Cadmium is a well-known nephrotoxic agent with extremely long biological half-time of 10–30 years in human. To investigate the evolution of cadmium-induced renal effects in the population, a number of 148 residents who lived in cadmium-polluted area were followed-up for 3 years after the reduction of cadmium exposure in rice. Urinary cadmium (UCd), β2-microglobulin (B2M) and albumin (ALB) were analyzed in 1995 and 1998, respectively. The results demonstrated that the changes of renal effects of residents depended on the levels of UCd before inflow of cadmium to human body declined. In cases where UCd were less than 10μg/g creatinine in 1995, evidence was found indicating significant decreases in proteinuria (i.e., B2M and ALB) 3 years later, whereas, in cases where the excretion of UCd exceeded 10μg/g creatinine in 1995, progression was observed. The study of dose–response relationships between UCd and B2M or ALB also showed that the cadmium-induced renal dysfunction might be reversible if UCd concentration was low-level before exposure decreasing, otherwise it might be irreversible or aggravated.

OBJECTIVE:To estimate the biological exposure limit (BEL) using benchmark dose (BMD) based on two sets of data from occupational epidemiology.METHODS:Cadmium-exposed workers were selected from a cadmium smelting factory and a zinc product factory. Doctors, nurses or shop assistants living in the same area served as a control group. Urinary cadmium (UCd) was used as an exposure biomarker and urinary beta2-microgloburin (B2M), N-acetyl-13-D-glucosaminidase (NAG) and albumin (ALB) as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S.A) was used to calculate BMD.RESULTS:The cut-off point (abnormal values) was determined based on the upper limit of 95% of effect biomarkers in control group. There was a significant dose response relationship between the effect biomarkers (urinary B2M, NAG; and ALB) and exposure biomarker (UCd). BEL value was 5 microg/g creatinine for UB2M as an effect biomarker, consistent with the recommendation of WHO. BEL could be estimated by using the method of BMD. BEL value was 3 microg/g creatinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected.CONCLUSION:BMD can be used in estimating the biological exposure limit (BEL). UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.

OBJECTIVE Based on two sets of data from occupational epidemiology, Benchmark dose (BMD) was applied to estimate biological exposure limit (BEL). METHODS Cadmium exposed workers were selected from a cadmium smelting and a zinc products factory and control group was selected from doctors or nurses and staff from shops living in the same area; Urinary cadmium (UCd) was used as exposure biomarker and urinary beta(2) microglobulin (UBM), NAG (UNAG) and albumin (UALB) were as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S) was used to calculate BMD. RESULTS Calculated abnormal prevalence was based on the upper limit of 95% of effect biomarkers in control group; There are significant dose response relationship between the prevalence of effect biomarkers (UBM, UNAG and UALB) and exposure biomarker (UCd); BEL was 5 microg/g creatinine for UBM as effect biomarker, It consists with the recommendation of WHO; BEL was 3 microg/g creatinine for UNAG as effect biomarker; BEL can be estimated by using the method of BMD; the more sensitive biomarker would used, the more occupational people would protected. CONCLUSION The application of BMD in estimating biological exposure limit (BEL) is proper. UNAG is suggested as most sensitive biomarker to be used to estimate BEL for cadmium exposure.

OBJECTIVE:To estimate the benchmark dose for osteoporosis caused by cadmium exposure in a Chinese general population with an epidemiological study. METHODS:The inhabitants living in both cadmium polluted and non-polluted areas served as the exposure group and the control group. Urinary cadmium (UCd) and Blood cadmium (BCd) were used as exposure biomarkers while the Z score was used as effect biomarker for the osteoporosis. RESULTS:The UCd and BCd in the habitants of the polluted areas were significantly higher than those in the habitants of the control area on average (P < 0.05) and the UCd and BCd in the habitants of the highly polluted areas were significantly higher than those in the habitants of the moderately polluted area on average (P < 0.05). The bone mineral density was significantly decreased in the groups of the highest UCd and BCd level compared with the 5 microg/g Cr group with the significant difference (P < 0.05). The morbidity of the osteoporosis would increase significantly with the increase of the cadmium exposure (P < 0.05) with the linear correlation (P < 0.05). BMDs were calculated using BMDS Version l.3.2 software and BMDLs were also determined. The BMDL of UCd for cadmium-induced osteoporosis was higher than those representing cadmium-induced renal dysfunction. CONCLUSION:High level of cadmium exposure can induce osteoporosis, which occurs later than renal damage related to cadmium exposure. The BMD is a practical method.

