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Background: Itai-itai disease is the most severe case of chronic cadmium (Cd) toxicity, which was endemic in Cd-polluted areas in the Jinzu River basin in Toyama prefecture, Japan. Akita prefecture also has Cd-polluted areas, but there have been no cases of "itai-itai disease"., Case Presentation: An elderly female farmer with Cd nephropathy residing in a Cd-polluted area in the northern part of the Akita prefecture was identified through hospital-based screening at Akita Rosai Hospital in Odate city. She had chronic renal failure with a high Cd exposure level and advanced renal tubular dysfunction. The shortening of height, bone deformities and fractures, abnormal bone metabolism suggesting osteomalacia, and renal anemia were also noted. Therefore, "itai-itai disease", similar to cases in the Jinzu River basin, was suspected., Conclusion: This is the first case of "itai-itai disease" in a Cd-polluted area in Akita prefecture.

The objective of this study was to assess the effect of environmental cadmium exposure according to urinary cadmium concentration (U-Cd) on noncancer mortality in a general Japanese population. We conducted a longitudinal study for 19 years in 2804 inhabitants (1107 men and 1697 women) in some cadmium nonpolluted regions in Japan. The participants were classified into quartiles based on U-Cd (μg/g cre) adjusted for urinary creatinine. Hazard ratio (HR) and 95% confidence interval (95% CI) for continuous U-Cd or the quartiles of U-Cd were calculated for noncancer mortality. By applying a Fine and Gray competing risk model, continuous U-Cd (+1 μg/g cre) showed significant HR for cardiocerebrovascular diseases (HR 1.05, 95% CI: 1.00-1.11), cerebrovascular diseases (HR 1.08, 95% CI: 1.01-1.16), and cerebral infarction (HR 1.11, 95% CI: 1.04-1.20) in men. However, notable significant HR for continuous and quartered U-Cd were not observed in women. In this study, U-Cd was associated with increased cardiocerebrovascular mortality in a general Japanese population, suggesting that environmental cadmium exposure is detrimental to the life prognosis in cadmium nonpolluted regions in Japan., (© 2020 John Wiley & Sons, Ltd.)

The aim of this study was to estimate the benchmark dose (BMD) as the threshold limit level of the cadmium (Cd) concentration in rice for itai-itai disease and/or suspected disease; it was based on the data that previously evaluated the association for such diseases with the Cd concentration in rice by using a logistic regression model. From 1971 to 1976, a total of 2446 rice samples were analyzed across the 88 hamlets in the Jinzu river basin. The mean Cd concentration in rice in each hamlet was used as the index of external Cd exposure of the entire population of the hamlet. We employed the incidence of itai-itai disease and/or suspected disease obtained from the available 55 hamlets. As the threshold, the lower limit of the BMD (BMDL) of the Cd concentration in rice for itai-itai disease and/or suspected disease was estimated using a logistic model, setting the benchmark response at 1% or 2%. The estimated BMDLs of the Cd concentration in rice for itai-itai disease and/or suspected disease were 0.62-0.76 and 0.27-0.56 mg kg -1 in men and women, respectively. The lowest BMDL was 0.27 mg kg -1 in women. In the present study, the threshold limit level of the Cd concentration in rice for itai-itai disease, which is the most severe form of chronic Cd poisoning, was estimated for the first time. This result provides important information about the worldwide standard for the Cd concentration in rice. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures.

The outbreak of itai-itai disease, which is the most severe stage of chronic cadmium poisoning, has occurred in the cadmium-polluted Jinzu River basin in Toyama. In this area, the river was contaminated by slags from a mine upstream; consequently, the soil in rice paddies became polluted with heavy metals including cadmium through irrigation water streams from around 1910 to the 1960s. The inhabitants of the Jinzu River basin used the river water for drinking and cooking until around 1960. In this paper, we review the geographical features of the Jinzu River basin and the endemic area of itai-itai disease, and reevaluated the studies conducted in 1970's by the Toyama Institute of Health, because these studies have revealed a clear relationship between renal dysfunction or occurrence of itai-itai disease and exposure to cadmium through irrigation water streams.

