Document 9LyJD8X2qvrO2wXNG2mdrqzBq

Nov entier 28, 1947 Dr. C. K. Blckerton Blackburn, Bard Hall, Box l34, ' 50 Haven Avenue, New York City 52. Dear Dp, Blackburn: I am g l a d i n d e e d , to bear from, you, having learned from the London office of Associated Ethyl Company Limited, and also from Dr. Fairley, of your being in this'courtly. I had intended getting in touch wlth you*, so that you might know that we shall be very pleased to have you visit us, and so a s , also, to have an opportunity to discuss with you the cases referred to in your- caper. I had a rather complete report on these cases some Weeks ago, and I felt it necessary to write to*the London office and to Dr. Fairley at once concerning them. Finding that you were to be here, I cannot but feel that it is important that we see you and present our views oh this subject. Whether you hear from Australia or not, promptly, I wish to assure you that-you are fully authorized to visit Cincinnati for the purpose of consulting with us on this and other problems which are of concern to Associated Fthyl. A number of the technical and medical representatives of the Company have been sent to this count!y and to Cincinnati at Company expense, for the purpose of an exchange of information, and it would be most unfortunate if you were not to do so if you can find the time during your stay. For our part, we shall welcome you and will under take to make your visit worth your while. Now as to the paper, I should prefer to leave its disposition until such a time as we can discuss the situation fully. I personally, believe, and have so expressed myself to Dr. Fairley, that your use of B.A.L. in these cases was without noteworthy effect upon the clinical outcome. The background of this opinion will require more evidence than I can put in a brief letter, but we have had occasion to study the effects of B.A.L. in a series of cases of lead, mercury, arsenic and other metallic poisoning, and we have also treated quite a number of cases of tetraethyl lead poisoning - not with B.A.L., but by other means. The course of the cases described by yourself was in no wise unusual, nor was recovery in any way remarkable. Certain other aspects of th problem have changed somewhat with; the years . and on the basis of experience, and therefore we should be reluctant to sponsor the appearance of an article which might wll result in controversy, and which would fall in some respects to present what is now known on this subject. I send you herewith one brief article, the only one we have published, to date, on B.A.L. It will serve to present only one aspect of our observations. Certainly it will show why the analytical findings in your cases may have been rendered somewhat erratic by the administration of B.A.L. We should be 4 isposed to feel that one should go very slowly /Dr. G. E. Bick.ert.on Blackburn - (2) - November 2 8 , 19^7 indeed in recommending the use of B.A.L. in the therapy of tetraethyl \ lead poisoning. I am frank to say that I should entertain very serious reservations concerning its use, even experimentally, in any case o: tetraethyl lead poisoning if I had any considerable doubt as to the likelihood of t h e survival of the patient. Your experience leaves me somewhat less fearful on this score, but I still have some concern as :o the possible effects of its use. . I shall retain your manuscript pnti-1 I hear from you further, in the nope that we shall have an opportunity to go over it together in some detail. I sincerely trust that yopr stay in this country will be interesting and profitable, and that we shall have an opportunity to share some portion of it with you. Sincerely yours, Eobert A . kehoe, M. D. i 0020052 > (J) O ^x b^ jc^ > 5$> v t? Dr 0 .11.Bickerton rlackbiirn, Bard kadi, Box 154 pO Haven Avenue. hew York 32., h.I. 21 Jq y ember 47 . Dr. Robert k, kehoe, University of Cincinnati College of iledibine, Cincinnati, Gn io . Dear Dr henoe, ' I an writing to you on the advice of Dr R.Loeb and Dr n.Gilnan of the College of Physicians and Surgeons, Columbia University, ken York, where I am at present. I have a Rockefeller foundation grant for about 'a year. I 'enclose a draft paper on the treatment of DDL poisoning with DAL. I was fortunate enough to treat two men poisoned with DDL as I am the medical adviser to the kthyl Company.'in h.3.,,'., Australia, and both men recovered. At the time I treated then issai I haa seen no reference to the efficacy, or otherwise, of 3AL in the treatment of lead poisoning but since then have -heard very conflictin'::- opinions. It was difficult to avoid the conclusion that DAL had been effective in the treatment of at least one of my patients. . I would appreciate your advice concerning the desirability of reporting these two cases and, if it is desirable to report; then, to whom I should submit the report for publication. I am aware that much more should have been done concerning the lead excretion studies and that the method of estimating the lead in the urine was probably quite inadequate circumstances precluded a fuller study. The kthyl Company has asked me to visit:Cincinnati while I am over here and I propose to do this as soon as I can - probably In a few months time. So far the request has been verbal so I will wait for more definite instructions. I hope my request does not cause you too much inconvenience, pours sincerely, C R Bickerton Blackburn s I ' VSSm -iOEBXL L?JJ) POISOTOS- fHlATED Wlfg BAL ( g^-diTTierca-ptoproTianoI, B r i t i s h An t i -Le w i s i te . ) G. 1. Bickerton Blackburn M*D. K.R.C.P'., M.R.A.C.P. 54 K E 0 0 2 0 i i - fi.' fi ' . -TETRA-EgHTT. T,T.AP POISOr iTO TREATS WITH BAL Z^imremovroTtmol. : . Br i t-is h , ^ i t i r l,e w is it e ) ' - ; f- C. R. B i c k e r to n B la c kb u rn M.I) ., H .R .C.F. , M.B. .C.P . : - T e t r a -e t h y l le a d i s a c o lo u r le s s and somewhat v o l a t i l e l i q u i d u s e d a s an ''a n ti-k n o c k * in g a s o l i n e . It is -in s o lxible in w ater but m is cible w ith f a t s in a l l p ro po rtio n s . In the presence o f s u n ligh t i t s a y decompose to - 1. 