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Blood Lead and Blood Pressure Relationship in the Adolescent and Adult US Population William R. Harlan, MD; J. Richard Landis, PhD; Robert L. Schmouder, MD, MPH; Nancy G. Goldstein, MPH; Lynne C. Harlan, MPH Heavy lead exposure has been connected to cardiovascular disease, but modest exposures encountered in the general environment have not been associated previously with disease risk. The relationship between blood lead levels and blood pressures was examined using data from the second National Health and Nutrition Examination Survey. A direct relation ship was found between blood lead levels and systolic and diastolic pressures fgr men and women and for white and black persons aged 12 to 74 years. Blood lead levels were significantly higher in younger men and women (aged 21 to 55 years) with high blood pressure, but not in older men or women (aged S6 to 74 years), in multiple regression analyses, the relationship of blood lead to blood pressure was independent of other variables for men, but not for women. Dietary calcium and serum zinc levels were inversely related to blood pressure. (347W4'ig85;253T53d-534) ~ '-------------- ~~ INTENSE and prolonged lead expo sure has a long historical association with toxic effects to multiple organ systems, including the cardiovascular system.1J Early observations of car diovascular toxic effects disclosed an increased incidence of stroke or renal impairment following heavy industri al exposures, and hypertension has been found in association with toxic reactions to lead following consump tion of lead-containing moonshine whiskey.' Recently, interest has shifted to possible harmful effects of lead at lower levels of exposure that are commonly found in the general population. Potential effects on child- From the School of Medicine (Drs Harlan and Schmouder) and the School of Public Health (Dr Landis end Mss Goldstein and Harlan). University of Michigan, Ann Arbor, Reprint requests to Towaiey Center. University of Michigan Medical School, Ann Arbor, Ml 48109 (Dr Harlan). hood intellectual development and on adult blood pressure have been de scribed in populations encountering common environmental sources.*'' The second National Health and Nutrition Examination Survey (NHANES-II) examined a representative sample of the US population and found that blood lead levels were related to ambient environmental exposures.'-' The levels for many children in this survey were above levels potentially associated with health effects, al though the threshold level for toxic effects remains controversial. In ado lescents and adults, toxic effects of low-level exposure to lead have received less attention, but several studies have indicated that commonly encountered lead exposure may be directly related to elevated blood pressure.'' These studies have demon strated a direct relationship between blood pressure and relatively low lev els of lead exposure.'* The relationship between lead and blood pressure has additional interest because it may clarify recent observa tions about the association between calcium intake and blood pressure.911 Lower dietary calcium intake is asso ciated with higher blood pressures. Lead and calcium follow similar metabolic pathways, and decreased calcium intake could aggrevate the toxic effects of lead exposure."1' Oth er nutritional factors and trace met als have been shown to aggrevate or ameliorate toxic effects of lead. To examine possible relationships be tween blood lead and blood pressure in a representative US population, we analyzed data from the adolescent ; and adult components of NHANESII." This survey includes extensive nutritional and trace metal data that permit examination of the blood lead and blood pressure associations as well as interactions among environ mental variables. A direct relation ship is documented between blood lead and blood pressure at relatively low blood lead levels in these analy ses. POPULATION AND METHODS The NHANES-li was conducted from 1976 to 1980 on a representative sample of the civilian, noninstitutionalized US popu lation aiied 6 months to 71 years. A probability sample of 27,801 persons was selected, and 20.322 were examined (73% response rate). The complex sampling 530 JAMA. Jan 25, 1985---Vol 253, No. 4 Blood Lead--Harlan et al TBH 35003 4 DUP050298663 design and details o( the examination procedures, laboratory performance, and quality control are contained in several reports.1"1* Examinations were performed in mobile examination centers, and the medical evaluation included medical histo ry', physical examination, anthropo metric measurements, dietary interview (24-hour dietary recall and food frequen: ey), laboratory tests, ECGs, and chest roentgenograms. A manual of operations, Bpecial interview and examination proto cols, and specifically trained interviewers and examiners were utilised to maintain