. However at present it a
common chemical agent of considerable commercial use.
5.1.1. Manufacture
It can be manufactured by a number of processes. Deacon process involves the direct oxidation of hydrogen chloride with oxygen
or air at 400 C to form chlorine using CuCl2 as a catalyst. Due
to the extremely corrosive reaction mixture, industrial use of this
method was difcult. Chlorine is now manufactured by electrolysis
of a sodium chloride solution (brine). The production of chlorine
results in the byproducts caustic soda (sodium hydroxide, NaOH)
and hydrogen gas (H2 ). These two products, as well as chlorine are
highly reactive. There are three industrial methods for the extraction of chlorine by electrolysis namely mercury cell electrolysis,
diaphragm cell electrolysis and membrane cell electrolysis.
5.1.2. Properties
Chlorine gas is pressurized and cooled so that it can be stored
in the liquid form. When liquid chlorine is released, it quickly turns

PS vapor is highly poisonous when inhaled. It was used in WWI


as a CWA with different names. It was called PS by the British, Aquinite by the French, and Klop (green cross) by the Germans. After
WWII, its use as CWA is obsolete.

5.2.2. Properties
Chloropicrin (tri-chloro(nitro)methane) is chemically CCl3 NO2 .
It is an oily, colorless and a faintly yellow liquid which decomposes
at 112 C to yield phosgene and nitrosyl chloride. It is more toxic
than chlorine but less than phosgene.
5.2.3. Uses
Industrial 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 and
seed.
5.2.4. Mechanism of human toxicity
Is the same as that of chlorine.
5.2.5. Clinical features
Three periods of trichlornitromethane intoxication have been
described which are irritation, latent (average 25 h) and development of pulmonary edema (Asauliuk, 1990). However if inhaled in
high concentrations, the latent period may not be present. Some
authors have also described low grade rhabdomyolysis associated

S. Chauhan et al. / Environmental Toxicology and Pharmacology 26 (2008) 113122

with its inhalation (Prudhomme et al., 1999). Because of its relative


inertness and the small size of its molecule, chloropicrin penetrates
gas mask lters causing vomiting. This makes the victim remove
the gas mask. For this reason, it is often mixed with other chemical
weapons.
5.2.6. Treatment
Is along the same lines as following exposure to chlorine.
5.3. Phosgene (CG)
CG was rst synthesized by Davy in 1812. It was developed into
a CWA by Haber. Since it was more lethal than chlorine, it was used
by Germany in 1915 during WWI resulting in 1069 casualties and
120 deaths. Subsequently allied forces also used it. It accounted for
85% of war causalities during WWI. Besides being a CWA, CG has
extensive industrial uses. Nearly 1 ton is produced annually by the
US alone.
5.3.1. Manufacture
CG is not a natural compound. It is manufactured industrially by
passing puried carbon monoxide and chlorine gas through a bed
of catalyst (porous carbon) at temperatures between 50 and 150 C.
Above 200 C, phosgene decomposes back into carbon monoxide
and chlorine. Also chloroform upon ultraviolet radiation in the presence of oxygen slowly converts into phosgene via a radical reaction.
It is also produced as a byproduct during thermal decomposition
of chlorinated hydrocarbons.

121

6. Behavioural agents/incapacitating agents


Following WWII, the US military investigated a wide range
of possible nonlethal, psychobehavioural chemical incapacitating agents. These included lysergic acid diethylamide (LSD-25),
ketamine, fentanyl, carfentanil and several glycolate anticholinergics. The only agent classied as CWA is 3-quinuclidinyl benzilate,
an anticholinergic compound. It is codenamed as BZ by NATO. It
is alleged that BZ was stockpiled by Iraq in large quantities, code
named Agent 15. It is also believed that BZ was the chemical warfare agent used to subdue terrorists in Moscow on 26 October 2002,
though the exact nature of the gas still remains unknown. It is
estimated that out of 127 deaths, BZ was responsible for 123 deaths.
6.1. Manufacture
It is manufactured by reacting methyl benzilate with 3quinuclidinol in an inert anhydrous aliphatic hydrocarbon solvent
in the presence of 715 mol% of metallic sodium based on the
methyl benzilate.
6.2. Properties
BZ is odorless gas. It can persist for three to four weeks in moist
air. It is extremely persistent in soil and water and on most surfaces.
6.3. Uses
There are no known uses except as CWA.

