Click for next page ( 38


The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 37
Appendix D Etiology and Consequences of Childhood Lead Poisoning The National Bureau of Standards estimates that 600,000 children in the United States have unacceptably high blood lead levels ( >40 yg Pb/dl).34 This estimate was based on data from large to medium sized standard metropolitan statistical areas (SMSA) in the East and Midwest only. The incidence of lead poisoning is highest among one- to five-year- old inner city children who live in substandard housing containing multiple layers of old lead paint.12,60,70 A relatively small number of cases result from exposure to improperly glazed pottery or exposure to industrial point sources such as smelters and battery factories. RISK FACTORS Multiple factors serve to increase the risk of lead poisoning in the 1-5 year old child. Among these are age, pica, diet and multiple sources of exposure. Age - The process of growth itself produces stress, making the child more susceptible to a host of disease agents which affect adults to a lesser degree. Both increased vulnerability of the brain and increased intestinal absorption of Pb have been identified as two significant risk factors related to age. Studies in both humans ' and animals13,72,83,90 have shown the brain to be most vulnerable during the "growth spurt" which, in humans, begins during the sixth month of pregnancy and continues into the third or fourth year postpartum (see Appendix B for a detailed discussion). Balance studies in adults have shown an intestinal absorption rate of 10 percent. Alexander and co-workers carried out lead balance studies over a three-day period in healthy children ranging from 3 months to 8-1/2 years of age. They found that healthy children absorb an average 53 percent of ingested lead and retain 18 percent.^ Animal studies also show a higher rate of intestinal absorption-I--' '31»43 prior to weaning than after weaning. Pica - The young child first learns to explore the world orally. From the time he is able to grasp and lift objects, he places everything in his mouth. This is a normal activity, which persists in 50 percent of the children until age three.«1'94 Beyond this age, pica is generally considered an aberrant behavior. Pica may be defined as the compulsive ingestion of non-food substances. The older child with pica may be highly selective in his choice of substances. Psychosocial factors are important components of repetitive and selective pica. ^ Pica for paint is believed to be essentially episodic, occurring perhaps two to three times per week. .. Variations in fecal lead output tend to confirm this observation. Pica for paint generally begins after the child learns to crawl or walk; however, later onset of pica for paint has been observed.21 Abdominal x-ray plates showed radiopaque material 37

OCR for page 37
in the intestinal tract in 35 percent of children seen in the Chicago Lead Clinic.84 Diet - Both dietary components and nutritional deficiencies have been found to increase the absorption of lead from the intestinal tract. Studies in rats^ and baboons49 have shown that the presence of lipids in the diet increases absorption. Kostial's studies of rats show greater absorption of lead if administered in milk than if administered in dry feed.5l,52 Animal studies involving dietary deficiencies of calcium, copper and iron have shown that these deficiencies increase the absorption of lead.^'47,64,92 In iong-terin experiments in growing rats, restriction of dietary iron and calcium to 20 percent of the Recommended Daily Allow- ance for growing young rats increased the absorption and retention of lead by a factor of two or more.64.92 This degree of reduction in dietary intake of calcium and iron has been reported in two- to three-year-old children from low-income families.63,98 ^ population survey of American children showed less than optimal calcium intake ranging between 12-14 percent for white children and 23-25 percent for black children. Iron deficiency, defined as hemoglobin levels <10 grams, was seen in approxi- mately 4 percent of white children from families above the poverty line, 10.8 percent of white children in families below the proverty line, 17.6 percent of Negro children in families above the poverty line and 15 percent of Negro children from families below the poverty line.1 Others93,98 have also reported dietary deficiencies of calcium and iron in young children. Iron deficiency is most prevalent among children 12-24 months of age.1'93 Sources of Exposure - The preschool-age child is exposed to mul- tiple sources of lead. These include dust, canned foods and liquids, and paint. The last is usually considered a "high dose" source of lead while the others in which the concentration of lead is much lower, are con- sidered "low dose" sources. It is the cumulative intake and absorption from these various sources that is important. Direct inhalation of average urban air (1-3 yg Pb/m3) is considered insignificant in comparison with the sources given above. Recognizing that city children showed a higher prevalence of ele- vated blood lead levels than did rural children and that not all children with elevations