Cadmium may have both direct and indirect effects on bone turnover. It is nephrotoxic and can interfere with vitamin D metabolism. Such perturbation may result in osteoporosis and osteomalacia. In this study, a total of 790 persons (302 males and 488 females) participated; they were all over 35 years old and resided in an area near a cadmium smelter in southeast China. All participants completed a questionnaire, and bone mineral density was measured by SPA-4 single-photon absorptiometry at the radius and ulna. Cadmium content of urine was determined by graphite-furnace atomic absorption spectrophotometry as a measure of dose. The decline in bone mineral density with age in a heavily polluted area was greater than that in a control area for subjects over 60 years of age of both sexes (p < 0.05). In single regression, forearm bone densities were negatively correlated with urinary cadmium excretion in both males and females (p < 0.001), whereas stepwise regression showed that forearm bone density decreased linearly with age (p < 0.001) and urinary cadmium (p < 0.01) in both sexes, suggesting a dose-effect relationship between cadmium dose and bone mineral density. Based on the World Health Organization criteria, (bone mineral density < -2.5 SDs below the normal young adult), the prevalence of osteoporosis in women increased from 34.0% in the control area to 51.9% in the heavily polluted area (p < 0.01) among subjects over 50 years old, and the odds ratio value was 2.09 (95% CI: 1.08-4.03) for the highly polluted area compared with the control area. A striking observation in the study was the marked increase of the prevalence of fracture in the cadmium-polluted area in both sexes. It was concluded that environmental exposure to cadmium is associated with an increased loss of bone mineral density in both males and females, leading to osteoporosis and increased risk of fractures, especially in the elderly and in females.

Human exposure to cadmium may occur in both occupational and general environments. We were interested in determining whether a combination of occupational and environmental exposure to cadmium results in different levels of severity of renal dysfunction relative to that arising from environmental or occupational exposure alone. We selected 44 residents, who once were employed in a smelter and lived in a cadmium-polluted area, as group A. Another 88 subjects, who never worked in the plant, but lived in the same area, were selected as group B. Group C consisted of 88 subjects who had no history of occupational exposure to cadmium and lived in a non-cadmium-polluted area. Statistical analysis demonstrated that there was no significant difference in age or gender among the three groups, nor were there significant differences in smoking habits. The prevalence of renal dysfunction as indicated by increased excretion of β2-microglobulin (B2M), N-acetyl-β-d-glucosaminidase (NAG) and albumin (ALB), was higher in group A than in group B. This finding suggests that exposure to cadmium both occupationally and environmentally results in a higher prevalence of renal dysfunction, relative to those who are exposed to cadmium only in the general environment. Therefore, this specific population, who once were occupationally exposed to cadmium and lived in polluted areas, should be identified. Furthermore, health examinations of this population should be conducted in time to prevent further health damage induced by cadmium exposure.

Osteoporosis is a common metabolic disease characterized by low bone mass and microarchitectural deterioration of bone tissue. Many factors are involved in the occurrence of osteoporosis. Cadmium can cause both osteomalacia and osteoporosis and these effects have long been investigated through various epidemiological or experimental studies. The present study examines a possible relationship between cadmium nephropathy and its effects on the skeleton in populations living in a polluted area in southeast China. Monophoton absorptiometry was used to measure bone mineral density in the population and the Z score (the number of SD from the difference between the measured bone density of the individual and the group mean value for sex- and age-matched controls) was introduced to define osteoporosis (Z score < -2). Osteoporosis caused by cadmium exposure was demonstrated in this study on a general population environmentally exposed to cadmium in China. It was found that there were significant differences in the prevalence of osteoporosis among the different urinary cadmium groups chi(2) = 18.84, P = 0.0008). The linear trend test gave chi(2) = 16.281, P = 0.00005. There was a dose-response relationship between cadmium exposure (urinary cadmium) and prevalence of osteoporosis. Of 31 subjects with osteoporosis, 23 subjects were suffering from renal dysfunction. The prevalence of renal dysfunction (74.19%) was significantly higher than that in those without osteoporosis (chi(2) = 16.53, P<0.001). Stratum analysis was performed to further assess the relationship between bone damage and renal impairment caused by cadmium. There was a significant difference between those with and without tubular damage (chi(2) = 19.92, P = 0.000) but not in those with and without glomerular damage (chi(2) = 0.08, P = 0.114). This showed that glomerular dysfunction plays a smaller role than tubular dysfunction in the causation of bone damage. It was found that the prevalence of osteoporosis increases with increasing values of parameters of tubular damage. Osteoporosis caused by cadmium is thus related to kidney dysfunction and especially to tubular damage and its severity but not to glomerular damage. The present study has thus demonstrated the combined adverse effects (osteoporosis and renal dysfunction) caused by environmental exposure to cadmium for the first time in Asia outside the endemic area in Japan. (C) 2004 Elsevier Inc. All rights reserved.

