A comparison between fecal cadmium and urinary beta2-microglobulin, total protein, and cadmium among Japanese farmers. An epidemiological study of cooperation between Japan and Sweden.

A study was made of 156 farmers living in a cadmium-exposed area and 93 farmers in a reference area. All were between 50 and 69 years of age. Cadmium intake from food was estimated from daily fecal cadmium content, body burden from urinary cadmium concentration, and cadmium-induced renal effects from urinary β₂-microglobulin (β₂-m) and total protein concentration. Average cadmium intake in the reference area was about 40 μg/day and in the exposed area about 150 μg/day. Average urinary cadmium excretion in the reference group was 2 μg/liter and in the exposed group 7.5 μg/liter. Average urinary β₂-m concentration in the reference group was 86 μg/liter and we defined tubular proteinuria as a β₂-m concentration higher than the average plus two standard deviations. With this definition the prevalence rate of tubular proteinuria was 3% in the reference group and 14% in the exposed group. Tubular proteinuria increased with age and with exposure duration. Increased total proteinuria was also more common in the exposed group but the prevalence rate ratio was 2.4 as compared to 4.4 for tubular proteinuria.     

Urinary beta2-microglobulin excretion among people exposed to cadmium in the general environment: an epidemiological study in cooperation between Japan and Sweden.

In a cadmium-exposed area, 138 farming women between 51 and 60 years of age and 40 reference women in the same age group were studied. Cadmium exposure was estimated from data on cadmium concentration in the individual farm's rice production, and on individual residence times. Possible cadmium exposure from the consumption of river water was also taken into account. The average urinary cadmium concentration was about twice as high in the exposed group as in the reference group. Cadmium levels in the blood among the exposed persons were also considerably elevated. Urinary β₂-microglobulin excretion was measured quantitatively as an indicator of renal tubular changes. Increased excretion was strongly related to residence time in the exposed area as well as to the use of contaminated river water in the household. Among the 35 women who had lived only at one place within the exposed area and who had not consumed river water, there was a tendency toward increased β₂-microglobulin excretion with an increased cadmium level in rice and increased residence time. There was also a correlation between cadmium levels in the blood and β₂-microglobulin excretion.     

The possible role of direct ingestion on the overall absorption of cadmium or arsenic in workers exposed to CdO or As2O3 dust

Six volunteers (two office and four cadmium (Cd)-exposed workers, all nonsmokers) from an electric condenser factory participated in a study involving the measurement of cadmium in air and in dust, the evaluation of hand and mouth contamination by cadmium, and the determination of fecal cadmium. The mean levels of total airborne cadmium measured with static and personal samplers were for the exposed workers 9.5 and 16.7 μg/m³, respectively, and for the office workers 0.3 and 0.5 μg/m³, respectively. In the office workers, hand contamination by Cd hardly changes over the workday (less than 10 μg/hand), whereas in the exposed workers important hand contamination by Cd was observed (up to 1,200 μg/hand during the workday and up to 300 μg/hand before lunch or before leaving the factory). Mouth contamination by Cd is rather similar in both groups on Monday morning, but increases 20- to 50-fold on Friday afternoon in the Cd workers against a slight increase for the office workers. The concentration of Cd in the feces was not much different between Sunday and Friday in the office workers, whereas in the exposed workers it was higher on Friday than on Sunday. There is suggestive evidence from a comparative study of fecal cadmium in two Cd-exposed volunteers who carried out their jobs with and without gloves that direct cadmium intake from hand contamination may contribute to the overall Cd absorption. A limited study in a glassware factory (As₂O₃ exposure) involving the measurement of total airborne arsenic, the determination of urinary arsenic, and the evaluation of hand and mouth contamination by arsenic before and after the workshift suggests that the high urinary arsenic levels (300 μg/g creatinine) are likely to be more related to an increased oral intake from contaminated hands than to an increased absorption from the lungs.     

Urine analysis for detection of cadmium-induced renal changes, with special reference to beta2-microglobulin. A cooperative study between Japan and Sweden.