structured and standardized conduct of the survey at all sites. Dietary intakes were determined by 24-hour dietary recall and by questionnaires about frequency of consumption of foods. The nutrient intake from the 24-hour recall was quantified for each person using a current nutrient data bank. The frequency of consumption of food groups was scaled to permit quantifi cation of customary food consumption for the six months preceding the examination. . Three blood pressures were recorded for each examinee: with the patient seated early in the examination, supine midway through the examination, and again seated near the end of the examination. The American Heart Association recommen dations on blood pressure recording were followed and an appropriate sized cuif selected. The first- and fifth-phase Korotkoff sounds were taken as systolic and diastolic pressures, respectively. The second seated blood pressure was used in these anslyses, but analyses using the first _ pressure with the patient seated or a mean of both pressures with the patient seated afforded similar results. Height and weight were measured in a standardized manner, and skin-fold thickness was mea sured in the triceps and subscapuiar areas using Lange skin-fold calipers. Blood for hematologic and nutritional analysis was obtained by venipuncture. After preparation, these samples were shipped to the Clinical Chemistry Divi sion, Center for Environmental Health, Centers for Disease Control, Atlanta, and analyzed.1' Blood lead was analyzed by atomic absorption spectrometry on oddnumbered samples from examinees aged 12 to 14 years.""' Specimens were analyzed in duplicate, and an extensive qualitycontrol system was used to ensure accu rate assessment without laboratory drift.' Serum zinc and serum copper were ana lyzed by atomic absorption spectrome try.-' The analysis of data from complex sam ple designs such as used in the NHANES-II requires special statistical techniques if the findings are to be projected as repre sentative of the US population." Alt statis tical analyses were performed using these analytic approaches, and, consequently, Blood Lead Concentration, gg/dL (Natural Logarithm Scale) Relationship between diastolic blood pressure and natural logarithm of blood lead concentration lor four race-sex groups aged 12 to 74 years during period 1976 to 1980. Sample sizes are limited at extremes of distributions and variability is increased. For black women, parentheses indicate that these points comprise only three or four persons. the results can be' extrapolated to the general population during the 1976-1980 period.2" The analytic strategies and the computer software used to implement these weighted analyses are described in detail elsewhere.""1 Because of skewed distributions, blood lead levels were trans formed to the natural logarithm for corre lational analysis. The relationships between blood pres sure and other variables were examined in two ways. Men and women were stratified into normotensive and hypertensive cate gories and mean values for relevant vari ables contrasted across the categories. Diastolic high BP was ^fined__as_9_.ni m Hg or above'for younger persons (aged 24 to 55 years) and for older persons (aged 56 to 74 years). Isolated systolic high BP was defined as systolic pressure of 160 mm Hg or greater and diastolic pressure less than 90 mm Hg. This condition was found primarily for those aged 56 to 74 years. Differences in mean values for these vari ables between the blood pressure sub groups were tested using an adjusted f statistic.*' Simple correlations between blood pres sure and blood lead were determined, and multiple linear regression models were used to explore and clarify the numerous joint relationships among selected vari ables and blood pressure. For example, , > blood pressure had numerous _ significant O ' relationships to age, weight, nutrient intake (including dietary calcium}" and trace metals. These joint effects on blood pressure were clarified by fitting the mul tiple linear regression models in a step wise manner using systolic and diastolic pressures as the dependent variables. This technique selects initially the independent or predictor variable that explains the greatest variance in the dependent vari able (systolic or diastolic pressure) and selects additional explanatory variables only if they make significant independent contributions after adjusting for the effect of previously selected variables. Thirtyfour variables were identified as having significant univariate correlations with blood pressure and were entered into this stepwise procedure. Separate predictive models were developed for men and wom en. The final predictive models contained l only variables making statistically signifi- j cant (P<.05) contributions after utilizing i techniques to adjust for the complex sur vey design and sample. To test for the effect of pharmacologic therapy, predic tive models were developed for the sub sample of persons who were not receiving JAMA, Jan 25, 1985--Vol 253, No. 4 Blood Lead--Harlan et al 531 TEH 0350035 DUPO 502 98664 Table 1.