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

AX5-59
Citation
Taupeau et al.
(2001)
Tchernitchin
et al. (1998a)
Tchernitchin
et al. (1998b)
Table AX5-4.3 (cont’d). Effect of Lead on Reproduction and Development in Mammals Effects on Females
Species/
Strain/Age
Mouse/C57blxC
BA, 8 wks old
Rat/Sprague-
Dawley, 14 days
old
Rat/Sprague-
Dawley, 20 or
21 days old
Wide (1985) Mouse/NMRI,
10 wks old
Wide and
D'Argy (1986)
Wiebe and
Barr (1988)
Wiebe et al.
(1988)
Yu et al.
(1996)
Mouse/NMRI,
adult
Rat/Sprague-
Dawley, adult
Rat/Sprague-
Dawley, adult
Rat/Sprague-
Dawley, adult
Dose/Route/
Form/Duration Endpoint
10 mg/kg-d Pb nitrate via i.v.
for 15 days
172 µg/g bw Pb from day 14
every 2nd day until day 20
(75 mg/g bw) Pb via i.v. one
time exposure at 1 or
24 before hormone
stimulation
20 µg/dL/g bw Pb chloride
via i.v. single exposure on
days 8, 12, or 16 after mating
20 µg/g bw by i.v. single
injection on GD 8
20 or 200 ppm Pb chloride in
drinking water; 3 exposure
durations; prior to mating
through weaning, GD 7 to
weaning, PND 21 to PND 35
20 or 200 ppm Pb chloride in
drinking water; 4 exposure
durations; prior to mating
through weaning, GD 7 to
weaning, PND 21 to PND 35,
prior to mating only
Neonatal and lactational
exposure to 0.3% Pb acetate
in drinking water (PND 30)
Low Pb concentration in the ovary caused dysfunction of folliculogenesis, with fewer
primordial follicles and an increase in atretic antral follicles.
Pb inhibits estrogen-induced uterine eosinophilia at 6 and 24 hr after treatment; Pb also
inhibits estrogen-induced edema in deep and superficial endometrial stoma at 24 hr but
not 6 hr after treatment; myometrial hypertrophy is inhibited under the effect of exposure
at 24 hr of treatment.
Enhanced some parameters of estrogen stimulation and inhibited other estrogenic
responses; interaction with responses to estrogen was different depending on whether Pb
pretreatment was 1 or 24 hr before hormone stimulation; estrogenic responses mostly
affected were uterine eosinophilia, endometrial edema, uterine liminal epithelial,
hypertrophy, and mitosis in various, but not all, uterine cell types, in some cell types,
estrogen-induced mitotic response developed earlier under the effect of Pb exposure.
Litter size and fetal survival varied significantly; small litters and increased numbers of
fetal deaths were observed in mice exposed to Pb on day 8 of intrauterine life; live fetuses
were normal with respect to weight and morphological appearance; ovarian follicle
counts revealed a significantly smaller number of primordial follicles in the latter group,
it suggested that the exposure to Pb at a time of early organogenesis caused the observed
fertility decrease by interfering with the development of the female germ cells.
Primordial germ cells showed a normal body distribution but were significantly fewer at
all four stages compared with those of control embryos of corresponding age; Pb had
interfered with the production or activity of alkaline phosphatase.
Treatment with Pb prior to mating resulted in significant increase in E2-receptor affinity
in 21-day old offspring without a change in E2 receptor number; treatment from day 7 of
pregnancy until weaning of the pups resulted in ~35% decrease in E2 receptors per mg
uterine protein when these offspring reached 150 days of age; Pb treatment from 21–35
days old or until 150 days resulted in a significant decrease in uterine E2 receptor number
at 35 and 150 day, respectively.
Exposure to Pb did not affect tissue weights but did cause a significant decrease in
gonadotropin-receptor binding in the pre-pubertal, pubertal, and adult females;
conversion of progesterone to androstenedione and dihydrotestosterone was significantly
decreased in 21-day old rats and in 150-day old females; significantly increased
conversion to the 5-alpha-reduced steroids, normally high during puberty.
Neonatal exposure to Pb decreased cold-water swimming endurance (a standard test for
stress endurance); delayed onset of puberty in males and female offspring, which was
exacerbated by swimming stress.
Blood Lead Concentration
(PbB)
PbB not reported
PbB 47 µg/dL
PbB not reported
PbB not reported
PbB not reported
PbB likely 4.0 ± 1.4 to 6.6 ±
2.3 µg/dL (similar design as
Wiebe et al. (1988)
PbB range 4.0 ± 1.4 to 6.6 ±
2.3 µg/dL
PbB 70 µg/dL
*Not including effects on the nervous or immune systems.
†
Candidate key study.
E2, estradiol; FSH, follicle stimulating hormone; GD, gestational day; GnRH, gonadotropin releasing hormone; HET, Binghamton Heterogeneous Stock; IGF1, insulin-like growth factor 1;
i.p., intraperitoneal; LH, luteinizing hormone; NOS, not otherwise specified; PbB, blood lead concentration; PND, post-natal day; p.o., per os (oral administration); SRIF, somatostatin; StAR,
steroidogenic acute regulatory protein.