Significance of urinary metallothionein in workers exposed to cadmium

Summary Cadmium in blood (Cd-B) and in urine (Cd-U) and metallothionein (Mt-U) and ₂-microglobulin in urine ( ₂m-U) were measured in 94 male Cd workers. The results were examined according to the workers' current exposure to cadmium (group C, n=73, workers currently exposed to Cd; group R, n=21, Cd workers removed from exposure or retired) and according to their renal status (group N, n=66, normal ₂m-U; group 1, n=28, ₂m-U>200 g/g creatinine). The interrelationships between Mt-U, Cd-U, Cd-B and years of cadmium exposure were examined in the various subgroups. The study of the correlations between these variables demonstrates that Mt-U is directly correlated with Cd-U but not with Cd-B or years of Cd exposure. The association between Cd-U and Mt-U is independent of the status of renal function and the intensity of current exposure to cadmium. Under moderate chronic exposure to cadmium, the fraction of Cd-U which is directly influenced by recent exposure (Cd-B) is small in comparison with that influenced by the cadmium body burden.     

Occupational exposure to cadmium and kidney dysfunction

Summary Investigations were carried out in an alkaline battery factory. The study group consisted of 102 persons and the control group of 85 persons. Cadmium in blood (Cd-B) and cadmium in urine (Cd-U), as well as ₂-microglobulin (B₂-M), retinol binding protein (RBP), amino acids in urine were determined. Exposure to cadmium was high; Cd-B and Cd-U concentrations were higher than recommended, 10 gmg/l and 10 gmg/g creat. in 65% and 56% of workers, respectively. Excretion of B₂-M and RBP in urine was higher than the accepted upper limits of 380 and 130 I g/g creat. in about 20% of the workers. A significant correlation was observed between: log Cd-U log Cd-B (r = 0.85), log B₂-M log RBP (r = 0.66), log Cd-U · log B₂- M (r = 0.52), and log Cd-U · log RBP (r = 0.55). To evaluate the admissible period of occupational exposure to cadmium, an integrated exposure index (Cd-B × years of exposure) is proposed. According to the dose-response relationship, an increase of low molecular protein excretion in urine can be expected in 10% of the cases at Cd-U amounting to 10 to 15 g/g creat. and Cd-B × years of about 300 to 400.     

Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium.

Cadmium (Cd) was the third heavy metal investigated in the European collaborative research project on the development and validation of new markers of nephrotoxicity. Fifty workers exposed to Cd and 50 control workers were examined. After application of selection criteria 37 workers (mean age 43) exposed to Cd for an average of 11.3 years; and 43 age matched referents were retained for final analysis. The average concentrations of Cd in blood (Cd-B) and urine (Cd-U) of exposed workers were 5.5 micrograms Cd/l and 5.4 micrograms Cd/g creatinine respectively. By contrast with lead and mercury, Cd had a broad spectrum of effects on the kidney, producing significant alterations in amounts of almost all potential indicators of nephrotoxicity that were measured in urine--namely, low and high molecular weight proteins, kidney derived antigens or enzymes, prostanoids, and various other biochemical indices such as glycosaminoglycans and sialic acid. An increase in beta 2-microglobulin and a decrease of sialic acid concentration were found in serum. Dose-effect/response relations could be established between most of these markers and Cd-U or Cd-B. The thresholds of Cd-U associated with a significantly higher probability of change in these indicators were estimated by logistic regression analysis. Three main groups of thresholds could be identified: one around 2 micrograms Cd/g creatinine mainly associated with biochemical alterations, a second around 4 micrograms Cd/g creatinine for high molecular weight proteins and some tubular antigens or enzymes, and a third one around 10 micrograms Cd/g creatinine for low molecular weight proteins and other indicators. The recent recommendation by the American Conference of Governmental Industrial Hygienists (ACGIH) of 5 micrograms Cd/g creatinine in urine as the biological exposure limit for occupational exposure to Cd appears thus justified, although for most of the effects occurring around this threshold the link with the subsequent development of overt Cd nephropathy is not established. In that respect, the very early interference with production of some prostanoids (threshold 2 micrograms Cd/g creatinine) deserves further investigation; although this effect might contribute to protect the filtration capacity of the kidneys, it might also play a part in the toxicity of Cd on bone.     

