Doc 0000022036

This page features a graphic of a vault door on the left, illuminated with a blue glow. To the right of the vault, white text is superimposed on a dark background. The text declares "THE BLACK VAULT" in a stylized font, followed by a message explaining that the document was obtained from The Black Vault, an online database of declassified government documents, specifically from the MKULTRA/Mind Control Collection, which contains over 20,000 declassified CIA pages. It also provides a URL for downloading the collection. No photographs, handwritten annotations, official stamps, forms, diagrams, tables, or redactions are visible. THIS DOCUMENT CONTAINS ~PAGES, COPY NO. _L OF _jL COPIES. AS A VEHICLE FOR INCAPACITATING AGENTS Prepared by: 24 December 1971 This report has been prepared by as a part of a Government Contract. The views e:x:pre_ssed are those of ] personnel and not nec~_ssarily those of the United States Government. i ... ';;'"toll!""":-"--...-'·~~~~------------------------------~------------- TABLE OF CONTENTS Protocol Statement List of Fi~ures and Tables . iii Problem .. 1 Discuss io::1 . l I. Potential Applications. 1 ----- ---- II. ~-- . t,I· . 3 III. Phys io 1o gica 1 Cons id~ rations. • 4 A. Introduction -- Nature of the Skin. 4 B. Theories of Penetration. 5 L C. Substances "Carried" . 5 D. Penetration Studies . . 6 1. Stratum Corneum. 6 2. To the Bloodstream. 8 . E. Fate and Metabolism \ 11 F. Local Reactions and Toxicity, . lZ G. Physiological Conclusions. 14 IV. Other System Factors. 16 V. Re·::ommendations. . . 18 Reference a. • • . . 19 ii .-~ LIST OF FIGURES - Page Figure 1 Section Through the Skin of the Human 51-.oulder • • . • • 4 LIST OF TABLES ------ I Table I Dermal Pene~ra,_tion Rates of Various _ c 'Mixtures. • . . . . . • • . . • . • . 9 II: .!::...$ A VEHICL.£ FOR INCAPACITATING AGENTS PROBLEM To evaluate, especially from the physiologic point of v:.ew, as a vehicle for personnel incapacitating agents. DISCUSSION I. Potential Applic<.tions For Incapacitation Jis a chemical with the rather extraordinary prope_r ty of penetrating skin rapidly. The ;:'ldn, long thought ':>f as a virtually im- , penetrable barrier or as an only slightly, slowly permeable one, is easily, - quicldy, and r-eversibly breached \ Furthermore, many chemicals, when dissolved can cross the barrier along with Such a proper:y lends Ito consideration as a posdble means of deliver- ing an incap~citating chernical agent via the skin. Those drugs which interfere with a person 1s state of consciousness - ·· inducing los:; of consciousness, panic, disorientation or hallucination -- could conceivably be administered, as well as drugs which incapacitate by causing motor C.ysfunction or muscular paralysis, or those which incapacitate by producing somatic preoccupation such as itching or burning. Since many incapacitating drugs requirefairly critical dosage, the usefulness of a \incapacitating agent mixture would probably be amited to individuals, where the dosage could be more carefully controlled which incapacitate by causing motor C.ysfunction or muscular paralysis, or those which incapacitate by producing somatic preoccupation such as itching or burning. Since many incapacitating drugs requirefairly critical dosage, the usefulness of a \incapacitating agent mixture would probably be amited to individuals, where the dosage could be more carefully controlled a.s to quantity and site of application. In a crowd situation, uniform dosage wou~d be quite hard to obtain. -2- ---·--·- II. * The lowest temperature at which vapors will ignite in air. III. Physiological Consideration5 r\. Introdu.::tion -- Nature o! the Skin,. A primary function of the skin is protection o£ the body. One way in which it· docs this is b·i serving as a barrier to penetration of chemicals -- harlTliul or otherwise -- ~nto the body through its surface. It is a formiciable barrier to such penetration. For example, the epidermis re'tard:s the diffusion of low r.:o~~cular weight, water solub~e nonelectrolytes {among the most diffusible of 7 substances) by a factor of over one thousand times. Fig•.1re 1. Section through the skin of the human shoulder To get from the surface of the skin t,, the circulatory system, a substance . must