Physiologically Based Models for Bone-Seeking Elements: V. Lead Absorption and Disposition in Childhood

• Published in: Toxicology and applied pharmacology Vol. 131; no. 2; pp. 297 - 308
• Main Author: Oflaherty, E.J.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.04.1995; Elsevier
• Subjects: Absorption; Biological and medical sciences; Bone and Bones - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Child, Preschool; Environmental Exposure; Humans; Infant; Lead - blood; Lead - pharmacokinetics; Medical sciences; Metals and various inorganic compounds; Models, Biological; Tissue Distribution; Toxicology; Human; Toxicokinetics; Distribution; Lead; Child; Modeling; Age; PBPK modeling; Heavy metal
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1995.1072

A physiologically based model of lead absorption and disposition, previously developed and validated for adults, hits been tested and calibrated for children. The model was modified to incorporate additional information on the age dependence of bone formation rate and to take into account increasing localization of bone modeling activity with age. A bone volume characterized by mature bone metabolic activity increases from zero at birth to the total bone volume by young adulthood. Bone formation rate is high from childhood through adolescence, with peaks at birth and around puberty. Bone resorption rate keeps pace at a rate that allows the orderly increase of bone mass. In general, the model reproduces childhood blood lead observations well, except in instances where lead is ingested at very high concentrations. Both bone and blood lead concentration are labile during early childhood because of the high rate of bone turnover. They respond rapidly to increases in lead exposure, and decrease almost as rapidly to near-preexposure concentrations when exposure returns to background levels. As the child grows, fractional bone formation and resorption rates decline and total bone lead turnover becomes more sluggish. From the time of peak bone mineralization rate in adolescence into early adulthood, the rate of bone turnover drops dramatically and the ability to reverse bone lead accumulation relatively rapidly is lost.