Document G6yy5JXrLdyM0oX8zgjp1KqLr

REPRINTED BY U.S. DEPARTMENT OF HEALTH. EDUCATION. AND WELFARE PUBLIC HEALTH SERVICE CENTER FOR DISEASE CONTROL ATLANTA. GEORGIA 30333 Recommendations for the Prevention of Lead Poisoning in Children '/ Committee on Toxicology Assembly of Life Sciences National Research Council Prepared for the Consumer Product Safety Commission S tt t i National Academy of Sciences Washington, D.C. July 1976 J ti N 30679 Oo The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the Councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the Committee responsible for the report were chosen for their special competences and with regard for appropriate balance* This report has been reviewed by a group ether-fhan the authors \ according to procedures approved by a Report Review Committee consisting of members of the National Academy of sciences, the National Academy of Engineering, and the Institute of Medicine. ii l / .... . . --J* ' * DUP040013245 04-0005-0404 a c k n o w l e d g me n t s This report was prepared under Contract C-75-0018 between the U.S. Consumer Product Safety Coamission and the National* Academy of Sciences. Responsibility for the report was assigned to the Committee on Toxicology which was assisted by a Subcommittee. The Subcommittee wishes to acknowledge with thanks the assistance of Maureen B. Barrett and Thomas 0. Wilson who served as consultants in the preparation of this report. / r iii \ 3'-/ DUP040013246 04-0005-0405 Ad hoc Connietee on Lead in Paint j J. Julian Chisolm, Jr., M.D., Baltimore City Hospitals, Chairman Eula Bingham, Ph.D., University of Cincinnati Robert A. Coyer, M.D., University of Western Ontario Paul B, Hammoud, D.V.M., Ph.D., University of Cincinnati Vaun A. Newill, M.D., Exxon Research and Engineering Company Pearl L. Rosser, M.D., Howard University College of Medicine James G. Wilson, Ph.D., The Children's Hospital Research Foundation, Cincinnati Staff Officer: Ralph C. Wands Consultants: Maureen B. Barrett Thomas 0. Wilson Committee on Toxicology Bertram D. Dinaan, M.D., Aluminum Company of America, Chalrm'an Yves Alarie, Ph.D., University of Pittsburgh Mary 0. Amdur, Ph.D., School of Public Health, Harvard University Joseph F. Boraelleca, Ph.D., MedicU College of Virginia, Virginia Commonwealth University John J. Burns, Jr., Ph.D., Hpffman-LaRoche, Inc. Arthur B, DuBois, M.D., John B. Pierce Foundation Laboratory, Yale University Seymour L. Friess, Ph.D., Naval Medical Research Institute Harold C. Grice, Ph.D., Department of National Health and Welfare, Canada Harold M. Peck, M.D., Merck Institute for Therapeutic Research Charles F. Reinhardt, 'M.D., E. 1. duPont de Nemours and Company Frank G. Standaert, M.D., Georgetown University School of Medicine and Dentistry Robert G, Tardiff, Ph.D., Environmental Protection Agency iv | * Concents Introduction What are the Adverse Effects of Lead? What Dose of Lead is Required to Produce Adverse Effects? What is the Estimated Lead Intake in a Child with Pica for Paint? What is the Lead Content of Currently Available Household Paints? What Future Research is Necessary or Desirable? Conclusions and Recommendations 1 3 /' 7 8 8 9 Appendices A. Dose-Effect, Dose-Response Concepts of Toxicology B. Toxicology of Lead in Experimental Animals C. CPSC-Supplied Animal Studies D. Etiology and Consequences of Childhood Lead Poisoning . Evaluation of the Hazard of 0.5 Percent Lead Paint F. Daily Permissible Intake (DPI), Reconsidered G. Lead Contents of Current Household Paints References 45 r*9 51 54 v P/ DUP040013248 04-0005-0407 Preface This document was prepared by the ad hoc Committee on Lead in Paint of the National Research Council, National Ac ".demy of Sciences under contract CPSC-C-75-0018, from the Consumer Product Safety Commission. The CPSC requested that the Academy recommend a "safe level" of lead in paints and other coatings based on an evaluation of four studies submitted to the Acadf jy by the CPSC, The Commission also requested additional advice and tecoramentatlons related to the safety of lead in paints and coatings. / The ad hoc Committee on Lead in Paint met December 13 and 14, 1974 to review the four studies in which lead coupounds used in paints were fed to rats and baboons. The studies reviewed were: 1. Purdy, Robert H, Southwest Foundation for Research (SWFRE). A Toxicological Investigation of Chronic Lead Paint Ingestion in the Juvenile Gaboon (Nov. 1974). Contract No. CPSC-C-74-159. 2, Kneip, T.J., V,P. Rulon, LA. Pfitaer, N, Cohen and D.H, Goldstein, New York University Institute of Environmental Medicine (NYU). Lead Toxicity Studies in Infant Baboons - A Toxicological Model for Childhood Lead Poisoning (Nov. 1974). Contract No. CPSC-C--74-153. 3. Castles, T.B. Midwest Research Institute (MRI) Lead Paint Ingestion Study (Feb. 1974). Contract No. 62-W-62CC and NPC. 4, Barltrop, D. St. Mary's Hospital Medical School (St, MHM's) Assessment of the Health Hazard of Various Lead Compounds Interim Report (Sept. 1974). Contract No. HSM-99-73-28. The first two studies were contracted by the CPSC, the third by the National Paint and Coating Association and the fourth by the Environ mental Health Service Division of the Center for Disease Control, U.S. Department of Health, Education, and Welfare. Since the studies supplied insufficient data for recommending a "safe level" of lead in paint, the Committee sent a preliminary report to the CPSC on December 20, 1974 in which it stated "..., this Committee believes it is desirable to retain the present recommended level (0.5 per cent) and to defer final action until data, adequate to support a change, have been obtained." A second meeting of the Committee was held on February 6 and 7, 1975 to determine a plan tor arriving at a recommended "safe level" of lead in paints and coatings. The Committee discussions centered on the etiology of childhood le3d poisoning with particular reference to the role of lead paint ingestion. The Committee decided to institute a literature vii D P DUP040013249 04-0005-0408 search for any data, in animals or humans, which would provide a basis ror recommending a "safe level" of lead in paint. The accumulation and evaluation of data from over 200 studies has required approximately One year. This report is the result. ; s .i \ viii I ! & 1 ! 1 DUP040013250 04-0005-0409 s Introduction The primary question that this report was designed to answer may he stated as follows; "Given the fact that some children eat paint., what is a safe level of lead in paint?" An answer to this question presupposes answers to three preliminary questions; namely: 1) What are the adverse effects of lead? 2) What dose cjf lead is sufficient to produce adverse effects? and, 3) What is the estimated daily intake of lead in a child with pica for paint? These questions are discussed succinctly in the above sequence in the body of this report. Following this is a discussion of the lead content of paints available on the current retail market and a discussion of future research needs. The Committee recommendations ap ear at the end of the report. Detailed discussions and supporting data for state ments made in the body of the report are given in the appendices. Detailed Appendices have been prepared which are designed to stand along in support of the report. Although the total amount of lead assimilated may be de rived from a variety of environmental sources, this report is concerned mainly with the absorption of lead due to the ingestion ,o.f lead-containing paints by young children. 1 DUP040013251 04-0005-0410 WHAT ARE THE ADVERSE EFFECTS OF LEAD? In man, lead exerts its effects ir. the renal, hematopoietic and nervous systems. The severity of effects is related to both the degree of illness and the frequency of recurring illness as well as the dosage and duration of exposure. There are basically three stages in childhood lead poisoning: 1) asymptomatic lead poisoning, in which no clinical ** symptoms are apparent, but in which measurable metabolic changes occur, 2) symptomatic lead poisoning, in which clinical symptoms such ns anorexia, vomiting, apathy, ataxia, drowsiness or irritability occur, and 3) lead encephalopathy with cerebral edema, in which coma or convulsions occur (see Appendix D). The sequelae of lead encephalopathy include seizure disorders, severe mental retardation and death* The sequelae of symptomatic but less severe lead poisoning includes seizure disorders as well as various behavioral and functional disorders, usually grouped under the heading of minimal brain dysfunction* Clinical studies suggest that the latter syndrome may include hyperactivity, impulsive behavior, prolonged reaction time, perceptual disorders and slowed learning ability. Recent evidence Suggests that minimal brain dysfunction might also follow asymptomatic lead poisoning. The Sequelae associated with each diagnostic category of iead poisoning do not necessarily occur in every child with a par ticular diagnosis. Each individual is unique in his response. The effects of lead in the hematopoietic system are reversible and therefore do not constitute sequelae. Lead interferes with the formation of hemoglobin at several stages. In addition, lead reduces the life span of the red blood cells and this results in lead induced anemia. In cases of encephalopathy, acute renal injury (Fanconi syn drome) may also occur, and in children this is reversible. The "critical effect" concept, provides a framework for examining the effects of lead. The term "critical effect" is used to mean first effect, rather than most serious effect. Since effects in the kidney do not appear in the early stages of lead poisoning, the kidney cannot be considered the site of the critical or first effect. It is not presently known whether the first effects occur in the neurologic or hematopoietic systems. Subtle neurologic effects are difficult to measure. There are currently no simple neurochemical tests for measuring early metabolic changes in the nervous system. However, several labora tory tests are currently available for measuring early effects in the hematopoietic systems. At the present time, the hematopoietic system is considered the site where the "critical effect" occurs (see Appendix A). If this is correct, then environmental limits, set to prevent reversible effects in the hematopoietic system, should serve to prevent potentially irreversible effects in the nervous system. ' WHAT POSE OF LEAD IS REQUIRE!? TO PRODUCE ADVERSE EFFECTS? In relation to lead, the general term "dose" may be variously interpreted to mean: I) the quantity of lead administered, 2) the 3 3? DUP040013252 04-0005-0411 33 .] quantity of lead absorbed* or 3) the quantity of ieao present in the' affected organs or tissues. In this report, we will use the terms "external dose" and "internal dose" whore necessary, to provide clarity. The external dose may be defined as the amount of lead entering the body through the gastrointestinal tract, lung, etc., some of which will be excreted before reaching the organs or tissues potentially affected by lead. The internal dose, or tissue concentration, say be defined as the amount of lead present in the organs or tissues. In experimental animals, the internal dose can be measured after sacrificing the animal. In humans, the analysis of tissue lead levels through biopsy or autopsy is rarely done; therefore:, it is necessary to use some other indicator of "internal dose." We will use blood lead concentrations as an indi cator of internal dose (see Appendix A). Individual Variability. We have found that individual variability influences the estimate of a dose necessary to prosuce an adverse effect. In a heterogeneous population, numerous factors modify the relationship between dose and effect in the individual so that some members of the population will appear to be affected by comparatively low doses of lead, while others will appear to be highly resistant, showing little or no effect at higher does. In general, however, the percentage of indi viduals in a population who exhibit a specific effect will increase in relation to an increase in dose. Not all factors which influence susceptibility are known. Therefore, this Committee feels that any estimate of a safe dose level should allow a margin of safety for highly susceptible individuals (see Appendix A) who are affected by relatively low doses. Known Conditions Affecting Susceptibility. Evidence in both animals and humans indicates that age and diet are primary factors influencing the absorption and effects of lead. Detailed discussions of these factors are given in Appendices B and D. Due to the very rapid rate of brain growth, the young animal or child is at greater risk for lead-induced neurologic damage than the adult. In humans, the "growth spurt" begins during the sixth month of pregnancy and continues into the third or fourth year postpartum. Glial replication and differentiation and cerebellar growth is most rapid during the first 18 months of life. Myelination continues into the third or fourth year of life. Permanent neurologic deficits