--Mean (SE) Body Mass Index. Calcium Food Intake, and Levels of Blood Lead, Serum Zinc, and Hemoglobin by Blood Pressure Category for Men and Women, US Population, 1976 to 1980 Variables by Subgroup Ages 21*55 yr Normal BP {<90 mm Hg) Diastolic High BP (>90 mm Hg) Sample size Blood lead. pg/dL Body mass index, kg/sq m Serum zinc, pg/dL Calcium foodst Hemoglobin. g/dL 1.043 { , 475 16.9,'(0.33) ' ; 17.9*(Q.49) 24.7 (0.13) 27.4*(0.26) 92.0 (0.76) 91.8 (0.90) 12.9 (0.33) ^11.i30-44) 15.1 (0.05) 15.5 (0.08) Sample size Blood !e8d. /ig/dL Body mass index, kg/sq m Serum zinc, Calcium foods Hemoglobin, g/dL t.316 11.5 (0.26) i 23.6 (0.19) 84.1 (0.55) 11.2 (0.40) 13.3 (0.05) Denotes statistical significance at P<.05. tScaled frequency of consumption. 263 12.3*(0.3S) 20.6*(O.43> 83.0 (1.07) (f0.0*D:0.53) 13.4 (0.11) Normal BP (<160 and <90 mm Hg) Men 660 16.4 (0.28) 2S.4 (0.18) 88.3 (0.96) 11.4 (0.41) 14.9 (o.oa) Women 769 t2.9 (0.34) 25.4 (0.21) 85.0 (0.51) 11.5 (0.42) 13.6 (0.06) Ages 56-74 yr Diastolic High BP {^90 mm Hg) 353 18.9 (0.50) 27.1 *(0.23) 86.9 (0.99) tG.5 (0.39) 15.0 (0.07) 320 12.9 (0.31) 29.2*{G.36) 82.S'(0.97) 10.2`(0.5t) 13.8 (0.09) Systolic High BP (2:160 and <90 mm Hg) 38 ^ t64> (1.37)-----' 24.9 (0.73) ai.i*(a.ii) 13.7 (1.93) 14.4*(0.18) 68 13.1 (1.10) 25.8 (1.13) 82.8 (1.79) 11.0 ( 1.17) 13.3 (0.24) antihypertensive therapy and the models compared with the entire group including those receiving therapy. No important differences were identified, so the reported results comprise all individuals having blood lead dHermmafions'. ' RESULTS Blood lead levels were directly related to systolic and diastolic blood pressures for men and women aged 12 to 74 years. The relationship between the natural logarithm of blood lead and diastolic pressures is illustrated for the four race-sex groups in the Figure. The correlation coefficients for white and black women were .11 and .22 (Pc.0005), respectively, and for white and black men were .16 and .11 (Pc.001), respectively. The rela tionship was essentially linear, but the means were less stable at either end of the distribution of lead values because of small sample sizes, partic ularly for the black subgroups. Be cause of the observed secular trend downward in blood lead levels during the 1976-1980 survey period,' compar isons were made for each of the four years in the survey. A similar linear relationship was found for each year of the survey. Men and women were stratified by blood pressure status and separated into two age groups (Table 1). Blood lead levels were significantly higher in younger men and women (aged 21 to 55 years) with high diastolic pres sure than in those with normal blood pressure (P<.05). However, in older 7 u v (/ Table 2.--Standardized )' >' Coefficients for Multiple Regression Models of Systolic and Diastolic Pressures in Men' Variable r2 n Age Age* Body mass indejc ...CwftishtXfeaight*) f Age (blacks) ( Race-*---- Blood lead (In scale*) Hemoglobin Serum zinc Systolic .236 2,823 .230 .100 .330 .042 .061 .074 -.048 Diastolic .274 2.618 .176 -.109 .328 .040 .070 .049 .114 -.038 `Blood lead analyzed on natural logarithm scale. Table 3.--Standardized Coefficients for Multiple Regression Models of Systolic and Diastolic Pressures in'WorTinn ' Variable________Systolic r2 n Age Age2 Body mass index (weight/height*) Serum zinc RBCs Dietary calcium Alcohol (oz/wk) .363 2,905 .430 .164 .290 -.058 .060 -.039 /> \: Diastolic .269 2,897 .212 -.039 .356 -.052 .105 -.048 .054 persons (aged 56 to 74 years), blood lead levels were not significantly dif- . ferent for any of the blood pressure categories and there were no impor tant trends. Serum zinc levels were significantly lower for older hyper tensive women and for men with isolated systolic hypertension. For younger persons, serum zinc levels tended to be lower in those with hypertension, but this was not statis tically significant. Dietary calcium intake (calcium foods) was signifi cantly lower in younger hypertensive men and women, but in the older group was significantly lower only for hypertensive women. These findings regarding calcium intake and blood pressure are similar to those from the earlier NHANES-I survey.' Men and women in both age ranges had signifi cantly greater body mass index {weight/height2) with diastolic blood pressure elevation, but no differences were found for systolic high blood pressure. Blood lead levels and serum zinc levels were higher for men than for women, except for serum zinc among those classified as having iso lated systolic high blood pressure, where there was no significant differ ence between men and women. Predictive models for systolic and diastolic blood pressures are pre sented Tdr" men (Table 