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

AX5-177
Table AX5-10.6. Effect of Lead Exposure on Liver Heme Synthesis
Concentration Duration Species Blood Lead Effects a Reference
75 mg Pb/kg b. wt.,
i.p.
Multiple time point
analyses 0–30 h
10 −5 ppm Pb nitrate Multiple analyses up
to 24 h
A. Triethyl Pb-3.5
and 8.0 mg/kg
b.wt.
Pb nitrate
3.5, 25, and
100 mg/kg
Single
Subcutaneous
B. In vitro,
10 −3 –10 −9 M
triethyl Pb or Pb
nitrate
5 µM Pb acetate or
Pb diethyldithiocarbomate
Pb uptake
studies 0.33–10 µM
Per OS eqimolar
doses (17 µM Me/kg)
of SnCl 2 or Pb
(CH3COO)2 every day
Multiple analyses up
to 28 days
30 min
Multiple analyses
from
0–20 h
C57 BL/6 mice — Pb poisoning decreases P-450 as a consequence of two different
mechanisms, a mechanism unrelated to heme where P-450 transcription is
inhibited (reduces the synthesis and activity), and a second mechanism
where by inhibition of heme synthesis occurs decreasing the heme
saturation of P450 and/or apo-P450 content.
RLC-GA1 Rat
liver cell line
Adult male
Fischer rats
Rat primary
hepatocyte
cultures
— Pb increases heme synthesis in RLC-GA1 in rat liver cell line, when
measured by the amount of 59 Fe incorporated into heme fraction.
Increased incorporation of 59 Fe into the heme fraction of the Pb treated
cells was the result of increased uptake of iron 59 Fe into the heme fraction
of Pb treated cells.
Cellular degradation of Pb was not significantly affected by Pb.
Control: 5.2 µg/dL
Triethyl Pb 8.0 mg/kg
b.wt.:
19.6 µg/dL
Pb nitrate
25 mg/kg b.wt.:
19.6 µg/dL
Pb nitrate
100 mg/kg b.wt.:
27.2 µg/dL
5 days Female rabbits Control:
3.48 µg/100 cm 3
Pb: 17.50 µg/100 cm 3
—
Triethyl Pb chloride has a similar potency to inorganic Pb nitrate in
inhibiting ALAD both in vitro and in vivo. Liver and blood ALAD have
similar sensitivities to Pb compounds. Inhibition is reduced in the
presence of Zn.
— Effect of Pb and diethyl dithiocarbomates on rat primary hepatocytes as
studied with Pb acetate and or Pb-diethyldithiocarbomate complex (Pb
DTC2l) labeled with 203 Pb indicated that (Pb DTC2l) complex caused a
more rapid and stronger inhibition of ALAD activity than Pb acetate.
Uptake of Pb was rapid and higher with the complex than Pb acetate.
The complex also inhibited the ALAD activity in vitro when incubated
with purified ALAD enzyme.
Pb decreased liver and bone marrow ALAD, but had no change in the
Aminolevulinic acid synthetase (ALA-S) and increased erythrocyte free
protoporphyrin.
Jover et al. (1996)
Lake and
Gerschenson (1978)
Bondy (1986)
Oskarsson and
Hellström-Lindahl
et al. (1989)
Zareba and
Chmielnicka (1992)