The relationship between cadmium exposure or body burden and the concentration of cadmium in blood and urine in man

Summary Cadmium concentration in whole blood (Cd-B) and in urine (Cd-U) has been determined in more than 100 workers exposed to cadmium and in a comparable group of non-exposed workers. The relationship between both parameters and the duration of employment or the intensity of current exposure has been analyzed.In control workers slightly exposed to environmental pollution by cadmium, Cd-U but not Cd-B is significantly correlated with duration of exposure.In exposed workers both Cd-U and Cd-B are correlated with the intensity of exposure but not with the duration of exposure. It is suggested that Cd-B reflects current exposure but that Cd-U may reflect body burden of cadmium when exposure is low (environmental pollution) and current exposure when exposure is high (industrial situations).This work was supported by the Commission des Communautés Européennes and the Fonds National de la Recherche Scientifique.     

Closer correlation of cadmium in urine than that of cadmium in blood with tubular dysfunction markers in urine among general women populations in Japan

Objectives  

The objectives of the present study are to investigate whether cadmium in blood (Cd-B) and cadmium in urine (Cd-U) correlate with each other irrespective of age among general populations and which one of Cd-B or Cd-U correlates more closely with three renal tubular dysfunction markers in urine of α₁-microglobulin (α₁-MG-U), β₂-microglobulin (β₂-MG-U) and N-acetyl-β-d-glucosaminidase (NAG-U).     

Reversibility of microproteinuria in cadmium workers with incipient tubular dysfunction after reduction of exposure

The study aimed at assessing the evolution of cadmium (Cd)-induced renal tubular dysfunction in Cd workers according to the severity of the microproteinuria observed at the time the exposure was substantially decreased. Male workers employed in the Cd production industry for whom formerly high exposure had markedly decreased by 1984 and for whom standardized medical data were available during two observation periods (1980–1984 and 1990–1992) were eligible for the study. A total of 32 Cd workers fulfilling this profile were divided into two groups on the basis of historical records of urinary Cd concentration (Cd-U) covering the period until 1984. The workers with Cd-U values of > 10 μg Cd/g creatinine were subdivided further on the basis of the urinary concentration of β₂-microglobulin (β₂MG-U) measured during the first observation period (1980–1984). In each group, the tubular microproteinuria as reflected β₂MG-U and the concentration of retinol-binding protein in urine as well as the internal Cd dose as reflected by the concentration of Cd in blood and urine were compared between the first and second (1990–1992) observation periods. Increased microproteinuria was often diagnosed in cases with Cd-U values of > 10 μg Cd/g creatinine. The evolution of tubular renal function has been found to depend on the extent of the body burden of Cd (as reflected by Cd-U) and the severity of the initial microproteinuria at time high Cd exposure was reduced or ceased. When reduction of Cd exposure took place while β₂MG-U did not exceed the upper reference limit of 300 μg/g creatinine, the risk of developing tubular dysfunction at a later stage was likely to be low, even in cases with historical Cd-U values occasionally > 10 but always <20 μg Cd/g creatinine. When the microproteinuria was mild (β₂MG-U > 300 and ≤1,500 μg/g creatinine) at the time exposure was reduced, and the historical Cd-U values had never exceeded 20 μg Cd/g creatinine, there was indication of a reversible tubulotoxic effect of Cd. When severe microproteinuria (β₂MG-U > 1,500 μg/g creatinine) was diagnosed in combination with historical Cd-U values exceeding 20 μg Cd/g creatinine, Cd-induced tubular dysfunction was progressive in spite of reduction or cessation of Cd exposure. Am. J. Ind. Med. 31:645–652, 1997. © 1997 Wiley-Liss, Inc.     