2, t r i e th y l le a d compounds w hich are w ate r s o lu b le Motor and a v i a t i o n 3f u e l s may c o n ta i n up to nil* o f t e t r a - e t h y l le a d p e r g a l l o n w ith o u t t h e i r vap o u rs b e in g t o x i c to mani-or e x p e rim e n ta l a n i m a ls . ^ ' - P o is o n in g, h as m ost o f t e n been, re p o rte d , in men e n gage d i n b le n d in g ga s o lin e o r cle a n in g out s to rage tanks th a t have co n tain ed leaded ga s o lin e f o r some tim e , ,a b s o r p tio n t a k i n g p la c e e i t h e r by, th e r e s p i r a t o r y t r a c t o r by the s kin , through both o f which te tr a -e th y l le ad e a s ily p as s e s . Sto rage ta n k s a re e s p e c i a l l y d an ge ro u s f o r t e t r a - e t h y l le a d may be p r e s e n t i n r e l a t i v e l y la r g e amounts in th e " s c a le " on th e tan k w a lls or in th e i n e v i t a b le "s lu d g e " on th e flo o r o f th e ta n k. Gle an in g o pe ratio n s le ad to lib e r a tio n o f vauour-; fro m th e ''s c a l e " o r "S lu d g e ".^ * ' ,- The t o x i c e f f e c t s f o l l o w i n g a b s o r p tio n o f t e t r a - e t h y l le a d a r e due to th e le a d c o n te n t and a r e , fu n d a m e n ta lly, p r e c i s e l y th e same a s th o s e o f p o is o n in g w ith in o rga n ic le a d compounds. Abs o rptio n o f te tr a -e th y l le a d i n t o th e c i r c u l a t i o n i s s o m e w h at;de laye d i n th e lu n g and s k in b u t Oacfe a f t e r le a vin g the c ir c u la tio n i t tends to reach r e la tiv e ly h igh co n ce n tratio n s in f a t t y t i s s u e s s u ch as tjbe b r a i n , l i v e r and s u bcu tan e o u s f a t . Su bs e q u e n tly - . 3 t o x i c e f f e c t s o h th e bo dy c e l l s , and e s p e c i a lly th e c l i a o f th e c e n tr a l . n ervous system where th e re m y be a h igh le a d co n ce n tra tio n . Staring a 3p e r i o d o f to 14 d ays a f t e r a b s o r p ti o n th e le a d c o n te n t o f th e v a r i o u s ti s s u e s becomes re d is tr ib u te d so th a t i t s d is tr ib u tio n i s u ltim a te ly th e same a s th a t fo llo w in g th e abs o rp tio n o f in o rga n ic le a d compounds. * . _ The c l i n i c a l f e a t u r e s o f "t e t r a -e t h y l le a d p o is o n i n g a re c h a r a c te r is tic a lly tho se o f an acu te encephalo pathy o ccu rrin g a fte r a * la te n t period w hich'w ill vary in te rs e ly w ith th e d e gre e -o f exposure. * * * D e ta ile d d e s c rip tio n s have been give n o f th e c li n i c a l fe a tu re s in a r t ic le s re vie w in g up to 78 cas e s o f po iso n in g pM in th is re p o rt o n ly b r ie f r e fe r e n c e w i l l be made to th e t y p i c a l f e a t u r e s . Within a few hours o f exposure th e s u b je ct d e ve lo ps in cre a s in g insom nia, weakness, r e s tle s s n e s s , an o re xia and trem ors o f h is hands. I f th e expo sure has been co n s id e ra b le th e re-m ay be Varyin g p s ych ic changes an d , o f t h e s e , e x c ite m e n t and m ania are commonest. Wild and. t e r r i f y i n g dream s, h a llu c in a tio n s , d is o r ie n ta tio n , p h y s ic a l a c t i v i t y and co n vu ls io n s may h e ra ld an atta ck: o f a c u te m ania. Oth e r s u b je c ts may appe ar . s ch izo p h re n ic. Ch a r a c te r is tic a lly th e re i s a slow p u ls e r a te , a normal o r subnormal te m pe ratu re , a lo w blo o d p r e s s u r e , l i t t l e o r no change in th e MB- e ryth ro cyte s * and a tendency to diarrh o e a ra th e r than co n s tip a tio n . Co lic M may o c c u r b u t i s n o t c h a r a c t e r i s t i c , g e n e r a l m u s cle p a i n s a re common h u t . n e u r i t i c phenomena are n o t s e e n . 2he c o n d i t i o n i s an acuite le a d e n c e p h e lo o a th y and th e u s u al s ig n s o f ch ro n ic le a d p o is o n in g do n o t o ccu r. When s e ve r e symptoms become e v i d e n t th e y do n o t d is a p p e a r c o m p le te ly . u n t i l r e c o v e r y i s e n s u in g - th e g e n e r a l syrrmtoias c o n tin u e to p r o g r e s s and ' ' 2. th e r e s re no tr a e ressi s e lo n s and r e la p s e s , I t is stated th at those cases \( ' w i t h s e ve re m an ia, r e p a i r i n g r e s t r a i n t , a r e "a lm o s t -u n ifo rm ly f a t a l *, Tre a tm e n t h as c o n s i s t e d o f s e d atio n ' f l u i d s , . and m a in ta in in g - th e u r i n e , a lk a lin e to favo u r th e e x cre tio n o f le ad o r i t s d e p o s itio n in bones.- \ H yp e r to n ic s o lu ti o n s :w e r e o f t e n g ive n t o com bat c e r e b r a l oedem a. . ' . 2 3i -d im e rc a p to p ro p a n o l, o r BAL ( B r i t i s h A u t i -L e w i c i t e ) was in tro d u c e d 8. '' by P e te rs e t a l . as an e f f e c t i v e an tid o te to Le w is ite . -, Subsequent , v. . -i n v e s t i g a t i o n s h ave shewn t h a t BAL i s an e f f e c t i v e a n t i d o t e a g a i n s t p o is o n in g . . . , 9, 10, 11. 12, 13. 14 .15 *16 * w ith arsenic,- m ercury, > gold and. bis m u th . In v itr o . it- w i l l combine w ith iro n , le a d , t i n , co ppe r, c o o a lt, n i c k e l , se le n iu m , and a n tim o n y p ro d u c in g c o lo u re d and m o s tly i n s o l u b l e compounds. BAL a c t s as ' ' an a n tid o te to m e ta lli c p o is o n s by fo rm in g s ta b le compounds w ith th e m e ta ls b y v i r t u e o f i t s own. two t h i o l gro u p s and th u s p r e v e n ti n g them from co m bin in g w i t h e s s e n t i a l t h i o l compounds in enzyme s ys te m s and so p ro d u cin g t h e i r to xic e ffe cts. 1The s t a b i l i t y and n o n -d i s s o c i ;-b i i t y o f th e BAL-m e tal 8 17 18 19compounds p r e v e n*ts t.b. era f.rom b e .in g ,,t o x .i c . , , , . Two men, who w e re e xp o s e d to t e t r a - e t h y l l e a d , and i t s d e r i v a t i v e s , w h ile th e y were c le a n in g o u t an a v ia tio n g a s o lin e s to ra ge tan k, d e ve lo pe d typ ic a l sign s o f lead encephalopathy. One h ad K i ld symotoms but th e o th e r had c o n vu ls io n s , and became m a n i a c a l. '' - Both, w e re t r e a t e d i n Ro ya l P r i n c e A l f r e d H o s p i t a l , Syd n e y, w i t h BAL and made co m p le te r e c o v e r i e s . BAL was us e d fo r th e tre a tm e n t o f t h e s e two men a s i t was c o n s id e re d p o s s ib le th a t as le ad i s so c lo s e ly r e la te d , ch e m ically, to gold i t s to x ic e f f e c t s sight s i m i l a r l y be c o u n te r a c te d . The p o s s i b i l i t y 0 f BAL fo rm in g an in s o lu b le .compound w ith th e le a d in th e t i s s u e s was co n s id e re d bu t was th o u g h t -to - b e o f ' l e s s importance:^ than; th e p r e v e n ti o n o f i r r e v e r s i b l e , ch a n ge s -4- in the ce n tral nervous system . ': CASS HISTORIES. r , - ; ' - C' _ '. ' CASK I . 