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1 Lead Poisoning Dr. Ben Balzer Dr. Ben Balzer Technical Advisory Board member Technical Advisory Board member The LEAD Group Inc. (General Practice) The.

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Presentation on theme: "1 Lead Poisoning Dr. Ben Balzer Dr. Ben Balzer Technical Advisory Board member Technical Advisory Board member The LEAD Group Inc. (General Practice) The."— Presentation transcript:

1 1 Lead Poisoning Dr. Ben Balzer Dr. Ben Balzer Technical Advisory Board member Technical Advisory Board member The LEAD Group Inc. (General Practice) The LEAD Group Inc. (General Practice) (Lead Education and Abatement Design Group) (Lead Education and Abatement Design Group) 6 September 2000

2 2 Lead Poisoning Lead has no known biological function. Lead has no known biological function. There is no proven safe lower limit for lead. There is no proven safe lower limit for lead. Lead Pb ++, competes with Ca ++, Fe ++ Lead Pb ++, competes with Ca ++, Fe ++ It is cheap, useful,easy to mine, therefore It is cheap, useful,easy to mine, therefore Lead is ubiquitous- in air, food, water, soil, ceilings etc. Lead is ubiquitous- in air, food, water, soil, ceilings etc. Leaded petrol means that all environmental dusts are high in lead-contaminating ceiling dust, topsoil, window wells etc. Leaded petrol means that all environmental dusts are high in lead-contaminating ceiling dust, topsoil, window wells etc.

3 3 Uses and Sources of Lead Paint (until 1970) Paint (until 1970) Petrol (tetraethyl lead) Petrol (tetraethyl lead) Household dust (via settlement of air pollution) Household dust (via settlement of air pollution) Ceiling dust Ceiling dust Occupational Occupational Solder Solder Ceramic glazes Ceramic glazes Pesticides (lead arsenate) Pesticides (lead arsenate) Cigarettes Cigarettes Mines, smelters Mines, smelters

4 4 More Uses and Sources of Lead TV's, Computer monitors TV's, Computer monitors Batteries, Bullets Sinkers Batteries, Bullets Sinkers Aviation Aviation X-ray shields X-ray shields Crystal-ware (high levels in decanters) Crystal-ware (high levels in decanters) Explosives Explosives Non-stick linings of pots (in the past) Non-stick linings of pots (in the past) Plastic colouring (wire, blinds) Plastic colouring (wire, blinds) Pewter Pewter

5 5 Absorption of Lead Lead goes down iron or calcium absorption pathway in GIT. Lead goes down iron or calcium absorption pathway in GIT. Children absorb lead well orally (~50%) cf adults poorly (~10%). Children also have more hand to mouth activity. Children absorb lead well orally (~50%) cf adults poorly (~10%). Children also have more hand to mouth activity. Lead absorption is enhanced if diet is poor in iron or calcium. Lead absorption is enhanced if diet is poor in iron or calcium. Pica is one of the worst risk factors. Pica is one of the worst risk factors. Lead can be inhaled. Lead can be inhaled. Tetraethyl lead can be absorbed via skin. Tetraethyl lead can be absorbed via skin.

6 6 Absorption of Lead

7 7 Contribution of Sources

8 8 Reduction of Lead hazards in the home

9 9 Distribution of Lead 95% long bones. 95% long bones. Binds into matrix. Binds into matrix. Released during osteolysis. Released during osteolysis. 4% brain,liver, kidneys. 4% brain,liver, kidneys. 1% blood. 1% blood. Crosses placenta, foetal BBB is open Crosses placenta, foetal BBB is open

10 10 Release of lead during osteolysis Pregnancy increases mobilization of lead from maternal skeleton Gulson BL, Jameson CW, Mahaffey KR, Mizon KJ, Korsch MJ, Vimpani G.. J Lab Clin Med 1997a;130:51-62 Pregnancy increases mobilization of lead from maternal skeleton Gulson BL, Jameson CW, Mahaffey KR, Mizon KJ, Korsch MJ, Vimpani G.. J Lab Clin Med 1997a;130:51-62 Mobilization of lead from the skeleton during the post-natal period is larger than during pregnancy. Gulson BL, Mahaffey KR, Jameson CW, Mizon KJ, Korsch MJ, Cameron MA, Eisman JA. J Lab Clin Med 1998a;131:324-9 Mobilization of lead from the skeleton during the post-natal period is larger than during pregnancy. Gulson BL, Mahaffey KR, Jameson CW, Mizon KJ, Korsch MJ, Cameron MA, Eisman JA. J Lab Clin Med 1998a;131:324-9 Lead is released in menopausal bone loss Lead is released in menopausal bone loss Lead levels have second peak in middle age- more in men than women (NHANES 3). Lead levels have second peak in middle age- more in men than women (NHANES 3). Lead follows calcium into and out of bone. Lead follows calcium into and out of bone.

