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

AX5-36
Table AX5-3.6 (cont’d). Key Studies Evaluating Chelation of Pb in Brain
Subject Exposure Protocol Chelator Observed Effects Reference
Monkey,
Rhesus,
11-yr-old with
history of
testing for
effects of
housing and
rearing and
which were
used in drug
challenge
studies, were
used after at
least 1.5 yrs
had elapsed
since the last
testing
Rat, male, LE,
PND 55
Rat, male,
F344, 7-wkold
male
~50 mg/kg/d Pb acetate, and
then doses were adjusted to
produce a target blood Pb of
35–40 µg/dL. Following 5 wks
of Pb exposure, the monkeys
were administered 204 Pb tracer
starting 4 days before chelation.
DMSA was administered for
5 days at 30 mg/kg/d, followed
by 14 days at 20 mg/kg/d.
At PND 55, rats were started on
an FI schedule, where a Pbinduced
increase in
interresponse time was
observed. Pb exposure was
then terminated and daily
injections of 75 or 150 mg/kg
CaEDTA were given for
5 consecutive days.
150 or 2000 ppm Pb for
21 days, then distilled water for
the next 21 days. Blood Pb
peaked at 37 and 82 µg/dL,
respectively. Chelation:
50 mg/kg by oral gavage,
3 times a week for up to
21 days; reduced blood Pb to
22 and 56 µg/dL, respectively.
DMSA Brain levels of Pb and tracer, measured in prefrontal cortex, hippocampus, and
striatum, were not different from controls, indicating that DMSA was not
effective in reducing brain Pb levels. They also found a poor correlation
between brain and blood Pb levels.
CaEDTA Chelation treatment failed to reverse the learning deficits in Pb-exposed
animals and further increased the proportion of short interresponse times. The
authors suggest that this effect may be due to the CaEDTA-mediated
redistribution of Pb from bone to brain.
DMSA Pb-induced increase in rearing behavior was observed. DMSA reduced the
Pb-induced effects on activity. Levels of brain glial fibrillary acidic protein
(GFAP) were also assessed in these animals. A Pb-induced dose-dependent
increase in GFAP was observed in hippocampus, cortex, and cerebellum,
which was reversed by DMSA treatment.
Cremin et al. (1999)
Cory-Slechta and
Weiss (1989)
Gong and Evans
(1997)