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U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE CENTERS FOB DISEASE CONTROL ATLANTA, GEORGIA 30333 OFFICIAL BUSINESS POSTAGE AND FEES PAID U.S. DEPARTMENT OF HHS HHS 396 THIRD CLASS BLK. RT. 25 i9898SNER30 7925 MR RONALD D 3NEE DUPONT 0E NEMOURS & CO ENGINEERING SVC DIV 1007 MARKET ST tvlLMINGTON* DE 19898 N33799 Special Issue / May 1981 II | I DEPARTMENT OF HEALTH AND HUMAN SERVICES / PUBLIC HEALTH SERVICE CENTERS; FOR DISEASE CONTROL / ATLANTA, GEORGIA 30333 I I 1 TEH 0532148 DUP050033237 Special Issue / May 1981 00-3746 DEPARTMENT OF HEALTH AND HUMAN SERVICES / PUBLIC HEALTH SERVICE CENTERS FOR DISEASE CONTROL / ATLANTA, GEORGIA 30333 TEH 0532149 DUP050033238 Prepared by Centers for Disease Control Center for Prevention Services Technical Information Services Editor: Caffilene Allen Atlanta, Ga. 30333 Trade names are used fpr identification only and do not represent an endorsement by the U.S. Depart ment of Health and Human Services or the Public Health Service. TEH 0532150 DUP050033239 Foreword Environmental Health Abstracts and Bibliography presents a survey of recently pub lished literature in the Field, Effort is made to keep the abstracts as current as possible and sufficiently informative to enable the reader to decide whether the original article would be of interest to him or her. The journals in which articles originally appeared should be checked for reprint addresses. The Centers for Disease Control is unable to supply reprints of articles which are cited in this publication. In compiling these abstracts we utilize the National Library of Medicine's interactive retrieval service, MEDLARS II. Under this system, both foreign and domestic biomedical periodicals are searched for material dealing with Or related to environmental health. We also utilize the libraries of Emory University, the Centers for Disease Control and other federal agencies. Abbreviations of periodical titles are those used by MEDLARS and listed in the National Library of Medicine's List ofJournals Indexed in Index Medicus. Future issues of Environmental Health Abstracts and Bibliography will be devoted to various environmental health topics. Individuals desiring to be placed on the mailing key to receive future issues as published should write to the Environmental Health Services Division, Center for Environmental Health, Centers for Disease Control, Atlanta, Georgia 30333. Vernon N. Houk, M.D. Director Environmental Health Services Division TEH 0532151 DUP050033240 Contents FOREWORD ............. ........................... ................................................................ ... iii GENERAL ...................................... .................................................................... .............................. 1 EPIDEMIOLOGY AND ETIOLOGY .............................. ..................... ..................... 5 DIAGNOSIS AND SCREENING........................ .......................................................... 9 RESEARCH AND EVALUATION..................... ........................................ ............ . 17 TEH 0532152 DUP050033241 GENERAL Exposure to Lead: Sources and Effects Anonymous. N ENGL J MED 1977 Oct 27; 297(17): 943-5. From authors' discussion: Recent data indicate that the sources of lead for children are multiple, and that body lead burdens below those associated with clinical symptoms can affect biochemical functions and neuropsychologic performance. Anemia is a long recognized effect of lead exposure. Lead, even in low concentrations, affects heme enzymes, notably cytochrome P-450 in the liver and red-cell D-aminolevulinic acid dehydratase. Lead inhibits brain adenyl cyclase at low concentrations in cere bellar preparations and in nigrostriatal preparations. Lead has also been shown to inhibit pancreatic adenyl cyclase. Interference with globin synthesis and col lagen synthesis has also been demonstrated at relative ly low concentrations of lead. In the heme pathway, lead acts at a number of sites, including the red-cell mitochondrion, where it interferes with the incorpo ration of iron into the tetrapyrrole ring, resulting in its replacement by zinc. For the young child, the most important target organ is the brain. The catas trophic effects of lead encephalopathy and the protean symptoms of lead poisoning have caused many clinicians to ask whether lesser levels of lead than those producing frank encephalopathy result in subtler forms of brain injury. Lead has been found in the umbilical cord blood of newborns. It has also been shown to be associated with severe reproductive damage in occupationally exposed women, and to be teratogenic in the laboratory animal. Possible sources of lead for children include old house paint, food stuffs, some newsprint, some ceramic tableware, and water in areas where the mineral content is low, the water acidic, and old leaded pipes still in place. The largest contributor to lead in the atmosphere is auto mobile emissions. cause any untoward neurophychiatric effects. Be tween 2.0 and 3.0mmol/1, results are conflicting, but those deviations from normality which are noted most likely stem from sub-clinical neuronal damage which has been described by Feldman, Haddow, Kopito and Schwachmann (1973). With blood lead levels in excess of 3.0Mmol/l, and particularly with prolonged exposure, neuropsychiatric effects are un doubtedly noted, increasing frequency as the child gets closer to developing clinical signs of frank intoxication and encephalopathy. Fetal Effects of Lead Exposure (Letter) J. Scanlon and J.J. Chisolm, Jr. PEDIATRICS 1972 Jan;49(l): 145-6. From authors' discussion: One part of the lead picture which needs a great deal of further study is the fetal effects of exposure to increasing amounts of lead from the environment. It has been demon strated recently that concentrations of lead found in the "average" child (20 to 40 Mg/100 gm whole blood) can inhibit 6 -aminolevulinic acid (ALA) dehydratase activity in both blood and brain. That study states that the brain enxyme activity correlated nicely (r = .78) with blood ALA dehydratase activity, suggesting that blood ALA dehydratase may be a useful measure of central nervous system enzyme activity. A small amount of umbilical cord blood from normal new born infants revealed a mean lead level of 22 Mg/100 gm (range 10 to 37 Mg)- It would be reasonable to expect that ALA dehydratase activity might have been diminished in utero at these lead levels. Exposure to Lead in Childhood: The Persisting Effects M.R. Moore. NATURE 1980 Jan 24:283(5745): 334-5. Lead and Human Behavior II.A. Walfron. J MENT DEFIC RES 1978 Mar; 22(1): 69-78. Author's abstract: There is little evidence that blood lead levels below about 2.0 a mol, in children From author's discussion: Of all the persons in the community, the newborn child is the most prone to injury from overexposure to lead for several reasons. The damage that may be caused will have the greatest long-term social and economic consequences. In the earliest studies of childhood overexposure to lead, it was clear that classroom performance was poorer in exposed children than in children who had TEH 0532153 DUP050033242 not been exposed. Thereafter, studies showed that mental retardation could be linked with overexposure to lead in drinking water and with high concentra tions of blood lead at or about the time of birth. In recent studies, a similar degree of diminished learning ability (IQ drop of 4-7 points) and behavioral changes, such as diminished attention span, have been associated with increased concentrations of lead in teeth. These studies by Needleman, et al. and Winnecke are the most convincing evidence to date of low level effects, since the use of tooth lead reflects long-term rather than recent exposure in these chil dren. Overexposure to lead of young children will have the greatest potential economic effects through in creased requirement for care in later life in those most severely affected and by diminution of intellec tual potential. Environmental Lead and Its Pediatric Significance D. Barltrop. POSTGRAD MED J1969 Feb;45(520): 129-34. Author's abstract: There is evidence that appreci able body burdens of stable and radioactive lead may be acquired by children, and also that part of the maternal intake of lead may influence the fetus. The rapid growth rate, immature metabolic apparatus, and varying dietary patterns which characterize the pediatric age groups suggest that standards for adult males might not be applicable. Numerous environ mental sources may contribute to the lead intake of children, but the metabolism of lead in this group is not well understood and deserves further study. Chronic Lead Intoxication in Children J.J. Chisolm Jr. DEV MED CHILD NEUROL 1965 Oct;7{5):529-36. Lead Poisoning D. Barltrop. ARCHDIS CHILD 1971 Jitn:46(247): 233-5. The difficulty of diagnosing lead poisoning in chil dren because of an initial lack of symptoms, the types of disturbances caused by lead poisoning, and the treatment for lead poisoning are discussed. Symptoms, which may take 5 to 6 months to de velop, may include metabolic disturbances which result jn delta-aminolevulini:caciduria, coproporphyrinuria, increased erythrocyte protoporphyrin and a "sideroachrestic" anemia. Disturbance of globin synthesis and mitochondrial abnormalities may also occur. One disturbance, the inhibition of the enzyme ALA dehydratase at blood lead concentrations hitherto regarded as "normal," may mean a revision of the definition of lead poisoning. To diagnose lead poisoning, three groups of diag nostic tests may be used: the detection of lead in blood, tests indicating disturbance of metabolism consistent with lead poisoning, and nonspecific tests such as the demonstration of anemia and glycosuria. Children with pre-encephalopathic lead poisoning and children with encephalopathy should be treated differently. Pre-encephalopathic children should be removed from the source of lead poisoning by ad mission to the hospital and treated with chelating drugs to remove the lead from soft tissue. The recur