11 11 Lead movement In childhood, blood lead levels reflect the environmental lead level ie exogenous lead. Protection requires placing barriers between the child and the lead. In childhood, blood lead levels reflect the environmental lead level ie exogenous lead. Protection requires placing barriers between the child and the lead. In adults, lead levels reflect the release of endogenous lead from bone, as well as the intake of exogenous lead. Protection requires prevention of exposure plus preservation of bone density. In adults, lead levels reflect the release of endogenous lead from bone, as well as the intake of exogenous lead. Protection requires prevention of exposure plus preservation of bone density.

12 12 Data from the US NHANES 3 study showing the second peak of lead levels in adulthood. Higher adult male levels reflect occupation and hobby. High risk occupations would be even higher. Women get a post- menopausal peak.

13 13 Lead and Race. Data from the UIS NHANES 3 study showing differences with race –probably reflecting differences in accommodation and occupation

14 14 Health Effects of Lead Concentration related Concentration related IQ/ delinquency related to total dosage in childhood IQ/ delinquency related to total dosage in childhood

15 15 Recommended Lead level <0.48 µmol/L (10µg/dL) < 0.48µmol/L (10µg/dL) = NHMRC Goal. < 0.48µmol/L (10µg/dL) = NHMRC Goal. >0.48µmol/L (10µg/dL) = elevated. >0.48µmol/L (10µg/dL) = elevated. >0.72µmol/L (15µg/dL) =substantially elevated. Notifiable level. >0.72µmol/L (15µg/dL) =substantially elevated. Notifiable level. 1.20µmol/L (25µg/dL) = dangerously elevated. 1.20µmol/L (25µg/dL) = dangerously elevated. >2.20µmol/L (45µg/dL)= Symptomatic. >2.20µmol/L (45µg/dL)= Symptomatic.

16 16 Symptoms from lead are rare!

17 17 Lead and Neurodevelopment Each 0.48 µmol/L (10µg/dL) in children. Each 0.48 µmol/L (10µg/dL) in children. = 4 to 7 IQ points (US Acad. Pediatrics). = 4 to 7 IQ points (US Acad. Pediatrics). Industry/ Australian government consensus of 3-5 IQ points. Industry/ Australian government consensus of 3-5 IQ points. Effects on behaviour are FAR WORSE. Effects on behaviour are FAR WORSE. Delinquency rates are 8 times higher in the top 30% of bone lead. Needleman Needleman, Herbert L. et al, "Bone Lead Levels and Delinquent Behavior," JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Vol. 275, No. 5 (February 7, 1996), pgs Delinquency rates are 8 times higher in the top 30% of bone lead. Needleman Needleman, Herbert L. et al, "Bone Lead Levels and Delinquent Behavior," JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Vol. 275, No. 5 (February 7, 1996), pgs Measurable adverse behaviour changes in 2 year olds Mendelsohn Alan L. Mendelsohn, Benard P. Dreyer, Arthur H. Fierman, Carolyn M. Rosen, Lori A. Legano, Hillary A. Kruger, Sylvia W. Lim, and Cheryl D. Courtlandt "Low-Level Lead Exposure and Behavior in Early Childhood Pediatrics 1998; 101: e10 Measurable adverse behaviour changes in 2 year olds Mendelsohn Alan L. Mendelsohn, Benard P. Dreyer, Arthur H. Fierman, Carolyn M. Rosen, Lori A. Legano, Hillary A. Kruger, Sylvia W. Lim, and Cheryl D. Courtlandt "Low-Level Lead Exposure and Behavior in Early Childhood Pediatrics 1998; 101: e10

18 18 Lead and IQ

19 19 Toxicology of Lead 1 Lead disrupts the main structural components of the blood-brain barrier by primary injury to astrocytes with a secondary damage to the endothelial microvasculature. Within the brain, lead- induced damage occurs preferentially in the prefrontal cerebral cortex, hippocampus and cerebellum. Some characteristic clinical features of lead poisoning may be attributed to this specific anatomical pattern. Lead disrupts the main structural components of the blood-brain barrier by primary injury to astrocytes with a secondary damage to the endothelial microvasculature. Within the brain, lead- induced damage occurs preferentially in the prefrontal cerebral cortex, hippocampus and cerebellum. Some characteristic clinical features of lead poisoning may be attributed to this specific anatomical pattern.

