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

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AX5-49<br />

Citation<br />

Johansson<br />

et al. (1987)<br />

Kempinas<br />

et al. (1988)<br />

Kempinas<br />

et al. (1990)<br />

Kempinas<br />

et al. (1994)<br />

Klein et al.<br />

(1994)<br />

Liu et al.<br />

(2001)<br />

Liu et al.<br />

(2003)<br />

Table AX5-4.2 (cont’d). Effect <strong>of</strong> <strong>Lead</strong> on Reproduction and Development in Mammals Effects on Males<br />

Species/<br />

Strain/Age Dose/Route/Form/Duration Endpoint<br />

Mouse/NMRI,<br />

9–10 wks old<br />

Rat/Wistar,<br />

adult<br />

Rat/NOS,<br />

pubertal<br />

Rat/Wistar,<br />

50 days old<br />

Rat/Sprague-<br />

Dawley,<br />

100 days old<br />

Mouse,<br />

MA-10 cells<br />

Mouse,<br />

MA-10 cells<br />

1 g/L Pb chloride in drinking<br />

water <strong>for</strong> 16 wks<br />

0.5 g/L and 1.0 g/L Pb acetate<br />

in drinking water <strong>for</strong> 90 days<br />

(1.0 g/L) Pb acetate in<br />

drinking water in addition to<br />

i.v. injections <strong>of</strong> Pb acetate<br />

(0.1 mg/100 g bw) every<br />

10 days, 20 days<br />

(1.0 g/L) Pb acetate in<br />

drinking water in addition to<br />

i.v. injections <strong>of</strong> Pb acetate<br />

(0.1 mg/100 g bw) every<br />

15 days, 9 mo<br />

0–1 g Pb acetate/L in<br />

drinking water + 0.1 mg/kg<br />

i.v. every 10 days <strong>for</strong> 20 days<br />

0–1 g Pb acetate/L in<br />

drinking water + 0.1 µg/kg<br />

i.v. every 15 days <strong>for</strong><br />

270 days<br />

0.1, 0.3, or 0.6% Pb acetate in<br />

distilled water <strong>for</strong> 21 days<br />

10 −8 to 10 −5 Pb acetate in<br />

vitro <strong>for</strong> 2 hr<br />

10 −8 to 10 −5 Pb acetate in<br />

vitro <strong>for</strong> 6 hr incubated<br />

Spermatozoa had significantly lower ability to fertilize mouse eggs; morphologically<br />

abnormal embryos were found.<br />

PbB exhibited a significant increase in both groups; decrease in hematocrit and<br />

hemoglobin, together with a rise in glucose levels; no signs <strong>of</strong> lesion were detected<br />

upon histological examination <strong>of</strong> testes, caput, and cauda epididymidis; an increase in<br />

ductal diameter, and a decrease in epithelial height were observed in the cauda<br />

epididymidis; concentration <strong>of</strong> spermatozoa stored in the caudal region <strong>of</strong> the<br />

epididymis exhibited a significant increase in Pb-treated animals.<br />

Basal levels <strong>of</strong> testosterone were higher both in the plasma and in the testes <strong>of</strong> acutely<br />

intoxicated animals; levels <strong>of</strong> LH were not affected in either group, nor was the LHRH<br />

content <strong>of</strong> the median eminence; density <strong>of</strong> LH/hCG binding sites in testicular<br />

homogenates was reduced by saturnism in both groups, apparent affinity constant <strong>of</strong> the<br />

hormone-receptor, complex significantly increased.<br />

Increased plasma and testicular testosterone concentrations; no effects on testicular<br />

weight; reduced weight <strong>of</strong> prostate; increased weight <strong>of</strong> seminal vesicle and seminal<br />

secretions.<br />

2–3-fold enhancement <strong>of</strong> mRNA levels <strong>of</strong> GnRH and the tropic hormone LH; 3-fold<br />

enhancement <strong>of</strong> intracellular stores <strong>of</strong> LH; mRNA levels <strong>of</strong> LH and GnRH and pituitary<br />

levels <strong>of</strong> stored LH are proportional to blood levels <strong>of</strong> Pb.<br />

Significantly inhibited hCG- and dbcAMP-stimulated progesterone production in<br />

MA-10 cells; steroid production stimulated by hCG or dbcAMP were reduced by Pb;<br />

expression <strong>of</strong> StAR protein and the activities <strong>of</strong> P450 side-chain cleavage (P450) and<br />

3ß-HSD enzymes detected; expression <strong>of</strong> StAR protein stimulated by bdcAMP was<br />

suppressed by Pb at about 50%; progesterone productions treated with 22Rhydroxycholesterol<br />

or pregnenolone were reduced 30–40% in Pb treated MA-10 cells.<br />

Pb significantly inhibited hCG- and dbcAMP-stimulated progesterone production from<br />

20 to 35% in MA-10 cells at 6 hr; Pb suppressed the expression <strong>of</strong> steriodogenesis acute<br />

regulatory (StAR) protein from 30 to 55%; activities P450 side-chain cleavage<br />

(P450scc) enzyme and 3ß-HSD were reduced by Pb from 15 to 25%.<br />

Blood <strong>Lead</strong> Concentration<br />

(PbB)<br />

PbB not reported<br />

PbB 65–103 µg/dL<br />

PbB ~40 µg/dL<br />

PbB 10–41 µg/dL<br />

PbB 8.5–40 µg/dL<br />

PbB 42–102 µg/dL<br />

PbB not applicable–in vitro study<br />

PbB not applicable–in vitro study

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