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Description of key information

Short description of key information on absorption rate: Dermal absorption of lead through unabraded human skin is considered to be minimal (< 0.1%) and thus absorption of inorganic lead compounds through the skin has previously been considered to be of less significance than absorption through the respiratory and gastrointestinal routes.

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Additional information

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.

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.

Discussion on absorption rate:

Human data are available and superced the animals studies that have been conducted - one of which is described here. Detailed studies on dermal uptake in humans are described in section 7.10.5. Dermal absorption of lead through unabraded human skin is considered to be minimal and thus absorption of inorganic lead compounds through the skin has previously been considered to be of less significance than absorption through the respiratory and gastrointestinal routes. The most recent guideline-conformed in-vitro dermal absorption study (Toner and Roper, 2005) has established absorption of lead to be less than 0.1%. Other quantitative estimates of dermal absorption are limited in reliability with the most rigorous study (Moore et. al. 1980) suggesting uptake on the order of 0.01 – 0.18%. However, the data from many published studies on this aspect largely lack compliance with current guideline requirements, and their reliability and relevance for human health risk assessment is questionable.