2) and for women (Table 3). The variance ex plained by the model (r2) and the sample size (n) are indicated in the first and second lines of each table. Each of these standardized regression coefficients is statistically significant (P<.05) when incorporating both the weights and the design effects into the final model. Age and body mass 532 JAMA. Jan 2S, 1985--Vol 253, No. 4 Blood Lead--Harlan et al TEH 0350036 DUP0502 98665 index were significant and indepen- groups. In the United States, blood increasing weight at older ages. i dent predictors of blood pressure in lead levels are relatively higher in Moreover, blood lead levels increase NHANES-II, as was previously found blacks than whites and higher in men with age, as does blood pressure. The in NHANES-I, conducted from 1971 than women, and, interestingly, these multiple regression analysis permits to 1975.' An age-squared term was same relative race-sex rankings apply separation of the unique effects of selected because the relationship be to blood pressures for younger per age, weight, and blood lead while tween blood pressure and age is cur sons. There is no ready explanation adjusting for the confounding effects vilinear across this wide age range.- for the race-sex differences in blood of generally parallel trends in age, For men older than 55 years of age, lead levels, although heavier occupa weight, blood lead levels, and blood diastolic pressure has a more rapid tional exposures, urban environment, pressure. Using this analytic tech increase in slope than for older wom and perhaps different metabolic han nique, blood lead was found to con en. Blood pressure increases more dling have been cited.31'1' The relation tribute independently to the predic- rapidly with age in black persons, ship of blood lead to blood pressure, tion of systolic and diastolic pressure primarily men, and the race variables has clinical relevai :. Younger men) in men, even after adjusting for the in Table 2 quantify this relationship. and women (aged fo 55 years) with\ contributions of more than 30 other For men, blood lead had a significant diastolic high blood-pressure had sig- \ variables (Table 2). Dietary calcium relationship to systolic and diastolic nificantly higher blood lead levels \ was among the variables having a pressure that is independent of the than those with normal pressures ) blood pressure relationship when con- relationships between other variables (Table 1). However, there were no sidered alone, and this is illustrated and blood pressure. Although the significant differences in blood lead by the significantly lower dietary . J' ^ simple linear relationship between levels in older men and women (agecf\ calcium intake in hypertensive per- ' \ blood lead and blood pressure was 56 to 74 years) with diastolic high \ sons (Table 1). However, when lead k statistically..significant forjwpmen, blood pressure or isolated systolic / was included in the_rncdel, dietary /* blood lead was not" Independently high blood pressure. In general, prevtoj^calclum_was not selected in the pre- \ related to blood pressure after acjjust- ous reports of an association between! diction of male blood pressure but ing for the joint effects of the other body lead and hypertension have was selected for female blood pres- I predictors in the model (Table 3). focused on heavily exposed individu sure, and blood lead was not. '-'Serum zinc was inversely related to als with high (>60 jig/dL) blood lead Although blood lead levels were lower blood pressure for both men and levels. An important exception is the on average for women than men at women. Dietary calcium intake was report of Beevers et al,' who studied every age and for both races, this inversely related in womenTbut not in individuals living in an area of Scot- /probably does not explain the lack of u, . . men. Alcohol intake' `whs' directly land with relatively high levels of>Kan independent lead effect in women, -)' v. refated to diastolic pressure in wom lead in the water supply. They found "Human and animal studies have indi en. Red blood cell count or hemoglo: that hypertensive men had signifi cated that at comparable levels of bin level was directly related to blood cantly higher blood lead levels (27 exposure, blood lead levels are lower pressure in women and men, respec /ig/dL) than normotensive men (24 for females than males and the toxic tively. The predictive models ex- jug/dL), although the ranges for both manifestations are less.5'23'2* In the plained more variance in blood pres groups were at levels customarily study by Beevers and colleagues,' sig sure (r3 of .23 to .36) than did similar considered "safe." Therefore, in this nificantly higher blood lead levels models from the NHANES-I that did US survey and in the Scottish study. were found for men with hyperten- not include trace metal measure significant relationships to blood"! sion than for normotensive