An analysis of total protein, β₂-microglobulin, glucose, and cadmium was performed on urine samples from people with Itai-itai disease and glomerular kidney disease, as well as on samples from a reference group. Blind analyses of creatinine, protein, and cadmium performed in Japanese and Swedish laboratories correlated well, but there was a tendency toward systematic differences between the laboratories' analyses of creatinine and protein. Within the range of the samples analyzed the difference was never larger than 30%. The use of three different methods of electrophoresis of urine proteins verified that the proteinuria in Itai-itai disease is tubular. On an average, urinary β₂-microglobulin excretion among Itai-itai disease patients was 100–300 times higher than among the reference group, whereas total protein excretion was only 7–17 times higher. In a group of women with different degrees of cadmium exposure urinary excretion of proteins was evaluated with qualitative determination of protein, electrophoresis, and radioimmunoassay of β₂-microglobulin. At slightly elevated β₂-microglobulin excretion the first two methods gave negative results and it was concluded that radioimmunoassay of β₂-microglobulin in urine is a sensitive indicator of cadmium-induced proteinuria.     

Significance of the excretion of urinary indicator proteins for a low level of occupational exposure to cadmium

Summary Urinary cadmium (Cd), N-acetyl-β-D-glucosaminidase (NAG), metallothionein (MT), β₂-microglobulin (BMG), and blood cadmium were determined in 79 workers who had been employed at a Cd pigment factory in Japan. The workers who had been dealing with Cd pigment manufacturing processes were estimated to be exposed to cadmium pigment dust at a maximum concentration of 3.0 [μg/m³/8 h for about 20 years. The urinary Cd level ranged from 0.2 to 9.7 μg/g creatinine with a geometric mean of 1.02 μg/g creatinine. Pearson's correlation coefficients between logarithm of urinary Cd and that of NAG, MT, and BMG in urine were 0.45, 0.62, and 0.05, respectively. The correlation coefficients between blood Cd and urinary NAG, MT, and BMG were 0.21, 0.40, and −0.074, respectively. When partial correlation coefficients were calculated to exclude the contribution of age factor, urinary Cd turned out to be significantly correlated with urinary MT (r = 0.55) and NAG (r = 0.52). The present results indicate that urinary Cd is more closely associated with urinary MT and NAG than with BMG, and suggest that MT and NAG could be good indicators of Cd absorption in a Cd-exposed population whose mean urinary Cd level is relatively low, or less than 10 μg/g creatinine.     

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.     

Environmental exposure to cadmium and renal function of aged women in three areas of Belgium

The relationship between environmental cadmium pollution and prevalence of signs of renal disturbance was investigated. Women over 60 years of age who had spent the major part of their life in a cadmium-polluted area in Belgium (Liège, n = 60) and who had never been occupationally exposed to cadmium constituted the “exposed” group. Women living in two areas less polluted by cadmium (Charleroi, n = 70, and Brussels, n = 45) served as “control” groups. The group of aged women from the Liège area has on the average a higher cadmium body burden, as reflected by an increased excretion of cadmium in urine, than the groups of aged women in the two other areas. The parameters selected for evaluating renal function (urinary excretion rates of total protein, amino acids, β₂-microglobulin, albumin) follow the same trend. Furthermore, a statistically significant correlation was found between the urinary excretion rate of cadmium and that of total protein, amino acids, β₂-microglobulin, and albumin. The results suggest that environmental pollution by cadmium as found in some industrialized areas in Europe may exacerbate the age-related decline of renal function in population groups nonoccupationally exposed to heavy metals.     

Dose-response analysis of cadmium in man: Body burden vs kidney dysfunction

The primary objective of this study was to develop dose-response relationships of cadmium in human beings. In vivo measurements of kidney, liver, urine, and blood cadmium, and urinary levels of β₂-microglobulin and total protein were obtained in 82 industrially exposed workers and 30 control subjects. The values of 200 μg/g creatinine for urinary β₂-microglobulin and 250 mg/g creatinine for urinary total protein were used to define the upper limit for normal kidney function. Forty-one of the cadmium workers (18 active, 23 retired) were classified as having abnormal kidney function; all control subjects had normal kidney function. Most workers with Cd above 70 ppm in the liver were judged to have some evidence of kidney abnormalities. The dose-response relationship for liver cadmium for the actively employed workers could be described by a linear logistic regression model:

$\text{ln}\text{p}\text{1?p}\text{0.118 ×}\text{liver cadmium (ppm)}\text{? 5.00}$

where p is the individual's probability of having kidney dysfunction. The loss of cadmium from the kidney following dysfunction prohibited a direct logistic analysis of the kidney cadmium data. However, when the linear relationship between kidney and liver cadmium for the subjects with normal kidney function was combined with the logistic equation for the liver, a predicted-response curve was obtained for the kidney. The logistic models predict a 50% probability of having kidney dysfunction at 38.4 mg for the kidney and 42.3 ppm for the liver, respectively.     

