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

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• The rate of penetration during this steady period was measured. The units used were "µg penetrating per min per mg of the dose of VX applied to the skin (µg/min/mg)". In effect, the units measured the percentage of the dose applied which penetrated during each minute the VX was left on the skin. • The rate of penetration through resected human skin was found to be 0.3 µg/min/mg. Penetration rates through resected back skin from a rabbit and through the back skin of an "intact" rabbit were found to be similar. From this it was concluded that VX would penetrate through the skin of man at a rate of 0.3 µg/min/mg. This rate of penetration was applied to derive LD50 estimates for man. Clearly, a specific amount of VX had to be absorbed before a man would be killed. If that amount was known it would be possible to find out, using the penetration rate, how long a dose of liquid VX had to be left on the skin for that amount to penetrate. The report of this work assumed that the absorbed amount to cause death was 15 µg/kg for man. For a man of an average weight of 70 kg, this is 1.05 mg. This figure appears to have come from US studies which administered VX by IV injection, from which the IV LD50 for man was estimated as 0.5 - 1 mg per man [28]. Using this amount, the study estimated LD50 for VX on skin: • a dose of 4 mg of liquid VX on skin would kill if left for about 15 hours (equivalently, LD50 for 15 hour death in man is 4 mg); • death would result earlier if a larger dose were used 10 - a dose of 40 mg of liquid VX applied to skin would kill if left for about 2 hours. Clearly then, LD50 varies according to the dose and the amount of time that dose is left on the skin. One consequence of this variation is that any estimate of LD50 for liquid VX on skin should cite how long it is assumed the dose is left on the skin. Very rarely in documents which mention VX was this time given: one exception appears in the next section. In 1959, the LD50 of VX was assumed to be 15 mg/man, although it "may be as high as 25 mg per man" [29]. The variation may be due, in part, to different assumptions about how long the liquid VX dose would remain on the skin. 10.2.2. Studies with volunteer medical officers Two studies were conducted with liquid VX in which volunteers from the Porton medical staff took part: one with VX applied to the bare skin and the other with VX applied onto clothing laid over the bare skin. In 1958 two volunteer medical officers each had a drop of 50 µg of radioactively tagged VX applied to their left forearm so that the rate of penetration of VX could be studied [30]. The drop was left on the skin for 30 minutes, during which time a Geiger counter was used to measure the rate of penetration. After 30 minutes the skin was swabbed, and then resected "down to the muscle". ChE was measured before exposure and at various times after the skin had been resected. The main results were that [30, 31]: • the penetration rate observed was about the same as predicted from the study with animals and resected human skin; • no depression of RBC, plasma or whole blood ChE was observed, although the BC in reviewing the work suggested that measurements should have been taken more frequently and the amount of VX secreted in urine should also be measured. 10 Recall that the penetration rate is expressed as a percentage of the dose applied which is absorbed every minute. So increasing the dose applied increases the amount absorbed every minute. 98
The second study with volunteer medical officers, to assess the penetration of VX through clothing, was carried out in 1960 [32] and had two parts: • three trials were conducted in which clothing contaminated with liquid VX was worn for periods of 4, 6 and 8 hours; • after "careful consideration of these experiments", two more trials were conducted with contaminated clothing left in place for 24 hours. Each of the five trials used 200 mg, which was then agreed as the LD50 dose for clothed man if the dose was left in place for 24 hours. [The second part of the experiment, therefore, exposed volunteer medical officers to the accepted LD50 dose: 200 mg on clothing left in place for 24 hours.] The clothing used was an outer layer of battledress serge over an inner layer of flannel shirting. VX drops of 1 - 2 mg were applied on this assembly over an area of about 160 cm 2 . The main results from this work were as follows [32, 33]. • In the first three trials no depression of ChE was observed, even after the trial in which the clothing was left in place for 8 hours. • In the 24 hour trials, ChE did not begin to fall until 14 hours into the experiment, and minimum levels of ChE occurred 24 hours after the contaminated clothing was removed. In one subject the maximum ChE depression was 74%, in the other 36%. • Plasma ChE was affected less than RBC ChE, recovering more quickly and to within 90% of normal by one week after the experiment; • The accepted 24 hour LD50 estimate of 200 mg was agreed [33] to be far too low, although that dose seemed to inhibit ChE by about 50% [32]. Animal experiments had suggested that the lethal dose was four times the dose which inhibited ChE by 50%. The 24 hour LD50 estimate was suggested to be 800 mg. 10.2.3. Studies with Service volunteers Studies of the penetration of liquid VX through skin were conducted with Service volunteers in November 1960 [34]. The report of this work was published in 1963 [35]. Drops of radioactively-tagged VX were placed on the skin in one of three locations: the back, the forearm, or the palm of the hand. The chosen area, excepting the palm, was shaved with an electric razor and a ring was attached to the skin. The rings used on the forearm and the palm were made of polythene with an internal diameter of 2.5 cm; those on the back were made of brass measuring 7 cm in diameter. VX was placed on the skin inside the ring in drops of 2 - 4 µg. Nylon film was stuck over the top of the ring. The assembly and VX were left in place for 6-10 hours, during which time a Geiger counter was used to take measurements. The assembly was then removed and the skin decontaminated, first by stripping with adhesive tape and then by washing with isopropanol and soapy water. The details of the exposures are given in Table 10.1. According to the volunteer records [34], 16 men took part in this study. No details are given of how the exposures shown in Table 10.1 were divided between these men. 99
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Page 7 and 8: Fifteen of the sixteen men were exp
Page 9 and 10: the nature of the smell differed fr
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