can result from an insult to the brain during the growth spurt. Studies of children malnourished during the first two years of life have shown permanent adverse effects on learning ability anc .general adjustment. Studies in rats and lambs administered lead during the growth spurt have shown slowed learning abilities which persist in the adult animal, even after blood lead levels have returned to normal. Behavioral changes, including hyperactivity, aggressiveness, tremors and repetitive grooming behavior, have been produced in rats poisoned during the "growth spurt." The brain of suckling rats has been shown to have a significantly higher rate of lead uptake than the brain of adult rats. This may, in part, account for the greater central nervous system (CNS) vulnerability observed in young animals. } j j 'j j J j ;j ; j i * \ I DUP040013253 j 04-0005-0412 Age also appears to modify the Intestinal absorption rate for lead. Alexander's balance study in eight healthy children showed that approximately 50 percent of dietary lead was absorbed. Kehoe's balance studies in adults showed that only 10 percent of dietary lead was .absorbed Studies in rats confirm these observations in humans (see Appendix B), Using the average dietary lead intake for normal "non-exposed" adults and the different absorption ratios and caloric requirements for children and adults, a 3-year-old child would absorb 12 times more dietary lead than an adult receiving the same diet (see Appendix F). Both dietary components and dietary deficiencies have been shown to alter the intestinal absorption rate of lead. In experimental animals, the intestinal absorption of lead is signif-ieanEly increased if lead is administered in oils, fats or milk rather than in a diet of dry feedSimilar studies are not available, nor would they be possible, in young children. Dietary deficiencies, including deficiencies of calcium, copper, and iron have been shown to increase the absorption of lead in rats. Dietary deficiencies of calcium and particularly iron have been repor-id to be prevalent among preschool age children, especially those in the lower socioeconomic groups. Because of the Japid growth rate during early childhood, iron stores are marginal even in apparently healthy children- Pica, as an additional risk factor, occurs among preschool age children:. Pica, the repetitive ingestion of non-food substances, occurs in at least 50 percent of children between 1.2 and 36 months of age. In summary, a variety of factors combine to make the young child less resistant to lower levels of lead than the adult. The habit of pica may lead to ingestion 'of lead-containing paint chips; the young age makes the child vulnerable to lead-induced neurologic damage; and both age and diet contribute to produce a relatively high intestinal absorption rate for lead. Relationship Between Dose and Effect. The effects of lead occur in the hematopoietic, neurologic and renal systems. Whether rhe critical (first) effect of lead occurs in the hentopoietic or neurologic system is unknown. Presently, the hematopoietic system is considered the critical site for lead's effect. Using blood lead (Pb-B) as a measure of the "internal dose" of lead, different effects can be seen as blood lead levels increase* Lead-induced anemia has been reported in both children and adults. Lead's Interference in the formation of hemoglobin results in the accumulation of free erythrocyte protoporphyrin (FEP) in blood and 5-arainolevulinic acid (ALA-U) in urine. In several small groups of women and children FEP begins to increase as levels rise above a range of 25-30 eg Pb/dl (micrograms of lead per deciliter). The urinary excre tion of ALA begins to increase in children and adults when blood lead levels reach a range of <3-50 wg Pb/dl. Decreasing hematocrit levels have been reported In children when blood lead levels exceed 40 ;ig Pb/dl while decreasing hemoglobin levels in both adults and children have been reported at levels equal to or greater than 50-60 tig Pb/dl. In summary, the first metabolic evidence of lead's effect in the hematopoietic system appears at approximately 25-30 pg Pb/dl, while anemia usually docs not 5 3/ DUP040013254 04-0005-0413 i appear until blood lead levels reach 50-60 yg Pb/dl (see Appendix D) i Neurologic changes, including slowed learning ability, paraplegia, clumsiness and hyperactivity have been produced by administering lead to , young experimental animals* The slowed le*. "ning ability appears to be an irreversible effect (see Appendix IS). { ( j ; :| i Studies in children have been difficult to perform. None by ' \ j itself has provided all of the requisite data* Only one truly prospective J study has been reported. Taken together, the several reports strongly suggest that both decreased cognitive functioning and an increased fre- j j quency of behavioral abnormalities become evident in groups of .school* aged children who have been unduly exposed to lead during the preschool 1 f years (see Appendix D). The behavioral aberrations which include ! hyperkinesis, short attention span and impulsive and aggressive conduct. | appear to be more important than minimal intellectual deficits in \ impeding progress in school. A similar observation was wade by Byers j and Lord over 30 years ago. In addition, a .higher frequency of seizure disorders and school failures are reported in children with lead poisoning. ] An increased frequency of neurologic effects has be$n demonstrated only | in those children with blood lead elevation? greater than 50-60 pg Pb/dl. 1 Severe mental retardation, blindness and death have been reported in children with lead encephalopathy* *n children, lead encephalopathy is usually associated with blood Lead levels greater than 120 pg Pb/dl. f Relationship Between External Dose and internal Dose. An estimate of the external dose (lead intake) necessary to produce a specific internal dose (blood lead) concentration must abcount for the chemical and physical form of lead ingested (see Appendix A). In children, up to 50 percent of dietary lead nay be absorbed and 50 percent excreted in the feces. Although balance data in children are limited they are in agreement with data from suckling animals which show a high rate of lead absorption ! (see Appendix B). Animal studies have also shown that lead in paint j films is less well absorbed than dietary lead. Lead chromate. One of the least well absorbed compounds found in paint, is absorbed approxi! nateiy one-third as well os the free salts of lead when added to the diet. Other lead compounds found ip paint, such as lead napbthenate, have higher rates of absorption but are still absorbed to a lesser extent . when incorporated into a paint matrix. Thus, 17 percent (1/3 x 50%) would be a conservative estimate for the amount of lead absorbed from paint by a young child (see Appendix E). 3arlcrop found a mean daily fecal excretion of 67.8 pg Pb/day in a group of two- to three-year-old children wi th a mean blood lead level of 20 pg Fb/<31* These data would be consistent with a dietary intake of 135 eg Pb/day if 50% is absorbed. On the basis of body weight for an average three-year-old child weighing 15 kg., Barltrop's group of children with a mean blood level of 20 pg Pb/dl would have a daily intake of 9.0 eg Pb/kg/day with an absorption of 4.5 pg Pb/kg/day. This agrees well with Alexander's estimates of dietary intake in young children (see Appendix D). : 6; i * 7> DUP040013255 l 04-0005-0414 There are no published data relating external dose to internal, dose in children with blood lead levels in' the range of 40-60 ;.g Pb/d!, Kehoe added lead to the diet of adult volunteers. His studies have shown that the absorption of 1.43 eg Pb/kg/day due to the added,lead was associated over a period of approximately nine months with an in crease in blood lead level of 17 jig Pb/dl (see Appendix E). One can calculate that if the absorption of 4.5 tJg Pb/kg/day will produce an average blood lead level of 20 pg Pb/dl in a two- to three-year-old child, then an absorption of an additional 1.43 jjg Pb/kg/day or a total of 5.9 pg/kg/day could produce a blood lead level of 37 yg Pb/dl. Similarly o.ne could calculate that the total absorption of 7,4 ;,g Pb/kg/day could produce a blood lead level of 54 yg Pb/dl. The external dose (amount of ingested lead) necessary to produce these blood lead levels will depend in part On the chemical and physical form of lead ingested. / Because of the dearth of information relating external dose to internal dose (blood level or other tissue concentration) in children, the calculations given above are only estimates based on the best available data. . i WHAT IS THE ESTIMATES LEAD INTAKE IN A CHILD WITH PICA FOR FAINT? Pica, the repetitive ingestion of non-food substances, occurs In approximately 50 percent of children between one and three years of age. This habit is considered normal behavior until about three years of aga. Psychosocial factors or organic brain damage may cause the persistence of pica beyond three years of age. Pica for paint generally begins at the time of ambulation or at about 10 to 12 months of age and is believed to be episodic, occurring perhaps two to three times per week (see Appendix D). } Abdominal x-ray films showed radiopaque materials in the ; intestinal tract in 35 percent of children attending the Chicago Lead Clinic- The best available clinical evidence indicates that children with pica may ingest one to three grams of paint per week (see Appendices D, E), If the paint contained the present legal limit of 0.5 percent lead (5,000 pg/g paint) , then the daily ingestion of lead from paint would be 714 pg Pb/day, 1,429 pg Pb/day or 2,143 pg Pb/day, respectively, for one, two or three grams of paint ingested per week. Calc listed on the basis of body weight for a two -y ear-old child weighing 12.3 kg, and using an absorption factor of 17 percent for lead from paint, the amount of lead absorbed would be 9.7 pg Pb/kg/day, 19.4 yg Pb/kg/day and 29.1 pg Pb/kg/day, respectively, for one, two and three grams of paint ingested per week (see Appendix E). The daily absorption of 4.5 pg Pb/kg/day has been found in children with essentially normal blood lead levels of approximatly 20 pg Pb/dl. The estimated daily absorption of lead from paint must be superimposed on the estimated absorption of lead from diet, in order to obtain a total daily absorption. Thus, the daily absorption of lead in a child with pica for paint (containing 0.5 per cent Pb) may be three to seven times that found in a child receiving a normal diet. For a child with pica for paint, a level of 0.5 percent lead in paint clearly represents a hazard. 7 3C DUP040013256 04-0005-0415 WHAT IS THE LEAD CONTENT OF CURRENTLY AVAILABLE HOUSEHOLD PAINTS? The Unit of 0.06 percent lead in paint was proposed to allow for trace amounts of lead present in the raw materials, for possible contamination during processing and for limits of precision in the analytical t-ethods of determining the lead content of paint. An industry formulary indicate that alternative, less toxic substances such as zinc and calcium salts may be used in place of lead as auxiliary driers. A market place survey conducted by the CPSC found that 70.8 percent of oil-based paints and 96.1 percent of water-based paints con tained less than the proposed limit of 0.06 percent lead in paint (see Appendix .G). The four colored oil-based paints which consistently exceeded this limit were black, green, yellow, and white. Among these paint colors, 50/2 of the black, 76% of the green, 62% of the yellow and 81.5% of the white contained <0.06% lead. These figures strongly suggest that at least some pain*; manufacturers have found it techno logically and economically possible to meet the proposed limit of 0.06 percent lead in most paints, '1 None of the members of the ad hoc Committee on Lead in Paint are paint technologists. Therefore, we could reach no conclusions relative to any possible change in paint quality if lead levels are reduced to trace amounts, la addition, the Committee members did not have the expet "rise necessary to predict the economic impact of meeting the proposed limit of 0.06 percent lead in paint. Based on the evidence in children and experimental animals, this Committee concludes that 0.5 percent lead in paint represents a hazard to young children with pica for pairt. < WHAT FUTURE RESEARCH IS NECESSARY OR DESIRABLE? Numerous studies of lead's effects have been carried out in experimental animals and humans; nevertheless, no single study has provided a comprehensive model for establishing a "safe Level" of lead intake in children. This Committee could arrive at estimates of safety only by collating the results of various studies. We feel that a comprehensive study, designed to determine the interrelationships between lead intake, absorption and effects would provide a more precise method for estimating a safe level of lead intake. Properly designed animal studies simulating conditions in human infants are needed to identify the relationships between external dose (dose of lead