rence of lead poisoning should be prevented. Chil dren with early or suspected encephalopathy should be treated with chelators and restriction of fluids to basal needs before the results of the laboratory tests are known. Author's abstract: The serious sequelae of lead intoxication during early childhood are mental retardation, behavior disturbances, convulsive dis orders, and nephropathy. The protean symptoms of this chronic disease and the paucity of specific ab normal physical signs make a biochemical approach essential for accurate diagnosis. Fundamentally, the diagnosis of plumbism requires the demonstration of an excessive body burden of lead together with some metabolic evidence of lead's toxic effects in the soft tissues. In children, serial determinations of the con centration of lead in whole blood provide the best means for following trends in total body lead burden and its distribution. Minimal elevations in blood lead concentration are often difficult to evaluate, and the edathamil calcium disodium (EDTA) mobilization test can then be most useful in revealing an increased body lead burden. The cornerstone of therapy is prompt interruption of abnormal lead exposure. Even so, the excessive intake is halted. In the long-term management of such patients, chelating agents might be used more effect ively than they are at present. They are now given mainly for the treatment of obvious acute sympto matic episodes. It is more logical to use these agents to reduce and maintain soft tissue lead concentrations as close to normal as is consistent with safety, The Susceptibility of the Fetus and Child to Chemi cal Pollutants. Behavioral Implications of Prenatal and Early Postnatal Exposure to Chemical Pollutants B. Weiss and J.M. Spvker. PEDlA TRICS1974 May; 53(51:851-9. From authors' discussion: Perhaps 25% of the children who survive an attack of acute encephalo- 2 TEH 0532154 DUP050033243 pathy from lead poisoning sustain severe permanent, neurological sequelae. But severe symptoms, because of the current emphasis on early detection, are be coming much less common. Subtle neurological deficits and behavioral impairments are more com mon developments. Often, however, the handicap is not recognized until after the child enters school. Such children frequently seem to constitute severe behavioral problems, even though they have been diagnosed as completely recovered from the poison ing. They are described as easily distracted, as display ing short attention spans, and as being hyperirritable and aggressive; they often are suffering from sensory and motor impairments demonstrable only with precise testing. 3 TEH 0532155 DUP050033244 SELECTED BIBLIOGRAPHY GENERAL Enger E, Kulling P, Werner P: Rid: of lead poisoning by swal lowing a curtain weight (Swedish). LAKARTIDNINGEN 1980 Mar 5 ;77(10):908. Anonymous: Exposure to lead: sources and effects. N ENGL J MED 1977 Oct 27;297(17):943-5. Barltrop D: Environmental lead and its pediatric significance. POSTGRAD MED J 1969 Feb;45(520):129-34. Barltrop D: The excretion of delta-aminolevulinic acid by children. ACTA PAEDIATR SCAND 1967 May;56(3): 265-8. Haas T, Wleck AG, Schaller KH, et al: The usual lead load in new-born infants and their mothers (German). ZENTRALBL BAKTERIOL (Orig B) 1972 Feb;l55(4):341-9. Moore MR: Exposure to lead in childhood: the persisting effects, NATURE 1980 Jan 2483(5745):334-5. Scanlon J, Chisolm JJ, Jr: Fetal effects of lead exposure. PEDIATRICS 1972 Jan;49(1): 145-6, Barltrop D: Lead poisoning. ARCH DIS CHILD 1971 Jun;46 (247):233-5. Waldron HA: Lead and human behavior. J MENT DEFIC RES 1978 Mar;22(l): 69-78. Barry PS, Mossman DB: Lead concentrations in human tissues. BR JIND MED 1970 Oct;27(4):339-5l, Carpenter SJ: Placental permeability of lead. ENVIRON HEALTH PERSPECT 1974 May ;7:129-31. Chisolm JJ, Jr: Chronic lead intoxication in children. DEV MED CHILD NEUROL 1965 Oct;7(5):529-36, Waldron T, Wells C: Exposure to lead in ancient populations. TRANS STUD COLL PHYSICIANS PHILA 1979 Jun;l(2): 102-15. Weiss B, Spyker JM: The susceptibility of the fetus and child to chemical pollutants. Behavioral implications of prenatal and early postnatal exposure to chemical pollutants. PEDIATRICS 1974 May ;53(5):851 -9. Abstracted \ 4 TEH 0532156 DUP050033245 EPIDEMIOLOGY AND ETIOLOGY Occupational Lead Exposure and Women K. Bridbord. PREV MED 1978 Sep;7(3):311-21. Author's abstract: The toxicity of lead has been known for approximately 2,000 years, but the issue of women exposed to lead in the workplace has received relatively little attention until recent years. The major thesis of this paper is that the fetus repre sents an organism which is sensitive to lead and that the fetus is exposed to lead through the mother by the fact that lead crosses the placental barrier. Fetal exposure to lead is, in the author's opinion, the critical issue involved in assessing occupational ex posure to lead among women of childbearing age. Multiple studies have demonstrated that concentra tions of lead in the mother's blood are comparable to concentrations of lead in umbilical cord blood at birth. Many investigators consider the demonstrated effects of lead upon the hematopoietic system to be the earliest effect associated with lead exposure. Control strategies which prevent significant altera tions in the heme synthetic pathway of the mother should prevent such changes in the fetus and thus protect against the more serious adverse effects of fetal lead exposure. Umbilical Cord Blood Lead Concentration: Relation ship to Urban or Suburan Residency during Gestation /. Scanlon. AM J DIS CHILD Apr 71;121(4J: 325-6. Author's abstract: No statistically significant relationship was shown for umbilical cord blood levels of lead and residency during gestation in either city or suburbs. There was also no significant relation ship found between maternal cigarette smoking and cord blood lead levels. These values for cord blood lead are the first noted in the literature. If atmospher ic contamination with lead continues at its present rate, further studies of cord blood lead concentration should be undertaken. Biological Effects of Exposure to Lead in Ambient Air Among Tokyo Inhabitants K. Tsuchiya, M. Sugita, and C.B, Park. KEJO J MED 1976 Dec;25(4):192-211. Authors' abstract : The purpose of this study was to examine whether the health of Tokyo inhabitants was affected by lead in the ambient air, on the basis of place of residence, age, and sex. The study came about as a direct result of public concern over a press report that people living near busy traffic inter sections were being poisoned by lead in the air. In 1970 and 1971, the laboratories of the Tokyo Metro politan Institute of Health and the Occupational Health Service Center performed laboratory tests on inhabitants who were concerned about air pollution and presented themselves to their local health depart ments. The results were then passed on to the Keio University School of Medicine for evaluation. The average lead levels in blood and urine were slightly higher in those persons living in houses which faced a main street than those living on side streets. However, there was no association found to exist according to the distance of the house from the main street. Blood lead levels were higher in males than in females. Lead levels in urine were also higher in males than in females. There was no particular association between age and lead levels in blood or urine. The average lead levels in blood and urine differed by district, but showed no systematic pattern or relationship to the population density. These seem to be due to techni cal differences between the two laboratories responsi ble for the testing, as well as to the difficulty in deter mining such small amounts of lead in blood and urine. In conclusion, according to the available techniques, there was no evidence of an increased level of lead in blood or urine as a result of lead in the ambient air of Tokyo, Occupational and Environmental Risks in and around a Smelter in Northern Sweden. I. Variations in Birth Weight S. Nordstrom, L. Beckman, and I. Nordenson. HEREDITA S1978;88(l):43-6. Authors' abstract: The Ronnskar smelter in northern Sweden emits a number of potentially toxic substances, of which arsenic, lead, and sulphur diox ide have caused most public concern. Birth weight was studied in the offspring of women working at the Ronnskar smelter and in four populations (A-D) at different distances from the smelter. In the offspring of employees and in two small industrial populations TEH 0532157 DUP050033246 (A and B) close to the smelter, a significantly de creased birth weight was found. This decrease showed a consistent parity dependence, affecting mainly later pregnancies. Occupational and Environmental Risks in and around a Smelter in Northern Sweden. III. Frequencies of Spontaneous Abortion HERED1TAS 1978;88(lJ:51-4. Authors' abstract: Frequencies of spontaneous abortion were studied in populations located at dif ferent distances from the Ronnskar smelter in north ern Sweden. The smelter emits a number of potential ly genotoxic substances such as lead, arsenic and suphur dioxide to the environment. In the population located close to the smelter, a significant increase of the abortion frequency was found, compared to more distantly located populations. Air-Borne Lead as an Environmental Toxin: A review R.M. Hicks. CHEM BIOL. INTERACT 1972 Nov; 5(6):361-90. From author's conclusion: The evidence reviewed here supports the conclusions that levels of lead in air in urban environments make a significant contri bution to the body burden of lead and that the major source of atmospheric lead is combustion of leaded petrol in motor vehicles. There is no doubt that, at high concentrations, lead is a toxin selective for the central and peripheral nervous systems, and that children are more susceptible to lead poisoning than are adults. There is no agreement as to whether the current atmospheric lead levels represent a health hazard. It is a matter of observation that, as more is learned about the side effects of chemical and other environmental pollutants, the lower