had a history of pica for paint, Lepow decided to examine the possibility of exposure from dust and dirt. She found a mean level of ll,000 yg Pb/g house dust. Samples of dust from the hands of children residing in these houses contained a mean level of 2,400 yg Pb/g dust with a mean weight of 1l,000 yg dust per hand sample. The authors suggested that lead emissions from automobiles contributed significantly to the high dirt and dust lead levels found in the city. Sayre and Vostal88*1^ found that house dust levels in inner city homes contained median concentrations of lead five times greater than that found in suburban homes and that the concentration of lead on the hands of a child was related to the concentration of lead in house dust from his home. Their first study88 did not differentiate between old and new inner city housing; the second study did.-^02 it was found that old inner city housing contained 33-486 yg Pb/sq. foot floor surface, new inner city housing contained 2-24 yg Pb/sq. foot and suburban housing contained 0-60 yg Pb/sq. foot. Since the dust lead levels in the newer inner city houses were significantly lower than in the older inner city houses, the authors concluded that the source of lead originated from with- in the homes, presumably from the powdering of old lead paints. 38

OCR for page 37
QQ Ter Haar3 examined dirt samples around 18 painted frame farm houses remote from traffic. The concentrations of lead in dirt were similar in both rural and city yards and decreased in relation to dis- tance from the house. In addition, Ter Haar studied the relative contribution of lead from fallout dust by measuring the fecal output of both stable lead and 210 pb in two groups of children. A naturally occurring tracer, 210 pb is almost absent from paint, but occurs in significantly higher concentrations in air-suspended particulates or dust fall. The first group of children was suspected of having elevated body lead burdens; the second group lived in good housing in which lead poisoning was not a problem. The first group had fecal lead outputs ranging from 4-1640 yg Pb/g; the second had outputs of 2-7 yg Pb/g. Despite the wide difference in total lead output, both groups had essen- tially identical outputs of ^10 Pb.^9 The conclusions reached were that lead paint from the houses was the principle cause of elevated soil lead levels and that lead from air-suspended particulates was not a significant source of lead intake in the children studies. Canned foods, particularly acidic foods such as fruits and fruit juices, have been found to contain higher concentrations of lead than similar food packaged in glass or plastic containers. Mitchell and Aldous found a mean lead concentration of 202 yg Pb/liter in canned foods and 35 yg Pb/liter in bottled products. Many of the canned baby foods analyzed in this study were fruit juices, some of which contained >500 yg Pb/liter. Canned evaporated milk had from 10 yg Pb/liter to 820 yg Pb/liter (mean 202 yg Pb/liter). The National Canners Association sponsored a study of lead intake in 333 infants aged 1-12 months (unpub- lished but cited by Kolbye, ^t jil50). Their estimate of dietary intake was 93 ± 36 yg Pb/day, or approximately 50 percent of the adult dietary intake. To one observing Mitchell's data, it seems obvious that wide variations in Pb intake could occur as a result of the parents' choice of food for their child. Paint provides the most concentrated source of lead potentially available to a young child. House paints containing the present legal limit of 0.5 percent lead would provide 5,000 yg Pb/g paint. Sachs°5 has indirectly estimated the quantity of paint ingested by a child with pica for paint. Model x-ray films were made, using known quantities of paint. These were then compared to abdominal x-ray films taken of children known to have pica for paint. Seven out of 10 randomly selected films showed radiopacities equivalant to an estimated 1 gram _5 of paint. At least one film was estimated to show 20 grams of paint. Generally speaking, lead intake in adults is from "low dose" sources such as food, water and ambient air. The child has additional sources of lead exposure from dirt, house dust and paint. Based on the data presented above, the most hazardous "high dose" source available to the average child is paint. Average Daily Intake of Lead in Normal Children - Alexander's studies in eight healthy children receiving a normal diet, showed a mean daily intake of 10.61 yg Pb/kg body weight.^ Of this amount, 5.47 yg Pb/kg/day were absorbed and 5.13 yg Pb/kg/day were excreted in the feces. Thus, the children absorbed approximately 50 percent of the lead 39

OCR for page 37
