Treatment for Sulphur Mustard Poisoning -A Review

K. Sugendran; Pravin Kumar; R. Vijayaraghavan

doi:10.14429/dsj.48.3894

K. Sugendran Defence Research & Development Establishment, Gwalior
Pravin Kumar Defence Research & Development Establishment, Gwalior
R. Vijayaraghavan Defence Research & Development Establishment, Gwalior

DOI: https://doi.org/10.14429/dsj.48.3894

Keywords: Antidotes, Treatment regime, Systemic toxicity, Chemical weapons, Geneva protocol, Intensive medical care

Abstract

Sulphur mustard (SM) is a chemical warfare agent of historical and current interest It is a wellknown blistering agent or vesicant SM was extensively used in world war I as a chemical weaponand has been stockpiled by several counbies since that time. SM serves as an ideal war gas and is favoured militarily for its ability to incapacitate rather than to kill. Its use resulted in large numbers ofcasualties requiring prolonged and intensive medical care. Despite Geneva Protocol of 1925, which categorically bnned the production, stockpiling and use of chemical weapons in wars, SM has beenused in several wars, including the Iran-Irnq war during the 1980s, which renewed interest in it.Though, the chemical we'dpons convention was signed by more than 160 counbies in 1993 and wassubsequently ratified by several counbies, the threat from this agent persists due to its clandestineusage during war and also by teITOrist groups. There is no effective and specific antidote for local andsystemic toxicity of SM despite scientific research for more than 75 years. Many compounds weretested as antidotes for SM, but very few of them have been shown to provide some protection. The present review is aimed at evaluating the treatment regime and other clinical measures used to treat SM victims and the various drugs and chemicals screened as antidotes for SM poisoning in experimental animals.

Author Biographies

K. Sugendran, Defence Research & Development Establishment, Gwalior

Dr K Sugendran obtained his MSc (Biochemistry) from Madras University and PhD (Biochemistry)from Jiwaji University, Gwalior. He worked at JlPMER, Pondicherry and subsequently at MadrasPort Trust Hospital in various capacities for a decade. He joined Defence Research & Development Establishment (DRDE), Gwalior, in 1987 and presently working on the development of antidoteagainst sulphur mustard intoxication. He has published 20 papers in national and international journals.

Pravin Kumar, Defence Research & Development Establishment, Gwalior

Dr Pravin Kumar obtained his MSc ( Pharmacology) from Gujarat University, Ahmedabad and PhD (Pharmacology) from Jiwaji University, Gwalior. He is presently working on inhalation toxicity studies of peripheral sensory irritants, evaluation of antidotal potential of newly synthesised WR-2721 analogs against sulphur mustard in toxication and in vitro neurotoxicity testing of chemicals using electrophysiological technique. He has published more than 25 research papers innational and international journals.

R. Vijayaraghavan, Defence Research & Development Establishment, Gwalior

Dr R Vijayaraghavan obtained his MSc (Pharinacology) from Madras University and PhD(Pharmacology) from Jiwaji University, Gwalior. He worked as Visiting Research Associate at University of Pittsburgh, USA, during 1991-93. Currently, he is Scientist E and Head, Pharmacology and Toxicology Division at the Defence Research & Development Establishment, Gwalior. His areasof research include inhalation toxicology and evaluation of antidotes against CW agents.

References

Wachtel, C. Chemical warfare. Chemical Publishing Company, Inc., New York, 1941.

Frank, S. Manual of military chemistry: Chemistry of chemical warfare agents, NTIS, Washington D.C., 1967, 108-20.

Dixon, M. & Needham, D.M. Biochemical research on chemical warfare agents. Nature,

,158,432-38.

Peters, R.A. Biochemical research at Oxford upon mustard gas. Nature, 1947,159, 149-51.

Peters, R.A. Biochernicallesion and its historical development. Brit. Med. Bull., 1969, 25, 223-33.

Somani, S.M. & Babu, sulphur mustard. Int. I. Toxicol., 1989, 27,419-35.

United Nauons Security Council. Report of the mission despatched by the Secretary General to investigate allegations of the use of chemical weapons in the conflict between the Islamic Republic of Iran and Iraq. UN. Security council, New York,1988. Report No. S-20134.

Wheeler, G.P. Studies related to the mechanism of action of cytotoxic alkylating agents. Annu Rev. Cancer. Res., 1962,22, 651-88.

Papinneister, B .;Fister, A.J.; Robinson, S.I. & Ford, R.D. Medical defense against mustard gas: Toxic mechanisms and pharmacological implications, CRC Press, Boca Ratan, 1991 p 359.

Pechura, C.M. & Rall, D.P. Veterans at risk. The health affects of mustard gas and lewisite. National Academy Press, Washington DC, 1993.

Papinneister, B.; Gross, C.L.; Meier, H.L.; Petrali, J.P. & Johnson, J.B. Molecular basis of mustard-induced vesication. Fund. Appl. Toxicol., 1985,5, 134-49.

Vijayaraghavan, R.; Sugendran, K.; Pant, S.C.; Husain, K. & Malhotra, R.C. Dennal intoxication of mice with bis (2-Chloroethyl) sulphide and the .protective effect of flavonoids. Toxicology, 1991, 69, 35-42.

Farco, P.E. The challenge of mustard gas keratopathy. Med. J. Australia, 990,152,55-56.

