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EC number: 235-252-2
CAS number: 12141-20-7
This study assessed the in vitro absorption of lead oxide in human skin
samples at 0, 111, and 1033 ug/cm2 concentrations over 24 hours. For the
111 ug/cm2 dose, 95.63% of the applied lead was removed during the wash
at 6 hours post-exposure. At 24 hours post-exposure, 99.51% of the
applied dose was not absorbed. The absorbed dose into the receptor fluid
was <0.01% (5 ng/cm2) and the dermal delivery was 0.13% (148 mg/cm2) of
the applied dose. For the 1033 ug/cm2 dose, 96.10% of the applied lead
was removed during the wash at 6 hours post-exposure. At 24 hours
post-exposure, 98.28% of the applied dose was not absorbed. The absorbed
dose was <0.01% (10 ng/cm2) and the dermal delivery was 0.05% (479
ng/cm2) of the applied dose. The authors concluded that the apparent
decrease in absorption as a function of dose may be attributable to the
considerable background from endogenous lead in the donor skin
restricting the reliability of the absorption factor at the low dose.
Note that observational studies in humans provide the basis for much of what is known about the toxicokinetics and toxicity of lead and are summarised in section 7.10. References to, and summaries of, the human data are made in the endpoint summaries of individual toxicological endpoints.
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 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.
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