1. Predicting Blood Lead Reduction Outcomes Craig J. Boreiko, Ph.D. International Lead Zinc Research Organization Prague 2013

2. Topics  Non-linear toxicokinetics  Pharmacokinetic Modeling  Predictions for blood lead increases  Predictions for exposure reduction

3. Dermal Exposure  Hand lead levels correlates with blood lead levels Hand to mouth activity a significant exposure pathway Uptake through the skin is generally insignificant (<0.08%).  Other behavior patterns will contribute (e.g. smoking).

4. Inhalation Exposure  Particulate lead must be deposited deep in the lungs in order for significant exposure via inhalation to occur  This is because exposure in the lungs is dependent upon the aerodynamic size of the particles www.icao.int

5. Inhalation Exposure  Particle inhalation and deposition vary as a function of particle size distribution  Every workplace and process has a unique PSD  In general, lead aerosols contain large particles that result in upper airway deposition and translocation to GI tract  1  g/m 3 lead in air can increase lead in blood anywhere from 0.05 to 1.0  g/dL

6. Effect of Mineralogy and Concentration Bioavailability (Hallfrisch et al)

7. Manton and Cook, 1984.

9.           Predicted Relationship Between Lead Ingestion and Blood Lead O’Flaherty PBPK Modeling Relationship Assuming Linearity 

10. Modelled Bone and Blood Lead as a Function of Exposure Duration

11. Impact of Exposure Reduction at Age 20 or 40

12. Summary  Non-linear toxicokinetics and bone lead complicate blood lead management  Steady state blood lead requires constant exposure reduction as body burden increases  The longer the exposure the greater the bone lead burden  The greater the bone lead burden, the higher the endogenous exposure