administered), absorption rate of various forms at various ages, internal dose, vul nerability of the brain (at various ages), influence of nutritional factors, time between exposure and appearance of effects, and permanence or reversibility of effects. In addition, we feel that studies in preschool-age children ate necessary to define more accurately the relationships between lead intake, absorption and effects and to provide more precise data regarding the amount of paint which a child with pica may ingest. Information 8 DUP040013257 04-0005-0416 I: 5 relative to the absorption and effects of minimal lead exposure in the human fetus and infant less than 12 months of age is virtually .non- existent .' Since studies in experimental animals indicate that the suckling animal is extremely vulnerable to the effects of lead, we feel that primary consideration should be given to examining the effects of lead in human infants less than one year of age, particularly in regard to effects in the neurologic system, CONCLUSIONS AND RECOMMENDATIONS The conclusions given below are based on what is known from studies in experimental animals and humans, Unfortunately, some factors which may influence a child's susceptibility to lead are poorly under stood. Studies in both experimental animals and children have shown that the brain is particularly vulnerable to permanent damage if injury to the developing brain occurs during infancy, in addition, young animals and children have been shown to absorb a higher proportion of ingested lead than adults. Animal experiments have shown a higher retention of ingested lead in animals receiving lipids or milk ini the diet than in those receiving dry feed. In addition, dietary deficiencies of calcium, copper, and iron increased the absorption of lead in experimental animals, Ho data relative to these points are available in children. However, the average child's diet contains both lipids and milk. Dietary defi ciencies, particularly iron deficiency, have been shown to exist in a significant number of American children. No firm data are available to elucidate genetic factors which may possibly influence susceptibility to lead. Although the best available evidence suggests that some children may ingest 1 to 3 grams of paint per week, there is no basis for assuming that 3 grams of paint is the maximum amount ingested. In summary, the conclusions and recommendations, where possible, are based on known available information in children; where information is lacking, they are based on the extrapolation of data from studies in either adults or in experimental animals which most closely approximate the conditions found in preschool-age children. Conclusions 1. Since the CPSC-suppiied studies did not adequately simulate the conditions found in yotiug children, particularly in relation to age and diet, we were unable, on the basis of these studies, to determine that 0,5 percent lead in paint is safe. 2. Since the first metabolic effects in children become evident when the blood lead concentration exceeds 30 pg/di, and since the most desirable means of controlling disease is prevention, we recommend that the total daily lead exposure, including exposure from food, ambient air and paint, for a one- to five-year-old child not exceed levels sufficient to raise the blood lead concentration above 30 pg Pb/dl. In order to allow far variations among individuals, the mean blood lead concentration for groups should not exceed 20 pg Pb/dl. Among two to three year old children an absorption of 4.5 pg/kg/day is apparently associated with a mean blood lead concentration of 20 pg/Pb/dl. 9 Aj J s' t 39 \ 1 DUP040013258 ! 04-0005-0417 3, Since contro.' of the lead paint hazard is difficult to accomplish once multiple layers have been applied in homes over two to three decades., and since control is more easily regulated at the time of manufacture, we recommend .that a limit for the lead content of paints be set and enforced at the time of manufacture. . 4, Since 0.5 nercent lead in paint represents a hazard to a child with pica for pa .nt, and since most currently available household paints contain <0.06 percent lead in paint, thus demonstrating that lead is not an essential ingredient for all paints, and since a reasonable allowance must be made for variations due to contamination of raw materials and detection limits and precision of analytical methods for analyzing the lead content of paints, we recomusnd that the deliberate addition of lead to paint for residential buildings or other surfaces accessible to young children be immediately discontinued and that a level not to exceed 0.06 percent lead in the final dried product be jet for regulatory purposes. Since paints without lead additives may con tain up to 0.03 percent lead, a level of 0.06 percent lead provides reasonable latitude for regulatory purposes, 5, Since a time allowance is necessary to implement these recommendations, and since extensions may be sought to delay compliance, we recommend that'variances be allowed only on the basis of demonstrated economic hardship and that none be allowed to extend beyond five.years, A time limit of five years will prevent accumulation of lead to dangerous levels from repeated applications. 6, Since most cases of serious childhood lead poisoning found today are clearly related to the ingestion of old lead paints, and since this hazard say be expected to exist in older homes fojr some time, we strongly recommend that research be conducted to determine methods for the removal of old lead paints, which will provide adequate safety for both the residents and the workmen performing the renovation procedures. j 7. Since the infant is most vulnerable to the effects of lead and since little is known about the relationship between lead dose and effect in the child from birth to one year of age, we recommend that the lead content of paints or coatings on infant toys and furniture should not exceed 0.06 percent lead and that food commonly fed to infants should contain the lowest practical level of lead as determined by FDA. 8. Since few studies in experimental animals have provided adequate designs to simulate the conditions found in a young child and since no research has been conducted on the relationship between lead dose ana effect in the human infant less than 12 months of age, and since few studies in preschool-age children have provided adequate information on the dose-response relationship for lead in the one- to five-year-age group, ue recommend that future research focus on these areas. '8 9, Lead continues to have diverse uses, the regulation of which falls under numerous different governmental agencies depending on 10 3? rr^'Tuff-'f-ni i*~ir''*Ttp'i >' * / DUP040013259 04-0005-0418 r i ' its use. We recommend that these various agencies coordinate their research efforts in relation to the dangers of lead and that they coor dinate their policies regarding the limits for human exposure from industrial sources, consumer products, air, food and water so that an Individual's total exposure from various sources falls within a range which allows a margin of safety for those individuals in the population who are affected by relatively low doses. i 11 DUP040013260 04-0005-0419  Appendix A Dose-Effect, Dose-Response Concepts of Toxicology The dose-effect, dose-response concepts of toxicology provide a framework for examining the biologic effects of toxic metals. These concepts and their application to human exposures to heavy metals are. discussed fully In "Effects and Dpse-Responue Relationships of Toxic Metals.Here we will initially summarize these concepts through a series of definitions and then discuss their specific application to lead. Critical Effect - The critical effect is not the most serious but rather the most sensitive and specific biologic change, beyond acceptable physiologic Variation, which is caused by the presence of a toxic substance. Although many different effects may occur, the critical effect is defined as the first measurable adverse effect. "Sub-critical effects" are measurable biologic changes which do not impair cellular function, but which are directly related to the concentration of a toxic substance. Critical Site - The critical site is the location in the body where the critical effect occurs. It may be a system, organ, cell type or cell component;. Dose - In experimental animals, an administered dose is readily quantified but this is not true of humans. For hximans we can estimate the amount taken in and for this we use the tern "external dose." Since this is an indefinite amount for humans we must relate response to a tissue level such as blood concentration and we use the term "internal dose" for this tissue level. The "external dose" is the quantity of a toxic agent which enters the organism through the lungs, gastrointestinal tract, skin, etc., a portion of which may be excreted before reaching the "critical site," The "internal dose" is the quantity of a toxic agent which is absorbed and reaches the critical site. Since the concentration of a toxic agent at the critical site can rarely, if ever, be measured in human studies, the concentration is measured in a body fluid such as blood or urine. The concentration of a toxic agent in blood or urine is then used as an indicator of the internal dose. Dos-r--Effect Relationship - The dose-effect relationship is a relationship in which a quantitative change in a metabo lite feffecc) is directly related to the concentration (dose) of a toxic substance. A typical dose-effect relationship is graphically illustrated by an "s" shaped curve when dose is plotted on the abscissa and degree of effect on the ordinate. 13 DUP040013261 04-0005-0420 Dose-Response Relationship - The dose-response relationship is a relationship in which the percentage (response) of a population exhibiting an effect is related to the con centration (dose) of a toxic substance. Those exhibiting an effect are termed "reactors," and those not exhibiting an effect, "non-reactors." A typical dose-response relationship is illustrated by an "s" shaped curve when dose is plotted on the abscissa and percent positive reactors is plotted on the ordinate. POSE-EFFECT r e l a t io n s h ip s f o r l e a d The effects of lead are seen in the neurologic, hematopoietic and renal system. Acute adverse functional effects in the kidney are generally seen in association-with symptoms and high levels of lead exposure in adults. Similarly, late lead nephropathy is also associated with prolonged high levels of lead exposure. Therefore, the kidney is not currently considered the first organ affected bv lead.29,'l Derangement of hemoglobin synthesis in the erythroid cells of the bone marrow is currently considered the critical effect for lead,'0,71,103 Increases in urinary 5-aminolevulinic acid (ALA-U), urinary coproporphyria (CP-U) and erythrocyte protoporphyrin (EP) are indicators of lead's effect in the hematopoietic system. In lead poisoning (and iron deficiency), it is the metalloporphyrin, zinc protoporphyrin, rather than free protopprphvrin IX which is present in excess in the circulating erythrocytes. 5 increased ALA-U and EP reflect viyo inhibition of the enzymes ALA-D and ferro chelatase by lead.70,71 The mechanisms responsible for the co;>roporphyrinuria of plumb.ism arc not well understood. Inhibition of ALA-D by lead has been extensively studied. jn a number of epidemiological studies in which ALA-D activity is measured _in vitro in hemolysates of peripheral blood, a significant negative log-normal relationship has been found between ALA-D activity and whole blood lead concentration. This relationship is found over a wide range in blood lead concentration, including the normal range (5_ro approximately 40 yg Pb/dl whole blood). More recently, Granie t ai have developed an assay for ALA-D in which the ratio of activated to non-act.ivated ALA-D activity can be measured. With this particular assay, a positive linear relationship between the ratio of activated to nun-activated ALA-D activity and blood lead concentration is found oyer a range of 20-90 yg Pb?dl whole blood. On the basis of this and kinetic studies, they^ propose that inhibition of ALA-D by lead is non-competitive and that there is probably no interaction with lead at concentrations of *15 yg Pb/dl whole blood. Under physiologic conditions in man, however, accumulation and increased excretion of ALA-U, the substrate of ALA-D, does not begin to occur until Pb-8 exceeds approximately 40 ug Pb/dl whole blood, a level at which most _in vitro assays for ALA-D indicate substantial inhibition. This has been interpreted as evidence that there is a substantial reserve of ALA-D adequate to meet physiologic needs at lower concentrations of lead in whole blood. For this reason, reduction in A1A-D activity, as measured 14 DUP040013262 04-0005-0421 in vitro in peripheral blood, is considered a sub-critical effect within . the context of the above definitions; while increases in ALA-U, CP-U and F.P are considered indicators of lead's critical effect on hema topoiesis. 