Urinary Cadmium Levels Research Articles

Potential Confounder: Bernard and de Burbure Respond

We thank Aschner for his positive comments and interesting suggestion regarding a possible influence of manganese on serum prolactin levels. We fully acknowledge that the four elements we studied (de Burbure et al. 2006) are probably not the only determinants of serum prolactin levels, especially because variations in blood or urinary levels explained only a few percent of the total variance. Other factors, including perhaps some other metals, most probably also contribute to modulate dopaminergic function and serum prolactin levels. Because the epidemiologic evidence suggesting a link between manganese and serum prolactin in children is recent, we did not measure this metal in our study. However, if we had measured blood manganese in the children in our study, it is far from certain that this factor would have emerged as a significant determinant, possibly confounding the relationships between neurologic markers and blood or urinary levels of cadmium, mercury, and lead. In the recent study by Wasserman et al. (2006), neurocognitive deficits were indeed not related to blood concentrations of manganese. As to the correlation between blood manganese at birth and cord blood prolactin levels reported by Takser et al. (2004), this association was not adjusted for possible exposure to lead, an indisputable confounder in this sort of study. This being said, we agree of course with Aschner that exposure to manganese should be considered in future studies investigating the developmental effects of heavy metals in the environment.

Blood and urine levels of Pb, Cd and Hg in the general population of the Czech Republic and proposed reference values

The Human Biological Monitoring (HBM) project was launched in the Czech Republic in 1994 as a part of the nation-wide Environmental Health Monitoring System to assess the exposure of the Czech general population to a broad spectrum of environmental contaminants. Over the years 2001–2003, the concentrations of lead (Pb), cadmium (Cd), and mercury (Hg) were determined in whole blood of 1188 adults (blood donors) and 333 children and in urine of 657 adults and 619 children. In adults, the median blood lead (B-Pb) level was 33 μg/l. Men had higher B-Pb levels than women (medians 37 μg/l vs. 25 μg/l). Significantly higher B-Pb levels were observed in smokers compared to non-smokers (36 μg/l vs. 31 μg/l). In children, no sex-dependent differences were observed (median 31 μg/l). In total, the median blood Cd level (B-Cd) in adults was 0.5 μg/l. Smokers showed a median B-Cd level about 3 times as high as non-smokers (1.3 μg/l vs. 0.40 μg/l). Neither sex- nor age-related differences were observed in B-Cd levels. In 65% of children, B-Cd levels were below the limit of detection (LOD). The overall median urinary cadmium level (U-Cd) in adults was 0.31 μg/g creatinine. Significantly higher U-Cd levels were found in women (median 0.39 μg/g creatinine) compared to men (0.29 μg/g creatinine). No significant differences were found between smokers and non-smokers. In more than 50% of children, the U-Cd level was below the LOD (=0.2 μg/l). The median blood mercury (B-Hg) level in adults was 0.89 μg/l. Significant differences were found between smokers (0.80 μg/l) and non-smokers (0.92 μg/l), and between men and women (0.86 μg/l vs. 0.94 μg/l). The median B-Hg level in children was 0.42 μg/l and no sex-related differences were observed. The median urinary mercury (U-Hg) levels were 0.63 μg/g creatinine in adults and 0.37 μg/g creatinine in children. Significantly higher U-Hg levels were obtained in women and non-smokers compared to men and smokers, respectively. The B-Pb, B-Hg, U-Cd, and U-Hg levels significantly correlated with age. The following reference values were recommended for the period 2001–2003: 80, 65 and 55 μg/l for B-Pb and 3.1, 4.0 and 1.5 μg/l for B-Hg in men, women and children, respectively; 1.1 μg/l and 1.2 μg/g creatinine for B-Cd and U-Cd, respectively, in adult non-smokers; 5.4 and 12.0 μg/g creatinine for U-Hg in men and women, respectively, and 3.7 and 5.5 μg/g creatinine for U-Hg in boys and girls, respectively. The previous reference values for B-Pb and B-Cd needed revision and were reduced.

Cadmium, lead and endometriosis

Cadmium (Cd) and lead (Pb) have been demonstrated to exert endocrine disrupting activities. Their possible role in endometriosis, an oestrogen-dependent disease, is unknown. We compared cadmium urinary excretion (CdU) and blood concentration of cadmium (CdB) and lead (PbB) in 119 patients with peritoneal endometriosis and/or deep endometriotic (adenomyotic) nodules of the rectovaginal septum and 25 controls. The mean levels of cadmium in urine and blood did not differ among the groups. Women suffering from endometriotic diseases showed lower levels of PbB than controls. These data do not support a role for cadmium in the onset or the growth of endometriotic diseases but suggest a possible relationship with lead.

