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

More documents

Recommendations

Info

G Agent Exposure Range mg.min/m 3 GA 1.8 - 9 GD 1 - 5.1 6.6 - 10.1* GE 5 - 14 GF 2.25 - 14 * Men exposed to these levels wore oro-nasal respirators. Table 8.1. Agents other than GB in "Aggressiveness study" The GB work in the aggressiveness study was split into two [43]. The first part involved exposures of 1.4 to 13.9 mg.min/m 3 and involved 48 men. Most of the men were exposed without protection, while some wore oro-nasal respirators to prevent inhalation. The second part considered only the eye effects of GB vapour. Fifty seven men wearing oro-nasal respirators were exposed to 7.3 - 36.7 mg.min/m 3 . The important result of the second part of the study with GB was that the effects induced showed little variation over 14-36.7 mg.min/m 3 , suggesting that the lowest point in this range was sufficient to inhibit completely local ChE in the eye. Together with results from the first part of the GB study and the earlier 1949 study, the conclusions drawn were that [27, 43]: • the threshold dose for inducing miosis by GB vapour was 1.4 - 4.5 mg.min/m 3 ; • GB vapour at 6.5 -11.5 mg.min/m 3 would harass, but not cause casualties; • larger doses would not induce greater effects on the eye and, therefore, that casualties would not arise solely from eye effects. The first part of the GB element of the aggressiveness study produced an important indication about the maximum safe vapour dose. Three men were exposed with no protection to a GB vapour at 13.9 mg.min/m 3 (t = 1.5 mins). All three suffered severe eye symptoms, and also suffered persistent tightness of the chest, with nausea and vomiting (these symptoms were deemed be early signs of systemic poisoning): • One of the three men, aged 37, was confined to bed under supervision. Red Blood Cell (RBC) and plasma ChE measurements were taken and compared to normal values for the general population. The comparison showed a "marked ChE inhibition". The minimum level of RBC ChE, six days after exposure, was 60 Warburg units 3 compared to a normal lower limit of 90 Warburg units. • RBC ChE was measured in the other two men exposed to this dose. The minimum levels in these two cases were 71 units and 74 units. The conclusion drawn in the report on these experiments was that a GB vapour dose of "14 mg.min/m 3 may be near to the maximum which men, even breathing quietly, may be safely exposed to without protection" [43]. The results of the first part of the work were available for the report published in August 1950 [27], which noted that a marked fall in ChE levels was observed at 13.9 mg.min/m 3 and concluded that GB vapour at 15 mg.min/m 3 cannot "be far removed from the lower limit of the zone of incapacitation" [27]. 8.4.4. Lethal dose estimation The possibility of linking blood ChE inhibition and symptoms raised by this research suggested further work to link the degree of ChE inhibition and the GB vapour dose inhaled. 3 As explained in Annex C, ChE was measured by various methods. The units used cited the method: here, the Warburg method was used. Further references to ChE will include merely "units". 66
Scientists hoped that, from these studies, it might be possible to associate different levels of ChE inhibition with threshold, harassment and casualty doses, and thereby estimate the lethal doses for man. Exploring this possibility demanded that the dose inhaled by a man be measured precisely. Exposing a group of men to a given concentration of vapour for a certain amount of time in the chamber was inadequate as the precise dose to which each man was subjected was not accurately measured. That dose depended on the rate at which a man breathed and on the amount of the vapour inhaled that was retained (i.e. not breathed out). A study was carried out in 1951 to find out how much of GB vapour inhaled by a man was retained [49]. Eight men participated. Two features of this study were new: • an oro-nasal respirator was modified, and the men inhaled GB vapour through the nose and exhaled through the mouth into a mechanism that sampled the exhaled air; • the vapour inhaled was not measured as a product of concentration and time, but as a precise amount of GB, measured in micrograms (µg). Doses of 107-113 µg were given. (Annex D contains a comparison of this new method of measuring a vapour dose with the method of measuring concentration and time). The study concluded that men retained 96% of the dose inhaled through the nose. US work [50] suggested that men retained 85% of a dose inhaled through the mouth. The new apparatus for inhaling vapour used in this study was modified for later work. It was adapted so that a measured dose could be inhaled in a single breath. This new and more precise technique for exposing men to GB vapour was used in 1952 in an attempt to link RBC ChE inhibition to dose [51]. This study, in which 105 men participated, used doses equivalent to vapour exposures of 2 to about 20 mg.min/m 3 . ChE was measured before and after exposure. The study therefore produced the average RBC ChE depressions at particular doses within this range. The variation in the individual (as opposed to average) ChE depressions was quite wide. It was concluded that the lethal dose of GB vapour could not be reliably predicted by extrapolating from the ChE depressions observed after exposure to sub-lethal doses. However, it was noted that more studies might allow a more reliable prediction to be made. Further work examining the importance of ChE depression was already being considered in 1951 as a possible technique for estimating the lethal dose of GB vapour to man [52]. The building blocks of the technique were as follows: a. Work with animals exposed to various GB vapour doses (up to the lethal dose) had shown that it was possible to represent "reasonably accurately" with a straight line the relationship between dose (measured in µg/Kg) and the logarithm (just another way of measuring) of percentage ChE inhibition. b. Human studies with sub-lethal doses of GB vapour suggested that a similar linear relationship between dose and ChE inhibition was reasonable. c. If it was then assumed that 90% ChE inhibition equates to the lethal dose, and the report notes that from animal work "this does not seem unreasonable" [52], then the linear relationship between dose and ChE inhibition in man can be extrapolated to derive an estimate of the lethal dose to man. The report concluded that it seemed possible to predict the lethal dose of GB vapour to man by this method. The preliminary prediction produced by the report [52] based on previous human studies was a L(Ct)50 of 112 mg.min/m 3 , with a range of 80-200 mg.min/m 3 . The fundamental idea, that lethal doses could be estimated from the ChE inhibition induced by exposure to low doses, was pursued in later work. 67
Page 1 and 2: Part III. Human studies with nerve
Page 3 and 4: 8.1. Discovery of the "Ideal War Ga
Page 5 and 6: Bren gun), map reading and visual i
Page 7 and 8: Fifteen of the sixteen men were exp
Page 9: the nature of the smell differed fr
Page 13 and 14: • even though the vapour exposure
Page 15 and 16: G Agent Bare skin Clothed skin GB 4
Page 17 and 18: lood supply. Nine of the 14 men who
Page 19 and 20: • After the incident the man's su
Page 21 and 22: 9.1 Adrian Committee Chapter 9. G A
Page 23 and 24: Service volunteers took part in stu
Page 25 and 26: Animal work in 1958 suggested that
Page 27 and 28: induced by the inhibition of ChE in
Page 29 and 30: • the GB dose to halve the pupil
Page 31 and 32: GB exposure (mg.min/m 3 ) Number of
Page 33 and 34: Animal work continued at Porton. In
Page 35 and 36: ing which is attached to the lens o
Page 37 and 38: • "the main problems, as far as v
Page 39 and 40: 10.1. Background 10.1.1. The nature
Page 41 and 42: Porton Medical Officers Service Vol
Page 43 and 44: The second study with volunteer med
Page 45 and 46: Condition Respiratory protection? L
Page 47 and 48: References Chapter 8 1. WO32/21200
Page 49 and 50: 43. COSHE 17 th meet 24 Sep 65. [C]
Page 51 and 52: 21. TG1009 Policy regarding tests o

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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?