Document gaVL4KZzyaZn3qoOBpOQ7JEyV

The School of Medicine Department of Pathology Brinkhous-Buliiti Building THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL The University of North Carolina at Chapel Hill Prcclimcal Ed. gldg 22SH . Chapel Hill. N.C. 27514 October 24,1984 MEMORANDUM TO: Dr. David Weil, ECAO: EPA'RTP FROM: Dr. Paul Mushak.UNC-oCj#^ ` RE: Review of J.L. Pirkle et al. " The Relationship Between Blood Lead Levels and Blood Pressure and Its Cardiovascular Risk Implications", Comments on the above ms are offered below,being restricted to such issues as: 1) reliability of the exposure index used, Pb-B; 2) experimental studies of the Pb-B and blood pressure relationship, and 3) serum chemistries vs. renal function. The blood lead values employed in the subject study are the same values which have been extensively and entirely employed throughout the NHANESII study protocol.These measurements have been found to be of an extremely high quality and have survived highly critical analysis in various quarters.The history of these assessments are already part of the data base in EPA files for the Lead in Gasoline phasedovn process, and will not be reviewed here. Suffice it to say that the exposure index used was both appropriate and entirely satisfactory. As cited by the authors in the eubject report, a number of articles have addressed the lead-blood pressure relationship in terms of the renin-angiotensin system and other relevant endpoints.The study of Webb and coworkers,as cited in the report,indicate that in adult rats assimilating Pb via the GI tract,that moderate increase, in Pb-B occasion increased blood pressure via heightened vascular reactivity to alpha-adrenergic receptor activation.Perry and coworkers in their study noted in the report found a quite robust effect for low level effect of lead fed chronically to rats on systolic pressure.In the aggregate, the various experimental data sets in the literature do support the human population observations in the NHANES II survey. With regard to the availability of certain serum chemistries in the NHANES II survey relating to the existence of kidney dysfunction in subjects studied by the authors,i.e., serum creatinine, serum BUN,etc., Dr. Pirkle has indicated to me that he will have serum creatinine values momentarily and will plug these values into the analyses.If this measure correlates with BP and Pb-B,then one has a mechanistic connection possible;if no correlation,then no kidney dysfunction factor would appear to be at work.Either outcome would not detract from authors' conclusions. N36696 DU P050298721