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EC number: 239-290-0
CAS number: 15245-44-0
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.
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 discusses 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.
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