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

AX5-178
Table AX5-10.6 (cont’d). Effect of Lead Exposure on Liver Heme Synthesis
Concentration Duration Species Blood Lead Effects a Reference
Pb 500 ppm in
drinking water
0.5 or 2.4 µM Pb
acetate in culture
medium
500 ppm Pb in
drinking water
A. Cu deficient diet:
1 mg/kg Cu in
the diet
B. Moderately
deficient:
2 mg/kg
C. High Zn diet:
60 mg/kg b. wt.
1200 mg/kg b. wt. Pb
acetate in diet, Sub
acute toxic studies
400 mg/Pb
0–100 µM Pb acetate
in the culture medium
14 days Male ddY mice — Urinary excretion of β-Aminoisobutyric acid (ABA) and δ-aminolevulinic
acid (ALA) increased significantly in mice exposed to Pb in drinking
water for 14 days. The degree of increasing excretion for ALA was higher
than urinary ABA. Liver and kidney ALA dehydratase was inhibited,
while ALA synthatase was not affected.
Analyses at multiple
time points,
0–28 days
Rat exposure 62 days
Human occupational
exposure
0.3–38 yrs.
Hepatocyte
cultures on 3T3
cells
A. Male Wistar
rats
B. Pb smelt
workers, males
4 wks Weanling
Sprague Dawley
rats
— Hepatocyte cultures on 3T3 cells produce and excrete porphyrins for
28 days. Pb exposure for 4 wks alters cell morphology and produces
cytotoxic effects that could be monitored by altered porphyrin excretion.
— Pb exposure significantly increases the urinary ALA (Aminolevulinic
acid) and Coproporphyrins (CP-III>CP-I in rats and exposed workers.
Urinary 5-hydroxy indole acetic acid was not influenced by Pb exposure.
— High Zn in the diet reduces plasma copper, but not plasma ceruloplasmin
activity or the recovery of plasma copper or ceruloplasmin activity after
oral copper sulphate of Cu-deficient rats. High dietary Zn also modifies
the response of plasma SOD activity to dietary copper , but does not
influence RBC SOD activity.
4 wks Broiler chickens — Liver porphyrin levels increased during Pb toxicosis. Concurrent
administration of selenium or monensin in the feed further enhances this
process.
19 h Primary Rat and
chick embryo
hepatocyte
cultures
— Formation of Zn protoporphyrins in cultured hepatocytes. Pb did not
specifically increase Zinc protoporphyrin accumulation or alter iron
availability in cultured hepatocytes.
Tomokuni et al.
(1991)
Quintanilla-Vega
et al. (1995)
Ichiba and
Tomokuni (1987)
Panemangalore and
Bebe (1996)
Khan and Szarek
(1994)
Jacobs et al. (1998)