Presentation on theme: "Lead Poisoning Dr. Ben Balzer Technical Advisory Board member"— Presentation transcript:
1Lead Poisoning Dr. Ben Balzer Technical Advisory Board member The LEAD Group Inc. (General Practice)(Lead Education and Abatement Design Group)6 September 2000
2Lead Poisoning Lead has no known biological function. There is no proven safe lower limit for lead.Lead Pb++, competes with Ca++, Fe++It is cheap, useful,easy to mine, thereforeLead 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.
3Uses and Sources of Lead Paint (until 1970) Petrol (tetraethyl lead)Household dust (via settlement of air pollution)Ceiling dustOccupationalSolderCeramic glazes Pesticides (lead arsenate)Cigarettes Mines, smelters
4More Uses and Sources of Lead TV's, Computer monitors Batteries, Bullets SinkersAviationX-ray shieldsCrystal-ware (high levels in decanters)ExplosivesNon-stick linings of pots (in the past)Plastic colouring (wire, blinds)Pewter
5Absorption of LeadLead 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.Lead absorption is enhanced if diet is poor in iron or calcium.Pica is one of the worst risk factors.Lead can be inhaled.Tetraethyl lead can be absorbed via skin.
9Distribution of Lead 95% long bones. Binds into matrix. Released during osteolysis.4% brain,liver, kidneys.1% blood.Crosses placenta, foetal BBB is open
10Release 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;130:51-62Mobilization 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;131:324-9Lead is released in menopausal bone lossLead levels have second peak in middle age- more in men than women (NHANES 3).Lead follows calcium into and out of bone.
11Lead movementIn 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.
12Data 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.
13Lead and Race. Data from the UIS NHANES 3 study showing differences with race –probably reflecting differences in accommodation and occupation
14Health Effects of Lead Concentration related IQ/ delinquency related to total dosage in childhood
17Lead and Neurodevelopment Each 0.48 µmol/L (10µg/dL) in children.= 4 to 7 IQ points (US Acad. Pediatrics).Industry/ Australian government consensus of 3-5 IQ points.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), pgsMeasurable 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
19Toxicology of Lead 1Lead 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.
20Toxicology 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.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):
21Toxicology of Lead 3The 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
22Toxicology of Lead 4At 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):479-84?Effect of lead on omega 3 and 6 fats.
23Lead and the Elderly Risk of dementia increases with lead burden Risk of accidental lead ingestion
24Dementia and lead 1The 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
25Dementia 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.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.
26Niklowitz WJ Neurofibrillary changes after acute experimental lead poisoning. Neurology 1975 Oct;25(10):927-34Following 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.
27Unresolved QuestionsHow much does lead contribute to cognitive decline and Alzheimer’s disease?Do bone preserving therapies or calcium supplements reduce cognitive decline?Is lead a modifiable risk factor for dementia?
28Incidence of Elevated Blood Leads Sydney 1996 Mira Et Al.
29Childhood Risk Factor Questionnaire Does your child….Have a brother or sister, housemate or playmate with an elevated blood lead level?No YesSometimes eat non-food items such as soil or paint?Have any of the following conditions sometimes associated with lead poisoning, eg iron deficiency anaemia, behaviour problem, learning problem or developmental delay?
30If 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 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 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).
31U.S. Lead Situation 1 1. 1978 Lead banned from paint 2. 1980's- Levels higher than Australia3. Late 1980's Removal of lead from gasoline4. 1980's Universal questionnaire screening5. 1991 Universal blood testing6. 1990's Public housing program7. 1990's Private housing program8. 1990's Massive EPA environmental program
32U.S. Lead Situation 29. ~1995 Title X regulations for sale of properties built before 1978.10. ~1997 Lead litigation compensation approaches asbestos in some states.11. 1998 Builders, tradesmen required to issue documents warning clients of risk when they renovate properties built before 1978.12. 1998 Successful reduction in community levels leads to reintroduction of questionnaire screening in some areas.