Process of TOXICOKINETICS

The toxicokinetics of Pb in humans has been extensively studied and several models have been published that simulate the absorption and complex distribution and elimination of Pb from blood, soft tissues, and bone.

1. Absorption:

      a. Respiratory tract: Inorganic Pb in submicron size particles can be almost completely absorbed              through the respiratory tract, whereas larger particles may be moved after deposition in the                  respiratory tract by mucociliary clearance toward the oropharynx and swallowed.

       b. Gastrointestinal tract: The fraction of ingested Pb absorbed from the gastrointestinal tract                     depends on many factors, including age, diet, nutrition, and physiological characteristics of Pb             in the medium ingested. Children can absorb 40–50% of an oral dose of water-soluble Pb                     compared to 3–10% for adults. Gastrointestinal absorption of inorganic Pb occurs primarily                 the duodenum by saturable mechanisms.

       c. Dermal: Inorganic Pb can be absorbed following inhalation, oral, and dermal exposure, but the             latter route is much less efficient than the former two, with the exception of hand-to-mouth                 behavior. Studies in animals have shown that organic Pb is absorbed through the skin.


2. Distribution:

    The distribution of Pb in the body is route-independent and, in adults, approximately 94% of the           total body burden of Pb is in the bones compared to approximately 73% in children. Pb in blood        is  primarily in red blood cells. Conditions such as pregnancy, lactation, menopause, and                      osteoporosis increase bone resorption and consequently also increase Pb in blood. Pb can be                transferred from the mother to the fetus and also from the mother to infants via maternal milk.


3. Metabolism:

     Metabolism of inorganic Pb consists of formation of complexes with a variety of protein and               nonprotein ligands. Organic Pb compounds are actively metabolized in the liver by oxidative               dealkylation by P-450 enzymes.


4. Excretion:

    Pb is excreted primarily in urine and feces regardless of the route of exposure. Minor routes of            excretion include sweat, saliva, hair, nails, breast milk, and seminal fluid. Elimination of Pb is            multiphasic, reflecting pools of Pb in the body that have varying retention times. The apparent            elimination half-time in blood varies with age and exposure history and ranges from 1 week to 2          years. Elimination of Pb from bone occurs with an apparent half-time of 1–2 decades.