OBSERVATIONS ON THE EFFECTS OF DECABORANE AND SEVERALPOTENTIAL ANTIDOTES IN THE RAT

LLOYD L. FOSTE, M.A.

WALTER N. SCOTT, Captain, USAF, MC

FOREWORD

This study was accomplished in the Phlysiological Chemistry Section, Bi-s-cwacesBranch, unde task No. 775305. The paper was submitted fer publication on 10 Augu't1967.

The animals involved in this study were maintained in accordance with the "Guideor Laboratory Animal Facilities and Care" as published by the National Academy

of Sciences-National Research Council.

The autbor are indebted to Lt. Colonel Harold L. Bitter for his encouragementand to Dr. A. A. Wykes for help with the design of the experiments.

This report has been reviewed and is approved.

GEORGEColonel, USAF, MCCommander

lI

ABSTRACT

Rats we= injected intraperitoneally with decaborane (B10H14 ) and 7bserved overs seven-day period to determine their toxic reactions, inAcluding death rate. Pyridoxine,

pyridoxal, and pargyline (MO-911) were tested in the decaborane-treated rats asantidotes for the observed manifestations of the boron hydride injection. In thesestudies pyridoxine (1 rmole/kg.) given simultaneously with decaborane preventedthe convulsions and hyperactivity usually seen in rats treated with decaborane alone(20 mg./kg.) and caused a significant decrease in the number of deaths. Pargylina,50 mg./kg., given with the decaborane gave no significant alteration of the CINSsymptoms, but significantly reduced the mortality rate. Pyridoxel phosphate and ahigher level of pyridoxine (2 mmoles/kg.) were without beneficial effect. Someimplications of the data are discussed.

III~o

OBSERVATIOK ON THE EM OF DECABORANE AND SEVERAPOTr AANTIDOTES IN THE RAT

L INTRODUCTION similar to those seen in animals treated withreserpine. As a result of these findings, many

Boron hy&ides have been in use for a num- of the efforts to obtain antidotes for deca-ber of years as chemical reagents. Afore re- borane have centered on the monoaminecently, further interest in their properties has oxidase inhibitors and the index of effective-been generated by their application as high- ness of a given drug as a decaborane antidoteenergy fiels and rocket propellants. Because has often been its ability tc moderate theof the hazards to individuals working with reserpine-like CNS symptoms and to preventboranes, a number of studies have been pub- the depletion of biogeni - amines (6).lished concerning their toxicity and theproblems of proper handling of these materials. The assumption, however, of a direct re-Such reports have Indicated that significant lationship be'ween the CNS effects and thehazards exist vith decaborane (B1oH1,) by all most important toxic reaction, death, does notpractical routes of exposure (1, 2). The vapor seem to be supported by previously publishedpressure of decaborane (and'most other boron data. The purpose of this study, therefore,hydrides) is suffic!ent to quickly reach toxic was to monitor the behavioral changes inconcentrations in an enclosed space. Workers animals treated with decaborane and variousaccidentally exposed to decaborane suffered antidotes and to correlate this subjective in-from .igns and symptoms of nervous system formation with the objective data gained fromtoxicity such as dizziness, weakness, headache, the mortality rate. It is hoped this informa-tremors, and involuntary contractions of tion may prove useful in the evaluation of pastskeletal muscles (8, 4). Rats exposed to studies of decaborane and in the design ofdecaborane vapors exhibited nervousness, un- future experiments.steadiness, slight convulsions, ataxia, and shak-ing motions of the head (5). In dogs, repeated II. SUMMARYadministration of gelatin capsules containingdecaborane at a dosage level of 3 mg./kg. Rats injected intraperitoneally with deca-caused listlessness, nervousness, ataxia, vomit- borane, 20 mg./kg., became convulsive, ataxic,ing, and tremors of the head (8). These and and alternately hyperactive and sedated; theother observations have illustrated that the majority (69%) died within a seven-day period.moet prominent symptoms of decaborane Pyridoxine, pyridoxal, and pargyline (MO-911)toxicity have been those related in some way at various dosage levels were tested as anti-to the central nervous system; these include dotes for the decaborane. The hyperactivitysedation, irritability, and convulsivns. and convulsions demonstrated by rats treated

with decaborane alone could be alleviated byBecause many of these symptoms are similar the simultaneous injection of 1.0 mmole, kg.