20 20 Toxicology of Lead contd Although the molecular targets for lead are unknown, a vast amount of evidence accumulated over many years has shown that lead disrupts processes that are regulated by calcium. Although the molecular targets for lead are unknown, a vast amount of evidence accumulated over many years has shown that lead disrupts processes that are regulated by calcium. Picomolar concentrations of lead can replace micromolar concentrations of calcium in a protein kinase C enzyme assay. Furthermore, lead activates protein kinase C in intact cells and induces the expression of new genes by a mechanism dependent on protein kinase C. We propose that the learning deficits caused by lead are due to events regulated by protein kinase C that most likely occur at the synapse. Bressler J, Kim KA, Chakraborti T, Goldstein GMolecular mechanisms of lead neurotoxicity. Neurochem Res 1999 Apr;24(4): Picomolar concentrations of lead can replace micromolar concentrations of calcium in a protein kinase C enzyme assay. Furthermore, lead activates protein kinase C in intact cells and induces the expression of new genes by a mechanism dependent on protein kinase C. We propose that the learning deficits caused by lead are due to events regulated by protein kinase C that most likely occur at the synapse. Bressler J, Kim KA, Chakraborti T, Goldstein GMolecular mechanisms of lead neurotoxicity. Neurochem Res 1999 Apr;24(4):

21 21 Toxicology of Lead 3 The cellular, intracellular and molecular mechanisms of lead neurotoxicity are numerous, as lead impacts many biological activities at different levels of control: at the voltage-gated channels and on the first, second and third messenger systems. These effects could be related to lead's ability to interfere with the regulatory action of calcium in cell functions. Finkelstein Y, Markowitz ME, Rosen JF Low-level lead- induced neurotoxicity in children: an update on central nervous system effects Brain Res Brain Res Rev 1998 Jul;27(2):168-76

22 22 Toxicology of Lead 4 At a neuronal level, exposure to lead alters the release of neurotransmitter from presynaptic nerve endings. Spontaneous release is enhanced and evoked release is inhibited. The former may be due to activation of protein kinases in the nerve endings and the latter to blockade of voltage-dependent calcium channels. This disruption of neuronal activity may, in turn, alter the developmental processes of synapse formation and result in a less efficient brain with cognitive deficits. Bressler JP, Goldstein GW Mechanisms of lead neurotoxicity. Biochem Pharmacol 1991 Feb 15;41(4): At a neuronal level, exposure to lead alters the release of neurotransmitter from presynaptic nerve endings. Spontaneous release is enhanced and evoked release is inhibited. The former may be due to activation of protein kinases in the nerve endings and the latter to blockade of voltage-dependent calcium channels. This disruption of neuronal activity may, in turn, alter the developmental processes of synapse formation and result in a less efficient brain with cognitive deficits. Bressler JP, Goldstein GW Mechanisms of lead neurotoxicity. Biochem Pharmacol 1991 Feb 15;41(4): ?Effect of lead on omega 3 and 6 fats. ?Effect of lead on omega 3 and 6 fats.

23 23 Lead and the Elderly Risk of dementia increases with lead burden Risk of dementia increases with lead burden Risk of accidental lead ingestion Risk of accidental lead ingestion

24 24 Dementia and lead 1 The relationship between performance on cognitive tasks and circulating levels of lead in blood and accumulated levels of lead in bone was examined in 141 middle-aged and elderly men Men with higher levels of blood and bone (tibia) lead copied spatial figures less accurately; men with higher levels of bone (tibia) lead had slower responses for pattern memory. These findings suggest that low levels of lead contribute to impairments in cognitive function among elderly men. Payton M, Riggs KM, Spiro A 3rd, Weiss ST, Hu H Relations of bone and blood lead to cognitive function: the VA Normative Aging Study. Neurotoxicol Teratol 1998 Jan-Feb;20(1):19-27 The relationship between performance on cognitive tasks and circulating levels of lead in blood and accumulated levels of lead in bone was examined in 141 middle-aged and elderly men Men with higher levels of blood and bone (tibia) lead copied spatial figures less accurately; men with higher levels of bone (tibia) lead had slower responses for pattern memory. These findings suggest that low levels of lead contribute to impairments in cognitive function among elderly men. Payton M, Riggs KM, Spiro A 3rd, Weiss ST, Hu H Relations of bone and blood lead to cognitive function: the VA Normative Aging Study. Neurotoxicol Teratol 1998 Jan-Feb;20(1):19-27

25 25 Dementia and Lead 2 /~/ the cross-sectional relationship between blood lead levels and a variety of measures of neuropsychological function in a large cohort of elderly women /~/ This study / demonstrates that blood lead levels as low as 8 micrograms/dl were significantly associated with poorer cognitive function as measured by certain neuropsychological tests. Even a slight decrement in cognition would have a large public health impact due to the large number of elderly at risk. /~/ the cross-sectional relationship between blood lead levels and a variety of measures of neuropsychological function in a large cohort of elderly women /~/ This study / demonstrates that blood lead levels as low as 8 micrograms/dl were significantly associated with poorer cognitive function as measured by certain neuropsychological tests. Even a slight decrement in cognition would have a large public health impact due to the large number of elderly at risk. Muldoon SB, Cauley JA, Kuller LH, Morrow L, Needleman HL, Scott J, Hooper FJ Neuroepidemiology 1996;15(2):62-72Effects of blood lead levels on cognitive function of older women. Muldoon SB, Cauley JA, Kuller LH, Morrow L, Needleman HL, Scott J, Hooper FJ Neuroepidemiology 1996;15(2):62-72Effects of blood lead levels on cognitive function of older women.