available from dietary sources. In contrast, Kehoe's studies in adults showed an absorption rate of approximately 10 percent for lead from dietary sources. These findings are in agreement with studies in experimental animals which show a higher intestinal absorption rate in the young than in the adult. Barltrop, ^t al studied the relationship between fecal lead output and blood lead levels in two- to three-year- old children. A mean fecal lead output of 67.8 yg Pb/day was observed in a group of 35 children with a mean blood lead level of 20 yg Pb/dl. Recalculated on a body weight basis for an average three-year-old child weighing 15 kg, the daily fecal lead output would be 4.5 yg Pb/kg/day. Assuming a 50 percent absorption rate, the daily intake necessary to produce this excretion would be 9.0 yg Pb/kg/day. This is not far different from Alexander's figure of 10.6 yg/kg/day. In addition, the mean blood lead level of 20 yg Pb/dl is comparable to that observed by others in normal "unexposed" children.40,59,70 CONSEQUENCES OF CHILDHOOD LEAD POISONING Permanent effects of lead poisoning include blindness, mental retardation, behavior disorders and death. Clinically obvious effects of this magnitude are associated with the later stage of lead poisoning in which encephalopathy occurs. ' Therapeutic intervention at this stage is only partially successful in preventing severe permanent deficits. Lead encephalopathy in children generally does not occur until blood lead levels exceed 120 yg Pb/dl. '0 The current focus of research interest involves studying whether or not more subtle but permanent effects result from less severe cases in which no symptoms, or only mild symptoms, are apparent. Lead exerts its toxic effects in the renal, hematopoietic and nervous systems. Kidney damage is a reversible effect seen in severe cases and no published data are available to suggest that damage occurs in asymptomatic cases. Adverse, but reversible, effects are seen in the hematopoietic system in asymptomatic cases. A current controversy centers around conflicting reports of neurologic damage occurring in asymptomatic or mildly symptomatic cases. Hematopoietic Effects - Lead-induced anemia has been reported in both adults and children. Lead causes multiple interferences in the formation of hemoglobin,'0 including inhibition of the enzymes, 6-aminolevulinic acid dehydratase (ALA-D) and ferro chelatase. The inhibition of these enzymes results in an accumulation of 6-aminolevulinic acid in urine (ALA-U) and "free" erythrocyte protoporphyrin (FEP) in blood. European studies have shown that increases in free erythrocyte protoporphyrin begin to occur in women and children when blood lead levels reach a range of 25-30 yg Pb/dl, and in men at 35-45 yg Pb/dl.8l,97,104,105 It is now known that it is zinc protoporphyrin rather than the free protoporphyrin IX which is present in excess in the circulating erythrocytes in lead poisoning and iron deficiency. -^ Population studies of children in the United States have rarely included a sufficient number of children 40

OCR for page 37
with < 20 yg Pb/dl to determine this lower threshold level. A second threshold is seen in children when blood lead levels reach the range of 35-40 yg Pb/dl.20,4l,75,87 The excretion of ALA-U begins to rise in both adults89'100 and children20 when blood lead levels reach the range of 40-50 yg Pb/dl. In children, quantitative collections of urine are required for ALA-U. The determination of ALA-U in random urine specimens from children is of little value.71,96 Hernberg has demonstrated that lead shortens the life span of the red blood cell and that this is a mechanism by which lead produces anemia.38 Tola has demonstrated a significant decrease in hemoglobin levels in new workers occupationally exposed to lead.100 Decreased hemoglobin levels became evident within two to three months, as Pb-B approached 50 yg/dl. Pueschel found a significant negative relationship between hemoglobin levels and blood lead levels in children.'8 Blood lead levels >60 yg Pb/dl were almost always associated with hemoglobin levels <10 g/dl. Betts11 found hemoglobin levels 100 yg Pb/dl. Rosen et^ jLL found a negative relationship between hematocrit and blood lead concentrations at levels exceeding 40 yg Pb/dl. Neurologic Effects - Subtle deficits in neurologic functioning are difficult to measure and even more difficult to attribute to a single cause such as lead poisoning. There is currently no set of neurochemical tests for measuring changes in the nervous system that is comparable to the set of tests (ALA-D, ALA-U, UCP and FEP) available for measuring changes in the hematopoietic system. Current measurements of neurologic changes are accomplished through the use of functional tests such as I.Q. tests. Confounding factors such as parential I.Q., parental education level, socio-economic status, birth trauma, etc., also influence the results of these tests. Studies purporting to show a relationship between I.Q. and exposure to lead should include control subjects carefully matched with study subjects for age, birth rank, parental I.Q. socio-economic status, nutrition, pica, etc. In addition, they should be prospective studies in which the presence or absence of exposure to lead in the early years is well documented. Most of the current controversy results because studies were undertaken without a proper design and lack either a proper control group or firm documen- tation of the degree of lead exposure during the early years of life. The studies of de la Burde2^'2^ meet most of the criteria of a prospective study. Both study and control children were drawn from an on-going Child Development Study at the Medical College of Virginia in Richmond. Mothers were followed during pregnancy and delivery and children followed for eight postnatal years. The study group consisted of 67 asymptomatic children who had a positive history of pica for paint or plaster, lived in deteriorated old housing, had positive urinary coproporphyrin tests and either a blood lead level >40 yg Pb/dl or blood lead >30 yg Pb/dl and positive radiographic findings for lead lines in the long bones. Because of the analytical problems inherent in blood lead methodology, as performed in the 1960's,^ we feel that this combination of criteria for selecting the study group was more reliable 41

