Chronic low-level lead toxicity in the rat: III An integrated assessment of long-term toxicity with special reference to the kidney
Fowler, BA; Kimmel, CA; Woods, JS; McConnell, EE; Grant, LD
HERO ID
53800
Reference Type
Journal Article
Year
1980
Language
English
PMID
| HERO ID | 53800 |
|---|---|
| In Press | No |
| Year | 1980 |
| Title | Chronic low-level lead toxicity in the rat: III An integrated assessment of long-term toxicity with special reference to the kidney |
| Authors | Fowler, BA; Kimmel, CA; Woods, JS; McConnell, EE; Grant, LD |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 56 |
| Issue | 1 |
| Page Numbers | 59-77 |
| Abstract | Male and female rats whose mothers had been exposed to Pb before and during pregnancy and lactation at exposure levels of 0, 0.5, 5, 25, 50, and 250 ppm Pb as Pb-acetate in drinking water were continued on the respective regimens for 6 or 9 months. Body weights of males and females were not significantly different from controls at 6 months of age; however, female body weights were significantly decreased at 250 ppm at 9 months of age. In males at 9 months of age, spleen weights were significantly increased at 250 ppm Pb and kidney weights were increased at 0.5 ppm Pb and above; in females the liver, pituitary, and heart weights were affected at 250 ppm Pb. No significant Pb effects were found in sperm counts or sperm morphology, hematology profiles, or serum chemistries. Blood, brain, femur, and kidney Pb levels as well as urinary ALA excretion were all significantly dose related. Histopathological lesions were noted in the spleen (250 ppm) and in the kidney as evidenced by cytomegaly/karyomegaly (beginning at 5 ppm in males; 25 ppm in females), nuclear inclusion body formation and increased numbers of iron-positive granules within renal proximal tubule cells. These effects were more marked after 9 months exposure. Ultrastructural studies revealed mitochondrial swelling and the presence of increased numbers of lysosomes within renal proximal tubule cells. Energy-dispersive X-ray microanalysis, performed on adjacent sections, showed the highest intracellular Pb concentrations in nuclear inclusion bodies within renal proximal tubule cells. Inhibition of renal mitochondrial respiration for both succinate and NAD-linked substrates was found in 50- and 250-ppm Pb exposure groups at 9 months but not at 6 months. Mitochondrial ?-aminolevulinic acid synthetase and ferrochelatase, but not ?-aminolevulinic dehydratase, were also found to be inhibited at these Pb levels at 9 months. The lowest exposure level resulting in a detectable effect of Pb (cytomegaly/karyomegaly in renal proximal tubule cells) was 5 ppm associated with a median blood Pb concentration of 11 ug/dl. |
| Doi | 10.1016/0041-008X(80)90131-3 |
| Pmid | 7444967 |
| Wosid | WOS:A1980KR98600007 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |