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

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AX5-127<br />

Table AX5-8.2 (cont’d). Regulation <strong>of</strong> Bone Cell Function in Animals—Systemic Effects <strong>of</strong> <strong>Lead</strong><br />

Compound<br />

Dose/Concentration<br />

Duration Exposure<br />

Route Species Effects Blood Level Reference<br />

PbCl 2<br />

0, 0.2, or 0.8%<br />

1 or 2 wks<br />

In diet<br />

PbCl 2<br />

0, 0.2, or 0.8%<br />

1 or 2 wks<br />

In diet<br />

Pb acetate<br />

1% <strong>for</strong> 10 wks or<br />

0.001–1% <strong>for</strong> 24 wks<br />

In drinking water<br />

Chicks Compared with control animals, Pb exposure significantly increased intestinal calbindin<br />

protein and mRNA levels in addition to plasma 1,25-dihydroxyvitamin D concentration.<br />

The effect was present after 1 wk <strong>of</strong> exposure and continued through the second week. In<br />

calcium-deficient animals increased plasma 1,25-dihydroxyvitamin D and calbindin protein<br />

and mRNA were significantly (p < 0.05) inhibited by Pb exposure in a dose dependent<br />

fashion over the 2 wk experimental period.<br />

Chicks Dose dependent increases in serum 1,25-(OH2)D 3 levels (and Calbindin-D protein and<br />

mRNA) with increasing dietary Pb exposure (0.1% to 0.8%) in experiments per<strong>for</strong>med on<br />

Leghorn cockerel chicks fed an adequate calcium diet.<br />

Rat<br />

Short term administration <strong>of</strong> 1% Pb resulted in significant increases in bone Pb. Total<br />

serum calcium and ionized serum calcium were significantly decreased, as compared to<br />

controls. Circulating levels <strong>of</strong> 1,25-(OH 2)D 3 were also decreased, though the rats were<br />

maintained on a normal calcium diet (0.95%). In the long term study, a dose-dependent<br />

increase in parathyroid weight occurred with increasing exposure to Pb in drinking water.<br />

Short term (10 wks) exposure<br />

Serum Calcium (mM) Ionized Calcium<br />

(mM) 1,25(OH)2D 3 (pM)<br />

Parathyroid Weight (µg/gland)<br />

*p < 0.01<br />

Long term (24 wks) exposure<br />

Pb in water<br />

0%<br />

0.001%<br />

0.01%<br />

0.1%<br />

1.0%<br />

p < 0.01<br />

Controls<br />

2.42 ± 0.03<br />

1.25 ± 0.03<br />

232 ± 18.9<br />

96 ± 34<br />

Normalized Parathyroid<br />

Weight (µg/g body wt)<br />

0.50 ± 0.06<br />

0.72 ± 0.25<br />

0.81 ± 0.28<br />

0.94 ± 0.27<br />

0.81 ± 0.29*<br />

Pb-exposed<br />

2.32 ± 0.02*<br />

1.15 ± 0.03*<br />

177 ± 10.8*<br />

178 ± 25*<br />

1,25(OH) 2D 3 (pM)<br />

241 ± 32<br />

188 ± 27<br />

163 ± 17<br />

206 ± 24<br />

144 ± 33*<br />

None given Fullmer (1995)<br />

None given Fullmer et al.<br />

(1996)<br />

Short term (10 wk)<br />

study:<br />

Control:<br />

< 0.02 µg/l<br />

Pb-exposed:<br />

> 5µg/l<br />

Szabo et al. (1991)

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