OCR for page 37
than a selection based on blood lead levels alone. Even so, the absence of serial blood lead levels, which were not feasible at the time, is the major weakness of this study. This weakness is largely overcome by dependence on x-rays and repeatedly positive urinary coproporphyrin tests. Positive bone x-rays.'-.'- and positive urine coproporphyrin tests are generally associated with blood lead concentrations equal to or greater than 60 yg Pb/dl. Lead levels in shed deciduous teeth were performed several years later on teeth from 29 of the lead-exposed children and 32 of the control children. The mean tooth lead level for the study group was significantly higher than the mean tooth lead level of the control group. The control group consisted of 70 children who had a negative history of pica for paint or plaster, lived in modern housing, did not visit older housing for day care and had negative tests for coproporphyrin in urine. In addition, all children were excluded from both groups who showed neurologic abnormalities or develop- mental lag either during the newborn period or at four months, if abnor- malities were noted on the Bayley scale at eight months, or if confirmed or suspected disease of the central nervous system was noted anytime before seven years of age. In addition, the groups were comparable in age, sex, race, mother's non-verbal I.Q., socio-economic status, family composition and possible sources of family upheaval such as death in the family, foster home placement or working mother. Neurological and psychological tests were administered to both groups at four years of age and again at seven years of age. Fifty-eight children from each group also had tests repeated at eight years of age. At four years of age, the most significant differences between the groups were in the areas of fine motor coordination and behavior. Failure on fine motor tests occurred almost twice as frequently in the lead-exposed group as in the control group. Deviation in overall behavior ratings occurred almost three times as frequently in the lead-exposed group. Mean I.Q. scores, as measured by the Stanford-Binet test, were 89 ± 13.1 for the lead-exposed group and 94 - 10.5 for the control group. At seven years of age, neurologic examination revealed deficits in more than twice as many children from the study group as from the control group. Full-scale I.Q., as measured on the Wechsler Intelligence Scale for Children revealed that the majority of children from both groups had average intelligence, although the mean I.Q.'s were statistically significantly (p <0.01) lower in the lead-exposed group. The frequency of results in the borderline or mentally defective range was higher in the lead-exposed group. Short attention span and minimal goal orientation occurred in 32 percent of lead-exposed children and 14 percent of control children. Poor academic progress was noted in 27.8 percent of lead-exposed children and 4.1 percent of control children. The number of children repeating at least one grade was higher in the lead-exposed group (25.9 percent) than in the control group (6.1 percent). Eleven lead-exposed children and four control children were receiving speech therapy for speech impediments. The authors felt that the most significant difference between the groups was in the area of behavior and that this was the primary cause for poor school performance. Among the lead-exposed group, five had been seen by psychiatrists, one had been institutionalized and three 42

OCR for page 37
were subject to seizures. None of these findings occurred in any of the control children. A review of school records revealed that hyperactivity, explosive behavior and frequent temper tantrums occurred in 19 lead-exposed children and 5 control children. The behavior problems which had been apparent at four years of age, but which were adequately handled in the home environment, persisted at seven years and prevented appropriate functioning in the school environment. It is of interest to note that these findings in asymptomatic children are similar to the findings of Byers and Lord in symptomatic children..