Estimation of benchmark dose as the threshold levels of urinary cadmium, based on excretion of total protein, β2-microglobulin, and N-acetyl- β- d-glucosaminidase in cadmium nonpolluted regions in Japan

Previously, we investigated the association between urinary cadmium (Cd) concentration and indicators of renal dysfunction, including total protein, β 2-microglobulin ( β 2-MG), and N-acetyl- β- d-glucosaminidase (NAG). In 2778 inhabitants ⩾50 years of age (1114 men, 1664 women) in three different Cd nonpolluted areas in Japan, we showed that a dose–response relationship existed between renal effects and Cd exposure in the general environment without any known Cd pollution. However, we could not estimate the threshold levels of urinary Cd at that time. In the present study, we estimated the threshold levels of urinary Cd as the benchmark dose low (BMDL) using the benchmark dose (BMD) approach. Urinary Cd excretion was divided into 10 categories, and an abnormality rate was calculated for each. Cut-off values for urinary substances were defined as corresponding to the 84% and 95% upper limit values of the target population who have not smoked. Then we calculated the BMD and BMDL using a log-logistic model. The values of BMD and BMDL for all urinary substances could be calculated. The BMDL for the 84% cut-off value of β 2-MG, setting an abnormal value at 5%, was 2.4 μg/g creatinine (cr) in men and 3.3 μg/g cr in women. In conclusion, the present study demonstrated that the threshold level of urinary Cd could be estimated in people living in the general environment without any known Cd-pollution in Japan, and the value was inferred to be almost the same as that in Belgium, Sweden, and China.

The effects of cadmium on the levels of insulin in smelters

To investigate the effects of cadmium on the levels of insulin and blood glucose in exposed workers. Ninety-eight cadmium-exposed workers in a smeltery in the mid-south district of our country were selected as the exposed subjects while the healthy doctors in the workers hospital who were not exposed to the cadmium were treated as the control. The subjects were grouped according to the exposure time, the blood cadmium and the urine cadmium. The variety of the level of serum insulin was investigated for the workers in different groups of the exposure time, the blood cadmium and the urine cadmium. The variety of the levels of the blood zinc and urine zinc were also determined. The relationships among the blood cadmium, the blood zinc and the serum insulin were analyzed. The level of blood glucose in the group of the exposure time of more than 20 years [(4.9 +/- 0.6) mmol/L] was significantly higher than that in the control group [(4.6 +/- 0.60) mmol/L] with significantly statistical difference (P < 0.01). The level of serum insulin in the group of the exposure time of more than 10 years [(8.58 +/- 4.91) microIU/ml] was significantly lower than that in the control group [(11.57 +/- 5.42) microIU] with the significantly statistical difference (P < 0.05) and the level of serum insulin would be decreased significantly with the increase of the blood cadmium and urinary cadmium. The level of the urine zinc was increased significantly in the workers of the exposure time of more than 20 years. The correlation analysis indicated that the negative correlation was found between the level of serum insulin and the level of blood cadmium, as well as between the level of the serum insulin and the level of the urinary cadmium; the positive correlation was found between the level of blood glucose and the level of insulin, as well as between the level of blood glucose and the level of C peptide in serum. The exposure to cadmium can cause the decrease of serum insulin and may affect the level of blood glucose.

Plasma Metallothionein Antibody and Cadmium-Induced Renal Dysfunction in an Occupational Population in China