Integrated indexes of occupational exposure as predictors of kidney dysfunction

The aim of the study was to evaluate the dose-effect and dose-response relationships between the integrated indexes Cd-A x t (mg/m3 x years of exposure) and Cd-B x t (microg/l x years of exposure), and the increase in retinol binding protein excretion in urine (RBP-U) and beta2-microglobulin concentration in serum (beta2M-S). The study was carried out in the nickel-cadmium battery factory in 1998-1999. Exposure to cadmium was formerly very high. The study group consisted of 116 persons for whom the results of determinations of Cd-B were available during two former observation periods (1983 and 1986-1988). The mean age of the group was 49 years and the mean period of exposure was 17 years. The dose-effect relationship between Cd-B x t and RBP-U or beta2M-S was much better (r = 0.642 and 0.513) than between Cd-A x t and RBP-U or beta2M-S (r = 0.173 and 0.127). There was also correlation between Cd-U (microg/g creatinine), measured in 1998-1999, and RBP-U or beta2M-S (r = 0.343 and 0.198). Urinary cadmium should, however, be used with caution as a dose estimate because its excretion may increase as a result of renal damage. According to the dose-response relationship, an increase in RBP excretion above 300 microg/g creatinine can be expected in 10% of subjects at the integrated exposure index (Cd-B x t) of about 450 microg/l x years, and an increase in beta2M-S above the accepted cut-off point of 2.4 mg/l can be expected in 10 % of subjects at Cd-B x t of about 190 microg/l x years. The data obtained confirmed the validity of the recommended at present health-based limit for occupational exposure of 5 microg/l of blood, as well as the superiority of the biological monitoring of exposure to cadmium over the environmental monitoring.     

Assessment of occupational exposure to cadmium in The Netherlands, 1980-1989.

One thousand five hundred fifty urine samples and 1,295 blood samples, collected from 919 workers, were analyzed for cadmium (Cd). The workers were employed at 16 different types of workplaces. In about 7.5% of the samples, the concentration of Cd exceeded the biological limit values proposed by the Dutch Expert Committee for Occupational Standards. Levels higher than these values were measured in both urine samples and blood samples of workers involved in electrochemical plating, in production of Cd-stabilizers and enamels, and in soldering with silver-cadmium solder. Significantly higher concentrations of beta 2-microglobulin (MG) were found in urine samples with CdU greater than 10 micrograms/g creatinine. Cd levels in urine increased with age.     

Renal function of workers with low-level cadmium exposure

The influence of occupational exposure to cadmium on renal function was examined in 27 male cadmium workers from plants with second-degree usage of cadmium. The levels of cadmium in the blood and urine and various protein concentrations in the urine and serum were determined. The urinary levels of beta 2-microglobulin, retinol-binding protein, and N-acetyl-beta-D-glucosaminidase were statistically significantly increased in workers with urinary cadmium levels above 50 nmol/l. SDS-PAGE electrophoresis with silver staining is probably a sensitive indicator of the early effects of cadmium on protein excretion. The currently recommended biological exposure limits may have to be lowered.     

Correlation between urine and blood concentrations, and dietary intake of cadmium and lead among women in the general population of Japan

Objective: To examine whether lead (Pb) in urine and cadmium (Cd) in blood, especially the former, can be used as markers of environmental exposure of general populations to these metals. Methods: Between 1991 and 1998, spot urine and peripheral blood samples, together with 24 h duplicates of food intake were collected from 607 non-smoking adult women in 30 survey sites (SS) in seven administrative regions all over Japan. Urine, blood and food duplicate samples were analyzed by inductively-coupled plasma spectrometry, for Cd and Pb in urine (Cd-U and Pb-U), in blood (Cd-B and Pb-B) and in food duplicates (Cd-F and Pb-F). Correlation between the measurements was examined by regression analysis. Results: The Cd-B correlated closely with Cd-U, and both Cd-B and Cd-U with Cd-F, on an individual basis (n = 607), on an SS basis (n = 30) and on a regional basis (n = 7). The Pb-U however did not correlate with Pb-B on a regional basis although they correlated with each other when analyzed on an individual as well as SS basis. Moreover, the correlation coefficients between Pb-U and Pb-B were much smaller than those between Cd-U and Cd-B. Neither Pb-U nor Pb-B showed significant correlation with Pb-F on any levels of statistical analysis. Conclusions: Both Cd-B and Cd-U can be employed as biomarkers of environmental Cd exposure. The reliability of Pb-U for use in place of Pb-B appeared to be small. Received: 21 January 1999 / Accepted: 2 November 1999     