^ Although Byers and Lord found little difference between lead-poisoned and control children, in relation to overall I.Q., the lead-poisoned children were found to have signifi- cantly poorer school performance. The results of several additional studies have suggested a relationship between increased lead absorption and neurologic deficits in young children. Albert ^t al^ obtained data on 371 children with varying degrees of lead exposure. A record of blood lead levels was obtained from the New York City Health Department blood lead registry. The mean age at time of blood test was 2.5 years. Relocation and evaluation of the patients took place 3-11 years after blood lead testing. The children were divided into five groups according to degree of exposure. Group I contained six children with lead encephalopathy, Group II contained 154 children treated for lead poisoning who did not have encephalopathy. Group III contained 65 children with blood lead levels >60 yg Pb/dl who were not treated, Group IV contained 57 children with <60 yg Pb/dl, but elevated tooth lead levels, and Group V contained 89 children with both low blood lead and tooth lead levels. Neurologic disorders, including mental retardation, organic brain syndrome, seizure disorders and behavior disorders, were found in 66.7 percent from Group I, ll.0 percent from Group II, 18.5 percent from Group III, 3.5 percent from Group IV and 4.5 percent from Group V. Psychometric tests were performed on 159 of the 371 children. A composite rating based on Intelligence Quotient, Bender- Gestalt quotient, Figure Drawing quotient and Purdue Pegboard error score was made by a clinical psychologist. Groups I and III had signifi- cantly lower ratings than Group V. Groups II and IV did not differ significantly from Group V. It is not surprising that the encephalopathy group showed neurologic deficits. The fact that the untreated children with >60 yg Pb/dl (Group III) showed a higher frequency of neurologic deficits than the diagnosed and treated cases of lead poisoning (Group II), led the suthors to conclude that this group contained children who should have received chelation therapy. Clinical records revealed that 37 of the 65 children in Group III had symptoms compatible with lead poisoning. Perino and Ernhart reported a significant negative relationship between blood lead levels and cognitive, verbal and perceptual abilities in 80 asymptomatic children, ages 3 years to 5 years, ll months, who had blood lead levels ranging from 10-70 yg Pb/dl. They also found a signi- ficant negative relationship between parental education level and blood lead levels in the children. Their "low lead" group (10-30 yg Pb/dl) did not differ significantly from the "moderate lead" group (40-70 yg Pb/dl) in socio-economic status, sex, age, parental intelligence, number of siblings, birth order or birth weight. 43

OCR for page 37
Landrigan and McNeil each studied different groups of asymptomatic children exposed to lead emissions from an ore smelter in El Paso, Texas. Both studies contained an exposed and a control group. Landrigan found impaired non-verbal cognitive and perceptual skills, as well as slowed finger-wrist tapping in his exposed group. McNeil found no significant intellectual or behavioral differences between carefully matched exposed and control groups. Several factors make it difficult to evaluate the results of these studies. The children studied had multiple exposures to metals, including lead, arsenic, copper, zinc and cadmium.^° Landrigan's criteria for selection of children for the study group were based on a blood lead level >40 yg/dl, while McNeil's criteria were based on residence in proximity to the smelter. In addition, normal hemoglobin and hematocrit levels found in these children"^ indicate that nutrition was probably adequate. This may have served as a protective factor in these children. Lansdown's^° study of British children exposed to lead emission from an ore smelter showed no significant correlation between blood lead levels and either intelligence quotients or behavior ratings. However, of the 215 school age children studied, only 12 had >50 yg Pb/dl and 31 had 40-49 yg Pb/dl. Thus, the correlation coefficients were heavily influenced by the 172 children with <40 yg Pb/dl. In addition, there was no attempt to match the study group with a control group of the same age, parental intelligence, socio-economic status, birth rank, family size, etc. q Retrospective studies carried out by Beattie et al and David ^t _al have suggested a relationship between lead exposure and I.Q. and lead exposure and hyperactivity, respectively. Neither study, however, provided adequate documentation of the degree of early lead exposure in the children studied. This committee realizes the difficulties inherent in designing and executing longitudinal studies in children to detect subtle neuro- logic differences between groups. Although no single study cited repre- sents a perfect model, we feel that the general trends seen in these studies indicate a relationship between asymptomatic lead poisoning and neurologic and behavioral handicaps. In conclusion, we feel that the question of individual susceptibility must be taken into account when setting "safe levels" of toxic substances. Studies of both hematologic effects and neurologic effects show varying degrees of response among individuals with equivalent exposure to lead. Hematologic effects begin to occur in some 1-5 year old children when blood lead levels reach the range of 35-40 yg Pb/dl, while an increased frequency of neurologic effects have been demonstrated only in those children with elevations in the range of 50-60 yg Pb/dl or above. 44