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

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AX5-47<br />

Citation<br />

Cory-Slechta<br />

et al. (2004) †<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 />

Rat/Long-Evans,<br />

adult<br />

Foote (1999) Rabbit/Dutchbelted,<br />

adult<br />

Foster et al.<br />

(1993)<br />

Foster et al.<br />

(1996a)<br />

Foster et al.<br />

(1998)<br />

Gandley et al.<br />

(1999)<br />

Gorbel et al.<br />

(2002)<br />

Monkey/<br />

Cynomolgus,<br />

adult<br />

Monkey/<br />

Cynomolgus,<br />

adult<br />

Monkey/<br />

Cynomolgus,<br />

adult<br />

Rat/Sprague-<br />

Dawley, adult<br />

Rat/(NOS),<br />

90 days old<br />

Pb acetate in drinking water<br />

beginning 2 mo be<strong>for</strong>e<br />

breeding until the end <strong>of</strong><br />

lactation<br />

0, 0.005, 0.01, and 0.025 mM<br />

PbCl2 in vitro; one time dose<br />

0–1500 µg Pb acetate/kg-d in<br />

gelatin capsules p.o. <strong>for</strong><br />

various durations: 9 control<br />

monkeys, 4 monkeys in<br />

lifetime group (birth to 9 yrs),<br />

4 in infancy group (first<br />

400 days <strong>of</strong> life), 4 in postinfancy<br />

exposure (from<br />

300 days to 9 yrs)<br />

0–1500 µg Pb acetate/kg-d in<br />

gelatin capsules p.o. from<br />

birth until 9 yrs <strong>of</strong> age:<br />

8 control monkeys, 4<br />

monkeys in low group<br />

(6-20 µg/dL), 7 monkeys in<br />

high group (22–148 µg/dL)<br />

0–1500 µg Pb acetate/kg-d in<br />

gelatin capsules p.o. <strong>for</strong><br />

various durations: birth to<br />

10 yrs (lifetime); PND 300 to<br />

10 yrs (post-infancy); birth to<br />

300 days (infancy); 3 control<br />

monkeys, 4 lifetime,<br />

4 infancy, 5 post-infancy<br />

Male rats received Pb acetate<br />

25 or 250 ppm in drinking<br />

water <strong>for</strong> 35 days prior to<br />

mating<br />

3 mg (P1) or 6 mg (P2) Pb<br />

acetate in drinking water <strong>for</strong><br />

15, 30, 45, 60, or 90 days<br />

Observed potential effects <strong>of</strong> Pb and stress in female; Pb alone (in male) and Pb plus<br />

stress (in females) permanently elevated corticosterene levels in <strong>of</strong>fspring.<br />

Six out <strong>of</strong> 22 males tested showed appreciable spontaneous hyperactivation, Pb did not<br />

affect hyperactivation, or associated capacitation.<br />

Suppressed LH response to GnRH stimulation in the lifetime group (p = 0.0370);<br />

Sertoli cell function (reduction in the inhibin to FSH ratio) (p = 0.0286) in lifetime and<br />

post-infancy groups.<br />

Mean PbB <strong>of</strong> 56 µg/dL showed no significant alterations in parameters <strong>of</strong> semen<br />

quality (count, viability, motility, or morphology).<br />

Circulating concentrations <strong>of</strong> FSH, LH, and testosterone were not altered by treatment;<br />

semen characteristics (count, motility, morphology) were not affected by treatment<br />

possibly because not all Sertoli cells were injured; degeneration <strong>of</strong> seminiferous<br />

epithelium in infancy and lifetime groups (no difference in severity between these<br />

groups); ultrastructural alterations in seminal vesicles, most prominent in infancy and<br />

post-infancy groups.<br />

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

(PbB)<br />

PbB 30–40 µg/dL<br />

PbB not applicable–in vitro study<br />

Lifetime group 3–26 µg/dL at<br />

4–5 yrs; infancy group<br />

5–36 µg/dL at 100–300 days,<br />

3–3 µg/dL at 4–5 yrs; postinfancy<br />

group 20–35 µg/dL<br />

PbB 10 ± 3 or 56 ± 49 µg/dL<br />

PbB ~35 µg/dL<br />

High dose reduced fertility; low dose altered genomic expression in <strong>of</strong>fspring. PbB 15–23 µg/dL or<br />

27–60 µg/dL<br />

Male rats, absolute and relative weights <strong>of</strong> testis, epididymis, prostate and seminal<br />

vesicles were found to significantly decrease at day 15 in P2 group and at day 45 in P1<br />

group, at day 60 these absolute values and relative weights returned to control values; at<br />

day 15 arrest <strong>of</strong> cell germ maturation, changes in the Sertoli cells, and presence <strong>of</strong><br />

apoptotic cells were observed; serum testosterone level was found to be lowered at day<br />

15 in both P1 and P2, and peaked at day 60, then returned to normal values.<br />

PbB not reported

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