BACKGROUND: As research progresses, there is a growing body of evidence indicating that urinary metallothionein (MT) levels may be elevated in individuals exposed to cadmium (Cd). This study aimed to investigate the potential association between urinary MT levels and causes of mortality among residents of the Kakehashi River Basin who have been exposed to Cd. METHOD: The study involved a total of 1,398 men and 1,731 women were conducted between 1981 and 1982, with follow-up until November 2016. The study employed the Cox proportional-hazards model to examine the association between higher urinary MT concentrations and the risk of all-cause or cause-specific mortality within the population. Furthermore, the Fine and Gray competing risks regression model was used to evaluate the links between specific causes of death. RESULTS: The findings revealed that elevated urinary MT concentrations were linked to increased all-cause mortality and higher mortality rates from renal and urinary tract diseases across all participants. Specifically, in men, higher urinary MT levels were associated with elevated all-cause mortality, while in women, increased concentrations were linked to higher mortality from endocrine, nutritional, and metabolic diseases, as well as cardiovascular diseases. Even after adjusting for competing risks, higher urinary MT concentrations were associated with tumor-related mortality in men and continued to be associated with cardiovascular disease mortality in women. CONCLUSIONS In conclusion, the results suggest that women may face a greater risk of adverse health effects due to prolonged exposure to Cd. Urinary MT levels could potentially serve as a biomarker for mortality from these diseases in populations chronically exposed to Cd.
Humans ; Male ; Female ; Cadmium/urine* ; Japan/epidemiology* ; Metallothionein/metabolism* ; Middle Aged ; Cause of Death ; Adult ; Follow-Up Studies ; Aged ; Environmental Exposure/analysis* ; Proportional Hazards Models

OBJECTIVES: Previous studies have demonstrated that the metals cadmium and arsenic exhibit estrogen-like effects and may influence the occurrence and development of gynecological tumors. This study aims to explore the association between urinary cadmium and arsenic levels and the prevalence of gynecologic cancers using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: Data from female participants in NHANES 2003-2018 were analyzed. Using R software, datasets (DEMO, BMX, etc.) were merged, and complete cases were retained by intersecting row names, yielding a total of 2 999 participants. After applying strict exclusion criteria, 2 802 participants were included: 83 with gynecologic cancer (cancer group) and 2 719 without (control group). Demographic, reproductive health, and urinary cadmium and arsenic data were collected. Binary Logistic regression models were employed to assess associations between urinary cadmium and arsenic levels and gynecologic cancer risk. RESULTS: High urinary cadmium and arsenic levels were risk factors for gynecologic cancers, with odds ratios (ORs) of 1.623 (95% CI 1.217 to 2.166) and 1.003 (95% CI 1.001 to 1.005), respectively. After propensity score matching (PSM), the trend remained; cadmium was still a statistically significant risk factor with an OR of 2.182 (95% CI 1.343 to 3.545), while arsenic's association, though not statistically significant, still trended toward risk (OR=1.004, 95% CI 0.999 to 1.009). Subgroup analyses showed that both cadmium and arsenic were risk factors for ovarian cancer (OR=1.745, 95% CI 1.178 to 2.586 and OR=1.005, 95% CI 1.002 to 1.008, respectively); these associations persisted after PSM. Additionally, cadmium increased the risk of endometrial cancer (OR=1.617, 95% CI 1.109 to 2.356). CONCLUSIONS Exposure to cadmium and arsenic is associated with an increased risk of ovarian and endometrial cancers. These findings suggest that reducing environmental exposure to heavy metals such as cadmium and arsenic may help prevent certain gynecologic cancers.
Humans ; Female ; Cadmium/urine* ; Arsenic/urine* ; Genital Neoplasms, Female/urine* ; Middle Aged ; Nutrition Surveys ; Adult ; Risk Factors ; Environmental Exposure/adverse effects* ; Aged

BACKGROUND: Previous studies have suggested that exposures to heavy metals (arsenic, cadmium, lead, and selenium) may be associated with differences in blood pressure. However, the findings of these studies have been inconsistent. This study was performed to examine the associations between urinary heavy metal concentrations and blood pressure among residents of four Asian countries (Bangladesh, Indonesia, Nepal, and Vietnam). METHODS: This cross-sectional study examined 1899 adults in four Asian countries. Urinary concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry. A questionnaire survey was administered regarding individual characteristics. Anthropometric measurements (height and weight) were performed. Systolic and diastolic blood pressures were measured after a short rest. Multiple linear regression models were applied to investigate associations between urinary heavy metal concentrations and blood pressure after adjustments for age, sex, and body mass index. RESULTS: The geometric means of the urinary concentrations of arsenic, cadmium, lead, and selenium were 84.6, 0.885, 2.09, and 16.5 μg/g creatinine, respectively. The urinary arsenic concentrations were slightly higher than those typically reported in non-polluted populations, while urinary cadmium, lead, and selenium concentrations were equivalent or slightly lower. The urinary lead concentrations were positively associated with both systolic and diastolic blood pressure, but urinary selenium concentrations were negatively associated with them. CONCLUSIONS Variations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.
Adult ; Arsenic/urine* ; Bangladesh ; Blood Pressure ; Cadmium/urine* ; Cross-Sectional Studies ; Environmental Exposure ; Female ; Humans ; Indonesia ; Lead/urine* ; Linear Models ; Male ; Metals, Heavy/urine* ; Middle Aged ; Nepal ; Selenium/urine* ; Vietnam

