Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

Lead is most easily taken up into the body through inhalation or ingestion – dermal uptake makes a negligible contribution to systemic lead levels. Once taken up into the body, lead is not metabolized. However, lead will distribute to a variety of tissue compartments such as blood, bone and soft tissues. The half-life of lead in the body varies as a function of body compartment. Lead in blood has a half life of 30 – 45 days – measurement of lead in blood thus provides an integrated assessment of average lead exposure (via all routes) over the preceding month. Lead is retained far longer in bones. Depending upon bone type, the retention time of lead can vary between 8 and 30 years. Such lead can both serve as a source of endogenous lead exposure and as a cumulative index of exposure over a time frame of years. Lead excretion is primary via urinary and biliary excretion routes.

Animal studies serve to validate mechanistic inferences derived from observational human studies. The majority of information pertaining to lead toxicokinetics has been accurately defined in humans of different ages and degrees of susceptibility to lead toxicity. A number of toxicokinetic models have been developed to predict the effects of external lead exposure upon internal or systemic levels of lead. The Integrated Exposure Uptake Biokinetic (IEUBK) is now widely applied to assess relationships between environmental lead exposure and blood lead in children. Due to limitations in the ability of the IEUBK model to assess the deposition and subsequent remobilisation of lead from bone, use of the IEUBK model is generally restrict to predict exposures in chidren six years of age or younger.

Physiologically-based pharmacokineitc models (e.g. the O'Flaherty Model) have been developed to predict lead uptake in humans of all ages but is most commonly applied in the assessment of adult exposures. Both the O'Flaherty and IEUBK models are available as computer simulation models and are discussed in greater detail in section 7.10.5.