The objective of this study was to investigate the possible effects of environmental cadmium (Cd) exposure on the levels of serum sex hormones in a Chinese population group. A total of 263 male volunteers were included. Blood samples were collected for the determination of serum testosterone (T), measured by radioimmunoassay, and follicle stimulating hormone (FSH) and luteinizing hormone (LH), both measured by enzyme immunoassays. Urinary and blood Cd were analyzed by atomic absorption spectroscopy (AAS). We found a dose–response relationship between urinary Cd excretion and the prevalence of abnormally high serum T levels, but, through multiple regression analysis, we could not trace exposure to Cd as a significant determinant of serum T levels. Exposure to Cd also failed to influence the levels of FSH and LH in serum. In contrast, we found that age, body mass index (BMI), and smoking habits are significant determinants of FSH and LH and of T and LH, respectively. We conclude that oral Cd exposure is not a critical determinant of hormone homeostasis in males, but lifestyle and some biological factors, such as age and BMI, are important. The relationship found between urinary Cd and high T levels may be of importance for male reproductive morbidity and should be investigated further.

镉的环境污染与人体健康影响的研究开始于1979年,终于2001年.从实验研究到外环境(镉污染区)污染源、污染途径、污染范围、污染程度、人群的镉摄入量及对人体健康的危害进行了由浅入深的调查研究.

In order to investigate the influence of occupational exposure to cadmium (Cd) on the levels of serum hormone, a cross-sectional study was undertaken in male workers. Creatinine-adjusted urinary cadmium (UCd) was used as the indicator of cadmium body burden in workers. The levels of serum testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined by radioimmunoassay and enzyme immunoassay, respectively. The results showed that with cadmium exposure, the levels of serum testosterone and LH were significantly increased after controlling for confounding factors such as age, smoking habits, and alcohol consumption. However, no significant cadmium-associated changes in the levels of serum FSH were found. At the same time, a significant negative correlation of serum testosterone levels with age was detected. In contrast, the levels of serum FSH and LH were significantly elevated with increasing age. When taking the marital status into consideration, only significantly elevated FSH levels were noted in married workers after controlling for confounding factors. These results indicate that occupational cadmium exposure and other factors such as age and marital status may independently contribute to alterations in the levels of serum sex hormones in males.

OBJECTIVE:To investigate the changes in serum levels of sex hormones in male workers occupationally exposed to cadmium (Cd).METHODS:Eighty-five Cd-exposed workers in a cadmium refinery in the south China and 76 local healthy subjects as control were selected in the study. Air samples in the workplaces were collected and detected for Cd concentration. Urinary Cd (UCd) level of the workers was measured by graphite atomic absorption spectrometry (AAS) and adjusted by urine level of creatinine (Cr), as an indicator of Cd-burden in the body of all subjects. Also, their serum levels of testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined with radioimmunoassay and enzyme immunoassay, respectively, and dose-effect relationship was evaluated.RESULTS:The serum testosterone levels in Cd-exposure group with 10.9-21.9 and > 21.9 micro mol/mol Cr were 13.00 and 11.37 nmol/L, significantly higher than that (9.31 nmol/L) in those with 0.0-2.2 micro mol/mol Cr. Significantly more increased level of LH (4.11 and 4.32 U/L) was detected in heavy exposure group in the workshop for electrolysis than in control group (2.52 U/L) and in the group with 0.0-2.2 micro mol/mol Cr of UCd (2.64 U/L). No changes in serum level of FSH were found related to Cd exposure.CONCLUSION:Occupational Cd exposure could independently contribute to the changes of serum levels of sex hormone in male workers.