30R.K. a m arrie d sto re m an age d y e a r s was a d m itte d 12.30 2' " ' ' ^ v to Royal Prin ce Alfre d H o spital at ^ a*si. on j$rd Ju n e . . ,/ ;? ^ '* ? On th e 19 th June h e had commenced to c le a n o u t a s to r a g e ;* p e t r o l ta n k th a t had c o n ta in e d a v i a t i o n s p i r i t some 2 y e a r s p r e v i o u s l y but r e c e n tly had co n tain e d w ate r. Be pro ce e d e d to remove th e " s lim e * from, th e w a lls and i n te r n a l "f i n s " u s in g a p ie c e o f tim be r, h e ld in h i s bare han ds, as a s crape r and d u rin g t h i s c le a n in g p ro ce s s he acqu ire d a number o f m inor a b ra s io n s on bo th han ds . fie wore rubber knee bo o ts bu t no r e s p i r a t o r and th o u gh "th e fum es w e re d r e a d f u l H, he s p e n t between 6 and 8 hours in th e tan k. Be fo re e a tin g h is lunch he washed h i s han ds in s o ap a n d 'w a te r. J, 2, On th e m o rn in g o f o th J u n e , h a v i n g s l e p t v e r y p o o r ly th e : ,, p r e v i o u s n i g h t , he f e l t t i r e d , "o f f - c o l o u r " and had some a n o r e x i a , b u t;.. co n tin u e d to c le a n th e ta n k. He s pe n t h a l f th e w o r k in g d a y, w e arin g n e ith e r glo ve s nor re s p ira to r, on th e flo o r o f the tank sco o ping up th e s lu d g e w i t h a t i n and th e n p o u r in g i t i n to a b u c k e t. One man . f i l l e d th e bucket on th e flo o r o f th e ..tank w h ile th e o th e r h aule d up `" ; i ,;4 th e f u l l bu cke t and d is p o s e d o f th e co n ta in e d s lu d g e . Each 10 -2 0 m in u te s ' th e two men would ch an ge t h e i r jp b s a s t h e - "fam es i n th e ta n k were so baa He s l e p t v e r y l i t t l e t h a t n i g h t-a n d 'h a d t e r r i f y i n g d re am s , h i s a p p e t i t e w as n o n -e x i s t e n t , and he f e l t i l l . ... ` . . .. 2On i s t June h e " f e l t a w fu l ", had d ia rrh o e a * marked n aus ea,; and some e p i g a s t r i c p a i n s . He was weak end n o t i c e d an a c h in g p a in i n h i s . 5- u p p e r and lo w e r ja w s . He was a d m itte d l b th e l o c a l h o s p i t a l w ith a d ia gn o s is o f a g a s ir o -in te s tin a l u p s e t which was ve ry p re vale n t i n th e town a t th e tim e . v A f t e r ad m is s io n h i s i n t e s t i n a l symptoms s e t t l e d down and.. 4 w ith in a day h is d iarrh o e a had ce as e d , but he s t i l l had narked an o re xia." He n o tic e d a p e c u lia r s e n s a tio n in h i s hands - he c o n tin u a lly wanted . 22to rub thera to g e t h e r . On th e m o rn in g o f nd Ju n e he was a l i t t l e con fused and in th e e a r ly afte rn o o n , had a c lo n ic f i t du rin g w hich he was un co n scio u s. Re co verin g from h is f i t he was s o re co nfused and v e r y r e s t l e s s . He was s e n t b y am bulance t o R o ya l P r i n c e A l f r e d H o s p ita l where-on* ad m is s io n h e e o u l n o t c l e a r l y r e c o l l e c t th e above d e ta ile d events. ; Th ere were no r e le v a n t f a c t s e l i c i t e d in h i s p a s t o r p e rs o n a l h isto ry. ' :. . On Exam in atio n : - He w as a yo u n g man who w rith e d on th e be d , m aking c u rio u s s t r e t c h i n g movements o f h i s lim bs and back and c o n tin u o u s ly r u b b in g h i s han ds o ve r h i s f a c e . He seemed to be l i t t l e i n t e r e s t e d i n h i s s u rro u n d in gs . He to n gu e was d r y and c o a te d and h i s s k i n warm, d ry and o f normal co lo u r. Th e re were a number o f s u p e r f i c i a l a b r a s io n s on th e backs o f bo th h an ds , life co m plain ed o f p a in s a l l o v e r h i s abdomen bu t th e r e was no lo c a lJ t e n d e r n e s s . Th e re was some trem or o f h i s e xte n de d hands. H is r a d ia l p u ls e was o f good volum e, Vk re gu la r and i t s ra te was 64 per min; h is a r t e r i a l blood pre s s u re was 412 0 / 5 5 n a o f m ercury, and h i s o r a l te m p e ra tu re 9 8 . P . His e ye lid s were w id e ly separated so th a t he appeared to be exophthalm ic but h is ' ' ` " . :.y. *,. ' " abn orm alities ^ V j ,^ -' &-- . * ..- . ' were found on p h y s ic a l . - , * exam ination. '. - . : Hfs w e igh t was ' - J " . ' V ."i '. ' 150 l b s . .. .' " . . . - * - ` ^ Tre atm e n t end P r o g r e s s : He was c o n f i n e d 't o bed and g i v e n I sodium phe n obarbiton e and morphine s u lph ate . He was give n 750 1. i 50s a l i n e w i t h % g lu c o s e and m l. sodium la c t a t e s o lu tio n in tra ve n o u s ly. Su bs e qu e n tly sodium c i t r a t e was give n o r a lly , in s u ffic ie n t q u a n tity to keep h is u rin e n e u tra l o r a lk a lin e to litm u s . He r e c e i v e d c a lc iu m 10l a c t a t e g r a i n s th re e tim e s a. d a y and had be e n g i v e n p a r e n t e r a l calciu m glu co n ate by h is lo c a l p ra c titio n e r be fo re be in g sen t to Sydney. 3 10 3Tre atm e n t w i t h -\L ( a ^ s o l u t i o n o f -d im e rca p to p ro p a n o l 10 3i n p e a n u t o i l w i t h $ b e n z yl be n zo ate ) wa commenced a t 2 .3 0 a.m . v/ hen (14 . 