Cessation Of Cadmium Exposure Research Articles

A longitudinal study on urinary cadmium and renal tubular protein excretion of nickel-cadmium battery workers after cessation of cadmium exposure.

This study aimed to predict the outcome of urinary cadmium (Cd) excretion and renal tubular function by analyzing their evolution through 10years after Cd exposure ceased. Forty-one female, non-smoking workers were recruited from the year 2004 to 2009 when being removed from a nickel-cadmium battery factory, and they were asked to provide morning urine samples on three consecutive days at enrollment and in every follow-up year until 2014. Urinary Cd and renal tubular function biomarkers including urinary β2-microglobulin (β2-m) and retinol-binding protein (RBP) concentrations were determined with the graphite furnace atomic absorption spectrometry and the enzyme-linked immunosorbent assays, respectively. The medians of baseline Cd, β2-m and RBP concentrations at enrollment were 6.19, 105.38 and 71.84μg/g creatinine, respectively. Urinary β2-m and RBP concentrations were both related to Cd concentrations over the years (β absolute-β2-m=9.16, P=0.008 and β absolute-RBP=6.42, P<0.001, respectively). Cd, β2-m and RBP concentrations in the follow-up years were all associated with their baseline concentrations (β absolute-Cd=0.61, P<0.001; β absolute-β2-m=0.64, P<0.001; and β absolute-RBP=0.60, P<0.001, respectively), and showed a decreasing tendency with the number of elapsed years relative to their baseline concentrations (β relative-Cd=-0.20, P=0.010; β relative-β2-m=-17.19, P=0.002; and β relative-RBP=-10.66, P<0.001, respectively). Urinary Cd might eventually decrease to the general population level, and Cd-related tubular function would improve under the baseline conditions of this cohort.

Seventeen-Year Observation on Urinary Cadmium and β2-Microglobulin in Inhabitants After Cessation of Cadmium-Exposure in Japan

The purpose of this study was to clarify the change and relationship of urinary cadmium (Cd) and beta(2)-microglobulin (beta(2)-MG) concentrations of inhabitants in Cd-polluted areas after soil restoration. The urinary Cd and beta(2)-MG concentrations of 25 males and 28 females did not show a significant change, 22 years after the Cd-polluted soil was restored. Once exposed to Cd, it was found to remain in the body, 22 years after the Cd -polluted soil was restored. However, this did not influence renal tubular dysfunction in most of the younger generation compared with elders heavily exposed to Cd.

Biological half-life of cadmium in the urine of inhabitants after cessation of cadmium exposure

We investigated the biological half-life of the urinary cadmium concentration (U-Cd) based on a 24-year follow-up study after cessation of cadmium exposure in a cadmium-polluted area. Spot urine samples were obtained from all inhabitants in this area in 1979, 1986, 1991, 1999 and 2003. Biological half-life was calculated in the inhabitants whose U-Cd was more than 5 μg l−1 (9 men and 12 women) or 5 μg g−1 creatinine (9 men and 19 women) using a one-compartment model. The estimated half-life and 95% confidence intervals were 13.6 years (9.0–28.2 years) and 13.9 years (9.6–25.6 years) for unadjusted U-Cd in men and women, respectively. For creatinine-adjusted U-Cd, they were 14.2 years (11.2–19.4 years) and 23.5 years (17.7–35.0 years) in men and women, respectively. The biological half-lives of U-Cd obtained in this study were identical with the values of total body burden determined by a different method.

Cadmium-induced renal dysfunction: New mechanism, treatment and prevention

Cadmium-induced renal dysfunction has hitherto been regarded as noncurative, with the renal dysfunction occurring when the cadmium concentration in the renal cortex exceeded a critical concentration for the renal cortex, 200 μg/g wet weight. However, we have identified a mechanism that is quite different from the above working hypothesis: cadmium induces hepatic dysfunction through cadmium-induced free radicals in the liver. Hepatic cadmium-thionein is released into the bloodstream upon hepatic dysfunction and enters the renal tubular lumen by freely passing through the renal glomeruli to result in injury to the brush border membrane of the proximal convoluted tubules. The critical concentration of plasma cadmium, an alternative biomarker for cadmium-thionein in the renal proximal tubules, for inducing renal dysfunction was found to be 100 &mu Cd/L and was quite independent of the cadmium level in the renal cortex. Cadmium-induced renal dysfunction was therefore considered reversible following cessation of cadmium exposure, when the renal dysfunction was not so serious, probably as a result of decreased levels of plasma cadmium-thionein. We also succeeded in improving cadmium-induced renal dysfunction through subcutaneous glycyrrhizin administrations, by lowering the plasma cadmium-thionein due to alleviation of the destruction of hepatic cells. We further succeeded in ameliorating cadmium-induced renal dysfunction through administration of acetazolamide, a carbonic anhydrase blocker, due to the depressed plasma cadmium-thionein associated with improvement of the hepatic dysfunction. J. Trace Elem. Exp. Med. 11:275–288, 1998. © 1998 Wiley-Liss, Inc.

Blood cadmium as an indicator of dose in a long-term follow-up of workers previously exposed to cadmium.