26 26 Niklowitz WJ Neurofibrillary changes after acute experimental lead poisoning. Neurology 1975 Oct;25(10): Following acute tetraethyllead intoxication in rabbits classic neurofibrillary tangles develop. As studied by electron microscopy, such tangles develop in hydropic degenerating neurons and consist primarily of bundles of 200 A diameter smooth tubules of enormous length. In two of 16 animals a few twisted tubules (periodicity of 800 A) also could be found. The significance of these lead-induced twisted tubules, so characteristic of Alzheimer's pre-senile dementia in man, is discussed. Following acute tetraethyllead intoxication in rabbits classic neurofibrillary tangles develop. As studied by electron microscopy, such tangles develop in hydropic degenerating neurons and consist primarily of bundles of 200 A diameter smooth tubules of enormous length. In two of 16 animals a few twisted tubules (periodicity of 800 A) also could be found. The significance of these lead-induced twisted tubules, so characteristic of Alzheimer's pre-senile dementia in man, is discussed.

27 27 Unresolved Questions How much does lead contribute to cognitive decline and Alzheimers disease? How much does lead contribute to cognitive decline and Alzheimers disease? Do bone preserving therapies or calcium supplements reduce cognitive decline? Do bone preserving therapies or calcium supplements reduce cognitive decline? Is lead a modifiable risk factor for dementia? Is lead a modifiable risk factor for dementia?

28 28 Incidence of Elevated Blood Leads Sydney 1996 Mira Et Al.

29 Childhood Risk Factor Questionnaire Does your child…. Have a brother or sister, housemate or playmate with an elevated blood lead level? No Yes Sometimes eat non-food items such as soil or paint?No Yes Have any of the following conditions sometimes associated with lead poisoning, eg iron deficiency anaemia, behaviour problem, learning problem or developmental delay? No Yes

30 If your child is aged between 9 and 48 months, does he or she: Live in, or frequently visit, a house* built before 1970 with peeling or chipping paint? Live in, or frequently visit, a house* built before 1970 with peeling or chipping paint? Live in, or frequently visit, a house* built before 1970 with or ongoing renovation where old paint (interior or exterior) has been burnt or sanded off, or where ceilings, walls or floors demolished? Live in, or frequently visit, a house* built before 1970 with or ongoing renovation where old paint (interior or exterior) has been burnt or sanded off, or where ceilings, walls or floors demolished? Live in, or frequently visit, a house near a lead releasing industry, eg lead mine, lead smelter, battery-recycling plant? Live in, or frequently visit, a house near a lead releasing industry, eg lead mine, lead smelter, battery-recycling plant? Live with an adult whose job or hobby uses lead? (eg lead mining or smelting, automotive repair, panel-beating, leadlighting, fishing sinker making, electronics, shooting instruction, car-battery service/ repair or manufacture). Live with an adult whose job or hobby uses lead? (eg lead mining or smelting, automotive repair, panel-beating, leadlighting, fishing sinker making, electronics, shooting instruction, car-battery service/ repair or manufacture).

31 31 U.S. Lead Situation Lead banned from paint Lead banned from paint 's- Levels higher than Australia 's- Levels higher than Australia 3. Late 1980's Removal of lead from gasoline 3. Late 1980's Removal of lead from gasoline 's Universal questionnaire screening 's Universal questionnaire screening Universal blood testing Universal blood testing 's Public housing program 's Public housing program 's Private housing program 's Private housing program 's Massive EPA environmental program 's Massive EPA environmental program

32 32 U.S. Lead Situation 2 9. ~1995 Title X regulations for sale of properties built before ~1995 Title X regulations for sale of properties built before ~1997 Lead litigation compensation approaches asbestos in some states. 10. ~1997 Lead litigation compensation approaches asbestos in some states Builders, tradesmen required to issue documents warning clients of risk when they renovate properties built before Builders, tradesmen required to issue documents warning clients of risk when they renovate properties built before Successful reduction in community levels leads to reintroduction of questionnaire screening in some areas Successful reduction in community levels leads to reintroduction of questionnaire screening in some areas.


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