It has been reported that anti-metallothionein (a metallothionein antibody) is present in the circulation of healthy subjects and in patients suffering from atopic dermatitis. The aim of this study was to investigate whether cadmium-induced renal dysfunction is related to the presence of the plasma metallothionein antibody (MT-Ab) in workers exposed to cadmium (Cd) occupationally. Plasma metallothionein antibody was determined by enzyme linked immunosorbent assay (ELISA) techniques, and both exposure assessment and risk assessment were conducted in cadmium-exposed workers in China. We demonstrate that there is a significantly increased prevalence of renal dysfunction with respect to the level of urinary cadmium in a dose-dependent manner. We found no significant correlations between the levels of MT-Ab and the external or internal exposure doses of cadmium (p > 0.05), but the levels of MT-Ab did correlate positively with two biomarkers of renal dysfunction-urinary beta2-microglobulin (UB2M; r = 0.218, p < 0.05) and N-acetyl-beta-D-glucosaminidase (UNAG; r = 0.302, p < 0.001)-in the cadmium-exposed workers. Workers who have high levels of MT-Ab display cadmium-induced tubular nephrotoxicity more frequently than those possessing low levels of MT-Ab; odds ratio (OR) 4.2; 95% confidence intervals 1.2-14.5 (p < 0.05). This study suggests that subjects that have higher MT-Ab levels more readily develop cadmium-induced renal dysfunction. Thus, the levels of plasma MT-Ab can be used as a biomarker of susceptibility to renal dysfunction in occupational cadmium exposure.

Graded Associations of Blood Lead and Urinary Cadmium Concentrations with Oxidative-Stress–Related Markers in the U.S. Population: Results from the Third National Health and Nutrition Examination Survey

Although oxidative stress has been proposed as a mechanism of lead and cadmium toxicity mostly based on in vitro experiments or animal studies, it is uncertain whether this mechanism is relevant in the pathogenesis of lead- or cadmium-related diseases in the general population with low environmental exposure to lead and cadmium. We examined associations of blood lead and urinary cadmium levels with oxidative stress markers of serum γ-glutamyltransferase (GGT), vitamin C, carotenoids, and vitamin E among 10,098 adult participants in the third U.S. National Health and Nutrition Examination Survey. After adjusting for race, sex, and age (plus serum total cholesterol in the case of serum carotenoids and vitamin E), blood lead and urinary cadmium levels both showed graded associations, positive with serum GGT and inverse with serum vitamin C, carotenoids, and vitamin E (p for trend < 0.01, respectively). These associations were consistently observed among most subgroups: non-Hispanic white, non-Hispanic black, men, women, all age groups, non-drinkers, drinkers, nonsmokers, ex-smokers, current smokers, and body mass index (< 25, 25–29.9, and ≥30). The strong association of blood lead and urinary cadmium levels with oxidative stress markers in this population suggests that oxidative stress should be considered in the pathogenesis of lead- and cadmium-related diseases even among people with low environmental exposure to lead and cadmium.

Exposure to Lead, Cadmium and Chromium among Spray Painters in Automobile Body Repair Shops

Environmental and biological monitoring of lead, cadmium and chromium levels in spray painters is reported. All of the study subjects worked in automobile body repair shops that had no standard spraying room. They were divided into 2 groups, those who wore an aerosol-removing respirator while spraying (n=20) and those who did not wear the respirator (n=50). Air in the breathing zone of each subject was sampled and analyzed for lead, cadmium and chromium levels. The subjects' blood lead levels and urinary cadmium and chromium levels were also measured along with those of a control group. The mean environmental and biological levels of these metals between the two groups of the painters were not significantly different (p>0.05). However, the biological levels of the metals were significantly higher in the study groups than in the control group (p<0.01). On-site observations revealed that improper use of an aerosol-removing respirator, lack of an isolated spraying room and poor personal hygiene habits caused the failure to prevent heavy metal exposure among the automobile spray painters.

Renal and Neurologic Effects of Cadmium, Lead, Mercury, and Arsenic in Children: Evidence of Early Effects and Multiple Interactions at Environmental Exposure Levels

Lead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children’s health is little known. We studied their effects on two main targets, the renal and dopaminergic systems, in > 800 children during a cross-sectional European survey. Control and exposed children were recruited from those living around historical nonferrous smelters in France, the Czech Republic, and Poland. Children provided blood and urine samples for the determination of the metals and sensitive renal or neurologic biomarkers. Serum concentrations of creatinine, cystatin C, and β2-microglobulin were negatively correlated with blood lead levels (PbB), suggesting an early renal hyperfiltration that averaged 7% in the upper quartile of PbB levels (> 55 μg/L; mean, 78.4 μg/L). The urinary excretion of retinol-binding protein, Clara cell protein, and N-acetyl-β-d-glucosaminidase was associated mainly with cadmium levels in blood or urine and with urinary mercury. All four metals influenced the dopaminergic markers serum prolactin and urinary homovanillic acid, with complex interactions brought to light. Heavy metals polluting the environment can cause subtle effects on children’s renal and dopaminergic systems without clear evidence of a threshold, which reinforces the need to control and regulate potential sources of contamination by heavy metals.