This investigation attempted to follow the tubular function of 46 workers initially examined in 1984 and heavily exposed to cadmium from 1955 to 1978 and the occurrence of renal stones among these workers. Three different markers of tubular dysfunction were also studied, and blood cadmium was evaluated as an estimate of dose after the cessation of cadmium exposure. Cadmium in blood (B-Cd) and urine (U-Cd) and the urinary excretion of beta 2-microglobulin (U-beta 2-microglobulin), protein HC (alpha 1-microglobulin) and N-Acetyl-beta-D-glucosaminidase (NAG) were determined. Although cadmium exposure ceased in 1978, 40% of the workers showed signs of tubular dysfunction both in 1984 and in 1993. The current B-Cd was the best dose indicator. Dose-response relationships were found for B-Cd and various tubular markers (U-beta 2-microglobulin, protein HC and NAG). Protein HC appeared to be the most sensitive, as well as an early, indicator of cadmium-induced tubular dysfunction. The levels of U-Cd had an average decrease of 48% for persons with a normal tubular function, 56% for those with slight tubular dysfunction, and 62% for workers with severe tubular damage. A history of renal stones was significantly more common for workers with high B-Cd levels. Cadmium-induced tubular dysfunction is irreversible and best assessed in an analysis of protein HC (alpha 1-microglobulin) in urine. B-Cd is the best dose estimate several years after the cessation of exposure, whereas U-Cd is less suitable for dose assessment in follow-up studies of persons with persistent tubular damage.

Progress of renal dysfunction in inhabitants environmentally exposed to cadmium.

The reversibility of beta 2-microglobulinuria, glucosuria, and aminoaciduria was examined in 74 inhabitants (32 males and 42 females) over 50 yr of age, who lived in a cadmium-polluted area. The subjects participated in two examinations conducted just after the cessation of cadmium exposure and 5 yr later. All urinary parameters did not show reversible changes. During the 5 yr the geometric mean concentrations of beta 2-microglobulinuria, glucosuria, and aminoaciduria indicated significant increases in excretion. In cases where greater than 1,000 micrograms/g creatinine of beta 2-microglobulinuria was observed (at the time cadmium exposure ended), almost all individuals exposed to cadmium showed deterioration of beta 2-microglobulinuria, whereas in the case of less than 1,000 micrograms/g creatinine of beta 2-microglobulinuria, no significant changes were observed. The present study indicates that cadmium-induced renal dysfunction in individuals environmentally exposed to cadmium is irreversible.

Reversibility of Cadmium-Induced Health Effects in Rabbits

Twenty-one male rabbits were divided into three groups: rabbits of two groups were given pelleted food containing cadmium chloride at a dose level of 300 micrograms Cd/g over periods of 44 or 19 weeks. Rabbits of the last group were given ordinary commercial pelleted food and served as controls. Cadmium increased urinary protein and amino acid by week 19 and increased it to a remarkably high level by week 44. After cessation of cadmium exposure, rabbits of the first group (44 weeks exposure group) showed only little recovery from cadmium health effects: proteinuria and aminoaciduria were slightly improved. Depressed hepatic functions were also slightly improved, but did not return to the control level in 24 weeks. Fat and bone metabolism also remained depressed below the control level. Anemia did not also readily recover. On the other hand, rabbits of the second group (19 weeks exposure) recovered from the effects of cadmium: proteinuria and aminoaciduria in most animals disappeared soon after the end of cadmium exposure, plasma GPT fell after 1 week, and hemoglobin and hematocrit returned to normal in 6-11 weeks. The above results show that after cessation of cadmium exposure, mild cadmium-induced health effects were reversible in a short period, while more severe effects were not readily reversible. High performance liquid chromatographic (HPLC) profiles of renal and hepatic cadmium-thionein (Cd-MT) during and after exposure to cadmium showed no correlation to the degree of cadmium health effects, and therefore, did not help to elucidate mechanisms of the recovery from cadmium-induced health effects, probably because cadmium not bound with metallothionein (non-MT-Cd) is responsible for inducing renal effects.

Reversibility of cadmium-induced health effects in rabbits.

Twenty-one male rabbits were divided into three groups: rabbits of two groups were given pelleted food containing cadmium chloride at a dose level of 300 micrograms Cd/g over periods of 44 or 19 weeks. Rabbits of the last group were given ordinary commercial pelleted food and served as controls. Cadmium increased urinary protein and amino acid by week 19 and increased it to a remarkably high level by week 44. After cessation of cadmium exposure, rabbits of the first group (44 weeks exposure group) showed only little recovery from cadmium health effects: proteinuria and aminoaciduria were slightly improved. Depressed hepatic functions were also slightly improved, but did not return to the control level in 24 weeks. Fat and bone metabolism also remained depressed below the control level. Anemia did not also readily recover. On the other hand, rabbits of the second group (19 weeks exposure) recovered from the effects of cadmium: proteinuria and aminoaciduria in most animals disappeared soon after the end of cadmium exposure, plasma GPT fell after 1 week, and hemoglobin and hematocrit returned to normal in 6-11 weeks. The above results show that after cessation of cadmium exposure, mild cadmium-induced health effects were reversible in a short period, while more severe effects were not readily reversible. High performance liquid chromatographic (HPLC) profiles of renal and hepatic cadmium-thionein (Cd-MT) during and after exposure to cadmium showed no correlation to the degree of cadmium health effects, and therefore, did not help to elucidate mechanisms of the recovery from cadmium-induced health effects, probably because cadmium not bound with metallothionein (non-MT-Cd) is responsible for inducing renal effects.