4 ntg/ kg m l. p e r 50 l b s ) w ere g i v e n b y in tra m u s c u la r i h je c M p n in to h is butto ck. 4.4S u b s e q u e n tly m g/ kg were i n je c t e d e a c h "fo u r h o u rs 3 2f o r d o s e s , th e n .2 m g/ kg w ere g i v e n tw i c e d a i l y from 2 3 rd Jun e to 32 7th J u n e . H is o n l y r e a c t i o n to AI. was t h a t he s a id th e s m e ll p u t him o f f h is fo o d. . ... , , ... On th e m o rn in g o f t h e -S jr d June he s t i l l appe ared, to be ' 8e x o p h th a lm ic; h i s to n gu e was c le a n and he w as d bp e y8* b u t b y m id -d ay h e h ad g r e a t l y im pro ve d. He w as th e n much c l e a r e r m e n t a lly end k r 0020060 w as t a k i n g some fo o d a s w e l l as f l u i d s b y m outh. He s t a t e d t h a t h i s ja w s were s t i l l s o re and th a t h is m uscle p a in s , tho ugh p re s e n t, were ,, l e s s s e v e r e . ` He f e l t t i r e d b u t was u n a b le to s l e e p w ith o u t s e d a t i v e s . On th e f o l l o w i n g d a y h e lo o k e d b e t t e r , b u t had cram ps i n h i s . c a lv e s w hich were a l i t t l e te n d e r, and be was ve r y r e s t l e s s and a c t i v e i i n be d * He w as r e f u s i n g a l l food; f o r he s a i d i t t a s t e d o f B Al. H is e ye s were 8d ry and s o re 8. He had no d ia r r h o e a o r v o m iti n g . S t a i n g : th e n e xt' two S a ys h is * c o n d i ti o n g e n e r a l l y improved, 'and' h e be gan to e a t more fo o d . He had some h e a d ac h e , was s t i l l e x c e s s iv e ly a le r t , M s p u p ils were d ila te d ., end he appeared to he e xo p h th alm ic. Co n s id e ra ble d i f f i c u l t y was e xpe rie n ce d in in d u cin g s l e e p . He co m plain e d o f some l o c a l p a in f o l l o w i n g h i s BtL i n je c t i o n s and vom ited once. On th e 2 7th Ju n e he w as v e r y r e s t l e s s and m e n t a lly a c t i v e in th e e a r l y m o rning, h u t to w ards m id -d a y became u n s ta b le , re fu s e d 12.15tre a tm e n t and commenced w a lk in g around i n th e w ard. At p.m. he became hypopmanic and e scape d in to th e s tr e e t fo r a few m in u te s . . Be was re tu rn e d w ith pe rs u as io n * to th e ward and give n m orphine s u lp h a te , 4*4 1.10h yo S e in e hydrobrbfiide -and BAL mg/ kg a t p.m . His m ental - c o n d itio n was co n fu s e d , e x c ite d and de lu d e d . ' 1.39At P*ra* h e had 3X1 e p i le p t i fo r m f i t w i t h t y p i c a l c l o n i c and to n ic phase s and in vo lu n ta ry m ic tu r itio n . H o llo w in g h i s ,!f i t H he was h a llu c in a te d , d is o r ie n ta te d and tended to become v i o l e n t . ... . He t o r e up h i s pyjam as and f r u s t r a t e d an a tte m p t to g i v e him h yp e r to n ic g l u c o s e i n t r a v e n o u s l y a f t e r some 50 a l . load be e n g i v e n .- In s p i t e o f ' l a r g e d o s e s o f h yo s e in e hydrobrom ide* D i a l and sodium ph e n o barbito n e h i s psychom otor a c t i v i t y was l i t t l e abate d tho ugh he was l e s s v i o le n t . At J.JQ p.m. he passed urin e in to h is bed. BAB was g i v e n i n 4 . 4 rag/ kg 1.10d o s e s a t p.m . , 4 *3 0 P*33* snd 8 .5 0 p.m . bu t he a s v e r y r e s t l e s s and co n fu s e d and was o n ly p a r t l y c o n tr o lle d w ith fo u r h o u rly h yo s cin e hydrobrom ide. _ 28Op th e th Jun e he c o n tih u e d to be h a l l u c i n a t e d , d e lu d e d and diso rien tated. He was q u i t e i r r a t i o n a l - la u g h in g and t a l k i n g to h im s e lf w h i ls t p ro w lin g round th e room, and was most u n co o pe rative * He w as somewhat q u ie te n e d w i t h Hem butal and s l e p t d u rin g th e l a t e r part o f the n igh t. 4*4BAL i n d o s e s o f mg/ kg was give n a t 2.33- arid 6 .3O a.m . and J .2 mg/ kg a t 8 .30 p.m . , . By th e n e x t day he had g r e a tly improved - he could t a l k r a t i o n a l l y f o r b r i e f p e r io d s , was more c o o p e ra tive and, a s s i s t e d 1 4*4Item but&l, s l e p t m ost o f th e d a y. He r e c e i v e d AL m g/ kg a t b amt and 6 p.m. e ach day u n t i l 3rd J u ly . 30 On th Jun e h e was v e r y much im pro ve d, w as q u i e t a l l d ay, ,, and o n ly required s e d atio n a t n igh t. ......... . 3Be tw e e n 2 3 th Ju n e and rd J u l y h i s m e n tal c o n d i ti o n im pro ved and was normal e xce p t fo r in so m nia, u n p le as an t dreams w hich were s t i l l v e r y tro u b le s o m e , and r e s t l e s s n e s s . He f e l t Hd o p e ytt most o f th e tim e on a c c o u n t o f th e Hembuhal h e was r e c e i v i n g . . He. i n c r e a s i n g l y co m plain e d o f m u s cle p a i n s w h ich made him w ant to strsibfct c o n t i n u o u s l y , h u t b y 3yd J u l y , th e s e movements cau s e d so much p 1t ^ th a t he co u ld o n ly s i t up w ith co n s id e rable d i f f i c u l t y . Boring; tim e he had some abdom inal c o l i c w ith fre qu e n t bowel a c tio n s (approxim ately three per day). . r On 3 rd J u l y h i s to n gu e w as d r y and d i r t y and he d i d n o t 4.4so w e l l . He was g i v e n BAL mg/ kg fo u rth h o u rly be gin n in g s t 6 p.m .' - '' 4By t h J u l y h e f e l t b e t t e r and he co u ld o b v i o u s l y move with, much l e s s d is co m fo rt and h is abdom inal p ain s had abate d . H is o p tis . d i s c s and. fu n d i were n o rm al. 4.4Ba L m g/ kg fo u rth h o u r ly was 4 CO . CO o o 02 O o Wi - 9- c o n tin u e d t i l l 10 .5 0 p .n . when, in e r r o r , he r e c e i v e d . a do s e o f 8 . 8 s g / k g . He d e ve lo p e d a marked r e a c t i o n w i t h p a r a s t h e s i a e o f h i s lim bs , fa c e ahd mouth; he was gid d y, p r o s tr a te d and d ys p n a e ic, ' and had a c o n s tr ic tiv e pain in h i s ch e s t. H is a r te r ia l blo o d p r e s s u r e r o s e t o 19 0 / 13 O m o f m e rcu ry. Th e s e symptoms w e re ; t r a n s i e n t and b y t h e n e x t m orning he was f e e l i n g much im proved o ve r h is co n d itio n o f th e previo us morning - h is m uscle pain s were le s s , he f e l t be tte r, and he had l e s s abdom inal d is co m fo rt. A l l th e ? symptoms t h a t had o cc u rre d th e p r e v io u s n ig h t had va n is h e d . 