men. ments.' pressure were found at lead levels 1 However, women with hypertension COMMENT previously considered "nontoxic." y did not have significantly higher jfl Many environmental factors can blood lead levels than normotensive $! Lead is ubiquitous in the human influence blood pressure, and initial women. vr environment and has no known meta analyses of NHANES-II indicated Nutrients and trace metals, espe bolic utility but does have a potential that more than 30 variablesJiad sta-__ cially cations, can ameliorate or for toxic health effects. In this survey tistically...significant associations, aggravate toxic effects of lead. Cal , of the US population conducted from many representing overlapping" or cium and zinc have metabolic and -.a ' / 1976 to 1980, there was a direct and confoundlng'felatronships. To deter physiological effects that compete,^, ! linear relationship between blood mine whether the lead relationship to with lead, and decreased intake of`f' /\ ''' lead"and bloocTpressure. This associa blood pressure was an independent calcium, in particular, can aggrevate tion was statistically significant for effect, multiple regression models the toxic effects of lead. Diets defi- .d-- systolic and diastolic pressures, and were developed. This analytic ap cient in calcium increase lead absorp- n the effect was found at blood lead proach adjusts for the contribution of tion and decrease excretion. In recog ft levels of lessthan 30 ug/dL. which is each predictive variable as it is nition of this effect, it was common to the current ("toxic" /definition for selected and adds new variables only provide workers in the lead industry occupational exposure.3' This direct if they contribute independently to with free milk to prevent occupation relationship was observed in men and the prediction. For example, age and al toxic effects of lead.3' In this sur women and in both races, despite body mass were both strongly related vey, the earlier NHANES-I, and other differing levels of blood lead and to blood pressure, and this relation population surveys, low calcium in blood pressure among the race-sex ship was partially confounded by take has been associated with higher JAMA. Jan 25. 1S85--Vol 253. No. 4 Blood Lead--Harlan et al 533 TEH 0350037 DU P050298666 blood pressures/'" The survey finding that lower dietary calcium and higher blood lead levels are associated with higher blood pressures is compatible with the known metabolic interac tions among these metallic cations. Zinc is similar to calcium in its tissue metabofic "'interactions with lead,1' and the multivariate modeljsuggests that 'zinc"Has' ~aH~"elfect Qn blood pressure that opposes the effect of lead. However, lower zinc levels per se are not associated with hypertension (Table 1). No causal inferences should be drawn from this cross-sectional sur vey about the blood pressure effects of lead, calcium, and zinc, although these observations from the general population are consistent with exten sive animal studies of lead toxic effects and trace metal interactions. Animal studies have investigated the ability of various levels of lead expo sure to alter blood pressure and explored mechanisms that linked lead exposure to elevated blood pressure. Recent animal studies have focused on relatively low levels of exposure and have found that blood pressure can be increased at blood lead levels of 40 jtg/dL.* The increased blood pressures developing at these low lead exposures have been characterized by increased plasma renin and altered vascular reactivity to a-adrenergic stimulation.14"** There is no direct evi dence that these mechanisms are important in humans, although a case report indicates renin suppression with hypertension in chronic lead intoxication, and these changes were attributed to lead deposition in the kidney/ Batuman et al* found in creased tissue lead that could be mobilized by chelation in hyperten sive persons. They suggested that renal toxic reactions were responsible for the hypertension. The patient populations studied by these workers had greater lead exposure than would be found in the general population, and the proposed mechanisms of renal damage or renin alteration may not be directly referable. Multiple environmental sources ex ist for human exposure to lead. Occu pational exposure, ambient environ ment, and consumption of water from lead piping have been linked to ele vated blood lead levels/5"" Analyses of data from this survey indicate that in the United States, a major alterable source for the general population is atmospheric contamination' with al- kyllead from gasoline,additives." The 37% decline in blood lead levels dur ing the years of this national survey, 1976 to 1980, and the high correlation (0.95) between lead production and blood lead are compatible with the conclusion that this represents a major environmental source/ During this period, lead additives to gasoline were reduced, as was total consump tion of automotive gasoline, and blood lead levels declined in the general population. Water, principally soft water, can contain elevated concen trations of lead apparently released from the piping/ However, a recent study in Boston, which has soft water, found no relationship between the lead content of water and blood pres sure/8 Our analyses of the NHANES- II data provide a link between blood y ^lead levels and blood pressure, but the 1 \cross-sectional nature of the survey 1 limits inferences of causality. 