the accepted "safe" levels become. This is particularly well-exempli fied by radiation. The maximum permissible levels of exposures for populations were established and in ternationally accepted, but, over the years, as know ledge about the biological action of radiation has in creased, the permissible levels have had to be pro gressively reduced until it is now generally accepted that there is no threshold or "safe" dose for radiation effects. The evidence is that attitudes toward environ mental lead pollution are following the same pattern, and it is now only a question of time before the legal action already taken in the U.S.A., Germany, Sweden, and Japan is followed by the rest Of the world. Levels of lead ingestion and inhalation producing increased body burden of lead and clinical toxicity in adults and children are compared with usual levels of exposure. Food, the major source of lead intake, along with air and water, provides the usual exposure to lead. The average intake of lead from these sources apparently produces no adverse health effects. The sources of unusual lead exposure in chil dren are most commonly urban street dirt, house dust, and paint. Several estimates have been made of the common levels of lead exposure for adults, the amount of lead Ingested that raises blood lead levels, and the amount of inhaled lead which is absorbed. Children apparently retain a greater percentage of lead than adults, but the normal, tolerable, and toxic levels of lead exposure for children are not clearly established. Organic lead compounds are highly toxic compared to inorganic lead compounds. It has not been determined which inorganic compounds are most likely to have toxic effects nor whether other components in the diet, such as milk, increase or decrease lead absorption in humans. Factors such as minerals, vitamins, fat, and protein content in the diet have been found, however, to influence amounts of lead absorbed and the distribution of lead within the body. Asbestos, Lead, and the Family: Household Rides A. Fischbein, J. Cohn, and G. Ackerman. J FAM FRA CT1980 Jun:10(61:989-92. Authors' abstract; Although the intrafamilial transmission of infectious diseases has long been recognized, the induction of environmental diseases in household contacts is being increasingly docu mented and requires a higher index of suspicion. An incidental radiographic finding, such as pleural thick ening or calcification, or even interstitial pulmonary fibrosis in a young person without obvious occupa tional exposure to asbestos, should prompt the physician to clarify the parental occupational history. Likewise, unexpected evidence of lead-induced ab normalities, such as elevated blood lead and/or erythrocyte protoporphyrin levels, should focus the examiner's attention on possible intrafamilial trans mission, treatment, and prevention. The Biochemistry of Brain Development and Mental Retardation A.N. Davison. BR J PSYCHIATRY 1977 Dec;l31: 565-74. Quantities of Lead-Producing Health Effects in Humans: Sources and Bioavailability K.R. Mahaffey. ENVIRON HEALTH PERSPECT 1977 Aug;l9:285-95. Author's abstract: Mental retardation may be associated with a number of environmental factors such as undemutrition, lead poisoning, or exposure to neuroactive drugs during a critical period of brain TEH 0532158 DUP050033247 development. Possible biochemical mechanisms oper ating in these various conditions and in animal models are reviewed in relation to the vulnerable period hypothesis. Small brains are common in the mentally retarded, and this may be related to a developmental abnormality, particularly at the level of the synapse. Effects of Lead on the Female and Reproduction: A Review W.M. Rom. MT SINAI J MED NY 1976 Sep-Oct; 43(51:542-52. Prom author's conclusion: Biologic evidence is available indicating that women may be more sus ceptible to toxic effects of lead. In several animal models, lead exerts a profound noxious effect on preg nancy and fetal development. In addition, the older history of lead's use in the workplace amply docu ments a deleterious effect on human reproduction. Whether lead is responsible for chromosomal ab normalities in exposed workers remains an unresolved issue. However, there may be no threshold limit at which adverse effects could not occur in the course of development of the human fetus. The Susceptibility of the Fetus and Child to Chemical Pollutants. Interaction of the Chemical Environment with the Infant and Young Child L. Finberg. PEDIATRICS 1974 May;53(5):831-7. Prom author's discussion: Lead has been an en vironmental hazard of man for a long time. For chil dren in the United States, the emphasis has properly been on acute and subacute toxicity. The prevalent form of the disorder has come from the ingestion of materials from crumbling surfaces of deteriorated housing--materials containing paint which, in turn, contained lead in the pigment, the drier, or both. The most endangered organ is the brain, and the end result may be death or cerebral dysfunction. Damage to other organs and systems (notably hematopoietic, hepatic, renal, and skeletal) are also seen, but with less devastating results. Sterility may Occur in adults with increased lead ingestion. Lead also finds its way into man through the food chain and, in increasing amounts, through the atmosphere from leaded gas line. TEH 0532159 DUP050033248 SELECTED BIBLIOGRAPHY EPIDEMIOLOGY AND ETIOLOGY Abbritti G, Briziarelli L, Cicioni C, et al: Increased lead ab sorption in children living in a country rich in ceramic factories (Italian), MED LAV 1979 Jul-Aug;70 (4):323-33. BaglanRJ, Brill AB,SchuIert A, et al: Utility of placental tissue as an indicator of trace element exposure to adult and fetus. ENVIRON RES 1974 Aug;3(l):64-70. Barudi W, Bielig HJ: Heavy metal content (As, Pb, Cd, Hg) of vegetables and fruits which grow above ground (German). Z LEBENSM UNTF.RS FORSCH 1980 Apr;17G(4):254-7, *Brid'oord K: Occupational lead exposure and women. PREV MED 1978 Sep-7(3).311-21. *Davison AN: The biochemistry of brain development and mental retardation. BR J PSYCHIATRY 1977 Dec;131: 565-74. Ferm VH: Teratogenic effects and placental permeability of heavy metals. CURR TOP PATHOL 1976;62:145-51, *Finberg L: The susceptibility of the fetus and child to chemi cal pollutants. Interaction of the chemical environment with infant and young child. PEDIATRICS 1974 May;53(5): 831-7. Fischbein A, Cohn J, Ackerman G: Asbestos, lead, and the family: household risks. 1 FAM TRACT 1980 Jun;10(6): 989-92. *Hicks RM: Air-borne lead as an environmental toxin. A re view, CHEM BIOL INTERACT 1972 Nov;5(6):361-90. *Mahaffey KR: Quantities of lead-producing health effects in humans: sources and bioavailability. ENVIRON HEALTH PERSPECT 1977 Aug;19:285-95. ""Nordstrom S, Beckman L, Nordenson I: Occupational and environmental risks in and around a smelter in northern Sweden. HI. Frequencies of spontaneous abortion. HEREDITAS 1978;88(l):51-4. ''Nordstrom S, Beckman L, Nordenson 1: Occupational and environmental risks in and around a smelter in northern Sweden. I. Variations in birth weight. HEREDITAS 1978; 88(l):43-6. *Rom WN: Effects of lead on the female and reproduction: a review. MT SINAI J MED NY 1976 Sep-Oct;43(5):542-52. " Scanlon J: Umbilical cord blood lead concentration. Relation ship to urban or suburban residency during gestation. AM J DIS CHILD 1971 Apr;121(4):325-6, Tsuchiya K, Sugita M, Park CB: Biological effects of expo sure to lead in ambient air among Tokyo inhibitants. KEIO J MED 1976 Dec25(4):193-21i. '^Abstracted TEH 0532160 DUP050033249 DIAGNOSIS AND SCREENING Lead Levels in Cord Blood P. Harris and M.R. Holley. PEDIATRICS 1972 Apr;49(4):606-8. Authors' summary: Blood lead levels were deter mined on 24 mothers during labor and on the blood of their newborns. The mean value for the mother's blood lead was 13.2 jug/100 gm and, for the cord blood, was 12.3 jug/100 gm of whole blood. These levels are lower than "normal" blood lead standards usually accepted in the diagnosis and treatment of childhood lead poisoning. Neonatal Lead Intoxication in a Prenatally Exposed Infant N. Singh, C.M. Donovan, and J.B. Hanshaw. J PEDIATR 1978 Dec;93(6): 1019-21. From authors' discussion: A presumptive diagnosis of fetal lead intoxication was made on the basis of a positive maternal history of exposure to lead associa ted with high blood lead and erythrocyte protopor phyrin levels. Exposure to lead occurred during the eighth month of pregnancy, but no treatment was given to the mother because she was asymptomatic, and because of concern for the potential fetal toxi city of calcium EDTA. The infant was born with chemical evidence of lead intoxication, but no neuro logic abnormality was detected at birth. The patient's delayed object permanence skills corroborates with the observation of Jenkins and Mellins, who reported that lead-poisoned children had the greatest difficulty with tasks calling for the naming of objects, visual memory, and simple conceptualizing. The delay in language skills of this child could be explained by slightly depressed cognitive skills, particularly her inability to imitate new speech sounds. Cognitive delay can also account for the delay in comprehen sion. The causative factor may be either the prenatal exposure to high lead or the home environment, which may not be stimulating enough to provide for cognitive and language development. This child ap pears to be at high risk for later learning problems, which may become demonstrable during early school years. Congenital Lead Intoxication A.E. Timpo, J.S. Amin, M.B. Casalino, and A.M. Yuceoglu. J PEDIATR 1979 May;94(5):765-7. From authors' discussion: We are reporting an in fant with fetal lead intoxication, who was also ex posed to chelation therapy with calcium EDTA in utero. A diagnosis of lead poisoning was made for a 17-year-old adolescent in her eighth month of preg nancy, who had been eating paint chips from the wall outside of her apartment during the last few months of her pregnancy. Chelation therapy with intravenous calcium EDTA, 1 gm twice a day for 3 days, was instituted. Therapy was well