5 14Prom th e th to th J u l y h i s p r o g r e s s was s te a d y and / o n l y in te r r u p te d b y th e de ve lo pm s n t o f a mild i n f e c t i o n in one b u tto ck which r a p id ly responded to Sulph adiazin e . n th e J t h J u l y he d e ve lo p e d a ra s h w h ich was e ryth e m a to u s : and m acu lar on th e arm and l e g s , b u t f i n e l y p a p u la r on th e p alm s J and s o l e s . A l l h i s p a in s va n is h e d , he became m e n ta lly q u i te norm al, and he re q u ire d d im in is h in g amounts o f s e d atio n each n ig h t. Afte r 10t h J u l y he had nausea^ o f t e n fith -vo m itin g ,. a f t e r e a ch i n je c t i o n o f 'BALi,n ;~. ; 2.9From 5 th to 13 th J u l y he r e c e i v e d m g/ kg BAL e i g h t h o u r ly 14 2 1.5and fro m `th to l s t J u l y mg/ kg tw ice a d ay. Blo o d p r e s s u r e r e a d in g s w e re u s u a l l y be tw e e n I5 0 -2 0 0 / IOO-IIO cm o f m e rcu ry d e p e n d in g o n how r e c e n t l y BAL had be e n g i v e n , b u t b y th e ' 1 514 t h J u l y h i s b lo o d p re s s u re was ? / So mm o f m e rcu ry. H is p u ls e - r a t e ran ge d be tw e e n 48 and 6 6 p e r m inute d u rin g th e f i r s t fiv e ! days, i n h o s p i t a l, d u rin g th e n e x t week between 60 and 75 pe r m in u te . 5 90and a f t e r th J u l y be tw e e n fO and pe r m in u te . H is o r a l te m p e ratu re varied be tw e e n 9 6 . 8 and $ 8 . 4 ^ d u r i n g t h e f i r s t te n d a ys a f t e r adm issio n but the. m a jo r ity .o f re a d in gs were below 9 8 ?. 28 . U n t i l th e t h J u l y h i s s le e p was a lw a ys in te rru pte d , b y dreams which gra d u a lly lo s t th e ir un ple as an t ch aracte r and on 50d i s c h a r g e from h o s p i t a l o n th J u l y h was s l e e p i n g and d re am in g n o r m a lly . H is r a s h d is a p p e a re d r a p i d l y a f t e r c e a s i n g BAI adm in istration . & labo rato ry Bata. - ... D a ily e xcre tio n o f le ad in the u rin e : Purnber o f d a ys s i n c e Urine lead content 24f i r s t , e xpo s u re to le ad ( ms n e r h o u rs ) < 23/6 4 24/ 6 28/6 2/7 4/7 5/7 6/ 7-- 9/7 - 5 9 13 15 16 17 18 20 2. Blo o d Co u n ts : 0.00 0 .30 0 ,11 0 .13 0 .12 .0 8 O.O3 O.O3 trace 37 ( adm ission V specimen) , (incom plete) j 250 0 - 2380 ' -- 2400 * 14.5 1002 3/ 6 Haem oglobin c o n c e n tr a tio n gramme p e r m l.; ve ry o ccas io n al s tip p le d red blood c e ll seen; to ta l: l e u c o c y t e s 14 *10 0 p e r c.mm. o f w h ich 8 l^ w ere ; ; n eutrophil gran ulo cytes. 9/7 13*7 100.-Haem oglobin '-co n ce n tra tio n gramme p e r m l.; - no s tipple d red blood c e lls seen; to ta l le u co cyte s ,/ . 777S0 O p e r c.iaa . o f w h ich $ w e re n e u tr o p h i l ' granulocytes* K 0020964 V* , 11 CASE I I . 34T . J . , age d * a m arrie d s to re m a n -d rive r w ith two c h i ld r e n , whs a d m itte d to l o y a l P r in c e A lfr e d H o s p ita l a t 2210 .3 0 p.m . on nd Ju n e . , 20On t h Jun e h e had a s s i s t e d R.K. in th e c o l l e c t i o n and d is p o s a l o f th e sludge on th e flo o r o f the tank already described. He wore p r o t e c t i v e ru bb e r kn e e b o o t s , ca n vas g l o v e s , b u t no r e s p i r a t o r w as worn. He a l s o n o t i c e d t h a t th e "fum e s " w ere v e r y bad in s id e th e tan k He d e ve lo p e d marked in s o m n ia, an o re xia., and a "s i c k l y f e e l i n g 2i n th e s to m ach" o n th e e v e n i n g o f o t h June and th e s e symptoms had i n c r e a s e d u n t i l h i s ad m is s io n t o h o s p i t a l . He had m ild d i a r r h o e a f o r a "fe w *days -,- w h ic h had ce as e d..o n : a r r i v a l i n Sydn e y*. . On ad m is s io n he f e l t ve r y t i r e d hut a p a rt from s l i g h t headache and tre m o r o f h i s h an d s , w h ich had be e n p re s e n t, f o r o n e d a y, he had no o th e r symptoms, ' c. = He a t t r i b u t e d h i s i n i t i a l g a s t r o - i n t e s t i n a l symptoms to .. "fo o d -p o i s o n i n g ", w h ich was p r e v a le n t a t t h i s tim e in th e H o te l in w hich he was s ta y in g , bu t th e developm ent o f in s o M ia and trem ors w ith marked a n o re xia cause d h i s to c o n s u lt a d o c to r , . ; H eitber h is past nor M s perso nal h is to ry revealed any rele van t facts . -/' ' . On Ex a m in a tio n ; He w as a r a th e r w o r r ie d , r u d d y -fa c e d , r e d -h a i r e d yo un g man. H is s k i n w as warm 'and d r y , h i s p u p i l s appe ared to be somewhat d ila te d but were o th e rw is e norm al, and a p a r t fro m e vid e n c e o f l a c k o f s le e p he ap pe are d well. He had a m oderate tremor o f bo th hands. H is a r t e r i a l blood pre s s u re was - 12 - A, 6612 0 / 7 5 ran o f m e r c u r y,. p u ls e r a t e p e r m in , and h i s o r a l* 96te m p e ratu re F . There were no o th e r abnorm al p h y s i c a l s i g n s . 125H is w e ig h t was Ik s ? " Tre atm e n t and P r o g r e s s : He was co n fin e d to feed end g i v e n b a r b i t o n e s e d a ti o n . H is u r i n e was ke p t n e u t r a l o r a l k a l i n e ' V- . in re a ctio n by o ra l potassium c itr a te ; s u ffic ie n t,flu id s were ' 2a d m in is te re d to ke e p h i s u r i n e volum e up to o r o v e r l i t r e s ppr die m , and calciu m la c t a t e was give n by s o u th . . . ' 3 10)42 3AIi ( ; -dim ercapfeopropanol in pe an u t o i l w ith 10% . be n zyl benzoate) was give n in tram u scu larly in to th e bu tto cks each fo u r h o u rs , commencing a t 12 .15 on 23rd Jun e , fo r fo u r d o s e s w h ich were 4 . 4 m g/ kg, 3 . 5 m g/ kg, 4 .4 jn g/ kg and 3 .5 s g / k g r e s p e c t i v e l y . * ' '. ' f o l l o w i n g the. f i r s t i n je c t i o n th e r e was a isod e r a te r e a c t i o n - he . s h iv e r e d , f e l t g id d y and th e n s w e ate d; he f e l t n au s e a te d , had some m u s cle p a i n s , and h e had o a in i n h i s abdomen and a t th e s i t e o f , th e in je c ti o n . B e a ctio n s c h a ra c te ris e d by nausea and vo m itin g, and u s u a lly w ith p ain s in h is e ars accompanied the n e xt th re e in je c tio n s o f BAL - i n e ach i n s t a n c e com ing on so ns T&?JQ m in u te s a f t e r th e i n j e c t i o n , : ; ' / .v.