低浓度镉暴露对工人肾功能及体液中铁和锌水平的影响

[目的]探讨通过呼吸道职业性接触镉的情况下,工人体液中铁和锌的水平与镉肾毒作用间的相互关系。[方法]随机抽取镉接触工人103人和对照组人员36人,分别测定镉接触标志物[血镉（blood cadmium,BCd）和尿镉（urinary cadmium,UCd）]、镉肾毒性的效应标志物[尿β2-微球蛋白（urinary β2-microglobulin,Uβ2-MG）、尿白蛋白（urinary albumin,UALB）和尿N-乙酰-β-D-氨基葡萄糖苷酶（urinary N-acetyl-β-D-glucosaminidase,UNAG）]和反映铁状态的生物标志物[血红蛋白（Hb）、血清铁蛋白（serum ferritin,SF）和血清转铁蛋白受体（serum transferrin receptor,sTfR）],测定血锌和尿锌来反映体液中锌水平,并分析这些标志物间的相互关系。[结果]镉接触工人的血镉、尿镉均明显增高,尿β2-MG和UALB均高于对照组,尿NAG、β2-MG和UALB均随尿镉水平的增高而增高,存在剂量-效应关系,Hb含量和SF低于对照组,贫血患病率高于对照组。接触组血锌和尿锌含量与对照组的差异无统计学意义,但是尿锌与尿镉和血镉间均呈正相关关系,尿镉高的工人尿锌浓度高于尿镉低的工人。[结论]职业性镉接触能引起体内铁储存量下降和贫血患病率增高,在体内镉蓄积到一定程度时,会引起尿锌排泄增加。     

Significance of cadmium concentration in blood and in urine in workers exposed to cadmium.

All the workers (n = 11) occupied in a small factory producing cadmium salts were followed up during several months. Four of them were newly employed workers. At regular time intervals the workers were equipped with a personal air sampler and cadmium concentrations in blood and in urine were measured. The total airborne concentration of cadmium at the different work places was very high. The median values ranged from 110 to 2125 μg/m³. In view of the hygiene practice of the workers, ingestion of cadmium may also have played a role in the overall exposure. After the start of the exposure, cadmium concentration in blood increases linearly up to 120 days and then levels off. This suggests that when equilibrium is reached cadmium level in blood is a good indicator of the average intake during recent months. The interpretation of the cadmium levels in urine is more complex. In seven workers exposed for more than 250 days cadmium level in urine seemed to reflect mainly current exposure. Our results suggest also the existence of three phases in the evolution of the Cd levels in urine after the onset of high exposure. A first phase of very short duration (0–15 days) is observed during which cadmium level in urine increases rapidly to reach a value of about 15 μg/g creatinine. This is followed by a second phase (15–120 days) during which cadmium level in urine increases more slowly. After 120 days there is apparently a rapid increase of the cadmium level in urine (third phase). The results obtained during this study as well as our previous clinical observations on workers exposed to cadmium lead us to propose a tentative biological threshold of 10 μg Cd/g urinary creatinine. It should be stressed that this proposal applies only to adult males occupationally exposed to cadmium and not necessarily to other groups of the general population.     

In vivo measurement of liver and kidney cadmium in workers exposed to this metal: Its significance with respect to cadmium in blood and urine

