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

AX5-20
Subject Exposure Protocol
Rat
PND 22
Rat
PND 42–64
Rat
PND 130–210
250 ppm Pb(Ac) 2
3–6 wks (electro) or 7-13 wks
(immuno)
100, 250, or 500 ppm
Pb(Ac) 2 in chow for 3-6 wks
0.2% Pb(Ac)2
in water
Adult rat Water—0.1-1.0% Pb(Ac)2
from GD 16 to adult
Adult rat 0.2% Pb(Ac) 2
in water
Adult rat 0.2% Pb(Ac) 2
in water PND 0-21
Rat
PND 90–130
Table AX5-3.2. Summary of Key Studies on Neurophysiological Assessments
750 ppm Pb(Ac) 2
chow from 50 days pre-mating to
experimental use
Rat 7–18 mo Water—0.2% Pb(Ac) 2
from GD 16 to experimental use
Rat
PND 13–140
750 ppm Pb(Ac) 2
chow from 50 days pre-mating to
experimental use
Peak Blood Pb
or [Pb] used Observed Effects Reference
30.8 µg/dL Reduces midbrain dopamine impulse flow and decreases dopamine D1
receptor sensitivity in nucleus accumbens.
Tavakoli-Nezhad
and Pitts (2005)
54.0 µg/dL Decrease in number of spontaneously active midbrain dopamine neurons. Tavakoli-Nezhad
et al. (2001)
Review paper examining glutamatergic components contributing to
impairments in synaptic plasticity.
Lasley and Gilbert
(2000)
75.4 µg/dL Deficits in synaptic plasticity in the dentate gyrus from early exposure. Gilbert et al.
(1999a)
117.6 µg/dL Biphasic dose-dependent inhibition of hippocampal LTP. Gilbert et al.
(1999b)
30.1 µg/dL Chronic Pb exposure significantly decreases range of synaptic plasticity. Zhao et al. (1999)
30.1 µg/dL Impairments in LTP and paired-pulse facilitation in the hippocampal DG. Ruan et al. (1998)
16.04 µg/100 mL NMDA-dependent forms of synaptic plasticity are more vulnerable than
NMDA-independent potentiation or paired pulse-facilitation.
Gutowski et al.
(1998)
— Impairs ability to maintain LTP over time in the dentate gyrus. Gilbert and Mack
(1998)
28.5 µg/dL Paired-pulse stimulation of CA3 region shows inhibitory mechanisms. Gutowski et al.
(1997)
Adult rat Water—0.2% Pb(Ac)2
from PND 0–adult
— Chronic Pb increases the threshold for LTP in dentate gyrus in vivo. Gilbert et al.
(1996)
Rat
PND 4–30
Hippocampal neurons 1–100 µM Pb Cl2 Identified the nicotinic acetylcholine receptor as a target for Pb. Ishihara et al.
(1995)
Rat 750 ppm Pb(Ac) 2
chow from 50 days pre-mating to
experimental use
16.2 µg/100 mL LTP and learning are impaired if exposed to Pb in the immature brain. Altmann et al.
(1993)
Abbreviations
GD—gestational day