70,71,105 Significant dose-effect relationships are found between these metabolic precursors of heme and the concentration of lead in body fluids. As an example, a dose-effect curve, using blood lead concen tration (Pb-B) as an indicator of internal dose and quantitative 24- haur output of ALA-U as an indicator of effect, is given in Figure .1. One can begin to see the typical s-shaped curve usually associated with this relationship, Differences in individual susceptibility can also be seen at each dose vPb-B) level. Zielhuis^^ and ochers^o,81,86 have found similar relationships for lead's effect on the hematopoietic system. These effects begin to occur when Pb-B levels reach the 40-60 Ug Pb-B range, although preliminary data suggest that. EP begins to in crease as Pb-B rises above 30 eg Pb/dl whole blood. Adverse effects in the hematopoietic system are reversible, } At the present time, there is no well-defined set of sensitive biochemical indicators of lead's effect on the nervous system. However, preliminary studies in rats^ use ncurochemical tests which may become useful as measures of neurologic changes in humans. Published reports to date have used functional tests to measure lead's effect oh the human nervous system. A relationship has been tentatively suggested between decreased intelligence,3,23,24,73 hyperactivity,21 behavioral and psychological changes,24and loss of fine motor function,78 young children with blood lead concentrations in the 50-70 ug Pb-B range. In some instances, the effects of load on the nervous System aie clearly irreversible. Sequelae are related to the severity and duration of signs and symptoms. The risk of permanent neurological complications increases with repeated acute clinical episodes of lead poisoning.^ Whether the effects reported in subclinical lead poisoning are reversible is unknown; however, de la Burdd's most recent study suggests that they are not.'" Currently, no data exist to show whether neurochemical or neurophysiological changes precede changes in the hematopoietic system. The hematopoietic system is currently considered the "critical'' or first system to be affected. It this is true, then medical intervention based on evidence of reversible effects in the hematopoietic system should prevent possible irreversible effects in the nervous system. D0SF.-P.ESPOSSE KE1-AT I QNSHIPS FOR LEAD The results of population surveys which measure both dose and effect in each individual may be expressed as dose-response curves. Figure 2^ illustrates this relationship for lead when Pb-B is used as an indicator of internal dose and erythrocyte protoporphyrin as an indicator of effect. Positive reactors are those individuals who exhibit an effect greater than the expected mean plus two standard deviations, 15 tf ii DUP040013263 04-0005-0422 The percentage of positive reactors for each blood lead group is plotted. Highly susceptible individuals show a. positive response at relatively low blood lead levels, while highly resistant individuals show a normal response at relatively high blood lead levels. Similar dose-response curves can be plotted for each measure of lead's effect, so that a series of dose-response relationships may be shown.105,106 For the groups charged with recommending "safe levels" of toxic substances, this approach to analysis of the data is helpful. However, appropriate interpretation of the data requires that the population under study be well-defined for factors such as age, sex, concurrent Illnesses, etc., which may influence test results. Background response nust also be considered. Background response refers to the percentage of the population exhibiting an effect caused by factors other than the specific agent under consideration. When using erythrocyte proto porphyrin as a measure of lead's effect, some "background response" may be expected due to the presence -of i.on def iciency in the population. Separate dose-response curves way be drawn to correct for background response. Based on inspection of Figure 2, an epidemiologist seeking to prevent early hematologic effects in 90 percent of the preschoolage population, would recommend that environmental lead sources not exceed a limit known to raise ?b-B levels to the neighborhood of 30 pg. '' Dose-response relationships for lead are generally not available because of inadequately designed population surveys which consist solely of the collection and analysis of biologic samples. The population characteristics, including these which influence background response, must be known. 'Ao published data are available for children less than one year of age. 16 DUP040013264 04-0005-0423 o srWPTOW&TiC PUWBISM ASrMPtOMATlC 26 1 "'1 \bs....... . * '* `iooo pgPb/VCM WHOLE DlOOD FIGURE I. Dose-effect relationship between an indicator of internal dose (Pb-B) and an indicator of effect (urinary excretion of ALA, ALA-D), (From Chisolm, J. Julian Jr-, Barrett, Maureen B., and Mellits, E. DavidDose-effect and doseresponse relationships for lead in children. J. Pediatr. 87:1152-1160, 1975- Reprinted with permission.) Note: 2 indicates 2 superimposed data points. 17 y6 DUP040013265 04-0005-0424 FIGURE 2. Dose-response relationship for the effects of internal doses of lead as ?b-B on erythrocyte protoporphrih. (From Chisolm, J. j., JrArh. Hig. Rada Xofcsikol. (Archives of Industrial Hygiene & lexicology), Suppl. to vol. 26, 1976 [in press!. Reprinted by permission.) m 18 DUP040013266 04-0005-0425 X<5 '.... Appendix B Toxicology of Lead in Experimental Animals SELECTION OF A PROPER MODEL Ethical considerations dictate that potentially dangerous experiments involving toxic metals be carried out in animals, not man. Unfortunately, no one species of animal is a perfect model for man. Therefore, it is crucial to insure that the organs or systems known to be affected by the toxic metal in man are closely approximated in the experimental animal species. Many recent animal studies involving lead have sought to study lead's effect on the nervous system. If the results of these studies are to be used to predict comparable effects in young children, then the stage and rate of brain growth in the animals studies are of crucial importance. Neural Development in Humans - Dobbing and Sands have described the quantitative growth and development of the hutban brain for the period from 10 weeks gestational age to seven postnatal years,22 The "growth spurt," the time of most rapid growth, begins in humans during mid pregnancy, Three major components of the brain were examined to delineate the period of growth spurt. Glial replication and differentiation extends to at least the end of the first postnatal year and quite possibly beyond 18 months (see Fig. 3). Myelination continues into the third and fourth years (Fig. 4). Cerebellar growth is most rapid during the first 18 months of postnatal life (Fig. 5 and Fig. 6). Approximately 83 percent of the human brain growth spurt is postnatal. Sutdies of malnutrition in human infants have shown that the brain Is particularly vulnerable during the growth spurt. Klein and associates studied the relationship between starvation, caused by pyloric stenosis, and intelligence. " Pyloric stenosis occurs between birth -and three months of age, is surgically correctable and is not associated with any particular socioeconomic or cultural group. Klein found that the brief period of starvation in infancy, prior to surgery, had permanent effects on learning abilities and general adjustment, as measured 5-14 years later, Hertzig et al2^ found reduced I.Q. levels in school-age boys who had been malnourished during the first two years of life* In humans, the initial exposure to lead in paint usually coincides with ambulation and so begins at 10-12 months postpartum, while exposure to lead from some canned nutrients may begin at or shortly after birth. Neural Development in Experimental Animals - Dobbing and associates have demonstrated the vulnerability of the developing brain to moderate hyponutrition in experimental animals.! Hyponutrition occuring during the growth spurt produced a permanent reduction in both body and brain weight as well as behavioral changes, Hyponutrition before this critical period had less severe effects on CNS development. 19 ! DUP040013267 04-0005-0426 The growth spurt in rats occurs during the first 25 days postpartum.25 Glial cell multiplication occupies the first half of this period. The second half extending to about the 25th postnatal day, is a period of rapid myelination. Dendritic authorization and synaptic connections are also occurring during this period, along with dramatic metabolic and neurochemical development and rapid cerebral growth. Demor strable and permanent clumsiness is associated with cerebellar deficits caused by hyponutrition during the growth spurt.^3 / Figure 7 shows the velocity of human brain growth compared to the rat, pig and guinea pig. Striking differences are apparent in relation to the stage of brain development at time of birth. There is a dearth of information regarding the rate of brain growth in primates other than man* Nothing could be found concerning the rate of brain growth in the baboon which would have permitted a direct comparison of the CPSC studies with man. However, Portman and associates,76,77 in studying the, rhesus monkey, found that 70 percent of the adult brain weight was obtained bv 165 days gestational age (mean age of birth). Alien and associates-* produced obvious behavioral abnormalities in infant rhesus monkeys exposed to lead. No obvious behavioral abnormalities occurred in adolescent or adult mankeys exposed to a similar dose. These findings are consistent with the concept that the baboons in the CPSG studies were beyond the comparable period of growth spurt in young children. Absorption Factor In Relation to Age - Studies in both humans and animals137^17^5 indicate that the rate of absorption of lead from the gastrointestinal tract is greater in the young than in the adult. Studies in rats (See Tables B1 and Bl.a) illustrate the rapid decrease in absorption of lead as age increases from birth. The balance data of Alexander et al in children are too limited to permit any statement concerning possible differences in the rate of absorption during early childhood; however, the average absorption of dietary lead found in these children (53%) is substantially greater than the 5 to 10% absorption found in adults. Scientists seeking to evaluate the CNS effects of lead in human infants should select animals experiencing rates of brain growth and rates of intestinal absorption comparable to the human infant. Momcilpvic and Kostial found that the uptake of lead in the brain of suckling rats was six to eight times greater than that found in the brain of the adult rat. Krigman ct al, by adding PbCOj to the diet of the mother, induced a four-fold increase of lead in the brain of sucklings over the amount found in the mother..53,54 Total brain growth was inhibited and myelin production was reduced in the brain and in the sheath about the axons. Reduced amounts of galaetolipids, cholesterol, plasmalogens and total phospholipids were observed in these animals. No data were reported for the lead content of milk or blood. SELECTION OF PROPER EXPERIMENTAL CONDITIONS Cnee the proper model has been selected to simulate a comparable rate of brain growth and comparable rate of intestinal absorption in 20 | | f ! | j j | f | | J j | ;{ | | j I 1 j | DUP040013268 04-0005-0427 't man, the experimental conditions, particularly those relating to diet and method of lea-' administration, should be selected to simulate those conditions seen in man. Diet - Most 'experimental animals are fed optimal diets. Studies in rats6**>92 reveal that dietary deficiencies of calcium, copper and iron increase the absorption of lead from the intestinal tract. Dietary deficiencies have been shown to exist in 3 significant number of American Children.i98 tn addition, fats and milk have been found ' to increase the absorption of lead in experimental animals,^3,51>52,68 In two groups of rats of the same age, lead absorption decreased to a greater extent in the group switched from a milk diet to a dry dood diet, while those who continued to receive a milk diet showed only an age-related decrease in absorption (see Table I, p. 28). Experi mental animals receiving dry feed diets containing ail nutrient require ments do not simulate a child's diet, which may contain both fats and milk and which may be Inadequate in other respects. r Method of Lead Administration - Administration of lead by injection in animals is the easiest method of determining th<^ exact quantity administered, but does not simulate the method of exposure In man. It is difficult to determine the amount of lead ingested from loose feed, some of which the animal scatters about his cage. Studies designed to determine the rate of gastrointestinal absorption in relation to dose administered must contain a provision for accurately measuring the quantity of lead actually ingested by the animal. In order to make valid comparisons, the