tolerated, without any discernible adverse effects On the fetus. The duration of exposure to lead in the infant is not certain. No obvious congenital malformations have been seen, but bone changes suggest prolonged exposure. Another toxic effect of lead is the alteration of red blood cell membrane permeability, which was ob served in this infant, as evidenced by increased osmotic resistance. Although long-term or repeated adminis tration of CaEDTA without zinc supplementation may be harmful to the fetus, the mother was treated, in spite of this concern, because of the dangerously high blood lead level. The treatment, however, did not adequately reduce the lead burden of the infant, who required further chelation therapy postnatally. Exposure of the developing central nervous system to even "subclinical" levels of lead has been reported to cause undesirable developmental consequences such as hyperactivity, learning disabilities, and mental re tardation. By 18 months of age, no detectable neuro logic or psychomotor developmental abnormalities had been noted in this infant. Nevertheless, the effects of the prolonged exposure to lead, in utero, on optimal brain development and function can only be ascertained by long-term follow-up. The Human Placenta's Lead Level as a Parameter of Ecological Lead Exposure: Its Validity in Comparison to the Lead Level in Blood, the Acitvity of DeltaAminolevulinic Acid Dehydratase and the Concentra tion of Free Erythrocyte Porphyrins of Newborns and Their Mothers (German) E. Engelhardt, K.H. Schaller, R. Schiele, and H. Valentin. ZENTRALBL BAKTERIOL (Orig B) 1976 Aug;l62(5-6):528-43. English summary : In order to estimate the ecologi cal exposure of lead, placenta and blood investigations Were made at four collectives from variously indus trialized regions (Ruhr region, Middle Frankonia 9 TEH 0532161 DUP050033250 Centre, Bavarian Forest). One hundred forty-eight normal births and 19 premature births were listed (in each case, mothers and newborns), as well as 12 abortions. We investigated the lead level in blood, the activity of delta-aminolevulinic acid dehydratase (ALA-D), the concentration of free erythrocyte porphyrin (FEP) and the placentas' lead concentra tion. Though in the Ruhr region (Dortmund), signifi cantly higher lead levels in blood were found com pared to the Bavarian Forest, the total results were in the normal range, less than 35 mug%. On an average, the mothers' blood lead level was around 1.4 times (ca. 5 mug%) above that of their newborns; analyz ing this statistically, highly significant correlations were found. However, for the ALA-D activity and the FEP results, no direct dependence on the lead levels in blood could be found. In the placentas, mean lead concentrations between 1,94 mug and 2.23 mug per gram dry-weight (30.6 mug-38,9 mug/100 g wetweight) were gained. Contrary to the measured results of lead in blood, the average placentas' lead level of the most and least industrialized regions were almost identical. A correlation between the mothers' [blood lead levels], respectively, their children's blood lead levels, and the placental lead concentrations could not be proved. No relation could be found between the results and the gestation ages. Final results-' 1. The placenta is not an ideal investigation object con cerning the environment's lead exposure. 2. It has no special barrier--or depot--function in lead metabo lism. .3. In order to estimate the environment's lead exposure, the determination of the lead level in blood will be, in the future, the optimal method. This in vestigation is of special value because of the validity of results and the practicability of getting the samples compared to other parameters and biological mater ials. centrations in the mentally retarded children. These results reinforce the probable association between lead exposure during pregnancy and the development of mental retardation of otherwise unknown etiology. Lead Levels in Human Placentas from Normal and Malformed Births D.G. Wibberly, A.K, Khem.J.K Edwards, andD.I. Rushton, J MED GENET 1977 Oct;14(S):339-45. Authors'abstract; Placental lead levels were studied in a series of Birmingham births classified by stillbirth, neonatal death, or survival beyond one week. There was an appreciable range of lead levels beyond one week. There was an appreciable range of lead levels even in normal births (0-15-3.56 micrograms/g) but, nevertheless, average results showed a pronounced excess of lead in those who failed to survive both birth and the neonatal period, There was no associa tion of placental lead with impaired birth weight among survivors but, in common with other authors, we noted a seasonal variation. The placentas from Indian women had lead levels similar to those from European women, and lower values were found in the normal sibs of stillbirths and neonatal deaths. The possibility is discussed that, under conditions of im paired fetal health in late pregnancy, the placenta may concentrate lead. Lead in Umbilical Cord Blood Correlated with the Blood Lead of the Mother in Areas with Low, Medium or High Atmospheric Pollution B. Zetterlund, J. Winberg, G. Lundgren, and G. Johansson. ACTA PAEDlATR SCAND 1977 Mar: 66(2):169-75. A Retrospective Analysis of Blood-Lead in Mentally Retarded Children M.R. Moore, P,A. Meredith, and A. Goldberg. LANCET 1977 Apr 2; 1(8014):717-9. Authors' abstract: Blood-lead concentrations were measured retrospectively in the blood contained on cards used for testing for phenylketonuria in the first 2 weeks of life. Cards which belonged to 80 of a group [consisting of] 77 children with mental retarda tion of unknown etiology and 77 controls, were identified. Of 77 usable cards, 41 were from mentally retarded children and 36 were from controls; 24 mental-retardation/control pairs were found. There was a highly significant trend towards higher bloodlead concentrations in the mentally retarded children. Water-lead concentrations in the maternal home during pregnancy correlated with blood-lead con Authors' abstract: Lead concentrations in 541 samples of umbilical cord blood from different parts of Sweden were determined. The mean concentra tion was 7.6 mug lead/lQO ml (=0.367 mumol/1). The blood lead values were also determined for 297 mothers, and a mean value of 8.7 mug/100 ml (=0.420 mumol/1) was found. There was a significant correlation between the blood lead level of the mother and the infant as studied in 253 pairs. The slope of the regression line was 0.5 (r=0.6). Signifi cantly lower blood values for both mother and infant were found in areas with low pollution as estimated from the lead content in moss. No seasonal variation could be ascertained. Hematocrit versus lead concen tration was also studied. A flameless atomic absorp tion method was used with a standard deviation of 0.9 mug lead/100 ml. The storage time and sample treatment were also studied. 10 TEH 0532162 DUP050033251 Blood Lead Values In Pregnant Women and Their Offspring JJ, Gershanik, G.G. Brooks, and J.A. Little. AM J OBSTBT GYNECOL 1974 Jun 15;119(4):508-11. Authors' abstract: Lead levels were determined from maternal and neonatal blood samples collected at a general-care hospital. Ninety-eight cord blood pair samples showed a high correlation of lead levels of mothers and corresponding infants with a product moment, correlation coefficient of 0.6377. Thus, neonates are born with lead levels comparable to maternal levels. Maternal Lead Exposure and Blood Lead Concentra tion in Infancy J.E. Ryu, E.E. Ziegler, and S.J. Fomon, J PED1ATR 1978 Sep;93(31:476-8, Authors' discussion: Infant H., a white girl, was born April 1, 1977, to a 25-year-old primigravida after an uneventful pregnancy of 40 weeks' duration. Birth weight was 2,982 gm; physical and neurologic examinations did not reveal any abnormality. The mother had been employed from March 1974 to February 11,1977 (i.e., until 7 weeks before delivery) by a manufacturer of electrical storage batteries and, in this occupation, was exposed to considerable amounts of lead dust. Continued observation of both mother and infant indicates that, in the absence of important postnatal exposure to lead, it appears that an infant exposed prenatally can substantially reduce the body burden of lead, at least relative to body mass, during the early months of life. Effects of Subtoxic Lead Levels on Pregnant Women in the State of Missouri M. S. Fahim, Z. Fahim, and D. G. Hall. RES COMMON CHEM PATHOL PHARMACOL 1976 Feb;13(2):309-31. Authors' abstract: Cords, placentas, placental membranes, and maternal and fetal blood were col lected from 249 women delivered in Columbia, Missouri (Region I). The same samples were obtained from 253 women delivered in Rolla, Missouri (Region II), near lead mining areas. The incidence of term pregnancies with early membrane rupture was 0.41% in Region I and 17% in Region H. The incidence of premature deliveries was 3% and 13.4%, respec tively, Lead concentration in blood and placental tissues of term pregnancies revealed no significant changes. In term with early membrane rupture, blood concentration of lead was higher, as was the case in placental tissues and cord. Lead concentration was highest in membrane tissues, in mug/100 grams (Regions I and II, respectively): placenta, 6.0+/-0.01 and 7.0+/-0.03; cord, 11.0+/-0.34 and 12.0 +/-0.18; membrane, 38.9 +/- 2.64 and 45.3 +/- 3.12. A high positive correlation (r = 0.2941) between lead con centration in maternal and fetal blood existed. Both were significantly (P < 0.01) higher in preterm pregnancies and early membrane ruptures than in term pregnancies. These data suggest that subtoxic levels of lead could increase the incidence of early membrane rupture and premature deliveries. Free Erythrocyte Porphyrins in Cord Blood M.A. Gottuso, B.F. Oski, and F.A. Oski, J PEDIATR 1978 May;92(51:810-2. Authors' abstract: Red cell free erythrocyte por phyrin determinations were performed on cord blood specimens from 236 term infants and on capillary blood specimens from 63 preterm infants weighing less than 1,500 gm, during the first week of life. These results were contrasted