first pe:1etrate the stratum corneum, or horny layer of the epidermis. This is a thin layer of dead, keratinized epithelial cells apprOYimately 101-1 thick. Once this is pasn:d, the stratum Malpighii, or living part of the epidermis (100 ~ or so th::.ck), then the papillary part of the dermio:; (100- 200 1-l thick in most places) must bt. traversed before the capillaries in the dermal ')apillae are reached. The stratum corneum constitutes by far the major part of the skin barrier insofar as resistance to diffusion is 7 concerned. If it can be bro;:ached, drugs ... an gain entrance to the body via -4- .. .. '·~. ------,~----'-------::"-.,_.--c-----,.1~~~ , ~. ~-----~---------~~-------------- ,I -") ',) -.,_ /1 IJ ··· ""Si;,:;,~~·~·.~~~J!i:!~!l~i~l'·l 'l!!?ll!!l!iM!!i!!!!!!lliillllii•BIIRBIBIIBIIIIIIIIIilll' --••.-..~-----·-,_-----·---- the skin-- eliminating the need to administer them orally, by injection, 1r by other routes. J)_._'[,heories of Penetration. The actual mcchan:sm of penetrat.ion of the human skin \is lar!;ely unknown, although. several th !aries have been advanced. There is little or no evidence in support of any of the theories, however. According to th(; most widely held hypothc>sis, the molecules \~eplace molecules of bound water in the stratum -:orneum. \bonds are less tight than HOH - HOH bonds and, therefore, temporary dissociation, allowing ito The page contains typed text indicating that the document has 25 pages and is copy number 1 of 3 copies. It also states "AS A VEHICLE FOR INCAPACITATING AGENTS" and is dated "24 December 1971". There is a handwritten annotation in the lower right corner, circled, reading "247". There are no photographs, diagrams, or other visual elements besides the typed and handwritten text. The page displays a standard disclaimer regarding the report's origin and the views expressed within. Visually, there is a faint black circular shape near the top margin, possibly a punch hole from a binder. The text "i" is present in the bottom right quadrant, likely a page number or indicator. A long, thin horizontal line stretches across the bottom of the page, possibly a footer with faint, illegible text above it. There are no photographs, stamps, forms, diagrams, tables, or evidence of experimental procedures visible on this page. have been advanced. There is little or no evidence in support of any of the theories, however. According to th(; most widely held hypothc>sis, the molecules \~eplace molecules of bound water in the stratum -:orneum. \bonds are less tight than HOH - HOH bonds and, therefore, temporary dissociation, allowing ito 7 chemicals to pass through, would be easier. In order ailow other substances to penetrate the stratum corneum, saturation of the inter molecular spaces may be necessary. As /says, "It is almost as if the penetrant is conducted through the horny-layer barrier by remaining .dissolved in c. continuous channel , \which occupies inter- molecular spaces." This "opening up" of a pathway tl-_rough the stratwn corneum occtLrs for a limited time only; jleaves the· stratum corneum open to penetration by other chemicals for 1-1/Z to 3 hours f only. It is suggested that by the end of this time the saturating quantity of ./l1as either diffused away from the stratum corneum or beer absorbed into the circulation. J i 7 Iligh concentrations are needed for effective penetration. \ This may be a res..llt of the 1:2 or 1:3 associational complex formed w~th water, \ l A 75% or greater has space remaining availablt> for association with tissue water molecules they can be removed from the stratum corneum and replaced C. Substances "Carried 11 Various investigators have conducted experiments Ip.n con june tion -5- ---- =~-=--~------------------------------------------- with a. wide variety of chemicals in hopes of getting them throngh the skin barrier. As a general rule, low molecular weight, nonionized chemicals pass through the moat quickly, those which are ionized and/or of higher _ molecular weight pass through more slowly, if at a-.1, and substances of high molecular weight such as insulin and ragweed a.llcrJen do not pass through 1 at all. Some subs!;,nces which have been tried and which do pen~trate the stratum corneum It should be strest>.:d that