This study evaluated the levels of As, Cd, and Pb in muscle and liver the cattle and chicken. The risk was estimated for the adult population of a midsized city in southeast Brazil, concerning the tolerable ingestion and cancer risk. Samples of muscle and liver (cattle and chicken) were collected (n = 250). Samples of mineral supplements for cattle (n = 4) and chicken feed samples (n = 4) were evaluated as one of many potential source of contamination. Muscle, liver, mineral supplement, and feed samples were dissolved in acid medium and analyzed by ICP-OES. Daily muscle and liver intake was estimated using a questionnaire (N = 427). Daily intake of trace elements by the population based on the consumption of cattle muscle, cattle liver, chicken muscle, and chicken liver was low, corresponding to 2.76%, 0.33%, 2.12%, and 0.22% of the Tolerable Intake defined by the WHO for As; 0.54%, 0.29% 0.55%, 0.01%, for Cd; and 0.80%, 0.07%, 0.62%, 0.02%, for Pb. The mean of total ingestion of As, Cd and Pb was 5.43%, 1.18% and 1.51%, respectively of Tolerable Intake defined by WHO. Cancer risk was lower than 5 × 10 -5 year -1 . The results indicate that the muscle and liver consumption is a source of As, Cd, and Pb. Consumers that ingest cattle and chicken muscle need attention in terms the risk of cancer related to intake of As and Cd. Feed and mineral supplementation remain as one of many sources of exposure of As, Cd, and Pb., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Cadmium is a heavy metal of increasing environmental concern that has long been associated to several human pathological processes. Recent population surveys have correlated cadmium non-occupational exposure to widespread idiopathic pathologies. Food and tobacco are reported to be the main exposure sources of cadmium to the general population, as phosphate fertilizers are rich in such a metal, thus contaminating the crops. Although its mechanisms of toxicity are not a consensus in the literature, it is well established that reactive oxygen species play a key role in this process, leading to the oxidation of several biological molecules. We have therefore assessed whether three environmentally realistic doses of cadmium alter the oxidative status of Wistar rat testis and eventually result in histological damages. Our results show that even the lowest environmental dose of cadmium was able to disturb the endogenous antioxidant system in Wistar testis, although an increase in lipid peroxidation was observed only within the group exposed to the highest environmental dose. Despite that no remarkable morphological changes were observed in any group, significant alterations in blood vessel lumen were reported for some cadmium-exposed animals, suggesting that endothelium is one of the primary targets involved in cadmium toxicity.

Objectives: Cadmium is a non-essential toxic metal with multiple adverse health effects. Cadmium has been shown to be associated with cardiovascular diseases, but few studies have investigated heart failure (HF) and none of them reported atrial fibrillation (AF). We examined whether cadmium exposure is associated with incidence of HF or AF., Design: A prospective, observational cohort study with a 17-year follow-up., Setting: The city of Malmö, Sweden., Participants: Blood cadmium levels were measured in 4378 participants without a history of HF or AF (aged 46-67 years, 60% women), who participated in the Malmö Diet and Cancer (MDC) study during 1992-1994., Primary and Secondary Outcome Measures: Incidence of HF and AF were identified from the Swedish hospital discharge register., Results: 143 participants (53% men) were diagnosed with new-onset HF and 385 individuals (52% men) were diagnosed with new-onset AF during follow-up for 17 years. Blood cadmium in the sex-specific 4th quartile of the distribution was significantly associated with incidence of HF. The (HR, 4th vs 1st quartile) was 2.64 (95% CI 1.60 to 4.36), adjusted for age, and 1.95 (1.02 to 3.71) after adjustment also for conventional risk factors and biomarkers. The blood cadmium level was not significantly associated with risk of incident AF., Conclusions: Blood cadmium levels in the 4th quartile were associated with increased incidence of HF in this cohort with comparatively low exposure to cadmium. Incidence of AF was not associated with cadmium., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: Cadmium is a human lung carcinogen and possesses estrogen-like activity. This combination of carcinogenic and estrogenic activity makes cadmium a contaminant of high concern for hormone-related cancers. Diet and smoking are the main sources of cadmium exposure. The aim of this study was to investigate the association between dietary cadmium intake and risk of breast, endometrial and ovarian cancer in Danish postmenopausal woman., Methods: We estimated dietary cadmium intake in the Diet, Cancer and Health cohort at enrolment 1993-97. The estimates were based on food frequency questionnaires and cadmium contents in all foods. Among 23,815 postmenopausal women we identified 1390 breast, 192 endometrial, and 146 ovarian cancer cases from enrolment through December 31, 2010 using the Danish Cancer Registry. Cox regression was used to analyse the association between dietary cadmium intake and cancer risk., Results: Mean dietary cadmium intake was 14 µg/day. Cadmium was not associated with breast cancer, incidence rate ratio (IRR) = 0.99, 95% confidence interval (CI): 0.87-1.13 per 10 µg higher dietary cadmium intake/day; endometrial cancer, IRR = 1.08, 95% CI: 0.76-1.53; or ovarian cancer, IRR = 1.15, 95% CI: 0.78-1.70. We found a positive association between cadmium and endometrial cancer for the women with BMI<25 (IRR = 1.50, 95% CI: 0.94-2.39), whereas an inverse association was seen for the women with BMI≥25 (IRR = 0.69, 95% CI: 0.42-1.12); p value for interaction = 0.02., Conclusions: Our study does not indicate that our estimated dietary cadmium intake is associated with hormone-related cancers in women.