-v . ,, - ' . ' : On; th e d a y f o l l o w i n g ad m is s io n hiss a n o r e x ia d im in is h e d and he began to e at w e ll. 9 30 2.2At . - P*m* on t h i s day he had m g/ kg o f BAL i n je c t e d in to h is bu tto ck and t h i s do se was s u bs e qu e n tly give n a t 9 .3 0 each m o rn in g and e ve n in g d u rin g th e n e x t fo u r d a ys . He c o n tin u e d to * - have p ain in h is bu tto ck and e ars fo llo w in g each in je c tio n . KET 0020068 - 13 - In th e e ve n in g o f th e 2 5 th Jun e he became ve r y "b r i g h t n and co m plain e d o f some h e a d ach e . As h i s r e s t l e s s n e s s , w h ich had been p re s e n t s in ce adm ission was in cre a s in g, he was give n morphine s u lp h a te i n th e e v e n i n g . He had n o t s l e p t w e l l s i n c e ad m is s io n i n s p i t e o f b a r b i to n e s e d a ti o n , and i t had be e n n o t i c e d t h a t h i s p a lp e b ra l fis s u re s were widened so th a t he appeared exophthalm ic. . H is p u p ils were co n s id e ra b ly d ila te d du rin g th is p e rio d . . On th e m o rn in g ana a fte r n o o n o f th e 2 7t h he became v e r y 1 r e s t l e s s and u p s e t abo u t h i s fr ie n d (Cas e I ) , and fo r a w h ile he was most u n co o p e ra tive . However, he responded to in cre a s e d s e d a t i o n w i t h p h e n o b arbito n e and s l e p t w e l l . As he was r a t h e r r e s t l e s s and u n k illi h g to s ta y in bed du rin g th e fo llo w in g th re e days he was k e p t h e a v i l y s e d ate d w ith p h e n o b a rb ito n e . BAL 3 . 9 m g/ kg 1.9w as g i v e n 6 h o u r ly on ?8 th J u n e , mg/ kg 6 h o u rly o n 29 th June ' 30 3 3-9and from th June to r d J u l y mg/ kg was g ive n tw ice d a i l y . . v From th e 3 0 th Jun e onwards h i s im provem ent was c o n tin u o u s ; h i s e ye s became norm al and l o s t th e ir e xophthalm ic appe aran ce , h i s ' p u p i l s c o n t r a c t e d , h e bec^ae ^^'v ^ i i e t -and mo ^ a m e n a b l e man an d, a p a r t from a minor i n fe c tio n in th e l e f t b u tto ck ( r a p i d ly cu red w i t h S u lp h a d ia e in e ) h e made an u n i n te r r u p te d r e c o v e r y . - The do s a g e ? 1.9 4o f SAL was re duce d to mg/ kg tw ice d a i l y on th J u ly and to 1,9 11m g/ kg d a i l y on th J u l y ; h e r e c e i v e d h i s l a s t d o s e on 14 th J u l y 12 /75H is a r t e r i a l blo o d p r e s s u r e was q mm o f m e rcu ry o n 140/802 9 th June and mm o f m e rcu ry on 14 th J u l y . H is fo n di were ^ re po rte d to be norm al on 4 th J u ly. ... .D u rin g th e f i r s t f i v e d a ys a f t e r ad m is s io n h i s p u l s e r a t e -ir. u- ran ge d be tw e e n 5 2 and 60 p e r m in u te w ith, b u t th re e r e a d in g s o ve r 60 ; 97h i s o r a l te m pe ratu re ran ge d be tw e e n and 98 F fo r th e scost p a r t. Labo rato ry fin d in gs : , 1. D a ily e xcre tio n o f le ad in the urin e: :v Bate Days s i n c e e xp o s u re Co n te n t o f le a d i n U rin e -- 4g-a tP e r,e h o u rs , vo lum e i n m ilt 24th dune 26th June 2 7-28 th dune 28- 29th June 13 0 - s t d u ly 2-3 r d J u l y 4- 51* J u ly 5-&th J u l y . 7- 7th J u l y 4 6 8 9 11 13 15 16 17 O.0 9 0 .0 9 0.79 0.50 0.45 0 .24 0 .0 3 trace trace . 3640 4340 3450 10 50 2 Blo o d Co u n ts : 23rd June 5*67Bed blo o d c e l l s m i llio n pe r c . hed, ; . haem oglobin co n cen tratio n 17 . 2 gram e pe r 10 0 m l. ; t o t a l l e u c o c y t e s 11,0 0 0 p e r c.rata., n e u tr o p h i l g r a n u lo c y t e s 9Q$* H0 s t i p p l e d ' c e l l s were seen. DISCUSSION. Th e re i s no q u e s tio n t h a t b o th th e s e men were s u f f e r i n g fro m th e e f f e c t s o f t e t t a - e th yl le a d abs o rp tio n * and th a t the ro u te o f abs o rptio n w as bo th th e lu n g s and th e s kin jTh o u gh b o th m e n h a d c h a n g i n g am ounts o f le a d in th e ir u rin e specim ens s *i i t was in te r e s tin g to n o te th a t s o re l e a d was fo und i n th e u r in e from T . J . ( Ca s e I I ) th an fa th e u r i n e from B . X . ( Ca s e I ) who was more s e r i o u s l y a f f e c t e d and had much g r e a t e r e xp o s u re Th e e x c r e tio n o f le a d in th e u r in e i s v a r i a b l e , and, in th e e xp e rim e n ta l an im al and man, th e re i s u s u a l l y more e x c r e te d b y th e bo w e l th an b y th e 1,2 ,2 0 ,2 1. kidn ey a fte r the absorption o f te tra -e tb yl le ad . i t ig also K g 0020068 !  - 15 - p o s s ib le tlm t th e r e p y w ith BAL e f f e c t s th e amount o f le a d re c o ve re d fro m u r i n e a s e i t h e r th e compound o f BAB and le a d may be r e l a t i v e l y i n s o l u b l e and ' V .: < ' , " ' ' . ' '^v ' 2 2 . .` th e re fo re , n o t a p p re c ia b ly e x c r e te d , o r th e method u s e d f o r th e e s tim a tio n o f th e le ad co n ten t in th e u rin e nay not be adequate fo r the d e te ctio n o f BAB-leadicom po unds. In vie w o f th e lim ita tio n s o f the, ad s o rp tio n method o f e s ti m a ti n g ' le a d in th e u r i n e and c o n s i d e r i n g t h a t B-.K. ( Ca s e I) r e c e i v e d 3much l a r g e r d o s e s o f AL th an d i d T . J . ( Ca s e I I ) i t . s e e m s more l i k e l y t h a t th e amounts o f le a d re co ve re d were n o t tru e in d ic a tio n s o f th e amounts a c t u a l l y p r e s e n t and t h a t th e BAL-le ad compound was n o t re c o ve re d c o m p le te ly by t h i s m e tho d. The i n t o x i c a t i o n , i n T . J . ( Ca s e I I ) was r e l a t i v e l y m ild when com pared w i t h t h a t o f E.Kl. ( Ca s e I ) who was s e r i o u s l y i l l f o l l o w i n g much g r e a t e r e x p o s u re . As th e c l i n i c a l f e a t u r e s o f th e two men w e re p a r a l l e l th e d i s c u s s i o n w i l l l a r g e l y . c e n t r e round th e more s e r i o u s l y a f f e c t e d man. . Th e c l i n i c a l f e a t u r e s o f bo th men w e re t y p i c a l l y th o s e . fo l l o w i n g th e absorption o f te tra -e th yl le ad . In B.K. ( Ca s e I ) minor symptoms ap pe are d t ..