to those obtained with reserpine treatment, of pyridoxine; this treatment also caused aseveral studies have been published to offer significant reduction (P < .01) in the seven-evidence that changes in tissue biogenic amine day mortality rate. Treatment of decaborane-metalbolism following dectborane exposure art injected rats %ith pyridoxal or with a higher

|1

dosage of pyridoxine gave no beneficial results. HI. METHODS

Rats injected with decaborane plus MO-911showed no significant reduction in CNS Male Sprague-Dawley rats (25C to 350 gin.)manifestations, although the seven-day mor- were used in this study. Thej, were injected

tality rate was significantly reduced (P = intraperitoneally with various combinations of.036). These studies of the various antidotes decaborane (in corn oil), pyridoxine (in normalfail to demonstrate any positive correlation be- saline or 27 mM sodium bicarbonate, pH 7.5),tween the alleviation of CNS symptoms and pyridoxal (in 0.5% methylcellulose), andthe reduction in mortality rate. MO-911 (in normal saline) (table I). The rats

TABLE I

Injection protocol1 Number of rats

Group Dosage Drug Medium Type injection dearf/studied

I 20 mg./kg, Decaborane Corn oil Single 31/45

I! 20 mg./kg. Decaborane Corn oil Simultaneous 36/45+

2 mmoles/kg. Pyridoxine Sodium bicarbonate

III 20 mg./kg. Decaborane Corn oil 80 minutes 9/15+ posttreatment

2 mmoles/kg, Pyridoxine Sodium bicarbonate

IV 20 mg./kg. Decaborane Corn oil 30 minutes 13/15+ pretreatment

2 mmoles/kg. Pyridoxine Sodium bicarbonate

V 20 mg./kg. Decaborane Corn oil Simultaneous 9/15

1.5 mmoles/kg. Pyridoxine Sodium bicarbonate

VI 20 mg./kg. Desaborane Corn oil Simultaneous 8/15+

1 mmole/kg. Pyridoxine Sodium bicarbonate

VII 2 mmoles/kg. Pyridoxine Sodium bicarbonate Single 0/15

VIII 20 mg./kg. Decaborane Corn oil Simultaneous 6/15

50 mg./kg. MO-911 Saline

+IX 20 mg./kg. Decaborane Corn oil Simultaneous 9/16

S +2 mmoles/kg. Pyridoxal 0.5% methylcellulose

X I 50 mg./kg. MO-911 Saline Single 0/15

X i 15 mg./kg. Decaborane Corn oil Single 2/15

X1! 15 mg./kg. Decaborane Corn oil Simultaneous 8/15+

2 mmoles/kg. Pyridoxine Sodium bicarbonate

2

were given free access to water and Purina followed by a deep sedation. Four hours laterChow prior to and during the course of the the animals were still sedated and they re-study. Following injection with the test acted sluggishly to sound and touch. However;material, the animals were observed closely when aroused they were quite irritable andover the first 8-hour period and then at fre- aggressive. Several animals were noted to bequent intervals for seven days. The rats were ataxic during this period. Eight hours aiterexamined for level of physical activity, muscle injection the animals were still lethargic andtremors, n,-iscular coordination, convulsive remained quiet when undisturbed. Their re-seizures, startle reaction (by tapping on the action to sound and touch seemed below normal,cage with a metal bar), and general physical and they exhibited sporadic involuntary mus-condition. cular contractions and an unsteady gait.

