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

AX5-17
Subject Exposure Protocol
Rat
PND 50
Table AX5-3.1 (cont’d). Summary of Key Studies on Neurochemical Alterations
750 or 1500 ppm Pb(Ac) 2
chow from 10 days pre-mating to
PND 50
Calcineurin in mixture 10–2000 pM
Pb(NO 3) 2
Adult rat Cerebrocortical membranes 0.01–4 µM
free Pb(Ac) 2
Adult rat
PND 2
0.2% Pb(Ac) 2
in water and chow
Peak Blood Pb or
[Pb] used Observed Effects Reference
31.9 µg/dL Reductions in NMDAR receptors result in deficits in LTP and spatial
learning.
Nihei et al. (2000)
Has a stimulatory (low) and inhibitory (high) effect on calcineurin. Kern and Audesirk
(2000)
Pb binds to the NMDA receptor channel in a site different from zinc. Lasley and Gilbert
(1999)
52.9 µg/100 mL GLU and GABA release are inhibited independent of Pb exposure
period.
Rat Cultured hippocampal neurons 0.01–10 µM Pb Cl 2 Inhibits glutamatergic and GABAergic transmission via calcium
channel.
Rat
PND 17
Rat
PND 7, 14, 21,
28
Rat
PND 7, 14, 21,
28
Rat
PND 22-adult
Rat
PND 28 56,
112
Cultured hippocampal neurons 0.1–10 µM Pb Cl 2 Increases tetrodotoxin-insensitive spontaneous release of GLU and
GABA.
750 ppm Pb(Ac) 2
chow from 14 days pre-mating to
experimental use
750 ppm Pb(Ac) 2
chow from 14 days pre-mating to
experimental use
Water—0.2% Pb(Ac) 2
from GD 16 to PND 21
Water—1000 ppm Pb(Ac)2
from GD 4-use
59.87 µg/dL NMDAR-2A subunit protein expression is reduced in the
hippocampus.
Lasley et al. (1999)
Braga et al. (1999a)
Braga et al. (1999b)
Nihei and Guilarte
(1999)
59.87 µg/dL Alters the levels of NMDA receptor subunits mRNA in hippocampus. Guilarte and
McGlothan (1998)
— Induces loss of septohippocampal cholinergic projection neurons in
neonates lasting into young adulthood.
Bourjeily and
Suszkiw (1997)
39.6 µg/dL Significant increase in [ 3 H]MK-801 binding after chronic exposure. Ma et al. (1997)