nea:t'ly all of these studies measured penetratioa only through the stratum corne~tm or into the skin. They do not imply penetration f.nto the bloodstream. Indeed, many of these substances, including· lI have been found to penetrate o·nly through the stratum corneum into tt.e epidermis and dermis, where they may form a reservoir. Some, such as {may remain in the stratum corneum for the most pa'rt. D. PenetE_<l.tion Studies. I. Stratum Corneum. There are two main {;>_::tors to consider in the penet.1"ation 1t hrough The image displays a table of contents for a document. There are no photographs, handwritten annotations, signatures, stamps, forms, diagrams, or visual evidence of experimental procedures. The page is entirely composed of text, organized into a structured table of contents with numbered and lettered sections, along with corresponding page numbers. There are no visible redactions or obscured content on this page. found to penetrate o·nly through the stratum corneum into tt.e epidermis and dermis, where they may form a reservoir. Some, such as {may remain in the stratum corneum for the most pa'rt. D. PenetE_<l.tion Studies. I. Stratum Corneum. There are two main {;>_::tors to consider in the penet.1"ation 1t hrough the skin baJ."rier ~- the speed of penetration and the quantitative amount of" penetration, Neither has been establ; shed with any degree of precision, but some figures are available. -6- ____ l .e ---r / four.d that l. So/o penetrated (as established by serial stripping of the skin's horny layer with cellophane tape) to the base of the horny layer i!'l. one minute. The liquid was applied as a "pool" by means of glass cylinders taped to the back of male Negro(!s. He alsc found that \in a glass cup produced wheaiing as early as two minute~ after application. For whealing to occl!r (most probably due to histamine liberation from the mast cells) pen<!tration below the stratum corneum mu~.t have occurred. These results were ol:tained with present in d·~~h above the area treated, hcw~ver -- r.ot with it spread over the skin or a·='p1ied in small quantities. [on the back 2..nd spread it with a glass rod. They noted signs of reaction (whealing, e<·pecially around the hair follicles) in 5 to 15 minutes. The differences in whe2..ling times between jwork may indicate that tl: ~ a!> sorption time is a. function of tr_e amount /enabling quicker penetration than \thin layer. ' / ohtained anesthesia of the eardrum (which has a stratwn cornec.m just like any at-'ler skin area) sufficient to allow {:ai:nl~ss myringotomy (cut ting of the eardrum) within one minute after wiping the eardrum with In another study, . 1p enetrated to the base o£ the horny layer ~n 20 minutes. In f the time was 55 m.inutes, and in \ lZO minutes was the time for pe:netraticn. These results em- phasizl;! the need to use high concentrations . r [vr rapid, maximun. ' pcne tration. Published st.ltlies on the quantitative penetration )have been almost nil. jin gel form on the elbow and let lt stand for 30 minutes. By then wiping off and weighing what remained at ~he -7- ·.~ l end of tha~ time, they. calculated tl,at ZS-40% of 1 had been ab- so,.bed. This was obviously::. ~ough determination only. \eight hours after dermal applic:a ~(ol\, "that on the elbow and let lt stand for 30 minutes. By then wiping off and weighing what remained at ~he -7- ·.~ l end of tha~ time, they. calculated tl,at ZS-40% of 1 had been ab- so,.bed. This was obviously::. ~ough determination only. \eight hours after dermal applic:a ~(ol\, "that ZOo/.~ of the applied dose was still in the epidermis. He did not l(lel'tion where or how th~ remaining 80% was distributed. .\is Th"se two studies demostratc that dermal application. .tto 41ssa:r-a:1ce that all of the compound will penetrate the skin. Furth·ermore, of -th~t DOrtton which does penetrate, S!":llne may remain h. the epide:r::-uis for a • - 00 L~ 0 consid~l"Ll.ble !ength of tim.o:. These studies were \alone; chemicals ''c~r:.-ied" !may or may not behave in like manner. At present, it woo.:.ld i.;.~ almost impossible to predict what the behavior of a g1ven r:hemical a':.lent \,would be with regard to p•~rcent absc.'"ption or penetration rate wit"out actua~ly running tests on that particular chemical. · .. · ·::cr-i.able which has been little investigated is the location of the skin to ·· ··,·:~t;trated. It is known that, with regard to such t~ir.gs as water diffusibility, ~:·~·: .