chemical form of lead administered to the animal should be the same as that ingested by a young child. Measures of Internal Dose - Many animal studies do not provide a measure of internal dose such as blood lead or tissue lead levels. Because of this, it is difficult to compare the results to human studies in which levels of lead in the blood-are known. Measures of Subtle Metabolic or Functional Effects - Experiments designed to produce dramatic effects, such as death, are only the first step in demonstrating the toxic effects of lead. We do not believe that the absence of dramatic clinical .symptoms at a particular dose level demonstrates the safety of that dose. Testing of animals for subclinical metabolic or functional effects, particularly those effects seen in the hematopoietic and neurologic systems, would be far more helpful in attempting to extrapolate the results of such studies to humans, RESULTS OF LEAD EXPOSURE IK YOUNG EXPERIMENTAL AMIHALS The work of Brown1"* appears to be an appropriate experimental model in terms of dose administered, age and neurodevelopmental stage. In addition, blood lead levels (Pb-B) were determined. Brown used suckling rats to investigate the vulnerability cf the brain in relation to its developmental stage. Lead acetate was administered to the dam by gavage (35 mg/kg/day). The pups were dosed through the maternal 21 i / / / >/ DUP040013269 04-0005-0428 milk either during days 1-10 or days 11-21, No further exposure to lead occurred throughout the study and the dose was controlled to prevent impaired physical growth. , Suckling rats fed maternal milk dosed with lead during postnatal days 1-10 showed significantly slower learning compared to those fed maternal milk with equal doses of Pb during days 11-21. Learning ability in the 11-21 day group was not significantly different from controls. Blood lead levels were significantly higher in the 1-10 day group (45.8 Mg Pb/dl) than in the 11-21 day group (20.4 pg Pb/dl), which did not differ significantly from controls (21.75 Mg Pb/dl). The higher olood lead levels found in the younger rats suggest a higher absorption rate for Pb during the 1-10 day period than during the 11-21 day period. It is significant that learning deficits persisted at the 8-10 week level, even though Pb-B levels had returned to normal. The persistence of effect was also seen i*i lambs after Pb-B levels had returned to normal. In an attempt to produce slowed learning in the 11-21 day group. Brown administered higher lead doses to the dams (35, 70 and 140 mg Pb/kg/day). Only when the dose was increased four-fofd, did the 11-21 day group show slowed learning comparable to that found in the 1-10 day group. This indicates that the brain is still vulnerable at the latter stage of development, but that a much higher dose is required to produce the same effect as seen in the younger animal. Additional animal experiments show impaired CHS function due to lead. However, none contain the combination of appropriate dose, age, neuro-developmental status and blood or tissue levels seen in Brown's study. The most common information lacking is the blood lead concentration, Pcntschew and Garro introduced an experimental model for studying the development of lead encephalopathy. ^ At parturition, ; maternal rats were fed a diet containing 4 percent lead. The sucklings received maternal milk containing 45.9 ppm Pb. Paraplegia was observed in 90 percent of the young animals near the end of the suckling period (23-29 days) and 85-90% of the paraplegic animals died. There were no data on blood lead levels in the pups, Rosenblum and Johnson65 used this model, but used mice fed smaller doses of lead than did Pcntschew and Garro, These mice had a high mortality rate, retardation of growth, delayed eye opening, broad-based gate, poorly developed righting reflex and changes in vascular and glial cells. There were no data on the lead concentrations in maternal milk or suckling's blood. More recently.Michaelson and Sauerhof, using a modification of the lead-in-maternal milk feeding model, were able to produce hyperactivity, aggressiveness, tremors, and repetitive grooming behavior without extensive histopathology.65,66 The maternal milk contained approximately 25 ppm lead. No blood lead concentrations were reported. Both Goiter and Michaelson,55 and Silbergeld and Goldberg,6 have experimentally produced hyperactivity using this same model. Goiter and Michaelson found a slight increase in norepinephrine. Silbergeld and Goldberg's work linked .lyperactivity to altered catecholamine metabolism.^ In addition, they applied current drug therapy, used in the diagnosis and treatment DUP040013270 04-0005-0429 of hyperactive children, to their control and experimental animals. CI5S stimulants (d- and l_-anphetamine and metbylphenidate) suppressed hyperactivity, whereas phenobarbital increased the activity in the animals exposed to lead. The same drugs glisten to control animals produced the opposite effects. Chloral hydrate suppressed the activity in both groups. The suppressed activity from d.-amphetamiae is similar to the response observed in some hyperactive children.90,91 There were no data on the lead concentration of the maternal milk or.of the Suckling's blood. Sobotka and Cook were able to demonstrate long-term behavioral deficits in neonatal rats administered oral doses of lead." Initially, the dose level did not produce obvious CNS disturbances. Feeding started at 3 days and continued through day 21 at dose levels of 9, 27 and 81 mg lead/kg body weight. Blood lead concentrations performed after 35 days showed 9 ug Pb/dl for control animals and 24 mS Pb/di for those receiving the highest dose. Activity in the high-dose lead group was decreased by administration of 3 mg amphetamine/kg body weight. We believe that properly designed animal studies, simulating conditions in human infants, are needed to identify the relationships between external dose (dose of lead administered), absorption rate (at various ages), internal dose (blood or tissue lead levels), vulnerability of the brain (at various ages), time between exposure and appearance of effect, and permanence or reversibility of effect. 23 i _ ....................... 1___________ * / \ DUP040013271 04-0005-0430 J FIGURE 3. Velocity curves showing incremental rates of DNA (2 peaks,) , cholesterol {single peak,._) and fresh weight (----- -) in whole human brain. Note the bimodel curve for DNA, representing neuroblast followed by glia.' multiplication. (From Dobbing.26 Bibl. "Nutr, Diet." 17:36-45, 1972, Publisher, S. Karger AG, Rasti. Reprinted with per mission.) J3 (From Dobbing and Sands.27 Arch. Dis. Child. 48:757-767, 1973. Ed,: Douglas Gairdner and Roger Robinson. Reprinted with permission.) i I- DUP040013272 04-0005-0431 FIGURE 5. Comparative fresh weights of 3 brain regions during growth. Weights for forebrain, cerebellum, and stem have been calculated as a percentage of adult value, and smooth lines drawn by eye through the points. "i FIGURE 6, Comparative values for total DNA-P, equivalent to to tal numbers of cells (see text), in 3 brain regions. Values shown for forebrain, cerebellum, and stem have been calculated as a percentage of adult value, and smooth lines drawn through the points. (From Dobbing and Sands.^ Arch. Dis. Child. 48:757- 767, 1973. Ed: Douglas Gairdner and Roger Robinson. Reprinted with permission.) 25 I-: DUP040013273 04-0005-0432 s FIGURE 7. Velocity of human brain growth (wet weight) compared with that in other species. Prenatal and postnatal age ex pressed as follows: human ------------ in months; guinea pig ----------- -- in days; pig------------- --- - in weeks; rat -------- in days. (From Dobbing, 25 Pediatrics 53:2-6. Jan. 1974. Re printed by permission.) 26 kC - DUP040013274 04-0005-0433 \ 'sJSuT" )I i "V zsZoZ--o.--p -o-o---?--p----n-o:--no s-j-c--v--o---_o___.s_o_._w__ss_o_......>t2Jm cssuTpiat tx uwvsi FIGURE 8. The relationship of weight ot parts of the brain to gestational age of rhesus monkeys, (From Portman e.t al.7^ drain Res. 43:197-213, 1972. Reprinted by permission.) 27 s~c DUP040013275 04-0005-0434 Table I The Effect of Milk oh the Absorption of Lead Age of Rats (days) Rats Keceivirg Milk Diet (Pere.ent^'^Pb absorbed) Control Rats* 203 (Percent Pb absorbed) 9 65.01 (16) 71.50 (12) 15 70.46 (15) 65.2a (16) 25 57.47 (14) 6.75 (15) 37 52.. 72 (17) 2.50 (15) * Control rats received only milk until day 15, when they began eating their mother's food.- Numbers in parentheses how the number of animals in each group. Adapted from Kostial, K,, Kello, D., Jugo, S. and Gtuden, N.: The effect of milk diet on toxic trace element absorption in rats. Pre sented before the XVIII International Congress on Occupational Health, Brighton, England, $ept. 14-19, 1975. ^ I j ! j | \ Table I-a CdiiriiRtesimtil o.taprptiorj ai a Unction of aye (ai-gz *d ) Att 4ayt 13 14 15 16 17 18 19 20 21 .22 24 25 27 29 32 33 37 39 89 + r+ 100.2= 99 ( 4)> 90.0 =11.2 i 61 97.0= 9 4 (12) 90.1= 8.0 < 9) 8G.5 = 9.7 ( 7) 71.1 = 13.7 (16) 78.4= 15.1 ( 5) 72.5 = 31.5 ( 6) 32,1 -a 9-9 (16) 25.6=12.1 (14) 266= 4.3 ( 4) 19.1= 4.4 ( 8) 23.1 = 13.5 ( 7) 9.7= 2.5 ( 6) 15.6= 4.6 ( 8) 4.7= 3.7 04) Sr 84.8= 6.4 (7) 79.4= 6.2 (8) 73.1= 8.5 (5) 54.4 = 10.6 (7) 35.6=15.0 (7) 15.3=118 (6) 8,2= 8.1 (5) tllpb * 83.3= 3.3 (6) 64.9= 3 6 (6) 89.7= 6.7 (6) 74.0= 13J ( 6 ) 42.4 = 11.9 (C) 36,9=10.2 (6) 15.2=12,3 (6) 16.0= 3.4 (3) 1 Number ot animili in jurrnihfiei. (Adapted from Forbes and Reina.^ J, Nutr. 102:647-652, 1972. Re printed by permission.) 28 Kl DUP040013276 04-0005-0435 Appendix C CP-SG-S applied Animal Studies Of the four studies submitted to the National Research"Council for evaluation, three were initially intended to answer the question "What is a cafe level of lead in paint?" The fourth study carried out by Baricrop under a contract from the Center for Disease Control was Intended to study the relative absorption of various lead compounds,* In evaluating these studies, this Committee sought to determine whether or not the animals studied represented a proper model for comparison to a young'child. The two crucial points considered were age and diec. A summary of the study designs and results are given in Tables I and It, Supporting data for statements 'made in this appendix relative to diet and age are given in Appendix 15. / AGE Age is an important factor in both the,susceptibility of the brain to the effects of lead and the Intestinal absorption rate of lead. Young animals, particularly suckling animals, are more susceptible to nervous system injury than juvenile or adult animals,5,13,25,26 lri addition, the intestinal absorption rate of lead is significantly higher in suckling animals (see Appendix B). The starting age of the rats used in the Midwest study16 ranged from 30-34 days, and in the St. Mary's study from 30-32 days. In rats, the "growth spurt" of the brain occurs during the first 24 days post partum. In humans, the "growth spurt" continues well into the third or fourth year postpartum. In rats, the intestinal absorption rate of lead drops significantly .at the time of weaning (approximately 22 days) and reaches adult values at about 30 days. Thus, the rats in both studies were too old for comparison to human infants and young children. This committee could find no data relative to the rate of brain growth in the baboon, in rhesus nonkeys, 70 percent of the adult brain weight is reached at the time of birth. The baboons used in the South west study'9 ranged in age from 18,2-31.0 months, and in the NYU study, from 3-23 months. The fact that all animals were weaned suggests that they were essentially beyond the vulnerable period. Extrapolation of the data on brain growth in rhesus monkeys also suggests this. Diet - The intestinal absorption of lead is influenced both by dietary composition and dietary deficiencies* In particular, a diet containing lipids or milk increases the absorption of lead. Several dietary deficiencies, including deficiencies of iron, calcium and copper. * The face that Barltrop's study (St. Mary's study) did not meet the criteria established by this committee should not be interpreted as a criticism of study design, since this study was not intended to determine a "safe level" of lead in paint. 