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

AX5-16
Subject Exposure Protocol
Rat
PND 16–18
Rat
PND 50
Rat
PND 7, 14, 21,
28, and 50
Rat
PND 21
Table AX5-3.1. Summary of Key Studies on Neurochemical Alterations
Hippocampal cultures 0.1 and 1.0 µM
Pb Cl 2
1500 ppm Pb(Ac) 2
chow 10 days before breeding and
maintained to sacrifice
1500 ppm Pb(Ac) 2
chow 10 days before breeding and
maintained to sacrifice
750 ppm Pb(Ac) 2
chow from GD 0 to PND 21
Cultured PC12 cells 0.03–10 µM
Pb(NO 3) 2
Adult rat Water—0.1–1.0% Pb(Ac) 2
from GD 15 to adult
Adult rat Water—0.1–1.0% Pb(Ac) 2
from GD 15 to adult
Peak Blood Pb or
[Pb] used Observed Effects Reference
Pb blockage of IPSCs were partially reversible while EPSCs were not. Braga et al. (2004)
31.9 µg/dL Decreases the NR1 subunit splice variant mRNA in hippocampus. Guilarte and
McGlothan (2003)
— Alters NMDAR subtypes and reduces CREB phosphorylation. Toscano et al. (2002)
46.5 µg/dL Increased expression of nicotinic receptors. Jett et al. (2002)
Pb acts as a high affinity substitute for calcium in catecholamine
release.
61.8 µg/100 mL Hippocampal GLU and GABA release exhibits biphasic effects from
chronic Pb.
Westerink and
Vijverberg (2002)
Lasley and Gilbert
(2002)
117.6 µg/100 mL NMDA receptor function is upregulated. Lasley et al. (2001)
Cultured PC12 cells 0.53 µM Pb(Ac)2 PKC is involved in TH upregulation but not downregulation of ChAT. Tian et al. (2000)
Embryonic rat Hippocampal neurons 100 fM–100 nM Decreases [Ca 2+ ]i and increases Ca 2+ efflux by a calmodulin-dependent
mechanism.
Rat 750 or 1500 ppm Pb(Ac)2
chow from 10 days pre-mating to
PND 14, 21, and 28
Ferguson et al.
(2000)
61.1 µg/dL Dose-response effect between level of Pb and expression of NR1 gene. Guilarte et al. (2000)
Cultured PC 12 cells 5–20 µM Pb(Ac) 2 Induces expression of immediate early genes but requires PKC. Kim et al. (2000)