Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

AX5-138
Table AX5-8.4 (cont’d). Bone Lead as a Potential Source of Toxicity in Altered Metabolic Conditions
Compound
Dose/Concentration
Duration Exposure
Route Species Effects Blood Level Reference
Pb acetate
1500 µg/Common
Pb/kg/d
~10 yrs, replaced by a
204 Pb-enriched dose
(50 days), then
206 Pb-enriched dose
(50 days), and finally a
207 Pb-enriched dose
(50 days, with reduced
concentration)
Orally, in gelatin
capsule
Pb acetate
1300 to
1500 µg/Common
Pb/kg/d
~10 yrs, replaced by a
204 Pb-enriched dose
(47 or 281 days), then
206 Pb-enriched dose
(50 or 105 days), and
finally a 207 Pb-enriched
dose (50 days, with
650 µg concentration in
only one primate)
Orally, in gelatin
capsule
Nonhuman
Primate
Nonhuman
Primate
Sequential doses of Pb mixes enriched in stable isotopes ( 204 Pb, 206 Pb,
and 207 Pb) were administered to a female cynomolgus monkey (Macaca
fascicularis) that had been chronically administered a common Pb isotope mix.
The stable isotope mixes served as a marker of recent, exogenous Pb exposure,
while the chronically administered common Pb served as a marker of
endogenous (principally bone) Pb. From thermal ionization mass spectrometry
analysis of the Pb isotopic ratios of blood and bone biopsies collected at each
isotope change, and using end-member unmixing equations, it was determined
that administration of the first isotope label allowed measurement of the
contribution of historic bone stores to blood Pb. Exposure to subsequent
isotopic labels allowed measurements of the contribution from historic bone
Pb stores and the recently administered enriched isotopes that incorporated
into bone. In general the contribution from the historic bone Pb (common Pb)
to blood Pb level was constant (~20%), accentuated with spikes in total blood
Pb due to the current administration of the stable isotopes. After cessation of
each sequential administration, the concentration of the signature dose rapidly
decreased.
Initial attempts to apply a single bone physiologically based model of Pb
kinetics were unsuccessful until adequate explanation of these rapid drops in
stable isotopes in the blood were incorporated. Revisions were added to
account for rapid turnover of the trabecular bone compartment and slower
turnover rates of cortical bone compartment, an acceptable model evolved.
From this model it was reported that historic bone Pb from 11 yrs of
continuous exposure contributes ~17% of the blood Pb concentration at Pb
concentration over 50 µg/dL, reinforcing the concept that the length of Pb
exposure and the rates of past and current Pb exposures help determine the
fractional contribution of bone Pb to total blood Pb levels. The turnover rate
for cortical (~88% of total bone by volume) bone in the adult cynomolgus
monkey was estimated by the model to be ~4.5% per yr, while the turnover
rate for trabecular bone was estimated to be 33% per yr.
Total blood Pb range:
31.2 to 62.3 µg/100g.
Inskip et al. (1996)
Various O’Flaherty et al.
(1998)