Biologic markers of oxidative stress and nephrotoxicity as studied in biomonitoring of adverse effects of occupational exposure to lead and cadmium

OBJECTIVES: In this work, we studied impregnation levels of workers occupationally exposed to lead (Pb) and cadmium (Cd), usefulness of early urinary markers of nephrotoxicity, and occurrence of oxidative stress as the underlying mechanism involved in Pb- or Cd-induced adverse effects. Thirty-five men were recruited from a nonferrous metal smelter. Pb and Cd in blood (B-Pb, B-Cd) and urine (U-Pb, U-Cd) were measured. Relations between oxidative stress markers (malondialdehyde, superoxide dismutase, glutathione peroxidase, selenium, glutathione reductase, glutathione status, 8-hydroxy-2'-deoxyguanosine) and exposure levels, on the one hand, and early urinary markers (alpha-1-microprotein, beta-2-microglobulin, retinol binding protein, alpha and pi-glutathione S-transferases) and exposure levels, on the other hand, were evaluated. RESULTS: Mean exposure levels were moderate (B-Pb = 395.71 microg Pb/L; U-Pb = 95.19 microg Pb/g creatinine; B-Cd = 5.83 microg Cd/L; U-Cd = 4.67 microg Cd/g creatinine). Changes in malondialdehyde, glutathione status, 8-hydroxy-2'-deoxyguanosine, and alpha-glutathione S-transferases were closely correlated with exposure levels and did not depend on tobacco consumption. We showed that these workers showed moderate Pb and Cd exposure levels. CONCLUSIONS: Taken together, the data suggests the use of alpha-glutathione S-transferases excretion in urine as a hallmark of early changes in the proximal tubular integrity that could later lead to clinical disease if exposure is not reduced.     

The effects of environmental cadmium exposure on kidney function: the possible influence of age

The study aimed to assess the possible influence of long-term environmental exposure to cadmium and age at the time of exposure on renal function. The study was a follow-up of the 1991-1994 project concerning 2000 inhabitants of a cadmium-contaminated area in the vicinity of a zinc smelter. Since the smelter was built in the late 1950s but was not operated until 1968, some of the inhabitants were not exposed to cadmium during childhood. For the follow-up, 308 persons who in 1993 presented with Cd-U levels > or = 0.5 microg/L adjusted for specific gravity (1.020) were selected in 2000. The study population included 136 people who were exposed to cadmium in childhood (former children) and 172 adults (unexposed adults) with no such exposure. These two groups were divided into subgroups according to Cd-U levels: < or =1 (group 1), 1-2 (group 2), and > or =2 microg/g creatinine (group 3). Urinary and blood cadmium and the markers of renal tubular dysfunction (beta2 M-U, RBP-U, NAG, NAG-A, NAG-B) and glomerular dysfunction (Alb-U and beta2 M-S) were measured. Persons with a history of occupational exposure to cadmium were excluded from this project. In group 3 of the unexposed adults, concentrations of RPB-U, NAG, NAG-B, and Alb-U were significantly higher than those in group 1. In former children, this could be observed only for RPB-U and Alb-U. Urine concentrations of these markers were higher in all of the subgroups of former children than in the groups of unexposed adults (except for NAG and its two forms). However, these differences were significant only for RBP-U in group 3. The findings indicate that early renal effects in the general population may occur at Cd-U concentrations above 2 microg/g creatinine and at lower levels for NAG-B. Moreover, cadmium exposure in childhood may have a stronger impact the renal function, particularly tubular reabsorption, than the exposure of a mature organism.     

Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity

Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency.     

Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity.

Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency.     

Urinary neutral endopeptidase in workers exposed to cadmium: interaction with cigarette smoking.

