Chronic exposure of mice to environmentally relevant, low doses of cadmium leads to early renal damage, not predicted by blood or urine cadmium levels.
Mice were exposed to cadmium (Cd) concentrations ranging from 0 to 100mg CdCl(2)/l in the drinking water for 1, 4, 8, 16 and 23 weeks. Urine samples were taken regularly, Cd content was determined in blood, liver, kidney and urine and histological analyses of the kidney were performed. Kidney cortex Cd content increased linearly with time and dose, while blood levels reached a plateau at 8 weeks and liver at 16 weeks in mice exposed to 100mg CdCl(2)/l after which both started to decrease. Urinary Cd levels were not correlated with the kidney Cd content. A multivariate regression model taking into account the actual Cd intake, calculated from the volume of water taken in by each animal and the exposure concentration, confirmed that blood is an indicator of acute exposure, while kidney Cd content is a reliable indicator of chronic exposure. The urinary protein content was significantly increased from 16 weeks on in mice exposed to 100mg CdCl(2)/l (p<0.05), while other signs of proximal tubular damage (glucosuria, enzymuria) were not detected. Histologically more vacuoles and lysosomes were present in the proximal tubule cells with increasing time and dose. The results indicate that chronic exposure to low doses of Cd induced functional and histological signs of early damage at concentrations in or below the ones generally accepted as safe. Our study does not corroborate the statement that urine Cd levels are a reliable indicator of total Cd body burden, at least when the body burden is low.
Thijssen
Sandy
S
Centre for Environmental Sciences, Transnationale Universiteit Limburg, School of Life Sciences, Hasselt University, Agoralaan building D, B-3590 Diepenbeek, Belgium. sandy.thijssen@uhasselt.be
Maringwa
John
J
Faes
Christel
C
Lambrichts
Ivo
I
Van Kerkhove
Emmy
E
D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000652:urine; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004781:Environmental Exposure / Q000032:analysis; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000652:urine; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015999:Multivariate Analysis; D010784:Photomicrography / Q000379:methods; D011507:Proteinuria / Q000652:urine; D012044:Regression Analysis; D013054:Spectrophotometry, Atomic; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
D015415:Biomarkers; D019256:Cadmium Chloride