The cadmium concentration in liver (CdL) and in kidney is measured in vivo by neutron capture γ-ray analysis in 309 male workers occupied in two Belgian zinc-cadmium plants. At the same time, blood cadmium (CdB) and the urinary excretion of β₂-microglobulin, albumin, total protein, calcium, and cadmium (CdU) is also determined. Among the 264 subjects retained for the statistical analysis 236 are still active at the plants (group A) while 28 others are retired Cd workers or workers removed from Cd exposure (group R). Group A comprises 149 subjects with normal renal function who are engaged in jobs not directly related to Cd production (subgroup Ala) and 87 Cd workers daily occupied with Cd production of whom 72 subjects (subgroup Alb) have not and 15 (subgroup A2) have sign(s) of renal dysfunction. Group R is subdivided into subgroups R1 (n = 10) and R2 (n = 18), subjects without and with renal dysfunction, respectively. Examination of the cumulative frequency distributions and the correlations between the various biological parameters in the different subgroups leads to the following conclusions: (a) calciuria is not much different among the subgroups, (b) CdB mainly reflects recent exposure to cadmium in the absence of Cd-induced renal damage, (c) CdU follows the body burden of cadmium but increases proportionately much more in workers with renal dysfunction particularly when signs of tubular dysfunction are present, (d) CdL is proportional to duration and intensity of Cd exposure in workers without as well as with renal dysfunction, (e) renal cortical cadmium (CdKc) is higher in subgroup Alb and Rl than in subgroup Ala but does not differ between Cd workers without (subgroup Alb) and with (subgroups A2 and R2) renal dysfunction. The latter finding can be explained by a progressive decrease of CdKc after the onset of the renal damage. This hypothesis is supported by the observations that in Cd workers from subgroup R2. CdKc negatively correlates with years of past exposure to Cd (r = ?0.59), that Cd workers with renal dysfunction (subgroups A2 and R2) excrete significantly more cadmium in urine, and that they show a much lower slope of CdKc versus CdL than those with normal renal function (subgroup Alb). The results of this investigation suggest that there exists a range of critical CdKc levels, i.e., approximately from 160 to 285 ppm. Beyond a CdKc of 285 ppm the probability is very high that all persons will show sign(s) of renal dysfunction. It has been found that kidney dysfunction is likely to develop in workers with CdL between 30 and 60 ppm and that almost all the Cd workers with CdL above 60 ppm evidence renal dysfunction. This study also demonstrates that in the absence of kidney dysfunction. CdU is correlated with the body burden of cadmium (r = 0.59), but that CdB is not. On the basis of the interrelationships among CdL, CdKc, CdU, and the indicators of renal function, it can be concluded that the probability of developing Cd-induced renal dysfunction in male Cd workers appears to be very low when the critical CdU level of 10 μg/g creatinine is not regularly exceeded. This CdU level corresponds to an average cadmium body burden of 160–170 mg.     

镉接触工人尿镉血镉与尿β_2MG RPB含量的跟踪研究

目的:跟踪调查镉接触工人停止接触镉后尿镉、血镉的变化及肾功能损害情况,寻找镉接触指标与肾功能损害指标的关系,初步探讨职业性镉引起的肾功能特点及规律。方法:选择深圳某镍镉电池厂29名镉中毒观察对象(尿镉连续2次超过5μmol/mol肌酐)为研究对象,分析尿镉、血镉含量与尿β2-微球蛋白(β2MG)、尿视黄醇结合蛋白(RPB)排出量的关系;并通过跟踪研究他们在停止接触镉1年后,接触指标(尿镉、血镉)及肾功能损害指标的变化的规律。结果:镉中毒观察对象在停止接触1年后,尿镉由(7.16±2.81)μmol/mol肌酐下降至(7.03±2.84)μmol/mol肌酐,尿镉含量下降没有显著性差异(P>0.05);血镉明显下降,由(5.8±1.81)μg/L下降至(3.5±1.24)μg/L,有显著性差异(P<0.01);尿β2-微球蛋白含量(中位数)由1.19μmol/mol肌酐上升至1.21μmol/mol肌酐,尿视黄醇结合蛋白含量(中位数)由0.39μmol/mol肌酐上升至0.42μmol/mol肌酐,统计学秩和检验结果显示均没有显著性差异(P>0.05)。尿镉与血镉存在明显的线性正相关,相关系数(r)为0.721,(P<0.01),回归分析得出的方程为:y=1.132x+3.656,(y代表尿镉,x代表血镉)。尿镉、血镉与尿β2-微球蛋白含量的相关系数分别为0.321,0.346,统计学上均没有显著性相关(P>0.05)。结论:职业性镉中毒观察对象停止接触镉1年后,血镉明显下降,尿镉含量下降不明显,尿镉与血镉存在线性正相关,尿β2-微球蛋白、尿视黄醇结合蛋白含量总体水平变化不显著,但有个别仍可以出现肾功能异常,镉对肾功能损害存在明显个体差异性。     

Application of the hybrid approach to the benchmark dose of urinary cadmium as the reference level for renal effects in cadmium polluted and non-polluted areas in Japan

Objectives

The aim of this study was to evaluate the reference level of urinary cadmium (Cd) that caused renal effects. An updated hybrid approach was used to estimate the benchmark doses (BMDs) and their 95% lower confidence limits (BMDL) in subjects with a wide range of exposure to Cd.

