children, the barometer of environmental lead · 2020-03-09 · environmental lead 1o6- lo5- io4- 4...

Children, the Barometer of Environmental Lead

CAROL R. ANGLE, M.D. Department ofPedintrics, Uniuersity ofNebraska Medical Center, Omaha, Nebraska

AND MATILDA S . McINTIRE, M.D.

Department of Pediatrics, Creighton Uniuersity School of Medicine, Omaha, Nebraska

THE EXPANDING DEFINITION of the new morbidity in pediatrics encompasses health-related environmental problems as well as the psychosocial domain. Pediatricians are increasingly concerned with the potential effects of prenatal and postnatal exposure to environmental toxins. Some of these toxins, such as formaldehyde, once considered relatively innocuous, recently have been shown to be responsible for significant symptoms at trace levels far below the previous threshold of detection. The halogenated hydrocarbons, particularly the polybrominated and polychlorinated biphenyls (PBBs, PCBs) and 2,3,7,8-te- trachlorodibenzo-p-dioxin (TCDD), are relative newcomers that have rapidly resulted in world-wide contamination of poten- tially high toxicity. At the far end of the time scale is lead, an environmental contaminant for so many thousands of years that complex extrapolations are needed to define its natural levels. The cumulative knowledge of the environmental contamination with lead and its biologic consequences for children and aduIts as well as animals, wildfowl, and vegetation provides an ecologic case study in which the methods of analysis are relevant to the examination of other environmental toxins.

Lead poisoning has existed since antiquity, with classic clin- 3

0065-31 01/62/0029-3-31-$03.75 8 1962, Year Book Medical Publishers, Inc.

4 C.R. ANGLE & M.S. MCINTIRE

ical symptoms correctly attributed to lead as early as the second century B.c.' It has, however, been only during the past two decades that the generalized risk from environmental contamination with lead has been recognized as a public health problem. Until the 1960s, lead poisoning was primarily considered an episodic problem occurring in young children with pica, as well as an occupational disease of lead and other industrial workers. The interaction of childhood lead poisoning with industrial sources was, however, well documented in many nine- teenth century reports of the reproductive toxicity in women employed in the painting of pottery and the general ill health of children living in mountain valleys where the meteorologic conditions favored a constant fallout of lead dust from industrial As important as these epidemics were in iden- tifying the risk of environmental lead intoxication, they represent the extremes in exposure resulting in severe lead poisoning with irreversible toxicity. A more basic question is whether the current levels of environmental lead pose a uni- versal risk by elevation of the body burden of lead in the general population to the threshold of toxicity.

Historical Aspects

Paleoarcheology proposes that environmental contamination with lead began more than 9,000 years ago with the hammer- ing and use of native copper, followed by cast copper objects about 7,000 years ago5 (Fig 1). In the next 1,000 years, metallurgists recognized the metallic impurities of smelted copper and developed the tin or arsenic alloys of copper that intro- duced the Bronze Age.' About 6,000 years ago, lead probably was first produced as a by-product of silver smelting. The discovery soon followed that a small amount of silver could be smelted from lead sulfide ore, with further purification of silver from the smelted lead-silver alloy by a second smelting process called cupellation. Until the Industrial Revolution, lead was primarily the residue of silver production, with about 400 tons of lead oxide obtained for each ton of silver yielded by cupellation.

The development of analytic methods to determine the purity of precious metals and the evolution of the concepts and tech- niques of weights and measures gave rise to the first wide-

ENVIRONMENTAL LEAD

1o6-

lo5-

io4- 4 W > ;j io3- z

Silver Coins

Dominance of AlhenS Rome H f - - - - 3

- 7 7

5000 4500 4000 3500 3000 2500 2000 1500 1000 500 P

YEARS BEFORE PRESENT Fig 1.-Estimate of world-wide production of lead over the past 5,000 yean as re-

lated to major hisurrical events. (Adapted from Patterson!)

spread use of silver coinage during the classic Greek period.' Not surprisingly there were wide discrepancies in the production of lead throughout the Old World. Wealthy countries had silver mines; they also applied their ingenuity to the abun- dance of lead. By-product lead was used in building construc- tion, pigments, cosmetics, ship sheathing, aqueducts, and gut- ter systems. Both the Athenians and the Romans prepared a product called sapa by simmering sweet grape juice with spices and herbs in covered pure lead kettles. Sapa, containing several thousand ppm lead, was added to green wine as a bactericide to prevent s o ~ r i n g . ~ The widespread utilization of sapa is thought to be the principal reason why human bones from the time of the Roman Empire have lead concentrations a t least four times contemporary values. Whatever the contribution of epidemic lead poisoning to instances of insanity and sterility in the ruling class and thus to the downfall of the Roman Empire, economists agree that exhaustion of the lead-silver mines was fiscally catastrophic to both Athens and Rome.' The health effects may have been beneficial. Lead smelting and refining had

6 C.R. ANGLE & 31,s. MCINTIRE

long been recognized as hazardous trades assigned to slave la- bor. When the mines were depleted, lead smelting became a local industry involving relatively few workers. It was not until the discovery of the New World and the exploitation of silver and lead deposits in Mexico and Peru that lead production again reached the level of that of the Roman Empire. Patter- sonJ has proposed that the transfer of 40,000 tons of silver from the New World was a major factor in the downfall of the Span- ish economy by the suppression of local industry, heavy pur- chases of foreign goods, and a negative balance of trade.