• in areas o£ the body are considerably more ;>ermeabl~ than others. For 7 ··'::,:~~:-ic, scrotal skin is <":onsiderably more permeable than abdominal skin. :·:.,·:-e ;1rc several variables whkh may be at work. The skin it>~elf (epidermis o~:;r: ·krmis) '•aries in thickness, and the stratum corr..eum itself may vary .:·. · l::~ot" thic~cness or structure. Other than on the soles of the feet and the :}.,;:~\s oi the hands, where the stratum corneum is considerably thicker, but ;~ .•.. ; .:-c higher :liffusivity, the stratum corneum varies :ittle in thickness. It :::.,\· \':1ry i.n nature, however, as in the forehead, where there is a less orderly, 7 :::or,, open arrangement of the cells. There may also be some difference. .:: !h:· thicknc s s and composition of the stratum corneum among various :n·oplcs -- for example, Negroes vis-a-vis Caucasians. To the Bloodstrearr. :.to:-;t of the pre~iou5ly discussed studies of time and rate o£ penetra tiun considered the stratum corneum and epiderrr.is only. If the site o£ -s- ,, '~ -' action of the "carried" drug is the epidermis-- fine, all of the major factors h<:ve been considered. But drugs which have the brain or body organs other than the skin as sites of action must This page contains a list of figures and tables from a document. It includes the titles and page numbers for "Figure 1: Section Through the Skin of the Human Shoulder" and "Table I: Dermal Penetration Rates of Various Mixtures." There are no photographs, diagrams, handwritten annotations, official stamps, or any visual evidence of experimental procedures. The page appears to be a standard index or table of contents. considered the stratum corneum and epiderrr.is only. If the site o£ -s- ,, '~ -' action of the "carried" drug is the epidermis-- fine, all of the major factors h<:ve been considered. But drugs which have the brain or body organs other than the skin as sites of action must go not only through the stratum ~;ornewn, but also through the remainder of the epidermis and then a portion th~ bef~;~re of dl;!rrnis they reach the bloodstream w!lich can transport them, This is where , may fall down . -l studied the influence . -··---]on dermal clearance (the time re- quired fo:r the circulation to remove injected substances from the dermis). Fluorescein, a fluorescent dye, was injected intradermally -- 0. I ml in 25'f'~, --~solutions. saline, and in 50% and 75% The c l.earanc e time for the control (in saline) was l. 8 hours and the times for the solutions we.te 3, 5. 5 and 18 hours, respectively. The effects lon dermal permeability were studied by measuring the penetration rate of 1% aqueous fluorescein through abdominal skin which had been stripped of its epidermis. J The results are summarized in the table below. TABLE I DERMAL PENETRATION RATES OF \r ARIOQ_§ Saline Control Penetration r:He, in ~g/cma /hr. 79.6 17. 5 1.3 0.6 In the case of !seems to inhibit or retard passage through the dermis. [offers no theory or hypothesis to account for this, stat- ing simply that "the diffusivity of connective tissue was probably being de- pressed 1 One qualification, however, is applied to the intact skin would probably not attain such hi&h concentrations ; ' ~xperiments, I;- in the dermis as were used in these so that dermal clearance .. -9- i. . : and pcrmc<~bility probably woul.d not be retarded as much in normal use as was observed under the expe rimcntal conditions. For incapacitating agents which act on the brain, the most important considera tion is not how fast ~ the f1orny laye~, but how q':i:_~~y_!.h., or a drug ad:-ninistere£. _ ) reaches the bloodstream. . _I using tagged Jgiven dermally, found traces of radioactivity in blood drawn as early as five minutes !wa.; applied, but the level ----~did not reach a maximu"m until 4~ 6 hours later, reaching a plateau where it remained for some time. One other published experiinent, -lV!hich gives times and blood concentrations for humans, showed ---- . )one hour The document page contains no photographs, diagrams, tables, or forms. It consists solely of typed text, with several lines