with those obtained from 398 normal infants and children aged 1 to 6 years. The mean FEP value for the infants was signi ficantly higher than that observed in the normal control subjects. In 10.5% of the term infants and 15.9% of the preterm infants, values in excess of 120 micrograms/dl RBCs, the highest value recorded in the normal subjects, were observed. Elevations in FEP values were not related to either blood lead concentration or hematocrit levels in the infants. Infants with elevated FEP values were found to have lower serum iron and transferrin saturation values than did infants with low FEP values. These findings suggest that elevations in cord blood FEP values may indicate a state of relative iron deficiency present at birth. The Susceptibility of the Fetus and Child to Chemical Pollutants. Heavy Metal Exposures: Toxicity from Metal-Metal Interactions, and Behavioral Effects JJ. Chisolm Jr. PEDIATRICS 1974 May;53(5): 841-3. From author's discussion: My discussion concerns several possible susceptibility factors to heavy metals that need further investigation. The susceptibility of the young child to heavy metals may be related to diet, or to the intake of protein, calcium or iron, Added to this is his rapid growth, which may be con sidered a stress factor. In the past, our attention has been directed to the acute and catastrophic effects of grossly increased lead absorption: convulsive dis orders, encephalopathy, and the signs of increased intracranial pressure. In the past five years, we seem to have observed fewer children with these acute dis orders. Recently, however, a 9-year-old child (con sidered psychotic and with pica) and a child who de ll TEH 0532163 DUP050033252 veloped the clinical picture of infantile autism after normal development until 3 years of age, have come to my attention. In both instances, blood lead con centrations were elevated and there were other met abolic evidences of lead toxicity; however, the chil dren did not show the classical, clinical signs of acute lead toxicity. Whether or not their increased lead absorption contributed to the observed behavioral disorders is, of course, not known; but the clinical histories are highly suggestive, their cases were chronic, and they did not show any immediate response to chelation therapy. These findings suggest that the role of lead should be considered in a wide variety of central nervous system disorders, even in the absence of classical, clinical syndromes of plumbism. Placental Transfer of Lead and Its Effects on the New born A. R. Clark. POSTGRAD MED J 1977 Nov;53 (625):674-8, Author's abstract: Following the baby's delivery, blood was taken from 122 mothers and their infants' cords for estimation of lead, hemoglobin, packed cell volume, and mean corpuscular hemoglobin concentra tion. All were residents in Kasanda, a township within a radius of 3,000 meters ofBroken Hill Lead Mine and Smelter, Zambia, where the annual mean atmospheric lead concentration Was 9.6 micrograms/m3 and the soil lead concentration 100-9400 ppm. Their mean blood levels were high, being 41.2 micrograms and 37 micrograms/dl for mothers and infants, respective ly, with a significant correlation (r = 0.77, P < 0,001). Thus an infant's blood lead at birth closely follows that of its mother, even at higher values. The increased lead level transfer, however, did not appear to ad versely affect the birth weight or red cell values of the newborn. Cord blood lead levels are being used in Broken Hill to monitor a community's exposure to lead. Lead in Teeth during the Perinatal Period AJ. Burkitt, G. Nickless, and M. V. Stack. POST GRAD MED J1975 Nov;51(601): 778-9. From authors' discussion: This report deals princi pally with observations of the concentration of lead in 50 developing dentitions. Dentitions prepared for analysis formed a selected population, since it was in tended to relate the findings to several arrangements of the data into groupings of comparable size: male/ female, urban/rural, stored/recent (50% of these sets of developing teeth had been stored for more than 10 years). The proportion of samples for which the pathologies included "central nervous system and/or Other malformations" was increased above the usual frequency encountered in order to be able to note any trend in trace metal analyses which might be related to these pathologies. The mean lead concentra tion was 5-6 ppm greater in the "recent" group of teeth. The observation of greater lead concentrations in dentitions obtained recently than In those stored for a number of years points toward an environmen tal change. Placental Transfer of Lead, Mercury, Cadmium, and Carbon Monoxide in Women, II. Influence of Some Epidemiological Factors on the Frequency Distri butions of the Biological Indices in Maternal and Um bilical Cord Blood J.P. Bucket, H. Roels, G. Hubermont, and R. Lauwerys. ENVIRON RES 1978 Jun;15(3): 494-503. Authors' abstract: We have investigated the influ ence of various epidemiological factors (smoking habits, residence, age, occupation, drinking habits, duration of pregnancy, number of previous preg nancies) in the exposure of 474 European pregnant women and their newborns to lead, mercury, cad mium, and carbon monoxide. Smoking has a statisti cally significant influence on carboxyhemoglobin level in mothers and newborns and on cadmium con centration in maternal blood. The association of smoking with a reduction of fetal weight was con firmed. A slight but statistically significant effect of environmental pollution by lead (urban and industrial > semirural > rural area) on lead intake by the preg nant mothers and its transfer to their fetuses was demonstrated. Some results suggest that, during preg nancy, lead could be mobilized from maternal tissue depots, but further investigations are required to con firm this tentative conclusion. No significant relation ships were found between the other epidemiological parameters and the various biological measurements performed on mother and cord blood, J Placental Transfer of Lead, Mercury, Cadmium, and Carbon Monoxide in'Women. I. Comparison pf the Frequency Distributions of the Biological Indices in Maternal and Umbilical Cord Blood R. Lauwerys, J.P. Bucket, H. Roels, and G. Huber mont. ENVIRON RES 1978 Apr;15(2):278-89. Authors' abstract: In 1975 and 1976, we did a survey among 500 pregnant women living in different areas of Belgium in order to evaluate the extent of exposure to heavy metals (lead, mercury, cadmium) during fetal life, their possible biological effects, and the epidemiological factors which may influence the intensity of exposure. Carboxyhemoglobin level was also determined, Comparison of the frequency distri TEH 0532164 DUP050033253 butions of the various hematological indices in maternal and umbilical cord blood indicates that the three heavy metals are transferred from the mother to the fetus, but the barrier role of the placenta is dif ferent for the three metals. There is no barrier for the transfer of mercury, a slight one for lead, and a more important one for cadmium. This explains that the correlation found between the cadmium concen tration in maternal (Cd-B) and fetal blood is much lower (although statistically significant: r = +0.38) than that found for lead and mercury (r > 0,6). For the range of blood lead concentrations (Pb-B) observed in the mothers and their newborns, there is no signi ficant correlation between Pb-B and erythrocyte porphyrin level. On the contrary, because of its high sensitivity to lead, the erythrocyte enzyme deltaaminolevulinate dehydratase (ALA-D) is negatively correlated with Pb-B in mother and newborn. The correlation is higher when ALA-D activity is ex pressed in percent of its activity found in the pre sence of the reactivator dithiothreitol rather than in absolute values. Carboxyhemoglobin levels (HbCO) of mother and newborn are highly correlated (r - +0.81, P < 0.001). In mother, HbCO is also slightly corre lated with Cd-B (r = +0.29, P <0.001) which suggests that both pollutants come at least partly from a simi lar source (smoking). Because of the different barrier effect of the placenta for CO and Cd, no significant correlation between both parameters is found in newborns. Placental Transfer of Lead, Mercury, Cadmium, and Carbon Monoxide in Women, III. Factors Influencing the Accumulation of Heavy Metals in the Placenta and the Relationship between Metal Concentration in the Placenta and in Maternal and Cord Blood H. Roels, G. Hubermont, J.P. Bucket, and R. Lauwerys, ENVIRON RES 1978 Jul;16(l-3):23647. Authors' abstract: The concentration of lead, mer cury, and cadmium was determined in placenta from 474 European women and was compared with the level found in maternal and newborn blood. The in fluence of some epidemiological factors (residence, smoking, drinking habit, age, occupation, previous pregnancies) on heavy metal accumulation in the placenta was also investigated. The median values of the three heavy metals in placenta were 7.5, 1.06, and 1.08 ug/100 g (wet weight) for lead, mercury, and cadmium, respectively. In comparison with maternal blood, the placenta does not concentrate lead nor mercury, but concentrates cadmium about 10-fold. Cadmium concentration in placenta was significantly correlated with that iri maternal blood (r - +0,38); for lead, the correlation was lower, al though still statistically significant (r = +0.22); for mercury, the level in placenta was not significantly correlated with the metal concentration in maternal bipod. Among the three heavy metals, only cadmium showed an increased accumulation in placenta of smokers. No significant effect of current residence, maternal age, or occupation on the accumulation of the heavy metals in placenta was observed. Maternal and Cord Blood Metal Concentrations and Low Birth Weight: A Case Control Study J.D. Bogden, I.S. Thind, D.B. Louria, and H. CaterinL AM J CLIN NUTR 1978 M;31(7): 1181-7, From authors' abstract and discussion; There has been speculation on the possible role of trace metals in contributing to the occurrence of low birth weight, but few data are available for most