BACKGROUND: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan. METHODS: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß-microglobulin and blood and urinary cadmium levels were measured. RESULTS: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß-microglobulin level higher than 10,000 μg/g cr. and a blood cadmium level higher than 6 μg/L or urinary cadmium level higher than 10 μg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy. CONCLUSIONS: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants. REGISTRATION NUMBER No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).
Aged ; Aged, 80 and over ; Cadmium ; adverse effects ; urine ; Cadmium Poisoning ; blood ; complications ; urine ; Creatinine ; urine ; Environmental Exposure ; adverse effects ; Environmental Monitoring ; Environmental Pollutants ; adverse effects ; urine ; Female ; Hospitals ; Humans ; Japan ; Kidney Diseases ; chemically induced ; urine ; Male ; Middle Aged ; Sex Distribution

Objective: To explore the relationship between environmental factors as urinary cadmium and type 2 diabetes mellitus (DM) in adults. Methods: Case-control study was adopted, including 166 cases and 427 controls. General characteristics of the subjects were collected by a structured questionnaire. FPG, biochemical indexes and urinary cadmium (UCd) were detected respectively, while UCd was corrected with creatinine. Unconditioned logistic regression model was applied to analyze the relationship between UCd and DM. Results: Levels of UCd appeared higher in cases with the following characteristics as: having primary school education (P=0.016), being female (P=0.013), being non-smokers (P=0.014) or non-alcoholic (P=0.025), and with BMI>25.00 kg/m(2) (P=0.040, P=0.025) than those appeared in the control group. Same results were shown in the 60-69 years (P=0.024) old group. Data from the unconditional logistic regression analysis showed that family history of DM (OR=3.19, 95%CI: 1.45-7.03), education status (OR=1.50,95%CI: 1.08-2.08) and UCd (OR=1.61, 95%CI: 1.08-2.41) were influencing factors on DM. Conclusion: A close association between UCd and DM was noticed. UCd appeared a risk factor on DM that called for setting up related prevention program to reduce the exposure of Cd and to control the risk on DM.
Adult ; Cadmium/urine* ; Case-Control Studies ; China/epidemiology* ; Creatinine ; Diabetes Mellitus, Type 2/epidemiology* ; Female ; Humans ; Risk Factors ; Socioeconomic Factors

Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.
Acetylglucosaminidase/urine ; Adult ; Aged ; Arsenic/*urine ; Bone Density ; Cadmium/*blood ; Case-Control Studies ; Chemical Industry ; Creatinine/urine ; *Environmental Exposure ; Environmental Pollutants/*analysis/blood/urine ; Female ; Humans ; Lead/*blood ; Male ; Middle Aged ; Regression Analysis ; Republic of Korea ; Spectrophotometry, Atomic

A survey involving 6103 participants from five Chinese provinces was conducted to evaluate the threshold value of urinary cadmium (UCd) for renal dysfunction as benchmark dose low (BMDL). The urinary N-acetyl-β-D-glucosaminidase (UNAG) was chosen as an effect biomarker. The UCd BMDLs for UNAG ranged from 2.18 μg/g creatinine (cr) to 4.26 μg/g cr in the populations of different provinces. The selection of the sample population and area affect the evaluation of the BMDL. The reference level of UCd for renal effects was further evaluated based on the data of all 6103 subjects. With benchmark responses (BMR) of 10%/5%, the overall UCd BMDLs for males in the total population were 3.73/2.08 μg/g cr. The BMD was slightly lower in females, thereby indicating that females may be relatively more sensitive to Cd exposure than are males.
Adult ; Aged ; Aged, 80 and over ; Cadmium ; toxicity ; urine ; China ; epidemiology ; Creatinine ; urine ; Dose-Response Relationship, Drug ; Environmental Pollutants ; toxicity ; urine ; Female ; Humans ; Kidney Diseases ; chemically induced ; Male ; Middle Aged ; Population Surveillance

OBJECTIVETo evaluate the endocrine disrupting effects of cadmium (Cd) using OECD enhanced TG407 test guideline.

METHODSSprague-Dawley (SD) rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg•BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary β2-microglobulin, organ weights and histopathology and estrous cycle were detected.

