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

AX5-58
Citation
Priya et al.
(2004)
Ronis et al.
(1996)
Ronis et al.
(1998a) †
Ronis et al.
(1998b)
Ronis et al.
(1998c)
Sierra and
Tiffany-
Castiglioni
(1992)
Srivastava
et al. (2004)
Table AX5-4.3 (cont’d). Effect of Lead on Reproduction and Development in Mammals Effects on Females
Species/
Strain/Age
Rat/Charles
Foster,
6–9 mo old
Rat/Sprague-
Dawley, various
ages
Rat/Sprague-
Dawley, adult
Rat/Sprague-
Dawley, adult
Rat/Sprague-
Dawley, adult
Guinea
pig/NOS, adult
Rat/Fisher 344,
adult
Dose/Route/
Form/Duration Endpoint
0.03 µM Pb in vitro for 1 h LH binding was dropped to 84% in Pb treated cells; Pb exposed cells showed 31%
reduction in the enzymes 17ß-HSDH and 17ß-HS; Pb can cause a reduction in LH and
FSH binding, which significantly alters steroid production in vitro and exerts a direct
influence on granulose cell function.
Pb acetate in the drinking
water or male and female rats
for the following durations:
PND 24–74 (pubertal
exposure); PND 60–74
(post pubertal exposure)
0.6% Pb acetate in drinking
water; ad libitum for various
durations as follows: GD 5 to
PND 1, GD 5 to weaning,
PND 1 to weaning
Ad libitum intake of Pb
acetate (0.05 to 0.45% w/v);
Pb exposure of dams until
weaning, exposure of pups
until day 21, 35, 55, 85
0.05, 0.15, or 0.45% Pb
acetate in drinking water
beginning GD 5 for 21, 35,
55, 85 days
0, 5.5, or 11 mg/kg Pb
acetate, oral dose from GD 22
until GD 52 or 62
12 mg/mL Pb acetate by
gavage for 30 days prior to
breeding until weaning
Data suggest that both the temporary and the long-lasting effects of Pb on reproductive
endpoints in male and female experimental animals are mediated by the effects of Pb on
multiple points along the hypothalamic-pituitary-gonad axis; exposure of male and
female Sprague-Dawley rats pre-pubertally (age 24–74 days) to Pb acetate in the
drinking water resulted in significant reduction in testis weight and in the weight of
secondary sex organs in males; these effects were not observed in rats exposed postpubertally
(day 60–74); there is convincing evidence that pre-pubertal female rats
exposed in utero and during lactation have reduced levels of circulating E2 and LH.
Female pups exposed to Pb from birth through adulthood or from GD 5 through
adulthood were observed to have significantly delayed vaginal opening and disrupted
estrus cycling; these effects on female reproductive physiology were not observed in
animals where Pb exposure was confined only to pregnancy or lactation.
Prenatal Pb exposure that continues until adulthood (85 days old) delays sexual
maturation in female pups in a dose-related manner; dose-dependent delay in sexual
maturation (delayed vaginal opening) among female rats following prenatal Pb
exposure that continued until adulthood (85 days old); a growth hormone-mediated
effect on growth that differs depends upon the developmental state of the animal birth
weight was significantly reduced and more pronounced among male pups; decreased
growth rates in both sexes were accompanied by a statistically significant decrease in
plasma concentrations of IGF1 through puberty and a significant increase in pituitary
growth hormone during puberty; growth suppression of male and female rats involves
disruption of growth hormone secretion during puberty.
Dose-responsive decrease in birth weight and crown-to-rump length was observed in
litters; dose-dependent delay in sexual maturity (delay in vaginal opening); decrease in
neonatal sex steroid levels and suppression of E2 during puberty; elevation in pituitary
LH content was observed during early puberty; E2 cycle was significantly disrupted at
the highest Pb dose; data suggests that the reproductive axis is particularly sensitive to
Pb during specific developmental periods, resulting in delayed sexual maturation
produced by sex steroid biosynthesis.
Hypothalamic levels of SRIF; lower serum concentrations of progesterone at higher
dose only; hypothalamic levels of GnRH and SRIF were reduced in a dose-dependent
manner by Pb treatment in both dams and fetuses; reduction of SRIF levels in 52-days
old fetus was particularly severe (92%) in the 11 mg group.
Pb decreased StAR protein expression and lowered E2 levels; suggested that the
primary action of Pb to suppress E2 is through its known action to suppress the serum
levels of LH and not due to decreased responsiveness of StAR synthesizing machinery.
Blood Lead Concentration
(PbB)
PbB not applicable–in vitro study
Maternal PbB 30–60 µg/dL
Offspring PbB >200 µg/dL.
Pups continuously exposed to Pb
225 to 325 µg/dL
Mean PbB in offspring at 0.05%
(w/v) 49 ± 6 µg/dL
Mean PbB in offspring at 0.15%
(w/v) 126 ± 16 µg/dL
Mean PbB in offspring at 0.45%
(w/v) 263 ± 28 µg/dL
PbB in dams 181 ± 14 µg/dL
PbB in pups ranged from 197 ±
82 to 263 ± 38 µg/dL, increasing
with age of pups
PbB not reported
PbB of dams 39 ± 3.5 SEM
µg/dL and offspring PbB 2.9 ±
0.28 SEM µg/dL