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

AX5-7
Table AX5-2.2 (cont’d). Lead, Erythrocyte Heme Enzymes, and Other Parameters
Dose and Route of
Exposure Duration Species Blood lead Effect Authors
Pb acetate 160 mg/L
in water
1.46 µmol/liter,
In vitro
Pb 0.34 µM/L–
1.17 µM/L,
subcutaneous
injection
0–60 pM Pb ion,
In vitro
200–500 ppm Pb in
drinking water
0.1–100 µM Pb ion,
In vitro
20–5 µg/kg body wt
1 mg/ kg body wt
8 wks Wistar rats $20!$40 µg/dL Pb increases blood and liver Pb, erythrocyte porphyrin content,
hypoactivity of both hepatocytic and erythrocytic ALAD.
— Fish from regions close to
the smelters and down stream
48 h Human whole blood
erythrocyte hemolysates,
normal and Pb intoxicated
individuals
1 h Male albino New Zealand
rabbits
— Smelter site fish had elevated Pb concentrations, decreased ALAD
activity and species differences in this inhibitory activity were
apparent that could be attributed to Zn levels.
— The effects of various divalent cations on erythrocyte
porphobilinogen are concentration and PH dependent. Zn restores
the Pb inhibited activity.
— Pb causes the most inhibition and Zn activation of rabbit Erythrocyte
porphobilinogen activity.Cu 2+ , Cd 2+ , and Hg 2+ are intermediary.
Each divalent ion has a characteristic effect on the PH- activity
relationship of PBG-S.
20 min Human erythrocyte lysates — Human erythrocyte lysate porphobilinogen activity is increased by
Zn 2+ with a Km of 1.6 pM and inhibited by Pb with a Ki of 0.07 pM,
Pb reduced the affinity for the substrate 5- aminolevulinate, non-
competitively.
14 or 30 days Male ddY mice 24–51 µg/100 mL Pb inhibits erythrocyte and bone marrow P5’N activity. Erythrocyte
ALAD activity was inhibited by 90%. Elevation of Urinary
excretion of ALA with no change in erythrocyte protoporphyrin and
urinary co porphyrin as against in the Pb exposed humans indicates
that protoporphyrin metabolism might be more resistant to Pb in
mice than humans.
5 min Human erythrocyte ghosts — Under normal incubation conditions Pb inhibits, Ca 2+ -Mg 2+ ATPase
with an IC50 of 6.0µM. Pb inhibits Ca 2+ - Mg 2+ ATPase related to
sulphahydryl groups above 1.0 µM Pb and by direct action of Pb
upon Calmodulin below 1.0 µM.
Pregnancy
through lactation
Erythrocytes from Sprague-
Dawley rats
— Na 2+ - K + - ATPase and Ca 2+ - Mg + - ATPase of erythrocyte membranes
from Pb-depleted animals did not change in P0 generation as
compared to 1 mg/kg b.wt Pb animals, where as in F1 generation Pb
depleted rats showed reduced activity.
Santos et al. (1999)
Schmitt et al. (2002)
Farant and Wigfield
(1987)
Farant and Wigfield
(1990)
Simons (1995)
Tomokuni et al.
(1989)
Mas-Oliva (1989)
Eder et al. (1990)