Despite the recognition of lead smelting as the cause of a clinical syndrome and the knowledge that lead was the major ingredient of sapa, the specific hazard of lead contamination in wine was not clearly recognized until the seventeenth century, when laws were passed throughout Europe and North America prohibiting its use, as noted by Benjamin Franklin in his report of the risk of New England rumg:

'The First Thing I remember of this kind was a general Discourse in Bos- ton, when I was a Boy, of a Complaint from North Carolina against New England Rum, that it poisn'd their People, giving them the Dry Bellyach, with Loss of the Use of their Limbs. The Distilleries being examin'd on the occasion, i t was found that several of them used Leaden Still-heads and Worms, and the Physicians were of Opinion, that the Mischief was occasioned by the Use of Lead. The Legislature of the Massachusetts thereupon pass'd an Act, prohibiting under severe Penalties the Use of such Still-heads and Worms thereafter. Inclos'd I send you a Copy of the Act. taken from my printed Law-Book."

The use of lead as a bactericide in the production of wine continued to be a common practice until Pasteur's discovery of bacteria and the introduction of sulfur dioxide.

With the Industrial Revolution, lead entered the market as a primary product rather than a by-product of silver. The rapid increase was accompanied by a growing recognition of its risks to worker^.'^ It was not until the twentieth century that the protection of lead workers first entered the public domain; the specific risks were documented and publicized by Alice Hamil- ton in her classic treatise."

The discovery by Kettering and by Midgely in 1921 of tetraethyl lead as a highly effective antiknock agent in internal combustion engines resulted in a new mode of atmospheric dis- persion. The regulatory history of the alkyl leads provides a cautionary tale. The US. Public Health Service, charged with

ENVIRONMENTAL LEAD 7

the protection of workers and the general public, recognized the neurotoxic hazard of the organic leads and imposed stringent controls on the transport and labeling of tetraethyl lead. It was decided, however, on the basis of inadequate animal tests, that gasoline exhaust posed no hazard and no restrictions were placed on either the automotive use of tetraethyl lead or on the burning of alkyl leads in other fuels."

Natural Levels of Lead

This new source of environmental lead contamination is in- delibly charted on the lead analysis of glacial snow (Fig 21, which documents the increased aerosol fallout of lead with increasing use of automobiles and airplanes.I3

Analyses of serial depositions of silicate dusts in polar snow are one of several methods used to determine the natural concentration of lead in air, water, and food in premetallurgic times. Another paleontologic technique has been the analysis of the 1ead:calcium ratio. As defined by Settle and Patterson," the natural cycle of lead from rock, water, and soil to plants, to herbivores, and then to carnivores involves a biopurification process due to the selective absorption of calcium over lead that is calculated as resulting in a thousandfold difference.

As shown in Table 1, this predicts that the average 1ead:calcium ratio of the earth's crust is reduced from 6.4 x

to a 1ead:calcium ratio of 3 x lo-' in prehistoric humans and other carnivores. Ericson et al.,I5 using ultraclean tech-

Fig 2.-Concentration of lead in snous (pgigrn) in samples of inland ice. Greenland, as cited by Heron et al.'"

C.R. ANGLE & M S . MCINTIRE

TABLE I.-PREDICTED AND MEASURED RATIO OF

LEAD: CALCIUM IN HUMAU BONES

PWa

Earth's crust 6.4 x 10'" Predicted, human bones 3.0 x lo-' Peru, 1500 b.p. 5.7 x lo-" American. mesent 2.9 x 10.'

niques, found this predicted value to be similar to the 1ead:calcium ratio of human bones from premetallurgic Peru. Bone analyses on contemporary British and American adults showed 1ead:calcium ratios 200-600 times higher than those of ancient Peruvians.