Low-level cadmium exposure in Toyama City and its surroundings in Toyama prefecture, Japan, with references to possible contribution of shellfish intake to increase urinary cadmium levels

Objectives This study was initiated to examine if exposure to cadmium (Cd) was high also outside of the previously identified Itai-itai disease endemic region in the Jinzu River basin in Toyama prefecture in Japan. Methods Morning spot urine samples were collected in June–August 2004 from 651 adult women (including 535 never-smokers) in various regions in Toyama prefecture, and subjected to urinalyses for cadmium (Cd), α 1-microglobulin (α 1-MG), β 2-microglobulin (β 2-MG), N-acetyl-β- d-glucosaminidase (NAG), specific gravity (SG or sg) and creatinine (CR or cr). Three months later, the second urine samples were collected from those with elevated Cd in urine (e.g., ≧ 4 μg/g cr), together with answers to questionnaires on shellfish consumption. Results The geometric mean (GM) Cd, α 1-MG, β 2-MG and NAG (after correction for CR) for the total participants were 2.0 μg/g cr, 2.4 mg/g cr, 104 μg/g cr and 2.8 units/g cr, respectively; further analysis with never-smoking cases only did not induce significant changes in these parameters. Analyses of the second urine samples from the high Cd subjects showed that there was substantial decrease (to about a half) in Cd in the 3-month period, and that the decrease was accompanied by reduction in α 1-MG and NAG (β 2-MG did not show elevation even in the first samples). The urinalysis results in combination with the results of the questionnaire survey suggest that the high urinary Cd was temporary and might be induced by intake of shellfish that is edible whole. Conclusions The overall findings appear to suggest that Cd exposure in Toyama populations (outside of the Itai-itai disease endemic region) was at the levels commonly observed on the coast of the Sea of Japan, and that the Cd level in urine might be modified by the intake of some types of seafood. Further studies are necessary to elucidate the relation of urinary Cd with seafood intake.

CADMIUM BODY BURDEN IN RELATION TO CONCENTRATIONS IN SOIL AND VEGETABLES IN AN ENVIRONMENTALLY EXPOSED POPULATION

ISEE-122 Introduction: It is well known that cadmium exposure may cause kidney damage, initially detected as a tubular dysfunction, assessed by measuring certain proteins and enzymes in urine. Recent studies have indicated that the kidney damage may occur also at low levels of environmental cadmium exposure. Cadmium body burden can be estimated by cadmium in urine (U-Cd), and a Swedish study (the OSCAR study) has shown a dose-response relationship with a ten percent prevalence of tubular proteinuria at U-Cd = 1.0. Aim: However, the exposure pathways are less clear and the present study aimed to assess the relative impact of different pathways of exposure to cadmium on the absorbed dose and body burden in a subgroup of the OSCAR population, who lived near a battery plant. The study also aimed to evaluate the contribution of locally produced food (vegetables) to total dietary cadmium intake. Methods: Cadmium levels in urine were determined in 492 individuals living near a closed down battery factory in Sweden. For each individual we created an environmental exposure-index based on emission data from the factory and number of years living at various distances from the plant. These data, as well as information on dietary habits and confounders, were collected via questionnaires. Samples of soil, carrots and/or potatoes were collected from 38 gardens and analyzed for cadmium. Results: Cadmium concentrations in carrots, potatoes and soil were high in the area near the factory. Daily consumption of potatoes and vegetables grown in the vicinity of the battery plant was estimated to increase cadmium intake by 40-60%. Increased U-Cd concentrations of cadmium (over 1.0 nmol/mmol creatinine) were significantly associated with intake of homegrown vegetables, environmental cadmium-exposure-index, female gender, age above 30 years and smoking an amount equivalent to one pack of cigarettes for more than 10 years. No increased U-Cd levels were shown in non-smokers, who did not eat homegrown vegetables, suggesting negligible exposure via ambient air. Conclusion: The present study shows that consumption of locally grown food constituted an important exposure pathway in subjects living near a nickel-cadmium battery plant, whereas exposure via ambient air was less important.