appearing bolded or underlined. There are no handwritten annotations, signatures, or stamped classifications visible. Some text appears to be lightly redacted or obscured, indicated by faint smudges and faint lines within the text fields. The overall presentation is that of a standard, typewritten report with clear section headings. The page contains typed text at the top, discussing dosage control in crowd situations. Towards the bottom, centered, is the page number "-2-". Below this, there is a horizontal line with what appears to be a complex drawing or diagram consisting of many small, intricate lines. At the very bottom of the page is another horizontal line, also with a series of short, interconnected lines. There are no photographs, handwritten notes, stamps, or obvious forms visible on this page. The content suggests a continuation of a document, with the diagram at the bottom being the most visually distinct element beyond the main text. radioactivity in blood drawn as early as five minutes !wa.; applied, but the level ----~did not reach a maximu"m until 4~ 6 hours later, reaching a plateau where it remained for some time. One other published experiinent, -lV!hich gives times and blood concentrations for humans, showed ---- . )one hour after admin- is tratiofl, but the peak level {approximately twice the one hour level) was not attained until four to eight hours after administration. --~-~~ These two experiments J It can be seen that a rneasurabl.e ·- l may penetrate to the bloodstream in as little as five minutl'!s. Whether or not chemicals "-carded" by ) can enter as rapidly would have to be determined experimentally. Other substances may or may not reach the bloodstream this quickly, depending on several factors such as molecular weight, configuration, solubility in tissue water and lipids, and reactivity to tissue components. The {in blood keeps building up to a peak which is only reached after several hours; such behavior would not be· acceptable for most brain-active incapacitating agents, for a dose powerful enough to incapacitate in five minutes would continue to increase for several hours, with serious and quite possibly fatal results. Unless the therapeutic * ratio of the drug is quite high, safety could not be insured. This, however, Ratio betw e en the lethal dose and an effcc tive dose. -10- -- J _,_, kXJQQ££ .IIIU&$5 . . . j assumes tha: the chemical agent would behave the same way which may not be the case. There is a possibility, b..1t only a slight one, that a peak c-oncentration of an incapacitating agent could be reached quickly. In this case, maximum effect of the drug would appear soon after adminis tration and a lower, safer dose could be used; the initial incapacitating dose would be the maximum dose received. --~-·----- 0~ report, ]sh<_>wed apparent worthwhile re- I sults in feed:.ng through the skin Such things as glucose, carotene (vitamin A}, vitamin n • and some amino acids 12 were absorbed in fairly significant amounts, as signified by blood levels and weight gain. The blood glucose level war-; l65o/o of the initial value within --·-----------·-, l 30 minutes application. The net elevation at that time, . ' which does not account for any glucose which may have already entered the bloodstream and then been metabolized, accounted for about 3o/o of the dose administered The page appears to be from a research document, with some textual content. A Roman numeral "II." is visible, possibly indicating a section or chapter. Below this, there's a line of text preceded by an asterisk: "The lowest temperature at which vapors will ignite in air." This is followed by a page number, "-3-". The rest of the page is mostly blank space, with some faint lines and dots that might be artifacts or remnants of previous markings. There are no photographs, stamps, forms, diagrams, tables, or redactions visible on this page. The overall impression is that of a sparsely populated page from a typed or printed report. The blood glucose level war-; l65o/o of the initial value within --·-----------·-, l 30 minutes application. The net elevation at that time, . ' which does not account for any glucose which may have already entered the bloodstream and then been metabolized, accounted for about 3o/o of the dose administered to the skin.