Methods

The total number of subjects was 1509 (650 men and 859 women) in non-polluted areas and 3103 (1397 men and 1706 women) in the environmentally exposed Kakehashi river basin. We measured urinary cadmium (U-Cd) as a marker of long-term exposure, and β2-microglobulin (β2-MG) as a marker of renal effects. The BMD and BMDL that corresponded to an additional risk (BMR) of 5% were calculated with background risk at zero exposure set at 5%.

Results

The U-Cd BMDL for β2-MG was 3.5 μg/g creatinine in men and 3.7 μg/g creatinine in women.

Conclusions

The BMDL values for a wide range of U-Cd were generally within the range of values measured in non-polluted areas in Japan. This indicated that the hybrid approach is a robust method for different ranges of cadmium exposure. The present results may contribute further to recent discussions on health risk assessment of Cd exposure.     

Dose-response relations between urinary cadmium and tubular proteinuria in cadmium-exposed workers

Cadmium in urine reflects the body burden in cadmium-exposed individuals. Urinary β2-microglobulin is frequently used as a marker of tubular proteinuria with an arbitrarily chosen value (34 μg/mmole creatinine) as the cut-off limit. Both this cut-off level and a lower limit (25 μg/mmole creatinine) were used in a study of the relationship between urinary cadmium and β₂-microglobulin in 561 cadmium-exposed battery workers. There was a clear dose-response relation between the urinary cadmium level and the prevalence of tubular proteinuria ranging from 0.8% in the lowest exposure group, excreting less than 1 nmole cadmium/mmole creatinine, to 46.4% (50.0 for the lower cut-off level) in the highest exposure group with a mean urinary cadmium of 15 nmole/mmole creatinine. The relation between urinary cadmium and tubular proteinuria was also assessed using probit analysis. There was a 10% response at a urinary cadmium of 3 nmole/mmole creatinine. The impact of age on the dose-response relation was explored in two age groups with the cut-off point at 60 years of age, showing a 10% prevalence of tubular proteinuria at urinary cadmium levels of 1.5 nmole/mmole creatinine in this older age group and 5.0 nmole/mmole creatinine in the category under 60 years of age. The study thus indicates that the present health-based limit (10 nmole/mmole creatinine) proposed by the World Health Organization (WHO) is too high and it is suggested that a new limit should be set to 3 nmole/mmole creatinine.     

Determination of carbonic anhydrase C and beta 2-microglobulin by radioimmunoassay in urine of heavy-metal-exposed subjects and patients with renal tubular acidosis.

Carbonic anhydrase C (CA-C) was measured by the radioimmunoassay in urine specimens from normal individuals, residents in mercury-polluted area, cadmium-exposed workers, lead-exposed workers, and patients with primary or secondary renal tubular acidosis. None of the urine in the normal subjects demonstrated CA-C levels above 40 μg/g creatinine. Some of the cadmium-exposed workers, residents in mercury-polluted area, and patients with renal tubular acidosis excreted large amounts of CA-C that were 10–250 times higher than the normal. Urinary β₂-microglobulin (BMG) was also determined in relation to the CA-C levels. Most of the subjects exposed to heavy metals had high levels of urine CA-C or BMG or both. Some individuals had high levels of urine CA-C although BMG levels were within normal values. These findings seem to suggest that the mechanisms of urinary excretion of these two proteins were different and the quantitative determination of urinary CA-C by radioimmunoassay appears to be also a useful and sensitive test for detecting the renal tubular disorders in environmental exposure of heavy metals or those in renal tubular acidosis.     

Low level exposure to cadmium and early kidney damage: the OSCAR study

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 (α₁-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.


Keywords: cadmium; environmental; tubular damage     

Renal function after reduction in cadmium exposure: an 8-year follow-up of residents in cadmium-polluted areas

