ERE596

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ERE596 Special Topics in Environmental Modeling
Toxicokinetics Models SUNY College of
Environmental Science and Forestry Gary
Diamond (diamond_at_syrres.com) September 2004
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Stable Lead Isotopes
Rabinowitz
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Rabinowitz et al. 1976 Study Design
(5 adult males)
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Rabinowitz et al. 1976
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Lead Biokinetics Post-1976

• Bone t1/2 decades
• Blood t1/2 month
• Bone ? blood transfer is accelerated by increased
  bone turnover (e.g. pregnancy)
• Fetal exposure to maternal bone lead

Pb
Bone 90
fast pool
Soft Tissue 10
slow pool

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Lead A Brief History
You are here
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Early Lead Milestones
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Early Lead Abundance
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Leggett, 1993
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300 ml of 15 mg Pb/L Roman wine
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Simulated 300 ml of 15 mg Pb/L Roman
wine Observed presumed still birth (de Wolff et
al. 2001)
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More Recent Lead Milestones
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U.S. Leaded Gasoline Phase-out and Blood Lead
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Bunker Hill Site History
Smelter Operating without Pollution Control
Emergency Response
Smelter Closure 1981
Superfund Assessment 1983
CDC Health Standard
Intervention/Remediation 1986
CERCLA 1980
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EPEIDEMIOLOGICAL FOLLOW-UP TO BUNKER HILL
EXPOSURES

• CDC (Stokes et al.1998) conducted a retrospective
  cohort study
• 281 adults (19-29 years of age) who lived in the
  BH area when they were 9 m 9 years of age,
  compared with an age- and sex-matched referent
  cohort of 287 from Spokane WA who never lived in
  the BH area.
• Exposure was significantly associated with
  outcomes of neuromotor and neurosensory tests,
  including peripheral motor nerve conduction
  velocity, finger vibration threshold, standing
  steadiness, hand-eye coordination, and cognitive
  tests.
• Outcomes were unrelated to current tibial bone
  lead levels (XRF), which were higher among the
  exposed group (4.6 ug/g mineral) than the control
  group (0.6 ug/g).
• Historic PbB for 43 in the exposed cohort had a
  mean of 49.3 ug/dL. Current PbBs were exposures,
  2.9 ug/dL control, 1.6 ug/dL. Correlation
  between current bone lead and historic PbB was
  0.39 (r).

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Effects of Lead Observed at Various Blood
Lead Concentrations ( mg/dL)
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Prospective Epidemiology

• Boston - Bellinger et al. 1987...
• Cincinnati - Dietrich et al. 1987...
• Cleveland - Ernhardt et al. 1986
• Port Pirie - Baghurst et al. 1987...
• Kosovo - Factor-Litvak et al. 1990...
• Mexico City - Rothenberg et al. 1989...

Prospective studies provide a convergence of
evidence for increased risk of undesirable
effects on neurodevelopment as neonatal blood
lead levels exceed 10-15 mg/dL, corresponding to
maternal blood lead levels of 12-18 mg/dL(US EPA,
1991)
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Comparison of Results of Early Prospective
Studies of Mental Development
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Comparison of Results of Early Prospective
Studies of Mental Development
0 - 6 Months
6 -24 Months
4 Years
Wasserman et al. 1994
Bellinger et al. 1987b
5 Years
7 Years
0
5
10
15
20
25
30
m
Blood Lead (
g/dL)
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Legacy of Bunker Hill

• How do we determine how much remediation is
  needed?
• What is the soil lead risk relationship?
• How do we relate soil lead and blood lead
  concentration in the context of other exposures?

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Models, models, and more models...
Rabinowitz et al. 1976
Bert, 1989
Carlisle and Wade,1992
Leggett, 1993
OFlaherty, 1993
Bowers et al. 1994
Stern,1994
U.S. EPA et al. 1994
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IEUBK Model for Lead in Children
Plasma - Extracellular Fluid
RBC
Tr. Bone
Cr. Bone
Other
Kidney
Liver
Urine
Feces
Other
Blood Lead
p
PbB
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New Perspectives on Lead

• Exposure and health risks can be indexed to blood
  lead (PbB)
• Health risks appear to be associated with PbB lt
  20 mg/dL
• U.S. surveys reveal age- and SES-related
  variability in PbB
• Mathematical models that simulate exposure and
  biokinetics, for estimating health risk

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And it gets badder and badder....
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6000 years later, we think lead is worse than we
thought, but we still dont exactly know why...