This study presents concentrations of Fe, Zn, Mn, Cu, Pb and Cd in livers, kidneys, muscles and bones of white-fronted geese Anser albifrons (geese) and spot-billed ducks Anas poecilorhyncha (ducks). Iron in livers, kidneys and muscles, Zn in muscles, Mn and Cd in every tissue, Cu in livers, muscles and bones and Pb in bones differed between species, and there were significant differences among tissues in both species. Essential elements such as Fe, Zn, Mn and Cu concentrations were within the background levels. Lead concentrations in livers of 7 of 14 geese and 7 of 19 ducks and in bones of 4 of 19 ducks exceeded background concentrations for waterfowl (5 μg/g dw for the liver, 10 μg/g dw for the bone). Almost all samples of both species had the background Cd concentrations in the liver (33 of 33 geese and ducks) and kidney (14 geese and 18 ducks). Tissue concentrations of Cd were greater in geese than ducks. In contrast, tissue concentrations of Pb in bones were greater in ducks than in geese. These different trends for Cd and Pb reflect a short and/or long term difference in exposure and degree of accumulation of these metals.

Introduction: Toxic heavy metals have adverse effects on human health. However, the risk of hematuria caused by heavy metal exposure has not been evaluated., Methods: Data from 4701 Korean adults were obtained in the Korean National Health and Nutritional Examination Survey (2008-2010). Blood levels of the toxic heavy metals cadmium, lead, and mercury were measured. Hematuria was defined as a result of ≥+1 on a urine dipstick test. The odds ratios (ORs) for hematuria were measured according to the blood heavy metal levels after adjusting for multiple variables., Results: Individuals with blood cadmium levels in the 3rd and 4th quartiles had a greater OR for hematuria than those in the 1st quartile group: 3rd quartile, 1.35 (1.019-1.777; P=0.037); 4th quartile, 1.52 (1.140-2.017; P=0.004). When blood cadmium was considered as a log-transformed continuous variable, the correlation between blood cadmium and hematuria was significant: OR, 1.97 (1.224-3.160; Ptrend=0.005). In contrast, no significant correlations between hematuria and blood lead or mercury were found in the multivariate analyses., Discussion: The present study shows that high cadmium exposure is associated with a risk of hematuria., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated., Methods: A population-based cohort of 41 089 Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases)., Results: Mean dietary cadmium exposure was 19 μg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers., Conclusion: Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.

Purpose: The aim of the study was to estimate the association between dietary intake of cadmium, a carcinogenic heavy metal, and risk of invasive postmenopausal breast cancer., Methods: Study subjects were 30,543 postmenopausal women in the VITamins And Lifestyle (VITAL) cohort who completed a food frequency questionnaire (FFQ) at baseline (2000-2002). Dietary cadmium consumption was estimated by combining FFQ responses with US Food and Drug Administration data on food cadmium content. Incidence of invasive breast cancer was ascertained through linkage of the cohort to the western Washington Surveillance, Epidemiology, and End Results cancer registry through 31 December 2009. Cox regression was applied to estimate adjusted hazard ratios (aHRs) and 95 % confidence intervals (CIs) for breast cancer with increasing dietary cadmium intake, adjusted for total energy intake, smoking history, consumption of vegetables, potatoes, and whole grains, multivitamin use, education, race, body mass index, physical activity, age at first birth, postmenopausal hormone use, and mammography., Results: Vegetables and grains together contributed an average of 66 % of estimated dietary cadmium. During a mean of 7.5 years of follow-up, 1,026 invasive postmenopausal breast cancers were identified. Among 899 cases with complete covariate information, no evidence of an association between dietary cadmium intake and breast cancer risk was observed (aHR (95 % CI), highest to lowest quartile cadmium: 1.00 (0.72-1.41), p (trend) = 0.95). No evidence was found for interactions between dietary cadmium and breast cancer risk factors, smoking habits, or total intake of calcium, iron, or zinc from diet, supplements, and multivitamins., Conclusions: This study does not support the hypothesis that dietary cadmium intake is a risk factor for breast cancer. However, non-differential measurement error in the estimate of cadmium intake is likely the most important factor that could have obscured an association.