A third approach to environmental contamination with lead has been the direct analysis of human bones. Although all such data are subject to considerable error from environmental contamination as well as the variabies of analysis, the concentration of lead in human bones (Fig 3) increased with the thousandfold increase in production about 2,500 years b.p. (see Fig I). Human bones obtained from premetallurgic societies in Peru," Egypt, Nubia, and ancient Denmark1' all have lead concentrations below 3 pglgm. In contrast, the concentrations of lead in English bones from the early days of the Roman Empire are elevated tenfold and increase to 300-400 pglgm by the time of the Norman Conquest.'* Bone lead concentrations above 200 pglgm generally are considered unequivocal evidence of chronic lead poisoning. Grandjean et al.3 analyses of Danish bones show similar increases in medieval times and peak concentrations in the eighteenth century." The content of lead in bone increases both with age and with bone density. Bany,18 in analyses of bones from contemporary English children 1-5 years of age, found vertebral levels of 0.3-6.5 pglgm, increasing to 1-9 pglgm at 11-16 years of age. The values for contemporary adults are widely divergent; they range from the 0.1-5.4 pgigm reported by Grandjean et a1.l6 in Denmark to 7.5-195 pgigm as reported by Schroeder and Tipton" in U.S. adults dying in the 1950s. Despite analytic errors, compelling evidence from multiple sources indicates that the contemporary urban American population absorbs a t least 100 times as much lead as that of premetallurgic populations and that the body burden is close to the detectable toxic thresholds for lead.

EWONMENTAL LEAD 9

/'-\ -

/ I \ / I

\\.ZOO

/ I I I I I I I I I

I I I -2

I 'D, n Peru I (0

E EOYD! 3 0 Nubis I * Denmark I r Britain-Roman Anglo- I '50

Saxon I U S .

0 Britain

YEARS BEFORE PRESENT Fig 3.-Lead concentration & g / p in bones from ancient Peru (Ericson et al.") and

Egypt, Nubia, and Denmark (Grandjean et al.''), Britain in the Roman and Anglo- Saxon (Waldron et al.'") eras, conte~poran' British children ( B q et al?'), and U.S. adults in the 1950s (Schroeder and T~pton").

Contemporary Epidemiology

Concern with the sources and level of environmental contamination with lead is far more than an academic exercise. In any individual case, immediate inquiry must be made concerning the incidence of pica, mouthing behavior, and the chronic ingestion of a multitude of high lead sources, including the fol- lowingz0:

HOUSEHOLD SOURCES OF LEAD ORAL INHALED Paint, plaster Stoves burning battery cases, wood/ Painted toys, cribs, railings nail rubble, and recycled oils House dust Lead shot reloading Soil-vard and street Newsprint


Lead water pipes (only if water pH low)

Teakettles, water heaters, boilers (lead solder)

Toothpaste Canned foods Milk-animal and human Wine, homemade Moonshine (from lead solder in car

radiaton and home stills) Glazed pottery and painted glassware Pewter pitchers and utensils Herbal medicine Cosmetics, Oriental

Industrial sources of lead, listed below, can pose a significant risk for children and adults by mass contamination of air and soil, as well as the heavily contaminated dust transported by the parent's clothing and car.

MAJOR INDUSTRIAL SOURCES OF LEAD Welding and cutting of lead-painted metal Spray painting Lead mining, smelting, and refining Soldering, solder grinding Battery reclamation Auto and ship repair Brass alloy foundries Lead crystal making Lead pigment production Lead casting and typesetting PVC plastics (lead salt stabilizers) Urban renewal projects

The US. lead industry produces about 1.3 million metric tons per year. Approximately one-half, primarily that in bat- teries and other metallic products, is reclaimed from scrap, with contamination of air, water, and soil during the recycling process. Genera1 environmental contamination with lead is increased by an estimated 600,000 metric tons annually in the form of pigments, gasoline additives, recycled petroleum products, ammunition, and other products not suited to reclamation.

As shown in the diagrammatic scheme of Figure 4, industrial fallout is heaviest in the urban environment, absorption is highest in the child and biologic sensitivity is greatest in the young child.'' At the time of implementation of the Lead Paint Poison Prevention Act in 1970 it was assumed that the elimination of substandard housing characterized by abnormally high lead in deteriorating surfaces of paint and plaster would eradicate lead poisoning. Data analyses, however, show no identifiable source of lead paint exposure in 32-45% of children with elevated blood levels.Z1 Other studies have shown a

ENVIRONMENTAL LEAD

Pb. PbBr. MI. SOr. PbEt4

AIR ---------7

Fig 4.-The environmental cycling of lead." Lead from industrial emissions enters the atmosphere primarily as inorganic lead, lead halides, sulfates, and oxides. Incom- plete combustion of tetraethyl lead results in organic lead concentrations that are 10- 15% of total atmospheric lead in urban areas, but these are rapidly degraded to the lead oxides found in urban dust and soil.

higher correlation of blood lead in preschool children with age, pica, mouthing behavior, and sociocultural factors than with the lead content of household paint.22 The general urban contamination with lead is the environmental risk factor for children. The relative contributions of air, dustfall, soil, house dust, water, food, and other sources have been the subject of multiple investigations.