29 DUP040013277 04-0005-0436 also Increase the absorption of lead. The average child's diet contains both fats and milk. In addition, a significant percentage of children in the U.S.A. have been found to have dietary deficiencies of both calcium and iron,119 . None of the animals in the CPSC-supplied studies received milk in their diets. With two exceptions, the diets did not contain added' fats or oils. Two baboons from the New York study were fed lead octoate (100 ng/kg/day and 500 pg/kg/day) in olive oil. After approximately 100 days, blood lead concentration ranged from 60 to 80 pg/.d.l in these animals. The St. Mary's study showed that lead compounds dissolved in vegetable oils were absorbed better than the same .compounds not mixed with oil. All(animals received diets formulated to provide optimum nutrition for the particular species of animal, used. In addition, the baboons from the New York study had dietary supplements of fruit and multivitamins twice a day and Imferpn'5' (iron) injections Co prevent anemia. We are forced to conclude that the nutritional status and dietary components of the study animals did not simulate tfie conditions found in the young child at risk for lead poisoning. Method of lead Administration - Neither of the baboon studies used old paint. The paint was pulverized to simulate the weathering found in old paints. Nevertheless, there is no assurance that this method closely approximates the weathered old paint films available to a child. The Midwest rat study may be considered a replication of earlier studies by Gage and Litchfield.32,33 The results confirm the earlier work and further document the higher availability of lead in older paint formulations. Both the St. Mary's study and the New York study had adequate controls for measuring the dose of lead administered. darltrop (St. Mary's study) combined the lead dose with feed and baked it into a hard stick form to prevent scattering. The diet was weighed before and after feeding to determine the amount actually consumed. The New York group fed the lead dose in a gelatin capsule sc that the consumption of the entire dose was easy to determine. In the Midwest study lead was mixed in the loose diet and in the Southwest study lead was administered in a Fig Newton. Measures of Internal Dose and Effect - Ail studies provided blood lead values for the control period and at various intervals during the study period. The control blood lead levels (mean approximately 10 pg Pb/dl) for all animals were significantly lower than those found in the average child living in an urban area (range of means 17-32 ug/dl).40>59 Tissue lead concentrations were provided as follows: Brain (SW and MW), bone (SW, NYU, MW), kidney (all studies), liver (SW, NYU and MW). The Southwest study provided the greatest number of measures for metabolic change. These included ALA-D, FEP, erythrocyte porphyrinogen synthetase, plasma acetylcholinesterase, blood choline concentration, corticosteroid acetyltronsferase and choline acetyltransferase. Both New York and Midwest provided measures of AtA-D, FEP and hematocrit. Most results 30 i \ i. * DUP040013278 04-0005-0437 shoves} values indicating no significant change after lead administration. Unfortunately, since the animals did not adequately simulate the physiologic state or dietary conditions of young children, wo feel Hut those results cannot he used to determine that similar doses of lead are safe for young preschool children, especially children less than three years of age. Significant Findings - We fee] that several significant findings' resultea from these studies. They are as follows:: 1. The presence of lipids in the diet increases the absorption of lead (New York and St, Mary's - see Table III). 2. Lead oetoate is absorbed more readily than lead chromate (St. Mary's), 3. A dose of 100 eg l'h/kg/day (as 0.28 percent' Pb paint) is sufficient to increase blood lead levels by approximately 12 pg Pb/dl (from .10 v Pb/dl to 2.2,3 yg Pb/dl) in juvenile baboons (New York). 4. ALA-!) activity is immediately depressed in all baboons when blood lead levels reach 50 pg Pb/dl (New York). 5. Plasma acetylcholinesterase is significantly decreased in baboons fee lead napthenate or lead oetoate at 200 ug/kg/day (Southwest). 6. Younger baboons show a greater uptake of lead In bone than older baboons (New York). 7. The chemical form and particle size influence -the absorption of lead (Midwest, St. Mary's and New York). b. Comparable doses of lead compounds incorporated into a pain: matrix are less well absorbed than the simple salts (New York). 9. Absorption and retention are related to the dose fed (St. Mary's) 10- Considerable variation in effects occurs in animals fed the same dose, thus indicating that even Inbred laboratory animals have varying degrees of susceptibility for lead (all studies). Additional Studies - The studies of Gage and Litchf ie'l.d32,33 ore often quoted as evidence that negligible risk is associated with the ingestion of lead in modern paint formulations. Their studies did show that lead in paint is about 1/3 -- 1/4 as well absorbed as inorganic lead salts. Thus, the New York study on lead oetoate is corroborated and the two studies form the basis for estimating that the paint matrix reduces absorption by a factor of 3-4. The studies of Gage and Litch field were carried out on rats weighing between 103 - 120 g which indicates that the animals were more than 30 days old. Thus, the neurp- logic development and intestinal absorption rates were not comparable to those of a young child. Based on the studies of Chisolm and Harrison1 in which a mean fecal lead output of 44 mg/day was found in children 31 j I j j j | 1 s C0 -V DUP040013279 04-0005-0438 with severe lead poisoning. Cage and Litchfield concluded that an intake of approximately 50 mg/day would represent a dangerous level.^ What the authors failed to realize was that this mean fecal Pb output was found in symptomatic children, most of whom had encephalopathy, and that although the mean fecal lead output was 44 mg Pb/day, the median output was 27 mg/day (range 5.04-104.0 mg Pb/day). In addition, the asymptomatic group of children described by Chisolm and Harrison^ all had 5 60 pg Pb/di in whole blood with positive roentgenographic evidence of lead storage in the bonus and a median fecal lead output of 1,11 mg Pb/day. Thus, Cage and Litchfield's estimate of a dangerous level of lead intake was based on a fecal lead output 40 times greater than that found in children with positive evidence of long-term lead exposure'and blood lead levels in a range associated with the appearance of neurologic damage. In summary, this committee was unable to recommend a "safe level" of lead in paint on the basis of the four studies provided by the CPSC. None of the studies were carried out on animals whose age and dietary components simulated the conditions of a young child. These studies do show that lead salts used as driers in paint arp less well absorbed than the same salts not Incorporated in a paint film. 32 &/ DUP040013280 04-0005-0439 33 DUP040013281 04-0005-0440 Table I Experimental Design (Cont'ci) j mi- | C3 DUP040013282 04-0005-0441 Table II Results from CPSC Supplied Data ... .. tj a ;j ms yrnu,.>m .1 }.) Jol I r Hi- i bt. y^ny ' s .>1 4rtenrii-<l Hi !,: > tm-- * >>t f-i j .k j i . a.w*.W x Vi . d'kil iiv Mp.l'il'Mlr l*it'ti. ml iTt,t.o-v i j l. * * . * VJ. .. ^ J R-* VtW . t, hy .1 n 11--1 > urir' at.): .i . ) -l.il.i {.. lint..* Bill- l4(-;<iat<* l'V.lm|l.`1 , [-.tlr.l !' * . . fr-tiir.-O I . -il- ir.i f.KM li* .*.. * j i*! t*.*-* ..tai4 fj i <}>. Ail1.1.1! !<( luw ,,:'.* u> i; t ! .!> . ! (t /ft*. ViJ 44 .*.(1 iliv **sl,-.dy **l.it.c* Jala v j > i.*r Mi*- it.au ir.il i | iim, In. *i... ~t >*.vnti >1 i.-i uvu ! an t 1 --*J .lo rn |..|i . t I*, j . i. I|.n,.v. * y..'4'. ;< ij 4 ........... li'.iJ * `vvtt.i.'o ot . A'A'5. So *xnil uant isItra-'iM' t*v* | WV ru lv.'l<<r 'jJ I'* 1 >1 (11 &r.-IJJ>k totw4jrd. \ 1-V-AU Irwu* t a .* Ill t l.' ir .'ii.l.. >-.i i a-r\* .J !< voJ ; *M-nt. v.t (, j..-rt *l- Jopr.r" . ** -ilj W.'irrv bl- <!! id JoVol s i rd. ra J stead* tl.Jlr , I'nt efUt.it l.'f, of 40 -k ' *r /f'r.i.t'is*d|tio r-o(>ul rd'dl ,iv ?i- Avvilva it.mt .to l.-.i * ^ituf>/ -til it.i'ia I-'vr i..-r ,(i^!,i v.on .mj it. I..yt <j;< i.-.t*. in ait . %-yt t.- *.H M.NJp vi-tr tit.i.Jyid l < **, i I J `IK Oltl I ..t )' -lit !r*i.lit 1 .m , valuri >dfv arrwnd y .X I.CAI O. t rilr (I.- i..itit-j fc.irv tlxt'i rnre*' t:. So-lll'1! pAtitllr |l( (.1 vrd f Joali t . ...Ur VIO-I'K*':. Uiii^Mte 4lXi-K`!^. 1^-44 .vi-r- UU' )-*4 f -.*it. Jlviti lu-c hiijniJ . .itijv iliilc-toni l.a I i i.l IrjD . t.i'lilmi,-Wi it. i . M'li.1 v .'m,ilnir.i Not 1* J.Ui-TSiuwd M^'li <1 I. .|"t I . J. ii s mJ b. o'd pjt',5*> i.-ntUMMn' iJil-.>r..*i. Jj i1,.o <1 r;wf>-*r. > is Mr. M-`Vi li*r f.tint . fv.i.i 'i|ix bn' l4l rrx .^UiT--T>t e <.'tr>iuii> ,^FfPji _ M liiatiliMl tfltlrientf Oat a ecle.-ted t* nn!v tween *.vrt*g values *n ail *.iri-y'-ntr t-r "i.t- <udicd. dw. ti.-.a i-vi i 4.*' W li.Sr-tr*J-..|*e I V |a| J IMtsl.J ( t. ivtaMl'%1'1. Hid .-e.Jif I dltleJ.rvt alf i.' Si-jd avail* ability, Dili n-'t i*a;,.u, I.. plot 11nit lt*W kti.divv Ji; t unl UU. V. 'tg'.ilt .*nt dill rf j 1 Xi-t drcrraincd 5>V bic-Ioti. itrytbfw yte porr-byrir.grn v b ik .-u __i l'S .hai>*r. X.n dVtorin-4 fJj+sMU' ir rJtj U h <l i bl* tf I. *ntl/ do reavoil in n|* S.-t U. lUk fed Mfitieiwir and mtiun1 at .'00 t/kt/d-w V.t lo.Irrenio-J V ( i2-.inrtr.i d X.-l dvirrninrd x.'l drtvfwm.'d t_lJT'li**1* -t-OW n'UHii,B }' aiitnlf trant dill riwi' between arterial and v t imw i lev*!*. N.t dot Vot d<tr(At^ HwwtnrjH bit dVtorwlned SMyufnJ; dil-i &<l tcfalKdlr'.p.iltcr (w fwllit io.ij .untitit y- v.nilu.tnt djtl..-itt.r bn V'l drtrrMiwd iu <i a.'.nitoK arid oxi-.-riawr-.ra] -i.nitt, i'llr;t l.r -in Ii-.i t(rii.<Mii' isnj;i runt. ?ilf.-ti-i>i.- .HiuirH at .work awl CrHer fctaititletlt rciiwuwnU iel detcriiil.nl HiwMitMfi /tu n-'t (om-Ettdt- V ( (r%pvn** in paint IcaJ >nisttiti Kdt tlrrrrtitnril Ki dctc.r^lncd Uitlit'vyir ii'nii!. i*t j<-u.-,K`trt<` bein' dctcrnifled It'itl*-. *:.! mil, .* t J . I1- Iiti.ll J.,Mb-vlr unfit , K'lt 0.1 |. t > leM I I . . and li'lut I IS* -if ,1 trren-ot <vbvv1-mi- , ^ ...... _ 35 V i DUP040013283 04-0005-0442 Table II Results (Cont'd) r--'w. --. ... .---.w W'-*. ------ .... .1 .............................. 1. HSdUMt OTHKR TliSrt In kMiXATli)*.'- ........,,,,............................................... ^ . Era In Lead j.tint vt SJ tRitt eie-vai loti. Does net done-rcsforihC relat i.m- Jvot dote.riplned v'ertuj s.u-ij^d cj I tranhi yt.t+* So *>i(LUU uart dlile<vv\xv. M ArU'isimd "o.t Jet* led in all groups at 1, s ad 1 > wiS't c*. r|i.t i on -ees J J l..r enitMl led KBS carle'uat*- paint i**..' ..g/K 1 Issue/. Sot del. ftri.fHd CV-UiL*' \* *1*JCl.tjran<*i%as.v ii' >iiU'N.t tuns not si> nlli* `tfr.V<tvd to A>*t Jcterniaed V*t determined i I 5t. Xvry'c Sot deterolned k*r>t det etml.i.ed -"ot doternsaed 3.uc "*T?a`d Content Sot drterm tried I'outiger an tools h*Ve greater up .IvvateJ al weeks in anliul fe< take. l,rei.mUerdrr .i: .**< old *rnoni|e paint. Lead Jwe. de.iH.e indicates doses ttn Jy*. stRiii uanii> kiesatt-d at b*nd to ">U0 iesd'-g/day lead ri n wMs, ;i (tatnt .it i voni-entTaMon of lead does not cause srgnl- .ttcknt inrtease in tissue bur den. N*> |*alnt data <C i or.ev te.siT L<mt rr.t Ko iif'iuJjcjnt different* t*> So significant Increase ,i. iweesr central* and ckperieientaf tissue byfiic. nnUuii.. Sol detected In all group* at Cont rol t..ab .total lead . ;.l - .and X weeks, f.srer-tiofi at B w.tvat on XiS-carbAnatr paint (l. ,f,it tissue). At .11 ilctoaiv Li.riHu.te . V'lii-lOO-:* i. J.Jfi.g i.,30 ,,* ?.ld ,K e*~- deterred lead in,#JJ groups so*. >r, a von-ikterit d. *e - so . j . n ,.. response teiatlonshlp. Livet Lead C.-Menr ;.v. rititer. u.e k>.tvr.a controls and esprrlnrnt ;i anlMlv. .40 sue burden. In.lfJ.. In it.. f and i) week*; ** epl at 1 i wv-i 4l)Ujt led both Uf ;bv*ut .'paint* had deteet.ahl.c lead .en.entratioiv. <" >mh i data. Table III Comparison of Lead Accumulation in Tissues of Weanling Rats.-- Lead acetate Dietary Concentration 0.02Z Lead acetate in oil 0.021 Kldoey Total lead JsR 11.28 U.32 20.23 22.fi Blood u* lead/100 nl 56.31 51.81 97.5 93.3 Bone Total lead ufe 5.87 6.08 9.03 11.53 .ft Bate from Barltrop.6 36 Li * i -v DUP040013284 04-0005-0443 Appendix D Etiology and Consequences of Childhood Lead Poisoning Tu National Bureau of Standards estimates that 600,000 children in the United States have unacceptably high blood lead levels ( >40 pg Pb/dl).34 xhis estimate was based on data from large to medium sized standard metropolitan statistical areas (5MSA) in the East and Midwest only. The incidence of lead poisoning is highest among one- to five-yearold 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'*5*and animals-^,72,83,50 have si own the brain to be most vulnerable during the "growth spurt" which, in humans, begins during the sixL{|emonth 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^'-^'"^ 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.61'9" 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.9^* 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 leans to crawl or walk; however, later onset of pica for paint has been observed.21 Abdominal x-ray plates showed radiopaque material 3/ \ L / / DUP040013285 04-0005-0444 in the intestinal tract in 35 percent of children seen in the Chicago Lead Clinic. Diet - Both dietary components and nutritional deficiencies have been found to increase the absorption ni lead from the intestinal tract. Studies in rats6 and baboons^ 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 Chan if administered in dry feed.51.52 Animal studies involving dietary deficiencies of calcium, copper and iron have shown that these deficiencies increase the absorption of lead.6'^',64,9~ n long-term 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,66This degree of reduction in dietary intake of calcium and iron has been reported in two- to three-year-old children from low-income families.63,96 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 tkj proventy line, 17.ft percent of Negro -children in families above the poverty line and 15 percent of Negro children from families below the poverty line.