OBJECTIVES: Structural impairment of the renal proximal tubular epithelium induced by cadmium (Cd) was investigated by measuring the concentration of neutral endopeptidase 24.11 (NEP), an ectoenzyme of the apical brush border, in the urine of 106 male workers employed in a Cd smelter (among whom 52 were occupationally exposed to Cd), and by comparing it with other tubular markers (low molecular weight proteins, lysosomal enzymes). METHODS: NEP (EC 3.4.24.11), beta-N-acetyl-glucosaminidase (NAG) (EC 3.2.1.30), and NAG-B isoenzyme activities were measured by fluorimetric assays, whereas the concentrations of retinol binding protein (RBP), beta 2-microglobulin (beta 2M), and Clara cell protein (CC16) were measured by automated latex agglutination techniques. RESULTS: An increased urinary excretion of NEP as well as microproteins was found only in subjects excreting more than 5 micrograms Cd/g creatinine. In this group, NEP concentrations were significantly higher in the subjects who smoked. This significant interaction could not be found for any other marker tested. CONCLUSIONS: The data suggest that NEP enzymuria is high even at low exposures to Cd (with a threshold of urinary cadmium excretion (U-Cd) at 5 micrograms/g creatinine), indicating early structural alterations. Moreover, its particular sensitivity to smoking could be useful in the detection of new population clusters potentially more susceptible to development of nephrotoxic insult.     

Possible effects of environmental cadmium exposure on kidney function in the Japanese general population

Objectives: To examine whether the current level of environmental exposure to cadmium (Cd) is associated with kidney dysfunction among general populations in Japan. Methods: A nationwide survey was conducted in Japan from 1991 to 1997 at 30 survey sites (with no known environmental heavy metal pollution), by the collection of 24-h food-duplicate samples, peripheral blood specimens and morning spot urine samples. In practice, 607 non-smoking adult women provided these samples. After being wet-ashed, the samples were analyzed for Cd in food duplicates (Cd-F), in blood (Cd-B) and urine (Cd-U) by inductively-coupled plasma mass spectrometry (ICP-MS). Urine samples were also analyzed for α₁-microglobulin (α₁-MG), β₂-microglobulin (β₂-MG) and retinol-binding protein (RBP), creatinine (cr) and specific gravity. Possible tubular dysfunction in association with Cd exposure was examined by simple, multiple and logistic regression analyses, and comparison among three different Cd-dose groups. To minimize the confounding effects of aging, 367 women from 41 to 60 years old were selected and subjected to the same statistical analyses. Results: The analysis of a whole population of 607 women showed that α₁-MG and possibly β₂-MG increased as a function of Cd-F, Cd-B and Cd-U. When the analysis was repeated with the selected population of 367 women aged 41–60, the Cd dose-dependent changes in α₁-MG and β₂-MG became less evident. The distribution of the selected population with α₁-MG above two low cut-off values of >4.9 and >8.4 mg/g cr or with β₂-MG above the lowest cut-off value of >400 μg/g cr, was biased toward the group with higher Cd-Ucr, but such bias was not significant for both α₁-MG and β₂-MG when higher cut-off values were employed. No bias was detected with RBP. Logistic regression analysis with α₁-MG, β₂-MG and RBP (with cut-off values given above) in combination with age, Cd-F, Cd-B and Cd-Ucr gave essentially the same results. Conclusions: The evidence for kidney dysfunction was of borderline significance in the present study population for which geometric mean Cd-F, Cd-B and Cd-U were 24.7 μg/day, 1.76 μg/l, and 3.94 μg/g cr, respectively. The findings might suggest at the same time that the safety margin is small for the Japanese general population regarding environmental Cd exposure. Received: 26 February 1999 / Accepted: 24 July 1999     

Distribution of blood lead, blood cadmium, urinary cadmium, and urinary arsenic levels in employees of a copper smelter