Our inquiry into the sources of environmental contamination began with the 1967 report of the National Air Surveillance Network showing that Omaha had the highest dustfall lead of 22 Midwestern cities. This exposure was attributed to the pres- ence of one of the largest lead refineries in the country plus two other industrial emission sources, all in close proximity to target areas of urban poverty23-27 (Fig 5). Data showed the pre- vailing winds to focus the emissions on this north central urban area. Since rational environmental standards require epidemiologic data, a long-term study was initiated in Omaha of the correlation of childhood blood lead with the lead content of air, soil, house dust, water, and milk. The majority of our studies involved the age group 6-11 years in order to eliminate the variable of differences in mouthing behavior and pica. Studies were initiated a t schools in north central Omaha and later a t suburban schools to assess blood and environmental

0 Suburban Scbml - 3 0 Mked commerc la i - 0 Urban Cornmerclei - C - II Lead Emisslon CIJ Sampler

Fig 5.-Map of Omaha showing the commercial (C), mixed commercial-residential (Mi , and suburban (SJ sampling sites and schools as related to three lead emission S O U ~ C ~ S . ~

lead in three general areas and populations: C-a commercial area in north central Omaha with an elementary school di- rectly adjacent to a battery plant, M-a mixed commercial-residential area also in the north central target area of industrial emissions and poverty, and S-suburban southwest Omaha.

EhTRONMENTAL LEAD 13

Almost all children and youth tested in areas C and M were black; those in S were predominantly white.

Air lead samples were 24-hour collections at six-day inter- vals in High-Vol samplers (0.1-1.0 plparticle size) a t a 15-foot elevation at three sites. Previous studies had shown no significant difference between air lead collected at four feet and 15 feet. Monthly dustfall was collected in plastic containers a t the same sites as the air samples. Soil samples were two-inch cores halfway between the building and the lot line for each home and each school. Household dust was collected from vacuum cleaner bags.

The range of concentrations of lead from these sources is shown in Table 2, which compares the levels in air, soil, house dust, and water in these areas of Omaha with that of national samples.2s

An early epidemiologic study investigated the correlation of the blood lead of urban schoolchildren 6-11 years of age a t C and M with residence in census tracts characterized by substandard housing (Fig 6). A topographic plot of the blood lead of schoolchildren according to their home residence showed blood lead to be unrelated to housing (Fig 7). The highest blood leads occurred in children living in the immediate proximity of

TABLE REPRESENTATIVE CONCENTRATIONS OF E~WONMESTAL LEAD

Air 1i.S.. ranee. urbans 0.5-2.0 ueim3 , . mah ha, i ed ian , 1980% 0.94 pgim" Omaha, median, refinery area, 1980% 8.13 pgimS Omaha, median. refinery area, 1981" 2.2 pgim"

Dustfall Omaha, urban, 1973-19i7n 1-26 mgim2/30 d Los Angeles, centrals 3.2-650 mg/m2/30 d Los Angeles, suburbsZC 1.4-10 mgim2i30 d

Street dust 75 Midwestern cities" 206-20,000 pgigm

Soil U.S., range" d00->10,000 pglgm Omaha, urban, 1973-19772' 16-4.792 pgigm

House dust U.S., range2' 279-11,000 pg!gm Omaha. 1973- 1977r 18-5,571 ~ g i g m

w r t o r . . ""-. 95% of 60 U.S. citiesZC Bennin~ton, VT. 1977=

Food EPA survey, 1977= 0.1-0.5 pgigm

C.R. ANGLE Sr a1.s. MCINTIRE

Fig 6.-Close.up of north central Omaha showing the percentage of substandard housing according to census tracts and the locztion of three lead emission sources. Air sampling was conducted a t two sites: .M (mixed commercial) and a t the urban high school and C (commercial) at the urban grade school just south of the battery plant in the center of the area!'"

the small battery plant and those living along the major traffic-ways.?5. 2"

Serial sampling of blood and environmental lead showed significant decreases over timep7 (Fig 8). In 1971, blood lead of schoolchildren living in the immediate vicinity of a battery plant averaged 37 pgldl, now considered in the toxic range. By 1977, the average blood lead had decreased to 22 pgldl in urban Omaha and to 14 kgldl in suburban children.

During the same period, the geometric mean of air lead decreased a t each of the three sites C (commercial battery plant), M (mixed urban), and S (suburban), although there was a n increase in 1977 associated with a n increase in total particulates (Table 3).

Dustfall lead, expressed as mgimp/30 d, were as shown in Ta- ble 4, with the number of samples in parentheses.


Fig 7.-Topographic plot of the blood lead (z axis) of 107 children living in north central Omaha with their individual residence plotted on the x and y axes. The thick- est black lines define streets canying more than 3.500 vehicles per lane per day. There is a shalp peak of blood leads of children living near the central battew plant and a ridge of increased values paralleling the major north-south street. There is little cor. relation of blood leads with substandard h o ~ s i n g . " ~ '

Fie 8.-Blood lead (Pb B. arithmetic means) of 1.232 samoles from 831 Omaha childyen, 1-18 years of age, 1'9i1-19ii ."

