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

AX5-33
Table AX5-3.6. Key Studies Evaluating Chelation of Pb in Brain
Subject Exposure Protocol Chelator Observed Effects Reference
Rat, male, LE,
PND 21
Rat, male, LE,
PND 21
Rat, female,
Wistar
Group 1: 50 ppm Pb acetate in
drinking water from PND 21
for 3–4 mo, after which they
were given i.p. injections of
75 or 150 mg/kg CaEDTA for
either 1, 2, 3, 4, or 5 days.
Group 2: 25 or 500 ppm Pb
acetate followed by a single
injection of either 75 or
150 mg/kg CaEDTA. Twentyfour
hour urine samples were
collected following CaEDTA
injections.
50 ppm Pb acetate from
weaning until testing 3–4 mo
later. The rats received either
25 or 50 mg/kg DMSA for 1, 2,
3, 4, or 5 days and tissues were
evaluated 24 h following the
last injection.
Given 206 Pb-enriched drinking
water at 210 ng Pb/mL for
36 h. Following an overnight
fast, the rats were injected with
one 0.25 mL i.p. injection of
0.11 mmol/kg DMSA. Pb
levels in blood, kidney, brain,
and tibia assessed 24 h later.
CaEDTA Group 1: Blood Pb declined after the first CaEDTA injection, but did not drop
further with subsequent CaEDTA and never dropped below control levels
(5 µg/dL). Pb levels in urine increased similarly with both doses of CaEDTA.
Pb was found to be mobilized from both bone and kidney and initially
redistributed to brain and liver. Subsequent CaEDTA injections caused
declines in brain and liver Pb levels, but no net loss of Pb.
Group 2: a single injection of 150 mg/kg CaEDTA caused marked elevation
of brain Pb, which called into question use of injections of CaEDTA in
clinical diagnostic procedures.
DMSA Blood Pb was decreased by DMSA dose-dependently, with levels dropping to