Marked pilo-erection was present in all theThe death rate in each group of animals animals. When the animals were startled by

was recorded, and the rate in each group com- sound, they became irritable and aggressive,pared to that of every other group by con- often fighting among themselves. Withinstructing 2 x 2 contingency tables. The actual 24 hours the animals were less aggressive andprobability for each of these contingency tables irritable when disturbed by noise and theirwas calculated by the formula activity increased, although it was still con-

siderably less than that of the controls. A fewProbab*lity (P)= animals had bloody discharges from the eyes

(as + b) ! (c + d) ! (a + e) ! (b + d)! and nares. After one week of observation,a I b I c ! d I nI the animals continued to demonstrate de-

creased activity and lethargy. Thirty-one ofas given in reference 7. the 45 animals treated in this group died;

10 died within 24 hours after injection, 22 with-It is recognized that some comparisons are in 48 hours, 25 within 72 hours, 29 within

more meaningful or are of greater interest than 96 hours, and 31 within 120 hours after theothers. Nevertheless, for completeness as well injection of 20 mg.,'kg. decaborane intrapeii-as for ease of reporting, the results of all com- toneally.parisons are shown. Note, however, that onlythose P values less than .1 are given in table II Group II (decanorane, 20 mg./kg., plus

simultaneous pyridoxine, 2 mmoles/kg.)

IV. RESULTS The rats were similar in reaction and be-havior to those in group I. The only observed

The data obtained by the observations can difference was that spontaneous convulsions inperhaps be best presented by describing group II were rare, but were readily inducedseparately the reactions of each group of by tapping on the cage. At the end of onetreated animals (table I). The death rate of week, only 9 animals survived of the 45 in-each group and its probability are given in jected; 20 animals died within the firsttable II. 24 hours after injection, and 36 within 48 hours

after the first injection. The survivors con-Group I (decaborane alone, 20 mg./kg, tinued to demonstrate decreased activity atof body weight) the end of the week.

Thirty minutes after injection of the Group III (decaborane, 20 mg./kg., anddecaborane the animals were deeply sedated posttreatment with pyridoxine,and inactive. They seemed to have a higher 2 mmoles/kg.)threshold to touch and sound, but whenstartled by a loud noise they often bhehaved The 15 treated animals used in this observa-erratically and were convulsed. This hyper- tion demonstrated reactions similar to reac-activity lasted from 80 to 90 seconds and was tions of group II animals. The only significant

3

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difference observed between the animsal in- 6 survived; 2 animals died within 24 hoursjected simultaneously with pyridoxine (group after injection, 5 within 36 hours, 6 withinI) and this group of "postinjecred" animals 72 hours, 7 within 96 hours, 8 within 120 hours,(2 mmoles pyridoxine/kg. 30 minutes after the and the ninth animal died on the sixth daydecaborane) was that the LAter group ex- after treatment. The survivors after one weekhibited no convulsive selzuzei and the death exhibited activity that was judged slightlytime was prolonged. Nine. o: the 15 treated below normal.

ninmals died during the onc-,nr-k observationperiod, with 5 deaths occurring "within 36 hours Group VI (decaborane, 20 mg./kg,, plusof injection, 7 within 48 hours, and a total of Gr ou Ir(doane, 20 mng.' kg.9 within the seven-day obseri'ation period. Thesix animals that survived for one week showed The 15 animals injected at this level ofdecreased activity and lip-d 2 small amount of pyridoxine were depressed 30 minutes after thebloody discharge from the eyes and ares. injection but did not display any convulsions

during the one-week observation period. Pilo-Group3 IV (decaborne, 20 ing./kg., and erection and sedation were observed in allpretreatment with pyridoxine, animals and several exhibited mild conjunctival2 mmoles/kg.) hemorrhages, but these were significantly re-

duced when compared with the treated animalsPreteatment of the 15 anitnals with in the first three groups. Within 24 hours,

pyridoxine 80 minutes prior to the decaborane this group of animals showed more spontaneousinjection caused no changes in the optimum activity than any other group of animals In-time of ctionulso (normally 80 minutes after jected with decaborane In combinatIon withthe injection of d~caborane) and did not alter pyridoxine. Only 8 animals died wthin thethe usual hype ief!.0tv. Four hours after in. one-week observation period; the mortalitySection tht Pn'mt1s iad a very unsteady gait rate In this group of animals was significantlyand were sedi~t and ataxic. Twenty-four hours lower (P < .001) compared to groups I, I, 11,after inj ,. , . their actlvity, was far below IV, wnd V.that of F,", .)ntrols and they remained ataxicand anox, !. Within the week, 18 animalsdied, of 15 that were treated; 7 deaths occarred Group VII (pyridoxine alone, 2 mmoles/kC. ofwithin 24 hours after injection, 9 within body weight)80 hours, 12 within 48 hours, and the 18thanimal died six days after Injection. After the Within one hour the animals' activity andanimals had been observed for one week, the reaction to sound and touch were far belowcondition of the two survivors was similar to normal. This mild sedation, together withthat of rats in group Ill. some unsteadiness of gait, lasted about 4 hours

