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

AX5-31
Subject Exposure Protocol
Rat, PND 110 Water—0.2% Pb(Ac) 2 from
GD 16-PND 21 or use
Table AX5-3.5. Summary of Key Studies on Cell Morphology and Metal Disposition
Rat C6 glioma cells and human
astrocytoma cells
Peak Blood Pb
or [Pb] Used Observed Effects Reference
C Reduction in hippocampal neurogenesis with no spatial learning
impairments.
5–10 µM Pb(Ac) 2
Directly targets GRP78 and induces its compartmentalized
redistribution. GRP78 plays a protective role in Pb neurotoxicity.
Rat pup astroglial cell culture 10 µM Pb(Ac)2 Oxidative stress in astroglia results from Pb impairment of the Cu
transporter Atpase (Atp7a).
Gilbert et al. (2005)
Qian et al. (2005a)
Qian et al. (2005b)
Rat, PND 60 1500 ppm Pb(Ac) 2 for 30–35 days 20.0 µg/dL Significant deleterious effects on progenitor cell proliferation. Schneider et al.
(2005)
Rat,
Cultured neurospheres 0.1–100 µM Differentially affects proliferation and differentiation of embryonic
embryos
Pb(Ac)2 neural stem cells originating from different brain regions.
Young rat PND 0–20 = 600 µg/dL
131.3 µg/dL Blood Pb during succimer chelation are not an immediate indicator
PND 20–40 = 20–60 µg/dL
of brain. Brain Pb values are slower to respond even though blood
Pb is normal.
Cultured oligodendrite progenitor
cells—PND 2
Cultured oligodendrite progenitor
cells—PND 2
1 µM Pb(Ac) 2
0.1–100 µM
Pb(Ac)2
Cultured cerebellar granule neurons 5–50 µM Pb(NO 3) 2
or Pb(ClO 4) 2
Pb inhibition of proliferation and differentiation of oligodendrocyte
cells requires PKC.
Huang and Schneider
(2004)
Stangle et al. (2004)
Deng and Poretz
(2002)
Interferes with maturation of oligodendrocyte progenitor cells. Deng et al. (2001)
Specific transport systems carry Pb into neurons. Mazzolini et al.
(2001)
Rat Cultured C6 glioma cells 1 µM Pb(Ac) 2 Induces GRP78 protein expression and GRP78 is a strong Pb
chelator.
Human,
1–4 yr
Rat and human Cultured rat astroglial,
human neuroblastoma
Cultured GH3, C6, and HEK293
cells
1 µM Pb(Ac)2
1–10 µM Pb(NO3) 2
Half-life of blood Pb was dependent upon exposure duration,
ranging 10–38 mo.
Immature astroglia vs. neuronal cells are most likely to bind Pb in
the brain.
Review paper addressing Pb-binding proteins in the brain and
kidney.
Cellular uptake of Pb is activated by depletion of intracellular
calcium.
Qian et al. (2000)
Manton et al. (2000)
Lindahl et al. (1999)
Fowler (1998)
Kerper and Hinkle
(1997)
Rat 2 g/l Pb(Ac)2 in weanlings for 3 mo 39 µg/dL Chronic low Pb levels induces blood brain barrier dysfunction. Strużyńska et al.
(1997)