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

AX5-30
Subject
Monkey,
cynomolgus,
5–6 yr
Monkey,
cynomolgus,
3 or 7 yr
Monkey,
cynomolgus,
8–9 yr
Monkey,
cynomolgus,
0.5 or 3 yr
Exposure
Protocol
Table AX5-3.4 (cont’d). Summary of Key Studies on Neurobehavioral Toxicity
1500 µg/kg/d Pb(Ac)2
continuously from birth, during
infancy only, or beginning after
infancy
Peak Blood Pb
or [Pb] Used Observed Effects Reference
36 µg/dL Post-infancy exposure impairs nonspatial discrimination reversal while
exposure during infancy exacerbates the effect.
1500 µg/kg/d Pb(Ac) 2 36 µg/dL Pb exposure during different developmental periods produce different effects
on F1 performance in juveniles versus adults.
1500 µg/kg/d Pb(Ac) 2
continuously from birth, during
infancy only, or beginning after
infancy
36 µg/dL Pb-treated monkeys in all three exposure groups learned more slowly, with
less impairment in infancy-only exposures, and showed perseverative
behavior.
2000 µg/kg/d Pb(Ac)2 115 µg/dL Decreased interresponse times and a greater ratio of responses per
reinforcement on the differential reinforcement of low rate schedule.
Rat, adult 16 mg Pb(Ac) 2
via gavage 30 days pre-
pregnancy to PND 21
Rat 0.5, 2.0, or 4.0 mM Pb(Ac) 2 in
drinking water
83.2 µg/dL Developmental Pb exposure results in enhanced acquisition of cocaine selfadministration.
11–50 µg/dL Pb-induced decreased retention in shuttle avoidance task. Pb-associated
increase in locomotor activity.
Rat, F344 ~42 µg/dL Pb-induced better performance using extra-maze spatial cues; Pb-treated rats
spent less time on the periphery of the maze.
Rat, LE, male 0.2% Pb(Ac) 2 from
PND 25 until testing at
PND 100
Rat, Wistar 750 ppm Pb(Ac)2
gestation and lactation
Rat, Wistar 0.03%, 0.09%,
or 0.27%
Pb(Ac)2
gestationally
~30 in Pb Pb-exposure + isolation: spatial learning deficits. Pb-exposure + enrichment:
performed better than the isolated Pb group. Pb-induced decreases in
hippocampal levels of BDNF, NGF-β, NT-3, and basic FGF.
PND 30:
25 µg/dL
PND 90:
0.113 µg/dL
~30, ~33, and
~42 µg/dL at
PND 0, tested at
PND 49
At PND 30 and 90: no Pb-associated changes in elevated maze behavior.
PND 30: decreased freezing, increased ambulation, and increased grooming.
PND 90: Pb-induced decreased freezing and increased ambulation.
Offspring of Pb-treated females mated with nonexposed males.
F2 generation at PND 30 and 90: increased ambulation and decreased
grooming.
Male offspring: all three doses impaired memory retrieval. Female offspring:
only the low dose affected memory retrieval. Motor performance and vision
were not affected by Pb.
Rice and Gilbert
(1990a)
Rice (1992a)
Rice (1992c)
Rice (1992b)
Rocha et al. (2005)
Rodrigues et al.
(1996a)
Salinas and Huff
(2002)
Schneider et al.
(2001)
Trombini et al.
(2001)
Yang et al. (2003)