Background and objective: Long-term exposure to cadmium (Cd) causes renal dysfunction, but the change in renal function with exposure is unknown. We assessed the evolution of Cd-induced renal effects after a reduction in dietary exposure to Cd in rice.Methods: Four hundred twelve residents in previously Cd-polluted and nonpolluted areas were examined twice, in 1998 and in 2006. Changes in blood Cd, urinary Cd, and kidney function [N-acetyl-β-d-glucosaminidase (NAG), β₂-microglobulin, and albumin in urine] were measured.Results: In the most polluted area, mean blood Cd was 8.9 μg/L and 3.3 μg/L in 1998 and in 2006, respectively, and urinary Cd was 11.6 and 9.0 μg/g creatinine. Urinary albumin in 1998 increased with urinary Cd, but no such exposure–response relation appeared for 2006 albumin versus urinary Cd 1998, indicating recovery. Other biomarkers of kidney function were also elevated in 1998. Partial recovery was observed for NAG among women and was suggested for β₂-microglobulin among young individuals. The probability of having β₂-microglobulin levels above the 95th percentile in 2006 was high in those with elevated β₂-microglobulin in 1998 [odds ratio (OR) = 24.8; 95% confidence interval (CI): 11.2, 55.3] compared with albumin (OR = 3.0; 95% CI: 1.2, 7.5) and NAG (OR = 2.6; 95% CI: 1.6, 4.4).Conclusions: Results suggest that a Cd-mediated increase in urinary albumin excretion is reversible upon substantial reduction of exposure. For markers of tubular effects, we observed a tendency toward improvement but not complete recovery. Data from repeated observations suggest that β₂-microglobulin may be more informative than NAG as an indicator for an individual’s future tubular function.     

Third International Symposium on Toxicology of Carbon Disulphide

An outbreak of cadmium intoxication in a jewelry factory provided an opportunity for evaluating the usefulness of diagnostic procedures used to evaluate human cadmium toxicity. Blood cadmium levels in workers exposed to cadmium were higher (.93 μg/100ml vs .38 μg/100 ml) than in unexposed workers. A dose-response relationship was noted between blood cadmium level and symptom prevalence in four symptoms (dyspnea, chest pain, dysuria, and dizziness). Segmental hair analysis revealed highest cadmium levels (up to 19 μg/gm) in segments formed prior to cadmium exposure, suggesting that extrinsic contamination was the primary source of cadmium in the hair. β₂-microglobulin levels were within normal limits. No significant renal or pulmonary dysfunction was noted. Symptoms ceased after a cadmium-containing brazing alloy used in jewelry production was replaced, yet urine cadmium levels remained persistently elevated in four workers. Blood cadmium determinations were found to be useful in evaluating symptoms potentially related to cadmium intoxication.     

Search for anti-laminin antibodies in the serum of workers exposed to cadmium,mercury vapour or lead

Summary Anti-laminin antibodies were sought for in the serum of workers exposed to mercury vapour (Hg, n = 58), lead (Pb, n = 38) or cadmium (Cd, n = 47). Thirty-one workers removed from Cd exposure for an average of eight years were also examined. Compared with control workers matched for age and socio-economic status, the prevalence of circulating anti-laminin antibodies was not increased in workers exposed to Hg (mean duration of exposure: 7.9 years and mean urinary excretion of Hg: 72 g/g creatinine) nor in those exposed to Pb (mean duration of exposure: 10.6 years and mean Pb levels in blood: 535 g/l). In contrast, anti-laminin antibodies were significantly more prevalent in Cd-exposed workers whose urinary Cd exceeded 20 g/g creatinine. This observation was made in both currently exposed workers and in workers removed from Cd exposure (mean duration of exposure: 9.4 and 24.6 years and mean urinary Cd: 7.8 and 13.4 g/g creatinine respectively). These autoantibodies were found in Cd workers with normal renal function as well as in those with increased proteinuria.     

Significance of the excretion of urinary indicator proteins for a low level of occupational exposure to cadmium

Urinary cadmium (Cd), N-acetyl-beta-D-glucosaminidase (NAG), metallothionein (MT), beta 2-microglobulin (BMG), and blood cadmium were determined in 79 workers who had been employed at a Cd pigment factory in Japan. The workers who had been dealing with Cd pigment manufacturing processes were estimated to be exposed to cadmium pigment dust at a maximum concentration of 3.0 micrograms/m3/8 h for about 20 years. The urinary Cd level ranged from 0.2 to 9.7 micrograms/g creatinine with a geometric mean of 1.02 micrograms/g creatinine. Pearson's correlation coefficients between logarithm of urinary Cd and that of NAG, MT, and BMG in urine were 0.45, 0.62, and 0.05, respectively. The correlation coefficients between blood Cd and urinary NAG, MT, and BMG were 0.21, 0.40, and -0.074, respectively. When partial correlation coefficients were calculated to exclude the contribution of age factor, urinary Cd turned out to be significantly correlated with urinary MT (r = 0.55) and NAG (r = 0.52). The present results indicate that urinary Cd is more closely associated with urinary MT and NAG than with BMG, and suggest that MT and NAG could be good indicators of Cd absorption in a Cd-exposed population whose mean urinary Cd level is relatively low, or less than 10 micrograms/g creatinine.