This study estimates the dietary exposure to cadmium (Cd), and associated potential health risks, for individuals living and working in a metal recycling community (n=132) in Vietnam in comparison to an agricultural (reference) community (n=130). Individual-level exposure to Cd was estimated through analysis of staple foodstuffs combined with information from a food frequency questionnaire. Individual-level exposure estimates were compared with published 'safe' doses to derive a Hazard Quotient (HQ) for each member of the study population. Looking at the populations as a whole, there were no significant differences in the diets of the two villages. However, significantly more rice was consumed by working age adults (18-60 years) in the recycling village compared to the reference village (p<0.001). Rice was the main staple food with individuals consuming 461±162g/d, followed by water spinach (103±51kg/d). Concentrations of Cd in the studied foodstuffs were elevated in the metal recycling village. Values of HQ exceeded unity for 87% of adult participants of the metal recycling community (39% had a HQ>3), while 20% of adult participants from the reference village had an HQ>1. We found an elevated health risk from dietary exposure to Cd in the metal recycling village compared to the reference community. WHO standard of 0.4mg Cd/kg rice may not be protective where people consume large amounts of rice/have relatively low body weight., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A review of the epidemiological literature on the potential effects of land contamination shows that the largest body of contaminant-specific research relates to cadmium (Cd). First, a brief outline of the key issues related to the study of health impact of land contamination is presented. The recent literature is then reviewed for evidence of associations and possible causal relationships between exposure to Cd from land contamination and health impact. A large number of studies focusing on Cd arise because of the ready availability of biomarkers of exposure and effect and the demonstrated link between soil Cd and itai-itai disease (severe renal and bone disorders) via dietary exposure in Japan and China. Where dietary differences yield lower exposures, links have been established between Cd in soil and biomarkers of renal or bone dysfunctions, but not to health impacts per se. Potential effects of Cd exposure were also investigated for other health outcomes, including hypertension, cancer incidence, preterm delivery, and semen parameters. In contrast to renal and bone disorders, results are generally inconsistent and require further lines of evidence. Residence in locations with elevated concentrations of Cd in soil is a poor surrogate for exposure, and there are examples where residents in locations with elevated concentrations of Cd in soil did not appear to suffer serious health consequences.

Cadmium (Cd) is one of the most toxic elements to which humans could be exposed at work or in the environment. The outbreak of itai-itai disease, which is the most severe stage of chronic Cd poisoning, occurred in the Cd-polluted Jinzu River basin in Toyama. In this area, the river was contaminated by slag from a mine upstream; as a consequence, the soil in rice paddies was polluted with heavy metals including Cd through irrigation water from around 1910 to the 1960s. The government of Toyama prefecture carried out an extensive survey on Cd concentration in rice and soil of the paddy fields and declared that the upper layer of a total of 1500 ha of paddy fields should be replaced by nonpolluted soil. Then, an intervention program of soil replacement in the polluted paddy fields was continually carried out from 1980 to 2011. As a result, Cd concentration in rice markedly decreased. The kidney is the organ critically affected after long-term exposure to Cd. Proximal tubular dysfunction (RTD) has been found among the inhabitants of the Jinzu River basin. The very recent report by the Environmental Agency in Japan in 2009 has disclosed that b2-microglobulinuria with RTD is still found at a high prevalence among the inhabitants of the Jinzu River basin of both sexes. Twenty patients with itai-itai disease (1 male and 19 females), who attended our hospital and received medical examination during 2000 to 2008, had applied for recognition as itai-itai disease patients to the government of Toyama prefecture. In this paper, the recent epidemiological and clinical features of itai-itai disease are discussed on the basis of a review of the cases of these 19 female patients.