before slowly subsiding over the subsequentGroup V (decaborane, 20 mg./kg., plus 24-hour period. At the end of one week, nosimultaneous pyridoxine, 1.5 mmoles/kg.) deaths had occurred in this group of 15 ani-

mals. Their physical condition was normal andThe 15 animals that were injected with a they demonstrated no effects of the injection.

lower dosage level of pyridoxine (1.5 inmoles/kg.) were well sedated within 30 miitres after Group VIII (decaborane, 20 mg/kg., plusthe injection of decabor.ne (20 mg./kg.)o By simultaneous MO-911, 50 mg./kg.)periodically observing this group of animals for24 hours following injection, it was seen that Thirty minutes after injection the animalsthey demonstrated reactions similar to those were sprawled in the cage in an irregular posi-shown by animals in groups III and IV, al- tion, deeply sedated and inactive. The animalsthough they had no convulsions. At the end of evidently could not walk; they exhibited con.one-week observations, 9 animals had died and vulsive seizures and erratic behavior at the

5

slightest provocatin. Four hours after inje- soud and touch was diminished. Three totion the animals were still sedated and had 5 hours after injection the animals becamepiio-erection, ataxia, and dulled responses to hyperactive, alert, inquisitive, and had verysound and touch. When aroused, however, the good reaction to sound and touch. Withinanimals were aggressive and became irritable 24 hours after injection their activity and re-

when touched. Eight hours after injection the sponses had returned to normal and theyanimals showed more activity, although this demonstrated no continuing ill effects fromwas well below that of the controls. Several the injection. At the end of one week, noanimals gave evidence of abdominal pain and deaths had occurred in this group of animals,discomfort, possibly as a result of a local re- and no difference could be observed betweenaction to the intraperitoneal injections. All this group and the control animals.other 3ymptoms were similar to those thatexisted 4 hours after injection. Twenty-four Group XI (decaborane alone, 15 mg./kg.)hours after injection this group of animals wasonly slightly less active than the controls. The animals were only mildly sedated with-Their gait was steady, and they responded in in 30 minutes after the injection. There werea normal manner to sound and touch. The no spontaneous convulsicns in this group noran-nals did not demonstrate pilo-erection or could they be induced. Within 4 hours theataxia, but several had a mild hemorrhage animals had a decrease in activity and an un-around the nares. Of the 15 animals treated, steady gait. Twenty-four hours later their6 died during the seven days; 3 animals died activity had increased but was still significant-within 48 to 54 hours after injection, 5 within ly less than that of the controls. Several72 hours after injection, and 6 within 96 hours animals had mild conjunctival hemorrhages.after injection. The death rate was lower Two of the 15 animals injected died. The Ithan that of groups I (P = .036), II (P - survivors showed no residual ill effects..005), and V (P = .001) and not significantlydifferent (P = .162) from that o" group VI Group XII (decaborane, 15 mg./kg., pluswhich was treated with 1 mmole pyridoxine simultaneous pyridoxine, 2 mmoles/kg.)plus 20 mg. decaborane/kg.

This group of 15 animals was injectedGroup IX (decaborane, 20 mg./kg., plus simultaneously with pyridoxine and the lowersimultaneous pyridoxal, 2 mmoles/kg.) dosage (15 mg./kg.) of decaborane. There

were no convulsions, but the animals were veryThe reactions and behavior of these animals mildly sedated withir dO to 45 minutes. The