· E. Fate and Metabolism-----.--, The metabolic pathways ltakes in the body are still relatively unknown: Gas ·chromatographic and radioactive tagging techniqiJ.es /show that it is excrete-:! as unchanged )and as two metabolic byproducts -- dimethyl jare excreted in the uri,ne;. \leaves ~he body via the lungs. Fee al elimination is negli- gible. \ Urinary excretion accounts !or most of the 1r emoval as the l lungs eliminate only 1-3%. Most subjects jby the dermal or any other route have a ) characteristic ''bad breath11 said to resemble This is caused by the presence of the which appears in the * _\ A rather special case, - 11- £.._ breath soon after administrrttion /and continues for Z4 hours or so. F. LoLal Re<'_ctions a'!d Toxicity. -iapplied dcrmally in the \concentration typically - is accompanied by transient burning, itching, and erythema (reddening). Its exothermic reaction with water causes an increase in skin temperature. ---.1 rn a significant number of cases, may cause whealing. This is \A assurncd lO bt a result of histamine liberation. study of over 1000 German patients who were given l dermally for a 15- minute perioC. per application yielded the following dala on skin reactions: 6 - o"lo showed no local reaction; 33% had a slight reaction (warmth, itching ar_d erythem<.); 56% had the 11typical" reaction {burning, itch~ng, erythema for 3 - 4 hou.rs, a:1d occasional local urticnria); 2 - 5"lo had a more severe reaction (dermatitis, urticaria, and occasional vesiculation). In cnly about 3. 5% was it necessary to discontinue therapy. This was due to the local skin reactions whi.ch disappeared upon discontinuation of the treat lnent. There were sometimes complaints of transient nausea and headache among those _\but no serious complicatiO::'lS. .I The "bad breath" was noticed in most subjects, and 50"lo or so reported they could 11taste11 the '\ In all of the studies done on humans (including over 4000 individuals .I in one of the studies} no serious side effects have been noted. The tem porary effec:s were those noted above, and no permanent changes or damage have been reported. * This page features a black and white diagram of a cross-section of human skin, illustrating various layers like the stratum corneum, stratum Malpighii, and papillary layer of the dermis, along with a blood vessel. The diagram is labeled and titled "Figure 1. Section through the skin of the human shoulder". Text sections include an introduction to the skin's protective function and a description of how substances penetrate its layers. There is a small numeral "7" next to a sentence, likely a citation marker. A page number, "-4-", is located at the bottom center. There are no photographs, stamps, handwritten annotations, or redactions visible on this page. so reported they could 11taste11 the '\ In all of the studies done on humans (including over 4000 individuals .I in one of the studies} no serious side effects have been noted. The tem porary effec:s were those noted above, and no permanent changes or damage have been reported. * I /tested ser.sitivity of the conjunctiva to drops of Two drops caused only temporary stinging and burning, and, in some cases, * The membrane covering the anterior eye and the ir_ncr surface of the eyelids. z- - 1 mild injecticn (congestion) of the conjunctival vessels. These effects soon disappear~d. \if dropped onto the eardrum, :rx:ay be painful, but will \ cause no long-lasting or permanent damage • .\was withdrawn as a clinical drug in the United States in 1965 by the Food and Drug Administration because of reported lens changes ·1 in dogs which had been given up to 5 grams per kilogram _, ___ -------~~- The FDA has subsequenlly allowed resum?tion of clinical testing.