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The Physicians Committee



Beyond Animal Research

By Jonathan Balcombe, Ph.D.
September 2005

Sarin: Terror in the Laboratories

Originally developed as a chemical warfare agent in 1938, the nerve gas sarin became a household word when it was used in a terrorist attack on the Tokyo subway system in March 1995 (one of three such incidents in Japan between 1994 and 1998). Long-term health effects on Gulf War veterans have also been attributed to possible low-level sarin exposure.1

Despite the pitfalls of trying to extrapolate across species, animals have been exposed to sarin in hundreds of laboratory experiments dating back at least to the late 1950s.2,3,4

A half-century on, there’s no sign of abatement. A few current examples:

  • In a U.S. Army study, researchers exposed groups of male and female rats to sarin vapor at various concentrations and durations ranging from five to 360 minutes to develop dose-response models and lethality concentrations.5
  • At the same facility, rats were forced to inhale sarin vapor for one hour on three successive days to study its effects on miosis (pupilary dilation).6
  • At the Israel Institute for Biological Research, more than one-third of rats died within 24 hours of a 10-minute exposure, and surviving rats (52 percent at six months) showed agitation, aggression, weight loss, and sporadic convulsions.7
  • At the same facility, restrained guinea pigs were exposed to sarin and then injected with three potential antidotes. Surviving animals had their lungs rinsed to assess inflammation.8
  • Dutch investigators exposed marmoset monkeys to sarin vapor to estimate lowest observable adverse effect levels on electroencephalograms (EEG).9
  • As part of an ongoing effort by the Canadian military to establish toxicity estimates for humans, mice were exposed to various levels of sarin for between 20 minutes and 12 hours until half of them died.10
  • At a military academy in Czechoslovakia, inbred mice were exposed for 60 minutes to study sarin’s effects on immune function.11

A 2003 report by an expert group convened by the British Department of Health concluded that rodent studies of nerve agents are “difficult to interpret” and “have little relevance” to the management of human poisonings.12 Such tests are also particularly cruel because the animals are given no pain relief or anesthesia for fear it would interfere with the results. Despite these glaring drawbacks, the tests go on, decade after decade.

The only reliable data on the effects and treatment of sarin exposure in humans comes from human clinical studies. The clinical manifestations of acute sarin poisoning have been reported in detail from terrorist incidents, as well as from wartime and industrial exposures.1,13,14,15

Understandably, there are clear ethical problems with deliberate exposure of healthy volunteers in the attempt to find prophylactic drugs; however, it’s equally clear that the effort to find prophylactic drugs will not be advanced by useless animal studies.

Jonathan Balcombe, Ph.D., is a PCRM research consultant with a background in ethology. He is the author of The Use of Animals in Higher Education, as well as many scientific papers on humane life science education and animal behavior. His recent scientific review showing that animal experiments are more stressful than previously understood was published in Contemporary Topics in Laboratory Animal Science.

Resources
1. Abu-Qare AW, Abou-Donia MB. Sarin: health effects, metabolism, and methods of analysis. Food Chem Toxicol. 2002;40:1327-1333.
2. Punte CL, Owens EJ, Krackow EH, Cooper PL. Influence of physical activity on the toxicity of aerosols and vapors; inhalation toxicity of paraoxon and sarin in rats. AMA Arch Ind Health. 1958;17:34-37.
3. Stewart WC. The effects of sarin and atropine on the respiratory center and neuromuscular junctions of the rat. Can J Biochem Physiol. 1959;37:651-660.
4. Coleman IW, Little PE, Grant GA. Oxime mixtures and atropine in the protection of mice and rats from sarin poisoning. Can J Biochem Physiol. 1960;38:1035-1043.
5. Mioduszewski R, Manthei J, Way R, Burnett D, Gaviola B, Muse W, Thomson S, Sommerville D, Crosier R. Interaction of exposure concentration and duration in determining acute toxic effects of sarin vapor in rats. Toxicol Sci. 2002;66:176-184.
6. Dabisch PA, Burnett DC, Miller DB, Jakubowski EM, Muse WT, Forster JS, Scotto JA, Jarvis JR, Davis EA, Hulet SW, Reutter SA, Mioduszewski RJ, Thomson SA. Tolerance to the miotic effect of sarin vapor in rats after multiple low-level exposures. J Ocul Pharmacol Ther. 2005;21:182-195.
7. Allon N, Rabinovitz I, Manistersky E, Weissman BA, Grauer E. Acute and Long Lasting Cardiac Changes Following a Single Whole Body Exposure to Sarin Vapor in Rats. Toxicol Sci. 2005 [Epub ahead of print].
8. Levy A, Chapman S, Cohen G, Raveh L, Rabinovitz I, Manistersky E, Kapon Y, Allon N, Gilat E. Protection and inflammatory markers following exposure of guinea pigs to sarin vapour: comparative efficacy of three oximes. J Appl Toxicol. 2004;24:501-4.
9. van Helden HP, Vanwersch RA, Kuijpers WC, Trap HC, Philippens IH, Benschop HP. Low levels of sarin affect the EEG in marmoset monkeys: a pilot study. J Appl Toxicol. 2004;24:475-483.
10. Bide RW, Risk DJ. Inhalation toxicity in mice exposed to sarin (GB) for 20-720 min. J Appl Toxicol. 2004;24:459-467.
11. Kassa J, Krocova Z, Sevelova L, Sheshko V, Kasalova I, Neubauerova V. The influence of single or repeated low-level sarin exposure on immune functions of inbred BALB/c mice. Basic Clin Pharmacol Toxicol. 2004;94:139-143.
12. Blain PG. 2003. Treatment of poisoning by selected chemical compounds. [cited 8 August 2005] Available from: http://www.dh.gov.uk/assetRoot/04/07/33/41/04073341.pdf
13. Nishiwaki Y, Maekawa K, Ogawa Y, Asukai N, Minami M, Omae K. Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack. Environ Health Perspect. 2001;109:1169-1173.
14. Murayama S. Peripheral nerve disorders—clinical pathological approaches. Rinsho Shinkeigaku. 1997;37:1103-1104.
15. Murata K, Araki S, Yokoyama K, Okumura T, Ishimatsu S, Takasu N, White RF. Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack. J Neurol. 1997;244:601-606.

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