Acute response to Sarin in veterans tested at Porton Down

 

AcknowledgementsFunding: Medical Research Council (G0200288, funds from the UK Ministry of Defence.  We thank the Ministry of Defence Veterans Policy Unit; 

Defence Science and Technology Laboratory, Porton Down; Porton Down Veterans Support Group

Thomas Keegan1, Claire Brooks2, Toby Langdon2, Sue Walker3, Lucy Carpenter2, Katherine Venables31Lancaster University LA1 4YD

2Department of Public Health, University of Oxford, Oxford OX3 7LF3Dstl Porton Down, Salisbury, SP4 0JQ

ISEE conference Dublin 2009

Background Porton Down is the UK’s centre for research into chemical defence. Up to 30,000 servicemen have been involved in tests at Porton Down since WWI. Mortality and cancer incidence has been examined in over 18,000 Porton Down veterans who took part in tests between 1941 and 1989 (BMJ 2009). Here we draw on data from that cohort to describe exposures to the nerve agent sarin and measures of associated acute biological effect.

Methods Data on chemical and non-chemical exposures were manually abstracted from the Porton Down historical archive. For every test, the name of the chemical(s) and date of test were abstracted. For nerve agents and vesicants, additional data were abstracted: exposure intensity, duration, route, presence of exposure modifiers. Maximum change in cholinesterase (ChE) was calculated. Data on pupil size change was also abstracted.

Results Nerve agent tests took place between 1945 and 1987, when 3597 veterans were involved in 4299 tests. The most commonly tested nerve agent was sarin (2980 veterans; 3511 tests). Most sarin tests were by inhalation (85%) with 8% dermal and 3% ocular. Over half of sarin tests (53%) were unprotected.  Data on change in ChE were available for 712 inhalation and 273 dermal tests. For unprotected inhalation, median percentage RBC ChE activity decreased with increasing sarin exposure (Ct = concentration x time): for sarin Ct <5 mg.min/m3, median ∆ RBC ChE was -25%; for Ct >10 mg.min/m3, median ∆ RBC ChE was -56%). For tests with chemical protection median RBC ChE activity also decreased with increasing sarin exposure. Change in pupil size was available for 744 sarin tests.

Conclusions Sarin was the nerve agent most frequently tested on veterans at Porton Down. Availability of data on exposure intensity and acute effect has allowed quantitative assessment of the effect on exposure of physical and chemical modifiers.

Table 2 (below) Number sarin tests by exposure route and nerve agent type. Porton Down 1945-1989.

Table 2 (below) Percentage change in red blood cell cholinesterase activity after inhalation exposure to sarin, by protection status. Table shows tests for which data on both Ct and change in ChE were available.

Table 1 (below) Number of human nerve agent tests at Porton Down, by nerve agent type and decade.

Unprotected Protected - chemical Protected - physical Protected - both All

n Med IQR Range n Med IQR Range n Med IQR Range n Med IQRRang

e n Med IQRRang

e

0-<5 25 12 8-15.93-

18.75 2 n/a n/a34.1-58.9 0 0 0 27 12 8-16.9 3-59

5<10 68 2516.4-32.4 -.09-72 31 30 16-46 -11-73 2 n/a n/a

-1.2-1.7 0 101 26 16-33 -11-73

10+ 272 45 35-53.3 5-68 295 49 41-55 -6-71 15 47 3-52 0-55 2 n/a n/a 40-54 584 48 39-54 -6-71

All 365 40 27-51 -.09-72 328 49 40-55 -6-58.9 17 46 1.7-49 2 n/a n/a 40-54 712 45 32-53 3-71

  Decade of test  

Nerve agents 1940s 1950s 1960s 1970s 1980s Total

GB Sarin 173 2,573 372 278 115 3,511

GA Tabun 197 201 0 0 0 398

GD Soman 0 142 7 0 0 149

GE 4 21 0 0 0 25

GF Cyclosarin 0 83 84 0 0 167

VX 0 0 49 0 0 49

Total 374 3,020 512 278 115 4,299

Chemical category

Total chemical tests

by group

Exposure route

Dermal

Inhalation and other

routes OcularNot

recorded

  n n % n % n % n %

Sarin (GB) 3,51128

8 8.2 2,972 84.611

0 3.1 141 4.0

Tabun (GA) 398 19 4.8 338 84.9 0 0.0 41 10.3

Soman (GD) 149 51 34.2 91 61.1 0 0.0 7 4.7

GE 25 0 0.0 25 100.0 0 0.0 0 0.0

GF 167 33 19.8 110 65.9 0 0.0 24 14.4

VX 49 16 32.7 0 0.0 33 67.3 0 0.0

Total 4,299 407 9.5 3,536 82.3 143 3.3 213 5.0