Sidell, F.R. & Hurst, C:G. Clinical considerations in mustard poisoning. In edited by S.M Somani Chemical warfare agents Academic Press Inc., 1992. pp. 51-66.

Vogt, R.F.; Dannenbarg, A.M.; Schofield. H.M.; Hynaes, N.A. & Papinneister, H. Pathogenesis of skin lesions caused by sulphur mustard. Fund. Appl. Toxicol., 1984, 4, 71-83.

Vijayaraghavan, R. Modifications of breathing pattern induced by inhaled sulphur mustard in mice. Archives Toxicology., 1997, 71, 157- 64.

Willems, J.L. Oinical management of mustard gas casualties. Ann. Med. Military Belgicae., 1989,3, 27-53.

Momeni, A.Z.; Enshaeih, S.; Meghdadi, M. & Amindjavaheri,M . Skin manifestationo f mustard gas, a clinical study of 535 patients exposed to mustard gas. Archives Dermatology., 1992, 128, 775-80.

Borak. J. & Sidell, F.R. Agents of chemical warfare: sulfur mustard. Ann. Emerg. Med., 1992, 2, 303-308.

Pravin Kumar; Sharma, U.S. & Vijayaraghavan, R. Study of the efficacy of CC-2 and Fuller's earth combination as a decontaminant against sulphur mustard (mustard gas) dermal intoxication in mice. Def. Sci. I., 1991, 41 ,363-66.

Reddy, P.M.K.; Dubey, D.K.; Pravin Kumar, & Vijayaraghavan, R. Evaluation of CC-2 as a decontaminant at various time intervals against topically applied sulphur mustard in mice. lnd. J. Pharmacal., 1996,28,227-31.

Wormser, U. Toxicology of mustard gas. Trends Pharmacal. Sci., 1991,12, 164-67.

Munro, N.B.; Watson, A.P.; Ambrose, K.R. & Griffin, G.D. Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning. Enviran. Health Perspect., 1990,89,205-15.

Yang, Y.C; Bam-,J A & Wad, JR Decontamination of chemical warfare agents. Chemical Reviews., 1992, 92,1729-743.

Cullumbine, H. Medical aspects of mustard gas poisoning. Nature, 1947, 4031,151-53.

Dacre, J.C. & Goldman, M. Toxicology and pharmacology of the chemical warfare agent

sulphur mustard, Pharmacal. Review., 1996, 48, 289-326.

Vojvodic, V.Z.; Milosarljevic, B.; Boskovic. & Bojamic, N. The protective effect of different drugs in rats poisoned by sulphur and nitrogen mustard. Fund. Appl. Toxicol., 1985,5,160-68.

Taylor, A.J.N. & Morris, A.J.R. Experience with mustard gas casualties, Lancet, 1991,337,42.

Sugendran, K. Biohemical and toxicological studies of bis (2-chloroethyl) sulphide, a

blistering agent in albino mice, Jiwaji University, Gwalior, 1994, PhD Thesis.

Callaway, S. & Pearce, KA. Protection against systemic poisoning by mustard gas di(2-chloroethyl) sulphide by sodium thiosulphate and thiocit in the albino rat. Brit. I.

Pharmacal., 1958,13, 395-98.

Balali-Mood, M. & Anari, M.R. Protective effects of N-acetyl cysteine and sodium thiosulphate on sulphur mustard poisoning in mice. In Proceedings of the third international symposium on protection against chemical warfare agents, Sweden, 11-16 June, 1989.

Anari, M.R.; Parasai, H. & Chamankhah, H. An investigation on protective effect of N-acetyl cysteine against acute intoxication of sulphur mustard in mice. In Proceedings of the first international medical congress on chemical warfare agents in Iran, Mashhad , 13-16 June, 1988.

Gray, p .1. A literature review on the mechanism of action of sulphur and nitrogen mustard. Defance Science & Technology Organisation (DSTO),1989. Australia. MRL-TR-89-24.

Whitfield, D. A literature review upon the toxicology mechanism of action and treatment of sulphur and nitrogen mustard poisoning. Porton Down, UK, 1987. Tech, Note No. TN-840.

Yourick, J.J.; Oark, C.R. & Mitcheltree, L.W. Niacinamide pretreatment reduces microvesicle formation. in hairless guinea pig cutaneously exposed to sulfur mustard. Fund. Appl. Toxicol., 1991,17,533-42.

Younck.. 1.1., Dawson, 1.S. & Mitchelttee, L. W. Sulphur mustard-induced icrovesication in hairless guinea pigs effects short-term niacinamide administration. Toxicol. Appl.

Pharmacol., 1992,.117, 104 -9.

Heyndrickx, A. Chemical warfare injuries. Lancet, 1991, 337, 430.

Holiday, E.R.J.; Philpot, L. & Stacken, L.A. Sodium ethanemonothiophosphonate, a weak

antidote to mustard gas. Biochemical Journal, 1950, 47, 632-39.

Sugendran, K; Jeevaratnam, K.; Vijayaraghavan, R. & Das Gupta, S. Therapeutic efficacy of saline and glucose saline against denllally applied sulphur mustard intoxication in mice. Def Sci. I., 1994,44, 21-23.

Treatment for Sulphur Mustard Poisoning -A Review

Abstract

Author Biographies

References

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