- ff ' / '.l . ' ' ' a fe w h o u rs a f t e r e xp o s u re b u t w i t h i n 48 h o u rs s e r i o u s symptoms w e re p r e s e n t - - th e e a r ly develo pm en t o f co n fu s io n , r e s tle s s n e s s and o f an e p ile p tifo n n a tta ck in dicate d m assive abso rptio n o f te tr a -e th yl lead* -- B . K . f s i l l n e s s was a t y p i c a l i n t h a t h i s s e ve re symptoms alm o s t - c o m p le t e ly r e m i t t e d , after some 16 h o u rs o f tr e a tm e n t, f o r 4 d a ys d u r in g w h ic h he f e l t w e l l . Th e s e symptoms r e tu r n e d w i t h in c r e a s e d s e v e r i t y and h e became m a n ia c a l, tried to e s c a p e .a n d had another e p i le p t i f o r m a t t a c k . , . Th e s e s e ve r e symptoms r e m itte d a f t e r 2 d a ys o f tre a tm e n t b u t he re m ain e d w e l l f o r o n ly 4 d a ys 1 b e fo r e symptoms were a g a in rem arked. On t h i s o c c a s i o n h i s symptoms were n o t r e l a t e d t o th e c e n t r a l n e rvo u s s y s t em bu t to h i s i - 16 - g e n e ra l m u s cu latu re sad abdomen. Such d e f i n i t e re m is s io n s o f s e ve re symptoms do n o t c h a r a c t e r i s t i c a l l y o c c u r i n s u b je c t s w ith t e t r e - e t h y l le a d p o is o n in g. . . ;V". / ' ^ Bo th o f th e re m is s io n s m entioned above and th e f i n a l a b o litio n o f the la s t recrudescence c lo s e ly follo w ed th e adm in istratio n o f large doses 3o f a L. Fu rth e rm o re , e ach r e c u rre n c e fo llo w e d w i t h i n 4 d a ys o f t h e re due tSc*h o f t h e d o s e o f BAL to a m a in te n an ce l e v e l . The p a t i e n t h i m s e l f v &s m o s t i n s i s t e n t t h a t BAL r e l i e v e d h i s m u s cle p a i n s and abdo m in al d is c o m fo r t i & h is la s t recrudescence. I t i s s u g g e s te d t h a t th e c o u rs e o f th e i n t o x i c a t i o n i n E . E . ( Cag# j) ' was as f o l l o w s ; t e t r a - e t h y l l e a d , abs o rbe d from th e lu n g s and s k i n , beojtx r e l a t i v e l y co n ce n tra te d i n th e c e n tr a l n e rvo u s syste m and, when th e covTound bro ke down, to i n o r g a n i c l e a d s a l t s , s ym p to m w e re produced.* a d m i n i s tr a t i o n -o f BAL a n o n -t o x i c compound w as formed w h ic h w as , pa?hap%. r e l a t i v e l y i n s o l u b l e ; w ith , r e d u c t i o n o f t h e d o s e o f SAL e i t h e r some, o f n o n -t o x i c BAIi-le s S. compound, was bro ke n up f r e e i n g i n o r n a t e le a d * o-r e li s e t e t r a -e t h y i le a d s t i l l p r e le n t in th e o rga n ic s ta t e co n tin ue d to h e esimverteg ' . .. . v ,, to to x i c in o rga n ic le a d ; in e ith e r o r bo th in s ta n ce s / th e re w ere i$a3yeu| $e am ounts o f BAL p r e s e n t to re n d e r th e le a d n o n -t o x i c and symptoms f u r t h e r a d m i n i s tr a t i o n o f l a r g e d o s e s o f BAL a g a in had a f a l l a n t i d o t a l b u t r e d u c ti o n i n d o s age o n ce c a r e r e s u l t e d i n th e re c u rre n c e o f GymptesM^f ' t h e s e l a s t symptoms w e re p r o b a b ly due to le a d d i s t r i o u t e d th ro u gh o u t o Tgan is m a s s u f f i c i e n t tim e had now e la p s e d fo r t h i s to oeesarg o n ce 3 - 17 a &f a a &e d o s age o f BAX, had a f u l l a n t i d o t a l e f f e c t . ' ' 3- I t i s d i f f i c u l t to atb'vld th e c o n c lu s i o n t h a t BA * was th e a c t i v e a ge n t in the production o f rem issio n s, e s p e c ia lly as other therapy did not change a p a r t from some v a r i a t i o n in th e d o s age o f s e d a ti v e s . v A l a r g e amount o f BAIi w as g i v e n to R .K. ( Cas e I ) who r e c e i v e d some 6l grammes i n a l l . I t i s c o n s i d e r e d , n e v e r t h e l e s s , t h a t l a r g e r d o s e s s h o u ld have been give n fo r a longer period o f tim e in the e a r ly s ta ge s o f h is in to x ic a tio n . I t has ben repo rted th at fo r the r e l i e f o f encephalo pathy fro m merc a y p o is o n in g fa r h ig h e r d o s e s a r e r e q u ir e d th an fo r o th e r fo rm s o f m e rcury i n t o x i c a t i o n and a s im ila r s e t o f circu m s tan ce s may p r e v a i l in le a d in to xicatio n . ' I t seems im portant to s tre s s th e apparent need fo r continued h igh d o s e s o f Bill, i n a c u te le a d e n c e p h a lo p a th y - s m a lle r d o s e s may le a d to f a i l u r e and, i t is p o s s ib le ,fco i l l e ffe c ts . Some a r s e n i c a l compounds when com bined 1w i t h mol o f SAL h a ve been fo un d t o be m ore t o x i c th an th e o r i g i n a l a r s e n i c a l 3; ` ' . ?- 2com pound, th o u gh . ts o ls o f BAL re n d e r them n o n -t o x i c . I t appears th at 4;4 4f u l l d o s e s o f BAL ( g/ kg) s h o u ld be g i v e n e ach h o u rs t i l l a l l symptoms 4*4h a ve s u bs id e d and th e n d o s e s o f rag/ kg give n 'th r e e tim e s a d ay fo r an o th e r 14 d a ys b e fo r e c e a s i n g i t 3 a d m in is tr a tio n ; Tre atm e n t s h o u ld be i n s t i t u t e d im m ediate ly expo sure to to x ic co n ce n tratio n s o f te tr a -e th y l le ad hag taken p la c e ;.. ^^ v ly ,-;.. ; "h To x ic e f f e c t s from BAL o cc u rre d i n b o th men, mi l a y i n T . J . and lim ite d to some lo c a l p a in a t th e s i t e o f in je c ti o n apd an earache fo llo w in g 4.4e a c h i n je c t i o n o f rag/ &g* R.K. ( Ca s e I ) , on th e o th e r han d, shewed b o th a c u te and ch ro n ic t o x i c i t y . 2On th e e v e n in g o f th e I t h d a y o f tre a tm e n t 8.8he r e c e i v e d ; i n e r r o r , rag/ kg in one do s e and r a p id ly develo pe d p r o s tr a tio n , a c o n s t r i c t i v e f e e l i n g In h i s c h e s t, dys pn o e a, lim b and o r a l p a r s e s th e s ia e , and a f e e l i n g t h a t "h e had no n o s e " . H is blo o d p r e s s u r e r o s e to I9 0 / 13 O m o f m e rcu ry a t t h i s tim e . Th e s e symptoms w e r e -t r a n s i e n t and h a d a l l c le a r e d b y th e n e x t d a y when he f e l t much im pro ve d. On th e 15 t h d a y o f BAL ad m in is tratio n he deve lo ped a ty p i c a l drug rash - he h a d a m aculo -erythem atous ra s h on h i s fo re arm s , arms, th ig h s and l e g s w hich was m ain ly on th e d o r s a l s u r fa c e s and a p a p u la r ra s h on bo th palm s and s o le s . Itc h in g was q u ite m arke d. The ras h r a p i d l y d is a p p e a re d o n c e s s a t i o n o f BAl i n je c t i o n s . . Sl-MMARY. ., : 1 . Two men s u f f e r i n g fro m t e t r a - e t h y l le a d p o is o n i n g h ave be e n r e p o r te d . 