were not different in any respect from those overall reaction was judged to be the samereceiving 20 mg. decaborane alone (group I). as for animals receiving the same amount of tThe sedation, irritability, and convulsions all decaborane alone (group XI). At the end ofappeared in the expected intensity. After a seven days 3 animals had died. The survivore.week, the survivors appeared to be unconcerned demonstrated no ill effects from the treatment.about food and water and showed a decreasein spontaneous activity. Nine animals died, V. DISCUSSIONof the 15 injected; 2 of the animals died within24 hours after injection, 4 within 30 hours, Rats injected with decaborane alone8 within 96 hours, and 9 within 120 hours (20 mg./kg.) demonstrated sedation, ataxia,after injection. and convulsions, and the majority (69%) died

within a seven-day period. It has been shownGroup X (MO-911, 50 mg./kg. of body weight) in this laboratory that this dosage of

decaborane causes 100% depletion of brainThirty minutes after injection all 15 rats norepinephrine within 24 hours (6). Pyri-

appeared to be very mildly sedated and ex- doxine, at the level of 1 mmole/kg., givenhibited a decrease in activity. Reaction to simultaneously, limited this depletion to only

* 6

50% while pyridoxine, in the dosage of analog is effective as a cofactor for the decar-2 mmoles/kg., completely obviated depletion of boxylating enzymes so important in aminebrain norepinephrine (9). Similar, though not metabolism. Thus, if one assumes that thesc striking, dose responses to pyridoxine were primary role of pyridoxal and its analogs inseen in the heart norepinephrine levels (9). alleviating the effects of decaborane restsThese and other data of the same sort naturally merely in the straightforwaid replacement ofhave been used as criteria in selecting suitable pyridoxal cofactor, there are a number of rea-antidotes for decaborane and indeed served P3 sons for expecting pyridoxal to be as effectiveguidelines for the dasign of the present study. as pyridoxine. This is not the case; pyridoxal

was not useful in preventing the CNS effectsAs one mnight have predicted from the re- and the death rate of animals treated with

sults of earlier studies (6, 9), the decaborane- 2 mmoles/kg. pyridoxal simultaneously withtreated rats injected with only 1 mmole/kg, the 20 mg./kg. decaborane was the same aspyridoxine (group VI) were less sedated, had that of the rats receiving only decaborane.no co-vuilsions, and returned to their normal This paradoxical ineffectiveness of pyridoxalactivity nore quickly than those rats treated in these experiments is paralleled by its in-with decsorane alone. Moreover, the death ability even to prevent depletion of the brainrate wf.s significantly lower (P = .001) in biogenic amines in this laboratory (6). Onethose rats simultaneously given 1 mmole/kg, possibility is the proposed differing cell perme-pyrido::ine. On the other hand, this study ability properties of the tw, forms of Be (10).demonstrates that 2 mmoleskg. of pyridoxine, However, this spculation does not explain thewhether given prior to (group IV), with lack of a dose-response relationship in the(group II), or following (group III) the pyridoxine-treated groups (IV, V, and VI).decaborane, effects no significant change in Administration of a slightly lower level ofeither the behavior or death rate. On the decaborane (15 mg./kg, together withcontra no, the rats were sedated, ataxic, and 2 mmoles/kg. of pyridoxine (group XII)) gaveconvulsive, and of the 75 rats making up results similar to those obtained with 15 mg./groups II, III, and IV, 77% died. This kg. decaborane alone (group XI) and withparadoxical effect is most surprising in view 20 mg./kg, decaborane and I mmole/kg.of the manifest dose-related beneficial effects pyridoxine (group VI). These data may beof pyridoxine upon brain and heart biogenic interpreted as evidence against a toxic effectamines. The data, however, may be interpret- of the 2 mmoles/kg. pyridoxine itself. Furthered as demonstrating an interesting dichotomy evidence that pyridoxine itself is not toxic isbetween biogenic amiale tetabolism and given by group VII, where the injection ofdecaborane lethality. Recent studies of pyridoxine (2 mmoles/kg.) alone resulted in nopyridoxal-req iring enzymes in this laboratory deaths and only relatively minor effects con-clearly demonstrate that other vital enzyme sisting of sorr. mild sedation and unsteadinesssystems may be more important in decaborane of gait during the first 24-hour period.toxicity than those of amine metabolism (10);the present data may represent further evi- The other drug tested in this study,dence of the same nature. pargyline, is a nonhydrazide monoamine

oxidase inhibitor. It has been shown that thisFurthermore, if one assumes that the compound almost completely prevents the

