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Health Effects of Lead Exposure

Health Effects of Lead Exposure. Susan K. Cummins, MD, MPH Senior Science Advisor Pediatric & Maternal Health Staff Office of New Drugs. Today’s Talk. Blood lead distribution & trends over time Trends in measurement and modeling of exposure Health effects in children and adults. 120%.

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Health Effects of Lead Exposure

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  1. Health Effects of Lead Exposure Susan K. Cummins, MD, MPH Senior Science Advisor Pediatric & Maternal Health Staff Office of New Drugs

  2. Today’s Talk • Blood lead distribution & trends over time • Trends in measurement and modeling of exposure • Health effects in children and adults

  3. 120% 100% 80% 60% 40% 20% 0% 1750 1820 1930 1950 1975 Lead in Arctic Snow Strata Percent of Current Concentration Year

  4. Geometric Mean Blood Lead Levels by Gender & AgeNHANES III, 1991 to 1994 Males Females Geometric mean blood lead level (ug/dL) Age (years) Env Health Perspect, 1998

  5. Geometric Mean Blood Lead Levels in Children 1 to 5 yearsNational Health & Nutrition Surveys 16 14.9 14 12 10 Geometric Mean Blood Lead Levels in ug/dL whole blood 8 6 4 3.6 2 2.7 2.2 0 1976-1980 1988-1991 1991-1994 1999-2000 NHANES II NHANES III NHANES III NHANES IV Source: CDC

  6. 13 ug/dL 3 ug/dL 2 ug/dL

  7. Children Deteriorated paint Contaminated dust, water, soil, food Occupational take-home exposure Folk remedies Imported ceramic pots, toys Many others Adults Occupational (90%) Hobbies (stained glass, packing shot) Folk remedies Imported ceramic pots Contaminated food Many others Common Lead Sources

  8. Uptake, Distribution, Metabolism and Excretion

  9. Primary Routes of Lead Exposure • Inhalation • Only particles of respirable size (< 1um) • Ingestion • Inhaled lead particles > 2.5 um in diameter • Absorption influenced by: • Presence of other nutrients (iron, zinc, calcium) • Age—Children ~ 50% Adults ~ 10-20%

  10. Exposure Scenarios Brief Acute Exposure Blood Lead Level Long Term Chronic Exposure Time

  11. Inhailed Air Ingested Dust, Food & Water Humans Blood Soft Tissue Feces, Sweat, Hair, Nails Kidney Bone Bone Lead Body Burden Adults – 90-95% Children – 80-95% Urine Lead Uptake, Deposition & Excretion Source: EPA

  12. Circulating Lead Increases with: • Physiologic states that heighten bone resorption-- • Pregnancy & lactation • Prolonged bed rest (fracture in traction) • Postmenopausal osteoporosis • Hyperthyroidism • Weightlessness

  13. Measuring Human Lead Exposure and Body Burden • Blood Lead Level • If brief exposure – half-time 35 days • If long term exposure – slower clearance, ongoing lead exposure equilibrates with stores in soft tissue & bone • Bone LeadLevel -- by K X-Ray Florescence • Measures cumulative body burden • Cortical bone (tibia) – clearance half-time decades • Trabecular bone – clearance half-time years to decades • Cumulative Blood Lead Index (CBLI) • Area under the curve of blood lead levels over time, estimates cumulative lead dose

  14. Blood Lead TrendsTreatment Lead Exposed Children Trial • First year— small BLL drop • Three years– No IQ impact NEJM, 2001

  15. Health Effects in Children

  16. Lead in Blood (ug/dL) Adverse Effect 150 100 80 70 60 30 25 10 5 Death Acute Encephalopathy Abdominal pain Microcytic anemia Attention Deficits Learning Disabilities School Failure Behavior Problems Reduced IQ Lead is a Systemic ToxicantHealth Effects in Children CDC Level of Concern 1978 1985 1991

  17. IQ Impairment from Blood Leads < 10 ug/dL • Canfield & Colleagues, NEJM in April, 2003 • 172 children • Serial Blood Lead measured every 6 months from 6 to 36 months, then at 48 & 60 months • Stanford-Binet IQ scales at 3 and 5 years • Impact of Blood Lead on IQ measured, after adjustment for maternal IQ and covariates

  18. IQ vs. Lifetime Average Blood Lead Concentration Canfield, NEJM 2003

  19. Effect Size • Linear Model, all Blood Leads: 4.6 point IQ decline for every 10 ug/dL increase in Blood Lead • Non-linear Model, only Blood Leads below 10 ug/dL: IQ decline of 7.4 points