2 . Bo th men w ere t r e a t e d w ith 2 :3 -d im e rc a p to p ro p a n o l (BM> o r . B r i t i s h A n t i - l e w i s i t e } and made f u l l r e c o v e r i e s . 2 33 . Go n tin u e d h i g h d o s a ge o f * -d iia e rc a p to p ro p a n o l ( 4 *4 rag/ kg . adm inistered a 1 0 so lu tio n in peanut o i l w ith 1 0 ben zyl be n zo ate in tra m u s c u la rly each 4 hours ) was n e c e s s a ry to produce . - a com plete an tid o tal e ffe c t. .... 4. Ac u te and c h ro n ic t o x i c phenomena fo llo w e d th e a d m i n i s tr a t i o n o f f t h e 2 : 3 -dim e rcapto pro pan o 1 s o lu ti o n i n bo th men bu t w ere h o t : V s e r io u s in, e i t h e r . . . ' V-^r ' : 3i ly th an ks a re due to Dr. -T.M.A. B a y, B io c h e m is t i n th e P a i r f a x In s titu te o f Patho lo gy, Royal Prin ce Alfre d H o s p ital, fo r the estim atio n s o f the co n cen tratio n o f lead in th e urin e specim ens. ' K E 002007 4 - k V" - 19 - r ef er ences. i M i . le h o e , R . A . : Te tr a -e th y l Le ad P o is o n in g. C li n i c a l An a lys is o f a 85 103 19 5s c r i e s o f ITo n -Fatal Cas e s ., J .A.M .A. : ?* `X 1 t >>* S s Ch l e , W .F.: T e t r a - e t h y l Le ad I n t o x i c a t i o n , and P o i s o n in g b y 1 R e la te d Compounds o f Lead. J .A.M .A. 105: 578* 1935 `- Ee h o e , H . A . , Thsmann, F. and Ch o la k , J . : An Ap p r a i s a l o f th e Le ad "> H azard s As s o c i a te d w ith th e D i s t r i b u t i o n and Us e o f Ga s o li n e . ,`i Co n ta i n in g T e t r a - E t h y l Le ad I I The Oc c u p a tio n a l Le ad Exp o s u re > ; o f F i l l i n g S t a t i o n Atte n d a n ts and Garage Me ch an ics . J . In d u s t. ; 18 42H yg. & To x i c o l. : , 19 3 6 . ;; * , , 4. * The A s s o c i a t e d E t h y l Company Ltd .# London. . . In fo rm a tio n c o n c e rn in g 1939th e P r o p e r t i e s , H an d lin g and M ix i n g o f E t h y l F l u i d . \. 5* Ke ho e , R . A . and Thsraann, E . : The Be h avio u r o f Le ad i n th e An im al 13 478 1931Organ ism . I I T e t r a -e t h y l Le a d . t o . J . H yg. : , * #. X| 6 . Ke ho e , E .A. t On th e T o x i c i t y o f T e t r a - e t h y l Le ad and In o r g a n ic Le ad 12 554S a l t s . J . Lab. A -Cl i n . Med. : , 19 2 7. Ji 7. C a s s e l l s , B .A.K. & Do d ds , E . C. : i i : 6 S l , .19 4 6 . ` "H T e t r a -E t h y l Le ad P o i s o n in g . ,,,,v .... - . . B.M.J. ,. ; 8 . P e t e r s , R . A . S to c k e n , L. A. and Thompson, R . H . S . : B r i t i s h A n t i Le w i s i te (BAL) Mature 156: 6l b t 1945* 7-': ' _ - ' . \''kr 4- . 'v:- ' . , fv/v'' 'j-V ' ',;^:VV-'V r 9. Ca r l e t o n , A . B . , P e t e r s , R. A. * S to c k e n , L.A,., Thompson, R . R . S . , and - * W illia m s * B . I . : The Tre atm e n t o f Co m p lic a tio n s o f Ars e n o th e ra p y - - w i t h BAL. J . C l i n . In v. 2 5 :4 9 7 , 15 4 6 . ' .10 Ah.~ , ' .` . ' v--- V ' V-^. ; ' . a.vv. --' " ' ' \ E a g l e . * M a g n u s o n , H . J . * and Fle is h m an * R. : The S ys te m ic Tre a tm e n t , - ' o f Experim ental Ars e n ic Po is o n in g (Mapharsan, Le w is ite , Ph e n yl . 25 451 1946-J`'r.;.v-vi Ars e n o x id e ) w i t h BAL J . C l i n . In v . *, . .;11 Lo n gco pe * , ! T.* Le u ts c h e r , J . A . * W in tro be , M .K., and J a g e r , V . : The ; Tre atm e n t o f A r s e n i c a l D e r m a t i t i s w i t h P r e p a r a ti o n s o f BAL. . J . C l i n . In v. 25: 528, 1946. ' .- " 12. Gilm an , A . , A l l e n , . . P . , P h i l l i p s , F . S . , and S t . Jo h n , E . t The Tre atm e n t o f Acu te S ys te m ic Mercu ry P o is o n in g in Exp e rim e n ta l 1An im a ls w ith BAL, Th i o s o r b i t o l , and BAL g l u c o s i d e , J . C l i n . In v . 25: 549. 1946. : < : 0020073 13. Lo n gco pe , W .T., Le u ts e h e r , J . A . s The Tre atm e n t o f c u te Me rcu ry P o is o n in g b y BAL J . C l i n . In v . 25*557 15)46. 1. f. t' --f .--r.. ' -.. --V '* - - .-V'. - . 014 . Began . B o o ts , B . H . , Gre ch in , A . p . : The Tre atm e n t o f Go ld f 2 3' B e r a a t i t i d e s , Use o f B a l { : -d i e r c a p to o r a p a n o l) . J .A.M .A, 133:752. 1947. . . 15. Lo c k i e , L . H . F o r e r o s s , B . U . , & Ge o rge , C . f , t Tre atm e n t o f Two r e a c t i o n s to Go ld . Re s po n s e o f Thro m bo penic Pu rp u ra and g ra n u lo c yto p e n ia to BAL th e ra p y. J .A.M .A. ' 133:754* 1947 A. 4.:16 . Cohen, & Goldman, The Tre atm e n t o f Acu te Go ld and A r s e n i c 2 3; . P o is o n in g.: Use o f BAL ( : ~ d iin e rcapto pro pan o l* B r i t i s h A n ti -Le w is i te ) J. A. M. A. 133: 749* 1947* ' 17 ' ' 2Ba rro n j E . S . G . ,. M i l l e r , . B . , B a r t l e t t , G . E . , Me ye r* J , & S in g e r T.P R e a c t i v a t i o n by B i t h i o l s o f Enzym es I n h i b i t e d by L e w i s i t e . B io ch e a J . 4 1:6 9 , 1947 . . .. ?.j. 18 . W| bb, E . C . , & 7an H e yn in ge n , B . : The a c t i o n o f B r i t i s h A n t i - L e w i s i t e 41 74 1947(BAL) on Enzyme S ys te a s Biochera J , :# . 19. S io e k e n , L . A . , Thompson, R . H . S . , & W h itta ke r* V . p . t B r i t i s h - A n t i - ; Le w is ite 4 An tid o ta l E ffe c ts Again s t Th erapeu tic Ars e n ica ls B io ch e a J . 41:47* 1947* . . 20. Ke ho e , B^A, :Lead Ab s o rp tio n and Le ad P o is o n in g . Med. C l i n . F . Am e rica 19 4 2 ( J u l y ) . ; 21. - JCehoe* ^ . A . , Ch o la k, J . , Hubbard, D .M ., Bambach , K . , KcITary, B . R . , . -l (. & S t o r y , R . Y. : Ex p e rim e n ta l S t u d i e s o n th e In g e s t i o n o f Le ad . -* Compounds. J , In d u s t. Hyg. & To x i c o l 2 2 :3 8 1 19 4 0 . > 2? . : P s n h a l l , L . T . : A Bap i d Method o f A n a ly s i n g U rin e f o r Le ad . - Le ad ' S t u d i e s XI. J . B i o l . Chem. 6 0 :4 8 5 , 19 2 4 . ` .. ') ` '' ' ' 2 3 . P e t e r s * R. A. A S to c k e n , L. A . : P r e p a r a ti o n and p h a rm a c o lo g ic a l 4 2 3 4. P r o p e r t i e s o f -h yd r o x y t s e t h y l - - ( -a m in o - -h y d r o z y p h e n y l) -l 3 2- d i t h i a - -a r s a e y c lo p e n ta n e ( Mar-jtiars ide-BAL cony.-mnd)/ ^ Biochem J . 41: 53* 1947* , 7K 0 0 2 0 <I