Document VJ4xDXDoaKNndeJ5pYjdO8Xb8

To R. IC S c a le s j Lj JL -*.j l -A-J INTER-OFFICE iciO M C-eorge R o u sh , J r . , M. D. Su e j e c t A d o e z s s -xOCa 0 1u A o d k e s s New O rleans Da t e O c to b e r 28, A s y o u h a v e r e q u e s t e d , I h a v e r e v i e w e d D r . K e h o e 's r e p o r t e n t i t l e d " R e p o r t o t h e P ro g re s s of an Investigation to D evelop a S tandard for the T o lerab le C o ncentration of L ead in the A m b ien t A ir" , d ated O cto b er 17, 1968. I w ill s ta te f ir s t m y co n clu sio n s c o n c e rn in g the rep o rt, and then I w ill deal w ith specific details of the rep o rt. I w ill su m m arize w hat I think a re the conclusions to be draw n, both for new concepts as p resen te d , as w ell as any changes in view point of D r. K ehoe: 1. D r . K e h o e s t a t e s t h a t th i s s tu d y is a p p l i c a b l e to o n ly h e a l th y in d iv id u a ls . 2. He s ta te s th a t the b o d y b u rd e n of le a d in m a n d o es in c r e a s e w ith age, r e f le c tin g his ex p o su re, and he does not once m en tio n the w o rd eq u ilib riu m in this re p o rt. 3. 20 ;ug of l e a d p e r cu. m. of a i r w o u ld r e s u l t in a p o t e n t i a l l y h a z a r d o u s e x p o s u r e for the g en eral population. 4. 10 pg of le a d p e r c u .m of a ir w as n o t te s te d o v e r a s u ffic ie n tly la r g e p o rtio n of the day to d eterm in e w h eth er it w ould produce an effect in man;' that is, a ris e . in the u rin a ry lead excretion. 5. H is d a ta w o u ld in d ic a te th a t 42 h o u r s p e r w e e k o f e x p o s u r e a t 20 pig p e r c u .m , of ' a ir w ill produce an effect on the u rin e excretion, and when the rem ain in g h o u rs of the w eek w ith exposure of 1 ug p er cu.m , of a ir is b reathed, this w ould p ro - . d u c e a n e q u iv a le n t e x p o s u r e to a n a v e r a g e e x p o s u r e of 5 to 6 pig p e r c u .rn .o f a i r . o. S in ce we a r e s e a r c h in g f o r the h ig H e a F Ie v e l o f 'e x p o s u r e th a t d o es n o t in c r e a s e th e u r i n a r y le a d , K eh o e c a lls o u r a tte n tio n to th e f a c t th a t 21 h o u r s p e r w e e k ex p o su re w as w ithout effect. This^is^ eq u al to an a v e ra g e ex p o su re of 3 to 4 ug per cu m. ' ' I w ill now tu rn to a review of the details of D r. K ehoe's rep o rt. - In the Introduction: T h e p o i n t i s m a d e t h a t K e h o e is s t u d y i n g r e a s o n a b l y h e a l t h y , n o r m a l individuals, and the p ro b lem of rela tin g this study to the health of the infirm ^if is l e f t u n a n s w e r e d . (T h e T h r e e C ity S tu d y d id lo o k a^f c h r o n ic d i s e a s e s , a n d the sta te m e n t is m ade "n eith er the ra n g e s of individual values n o r the m ean s of lead concentrations in the blood in the grouped c a se s a re re m a rk a b le "). . 0 0 .12'944 N15284 F o r the f ir s t tim e, to nay know ledge, D r. Kehoe says that, at this low lev el of ex p o su re, acc u m u latio n does o ccu r (in the past, K ehoe said that th e re w as no accu m u la tio n a fte r 30). In s e v e ra l co n tex ts, D r. Kehoe re f e r s to a c c u m u l a t i o n - on th i s o c c a s i o n j u s t m e n tio n e d , a g a i n on P a g e 2, w h e n he m entions se le c tiv e ab so rp tio n into the sk e le to n , and th en on P age 7, w hen he sta te s th at the fail in blood lead again is due to the selectiv e ab so rp tio n of lead into the skeleton. * D r. Kehoe calls the accum ulation th at o ccu rs insignificant, but, insignificant in p o tential fo r producing h arm fu l effect. I believe th at D r. Kehoe is looking fo r the e a rlie s t m e asu re of accum ulation, a m e a su re of exposure, and far below any level that could produce a health effect. O n P a g e 2, h e s a y s t h a t w e c a n 't d e fin e th e e x p o s u r e of m a n in a n y p r e c i s e t e r m s , and co rre c tly so. I believe that the exposure of m an lies som e place betw een his exposure at am bient levels plus his exposure at tim es w hen the levels a re in c re a se d i. e., on o r n e a r th e ro a d w a y s . ' , F u r t h e r on P a g e 2, w h e n h e ta l k s o f l e a d b e in g s e l e c t i v e l y b e i n g ta k e n u p b y b o n e , th e re is no m ention.of an e q u ilib riu m sta te as he had e x