  20. Cumulative Frequency Distribution Verbal IQ Blood Lead & IQ • Blood lead > 10 ug/dL lowers IQ by 2 to 4 points • Doubles low IQ • Halves high IQ • Blood lead 1 to 10 ug/dL lowers IQ by 7 points

  21. Lead Poisoning Causes Anemia • Hypochromic, microcytic red blood cells • Mimics & may occur with iron deficiency • Rare with Blood Lead Levels < 35 ug/dL • High Free Erythrocyte Protoporphyrin (FEP)

  22. Other Health or Behavioral Effects in Children & Youth • Executive function disorders • Complications of ADHD & school failure • Delayed onset of puberty • Dental carries • Reduced linear growth

  23. Health Effects in Adults:Adult WorkersGeneral Population

  24. Acute Exposue Chronic Exposue Lead in Blood (ug/dL) Fatigue, Apathy Gastrointestinal complaints Distal motor neuropathy Gout, Arthritis Impaired concentration Renal disease Microcytic anemia Headache Confusion Abdominal pain Nausea, Vomiting Microcytic anemia 150 100 80 70 60 30 Lead is a Systemic ToxicantHealth Effects in Adults

  25. Health Effects in Adult Workers • Hematological:Microcytic anemia • Neurological: • Irritability, headache, poor memory, tremor, depression • Acute encephalopathy • Peripheral neuropathy-- slowed nerve conduction, motor > sensory • Gastrointestinal: colic, constipation, anorexia, nausea, vomiting • Renal toxicity: • Gradual decline in renal function & interstitial fibrosis • Hypertension, hyperuricemia with/without gout

  26. Reproductive Effects in Adult Workers • Males • Impotence • Reduced sperm counts & production • Malformed sperm with reduced motility • Females • Menstrual disturbances • Sterility • Spontaneous abortions • Stillbirths • Both -- genetic damage to germ cells

  27. Carcinogenesis • 2004—National Toxicology Program • Found Lead & Lead Compounds, “Reasonably anticipated to be human carcinogens” • 2006—WHO, IARC Monograph • Inorganic Lead Compounds —probably carcinogenic to humans • Organic Lead Compounds —not classifiable as to their carcinogenicity to humans

  28. Health Effects in Adults From Low Level Exposure • Hypertension & Renal Disease • Cardiovascular Disease • Cognition

  29. Lead Exposure and HypertensionAdults • Multiple Reviews and Meta-Analyses of.. • 30 original observational studies with • Approximately 60,000 participants • Conclusion: Low level lead exposure is associated with hypertension • For every 2-fold increase in blood lead (e.g. from 5 to 10 ug/dL) 0.6 to 1.25 mmHg increase in systolic blood pressure • Findings supported by animal studies

  30. Lead Exposure and Cognitive Function • Meta-Analysis conducted in 2007 • Study participants had environmental exposure or current or past occupational exposure to lead • Supported an association between lead dose and decrements in cognitive function in all three cohorts • Affected cognitive domains: verbal & visual memory, motor & psychomotor speed, manual dexterity, attention, executive functioning, peripheral motor strength • Dose-response relationship in nearly all studies EHP, 115:483, 2007

  31. Lead Effect Studies within the Normative Aging Study • From cohort of 2,280 Boston resident men, selected a subset of 719 men without occupational exposure at entry • Enrollment began 1961 • 21 to 80 years old at enrollment • Few employed in lead occupations • No chronic diseases or HTN at entry • Follow up every 3 to 5 years (survey, physical exam, laboratory work)

  32. Lead Burden Assessment Normative Aging Study • 1991: Blood lead & bone lead measured • Blood Lead Distribution (n and percent): • Below 5 ug/dL (270) 38% • 5 to 10 ug/dL (361) 50% • 11 to 20 ug/dL (80) 11% • > 20 ug/dL (8) 8% • Bone Lead Burden (range and geometric mean): • Tibia: (<1-51 ug/g bone) & 20.8 ug/g bone • Patella: (3-77 ug/g) & 29.8 ug/g bone • Bone lead level correlated with & was the major contributor to blood lead level

  33. Conclusions • Lead is a systemic toxicant with no evidence for a “safe” exposure threshold • Integration of bone lead with blood lead measurements allows for more precise categorization of lead exposure • Recent evidence demonstrates harm in the from low level lead burdens in children & adults

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