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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

Health Effects of Lead Exposure

Susan K. Cummins, MD, MPH

Senior Science Advisor

Pediatric & Maternal Health Staff

Office of New Drugs

today s talk
Today’s Talk
  • Blood lead distribution & trends over time
  • Trends in measurement and modeling of exposure
  • Health effects in children and adults
lead in arctic snow strata

120%

100%

80%

60%

40%

20%

0%

1750

1820

1930

1950

1975

Lead in Arctic Snow Strata

Percent of Current Concentration

Year

geometric mean blood lead levels by gender age nhanes iii 1991 to 1994
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

geometric mean blood lead levels in children 1 to 5 years national health nutrition surveys
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

slide6

13 ug/dL

3 ug/dL

2 ug/dL

common lead sources
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
primary routes of lead exposure
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%
exposure scenarios
Exposure Scenarios

Brief Acute Exposure

Blood

Lead

Level

Long Term Chronic Exposure

Time

lead uptake deposition excretion

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

circulating lead increases with
Circulating Lead Increases with:
  • Physiologic states that heighten bone resorption--
    • Pregnancy & lactation
    • Prolonged bed rest (fracture in traction)
    • Postmenopausal osteoporosis
    • Hyperthyroidism
    • Weightlessness
measuring human lead exposure and body burden
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
blood lead trends treatment lead exposed children trial
Blood Lead TrendsTreatment Lead Exposed Children Trial
  • First year— small BLL drop
  • Three years– No IQ impact

NEJM, 2001

lead is a systemic toxicant health effects in children

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

iq impairment from blood leads 10 ug dl
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
effect size
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
blood lead iq

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
lead poisoning causes anemia
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)
other health or behavioral effects in children youth
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
lead is a systemic toxicant health effects in adults

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
health effects in adult workers
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
reproductive effects in adult workers
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
carcinogenesis
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
health effects in adults from low level exposure
Health Effects in Adults From Low Level Exposure
  • Hypertension & Renal Disease
  • Cardiovascular Disease
  • Cognition
lead exposure and hypertension adults
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
lead exposure and cognitive function
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

lead effect studies within the normative aging study
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)
lead burden assessment normative aging study
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
conclusions
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