metals. Twentyfive women giving birth to infants weighing between 1,500 and 2,500 g (cases) and 50 women giving birth to infants weighing more than 2,500 g (controls) were studied. The cases and controls were matched for age (+/- 4 years), race, and socioeconomic status. Cord blood and maternal blood collected at delivery were analyzed by atomic absorption spectrophoto metry for calcium, magnesium, copper, lead, and iron. We found no significant differences, for either mater nal or cord blood, between lead concentrations of the low birth weight and normal birth weight groups, but it should be noted that all maternal and cord concen trations in the study were below established toxic levels. However, for both groups, the lead concen trations were higher in the maternal blood (15.6 jug/ 100 ml) than in the cord blood (13.3 jug/100 ml). These differences are statistically significant (paired t test, t ~ 4.96, P < 0.00 i), though the 2.3 jug/100 ml mean difference between maternal and cord blood is just detectable by the method of analysis used. Our data are in agreement with other studies in which slightly higher concentrations were also found in maternal blood than in cord blood. This observation has prompted speculation that fetal tissues might remove lead from blood more efficiently than ma ternal tissues. Temporary Increase in Chromosome Breakage in an Infant Prenatally Exposed to Lead W.H. Qazi, C. Madahar, and A,M. Yuceoglu. HUM GENET 1980 Feb;53(2):201-3. Authors' abstract: An infant exposed to high levels of lead in utero was found to have increased numbers of cells with chromosome breaks in blood samples obtained at 6 weeks and 3 months of life. Later samples did not show significant abnormality. Physical and neurological examinations of the patient up to 18 months of age gave results within normal limits. 13 TEH 0532165 DUP050033254 SELECTED BIBLIOGRAPHY DIAGNOSIS AND SCREENING Adebonojo FO: Subclinical lead burden: relation to hemo globin and hematocrit values. PA MED 1975 Mar;78(3): 63-5. Araki S: Effects of urinary volume on urinary concentrations of lead, delta-aminolevulinic acid, coproporphyrin, creati nine, and total solutes. BR J IND MED 1980 Feb;37(l): 50-4, Bailey EN, Kiehl PS, Akram DS, et al: Screening in pediatric practice. PEDIATR CLIN NORTH AM 1974 Feb;21(l): 123-65. porphyrins of-newborns and their mothers (German), ZENTRALBL BAKTERIOL (Orig B) 1976 Aug;162(5-6): 528-43. *Fahim MS, Fahim 2, HallDG: Effects of subtoxic lead levels on pregnant women in the state of Missouri. RES COMMUN CHEM PATHOL PHARMACOL 1976 Feb;13(2):309-31. *Gershanik JJ, Brooks GG, Little JA: Blood lead values in pregnant women and their offspring. AM J OBSTET GYNECOL 1974 Jun 15;119(4):508-11, *Gottuso MA, Oski BF, Oski FA: Free erythrocyte porphyrins in cord blood. J PEDIATR 1978 May 92(5) :810-2. *Bogden JD, Thind IS, Louria DB, Caterini H: Maternal and cord blood metal concentrations and low birth weight-a case-control study. AM J CLIN NUTR 1978 Jul;31(7): 1181-7, Brockhaus A, Freier I, Ewers U, et al: Concentrations oflead and Free erythrocyte porphyrin in the blood of adult urban men in northwest Germany (German). INT ARCH OCCUP ENVIRON HEALTH 1980;46(l);59-70. *Buchet JP, Roels H, Hubermont G, Lauwerys R: Placental transfer of lead, mercury, cadmium, and carbon monoxide in women. II, Influence of some epidemiological factors on the frequency distributions of the biological indices in maternal and umbilical cord blood. ENVIRON RES 1978 Jun;15(3) :494-503. *HarrisP, Holley MR: Lead levels in cord blood. PEDIATRICS 1972 Apr;49(4):606-8, *Kantor AF, Curnen MG, Meigs JW, Flannery JT: Occupations of fathers of patients with Wilm's tumor. J EPIDEMIOL COMMUNITY HEALTH 1979 Dec:33(4):253-6. *Kuhnert PM, Erhard P, Kuhnert BR: Lead and delta-amin olevulinic acid dehydratase in RBCs of urban mothers and fetuses, ENVIRON RES 1977 Aug;14(l):73-80. *Lauwerys R, Buchet JP, Roels H, Hubermont G: Placental transfer of lead, mercury, cadmium, and carbon monoxide in women. I, Comparison of the frequency distribution of the biological indices in maternal and umbilical cord blood. ENVIRON RES 1978 Apr;15(2):278-89. *Buikitt AJ, Nickiess G, Stack MV: Lead in teeth during the perinatal period. POST GRAD MED J 1975 Nov;51(601): 778-9. ' Caudarella R, Baldi E, Biagini G,et al: Urinary electrophoretic study in workers with long-term exposure to lead (Italian). G CLIN MED 1979 Nov;60(l 1) :881-91. *Chisolm JJ, Jr: The susceptibility of the fetus and child to chemical pollutants. Heavy metal exposures: toxicity from metal-metal interactions, and behavioral effects. PEDIA TRICS 1974 May;53(5):841-3. *Clark AR: Placental transfer of lead and its effects on the newborn. POST GRAD MED J 1977 Nov;53(625):674-8.* Maruna RFL, Maruna H, Altmann P, et al: Aminolevulinic acid excretion in women before and after delivery and in their newborn infants (German). WEIN KLIN WOCHENSCHR 1975 Oct 31;87(20):692-5. ''Moore MR, Meredith PA, Goldberg A: A retrospective analy sis of blood lead in. mentally retarded children. LANCET 1977 Apr 2;i(S014):717-9. *Pearl M, Boxt LM: Radiographic findings in congenital lead poisoning. RADIOLOGY 1980 Jul;136(I):83-4. *Qasi QH, Madahar C, Yuceoglu M: Temporary increase in chromosome breakage in an infant prenatally exposed to lead. HUM GENET 1980 Feb;53(2):2Pl-3. *Engelhardt E, Schaller KH, Schiele R, Valentin H: The human placenta's lead level as a parameter of the ecological lead exposure. Its validity in comparison to the lead level in blood, the activity of the delta-aminolevulinic acid de hydratase and the concentration of the free erythrocyte Rajegowda BK, Glass L, Evans HE: Lead concentrations in the newborn infant. J PEDIATR 1972 Jan;80(l):116-7. *Roels H, Hubermont G, Buchet JP, Lauwerys R: Placental transfer of lead, mercury, cadmium, and carbon monoxide 15 TEH 0532167 DUP050033255 in women. III. Factors influencing the accumulation of heavy metals in the placenta and the relationship between metal concentration in the placenta and in maternal and cord blood. ENVIRON RES 1978 Ju];i6(l-3):236-47. *Ryu JE, Ziegler EE, Fomon $1: Maternal lead exposure and blood lead concentration in infancy. J PEDIATR 1978 Sep93(3):476-8. * Singh N, Donovan CM, Hanshaw IB: Neonatal lead intoxica tion in a prenatally exposed infant. I PEDIATR 1978 Dec; 93{6):1019-21. *Timpo AE, Amin JS, Casalino MB, Yuceoglu AM-' Congenital lead intoxication. I PEDIATR 1979 May;94(5):765-7. *Wibberley DG, Khera KA, Edwards JH, Rushton DI: Lead levels in human placentae from normal and malformed births. J MED GENET 1977 Oct;14(5):339-45. *ZetterIund B, Winberg 1, Lundgren G, Johansson G: Lead in umbilical cord blood correlated with the blood lead of the mother in areas with low, medium or high atmospheric pollution. ACTA PAEDIATR SCAND 1977 Mar;66(2): 169-75* *ZiegIer EE, Edwards BB, Jensen RL, et al; Absorption and retention of lead by infants. PEDIATR RES 1978 Jan; 12(l):29-34. ^Abstracted 16 TEH 0532168 DUP050033256 RESEARCH AND EVALUATION Levels of Lead in Blood and Hematocrit: implications for the Evaluation of the Newborn and Anemic Patient I. A. Kochenand Y. Greener. PEDIATR RES 1973 Nov; 7(11 ):93 7-44. From authors' speculation: It has been assumed that the clinical evaluation of a given level of lead in blood requires correction for anemia. This was based on the assumption that the intake of lead by the blood is limited by the reduced circulatory erythro cyte volume. This study has shown that the erythro cyte is present in considerable excess in the leaderythrocyte interaction within the commonly en countered range of hematocrit and levels of lead in blood. This would indicate that hematocrit variation has little influence on intake of lead by blood and that correction of levels of lead in blood for anemia is unnecessary. The presence of similar levels of lead in blood for neonates and mothers indicates that an equilibrium exists between levels of lead in fetal and maternal blood which is unaffected by the difference in fetal and maternal hematocrits. This suggests that the extent of lead exposure and the lead burden in soft tissue may be similar in the mother and fetus. Transport of Lead 203 and Calcium 47 from Mother to Offspring K. Kostial and B. Momcilovic. ARCH ENVIRON HEA LTH 1974 Jul;29( 1):28-30. Authors' abstract: The transfer of lead 203 and cal cium 47 from mother to fetuses and litter was ex amined 48 hours after a single intravenous appli cation of both radioisotopes to rats on the 18th day of pregnancy and on the fourth and 15th day of lactation. The transplacental transport of lead was eight times lower than that of calcium while the transmammary transport of lead was four times lower. The highest transfer of both radioisotopes from mother to litter was observed during the late lactation period. Transfer of Lead Via Placenta and Milk M. Green and N. Gruener. RES COMMON CHEM PATHOL PHARMACOL 1974 Aug;8(4):735-8. Authors' abstract: The kinetics of maternal-fetal transfer of lead, as well as through milk, has been investigated in the rat. It was found that lead can be transferred at different stages of gestation. Lead transport is rapid so that the fetus is in equilibrium with the mother 24 hours after injection. Significant amounts of lead are transferred to the nursing rats even a week after a single administration. The lead was found to be concentrated in the head more than in other parts of the body. Investigations of Factors Influencing Exposure and Response to Lead, Mercury, and Cadmium in Man and in Animals II.A. Roets, J.P. Bucket, A. Bernard, G. Hubermont, R. R. Lauwerys, and P. Masson, ENVIRON HEALTH PERSPECT1978 Aug:25:91-6. Authors' abstract: The susceptibility of the heme biosynthetic pathway to lead, as reflected by in creased free erythrocyte porphyrin (FEP) concentra tion, is in humans, as well as in rats, in the order of the young being either equally or more susceptible than females who are, in turn, more susceptible than males. The difference between adult male and female rats can be explained at least partially by the inter action of estradiol and progesterone with the FEP re sponse to lead; the hormonal