C.R. ANGLE & M.S. MCWTIXE

TABLE 3.-AIR L E . ~ (pglm')

TABLE 4.-DUSTFALL LEAD

TABLE 5.-SOU LEAD

GM U N G E

Site C (69) 262 53-1,615 Site M (56) 339 20-4,792 Site S (51) 81 16-341

Table 5 shows the geometric mean and ranges of soil Pb (pgl gm), with the number of samples in parentheses.

House dust lead (pglgm) at the three sites showed no significant urban-suburban difference in the geometric mean (number of samples in parentheses) (Table 6).

Milk and water analyses had shown no urban-suburban difference, with all milk in Omaha coming from a common milkshed. Similarly, all water samples, collected as 30-day samples from 20 homes, had lead concentrations below 10 pgl L. This low concentration of lead is consistent with the high pH (8.5-9.5) and the low plumbosolvency of Omaha tap water.

The major grocery chains in Omaha are equally distributed in the three areas and food analysis was not a part of the study.

The data then were analyzed for the age groups 1-5 years and 6-18 years for urban and suburban children to determine the correlation of blood lead with concentrations in air, soil,

18 C.R. ANGLE B; b1.s. MCINTIRE

A multivariate correlation of blood lead (Pb B) with the lead content of air (Pb A), soil (Pb S), and house dust (Pb HD) was derived:

Pb B = Bk Pb AoaJ Pb So'' Pb HDao'

This Omaha equation (Table 8) was applied to four other community s t ~ d i e s ~ ~ - ~ = and showed a n excellent prediction of blood lead with a relatively narrow range of background lead (Bk) of 4.8-8.1 pgldl.

Charney, Sayre, and Coulter2? recently have re-examined their long-term environmental studies in Rochester, New York. Stepwise correlatlons establish the lead content of household dust and of the dust on the hands, mouthing behavior, and pica as the critical variables in blood lead for children under 6 years of age. No single factor accounted for more than 50% of the variance in blood lead.

Roels et al.,38 in their long-term studies of Belgian children attending schools a t 1 and 2.5 k m from a lead smelter and in urban and rural areas, have shown the high correlation of

TABLE 8.-THE OMAHA EQUATIOX .AND FOUR COMWJNITY STUDES

Idaho 1.0 500 3.000 26.7 8.1 26.4 2.0 1,000 3.000 28.1 28.9

Los Angeles Lancaster 0.64 66 i66) 9.6 4.8 9.7 Los Angeles 6.3 1,000 (1,000) 14.6 16.4

Toronto Control 0.82 99 713 17 6.9 17.2 Smelter 3.01 1.715 1,550 27 25.1

El Paso 1977 1.3 427 1,479 20.1 6.6 20.3 1972 4.4 1,791 22,191 31.2 29.4

The regression equation Pb B = Bk Pb Xoo3 Pb So'' Pb HDoa' was applied to the means of Pb A. Pb S, Pb HD, and Pb B of four epidemiologic studies of children. Idaho data are taken from the predicted equation of Yankel et aLu with the sub- stitution of the average household dust a s cited bv Ashley." Toronto data are from Roberts et al." The Pb HD cited for El Paso'' actually is for exterior dust. Los Angeles dataU equate soil with house dust. Background Pb B (Bkl was estimated by substituting community data a t the lower Level of Pb A in the Omaha equation. This Bk then was used to predict Pb B a t the highec Pb h Estimated Bk in idaho was identical to that in Omaha. The Omaha regression predicts Pb B w ~ t h m 2 pgl dl in all four studies. P r o m Anj1eC .R . McIntire XS.: Environmental lead and children: The Omaha study. J , oricoi Encrron. Heolih 3855, 1979. Used by per. mission.)


blood lead with playground dust and air lead. The lead on the children's hands was significantly related to the environmental values. Partial correlations showed that the lead on the hands (Pb HI was quantitatively the major contributing factor (r = 0.976) to blood lead (Pb B). The correlation of blood lead and lead on the hands in 11 year olds was:

Pb B = -4.33 + 11.54 log Pb H This equation predicts an increase in blood lead from 18.8 to

22.2 pgldl as the lead on the hands increases from 100 to 200 pglgm. Roels et aL3' concluded, as we did, that although the fallout from the air is the starting point of environmental contamination, the enhanced daily intake of lead by the oral route is the primary identifiable factor predicting the blood lead of schoolchildren. As observed by Yankel et al.,33 the cleanliness factor of individual homes also contributes to the variance in the blood lead of children of all ages living in areas of similar environmental contamination, just as the amount of mouthing behavior is a major variable in preschool children.

Absorption and Metabolism of Lead (Fig 9)

One of the most important conclusions from these multiple epidemiologic studies of blood lead is that the greater intestinal absorption of lead by children than by adults appears to be a significant factor far beyond early infancy. In both children and

Fig $.-Absorption and metabolism of lead.