Health effects of cadmium exposure in the general environment in Japan with special reference to the lower limit of the benchmark dose as the threshold level of urinary cadmium

This study investigates renal dysfunction in areas without known environmental cadmium pollution and calculates the threshold level of urinary cadmium. Urinary total protein, beta2-microglobulin (beta2-MG), and N-acetyl-beta-D-glucosaminidase (NAG), used as indicators of renal dysfunction, and urinary cadmium concentration, used as an indicator of cadmium exposure, were measured in two sets of 24-hour urine samples from each of 828 participants (410 men, 418 women), aged 40-59 years and living in three areas without any known environmental cadmium pollution. In multiple regression and logistic regression analyses the association between indicators of cadmium exposure and indicators of renal dysfunction were studied. The lower 95% confidence limit of the dose (benchmark dose) corresponding to a 5% (BMDL5) or 10% (BMDL10) level of each indicator of renal dysfunction above the background level) was calculated as the threshold level of urinary cadmium. With all the expressed units [g creatinine(-1) and day(-1)] in the multiple regression analysis, the partial regression coefficients showed a significant association between urinary cadmium concentration and total protein, beta2-MG, and NAG for both genders, except for total protein for women (g creatinine(-1) and day(-1). The same results were obtained for both genders in the logistic regression analysis. The BMDL10 was 0.6-1.2 microg/g creatinine and 0.8-1.6 microg/day for the men and 1.2-3.6 microg/g creatinine, and 0.5-4.7 microg/day for the women. Cadmium exposure and the levels of the indicators of renal dysfunction were associated among the men and women aged 40-59 years in areas without any known environmental cadmium pollution. The threshold level of urinary cadmium in Japan seems to be almost the same as in Belgium and Sweden.

Tubular and Glomerular Kidney Effects in Swedish Women with Low Environmental Cadmium Exposure

Cadmium is a well-known nephrotoxic agent in food and tobacco, but the exposure level that is critical for kidney effects in the general population is not defined. Within a population-based women’s health survey in southern Sweden (Women’s Health in the Lund Area, WHILA), we investigated cadmium exposure in relation to tubular and glomerular function, from 1999 through early 2000 in 820 women (71% participation rate) 53–64 years of age. Multiple linear regression showed cadmium in blood (median, 0.38 μg/L) and urine (0.52 μg/L; density adjusted = 0.67 μg/g creatinine) to be significantly associated with effects on renal tubules (as indicated by increased levels of human complex-forming protein and N-acetyl-β-d-glucosaminidase in urine), after adjusting for age, body mass index, blood lead, diabetes, hypertension, and regular use of nephrotoxic drugs. The associations remained significant even at the low exposure in women who had never smoked. We also found associations with markers of glomerular effects: glomerular filtration rate and creatinine clearance. Significant effects were seen already at a mean urinary cadmium level of 0.6 μg/L (0.8 μg/g creatinine). Cadmium potentiated diabetes-induced effects on kidney. In conclusion, tubular renal effects occurred at lower cadmium levels than previously demonstrated, and more important, glomerular effects were also observed. Although the effects were small, they may represent early signs of adverse effects, affecting large segments of the population. Subjects with diabetes seem to be at increased risk.

Smoking-induced increase in urinary cadmium levels among Japanese women

To examine if cigarette smoking will induce elevation in cadmium (Cd) in urine. Information on smoking habits, and urinary levels of cadmium (Cd-U), alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), creatinine (CR or cr), and urine specific gravity (SG or sg) was cited from a combination of three previously established databases on adult Japanese women. After exclusion of those with unclear answers on smoking habits (412 cases), the combination (12,846 cases) gave 11,092, 1420 and 334 cases of never, current and former smokers, respectively, for present statistical analyses. Multiple regression analyses taking Cd-U as a dependent variable and 11 regions of urine collection, age and smoking habits as independent variables showed that age and regions were powerful confounders in the analysis for the effects of smoking on Cd-U. To exclude the confounding effects, current and former smokers were paired with age- and region-matched never smoking controls in subsequent analyses. In addition, former smokers were paired with age- and region-matched current smokers. The comparison of the paired cases showed that Cd-U for current smokers was significantly higher than that for never smokers. The levels for former smokers were however not higher than the levels for never smokers. When classified by the number of cigarettes consumed per day, Cd-U for current smokers increased dependently to the number of cigarettes (about 0.09 microg/cigarette/day) with leveling off at 15 or more cigarettes. There was a subtle cigarette dose-dependent increase in alpha(1)-MG, but the increase was insignificant in case of beta(2)-MG. Estimation of the amount of Cd absorbed due to cigarette smoking followed by comparison with the increase in Cd-U suggested that almost all Cd absorbed will be excreted into urine. Among currently smoking Japanese women, cadmium in urine increased in a manner dependent to the number of cigarettes consumed daily. Thus, smoking is a confounder of Cd-U evaluation even among the population with relatively high dietary Cd burden.