* Others'^,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,**^ 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 Whil" 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 pg Pb/w-5) is considered insignifit ant in comparison with the sources given above. Recognizing that city children shoved 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, Lepov^ decided to examine the possibility of exposure from dust and dirt. She found a mean level of 11,000 pg Pb/g house dust. Samples of dust from the hands of children residing in these houses contained a mean level of 2,400 pg Pb/g dust with a mean weight of 11,000 eg 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 ci;ty. Sayre and Vostal,,02 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 study 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 pg Pb/sq, foot floor surface, new inner city housing contained 2-24 pg Pb/sq. foot and suburban housing contained 0-60 pg Pb/sq, foot. Since the dust lead levels in the newer inner c,ty 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. /' 3$ DUP040013286 04-0005-0445 Ter Haar" 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 distance from the house. In addition. Ter Haar studied the reiativ. contribution of lead from fallout dust by measuring the fecal output of both stable lead and 210 pv, in two groups of children. A naturally occurring tracer, "If) 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 pg Pb/g; the second had outputs of 2-7 pg Pb/g. Despite the wide difference in total lead output, both groups had essen- tially identical outputs of Pb.^ 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 Addons'3' found a mean lead concentration of 202 yg Pb/liter in canned foods and 35 pg Pb/liter in bottled products. Many of the canned baby foods analyzed in this study were fruit juices.- some of which contained >500 pg Pb/liter. Canned evaporated milk had from 10 pg Pb/liter to 820 Pg Pb/liter (mean 202 pg Pb/liter), The National Canners Association sponsored a study of lead intake a in 333 infants aged 1-12 months (unpub lished but cited by Kolbye, et a 1^1. Their estimate of dietary intake was 93 36 pg Pb/dajr, 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. Faint 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 pg Pb/g paint. Sachs-* 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 -/ere 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 equivalent to an estimated 1 gram ^ 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 avbient 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 pg Pb/kg body weight,^* Of this amount, 5.47 pg Pb/kg/day were absorbed and 5,13 pg Pb/kg/day were excreted in the feces. Thus, the children absorbed approximately 50 percent of the lead '' I j :i J f I I ^I j | l f { j J J >( v __________ ___________ i & ) 1 ___ - c# \ DUP040013287 04-0005-0446 / \ , . -/ / i t l' ; ' * r "1 available frota dietary sources. In contrast, Kehoe'c studies in adults showed an absorption rate of approximately 10 percent for lead front dietary sources.'1*' These finchngs are in agreement with studies in experimental animals which show a tit'iul absorption rati in the young than in the adult. 'Karltrcp, et 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.S yg Pb/day was observed in a group of 35 children with a mean blood lead level of 20 pg Pb/dl, Recalculated on a body weight basis for an average three-year-old child weighing 7 5 kg, the daily fecal lead output would he 4.5 Mg Pb/kg/day, Assuming a 50 percent absorption rate, the daily intake necessary to produce this excretion would be 9.0 ag Pb/kg/day. This is not far different from Alexander's figure of 10,6 ng/kg/day. In addition, the mean blood lead level of 20 pg Pb/dl is .cornearuble to that observed by others in normal "unexposed" children.^.* 55,70 CONSEQUENCES OF CHILDHOOD LEAP 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 'tft which encephalopathy occurs.Therapeutic intervention at this stage is only partially successful in preventing severe permanent deficits. 17 Lead encephalopathy in children generally does not occur until blood lead leveLs exceed 120 pg Pb/dl. The current focus of research interest involves studying i bother 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. Rida sy damage ,'s a reversible effect seen in severe cases and no published .nta are available to suggest that damage occurs in asymptomatic cases. Adverse, but reversible, effects are seen in the heaatopoieti.c 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,^ including inhibition of the enzymes, 6-aminolevulinic acid dehydratase (ALA-D) and ferro cheXKfase. The inhibition of these enzymes results in an accumulation of -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 pg Pb/dl, and in men at 35r45 jig Pb/dl.hi,97,104,105 It xs nov) 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.55 Population studies of children in the United States have rarely included a sufficient number of children 40 C9 DUP040013288 04-0005-0447 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/di.20*41,75,87 Tjle excretion of ALA-U begins to rise in both adults4^ .100 and children*-0 when blood lead levels reach the range of 40-50 yg Pb/dl. In children, quantitative collections of urine are required for ALA-0. The determination of ALA-U in random urine specimens from children is of little valu".21*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,28 Tola has demonstrated a significant decrease in hemoglobin levels in new workers occupationally exposed to lead.!011 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.2 Blood lead levels >60 .yg Pb/dl were almost, always associated with hemoglobin levels <10 g/dl. Betts1,1- found Hemoglobin levels <11 g/dl in 36 percent of children with 37-60 yg Pb/dl, 71 percent with 60-100 yg Pb/dl and 89 percent with >100 yg Pb/dl* 'Rosen et al- found a negative relationship between hematocrit and blood lead concentratiqjns at levels exceeding 40 yg Pb/dl. i 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.O., parental education level, socio-economic status, birth trauma, etc., also influence the results of these tests. Studies purporting to snow a relationship between 1.0, 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 Burde^*^* meet most of the criteria of a prospective study. Both study and control children were drawn from an on-going Chili 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 6.7 asymptomatic children who had s positive history of pica for paint or plaster, lived in deteriorated old housing, had positive urinary copreporphyrin tests and cither 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,44 we feel that this combination of criteria for selecting the study group was more reliable 41 l L ?0 04-0005-0448 I '3? \ j j -. - f 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*-1* 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 piaster, lived in moderi 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 >-hree times as frequently in the lead-exposed group. Mean l.Q. scores, as measured by the Stanford-Binet test, were 89 i 13.1 for the lead-exposed group and 94 i 10.5 for the control group. Ac 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 l.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.Vs 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 27.3 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 04-0005-0449 i / 7 -- 8tt Appendix E Evaluation of the Hazard of 0,5 Percent head Paint Ho single study of children with pica for paint has combined the numerous measurements necessary to estimate a "safe level" of lead / in paint. Therefore, a decision regarding the safety of 0.5 percent lead paint must be made by relating measurements found in various studies. Ultimately, the estimated intake of paint chips in a child with pica must be related to the appearance of adverse effects in that child. The potential hazard of ingesting lead-containing paints is related to the average amount absorbed on a dally or weekly basis over a period of months. The percentage of ingested lead that is actually absorbed from the gastrointestinal tra-t into the body varies according to the chemical and physical fora of the ingested lead (i.e., paints, dust, etc.), age and other factors. Differences in the rates of absorption of lead from each source can he largely compensated, if the available data are recalculated as jig Pb absorbed/kg body weight/day. In this way, a reasonable estimate of the amount of paint containing 0.5 percent lead necessary to raise Pb-B to a hazardous level can be made. We will use two methods for estimating the hazard of paint containing 0.5 percent lead: Method A - The first method of estimating the safety of 0.5 percent lead paint will be made by relating estimated point intake to fecal lead outputs found in children with blood lead levels (Pb-B) >60 U.g Pb/dl. Pica for paint has been observed to be episodic, occurring up to two to three times per week. The analysis of lead in consecutive fecal samples seems to confirm this observation.*^ Through the use of abdominal x-rays, Sachs has demonstrated that some children with pica for paint are capable of consuming more than 1 gran of paint in the 24-36 hour period preceding the tine of x-ray.One child was esti mated to have consumed 20 grams of paint during this time. v* An estimated range of lead intake can he calculated, using a figure of 0.5 percent lead in paint (5000 Ug Pb/g paint), a figure of 1 gram paint per ingestion and a figure varying from one to three for frequency of ingestions per week. The estimated weekly intake is then divided by Seven to obtain an average daily intake. Using these figures, the average daily intakes would be 714 yg Pb, 1,429 yg Pb and 2,143 yg Pb, respectively, for one, two and three ingestions per week. It is estimated that 50 percent of lead from foods is absorbed by a young child.^ However, studies in rats have shown that lead chromate in paint films is not as well absorbed as the simple inorganic salts of lead. Gage and Litchfield-** estimate that lead chromate pigment in paint is absorbed one-fourth to one-third as well as the simple inorganic salts, when incorporated into standard laboratory rat feed, and that lead napthenate is absorbed about one-half as well. Similarly, lead octoate in dried ground paint, when fed to monkeys, yields Pb-B's one-third to 45 \ ___ -- "r: 7.DUP040013291 04-0005-0450 one-half as high as when lead octoate is fed directly. These data indi cate chat lead compounds, incorporated into a paint matrix,- are absorbed only one-fourth to one-half as well as the free lead salts. We will use an average of one-third for estimating a child's absorption of lead from paint. This average is used because a variety of lead compounds are used in paint. Tims, if children absorb 50 percent of dietary lead, experi mental data Indicate that they will absorb only one-third of this amount or an average of 17% of the lead from paint. Table 1 gives the estimated amounts of lead absorbed and excreted, based on an absorption factor of 172 and estimates of weekly intakes of 1, 2 or 3 grams of 0.5 percent paint. Average daily intakes are also calculated on a per kilogram basis for an average two-year-ojd child weighing 12.5 kg. (tlcvlei.ed i**d T.bl, 1 .nd Absorbed ,0*e l.ro* I'atn.t flee Amount <nt P*int Inl>o tl Pein.t CoM'On* 0. 5 tvr ton* P.b (5, 000 \i?. Pb/g ptnt| (uS PWiUy) (mb 1'b/Hg/dayJ.* l l y Tor 714 1. 429 ,t 143 57.1 1.14. 3 171.4 twoyetr M Mild wrlghinj 12. 5/Ag? Amount Ph Abeorb.ed (17 pfttcent) Pb/ (*jg Pb/cUy) Vcg/.<5y)* Amount Pb Excreted in Fti (83 percent) (me rt) U1 9.7 593 243 19. 4 1,166 364 29. i 1,779 Chisolm and Harrison found a median fecal lead output of 1,110 ug Pb/day in asymptomatic children with blood lead levels >60 yg Pb/dl and positive roencgenographic evidence of lead storage in bones. Some also had elevations in urinary coproporphyrin levels. Bar.ltr.op found fecal lead outputs ranging from 570 - 1,900 yg Pb/stpol sample in three two-year-old symptomatic children with blood lead levels ranging from 68-92 pg Pb/dl, positive roentgenographic evidence of lead storage and hemoglobin levels >10 g/dl.