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Part III - Historical Survey of the Porton Down Service Volunteer ...

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GB drops on bare skin (mg) No. <strong>of</strong> volunteers<br />

0.5 5<br />

1 4<br />

2 4<br />

4 4<br />

8 4<br />

10 3<br />

15 8<br />

20 3<br />

25 2<br />

30 1<br />

40 6<br />

Table 8.5. GB doses used in October/November 1951<br />

The degree <strong>of</strong> ChE inhibition varied considerably between <strong>the</strong> individuals participating in this<br />

study, which prompted <strong>the</strong> next human study that sought to understand better <strong>the</strong> factors<br />

affecting <strong>the</strong> penetration <strong>of</strong> liquid GB through skin [67]. The report <strong>of</strong> <strong>the</strong> study was published<br />

in 1954 [67] but entries in <strong>the</strong> experimental records show that <strong>the</strong> exposures were carried out<br />

in late 1951 and in 1952 [48, 65]. In this study <strong>the</strong> liquid GB placed on <strong>the</strong> arms <strong>of</strong> volunteers<br />

was tagged so that it could be tracked. Some liquid GB was dyed and its activity on <strong>the</strong> skin<br />

watched under magnification. O<strong>the</strong>r drops were tagged with radioactive phosphorus<br />

(called 32 P) and <strong>the</strong> activity <strong>of</strong> <strong>the</strong> GB was tracked with a Geiger counter. The degree <strong>of</strong><br />

radioactivity could be controlled. Thirty five volunteers took part in this study [67].<br />

• Twenty men received a 2 mg drop <strong>of</strong> GB on each forearm. The drop on one <strong>of</strong><br />

<strong>the</strong> forearms was covered in nylon film to prevent <strong>the</strong> GB evaporating. The arm<br />

with <strong>the</strong> uncovered drop was held still inside a fume cupboard.<br />

• Fifteen men had a drop <strong>of</strong> GB placed on <strong>the</strong>ir arm, and in each case <strong>the</strong> drop<br />

was covered by nylon film. Five men received a 0.6 mg drop; five a 2 mg drop<br />

and five a 3.5 mg drop.<br />

The GB drops were monitored to find out how long it took <strong>the</strong>m to clear <strong>the</strong> skin ei<strong>the</strong>r from<br />

penetration or evaporation. Similar investigations were conducted with rabbits. The main<br />

conclusion <strong>of</strong> <strong>the</strong> work [67] was that <strong>the</strong> fat in skin (sometimes referred to as "lipid") played<br />

some part in <strong>the</strong> penetration <strong>of</strong> GB and might absorb GB to prevent its penetrating fur<strong>the</strong>r<br />

through <strong>the</strong> skin to <strong>the</strong> blood capillaries beneath.<br />

The study was extended to explore <strong>the</strong> influence <strong>of</strong> skin fat on liquid GB penetration. Fat is<br />

present on <strong>the</strong> skin and below <strong>the</strong> skin surface. Surface skin fat was removed from clipped<br />

rabbit skin by soaking in acetone, with liquid GB <strong>the</strong>n placed on <strong>the</strong> skin. A marked<br />

difference in penetration rate was found in rabbits with surface skin fat removed, compared to<br />

<strong>the</strong> rate in rabbits with skin fat intact. The work was repeated with humans.<br />

• The amount <strong>of</strong> fat normally present on <strong>the</strong> forearm skin <strong>of</strong> man was sampled from<br />

100 men. The mean amount was found to be 81.6 µg/cm 2 .<br />

• Fourteen men took part in a study to compare <strong>the</strong> rate <strong>of</strong> penetration <strong>of</strong> liquid GB<br />

through normal skin and "de-fatted" skin. An area <strong>of</strong> <strong>the</strong> left arm was "de-fatted"<br />

by soaking with acetone to remove surface skin fat. The 14 men <strong>the</strong>n had a 2 mg<br />

drop <strong>of</strong> GB placed on each arm. The activity <strong>of</strong> <strong>the</strong> GB on each arm was<br />

monitored to compare <strong>the</strong> penetration rate through normal skin and de-fatted<br />

skin.<br />

The conclusion from this work was that <strong>the</strong> amount <strong>of</strong> surface and sub-surface skin fat affects<br />

<strong>the</strong> degree <strong>of</strong> penetration <strong>of</strong> liquid GB. The less fat that is present, <strong>the</strong> more deeply through<br />

<strong>the</strong> skin GB will penetrate and <strong>the</strong> larger <strong>the</strong> proportion that would be expected to reach <strong>the</strong><br />

72

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