Objectives-To study the dose-response relation between cadmium dose and renal tubular damage in a population of workers and people environmentally or occupationally exposed to low concentrations of cadmium. Methods-Early kidney damage in 1021 people, occupationally or environmentally exposed to cadmium, was assessed from cadmium in urine to estimate dose, and protein HC ( 1 -microglobulin) in urine to assess tubular proteinuria. Results-There was an age and sex adjusted correlation between cadmium in urine and urinary protein HC. The prevalence of tubular proteinuria ranged from 5% among unexposed people to 50% in the most exposed group. The corresponding prevalence odds ratio was 6.0 (95% confidence interval (95% CI) 1.6 to 22) for the highest exposure group, adjusted for age and sex. Multiple logistic regression analysis showed an increasing prevalence of tubular proteinuria with urinary cadmium as well as with age. After adjustment to the mean age of the study population (53 years), the results show an increased prevalence of 10% tubular proteinuria (taking into account a background prevalence of 5%) at a urinary cadmium concentration of 1.0 nmol/mmol creatinine. Conclusion-Renal tubular damage due to exposure to cadmium develops at lower levels of cadmium body burden than previously anticipated. (Occup Environ Med 2000;57:668-672)

No abstract

Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia. We have examined whether long-term low-level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16 -81 years, environmentally or occupationally exposed to cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used as a marker of renal tubular damage. There was a clear dose-response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age. There was a dose-response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.

Ahstrtrcr: Over 99% of the lead present in blood is usually found in erythrocytes. To investigate the nature of this selective accumulation of lead in erythrocytes, the specific binding of lead to proteins in human erythrocytes was studied using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The principal leadbinding protein had a mass of approximately 240 kDa, and adsorption to specific antibodies showed that the protein was 6-aminolevulinic acid dehydratase (ALAD). Thus, the previous notion that lead in erythrocytes was bound primarily to haemoglobin has to be revised. Furthermore, in lead-exposed workers, the percentage of lead bound to ALAD was influenced by a common polymorphism in the ALAD gene. Specifically, in seven carriers of the ALAD2 allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD' allele whose erythrocytes were matched for blood-lead concentration. The small difference was statistically significant in Wilcoxon matched-pairs signed-rank test (P=O.O3). No ALAD allele-specific difference in ALAD-bound lead was found among 20 unexposed controls. Perhaps the difference in ALAD-bound lead can provide an explanation for the previously reported finding of higher blood-lead levels among carriers of the ALAD2 allele than among ALAD' homozygotes in lead-exposed populations.

In 14 retired lead workers, followed for over 18 years after end of exposure, repeated analyses of lead levels in finger bone by an in vivo X-ray fluorescence method revealed a decrease of lead concentration. The data were analysed using an exponential retention model. For the whole group the biological half-time was 16 (asymptotic 95% confidence interval, CI 12,23) years. The median of the estimated bone lead levels at the end of exposure was 85 micrograms.g-1 above the "background" (3 micrograms.g-1). A simultaneous follow-up of blood lead levels displayed a decrease, which could be described by a tri-exponential retention model with group half-times of 34 (CI 29,41) days, 1.2 (CI 0.9,1.8) years, and 13 (CI 10,18) years, respectively. The median of the estimated blood lead levels at the end of exposure for the three components were 0.49, 0.61, and 1.1 mumol.l-1 above the "background" (0.38-0.56 mumol.l-1), respectively. The well-documented decrease of lead exposure in the general population over the years, urged the use of a decreasing "background" of blood lead during the time of the study. The slowest of the three components represented the skeleton (probably mainly cortical bone), as did mainly probably also the intermediate one (trabecular bone). The data show the rather slow turnover of lead in the skeleton, the usefulnes of in vivo skeletal lead measurements as a long-term exposure index, and the importance of bone as a source of "endogenous" lead exposure.

Objectives-To test a simple procedure for preparing samples for measurement of lead in blood plasma (P-Pb) and whole blood (B-Pb) by inductively coupled plasma mass spectrometry (ICP-MS), to measure P-Pb and B-Pb in lead workers and controls, and to evaluate any differences in the relation between B-Pb and PPb between people. Methods-P-Pb and B-Pb were measured by ICP-MS in 43 male lead smelter workers and seven controls without occupational exposure to lead. For analysis, plasma and whole blood were diluted 1 in 4 and 1 in 9, respectively, with a diluted ammonia solution containing Triton-X 100 and EDTA. The samples were handled under routine laboratory conditions, without clean room facilities. Results-P-Pb was measured with good precision (CV = 5%) even at concentrations present in the controls. Freeze storage of the samples had no effect on the results. The detection limit was 0*015 gye.The P-Pb was 0 15 (range 0.1-0.3) ug/l in controls and 1-2 (0.3-3.6) ug/l in lead workers, although the corresponding BPbs were 40 (24-59) ugll and 281 ug/l (1,ug Pb/l = 4'8 nmolIl). B-Pb was closely associated with P-Pb (r = 0.90).The association was evidently non-linear; the ratio B-Pb/P-Pb decreased with increasing P-Pb. Conclusions-By means of ICP-MS and a simple dilution procedure, P-Pb may be measured accurately and with good precision down to concentrations present in controls. Contamination of blood at sampling and analysis is no major problem. With increasing P-Pb, the percentage of lead in plasma increases. In studies of lead toxicity, P-Pb should be considered as a complement to current indicators of lead exposure and risk. (Occup Environ Med 1996;53:736-740)

No abstract

No abstract