ABSORPTION

FOOD INDUSTRY WAiER TRAFFIC DUST

GI I LUNG I

lOZtAdu1 t I

4OZlChiId I 401 I- - - -., , < - - - - - I

I I

BILE GI OTHEE URINE FECES ELIMINATION SWiAT

HAIR NAILS

C.R. ANGLE & M.S. XCINTIRE

TABLE 9.-PROJECTED EXPOSURE &YE NET A8SORFTION OF LEAD IN URBAN CHIWREN

&T.U(E ABSORBED ROKTE CONCEWR.WON PER DAY ABSORBED (irg;dap)

Water 10 pgiL

0.2 gm 17%

Paint 10,000 pg!gm 0.2 gm 17%

adults, the absorption of inhaled lead of 0.1-1.0 piparticle size is 35-40% of the respired l ~ a d . ~ ' , ~ ' . ~ ~ Adults absorb approximately 10% of ingested lead whereas infants and young children may absorb as much as 40%. Insufficient data are available to define possible age-related differences in biliary secretion." Estimates of the exposure and net absorption in children are given in Table 9.2S~39.i'

Mahaffeym indicates that the maximal permissible exposure of young children to lead should not be greater than 100-150 pgiday. Ziegler et al." concluded from individual balance studies in children 2-25 months of age that a n intake of food lead of less than 50 pglday may achieve a negative lead balance.

Absorbed lead is transported in the blood, with about 95% bound to hemoglobin. Plasma lead rarely exceeds 2-3 ~ g l d l . The binding of a small but variable amount of lead to a low molecular weight protein of the red cell has been described by Raghavan and G ~ n i c k . ' ~ Experiments in human volunteers by Chamberlain et a1.44 showed that the blood lead peaks about one day after injection, ingestion, or inhalation. The clearance of lead from the blood seems to follow several rates of decay, with one as short as five days and the longest being six month^.'^ Soft tissue lead has a turnover time of 30-40 days. i PharmacokineticaIIy, the third and largest compartment is 1 bone lead, which accounts for 95% of the total body burden i n I adults and about 70% in young ~h i ld ren . '~ The residence time in bone is a t least 30 years. This lifelong skeletal storage is the basis for the EDTA challenge test, which will provoke a n increased urinary lead many years after termination of exposure. Since blood lead has the most rapid turnover of all of the body i

Lead poisoning is defined a s existing whenever a child has any one or more of the following: 1. Two successive blood lead levels

equal to or greater than 70 pgidl with or without symptoms

2. E P level equal to or greater than 250 pgldl whole biood and a confirmed elevated blood lead level equal to or greater than 50 ~g:dl with or without symptoms

3. E P level greater than 109 pgidl associated with a confirmed elevated blood lead level ( ~ 3 0 pgidl) with compatible symptoms

4. Confirmed blood lead level greater than 49 pgidl with comoatible svmotorns and . . evidence of taxicitv i e e . . abnormal EP, calcium disodlum EDTA rnob11w.atlon test, unnary aminolevulinic acid excretion or

ENVIRONMENTAL LEAD

compartments, more stable indices, such as erythrocyte protoporphyrin IX (EP), frequently are used to define exposure. The current definitions of excessive lead absorption as given by the CDCd7 are shown in Table 10.

Biotoxicity of Lead

Lead interferes with the synthesis of heme by enzymatic inhibition of three major enzymes4': (1) delta-aminolevulinic acid synthetase (ALA-S), the mitochondria1 enzyme that catalyzes

mature red cell. Ferrochelatase activates the incorporation of

TABLE 10.-CLASSIFICATION USED IN SCREENING PROGRAM OF THE CE~TER FOR DISEASE CONTROL

: Lend toxicity: erythrocyte protoporphyrin (EP) equal to or greater than (2) 50 pg! dl or functional derangements caused by lead Lindue lead absorption: confirmed blood lead levels of 30-69 pgidl associated with EP levels of 50-249 irgidl whole blood Elevated blood lead: a confirmed blood lead of 30 ~ g i d l or greater

urinziy coproporphyrin excretion)


TABLE 11.-BIOLOGIC CHAYGES 11" CHILDREN

BLOOD LEAD LEVEL (kg Pbidl) EFFECT -

0-10 Py-5' nucieotidase inhibition 10 ALXD inhibition 15 Erythrocyte pmtoporphyrin elevation 40 Increased urinary .%LA excretion 40 Anemia 40 Copropo~hynn elevation 7-60 (CTS) defie~ts

50-60 Per~pheral neuropath~es 50-70 Lead hnes in bones 80-100 Encephaiopathlc symptoms

the ferrous ion into the center of the protoporphyrin ring, with formation of heme. Since hemoglobin synthesis is heme dependent, lead inhibits the formation of hemoglobin a s well a s the heme-dependent proteins of the P450, b5, and other cyto- chromes of hepatic mitochondria.

Red cell protoporphyrins are elevated in the peripheral blood a t blood lead levels as low as 20 pg/dl and persist for the life span of the red cell, thus reflecting the average exposure over three months.

