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

AX5-23
Subject
Exposure
Protocol
Rat, SD 0.2% Pb(Ac) 2 during gestation
and lactation, postweaning
only, or continuously
Rat, LE, male 50 or 250 ppm Pb(Ac) 2
chronically from PND 21
Rat, LE, male 50 or 250 ppm Pb(Ac)2
chronically from PND 21
Rat, LE, male 50 or 250 ppm Pb(Ac) 2
in water PND 21-use
Table AX5-3.4 (cont’d). Summary of Key Studies on Neurobehavioral Toxicity
Peak Blood Pb
or [Pb] Used Observed Effects Reference
PND 56: 3.8,
25.3, and
29.9 µg/dL
25.1 and
73.5 µg/dL
25.1 and
73.5 µg/dL
Rat, LE, male 50 or 500 ppm from weaning 30.3 and 58–
94 µg/dL
Rat, LE, male,
PND 21
50 ppm PbS
8–11 mo
6–8.5 mo 50 or 500 ppm
3–5 mo
Rat, LE, male,
PND 21
Rat, F344,
PND 21
8 mo,
16 mo
All Pb-treated groups: impaired learning acquisition but unimpaired memory
retention; possible alterations in AMPA receptor binding.
Pb-induced decrements in accuracy on the learning component, but not on the
performance component compared; Pb exposure impaired learning by
increasing preseverative responding on a single lever, even though such
repetitive responding was not directly reinforced.
Pb exposure: attenuated the decline in learning accuracy and the increases in
preseverative responding produced by MK-801; dose-effect curves relating
MK-801 dose to changes in rates of responding were shifted to the right.
73.5 µg/dL Pb-induced potentiation of the accuracy-impairing effects of NMDA by further
increasing the frequencies of errors and likewise potentiated the drug’s ratesuppressing
effect; learning impairments are not caused by changes in
dopaminergic function.
50-ppm group: no effects. 500-ppm group: response rates initially decreased,
then reached control levels, primarily due to longer interresponse times.
FI response rates are more sensitive to perturbation by Pb than FR.
~20 µg/dL Decreased FI response rates (i.e., longer IRTs and lower running rates)
compared to controls.
Demonstrated no consistent changes in FI performance, suggesting that once a
behavior has been acquired, it may be resistant to the adverse effects of
subsequent Pb exposure.
Chen et al. (2001)
Cohn et al. (1993)
Cohn and Cory-
Slechta (1993)
Cohn and Cory-
Slechta (1994a,b)
Cory-Slechta
(1986)
Cory-Slechta
(1990a)
50 or 250 ppm Pb(Ac) 2 73.2 µg/dL Increased sensitivity to the stimulus properties of dopamine D 1 and D 2 agonists. Cory-Slechta and
Widowski (1991)
2 or 10 mL/kg/d Pb(Ac) 2 for
9.5 mo
13–18 µg/dL
steady state
Young and old rats: increased VI and FI response rates; adult rats: decreased
response rates on both schedules. Effects on FI seen with 2-mg dose and VI
with only the 10-mg dose.
Cory-Slechta
and Pokora
(1991)