Metallothionein gene expression in peripheral lymphocytes and renal dysfunction in a population environmentally exposed to cadmium

In order to study the validity of metallothionein (MT) gene expression in peripheral blood lymphocytes (PBLs) as a biomarker of cadmium exposure and susceptibility to renal dysfunction, MT mRNA levels were measured using reverse transcription polymerase chain reaction (RT-PCR) in PBLs from residents living in a cadmium-contaminated area. MT mRNA levels were found to increase with the increase of blood cadmium (BCd) and urinary cadmium (UCd) levels. Basal MT mRNA levels were significantly correlated with the logarithm of BCd levels and the logarithm of UCd levels confirming that MT expression in PBLs is a biomarker of cadmium exposure and internal dose. An inverse relationship was observed between in vitro induced MT-mRNA level in PBLs and urinary N-acetyl-β- d-glucosaminidase (UNAG) suggesting that MT gene expression in PBLs may be used as a biomarker of susceptibility to renal toxicity of cadmium.

Urinary Cadmium and Serum Levels of Estrogens and Androgens in Postmenopausal Japanese Women

Recent laboratory studies have suggested that cadmium is an estrogenic compound and may be a potential risk factor for breast cancer. We investigated the relationship between urinary cadmium concentrations and serum concentrations of estrone, testosterone, and dehydroepiandrosterone sulfate in 164 postmenopausal Japanese women. There was a significant positive association between the urinary cadmium and serum testosterone levels after controlling for age and body mass index. The mean testosterone level was 28% higher in women with high urinary cadmium (> or = 3.00 microg/g creatinine) than in those with low urinary cadmium (< 2.00 microg/g creatinine). Urinary cadmium was not significantly associated with serum estrone and dehydroepiandrosterone sulfate levels. Additional adjustment for smoking, alcohol and reproductive factors including known risk factors for breast cancer did not substantially alter the results. Data suggested that cadmium exposure is associated with increased testosterone levels. As high testosterone levels have been associated with the risk of breast cancer, the involvement of cadmium exposure in breast cancer risk should be evaluated in future studies.

Blood Pb, Urine Cd and Health Assessment of Residents in the Vicinity of Abandoned Mines in Gyeongsangbuk-do

Objectives: The objective of this health assessment is to evaluate the health risks that may result from exposure to abandoned mine tailings in Gyeongsangbuk-do. The tailings are remnants from an earlier flotation mill and mining operation that was in business from the early 1930’s until 1970. M e t h o d s: The soil, stream water, and drinking water in and around three abandoned mine areas, Soochul, Gumjang, Darock, and three control areas located in Gyeongsangbuk-do were analyzed for level of Cd, Pb, Cu, As, and Hg. Potential chronic health effects were evaluated by interview and medical examination. Results: Some soil and stream samples exceeded the Korean standard for soil contamination in farmland and the Korean standard of water contamination in streams respectively. Blood lead (5.37 μg/dl) and urine cadmium (2.79 μg/g Cr) levels of the residents in the vicinity of the abandoned mine sites were significantly higher than of the residents in the control areas (blood lead, 4.34 μg/dl; urine cadmium, 1.62 μg/g Cr). There were no significant differences between the mining and control areas in terms of blood pressure, Hb, BUN, creatinine, SGOT, SGPT, fasting blood sugar, and the prevalence of potential chronic diseases. Conclusions: The results of the assessment suggested that the three abandoned mine sites do not pose an apparent health risk to nearby residents. Nevertheless, the elevated blood lead and urine cadmium levels in the residents of the abandoned mine site suggested that it might be an important source of heavy metals contamination. Therefore, a nationwide evaluation program is needed to assess the potential health risks of residents living in the vicinity of abandoned mine sites.