The usual assay of erythrocyte protoporphyrins (EP) measures protoporphyrin IX, coproporphyrin 111, uroporphyrin I, and ~oss ib ly others. Assay of free erythrocyte protoporphyrins . - (FEP), so named under the mistaken ;mpression t h a t th&were metal free, primarily measures protoporphyrin IX and coproporphyrin 111. The hematocytofluorometers used in most lead icreenmg program.; measure the ratio of fluorescence t o hemc- olobm as con~oared to a ;car,dxd of n n c ~rotoporphyrin 'ZPI' . .

validity is affected by hemoglobin concentrations and the pres- ence of unoxygenated hemoglobin or methemoglobin, bilirubin, and other substances. FEP is elevated in iron-deficiency anemia, erythrocyte protoporphyrinurias, febrile chronic infec- tions, and other disease and deficiency states.4g

Table 11 is a summation of the thresholds for specific biologic changes in children.28 "

Our studies of the subclinicaI effects of lead include investigations of its inhibitory effect on pyrimidine-5'-nucleotidase (PY-~N)~" - "~ in the red cell cytosol. This enzyme has specific af- fiky for the pyrimidine nucleotides, predominantly uridine


monophosphate and cytidine monophosphate. Phosphorolysis

Fig 10.-Blood lead in &dl a s related to activity of pj-rimidine-5'-nucleotidase (P5N) in units defined as the hydrolysis of 1 n mol CMPlminlgm hemoglobin in 15 ~ h i l d r e n . " ~

n

PSN UNITS/GM HEMOGLOBIN

C.R. ANGLE & M.S. MCINTIRE

Fig 11.-Red cell content of cytidine phosphate XTPl as related to blood lead. The mean 2 SD of CTP in 13 children with blood lead <30 &dl n a s 0.22 = 0.47 n mow 10'' red blood cells. Red blood cells from 11 children with blood lead 30-70 ~ g i d l had a significantly (P <005) increased content of CTP, with a mean c SD of 8.31 t 6.21 n moLu

dence that the residue of pyrimidine nucleotides relates more to the level of enzyme activity in the reticulocyte than in the mature red cell. The accumulation of erythrocyte pyrimidines thus reflects the net exposure to lead during the antecedent three months. Familial studies of congenital deficiency of pyrimidine-5'-nucleotidase show an increase in mild mental retardation." Any possible association between this observation and the neurologic effects of lead is, a t this point, speculative.

The major question concerning asymptomatic increases in blood lead to 20-40 pgldl is whether the association with mental retardation is causal or an indirect effect related to sociocultural factors. This is the subject of intense investigation, as reported by Needleman,5'.'8 analysis, as reviewed by Cowan and Leviton," and controversy, as noted by Ernhart et al.'O Clinical lead poisoning is associated with a significant risk of gross neurologic defi~it.''.'~ In one of our early studies of children with lead encephalopathy, we found 87% of children to have gross neurologic ~equelae. '~ Perlstein and Atalla,'* in 1966, cited -mental retardation in 24% of children with clinical lead poisoning and in 9% of those with blood lead over 60 pgldl but without toxic symptoms.

ENVIRONMENTAL LEAD

Fig 12.-Data from three children 2-3 years of age treated for an elevated blood lead with EDTA 76 mgikgld IM x 4 d. The prompt decrease in blood lead (Pb B) was associated with restoration of red cell pyrimidine-6'-nucleotidase (P5N) to normal. There was no significant change in the red cell content of cytidine triphosphate (CTPI or of zinc ; protopo2phyrins V2P).Y

DAY OF CHELATION THERAPY

C.R. AYGLE & MS. &lCLUTIRE

Provocative insight into the possible interaction of the effect

lum. and the better correlation of neurobehavioral function :

with protoporphyrin levels than blood lead, as well as the sirn- 1 ilarity to the neurotoxic porphyrias.

In addition to the effect of lead on red cell and neural tissue as the primary target organs, lead exerts a toxic effect on almost every organ system. As reviewed by Eisinger," lead forms complexes with the phosphate groups ofnucleic acids, binds re- versibly with the sulfhydryl groups of enzymes and other proteins, and forms large-sized molecular aggregates with protein, such as those readily visible in the renal tubules. Many of the biologic changes are more evident in adults with chronic exposure than in children and are summarized in Table 12.28

Legislation for Environmental Lead

Although more is known about lead than almost any other environmental toxin, obvious deficiencies exist in available sci-

TABLE 12.-THRESHOLDS OF BLOOD LEAD LEVELS FOR BIOCHEMICAL ~ W D CLINICAL EFFECTS ON ADULTS

BLOOD LEAD (pgidl) EFFECT

0-10 Inhibition of pyrimidine-5'-nucieotidase 10 ALAD inhibition 15 Elevation of erythrocyte protoporphyrin 20-15 Chromosomal abnormalities 30 Toxicity to fetus 30-40 Reduced fertility, altered spermatogenesis 40-80 Anemia 40-50 Increased red cell cytidine triphosphate 40-60 Psychologic. sensory, and behavioral changes 40-60 Decreased motor conduction velocity 50-60 imoaired kidnev function (acute chanees tubular

