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

AX5-32
Subject Exposure Protocol
Table AX5-3.5 (cont’d). Summary of Key Studies on Cell Morphology and Metal Disposition
Rat 50 or 250 µg/mL Pb(Ac) 2 for 30, 60,
or 90 days
Frog
tadpoles
Elvax implantation for 6 wks 10 !10 to 10 !6 M
Pb Cl 2
Peak Blood Pb
or [Pb] Used Observed Effects Reference
48.9 µg/dL Low dose, long-term exposure significantly decreases cerebral
spinal fluid concentrations of TTR.
Stunted neuronal growth from low Pb levels are reversible with
chelator.
Zheng et al. (1996)
Cline et al. (1996)
Rat Cultured hippocampal neurons 100 nM Pb Cl 2 Possible neurite development inhibition via hyperphosphorylation. Kern and Audesirk
(1995)
Human Pb-binding proteins isolated from
cortex
Rats
PND 7–60
100–2000 ppm Pb(Ac) 2 in water for
adult rats
Rat, adult Radiolabeled Pb perfused across
whole brain
10–2000 nM Characterizes two cytosolic Pb-binding proteins-thymosin beta 4
Pb(Ac)2 and an unidentified protein.
72.5 µg/dL Elimination half-life of Pb from all regions of the brain was about
20 days. There was no evidence of selective regional accumulation
of Pb.
9.7 mL/100 g Review paper examining the passage of Pb across the blood-brain
barrier. Suggests it is actively transported via Ca-ATP pump.
Review paper indicating that Pb either structurally alters nuclear
protein p32/6.3 or inhibits a protease for which it is a substrate.
Review paper discussing Pb removal from bone; the half-life of Pb
in bone is about 20 yr while in blood it is 1 mo.
Quintanilla-Vega
et al. (1995)
Widzowski and
Cory-Slechta (1994)
Bradbury and Deane
(1993)
Shelton et al. (1993)
Wedeen (1992)
Rat, adult Radiolabeled albumin C Discovered that albumin rarely enters brain from blood. Bradbury et al.
(1991)
Guinea pig,
chicken, and
rat
Mouse neuroblastoma
2a cell line
Dog and rat Mouse neuroblastoma
2a cell line
Adult rat Pb binding protein of kidney
and brain
Rat Perfusion of 0.5 MBq of Pb-203
isotope for 0.5–4 h
C Results indicate a positive correlation between p32/6.3 levels and
neuronal maturation.
50–100 µM Pb Examined the relationship between Pb and nuclear protein p32/6.3
and its abundance in intranuclear inclusion bodies.
0.1–1.6 µM Attenuation of Pb inhibition of ALAD involves sequestration of Pb
and a donation of zinc to the enzyme.
615 µg/dL Injections of Pb-203 showed a linear uptake into three regions of
the brain, suggesting that the blood-brain barrier is rate-limiting.
Human C 160 µg/100 mL Blood Pb half-life is affected by duration of exposure, age, and
length of follow-up.
Klann and Shelton
(1990)
Klann and Shelton
(1989)
Goering et al. (1986)
Bradbury and Deane
(1986)
Hryhorczuk et al.
(1985)
Human C >60 µg/dL Blood Pb half-life is dependent upon the length of exposure. O’Flaherty et al.
(1982)