Reproducibility of Urinary Cadmium, α1-Microglobulin, and β2-Microglobulin Levels in Health Screening of the General Population

The present study examined whether levels of cadmium, and alphal- and beta2-microglobulin in urine (Cd-U, ac-MG-U, and beta2-MG-U, respectively) were reproducible in urine samples collected from the same subjects on multiple occasions. For this purpose, two databases on background exposure to cadmium in Japan-one from study I between 2000 and 2001 and the other from study II in 2002-were revisited to find 231 apparently healthy, nonpregnant, nonlactating adult women who participated in both studies and thus had provided two urine samples. The databases contained information on Cd-U, alphal,-MG-U, and beta2-MG-U, creatinine (CR), and specific gravity (SG) as well as smoking and other lifestyle factors. Of the 231 women, 195 who had never smoked were selected for the present analysis. Cd-U as well as alpha1-MG-U were reproducible (e.g., with correlation coefficients [r] between study I and II results of 0.4 to 0.6) when measured on two occasions 9 to 10 months apart. The r values were lower for beta2-MG-U (r0.3). Exclusion of urine samples with inadequate urine density(i.e., CR <0.5 or >3.0 g/L or SG <1.010 or >1.030) resulted in substantial improvement of the agreements between the two measures (e.g., r = 0.6 to 0.7 for Cd-U and alpha1-MG-U). CR and SG correlated closely with each other, especially in low-density urine samples (r >0.9), and therefore the effects of CR and SG could not be evaluated separately. In the overall evaluation,single determination (i.e., without repeated urine sampling) of Cd-U and alpha1-MG-U should be acceptable, and it may also be acceptable for beta2-MG-U. Use of samples with adequate urine density rather than application of density correction to low-density urine samples in recommended.

Metals in urine and peripheral arterial disease.

Exposure to metals may promote atherosclerosis. Blood cadmium and lead were associated with peripheral arterial disease (PAD) in the 1999–2000 National Health and Nutrition Examination Survey (NHANES). In the present study we evaluated the association between urinary levels of cadmium, lead, barium, cobalt, cesium, molybdenum, antimony, thallium, and tungsten with PAD in a cross-sectional analysis of 790 participants ≥40 years of age in NHANES 1999–2000. PAD was defined as a blood pressure ankle brachial index < 0.9 in at least one leg. Metals were measured in casual (spot) urine specimens by inductively coupled plasma–mass spectrometry. After multivariable adjustment, subjects with PAD had 36% higher levels of cadmium in urine and 49% higher levels of tungsten compared with noncases. The adjusted odds ratio for PAD comparing the 75th to the 25th percentile of the cadmium distribution was 3.05 [95% confidence interval (CI), 0.97 to 9.58]; that for tungsten was 2.25 (95% CI, 0.97 to 5.24). PAD risk increased sharply at low levels of antimony and remained elevated beyond 0.1 μg/L. PAD was not associated with other metals. In conclusion, urinary cadmium, tungsten, and possibly antimony were associated with PAD in a representative sample of the U.S. population. For cadmium, these results strengthen previous findings using blood cadmium as a biomarker, and they support its role in atherosclerosis. For tungsten and antimony, these results need to be interpreted cautiously in the context of an exploratory analysis but deserve further study. Other metals in urine were not associated with PAD at the levels found in the general population.

Low level cadmium exposure, renal and bone effects - the OSCAR study

It is well known that high cadmium exposure causes renal damage, osteoporosis and osteomalacia, whereas the dose-response relationships at low-level exposure are less well established. WHO estimated (1992) that a urinary excretion of 10 nmol/mmol creatinine would constitute a 'critical limit' below which kidney damage would not occur. Later, Belgian and Swedish studies have shown signs of cadmium induced kidney dysfunction in the general population already at urinary cadmium levels around 2-3 nmol/mmol creatinine. The Swedish OSCAR (OSteoporosis-CAdmium as a Risk factor) study comprised 1021 individuals, exposed to cadmium in the environment. Blood and urinary cadmium were used as dose estimates. Protein HC (alpha-1-microglobulin) was used as an indicator of renal tubular damage. Forearm bone mineral density (BMD) was assessed with DXA (dual energy x-ray absorptiometry) technique. The study showed that tubular proteinuria occurred at much lower levels of cadmium dose than previously known. A negative dose-effect relationship was found between cadmium dose and BMD for people at the age of 60 or older. In this age group, there was also a dose-response relationship, showing a three-fold increased risk of low BMD in the group with urinary cadmium over 3 nmol/mol creatinine, as compared to the lowest dose group. There was also evidence of an increased risk of forearm fractures with increasing cadmium levels in the population 50 years of age or older. The potential public health consequences of low level cadmium exposure should be recognized, and measures taken to reduce cadmium exposure to an absolute minimum.