An assessment of the dose response relationships between cadmium exposure and its adverse effects on kidney,bone and male reproduction,would be performed in a polluted area near a smelting factory. Population groups with different levels of cadmium exposure via rice were compared with controls concerning:measured cadmium concentration in urine (UCd) and blood,estimated cadmium uptake,(exposure biomarkers) and renal effect biomarkers (urinary beta 2 microglobulin,NAG,retinol binding protein,and albumin). Bone density was measured in the same population groups by external measurements. Male persons were invited to join a sex hormones test. Specific prostate antigen (SPA),an index used for the diagnosis of prostate cancer,was measured in the male participants. There were significant differences in urinary cadmium concentration of residents in the different areas and these differences were related to the extent of exposure to cadmium. It was also obvious that urinary cadmium concentration in females were higher than those in males,even in each subgroup. It was shown that all the UCd values were less than 5 μg/L in the control area. In the medium exposure area,most of the UCd values also were lower than 5 μg/L. On the contrary,in the high exposure area most of the UCd values were more than 5 μg/L and higher UCd values were almost exclusively found in this area. The studies generated new and important knowledge about the dose response relationships for kidney dysfunction using biomarkers. In other words,the prevalence of renal dysfunction was increased following the increase in dose of cadmium exposure. The occurrence of kidney dysfunction caused by cadmium exposure is related to the extent of cadmium exposure. The hierarchical classification of glomerular and tubular damage was applied to analysis the relationship with cadmium exposure(cadmium in urine and blood and cadmium uptake). There were significant differences between total,glomerular and tubular damages and cadmium exposure. Cadmium is one of the factors which may cause adverse health effects on bone i.e. osteomalacia and osteoporosis. There was a dose response relationship between cadmium exposure and the prevalence of osteoporosis. The prevalence of renal dysfunction was significantly higher in the osteoporosis individuals than that in those without osteoporosis. Stratum analysis was performed to further analysis the relationship of bone and renal impairment caused by cadmium. Osteoporosis caused by cadmium was related to kidney dysfunction,especially to tubular damage and its severity,but not to glomerular damage. The prevalence of positive serum PSA increased following the cadmium exposure with dose dependent fashion. It may be related to the occurrence of prostate cancer induce by cadmium exposure. [Conclusion] Dose response relationships between cadmium exposure and its adverse effects on kidney,bone and male reproduction,was found in a population, environmentally exposed to cadmium.

This paper presents the main findings of a study on health effects of environmental cadmium pollution in China, performed in 1998, i.e. approximately 25 years after the first warnings of such effects were published in Ambio. Forearm bone mineral density (BMD) and renal dysfunction were assessed in population groups exposed to cadmium via rice. Decreased BMD was found in postmenopausal women with elevated urinary cadmium (CdU) or cadmium in blood (CdB) and among men with elevated CdB. Also, clear and statistically significant dose-effect and dose-response relationships were found between CdB or CdU and renal dysfunction (increased excretion of retinol-binding protein). This is the first report of bone effects among Cd-exposed population groups in Asia outside Japan. The report is also of interest since it demonstrates that bone effects, a comparatively severe adverse health effect of Cd, in combination with renal dysfunction, still occurs in environmentally exposed population groups in Asia. Recent reports on bone effects in Cd-exposed population groups in Europe are discussed.

Cadmium, an environmental pollutant, can have adverse effects on the human body. The kidney is the critical organ. In order to improve the understanding of the dose-response relationship between cadmium exposure and health effects, and especially renal dysfunction, a study on a general population group in China was performed. This study was therefore concerned with cadmium exposure biomarkers, such as the concentrations in blood (BCd) and urine (UCd), and effect biomarkers of renal dysfunction, such as β2-microglobulin (β2m), retinol binding protein (RBP) and albumin (ALB). To improve the evaluation of exposure levels in relation to the adverse health effects of cadmium exposure in the general population, a quality control program was conducted to determine analytical quality in the determination of cadmium in blood and urine and for β2m, creatinine, ALB and RBP. The measurements showed that analytical quality was adequate. The exposure and effect biomarkers were studied in the population groups living in three areas, namely a control area and two Cd polluted areas. In the highly exposed area, most of the BCd values were higher than 5 μg/l and most of the UCd values were higher than 5 μg/g creatinine. β2-microglobulin, retinol binding protein, and albumin in urine were all significantly higher in the population living in the heavily polluted area than in that in the control area. Based on data from all three areas, a marked dose-response relationship between UCd or BCd and the prevalence of renal dysfunction was demonstrated. The number of abnormalities in kidney was related to the level of cadmium exposure. Only one index of renal tubular dysfunction was affected in subjects exposed to low levels of cadmium, but more than two indices of renal function were affected in those exposed to high levels.