p re sse d on n u m ero u s occasions in the past. He does state, again c o rre c tly so, that blood is a poor r e fle c to r of the body b u rd en of lead, but it is a rough ap p ro x im atio n of the body burden. The tru e c o rre la tio n betw een the two is not known. This fact does c re a te problem s w hen we a re trying to evaluate the effect of am bient lead on m an w hen we m e a su re blood leads. ' O n P a g e 2 a n d P a g e 3, D z\ K e h o e d i s c u s s e s th e m o v e m e n t of l e a d f r o m s o f t t i s s u e s into bone w h ere it is re la tiv e ly u n av ailab le and th at this co n stitu tes a safety facto r. This im plies fu rth e r that th e re is an accum ulation, but also that we a re using up a safety factor at levels found in.am bient air. A ls o c n P a g e 3, h e s t a t e s t h a t in th e r e c e n t -past, p o r p h y r i n s a n d d e l t a a m in o levulenic acid ab n o rm alities have b eco m e ap p aren t. The effect of lead on p o rp h y rin m e ta b o lism has b een known in the e a rly '5 0 's, if n ot in the '4 0 's. . On P ag e 4, D r. K ehoe s ta te s th a t a stu d y of b lo o d an d u rin e co n ten t of le ad can insure freed o m fro m lead intoxication. I believe that this re p re se n ts a poor choice of w ords, since all agree""that the p ro b le m is not fra n k lead poisoning, but ra th e r freed o m fro m all biologic effects of lead - w hich K ehoe undoubtedly m eant. - 2- 0012945 A l s o o n P a g e 4, h e s t a t e s t h a t h i s c r i t e r i o n of h e a l t h i s b a s e d o n : 1. A c r i t e r i o n th a t has s to o d the t e s t of tim e ( c e r t a in l y d e f e n s ib le ) ; and, 2. Is c o r r e c t in p rin cip le. lie docs not need to defend his study on th is b a sis, lie is only te s tin g , to d eterm in e the firs t evidence th a t th e re is a ris e in u rin e o r blood lead as a reflectio n of exposure - long before th e re is effect on porp h y rin s, ALA, o r any other biologic effect. In the E xperim ent: . T u rn in g to D r. K e h o e 's d is c u s s io n of the E x p e r im e n t, on P a g e 6, D r. K eh o e s a id th a t in 1967 his su b je c t w as e x c re tin g an in c re a s e d am o u n t of le a d (and th e re f o r e even at this lev el of ex p o su re he w as responding w ith an in c re a s e in u rin a ry lead). I w ill calculate as G oldsm ith probably w ill do: 42 hours p er w eek = o hours p er day. 6 /2 4 x 20 m 3 (re s p ire d ) / d a y x 20 u g /m 3 = 100 pg in h a led in the c h a m b e r. I S / 2 4 x 20 m 3/ d a y x 1 u g / m 3 = 15 jig i n h a l e d d u r i n g t h e r e m a i n i n g d a y . 115 ug re p re s e n ts the to tal lead inhaled p e r day. n e r e i o r * 11 D r . K e n o e ' s e x p e r i m e n t is c o ;c t , 115 jig sr a a y p r o d u c e s a e sp o n se , and if the 115 ug w e re in h aled a t a c o n sta n t le v e l o v er the e n tire 24 h o u rs , th e n 1 1 5 /2 4 = 5 to 6 jig p e r m 3 w ould be th e c o n c e n tra tio n w h ic h w o u ld p ro d u c e a resp o n se, an in crease in u rin a ry lead. F u r t h e r , in th i s s a m e p a r a g r a p h o n P a g e 6, D r. K e h o e s t a t e s t h a t 21 h o u r s o f ex p o su re p e r w eek d id n 't p roduce a re sp o n se . U sing the sam e m ethod of calculation as above: 21 h o u r s p e r w e e k = 3 h o u r s p e r d a y an d l / 8 x 20 x 20 = 50 pg. 7 / 8 x 20 x I = 17. 5 ug, an d 67. 5 jig p e r d a y = th e to t a l le a d i n h a l e d / d a y th a t d id n o t p ro d u ce a r is e in urinax-y lead . A gain, 67. 5 p g / 20 m3 = 3 -4 u g / m 3 w ould-be the co n cen tratio n w hich could be inhaled w ithout effecting the u rin a ry ex cre tio n of lead. Since D r. K ehoe say s th at 31. 5 h o u rs /w e e k produced a dubious change, this level of exposure w ould be in term ed iate b e t w e e n 3 t o 4 i g / m 3 a n d 5 t o 6 j x g / m 3. On P age 7, D r. K ehoe re a lly extends his ex trap o latio n . Ke sta te s th at if his e x p e ri m ent had been continued for 4 l/ 2 y e a rs, then the blood lead w ould have begun to ris e . (Again, giving evidence of an in c re a s e in body burden). Ke a lso adds th a t the effect observed on blood, th at is, a fall in the co n cen tratio n of lead is evidence of th resh o ld of detection, and (without statin g so in so m any w o rd s),'h e say s, this is a th resh o ld of in c re asin g body b urden - even though the co n cen tratio n of lead is fa ll ing. This obviously is only his 'in te rp re ta tio n of th is phenom enon. h e 0012346 In the D is c u s s io n (on P ag e 8), he s ta te s th a t is e v id e n t th a t 20 jig v/ill n o t be to l e r a te d by the hum an population, and he goes fu rth e r to state that if this ex p o su re w ere to continue through a lifetim e, it can h ard ly fail to be potentially h azard o u s. T his is q u ite an e x t r a p o l a t i o n fro m , a n 18 m o n th e x p e r i m e n t in one m a n th a t p r o d u c e d a r i s e in u rin e lead fro m . 