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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.
Literature:
1. Abu-Qare AW, Abou-Donia MB. Sarin: health effects, metabolism,
and methods of analysis. Food Chem Toxicol 2002;40:1327-33.
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;17:34-7.
3.
Stewart WC. The effects of sarin and atropine on the respiratory
center and neuromuscular junctions of the rat. Can J Biochem
Physiol 1959;37:651-60.
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;38:1035-43.
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;66:176-84.
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;21:182-95.
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;24:475-83.
10. Bide
RW, Risk
DJ. Inhalation toxicity in mice exposed to sarin (GB) for
20-720 min. J Appl Toxicol 2004;24:459-67.
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;94:139-43.
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;109:1169-73.
14. Murayama
S. Peripheral nerve disorders—clinical pathological
approaches. Rinsho Shinkeigaku 1997;37:1103-4.
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;244:601-6.
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