A cross-sectional medical examination of a copper smelter work force included determination of blood lead (Pb-B), zinc protoporphyrin (ZPP), blood cadmium (Cd-B), urinary cadmium (Cd-U), and urinary arsenic (As-U), since it was known that such metal impurities were present in the copper concentrate. A total of 776 copper smelter employees (680 active and 96 retirees and ex-employees) were examined. Another 144 men, never employed in the smelter, but who had worked in copper mines (and sometimes in gold mines) were also examined. Mean Pb-B, ZPP, Cd-B, and As-U were significantly higher in active copper smelter employees than in retirees or miners, indicating exposure and absorption in the copper smelter. Significant correlations between Pb-B and Cd-B, and Cd-U and As-U were present, confirming the common source of absorption. Although there was evidence for an increased lead absorption, this was very moderate, with practically no Pb-B levels in excess of 60 micrograms/dl. A marked effect of smoking on blood cadmium levels was present; nevertheless, for all smoking categories Cd-B levels were significantly higher in active employees, indicating the independent contribution of exposure to cadmium in the smelter. Cd-U did not exceed 10 micrograms/g creatinine, the generally accepted "critical" level for the kidney, but was higher than 2 micrograms/g creatinine, a level very rarely exceeded in the general population, in a sizable proportion of those examined. The highest Cd-U levels were found in retired copper smelter employees; age might have been a contributing factor, besides a longer duration of exposure in the smelter.     

Time trend of cadmium intake in Korea

Objectives

The aim of this study was to elucidate past and current levels of cadmium (Cd) intake among the general populations in Korea.

Methods

For this purpose, publications reporting dietary intake of cadmium (Cd-D), cadmium concentration in blood (Cd-B) and that in urine (Cd-U) in Korea were retrieved through literature survey for a period from 1975 to 2015.

Results

In practice, 9, 21 and 14 articles were available on Cd-D, Cd-B and Cd-U_cr (Cd-U as corrected for creatinine concentration), respectively. Linear regression analyses of the reported values as a function of years (i.e., the year when each survey was conducted) showed steady decreases in all of the three exposure markers of Cd-D, Cd-B and Cd-U_cr. Factors possibly contributing for the reduction were discussed including the government-set guideline of 0.2 mg/kg for rice and changes in food habits among general populations.

Conclusions

There have been steady decreases in Cd-D, Cd-B and Cd-U_cr. The current estimates for Cd-D, Cd-B and Cd-U_cr were 6.0–7.4 μg/day, 0.73–0.83 μg/L and 0.60–0.95 μg/g cr, respectively.

     

Dietary exposure to cadmium at close to the current provisional tolerable weekly intake does not affect renal function among female Japanese farmers

Dietary cadmium (Cd) exposure and renal tubular function were investigated in 1381 female farmers from five districts in Japan (Japanese Multi-centered Environmental Toxicant Study project; JMETS). Dietary Cd exposure of the five populations was assessed from the individual Cd concentrations of the rice consumed by the study participants and the quantities of rice consumed daily. The populations showed a sequential difference in dietary Cd exposure, ranging from a level as low as that of the general Japanese population to one close to the current provisional tolerable weekly intake (PTWI). The levels of urinary Cd excretion, an indicator of Cd accumulation in the kidneys, increased along the same sequential pattern as dietary Cd exposure. However, no differences were observed among the populations in levels of urinary alpha 1-microglobulin and beta 2-microglobulin excretion, which are indicators of renal tubular function. These results indicate that the current PTWI is sufficient to prevent Cd-induced renal dysfunction among the general population.     

Occupational cadmium exposure in jig solderers

The cadmium body burden, blood and urine cadmium concentrations, and renal function were studied in a group of 53 cadmium solderers. The results showed raised blood and urine cadmium concentrations and raised cadmium body burden in all workers (31) with more than five years exposure, with 27 having urine cadmium concentrations in excess of the proposed biological threshold of 10 nmol/mmol creatinine. Renal tubular dysfunction was found in 17 of the subjects with more than five years exposure and in one this was associated with glomerular dysfunction. These data indicate that cadmium body burden and frequency of tubular dysfunction in end users of cadmium may be as high as those found in smelters or production workers. Subjects with tubular dysfunction did not show greatly increased urine cadmium concentrations compared with those without dysfunction, supporting a previous suggestion that tubular dysfunction occurs before the wash out of cadmium from the kidney. At the time of our study, cadmium exposure stopped as cadmium free soldering rods were introduced. Repeat urine samples from 19 subjects, one to two years after exposure ended indicated that there was no further increase in the level of excretion of low molecular weight proteins, perhaps indicating that the tubular proteinuria does not increase or more severe renal dysfunction develop without continuous exposure.