5.3.2. Properties
It is stored as a liquid under low temperatures and pressures
with a boiling point of 8.2 C. Therefore at room temperatures CG is
a poisonous gas. It forms a colorless or a white to pale yellow cloud
with a pleasant odor of newly mown hay but at higher concentrations it gives an offensive odor. It is 3.5 times heavier than air and
tends to accumulate in low lying areas.
5.3.3. Uses
Since WWII, CG has found extensive industrial uses. It is widely
used in chemical industries such as pharmaceuticals, dyes, pesticides and polyurethane for foam rubber products.
5.3.4. Mechanism of human toxicity
Is same as that of chlorine.
5.3.5. Clinical features
Following exposure, coughing, burning sensation in the throat
and eyes, choking and breathlessness develops. This is followed by
a symptom free period which varies from 2 to 48 h followed by
acute lung injury (Nelson, 2002). Acute lung injury is precipitated
by exercise as was frequently reported in the WWI. In persons who
remain asymptomatic and whose lungs appear clear on chest lms
obtained 8 h after exposure acute lung injury is unlikely to develop.
5.3.6. Treatment
Removing the casualties from the site by well protected personnel. Removal of clothing and liberal bath in soap water helps to
decontaminate. Exposure to CG may cause acute lung injury as late
as 48 h. There is no antidote. Treatment is symptomatic and supportive. The role of steroids is not proven (Diller, 1985). Exposed
people should be observed for up to 48 h. If the patient survives for
more than 48 h, the prognosis is excellent (Evison et al., 2002). In
experimental studies, N-acetylcysteine and Ibuprofen has shown
promising results in phosgene induced lung injury.

6.4. Mechanism of human toxicity


BZ is a competitive inhibitor of the neurotransmitter acetylcholine. The organs primarily affected are those innervated by
parasympathetic nerves. These include the central nervous system,
eye, heart, respiratory system, skin, gastrointestinal tract, and urinary bladder. Sweat glands though innervated by the sympathetic
nervous system, are also affected.
6.5. Clinical features
The LCt50 is estimated to be around 380040,000 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 near
vision), increase in heart rate, nausea, vomiting, ushing, dryness
of skin, mouth and throat, urinary retention and hyperthermia.
The clinical course is divided into four phases:
Phase 1: (04 h after exposure), characterized by parasympathetic
blockade and mild CNS effects
Phase 2: (420 h after exposure), characterized by stupor with
ataxia and hyperthermia
Phase 3: (2096 h after exposure), in which overt delirium is seen
but often uctuates from moment to moment.
Phase 4: characterized by paranoia, deep sleep, reawakening,
crawling or climbing automatisms, and eventual reorientation
6.6. Treatment
No specic antidote has been found to reverse the action of QNB
denitively. Physostigmine, a cholinergic agent, has not been found
to be very efcacious in BZ poisoning. Supportive care remains the

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best therapy. However, if the exposed patient is markedly agitated,


benzodiazepines can be administered.
7. Detection of CWAs
As a countermeasure against CWA use, detection and identication are very important. The detection of CWAs can be difcult
as they are frequently rapidly degraded and hence difcult to
detect. It may be useful to look for their metabolites and degradation products. Any system developed should be accurate with
low false positive and negative alarms, especially in the context of
a complex battleeld environment. Detection equipment such as
gas detection tubes and ion mobility spectrometers are used for
on-site detection. Common techniques used for detection include
atmospheric pressure and chemical ionization (APCI) and ame
photometric detection. There are several commercially available
alarm 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 population and environmental, legal and political factors. Previously
the most common disposal methods for CWAs were land burial,
sea dumping, detonation and open-pit burning. All these methods
posed great threat to the environment as well as to the health of
unsuspecting population residing in the vicinity. At present, two
technologies are adopted for destroying CWAs: incineration and
chemical degradation. Under the incineration process, CWAs are
taken to the demilitarization facility, where the chemical agent
is removed from the munitions or bulk containers by automated
equipment. This puts the workers at the demilitarization plant at
a very low risk of exposure. Chemical degradation is done using
chemicals, namely alkalis and oxidants, which reduce and often
negate the toxicity of chemical agents.
9. Conclusion
The use of CWAs still remains a potential threat despite the
CWC prohibiting their use. They are relatively easy to manufacture
with a potential to cause signicant morbidity and mortality. These
agents can, and have been effectively used in warfare in small scale
operations and terrorist attacks. Knowledge about these agents is
very important to plan a response in an emergency. If timely protective action is taken and exposed persons treated immediately,
the mortality and morbidity can be considerably reduced. International treaties such as the CWC should help to control proliferation
of chemical weapons along with the safe destruction of existing
ones.
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