pyridoxine acts directly as an antidote (or as a depietion of brain norepinephrine caused byreplacement for pyridoxine destroyed by the decaborane (6); the effect is similar to thatboron hydride), then one would expect obtained with high doses of pyridoxine. Thepyridoxal to be just as effective in subverting present study demonstrates further thatthe lethality of decaborane, since it has been pargyline, 50 mg./kg.. given simultaneouslyshown in vitro that pyridoxal phosphate is as with 20 mg./kg. decaborane (group VIII), haseffective as pyridoxine for transamination re- a protective action against decaborane in termsactions (11). In addition, only the pyridoxal of significantly lowering (P - .036) the

7

incidence of death as compared to that caused well as the efficacy of pyr',doxine and pargylineby decaborane alone; this protection is not (and the ineffectiveness of pyridoxal) In re-different (P = .159) from that obtained with ducing and preventing these manifestations.I mmole pyridoxine. However, pargyline treat- We feel these data are especially intriguingment was not associated with any significant since "4hey do suggest that the primary pro-reduction in seizures, sedation, or the othez tective benefits derived from drugs enhancingCNS effects usually associated with decaborane bingenic amine metabolism of the brain maytoxicity. Indeed, this seems to illustrate once not be directly related to this metaboic role,more that the CNS symptoms (and brain amine and that it may prove more fruitful to examinelevels) may not be directly associated with the other metabolic systems. Hlopefully, studieslethality of decaborane. in progress will help to clarify the role of

pyridoxine and its analogs in some of theseIn sum, this study has described the "oxic enzyme systems and thus help in the treatmen L.

and lethal effects of decaborane in the rat as of boron hydride reactions.

REFERENCES

1. Cordasco, E. M., R. W. Cooper, J. V. Murphy, and pentaborane.9 (B.H.) as modified by hydra-C. Anderson. Pulmonary aspects of some toxic zines and pronynylamines. SAM-TR.66.112,experimental space fuels. Die. Cheat 41:68 Dec. 1968,(1962).

7. Fisher, R. A. Statistical methods for research2. Karckow, E. H. Toxicity and health hazards of workers, 12th ed. Edinburgh: Oliver & Boyd,

boron hydrides. A.M.A. Arch. Industr. Hygiene 1964.8:887 (1953).

8. Hill, W. H., and J. L. Svirbely. Boron analysis.8. Tamas, A. A. Health hazards of borane '"els and Progress report for 1958-1954 and summary of

their control. Aeromedical Laboratory, Wright 19.52.1954 atudies on chemistry of boron hydridesAir Development Center, Air Research and and toxicity of boranes. Contract reportDevelopment Command, United States Air MLCR 42, Chemical Corps Medical Laboratories,Force, Wright-Patterson AFB, Ohiv, pp. 9-15, Army Chemical Center, Md., 1984.198.

9. Wykes, A. A., and J. H. Landez. Modific t.'.- f4. Lowe, H. J., and G. Freeman. Boron hydrides the tissue norepinephrine end serotonin deplet-

(borane) intoxication in man. A.M.A. Arch. ing action and toxic effecte of decaborane-14Industr. Health 16:627 (1957). by pyridoxine hydrochloride and pyridoxal

phosphate. (Abstract) Fed. Proc. 26:2 (1967).5. Svirbely, J. L. Subacute toxicity of decaborane

and pentaboran3 vapors. A.M.A. Arch, Industr. 10. Scott, W. N., H. D. Cole, J. H. Landez, and A. A.Hygiene 10:808 (1954). Wykes. Transaminase inhibition y decaborane.

Proc. Soc. Exp. Biol. Med. (In prehs)6. Wykes, A. A., and J. H. Landez. Toxicology of

boron hydrides-studies of alterations in tissue 11. Holtz, P., and D. Palm. Pharmacologic aspectsamines by toxic decaborane-14 (B10H14) and of vitamin Be. Pharmacol. Rev. 16:118 (1964).