Background: The rising prevalence of chronic kidney disease (CKD) and subsequent end stage renal failure necessitating renal replacement therapy has profound consequences for affected individuals and health care resources. This community based study was conducted to identify potential predictors of microalbuminuria in a randomly selected sample of adults from the North Central Province (NCP) of Sri Lanka, where the burden of CKD is pronounced and the underlying cause still unknown., Methods: Exposures to possible risk factors were determined in randomly recruited subjects (425 females and 461 males) from selected areas of the NCP of Sri Lanka using an interviewer administered questionnaire. Sulphosalicylic acid and the Light Dependent Resister microalbumin gel filtration method was used for initial screening for microalbuminuria and reconfirmed by the Micral strip test., Results: Microalbumnuria was detected in 6.1% of the females and 8.5% of the males. Smoking (p < 0.001), alcohol use (p = 0.003), hypertension (p < 0.001), diabetes (p < 0.001), urinary tract infection (UTI) (p = 0.034) and consumption of water from wells in the fields (p = 0.025) were associated with microalbuminuria. In the binary logistic regression analysis, hypertension, diabetes mellitus, UTI, drinking well water in the fields, smoking and pesticide spraying were found to be significant predictors of microalbuminuria., Conclusions: Hypertension, diabetes mellitus, UTI, and smoking are known risk factors for microalbuminuria. The association between microalbuminuria and consumption of well water suggests an environmental aetiology to CKD in NCP. The causative agent is yet to be identified. Investigations for cadmium as a potential causative agent needs to be initiated.

The Khanty-Mansi Autonomous District (KMAD) occupies a prominent place in the economy of Russia in oil and gas production and energy generation. The development of hydrocarbon raw material extraction in the district does great damage to the environment and nature. This results in the accumulation of toxic chemical elements in man. The levels of lead, cadmium, calcium, and zinc were measured in the hair of indigenous and non-indigenous populations of the district. High lead and cadmium and low calcium and zinc concentration were found in indigenous adults and children in the KMAD.

Introduction: Impulsiveness, hyperactivity, and attention deficit are the most frequent neurocognitive disorders of childhood. Leaving aside the putative role of environmental and nutritive factors, the etiology and pathogenesis of these disorders remains unknown. The aim of this study was to examine the relationship between the concentration of lead, cadmium, and polyunsaturated fatty acids, and functioning of the child with developmental disorders., Material and Methods: The study enrolled 78 children with behavioral disorders. The mean age of the children was eight years. Standardized tools were used: Manfred Cierpka Family Assessment Measures, Children's Health Questionnaire Parent Form-28, and ADHD-Rating Scale-IV. Concentrations of lead and cadmium in venous blood, lipid profile, and the percentage of some omega-3 and omega-6 fatty acids in the erythrocyte membrane were measured., Results: A correlation between higher levels of lead in blood of the child and impulsive and hyperactive behaviors at home was observed. Concentrations of cadmium correlated with increased incidence of attention deficit at school. Analysis of the health profile revealed that lead and cadmium correlate with some of the elements that make up the image of a properly functioning child. Reduced levels of AA and EPA positively correlated with the incidence of hyperactive and impulsive behaviors. Reduced levels of GLA impaired the acceptance of norms and values. Levels of EPA and DHA had an impact on the overall state of health of the child, as well as on physical activity and feeling of loneliness., Conclusions: 1. Developmental disorders at school and difficulties in functioning at home may be the consequence of dysfunctions caused by lead and cadmium. 2. Deficiencies of AA, GLA, DHA, and EPA fatty acids or a disorder of their metabolism affect the behavior of the child in the form of hyperactivity, impulsiveness, and attention deficit.

Background: Limited epidemiologic data are available concerning the cardiovascular effects of cadmium exposure, although recent studies suggest associations with myocardial infarction and peripheral arterial disease. We examined the associations of cadmium exposure with cardiovascular disease in nationally representative general Korean adults., Methods: We used cross-sectional data on blood cadmium and self-reported diagnoses of ischemic heart disease (IHD), stroke, and hypertension in a sub-sample of 1908 adults, aged 20 years and older, who participated in the 2005 Korea National Health and Nutrition Examination Survey (KNHANES). We used survey logistic regression models accounting for the complex sampling design to estimate the odds ratios (OR), adjusting for age, education, income, alcohol, smoking, body mass index, waist circumference, family history of hypertension, blood pressure, and blood lead., Results: The geometric mean of blood cadmium was 1.53 μg/L. After adjusting for potential confounders, an interquartile range (IQR) increase in blood cadmium (0.91 μg/L) was found to be associated with an increased risk for IHD (OR 2.1, 95% confidence interval (CI) 1.3-3.4). An IQR increase in blood cadmium was found to be associated with an elevated risk for hypertension only among men (OR 1.4, 95% CI 1.1-1.8) but not among women. No association was observed with stroke in both genders., Conclusions: These findings suggest that cadmium in blood may be associated with an increased risk for IHD and hypertension in the general Korean adult population., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: An association between cadmium exposure and bone mineral density (BMD) has been demonstrated in elderly women, but has not been well studied in youths and men. Some studies report either no or a weak association between cadmium exposure and bone damage., Objectives: This study was designed to investigate the relationship between the urinary cadmium (U-Cd) levels and BMD of females and males of all ages., Methods: A total of 804 residents near an industrial complex were surveyed in 2007. U-Cd and BMD on the heel (non-dominant calcaneus) were analyzed with AAS-GTA and Dual-Energy X-ray absorptiometry, respectively. Demographic characteristics were collected by structured questionnaires. Osteoporosis and osteopenia were defined by BMD cut-off values and T-scores set by the WHO; T score>-1, normal; -2.5