Air

27 ENVIRONMENTAL LEAD

TABLE I~.--F%DERAL REGULATION OF E~VIROXME~TAL LEAD

SUBSTANCE SOLWEDATE REGLWTIOH

Paint CDC-1970

HUD-1976 Le paint prohibited in housing in which truction, or rehabilitation is federally

.5, 95.14, 35.24, 35.56, 36.62 CPSC- 1978 aint and surface coatings, furniture, and

or other articles for children, maximum

e-lead, maximum

Large hoilowu~are, 2.5 pglml Silver-plated baby cups, 0.5 iglml

Guidelines 7417.00, 1417.01 EPA-1973 Reduction of lead in gasoline to 0.5 gmigal by 1979

40 CFR 80.20 Other criteria of Clean Air Act simultanwusly

reduced utilization, since lead inactivates cata l j ic convemrs

EPA-1978 National air quality standard for lead 1.5 pglms, maximal arithmetic mean per quarter

40 CFR 50.12 OSK4-1978 Workplace air 50 pglm3 maximum, 8-hour average

29 CFR 1910.1025 Fresh fruits and EPA-1971 Lead arsenate residue, maximum, 1 pglgm

vegetables 40 CFR 180.194 Water EPA-Pending Drinking water, maximal contaminant lead, 50

wgn 40 CFR 141.11

entific information. Regulations represent a compromise between maximal protection extrapolated from incomplete scien- tific data and the political and economic realities. As an example, no effort has been made to regulate the lead content of processed food, although voluntary effort has significantly reduced the lead content of infant food^.'^" Table 13 is a summation of current federal regulatory actions governing human exposure to lead.28

The most impressive aspect of the regulatory activities over the past decade has been the associated decline in childhood blcod lead. Our studies in Omaha showed generalized decreases in mean blood lead from 1971 to 1977 that correlated with en-


vironmental assays, with quality control to rule out decreases in blood lead over time due to variances in methodology. Schneider et a1.@ noted major decreases in the number of symptomatic children disclosed by community lead screening. Even though these data have not been critically analyzed as indepen- dent of demographic variables, the current case finding of 3%- 5% is one-third to one-fifth earlier surveys. Billick et aL61 in New York City noted a decline in the geometric mean blood lead of black children 25-36 months of age from 29 ~ g l d l in 1970 to 21 pgidl in 1976 and HUD data show a similar trend in Louisville, Kentucky.'' As the mean blood lead declines so does the risk for symptomatic lead poisoning and its neurologic and other health-related sequelae.

The evidence that the regulation of environmental lead cor- relates with the mean blood lead in children throughout the country establishes the need to continue to monitor blood lead as a barometer of environmental pollution. The proposed revi- sions of the Clean Alr Act have the potential of increasmg am- bient lead. The documentation of the health-related benefits of decreased environmental exposure to lead provides powerful support for the need to secure the gains of the past decade. Pe- diatricians and all others concerned with the health of chlldren should urge that thls protection be maintained.

REFERENCES

1. Aub J.C., Fairhall L., Minot A., et al.: Lead poisoning. Medicine 41, 1925. 2. Angle C.R., Mcintire M.S.: Lead poisoning during pregnancy. Fetal tolerance of

calcium djsodium edetate. Am. J. Dis. Child. 108:136, 1964. 3. Paul C.: Etude sur I'intoxication lente par les preparations des plomb. Arch. Gen.

Med. 15:513. 1980. 4. Oliver T.: Lead poisoning and race. Br. .Wed. J. 1:1096. 1911. 5. Patterson C.C.: An alternative perspective-lead pollution in the human environ-

ment. in. Lead in the Human Enuironment. Washington. D.C., National Academy of Science. 1980. pp. 278-282.

6. Patterson C.C.: Native copper, silver and gold accessible to early metallurgists. Am. Antiquity 36:286, 1971.

7. Seltman G.T.: Greek Coins. 2d ed. London, Methuen, 1955. 8. Patterson C.C.: Silver stocks and losses in ancient and medieval times. Econ. His-

tory Rev. 25:205, 1972. 9. Franklin B.: Man, medicine, and work in America: A historical series. 111. Benja-

min Franklin and his awareness of lead poisoninn. Felton J.S. J. Occrr~. .Wed. *

9543, 1967. 10. Tanquerel des Planches L.: Trait6 des maladies de plomb ou Saturnines 1-11, Pans .

1R39

11. Hamilton A.: Industrial Poisons in the United States. New York. Macmillan. 1929. 12. Advisory Committee on Tetraethyl Lead: Public health aspects of increasing te.

traethyl lead content in motor fuel. USPHS Publication No. 712, 1969, Washing- ton, D.C.

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