influence on FEP does not seem to be mediated through changes in plasma iron. The classical "tubular type" proteinuria in workers chronically exposed to cadmium has two (not necessarily concomitant) components, namely, a tubular-type and a glomerular-type component characterized by increased excretion of low and high molecular weight proteins, respectively. No synergistic effect of cadmium and lead on the proteinuria of workers simultaneously exposed to both metals was observed. Mercury (most likely methylmercury) is freely transferred from the mother to the fetus; there is only a slight placental barrier for lead and a rather strong one for cadmium. Compared to maternal blood, placenta does not accumulate lead or mercury but concentrates cadmium about 10-fold. TEH 0532169 DUP050033257 Lead-Induced Behavioral Dysfunction: An Animal Model of Hyperactivity E.K. Silbergeld and AM. Goldberg. EXP NEUROL 1974 Jan;42(l):146-57. Authors' abstract: Although clinically, lead poison ing is thought to cause several serious behavioral problems, a causal relationship between lead ingestion and behavioral dysfunction has not been shown. Epidemiological evidence exists for the coincidence of lead exposure and hyperactivity syndromes in children. An animal model of lead poisoning was developed in which suckling mice were exposed to lead acetate from birth indirectly through their mothers and then directly after weaning. For the first 60 days, no deaths of offspring occurred due to lead, but their growth and development were signifi cantly retarded. Activity of offspring was measured between 40 and 60 days of age. Treated mice were more than three times as active as age-matched con trols. Treated and control mice were given drugs used in the treatment and diagnosis of minimal brain dys function hyperactivity in children: d- and /-ampheta mine, methylphenidate, phenobarbital, and chloral hydrate. Lead-treated hyperactive mice responded paradoxically to all drugs except chloral hydrate: that is, d- and /-amphetamine and menthylphenidate suppressed hyperactivity, while phenobarbital in creased their levels of motor activity. Chloral hydrate was an effective sedative. Implications of these find ings are discussed for the study of the central effects of lead poisoning, and for the relationship between lead poisoning and minimal brain dysfunction hyper activity. Effect of Chronic Lead Treatment on Renal Function G.H. Hirsch. TOXICOL APPL PHARMACOL 1973 May ;25(11:84-93. When rats were fed diets containing 1% or 2% lead acetate for 10-40 weeks, the kidney weight foody weight ratio was increased. Renal tissue water content was not changed. Accumulation of PAH and TEA by renal cortical slices from treated rats was not altered, but the capacity of kidney slices to synthesize glucose and metabolize pyruvate was decreased. Doses of 200 ppm lead or less had no effect on these parameters. Rats treated with 1% or 2% lead acetate showed an increase in the percentage of an injected dose of PAH excreted in 2 hours. Treatment of dams at parturition with 2% or 4% lead acetate resulted in an increase in the kidney weightfoody weight ratio in the off spring at 30 days of age, an increase in PAH intake by renal cortical slices, and a decrease in renal gluconeogenesis. Histologic examination of kidneys after lead treatment showed varying degrees of vacuolar degeneration and cellular necrosis, and the presence of some lead inclusion bodies. Copper, Manganese, Zinc, Nickel, Cadium and Lead in Human Fetal Tissues C.E'. Casey and M.F. Robinson. BR J NUTR 1978 May;39(3):639-46. Influence of Sex Hormones on Free Erythrocyte Protoporphyrin Response to Lead in Rats J.P. Bucket, H. Roels, and R. Lauwerys. TOXICO LOGY 1978 Apr;9(4): 361-9, Authors' abstract: Following oral administration of lead, a difference in free erythrocyte protoporphyrin (FEP) increase was found among adult male, adult female and suckling rats: young animals are more susceptible than adult female rats which, in turn, exhibit a greater FEP increase than adult male animals. This observation parallels that made previously in humans. Possible difference in iron metabolism does not appear to explain the sex-linked difference in FEP response to lead. Sex hormones, mainly progesterone, seem to play a role, but their interaction with lead on the FEP response is restricted to female rats and apparently is not mediated through changes in 5-ami nolevulinic acid synthetase activity. Authors' abstract: 1. Concentrations of copper, manganese, zinc, nickel, cadmium, and lead were measured in samples of liver, kidney, brain, heart, lung, skeletal muscle and vertebral bone from forty fetuses of 23-43 weeks gestation. 2. Cu concentrations in the liver were up to 100 times those in other tissues, but only those in the brain showed a significant in crease with gestational age. 3, Mn concentrations were similar in all tissues; the over-all range was 0.35-9.27 micrograms/g dry matter (DM). 4. Concen trations of Zn in the liver were much higher than in other tissues and decreased with gestational age, whereas levels in skeletal muscle increased. 5. In all tissue, Ni concentrations were within the range 0.04-2.8 mierograms/g DM and levels in kidney and muscle decreased significantly with age. 6. Cd was detected in most of the tissue samples, and concentra tions were within the range 0.01-0.58 microgram/g DM. 7. Concentrations of Pb, where it was detected, varied from 0.1 to 2.4 micrograms/g DM in the soft tissues and from 0,4 to 4.3 micrograms/g DM in the bone samples. TEH 0532170 DUP050033258 Cardiac Effects pf Chronic Lead Poisoning B.J. Williams, W.H. Griffith, CM. Albrecht, and J.H. Pirch. CLINICAL CHEMISTRY AND CHEMI CAL TOXICOLOGY OF METALS (Brown SS ed.) 1977; Amsterdam, Elsevier(North Holland, pp 12730. Authors' abstract: Lead exposure of rats during the nursing period results in an increase in the sensitivity of the heart to norepinephrine-induced cardiac arrhy thmias. This sensitivity is not accompanied by in creased responsiveness to other cardiovascular effects of norepinephrine, such as the vasopressor effect and the stimulation of cyclic AMP accumulation in the heart. The presence of high concentrations of lead in the heart is not required for the expression of cardiotoxicity. The possibility that lead is retained in criti cal areas within the heart has ..not, however, been ex cluded. It rather appears that early exposure of rats pro duces effects which develop slowly, and are seen only after maturity. These data suggest the possibility of a relationship between chronic subclinical lead expo sure and cardiac abnormalities. Pharmacological and Neurochemical Investigations of Lead-Induced Hyperactivity E.K. Silbergeld and A.M. Goldberg. NEURO PHARMACOLOGY 1975 May-Jun;14(5-6):431-44. Authors' abstract: Mice, chronically exposed to inorganic lead from birth, demonstrate levels of spontaneous motor activity approximately three times higher than coetaneous controls. In addition, their behavioral responses to (+)- and (-)-amphetamine, methylphenidate, and phenobarbital are altered. To further clarify the mechanism of action of lead involved in the induction of hyperactivity and al tered pharmacological response, lead-treated mice were administered apomophrine, atropine, neostig mine, physostigmine, x-methylparatyrosine, benztropine, ehiorpromazine, L-3,4-dihydroxyphenylaIanine (L-DOPA), fenfluramine and 2-dimethylaminoethanol. A comparison of the effects of these compounds on motor activity and reactivity showed significant dif ferences between control and lead-treated hyperactive mice. Neurochemical investigations of ..lead-induced hyperactivity were undertaken in chronically treated hyperactive mice by measurement of steady state levels and of synaptosomal transport. The so-called high affinity transport systems were studied for the following putative neurotransmitters, precursors, and amino acids: choline, tyrosine, phenylalanine, norepinephrine, dopamine, leucine, glycine, 5-hydroxytryptamine and y-aminobutyric acid. Significant changes in high affinity synaptosomal transport were found for choline, dopamine, and tyrosine. The trans port systems of other suspected neurotransmitters and the amino acid leucine were not different between lead-treated and coetaneous control mice, In addi tion, steady-state levels of acetylcholine, dopamine, and norepinephrine were measured in forebrains. Norepinephrine levels were increased, while dopamine and acetylcholine levels were not different in leadtreated animals. Concentration of Trace Metals in the Blood of Chil dren H.T. Delves, B.E. Clayton, and J. Bieknell, BR J PREVSOCMED 1973;May 27(2):100-7. Authors' abstract: Samples of whole blood taken from a control group of children and from a group pf children suspected of having lead poisoning have been analyzed, by atomic absorption spectroscopy, for 12 metals--lead, copper, zinc, cadmium, manganese, strontium, chromium, iron, bismuth, lithium, nickel, and cobalt. The main clinical features leading to the laboratory request for a blood lead estimation were severe pica, usually associated with mental retarda tion, anemia, convulsions, or abdominal pain. Many samples from the patients contained significantly high concentrations, relative to the control group, of the first seven metals listed, whereas other samples from the patients contained significantly low concentra tions of iron, copper, and zinc. It was not possible to find any consistent clinical patterns which could be related to these changes. Effects of Dietary Lead and Zing on Fetal Organ Growth P. V. Dilts Jr. and R.A. Ahokas. AM J OBSTET GYNECOL 1980 Apr l;136(7):889-96. Authors' abstract: In order to further understand the effects of ingested lead (Pb) on the fetus and the possible interaction of the trace element zinc (Zn) with Pb, groups of rats with dated pregnancies were fed 0, 10, 50, 100, 200, or 500 mg/L of Pb in water throughout pregnancy. Diet was provided ad libitum. A group pair fed with the 200 mg/L of Pb group and a group fed both Zn and Pb, 200 mg/L, were also studied. Placental weight remained constant, but cell division and total protein level in the placenta were decreased, while placental cell size increased markedly. In the fetal carcass and liver, the weight, cell division, and protein were decreased, but cell growth decreased. Organ dry weight varied with wet decreased, while its cell division, growth, and protein were unchanged. The weight, cell division, and protein level of the kidneys were unchanged, but their cell growth decreased. Organ dry weight varied with wet weight, while the percentage of water was unchanged. Whether pair feeding and Zn supplements improve carcass and liver weight is questionable. 