RESULTSCd could significantly decrease animals' body weight (P<0.05). Serum luteinizing hormone (LH) at 10-20 mg/kg•BW groups and testosterone (T) at 2.5 and 10 mg/kg•BW groups decreased significantly (P<0.05). However, no statistically significant change was found in urinary β2-microglobulin among Cd-treatment groups (P>0.05). Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg•BW groups showed significant increase (P<0.05). While among male rats in 2.5, 10, 20 mg/kg•BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased (P<0.05). Moreover, no histopathological change was observed in kidney.

CONCLUSIONResults suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive.

Animals ; Body Weight ; drug effects ; Cadmium ; toxicity ; Eating ; drug effects ; Endocrine Disruptors ; toxicity ; Female ; Hormones ; blood ; Kidney ; drug effects ; Male ; Organisation for Economic Co-Operation and Development ; Random Allocation ; Rats, Sprague-Dawley ; Uterus ; drug effects ; beta 2-Microglobulin ; urine

OBJECTIVETo evaluate the levels of lead (Pb) and cadmium (Cd) in blood and urine among general population in China, and thereby analyze their prevalent features.

METHODSA total of 18 120 subjects from general population aged 6-60 years were recruited from 24 districts in 8 provinces in eastern, central and western China mainland from 2009 to 2010, by cluster random sampling method. The blood samples and urine samples of these people were collected. The questionnaire survey was used to collect the information of the living environment and health conditions.Inductive coupled plasma mass spectrometry was applied to test the Pb and Cd levels in the samples, and the distribution of Pb and Cd in blood and urine for different ages, genders, areas and life habits were then analyzed.

RESULTSAmong the general population in China, the geometric mean (GM) of blood Pb concentration was 34.9 µg/L; the GM of blood Pb in male and female groups were 40.1 and 30.4 µg/L (Z = -28.05, P < 0.05), respectively; the GM from eastern, central and western China were 31.2, 38.8 and 58.9 µg/L (χ(2) = 1 483.33, P < 0.05) , respectively. The GM of urine Pb of the whole population was 1.05 µg/L;while the GM in male and female groups were 1.06 µg/L and 1.05 µg/L (Z = -0.73, P > 0.05) , respectively;the values from eastern, central and western China were 0.76, 2.85 and 3.22 µg/L (χ(2) = 1 982.11, P < 0.05), respectively. The GM of blood Cd concentration among general population was 0.49 µg/L; and the values in male and female group were 0.60 and 0.41 µg/L (Z = -11.79, P < 0.05) , respectively; the GM from eastern, central and western China were 0.45, 0.65 and 0.67 µg/L (χ(2) = 69.87, P < 0.05), respectively; the GM of urine Cd concentration of the whole population was 0.28 µg/L, while the GM in male and female groups were 0.29 and 0.28 µg/L (Z = -3.86, P < 0.05), respectively; the values from eastern, central and western China were 0.29,0.42 and 0.18 µg/L (χ(2) = 402.76, P < 0.05), respectively. the Spearman's rank correlation coefficient for Cd in blood and Cd in urine was 0.22, for Pb in blood and Pb in urine was 0.21. Both the correlations were statistic significant (P < 0.05).

CONCLUSIONThe Pb and Cd levels in blood and urine were relatively higher among general population in China varying by gender and area. There were positive correlations between Pb and Cd levels in blood and those in urine.

Adolescent ; Adult ; Cadmium ; blood ; urine ; Child ; China ; epidemiology ; Cross-Sectional Studies ; Environmental Exposure ; Female ; Humans ; Lead ; blood ; urine ; Male ; Middle Aged ; Sentinel Surveillance ; Young Adult

OBJECTIVEThe aim of this study was to investigate the association between urinary cadmium and clinicopathological characteristics of breast cancer.

METHODSThe clinicopathological characteristics of 240 patients with breast cancer were obtained and urine specimens were collected from October 2009 to July 2010. The concentration of urinary cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). χ(2) test and Wilcoxon rank sum test were used to analyze whether urinary cadmium is associated with clinicopathological characteristics of breast cancer.

RESULTSThe median concentration of urine cadmium of 240 patients was 1.99 µg/g (25th percentile, 1.32 µg/g; 75th percentile, 2.88 µg/g). HER-2 positive rate, regional/distant metastasis rate, and advanced stage rate in patients with the highest tertile of cadmium concentration were significantly higher than those in the patients with second and lowest Cd tertiles (P = 0.042, P = 0.028 and P = 0.017, respectively), and 28.2% vs. 16.5% for HER-2 and 47.2% vs. 32.0% for regional/distant metastasis, respectively. There were still significant associations between urinary cadmium levels and these clinicopathological parameters after being adjusted in age by unconditional logistic regression model, respectively (P < 0.05).

CONCLUSIONSThe results of this study suggest that urinary cadmium levels are associated with the HER-2 status, regional/distant metastasis status and stages of breast cancer, respectively. Cadmium may induce highly aggressive breast cancer in humans.

Adult ; Age Factors ; Breast Neoplasms ; metabolism ; pathology ; urine ; Cadmium ; urine ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Receptor, ErbB-2 ; metabolism