^ Prom the estimates given in Table I and the studies of Chisolm and Harrison and Barltrop and Killala, it appears that the ingestion of between 1 and 2 grams of paint (containing 0,5 percent Pb) per week could produce fecal lead outputs equal to those found in children with >60 yg Pb-B. Clinical studies in children have indi cated that blood lead levels >60 yg Pb/dl are associated with increased risk of later CHS effeets.3>23,24,o7,73 In contrast, Alexander's balance studies in eleven healthy children receiving a normal diet showed a mean lead intake of 10.61 yg Pb/kg body weight/day and a mean fecal lead output of 5.13 yg/kg/day. Using the 46 DUP040013292 i 04-0005-0451 figures from Table I, a 12.5 kg child consuming 1 gram of 0.5 percent PB paint per week would have a daily lead intake of 57.1 pg Pb/.kg body weight, a five-fold increase above that found in a normal diet. Two grams ot paint would produce an eleven-fold increase and 3 grams, a sixteen- fold increase, , Since the best available clinical evidence indicates that Children with pica can and dp ingest 1-3 grams of paint per week and, since the ingestJon *, between 1 and 2 grams of 0.5 percent lead paint per week would be sufficient to produce daily fecal lead outputs equivalent to those found in children with >60 pg Pb-B, a level of 0.5 percent lead in paint cannot be considered a "sate level." Method B - An alternate method for determining the safety of 0,5 percent lead paint is based on the absorption studies carried out by Kehoe on adult volunteers.^ Kehoe found that blood lead levels increased 17 pg/.di over a period of nine months for each additional mg of lead administered per day. Lead acetate or lead chloride were administered with the diet at dosages of 0*3, 1,0, 2.0 and 3,0 mg Pb/day. Increases in blood lead levels were proportional to dosage, jFor the sake of sim plicity, we will discuss the subject receiving 1.0 mg Pb/day. An observed intestinal absorption rate of 10 percent resulted in an absorption of 100 ug Pb/day, Calculated on a body weight basis for a standard 70 kg man, this represented 1.43 pg Pb absorbcd/kg/day. Thus, the absorption of 1.43 Pg Pb/kg/day would be sufficient to produce a rise in blood lead of 17 pg/dl and an absorption of 2.86 pg Pb/kg/day could produce a rise of 34 pg/dl. Similar increments in blood lead concentration have recently been reported by Scuik? who has administered iead acetate at 20 pg Pb/kg/day to 5 adult male and 5 adult female volunteers over a period of 12 weeks. If one assumes an absorption of 102 of the dose, the rate recently found by Rabinowitz ex al.,8-0 then these healthy volunteers would have absorbed 2.0 yg Pb/kg/day. In Stuik's subjects blood lead concentrations increased by.17.7 pg Pb/dl in the females and 20.3 pg Pb/dl in the males after 2-1/2 weeks. These short-term studies essentially confirm and extend the earlier long-term study of Kehoe in adult volunteers. The average blood lead level in normal unex.pos.cd children is approximately 20 pg Pb/dl.^ Early metabolic changes in the hematologic system begin to occur in children when blood lead levels reach the range of 30-40 pg Pb/dl. From the standpoint of preventive medicine, it would seem appropriate to insure that mean blood lead levels for groups do not exceed 20 pg Pb/dl. An additional daily absorption of 1,43 pg Pb/kg/day could increase blood lead levels from 20 pg Pb/dl to 37 pg Pb/dl, while an additional absorption of 2.86 pg Pb/kg/day could increase levels to 54 pg Pb/dl, Based on an absorption factor of 17 percent for lead tn paint. Table 11 shows the amount of lead intake necessary to produce absorption of either 1,43 pg/kg/day or 2.86 pg/kg/day. Total daily intakes are also calculated for an average one-year-old 10 kg child antf a two-yearold 12.5 kg child, 47 DUP040013293 04-0005-0452 nix* ix C*lcuUttd Dally titiiui I< aal Aaaociaiad lotaroai 0m incruM (n llood Usd (Pb-I) Cui/41) Miorbfd Each Day (j j J Pb/kj/dsy) Necessary Intake to produce Corresponding ,Absorption* 6>t Pb/he/4yl Tots! .ir.Uk* Necessary ior 10 kg child 1)4 Pb/dy) Total Intake Nvtcmry/or 12. 5 kg child it,* w>/dy> IT ,* H i,u H. ex M. 1 168. 1 JOS, t 21Q5 Baaed on Absorption factor of 17 percent fot i99g tp Miac. Atraorption of Itaf from food* ia approximately $9 jrccat.^ The safety of 0,5 percent lead paint can be determined from Table II* The ingestion of 16,82 mg paint/day or 33.64 xag paint per day containing 0.5% lead would result in raising blood lead levels by 17 pg/dl or 34 ug/dl, respectively, in a 10 kg cHtfld. Similarly, a 12.5 kg child would need to ingest either 21.02 mg paint/day or 42.06 mg paint per day. King and Schaplowsky have summarized the work of Sachs wherein she demonstrated that Some children can consume more than 1 g (1,000 xag) paint per week or 143 mg paint per day. Tor a child with pica for paint, a level of 0.5 percent lead in paint clearly represents a hazard. Because multiple factors serve to modify lead intake, absorption rates and individual susceptibility, the foregoing mathematical calcula tions Used for determining the hazard of 0.5 percent lead paint, cannot be considered suitable for application to every child. Age, frequency of pica, dietary constituents, and nutritional status all contribute toward increasing or decreasing the amount of lead absorbed by any one individual (see Appendix D). The first method used for determining the hazard of 0*5 percent lead paint is based on relating lead intake to the appearance of early clinical illness and significant risk of later CNS effects. The second method relates lead intake to blood lead levels known to be associated with the appearance of early metabolic effects in children. In either case, a level of 0.5 percent lead in paint cannot be considered a "safe level." 48 DUP040013294 04-0005-0453 Appendix F Daily Permissible Intake, Reconsidered In 1971, an ad hoc committee convened by the Bureau of Community Environmental Management, Public Health Service, DHEW, proposed the con cept of a daily permissible intake (DPI) to be used as a reference point for establishing policies to prevent childhood lead poisoning. * Based on the knowledge available at that time, the committee decided that blood lead levels should not exceed 40 us Pb/dl and that the DPI for children should not exceed 300 ug Pb/day. Kehoe's balance studies,carried Out On adult volunteers, were used as a reference for establishing a daily lead intake*which would result in levels <40 ug Pb/dl. in adults, Kehoe found an intestinal absorption rate of 10 percent for lead ingested in the diet. The one volunteer whose blood lead level did not consistently exceed 40 Ug Pb/dl had a daily intake of approximately 600 ug Pb/day. Unfortunately, the studies on this volunteer were discontinued after 15 months. Therefore, the effect of chronic exposure to 600 ug Pb/day was not established. More recent evidence indicates that the absorption of dietary lead is approximately 50 percent in young children. Alexander^ found that an intake of 10 ug/kg/day resulted in a daily fecal excretion of 5 ug/kg/ day.. Sarltrop found that children with a fecal excretion of approximately 5 ug/kg/day had a geometric mean blood lead level of 20 ug Pb/dl with a range of 11-3:8 ug Pb/dl. Studies in suckling animals suggest that the intestinal absorption rate of lead from milk may be as high as 70-90 percent-3**51 These studies suggest that the absorption rate of lead in children less than one year of age may be higher than 50 percent. In addition, the brain of infant rats accumulates lead to a greater extent than the brain of adult rats. 8 Based on this new information, the daily absorption of lead from diet can be recalculated. The caloric requirement of a three year old child weighing 15 kg is one-half of the calorie requirement of an adult weighing 70 kg, Tepper, cited in King,^-* reported that the average adult diet contained 220 ug Pb/24 hrs. If a three year old child consumed the same diet, reduced to one-half to meet his caloric requirements, his dietary lead intake would be 110 ug Pb/24 hrs. Based on a dietary absorp tion factor of 10 percent, the adult would absorb 22 ug Pb/24 hrs or 0.31 Ug Pb/kg body veight/day ((220 x 10 percent) * 70 kg). Based on the dietary absorption factor of 50 percent, the child would absorb 55 Ug Pb/24 hrs or 3,67 ug Pb/fcg body weight (110 x 50 percent * by 15 kg). Thus, when dietary lead absorption is expressed in terms of body weight, it can be calculated that the chile would absorb 12 times as much lead as an adult receiving the same diet. The safety of blood lead levels in the range of 25-40 ug Pb/dl has recently been questioned. Early hematologic changes can be seen in women and children when blood lead levels reach 25-30 ug Pb/dl,Neurologic changes have not been documented at this low level. No data are available relating blood lead levels to possible adverse effects in children less than one year of age. 49 : 323 nrraraavawws / 7? DUP040013295 04-0005-0454 Because of new evidence available in both human and animal studies. this Committee believes that Che DPI should be recalculated. Specifically, consideration should be given to: 1. Lowerins the currently acceptable blood lead level of 40 yg Pb/dl for children. ! 2. Accounting for a higher intestinal absorption rate in young children. 3. Allowing a "safety factor" for children less than one year of age, since no data regarding effects or absorption rates is known for this group. 4. Expressing the DPI on either a body weight (eg Pp/;kg/day) or caloric (yg Pb/Kcal) basis. The World Health Organ!zation, FAO, has recently recommended that lead intake in adults should not exceed 3.0 mg of lead per week (429 yg of lead per day).^3 For a standard 70 kg man, this would be equivalent to 6.12 yg of lead per kg/day. & 50 DUP040013296 04-0005-0455 Appendix G Lead Contents of Current Household Paints In 1974, CPSC conducted a market place survey to evaluate the for mulations of paint on the retail market.^01 Five hundred selected house hold paint samples were collected by ten state agencies under contract to the CPSC. The paints selected for the survey were representative of the types and colors in current usage. Table I gives the annual percentage of sales for each type of paint. Table 1 Household Paint Marketing Data 1. Interior Finishes (wail, ceiling, trim, etc.) Percent 60 Water Emulsion (latex), acrylic, vinyl 'acetate, etc. Oil or alkyd based (includingenamels) Metal enamels, etc. Primers and/or sealers Stains and/or varnishes Percent 25 20' 5 5 5 2. Exterior Finishes (house, etc.) 40 Water Emulsion (latex), acrylic, vinyl acetate, etc. Oil or alkyd based (including enamels) Metal enamels, stains, varnishes, primers, sealers, etc. 15 15 10 TOTAL 100 percent Four hundred and eighty-nine samples were analyzed for lead con tent. The results of paint analyses are given in Table XI (See next page). Ninety-two percent of oil based paints and 99 percent of water based paints contained less than the current statutory limit of 0,5 per cent lead. In addition, 70,8 percent cf oil based paints and 96.1 percent of water based paints contained less than the proposed limit of 0.06 per cent lead. Four colored oil based paints (black, green, yellow and white) consistently ex.eeded the 0.5 percent lead limit. Table III shows the results of lead analyses for these colors. / 51 / ?0 j j \ I I . II ........... irit'** ! DUP040013297 04-0005-0466 Table 11 Leal Content of Household Faint* <3b - .Percent Lead* Oil Baaed Kt*.i.b*f Percent Latex Number Percent Tola* Number Percent Dp nti ''rrn to IV i Statutory Lrr>it >1. 50 1-1.40 0. 50-0. 99 6 2, 1} 00 * 03 1. I> 8 percent 0 3 i.percent 3 14 4. 9) Z 1.0 16 (Cv^form to 157 . .'jtalutpry 0. 25-0. 49 0. .10-0. 24 0.06*0. .09 <. ft'. 21 34 5 20t 7. <1 1 12. 0(,92 percent 3 .* - 70. ft) 2 197 0. 5 22 1.5 59per.cent 37 l. o 7 96. ) 398 TOTALS 284 109 205 100 *Per.cent by weight baaed .on fine) dried aoltdii. 489 i.r C.6 > 5 percent 3-3 4. S 7. 6 95 percent Is 4 81.4 100 Percent Lead* i.O 0.50-0.99 0,06-0.49 >0.06 Total Lead Conteut of Oil Eased Household Paints Black** Creeo Bellow Ter f Cent 3 12.5 ;3 12.5 6 25.0 12 50.0 24 100.0 Per # Cent 2 8.0 0 6.0 4 16.0 19 76.0 23 100.6 Per i Cent 3 19.0 1 6.0 2 13.0 10 62.0 16 100.0 White Per f Cent 1 1.7 1 1.2 13. 16.0 66 81.5 81 99.9 Percent by weight based on final dried solids. Including charcoal The proposed limit of 0.06 percent lead in paint was originally intended to allow for variations due to .impurities in raw materials, con tamination during processing and detection limits for the analytical methods used in determining the lead content of paints. The proposed limit does not allow a margin for lead additives, including dryers. An industry formulary^ indicates that trace amounts of cobalt and manganese are used as essential driers and that lead is used as an auxiliary dryer. Zinc and calcium are listed as alternative auxiliary dryers. 52 DUP040013298 04-0005-0457 This Committee has no expertise in either paint technology or economies; therefore, no conclusions could be reached relative to either a change In the quality of paint or the economic impact which might re sult from reducing the level of lead in paint to trace amounts. Never theless,. the data from Tables II and III clearly demonstrate that the production of paint with <0.06 percent lead is possible. More importantly, a large proportion of paints sold in the current retail market already meet the proposed limit of 0.06 percent lead. /> 'J 53 DUP040013299 04-0005-0458 i t .4 ; i 1 ! il \ >. \ 5?3 LEAD IN PAINT REFERENCES 1. Abraham, S., Lowensiein, F. 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