Predicting Blood Lead Reduction Outcomes Craig J. Boreiko, Ph.D. International Lead Zinc Research Organization Prague 2013
Topics • Non-linear toxicokinetics • Pharmacokinetic Modeling • Predictions for blood lead increases • Predictions for exposure reduction
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).
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
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 mg/m3 lead in air can increase lead in blood anywhere from 0.05 to 1.0 mg/dL
Effect of Mineralogy and Concentration Bioavailability(Hallfrisch et al)
Predicted Relationship Between Lead Ingestion and Blood Lead O’Flaherty PBPK Modeling Relationship Assuming Linearity
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