· There was fairly extensive -----------~in humans in this co1:mtry befol'e the j FDA ban, Lh~s_Eeen available as a prescription drug ,, ____ \No evidence of any human eye toxicity due to !has been obsel'ved . J even in the highest experimental doses given i (1 g/kg per day for lZ weeks in one study, '30 g per day for -~-,p- - t - o - - 2 - 1 1 m onths in another). Z? Rhesus monkeys have been given 1 - 3 ml of . per of ia' kg orallr or 1, 3, or 9 ml/kg deunally daily for periods up to months and no toxi~o_logic or pathologic changes have been seen, other than skin reactions. \Mo_nkeys have been given intravenous do::. , as high as 4g/kg with no d~atis. J * No estimates of an LD have been made for monkey or man, but in view of 50 the high exp<!rimental doses that have been given already, the LD would be 50 far higher than any dose which would be given for pu=poses of 11carrying11 an inc a p a~ ita nt. Substances given in combination \ howeve=, may result in an .1 re~orted altered toxicity. an interaction between alcohol in 1967. He claims to have found increased rates of mortality in rats given * The dose lethal to sooro of those to whom it is admir.istered. 13- ~ --·---~, high doses j This page is a typed document containing text related to the penetration of substances into the stratum corneum, likely a scientific or technical report. There are no photographs, handwritten annotations, signatures, stamps, forms, diagrams, tables, or visual evidence of experimental procedures or facilities. The only visual elements are the typed text and a page number "-5-" at the bottom center. There are also some scattered vertical lines that appear to be parts of redactions or structural elements from the original document source, but they do not obscure any significant portion of the text. given in combination \ howeve=, may result in an .1 re~orted altered toxicity. an interaction between alcohol in 1967. He claims to have found increased rates of mortality in rats given * The dose lethal to sooro of those to whom it is admir.istered. 13- ~ --·---~, high doses j after previously having been injc.:tcd wilh alcohol. He also said he found mare psychornotor impairment in humans given alcohot (orn.Ly) and (v'.a the skin) than would be expected from alcohol alone, This intcrac• ion should be inve:;;tigated further to be considered for usc in incapacitation since there could bn complications if the ------- --{were used on drunken subjects. Interactions between various drugs other than alcohol \~hould also be investigated further. One group of investigators found that ~?~ creased the t:)xicity (as reflected by a change in the m ). -...... 50 \ !administered orally to rats by a factor of up to six times. I Thus, ther~ is a possibility could facilitate the body1 s absorption of drugs from s.1ch sites as the gastrointestinal tract. Such facilitated absorp tion could conceivably cause an otherwise safe dose o.: a drug to become a serious or possibly fatal dose when given It <":an be seen, on the basis of the fairly extensive wo:::-k which has been done·,· j applied exterr..ally in small quantities can be expected to have temporary, local effects causing some annoyance and dis~~omfort, but no lon~-term or permanent damage. Whether or not thi1i would be true of \mixed with a given chemical agent would depend upon the nature of the chemical and how it acts in conjunction \ Such knowledge would have to be established by experimentation, using the specific chemical agents to be conside::.-ed. It would be quite desirable to have further data on the intera.:.:tion of alcohol \ as well as any other drugs which potential subjects migl-.t take before or /administraLon. G. Physiological ConclusiOn.J!. For use as a "carrying11 agent for incapacitants, !would have to be used in fairly high concentrations, probably To assure useful speed pf penetration and to ensure penetration it would have to be applied in volume, perhaps one r.1l or more, as shown by various investigators. \ -14- ) can fairly well be rulc-cl out as a means of quick delivery for psychotropic agents, or any other agent with the internal organs as a tar[!Ct. The chance:5 are very good that any be applied in volume, perhaps one r.1l or more, as shown by various investigators. \ -14- ) can fairly well be rulc-cl out as a means of quick delivery for psychotropic agents, or any other agent with the internal organs as a tar[!Ct. The chance:5 are very good that any agent delivered \would not reach peak blood levels for several hours. For a drug to be effective quickly (say, reaching the blood in significant amou:tts in five minutes) it WOltld have to be administered as quite a large dose. This is because, so far as is kr.own, only a small percentage of the administe