Urinary &bgr;2-microglobulin and N-acetyl-&bgr;-d-glucosaminidase have been recommended as sensitive indicators of renal dysfunction induced by cadmium. However, an increase in urinary calcium in early renal damage induced by cadmium has been reported both in humans and in animal experiments. To investigate the feasibility of using urinary calcium as a biomarker of renal dysfunction induced by cadmium, two areas were selected in this study, namely, a polluted area with a 3.71 mg/kg cadmium concentration in rice and a control area with a 0.07 mg/kg cadmium concentration. The total number of participants was 499, made up of 252 in the control group and 247 from the cadmium-polluted area. Urinary cadmium, urinary calcium, and zinc concentrations were measured by atomic absorption spectrometry, and &bgr;2-microglobulin and N-acetyl-&bgr;-d-glucosaminidase in urine were analyzed. The levels of urinary cadmium and urinary calcium in persons from the exposed area were significantly higher (P < 0.05) than those in the control area for both men and women, but there was no significant difference regarding urinary zinc between the two areas. A significant dose-response relationship between the prevalence of hypercalciuria and the excretion of urinary cadmium was observed, and a significantly increased prevalence of calciuria was found when excretion of urinary cadmium exceeded 2 &mgr;g/g creatinine. The findings were similar to those for excess urinary secretion of &bgr;2-microglobulin and N-acetyl-&bgr;-d-glucosaminidase. Because cadmium can affect Ca2+ uptake by tubular cells, with decreased renal Ca2+ reabsorption, calciuria may reflect tubular cell damage caused by cadmium. It was concluded that cadmium exposure can result in increased excretion of urinary calcium in a general population and that there is a significant dose-response relationship. Urinary calcium can therefore be used as a biomarker of renal dysfunction induced by cadmium.

Objective To investigate the prognosis of renal dysfunction of general population removal cadmium exposure.Methods One hundred and fourty eight residents who lived in cadmium-exposed area was followed up for three years after exposure removal.Urinary cadmium,β\-2-microglobulin and albumin were analyzed in 1995 and 1998,respectively.Results The changes of renal dysfunction of residents after removal from exposure depend on the levels of urinary cadmium before exposure stopping. The renal dysfunction of residents with initial low-level urinary cadmium would be reversible, but it would be irreversible or aggravated for residents with high-level urinary cadmium. There was significant decreased excretion of urinary β\-2-microglobulin and albumin of residents,whose urinary cadmium concentration was lower than 5 μg/g creatinine in 1995 and 1998.However,there was a significant increased excretion of urinary β\-2-microglobulin and albumin of those residents with initial urinary cadmium higher than 10 μg/g creatinine.The study of dose-effect relationship between urinary cadmium and urinary β\-2-microglobulin and albumin also showed that the renal dysfunction induced by cadmium might be reversible if urinary cadmium concentration was low level before exposure stopped,or it might be irreversible or aggravated.Conclusion The prognosis of renal dysfunction of general population to cadmium related to the intensity of cadmium exposure before cadmium exposure stopping.

N-Acetyl-β-D-glucosaminidase (NAG) and its isoenzymes in urine have been studied in a population group residing in a polluted area in China. The area studied was contaminated by industrial wastewater from a nearby smelter that discharged cadmium-polluted wastewater into a river used for the irrigation of rice fields. Cadmium concentrations in rice were 3.70, 0.51, and 0.07 mg/kg for the highly and moderately polluted areas and the control area, respectively. Cadmium concentrations in urine exceeded 5 μg/liter in the majority of subjects in the most highly polluted area. There was a marked dose-dependent increase in NAG and NAG B content of urine related both to urinary cadmium and to the calculated cadmium uptake. It is concluded that urinary NAG and its isoenzymes could serve as a sensitive biomarker of renal dysfunction in cadmium-exposed populations. The mechanisms underlying the increase in NAG and its isoenzymes after cadmium exposure need to be studied further.

<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">镉污染区居民食用米镉含量与尿镉水平跟踪调查浙江省医学科学院（杭州３１００１３）汪再娟孔庆瑚金峰杨寅楣某镉污染区位于某冶炼厂东南面，约３００～２０００ｍ，此区内以种植水稻、柑桔、蔬菜作物为生者近２０００人。该厂冶炼铅、锌等金属，偶尔炼镉，至今已有３５年...</span>