Document p6REm8a6rBZEgkYqpkdaonaB

^ r si t c d e p a r t m e n t o f v e t e r in a r y p h y s io l o g y a n d p h a r m a c o l o g y 205 TEMP ORARY EAST OF H AECKER ST. P AUL, MINNESOT A 55101 October 4 , 1971 Dr . R. A. Kehoe Kett er in g Laboratory College o f Medicine Un ive r s it y o f Cin cin n a t i Cin cin n a t i, Ohio 45219 ,, Dear Doctor Kehoe, ' I have consider ed the issu e s you r a is e concer ning an apparent d iffe r e n ce in lead metabolism, depending upon the magnitude o f intake by in h a la t io n . As you p oin t o u t , your stu d ies in d icat ed an e s s e n t ia lly con stan t r a t e of accumulation o f lead as a r e s u lt o f d a ily or al a d m in ist r a t ion . I do not fe e l, however, t h a t the evidence you c it e r egar din g what happens with the in h a la t ion o f high con cen tr ation s o f lead leads to the conclusion t h a t the r a t e o f accumulation in the t o t a l body taper s o ff in t h is ca s e . I thin k your argument r e s t s on the assumption t h a t accumulation does not occur i f the blood le ve l and r a t e o f u r in ar y excr etion p la t e a u s. This would o f course be tr ue i f one could t r e a t the whole body as one k in e t ic compartment with r efer en ce to le a d . I think you would agree t h a t ther e is good reason to b e lie ve t h a t the body cannot be tr eated in t h is manner. F ir s t , I would c it e your own data on human experimental su b je cts r e ce ivin g lead o r a lly . M. R. is illu s t r a t iv e . Your graphs show him to be accumulating lead a t a more or le s s con stan t r a t e over 38 per iods o f 28 d ays. Ye t , a ft e r 3-7 per iods o f 28 days h is blood lead leveil seems to have reached a near - p la t e a u . The same appears to be tr ue o f h is u r in ar y lead excr etion a ft e r seven 28 day p e r iod s. I t seems to me t h a t t h is in d ivid u a l and other s r e ce ivin g lead o r a lly behave in e s s e n t ia lly the same manner as your su b je ct s r e ce ivin g r ath er lar ge amounts o f lead by in h a la t io n . In both cases the data suggest to me attain m ent o f a vir t u a l eq u ilib r iu m o f in put and output o f lead in er yth r ocytes and a cor r esponding p lateau o f ur in ar y lead e xcr e t io n . I suspect t h a t i f a t o t a l lead balance could have been measured in your su b je ct s br eath in g high con cen tr ation s o f le a d , you would have observed accum ulation, as you did in the su b je ct s r e ce ivin g lead o r a lly . COLLEGE OF VETERINARYMEDICINE HEALTH SCIENCES CENTER N5991 RSITY G DEP ART M E N T OF VE T E RIN AR Y P H YSIO LO GY AND P H ARM ACOLOGY 205 TEMP ORARY EAST OF H AECKER ST. P AUL, MINNESOTA 55101 2 As you p oin t ou t , the important p oin t is t h a t ther e is no evidence of long-ter m incr ease o f lead in the blood under con d ition s o f con stan t r a t e o f exposure and a s s im ila t io n . The presumption t h a t the concentr ation o f lead in the blood r e fle c t s in a general way the magnitude of the t o xico lo g ica lly s ig n ific a n t pool o f lead in the body could stand some fu r t h e r exam ination. I t i s , however, the b est index o f hazard we have fo r both man and an im als. I am cu r r e n t ly t r yin g to assess the p r e cision with which blood lead and ^ .h elatable lead r e fle c t q u a n t ifia b le p ar am eter s o f t o x ic it y . I t seems to me t h a t t h is is one o f the ar eas in need of some a t t e n t io n . I guess t h a t the only p oin t on which we seem to d iffe r is with r efer en ce to whether or not your su b je ct s in h a lin g lead a t ISO^ / n r * experienced a con tin u in g accumulation o f lead in the body a ft e r blood lead and ur inar y lead excr etion had e s s e n t ia lly leveled o ff. I do enjoy an exchan ge'of views on matters of t h is s o r t when both p a r t ie s are only seeking the t r u t ij, as is the case in t h is in s t a n ce . In t h is era o f inflamed s e n s ib ilit ie s , exchanges on environmental matters are not always so r a t io n a l. Sin ce r e ly, P. B. Hammond Pr ofessor PBH/ vl k COLLEGE OF VETERINARYMEDICINE