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

AX5-34
Table AX5-3.6 (cont’d). Key Studies Evaluating Chelation of Pb in Brain
Subject Exposure Protocol Chelator Observed Effects Reference
Rat, female,
Albino
Rat, male, SD
rats at 6–7 wks
Rat, male,
Wistar
100 ppm Pb acetate in drinking
water for 4 wks. During the last 2
days of that exposure, the rats were
administered two i.p. injections of 1
µg stable 204 Pb tracer. Animals then
received 1 to 5 consecutive days of
150 mg/kg CaEDTA ; assayed 24 h
following the last injection.
Chelation with ongoing Pb
exposure; blood Pb were ~45 µg/dL;
550 ppm Pb acetate in drinking
water for 35 days.
Group 1: continued on Pb only for
21 days.
Group 2: received continued Pb
plus oral DMSA at 16, 32, 120, or
240 mg/kg/d for 21 days.
Group 3: discontinued on Pb after
the first 35 days and received oral
DMSA (16, 32, or 240 mg/kg/d).
Dosed with 1000 ppm Pb in
drinking water for 4 mo, then treated
for 5 days with: saline; 25 mg/kg
DMSA orally, twice daily; 75 mg/kg
CaEDTA i.p. once daily; or
25 mg/kg DMSA twice daily plus
75 mg/kg CaEDTA i.p. once daily.
Blood Pb resulting from these
treatments were 46, 22, 28, and 13
µg/dL, respectively and brain Pb
levels were 49, 38, 26, and 22 µg/g,
respectively.
CaEDTA No redistribution of endogenous Pb into the brain following one
CaEDTA dose, no measurable reduction in brain or bone Pb levels, and
reductions in both kidney and blood Pb levels. Additionally, over the
first day of treatment, CaEDTA reduced the 204 Pb tracer more
effectively than the Pb from chronic exposure, indicating greater
biologically availability of Pb from recent exposures.
DMSA DMSA treatment increased urinary Pb and decreased levels of Pb in
blood, brain, bone, kidney, and liver, even with continued Pb exposure.
CaEDTA and
DMSA
The combined treatments produced an additive response in urinary Pb
elimination and elimination from blood, liver, kidney, brain, and femur.
Seaton et al. (1999)
Pappas et al. (1995)
Flora et al. (1995)