025 to . 0425 m g /d ay . C oncerning D r. X eh o e's sta te m e n t th a t even a 73 hour ex p o su re is not s u ffic ie n t to in s u r e th a t 10 y ig /m 3 is a s a fe a m b ie n t s ta n d a r d is in d e ed a r e - . a s s e s s m e n t of his data. H ow ever, rev ie w in g his p a p e r of 1966 en titled ' " C rite ria for H um an Safety fro m C ontam ination of the A m bient A tm osphere w ith L e a d " , a n e x p o s u r e o f 42 h o u r s o f e x p o s u r e a t 10 j i g / m 3 p r o d u c e d a c h a n g e i n u r i n e e x c r e t i o n . T h e n . 31 x 20 m 3/ d a y x 10 p g / m 3 =. 62 p g , a n d . 69 x 20 x 1 = 13. S; a t o t a l of 75. 8 u g / d a y is t h e n c a l c u l a t e d a s th e a m o u n t t h a t w i l l p r o d u c e an increase. ' T his use of two se ts of data su g g ests th at the actu al am ount w hich w ill p ro d u ce a chang is the s a m e fo r the 10 o r 20 p g e x p o s u re le v e l. T h a t is, th e c o n c e n tra tio n x tim e f o r both of th ese ex p o su res is about equal. I b e l ie v e t h a t m y u s e of D r. X e h o e 's d a t a is r e a s o n a b l e a n d a l o g i c a l c o n c l u s i o n u s i n g th i s d a ta / is th a t about 5 pg does r a is e the e x c re tio n of le ad in the u rin e . The A lb a n y -B irm in g h a m stu d y of A P I-L IA should su b sta n tia te D r. K eh o e's conclusions (this stu d y w ill ex p o se 6 p r is o n e r s to 10 to 20 p g /m 3 fo r 22 h o u rs p e r d a y f o r up to 4 m o n th s, but only a f te r a s im ila r study had been com pleted in an im als. ) H o w wo w e r e l a t e D r . K e h o e ' s f i n d i n g s ^ i n t h i s e x p e r i m e n t a l s e t t i n g ^ t o t h e p r a c t i c a l p r o b l e m of le ad in a ir? D r. K eh o e's stu d y w as d e sig n e d to stu d y the p h y sio lo g ical handling of le ad in the ran g e in w hich it is found in the am b ie n t a ir. The Six C ity su rv e y h as b een d esig n ed to evaluate the influence of lead in a ir on blood lead - it is in terestin g that th o se c o n ce rn ed w ith this study have ag reed that the sam p lin g tool should be lead in blood b ecau se of the e x tre m e v aria b ility of lead in u rin e, w h e re a s, the blood b e tte r re fle c ts the body burden. T h i s s t u d y w i l l t h e n t e l l u s w h e t h e r t h e c o n c e n t r a t i o n o f l e a d in a i r , a n d h e r e w e k n o w Hi a t this is the actu al lead to w hich m an is ex p o sed ,h as produced an effect on the body bur'ion. . i. T he next point to be m ade is that, if the le v el of e x p o su re (the le ad in a ir) does p ro d u ce a m e a su ra b le response,-, then the next p ro b le m w ill be to decide w hat is the m a x im u m a c c e p t able resp o n se; th at is, w ithout h a z a rd . D r. K ehoe has not attem p ted to a n sw e r this question, but ra th e r, by in feren ce, he b eliev es th a t the lev el th at p ro d u ces a change in u rin a ry lead ex cre tio n should be the a ir quality stan d ard . I believ e the an sw er is b e st obtained by looking at populations w hich have significantly higher lev els of exposure, e ith e r n atu rally or as a resu lt of occupational exposure, and of course, occupational exposures a r e u s u a ll y h ig h e s t. LLA h a s f o r m u l a te d d e fin ite p la n s to do e x a c tly th i s . HE 001234 l' When the A lbany-B ir m ingham , Six City, and the study of occupational pooul 7.*.J O com pleted, we w ill be in a b e tte r position to decide on the a ir quality c r ite r ia for lead If th e re a re q u estio n s co n cern in g this rev iew , I a m s u re th a t I sh all h e a r th erra / G R /n cc : D r. G. F. K irb y " G e o ^ g e /ilo u s h , J r . , M. D. - a- KJF 0012948