8

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DOCUMENT CONTROL DATA, R&D(Security classflicatlon of fill*, body of abstrct and ndaxi antiotatlon a l be entered when the op. nil rpout t $1488tletd

I. ORIGINATINO ACTIVITY (Corporata author) I&Z. RZPORT ACCURITY C LASSIrICATION

USAF School of Aerospace Medicine ' UnclassifiedAerospace 1edical Division (AFSC) aourBrooks Air Force Base, Texas L_

3. REPORT TITLE

OBSERVATIONS ON T.E EFFECTS OF DECABORANE AND SEVERAL POTENTIAL ANTIDOTESIN THE RAT

4. DESCRIPTIVE NOTES (Typo of report and Incluive date&)

May 1966 -May 1967A. AUYHOR(5) (L8 name, tint name, Itlle)

Foster, Lloyd L.Scott, Walter N., Captain, USAF, MC

. REPORT DATE 7f. TOTAL No. OP PARE2 " b. No. air s

October 1967 8 N 118. CONTRACT OR GRAhr NO. So. ORIGINATORI RKPORT NUMBM()

b. PRoJECT NO. 7753 SAm-TR-67-103

c.Task No, 775305 9b. g.NrRo;PORT NO(* ) (Any *,h- .,n .,, ,,tmay b~e..id

d.

10. AVAILANILITY/LIMITATION NOTIC9S

This document has been approved for public release and sale; itsdistribution is unlimited.

11. SUPPLIMINTARY NOTES 12. SPONSORINO MILITARY ACTIVITY

USAF School of Aerospace MedicineAerospace Medical Division (AFSC)

I_ Brooks Air Force Base, TexasIS. ABSTRACT

"\ Rats were injected intraperitoneally with decaborane (BlOHI4) andobserved over a seven-day period to determine their toxic reactions, includingdeath rate. Pyridoxine, pyridoxal, and pargyline (140-911) were tested in thedecaborane-treated rats as antidotes for the observed manifestations of theboron hydride injection. In these studies pyridoxine (1 mmole/kg.) givensimultaneously with decaborane prevented the convulsions and hyperactivityusually seen in rats treated with decaborane alone (20 mg./kg.) and causeda significant decrease in the number of deaths. Pargyline, 50 mg./kg., givenwith the decaborane gave no significant alteration of the CNS symptoms, butsignificantly reduced the mortality rate. Pyridoxal phosphate and a higherlevel of pyridoxine (2 mmoles/kg.) were without beneficial effect. Someimplications of the data are discussed.

DD JAN04 1473 UnclassifiedSecurity Classification

Unclassified

Sectmity CKas -,NK A iLt S LIK C

,toET.--i T * jw OLE ,W7 ROLC Wi

Toxicology

,ece~borane-14Pyridoxine

?y-ridoxalPargyine !r.drochloridePecaborane antidotes

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7b. NUMBER OF REFERENCES: Enter the total number of It is highly desirable that the abstract of classified reports.derences cited in the report. be unclassified. Each paragraph of the abstract shall end with8a. CONTRACT OR GRANT NUMBER: If appropriate, enter an indication of the military security classification of the in.the applicable number of the contract or grant under which formation in the paragraph, represented as (TS). (S). (C). or (U)the report ws written. There is no limitation cn the length of the abstract. How-

8b, Bc, & 8d. PROJECT NUMBER: Enter the appropriate ever, the suggested length is from 150 to 225 words.

military department idontificatlon, such as project number, f 14subproject number, system numbers, task number, etc. 14KEY WORDS. Key words are technically meaningful terms

or short phrases that characterize a report and may be used as

9a. ORIGINATOR'S REPORT NUMBER(S): Enter the offl- index entries for cataloging the report. Key words must becial report number by which the document will be identified selected so that no security clastification is required. Identi.and controlled by the originating activity. This number must fiers, such as equipment model designation, trade name, militarybe unique to this report. project code name, geographic location, may be used as key

9b. OTHER REPORT NUMSER(S). If the report has been words but will be followed by an indication of technical con.assigned any other report nrubera (etther by the orp..nator text The assignment of links, rules, and wez-lhts is optionalI or by the sponsor), also enter this number(s).

10. AVAILABIL7TY/LIMITATION NOTICES. Enter any lir-*itations on further disseminatton of the report, other than those

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