1 This study was supported by grant AG 04401 from the National Institutes of Health and a pilot grant from the Michigan Diabetes Research and Training Center-. 1. Tanquerel des Planches L: Traite des mala dies de plomb on saturnines. Paris, 1839, pp 550. 2. Baker EL, Landrigan PJ, Barbour AG, ct al: Occupational lead poisoning In the United States: Clinical and biochemical findings related to blood lead levels. Br J Ind Med 1979;36:314322. 3. Me Allister RG, Michelakis AM, Sandstead HH: Plasma renin activity in chronic plumbism. Arch Intern Med 1971;127:919-923. 4. Needleman HL, Gunnoe C, Leviton A, et al: Deficits in psychologic and classroom perform ance of children with elevated dentine lead levels. N Engl J Med 1979;300:689-695. 5. Beevers DG, Erskine E, Robertson M, et al: Blood-lead and hypertension. Lancet 1976;2:1-3. 6. Mahaffey KR, Annest JL, Roberts J, et al: National estimates of blood lead levels: United States, 1976-2980: Association with selected demographic and socioeconomic factors. N Engl J Med 1982;307:573-579. 7. Annest JL, Pirkle JL,, Makuc D, et al: Chronological trend in blood lead levels between 1976-1980. N Engl J Med 1983;308:1373-1377. 8. Batuman V, Lundy E, Maesaka JK. et al: Contribution of lead to hypertension with renal impairment. AT Engl J Med 1983;309:17-21. 9. Harlan WR, Hull AL, Schmoudcr RL. et al: Blood pressure and nutrition in adults: The National Health and Nutrition Examination Survey. Am J Epidemiol 1984;120:17-28. 10. Keateloot H, Gebocrs J: Calcium and blood pressure. Lancet 1982;1:813-815. 11. Garcia-Palmieri MR, Costas R, Cruz-Vidal References M, et al: Milk consumption, calcium intake and decreased hypertension in Puerto Rico. Hyper tension 1984;6:322-328. 12. Mahaffey KR, Michaclson 1A: The interac tion between lead and nutrition, in Needleman HL (ed): Low Level Lead Exposure: Tke Clinical Implications of Cun-ent Research, New York, Raven Press, 1980, pp 159-200. 13. Six KM, Goyer RA: Experimental en hancement of lead toxicity by low dietary cal cium. / Lab Clin Med 1970;76:933-942. 14. Plan and Operation of the Second National Health and Nutrition Survey, 1976-00, Dept of Health and Human Services publication (PHS) 81-1317. Hyattsville. Md, National Center for Health Statistics, 1981. 15. Laboratory Procedures Used by ike Clini cal Chcmistt'y Division, Cental's for Disease Control, for the Second National Health and Nutrition Examination Survey (NHANES II) I976-IS80. Atlanta, Centers for Disease Control, 1981. 16. Barthat WF, Smrek AL, Angel GP, et al: Modified Delves cup atomic absorption determi nation of lead in blood. J Assoc Off Anal Ckem 1973;50:1252-1256. 17. Delves HT: A micro-sampling method for the rapid determination of lead in blood by atomic-absorption spectrophotometry. Analyst 1970;95:431-438. 18. Clinical Applications of Atomic Absorption/Emission Spectroscopy. Lexington, Mass, Instrumentation laboratory Inc. 1972. 19. Analytical Methods for Absorption Spec troscopy. Norwalk, Conn, Perkins-Elmer Corp, 1973. 20. Landis JR, Lepkowski JM, Eklund SA, et ah A Statistical Methodology for Analyzing Data From a Complex Sun'ey: The First National Health and Nutrition Examination Survey, Dept of Health and Human Services publication 821366. Hyattsville, Md, National Center for Health Statistics, 1982. 21. Survey Research Center Computer Sup port Group: OSIRIS IV User's Manual Ann Arbor, Mich Institute for Social Research. 1979. 22. NIOSH Recommendations for occupation al health standards. MMWR 1983;32:665-676. 23. Kostial K, Maljkovic T, Jugo S: Lead acetate toxicity in rats in relation to age and sex. Arch Toxicol 1974;31:265-269. 24. Environmental Health Criteria, S-Lead. Geneva, World Health Organization. 1977. 25. Mahaffey KR: Nutritional factors and sus ceptibility to lead toxicity. Environ Health Persped 1974;7:107-111. 26. Webb RC, Winquest RJ, Victery W, et al: In vivo and in vitro effects of lead on vascular reactivity in rats. Am J Physiol 19SI;241:H21iH216. 27. Current trends: Results of blood lead determinations among workers potentially ex posed to lead--United States. MMWR 1983; 32:216-219. 28. Sparrow D, Sharrett AR, Garvey AJ, ct al: Trace metals in drinking water Lack of influ ence on blood pressure. J Chronic Dis 1984; 37:59-65. 534 JAMA, Jan 25, 1985--Vol 253, No. 4 Blood Lead--Harlan et al TEH 0350038 DU PO50298667