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

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AX5-129<br />

Table AX5-8.3. Bone Cell Cultures Utilized to Test Effects <strong>of</strong> <strong>Lead</strong><br />

Compound<br />

Dose/Concentration<br />

Duration Exposure<br />

Route Species Effects Blood Level Reference<br />

Stable “Pb”<br />

5 mg/mL in drinking<br />

water given during<br />

gestation.<br />

On GD 18, 50 µCi<br />

210 Pb given i.v. to<br />

pregnant dams<br />

210 Pb nitrate<br />

6.5 to 65 µM<br />

5 min to 2 h<br />

In medium<br />

210 Pb nitrate<br />

5 µM<br />

20 hours<br />

In medium<br />

Pb acetate<br />

0 to 50 µM<br />

20 h<br />

In medium<br />

Rat<br />

(fetal bone<br />

organ culture)<br />

Mice<br />

(bone cell<br />

isolation from<br />

calvaria)<br />

Mice<br />

(osteoclastic<br />

bone cell<br />

isolation from<br />

calvaria)<br />

Mice<br />

(osteoclastic<br />

bone cell<br />

isolation from<br />

calvaria)<br />

PTH (3885 IU/mg bone) enhanced cell-mediated release <strong>of</strong> 210 Pb from bone. Release<br />

<strong>of</strong> 210 Pb was accompanied by proportional loss <strong>of</strong> stable Pb and calcium from treated<br />

bones.<br />

Time: Release <strong>of</strong> 210 Pb (EM/CM ratio)<br />

0 min 1.00<br />

10 min 0.82 ± 0.05<br />

2 hr 1.12 ± 0.04<br />

6 hr 1.59 ± 0.08*<br />

24 hr 3.69 ± 0.15*<br />

48 hr 3.75 ± 0.09*<br />

48 hr 0.78 ± 0.14* (in presence <strong>of</strong> 30 mU/mL salmon calcitonin)<br />

*Different from 1.00, p < 0.01.<br />

Uptake <strong>of</strong> 210 Pb by OC cells rapid.<br />

OC cells have greater avidity <strong>for</strong> Pb compared to OB cells.<br />

OC cell uptake <strong>of</strong> Pb almost linear vs. little increase in Pb uptake by OB cells with<br />

increasing Pb concentrations in media.<br />

15–30% release <strong>of</strong> 210 Pb label occurred in OC cells over 2 h time period.<br />

Physiological concentrations <strong>of</strong> PTH resulted in marked increase in 210 Pb and 45 Ca<br />

uptake by OC cells. 210 Pb uptake linear over PTH concentrations <strong>of</strong> 50 to 250 ng/mL).<br />

Media concentrations <strong>of</strong> Pb $26 µM enhanced calcium uptake by cells.<br />

Three readily exchangeable kinetic pools <strong>of</strong> intracellular Pb identified, with the<br />

majority (~78%) associated with the mitochondrial complex.<br />

Cultures were labeled with 45 Ca (25 µCi/mL) <strong>for</strong> 2 or 24 h and kinetic parameters<br />

were examined by analysis <strong>of</strong> 45 Ca washout curves.<br />

In kinetic analysis using dual-label (1–2 µCi/mL 210 Pb and 25 µCi/mL 45 Ca) wash out<br />

curves, the Ca:Pb ratios <strong>of</strong> the rate constants were ~1:1, suggesting similar cellular<br />

metabolism.<br />

Not given/not<br />

applicable<br />

Rosen and Wexler<br />

(1977)<br />

Not applicable Rosen (1983)<br />

Not applicable Pounds and Rosen<br />

(1986)<br />

Not applicable Rosen and Pounds<br />

(1988)

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