19 TEH 0532171 DUP050033259 Lead, GABA, and Seizures: Effects of Subencephalopathic Lead Exposure on Seizure Sensitivity and GABAergic Function E.K. Silbergeld, L.P. Miller, S. Kennedy, and N. Eng. ENVIRON RES 1979 Aug;19(2):371-82. Authors' abstract; Seizures have been described as the endpoint of lead (Pb) intoxication in both humans and animals. Alterations in blood-brain barrier in tegrity may underlie some cases of Pb-induced seizures, but seizures can also occur in the absence of changes in blood brain barrier. Exposure of rats to two levels of Pb below those producing overt enceph alopathy sensitizes them to the behavioral effects of the convulsant agents pierotoxin, isoniazid, mercaptopropionic acid, and strychnine, but not pentylenete trazol (PTZ). Pb exposure affects several aspects of regional. GABAergic function: GABA-transaminase (GABA-T) and glutamic acid decarboxylase (GAD) activities, GABA levels, and apparent rate of GABA synthesis. The results indicated that Pb increased GAD activity, decreased GABA-T activity, and in creased the apparent rate of GABA synthesis. How ever, these changes were not observed consistently in all regions studied, Pb exposure also inhibited the uptake and release (unstimulated and K-stimulated) of (14C) GABA; this effect was observed in both Pb treatment groups and in all brain regions except the cerebellum. The results support an hypothesis of a neurochemical basis for Pb-induced seizures, involving inhibition of GABAergic neurotransmission. Concentrations of Lead in Capillary Blood of New borns N.P. Kubasik andM.T. Volosin. CUN CHEM 1972 Nov;l 8(111:1415-6. and cytochrome oxidase activities of mitochondria isolated from human term placentas was determined. Placentas were obtained from both toxemic and nontoxemic patients. All enzyme assays were spectrophotometric and the resultant activities expressed as a ratio to the mitochondrial protein content. The results indicate differences in enzyme activities assoc iated with toxemia and due to the added metals. In creasing concentrations of cadmium ion in the enzyme mixtures resulted in a progressive increase in succinic dehydrogenase activity in both the normal and toxemic mitochondria at levels up to 43,0 mumoles. Lead and zinc ions inhibited succincie dehydrogenase activity at all levels added. Developmental Effects of Lead J.P. Bederka, Jr. andJ.S. McLelhn. SURVIVAL IN TOXIC ENVIRONMENTS. New York, Academic Press, 1974, pp 515-20. From authors' summary: It appears that relatively high levels of lead entering the fetal and, perhaps, neonatal mouse via the maternal route result in mi croscopic teratogenic effects and decreased fetal birth weight in mice. Effects on postnatal development in the form of increased mortality, slower rate of body weight gain, and depressed gross motor activity are also seen during the first 35 days of life in mice. Similar effects upon development at present body levels of lead are possible in the more sensitive members of the human and other species. Any con tribution of maternal lead toxicity to the neonatal developmental toxicity remains to be elucidated. Authors' abstract: Lead concentrations in whole blood have been determined for a random sampling of newborns (aged 1-8 days) with the use of a micro technique involving carbon rod atomization and atomic absorption spectrophotometry. The mean lead concentration for the newborns (13.8 4.5 ng/100 ml of whole blood) differed significantly from that of pediatric populations at low (22.6 6.1) and high lead (32.1 10.4) risk. The concentration of lead in amiotic fluid was less than 20 ng/100 ml of fluid. The significance of the newborn lead values and their role in fetal development remains to be determined. Effects of Trace Metals on Placental Metabolism E.B. Dawson, W,D. Cravy, R.R. Clark, and W.J. McGanity, AM J OBSTET - GYNECOL 1969 Jan 15; 103(2):253-6. Authors' abstract: The effect of the trace metals, cadmium, lead, and zinc, upon succinic dehydrogenase The Distribution and Accumulation of CD, Zn, Pb, Cu, Co, Ni, Mn and K in Human Teeth from Five Dif ferent Geological Areas of Finland. R. Lappalainen, and M. Knuuttila, ARCH ORAL BIOL 19 79;24(5):363-8, Authors' abstract: Concentrations of metal were determined in teeth extracted from persons living in areas of Finland where the bedrock is primarily siltstone, orthogeneiss, svecofennidic schist, rapikivi granite or kinzigite. The whole teeth were ground to powder, dissolved in HC1 and HNO3 (2:1 v/v); the metals were analyzed by atomic absorption spectro photometry, Only the concentration of Zn differed significantly in the various geological areas. Zn and Pb accumulated slightly with age at an average rate of 4.48/ig/g and 0.16pg/g per year, respectively. No ac cumulation of the other trace elements was found. 20 TEH 0532172 DUP050033260 SELECTED BIBLIOGRAPHY RESEARCH AND EVALUATION *Bederka JP, Jr., McLellan JS. Developmental effects of lead. In: Kahn MA, Bederka JP Jr. ed. Survival in toxic environ ments. New York, Academic Press, 1974:515-20. *Buchet JP, Roels H, Lauwerys R: Influence of sex hormones on free erythrocyte protoporphyrin response to lead in rats. TOXICOLOGY 1978 Apr$(4):361-9. Carelli G, Rimatori V, Sperduto IS: Blood lead analysis by wet ashing, solvent extraction and flameless atomic absorption spectrophotometry (Italian). MED LAV 1979 Jul-Aug; 70(4) :313-7. arsenate poisoning part 4). OSAKA CITY MED J 1979; 25(l):45-50. *Kochen JA, Greener Y: Levels of lead in blood and hemato crit: implications for the evaluation of the newborn and anemic patient. PEDIATR RES 1973 Nov;7(l l):937-44. *Kostial K, Momcilovic B: Transport of lead 203 and calcium 47 from mother to offspring. ARCH ENVIRON HEALTH 1974 Ju!;29(l):28-30> Krall V, Sachs H, Rayson B, et al: Effects of lead poisoning on cognitive test performance. PERCEPT MOT SKILLS 1980 Apr;50(2):483-6. *Casey CE, Robinson MF: Copper, manganese, zinc, nickel, cadmium and lead in human fetal tissues. BR J NUTR 1978 May;39(3):639-46. Cole R, Cole J: Correlation between disturbed heme synthesis and fetal malformation (letter). LANCET 1976 Sep 18;2 (7986):640, "Kubasik NP, Volosin MT: Concentrations of lead in capillary blood of newborns. CLIN CHEM 1972 Nov;18(ll):1415-6, *Lappalainen R, Knuuttija M: The distribution and accumula tion of Cd, Zn, Pb, Cu, Co, Ni, Mn, and K In human teeth from five different geological areas of Finland. ARCH ORAL BIOL 1979;24(5):363-8. "Dawson EB, Cravy WD, Clark BR, McGanity WJ: Effect of trace metals on placental metabolism. AM J OBSTET GYNECOL 1969 Jan 15:103(2):253-6. Dawson EB, Croft HA, Clark RR, McGanity WJ: Study of nine cation levels in term placentae II. Changes associated with toxemia of pregnancy and fetal prematurity. AM J OBSTET GYNECOL 1969 Apr 15 ;103(8): 1144-7. *Delves HT, Clayton BE, BicknelJ J: Concentration of trace metals in the blood of children. BR J PREV SOC MED 1973 May27(2):100-7. *Dilts PV, Jr, Ahokas RA: Effects of dietary lead and zinc on fetal organ growth. AM J OBSTET GYNECOL 1980 Apr 1; 136(7):889-96, Goiter ;M, Michaelson 1A: Growth, behavior, and brain cate cholamines in lead-exposed neonatal rats: a reappraisal, SCIENCE 1975 Jan 31;187(4174):359-61. *Green M, Gruener N: Transfer of lead via placenta and milk. RES COMMON CHEM PATHOL PHARMACOL 1974 Aug;8(4):735-8. *Hirsch GH: Effect of chronic lead treatment on renal func tion. TOXICOL APPL PHARMACOL 1973 May25(l): 84-93. Horiguchi S: A case of lung cancer due to exposure to arseni cal compounds in an insecticides factory. (Studies on lead Martinez Vea A, Soriano Marin E, Segura Porta F, Garcia Sanmiguel J: Lead encephalopathy in the adult. An unusual form of poisoning (Spanish). REV CLIN ESP 1979 Dec 31; 15S(6):467-9. Mikhail TH, El-Sawaf HA, Ibrahim KM, et al: Evaluation of the effect of lead exposure on the liver in Egyptian lead tank welders. Z ERNAEHRUNGSWISS 1980 Mar;19(l): 50-6. Pambuccian G, Filcescu M : Reactional lesions of the gingiva caused by chronic exposure to lead (French). MORPHOL EMBRYOL (BUCUR) 1980 Jan-Mar;26(l):47-9, *Roels HA, Buchet JP, Bernard A, et al: Investigations of factors influencing exposure and response to lead, mercury, and cadmium in man and in animals. ENVIRON HEALTH PERSPECT 1978 Aug25:91-6, Rutter M: Raised lead levels and impaired cognitive/behavioral functioning: a review of the evidence. DEV MED CHILD NEUROL (SUPPL) 1980 Feb;(42):l-36. "Silbergeld EK, Miller LP, Kennedy S, Eng N: Lead, GABA, and seizures: effects of subencephalopathic lead exposure on seizure sensitivity and GABAergic function. ENVIRON RES 1979 Aug;19(2) :371-82. *Silbergeld EK, Goldberg AM: Lead-induced behavioral dys function: an animal model of hyperactivity. EXP NEUROL 1974Jan-42(l);146-57. 21 TEH 0532173 DUP050033261  Silbergeld EK, Goldberg AM: Pharmacological and neurochemical investigations of lead-induced hyperactivity. NEUROPHARMACOLOGY 1975 May-Jun;14(S-6):431-44. Van Gelder GA, Carson TL, Smith RM, et al: Neurophysiologic and behavioral toxicologic testing to detect subelinical neurologic alterations induced by environmental toxicants. J AM VET MED ASSOC 1973 Nov 1 ;163(9): 1033-5. Williams BJ, Griffith WH, Abfecht CM, et al: Cardiac effects of chronic lead poisoning. In: Brown SS, ed. Clinical chem istry and chemical toxicology of metals. Amsterdam, Elserier/North Holland, 1977:127-30. Woitowitz HJ: Open silico-tuberculosis after silicosis and pos sible lead poisoning (letter) (German). FORTSCHR MED 1980 Mar 6;98(9):329. Abstracted tr.S, GOVERNMENT PRINTING OFFICE s ?4-0-010A593 22 44K54984S123 TEH 0532174 DUP050033262