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

AX5-40
Citation
Fox et al.
(1997) †
Gandley et al.
(1999)
Govoni et al.
(1984)
Hamilton et al.
(1994)
Han et al.
(2000)
Hanna et al.
(1997)
Table AX5-4.1 (cont’d). Effect of Lead on Reproduction and Development in Mammals Effects on Offspring
Species/
Strain/Age
Rat/Long-Evans
hooded, adult
Rat/Sprague-
Dawley, adult
Rat/Sprague-
Dawley, adult
Rat/Sprague-
Dawley,
25 days old
Rat/Sprague-
Dawley, 5 wks
old
Mouse/Swiss
ICR
preimplantation
embryos
Dose/Route/
Form/Duration Endpoint
0.02 or 0.2% Pb acetate in
drinking water from PND 0–
PND 21; 8 female pups per
litter control pups; 8 pups per
litter low level exposure;
8 pups per litter moderate level
exposure (number of litters per
dose unspecified)
Male rats exposed to 25 or
250 ppm acetate Pb in drinking
water for at least 35 days prior
to breeding
2.5 mg/mL Pb acetate in
drinking water from GD 16 to
postnatal week 8
Pb acetate in drinking water at
250, 500 or 1000 ppm; 8 wks
prior to mating through GD 21
250 mg/mL Pb acetate in
drinking water for 5 wks
followed by 4 wks no exposure
(mated at end of 4-wk no
exposure period)
In vitro incubation of two- and
four-cell embryos with 0.05–
200 µM Pb acetate for 72 hr
(time required for blastocyst
formation)
Developmental and adult Pb exposure for 6 wks produced age and dose-dependent
retinal degeneration such that rods and bipolar cells were selectively lost; at the
ultrastructural level, all dying cells exhibit the classical morphological features of
apoptotic cell death; decrease in the number of rods was correlated with the loss of
rhodopsin content per eye confirming that rods were directly affected by Pb (p < 0.05);
single-flash rod ERGs and cone ERGs obtained from Pb-exposed rats demonstrated that
there were age- and dose-dependent decreases in the rod a-wave and b-wave sensitivity
and maximum amplitudes without any effect on cones; in adult rats exposed to Pb for
3 wks, qualitatively similar ERG changes occurred in the absence of cell loss or
decrease in rhodopsin content (p < 0.05); developmental and adult Pb exposure for
three and 6 wks produced age- and dose-dependent decreases in retinal cGMP
phosphodiesterase (PDE) activity resulting in increased CGMP levels (p < 0.05); retinas
of developing and adult rats exposed to Pb exhibit qualitatively similar rod mediated
ERG alterations as well as rod and bipolar apoptotic cell death (p < 0.05); similar
biochemical mechanism such as the inhibition of rod and bipolar cell cGMP PDE,
varying only in degree and duration, underlies both the Pb-induced ERG rod-mediated
deficits and the rod and bipolar apoptotic cell death (p < 0.05).
Fertility was reduced in males with PbB in range 27–60 µg/dL, Pb was found to affect
initial genomic expression in embryos fathered by male rats with blood Pb levels as low
as 15–23 µg/dL; dose-dependant increases were seen in an unidentified set of proteins
with a relative molecular weight of ~70 kDa.
Decreased sulpiride binding in the pituitary is consistent with the elevated serum PRL
concentrations previously described in Pb-exposed rats; DOPAc concentrations were
reduced by 21% in Pb-treated rats.
Blood Lead Concentration
(PbB)
PbB weanlings 19 ± 3 (low
exposure) or 59 ± 8 µg/dL
(moderate exposure), adult
7 ± 2 µg/dL (at PND 90)
PbB 27–60 µg/dL (fathers)
15–23 µg/dL (offspring)
PbB 71 ± 8 µg/dL
Altered growth rates; reduced early postnatal growth; decreased fetal body weight. PbB 40–100 µg/dL
Pups born to Pb-exposed dams had significantly (p < 0.0001) lower mean birth weights
and birth lengths.
Exposure of embryos to Pb was only toxic at 200 µM, which reduced cell proliferation
and blastocyst formation.
PbB 10–70 µg/dL
PbB not reported