Physiologically based models for bone-seeking elements. II. Kinetics of lead disposition in rats

For toxicants with long residence times in the body, body burden is determined largely by exposure history rather than by current exposure. There is a need for physiologically based toxicokinetic models capable of integrating exposure over time by incorporating growth, development, and aging. Such a model is presented for lead kinetics in the growing rat from birth to adulthood. The model incorporates age dependence of the physiologic and metabolic processes that control lead distribution to bone and soft tissues, as well as age dependence of lead absorption from the gastrointestinal tract and age dependence of elimination of lead. The essential features of bone structure and metabolism are integrated into a framework that determines bone lead kinetics. Parameter values used in the model are taken from the literature or are estimated from the best visual fit of the model to data from chronic and short-term studies of lead exposure in rats. The model accommodates any pattern of lead exposure. The uptake of lead by bone varies with the age at which exposure occurs. The predictions of the model are compared with data from a chronic study in rats in which lead exposure was discontinued after exposure periods varying from 3 to 12 months.