Purpose: The cadmium-polluted Jinzu River Basin in Toyama, Japan, where nephropathy and itai-itai disease were endemic among resident farmers decades ago, has been almost completely restored. The aim of this study is to investigate whether inhabitants there would still exhibit cadmium accumulation and its effects on kidneys, bones, and erythropoiesis., Methods: We performed a cross-sectional study of 150 subjects from the polluted area and 144 controls from the same prefecture. Participants included female inhabitants from 34 to 74 years of age who underwent examinations to gather anthropometrical and medical information, obtain rice, blood and urine samples, and measure bone mineral density., Results: Cadmium concentration in rice from the polluted area was lower than the level in the control area. Blood and urinary cadmium and urinary β(2)-microglobulin levels were higher in subjects from the polluted area than controls, and the urinary β(2)-microglobulin was independently affected by urinary cadmium. Bone mineral density did not differ between the two areas, but it was affected by renal tubular function in subjects from the polluted area. Serum bone alkaline phosphatase was lower in subjects from the polluted area compared to controls. We detected three cases of cadmium nephropathy among the subjects. One of them suffered from a renal anemia type of itai-itai disease., Conclusion: Inhabitants in the formerly polluted area still had high cadmium accumulations and showed a characteristic natural history of chronic cadmium toxicity, indicating that the risk remains for developing nephropathy or itai-itai disease in the future.

Background: It is unclear whether environmental cadmium exposure is associated with cardiovascular disease, although recent data suggest associations with myocardial infarction and peripheral arterial disease., Objective: The objective of this study was to evaluate the association of measured cadmium exposure with stroke and heart failure (HF) in the general population., Methods: We analyzed data from 12,049 participants, aged 30 years and older, in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) for whom information was available on body mass index, smoking status, alcohol consumption, and socio-demographic characteristics., Results: At their interviews, 492 persons reported a history of stroke, and 471 a history of HF. After adjusting for demographic and cardiovascular risk factors, a 50% increase in blood cadmium corresponded to a 35% increased odds of prevalent stroke [OR: 1.35; 95% confidence interval (CI): 1.12-1.65] and a 50% increase in urinary cadmium corresponded to a 9% increase in prevalent stroke [OR: 1.09; 95% CI: 1.00-1.19]. This association was higher among women [OR: 1.38; 95% CI: 1.11-1.72] than men [OR: 1.30; 95% CI: 0.93-1.79] (p-value for interaction=0.05). A 50% increase in blood cadmium corresponded to a 48% increased odds of prevalent HF [OR: 1.48; 95% CI: 1.17-1.87] and a 50% increase in urinary cadmium corresponded to a 12% increase in prevalent HF [OR: 1.12; 95% CI: 1.03-1.20], with no difference in sex-specific associations., Conclusions: Environmental exposure to cadmium was associated with significantly increased stroke and heart failure prevalence. Cadmium exposure may increase these important manifestations of cardiovascular disease., ((c) 2009 Elsevier Inc. All rights reserved.)

Cadmium is a metallic impurity in various minerals. The two main cadmium exposure sources in general population are food and tobacco smoking. Its industrial exploitation has grown in the early twentieth century. Cadmium is used in accumulators or alkaline batteries (80%) and in pigments for paints or plastics (10%), in electrolytic process by deposit or by cadmium plating on metals or to reduce melting points (welding rods...). Cadmium is a cumulative toxic substance whose half-time for elimination is about 20 to 40 years and it is mainly stored in the liver and kidneys. Inhalation of cadmium oxide fumes may cause inhalation fevers or chemical pneumonitis. Cadmium chronic poisoning causes mainly renal tubulopathy and could be the cause of osteomalacia and diffuse osteoporosis. Cadmium is classified as certain carcinogen agent for humans by International Agency for Research on Cancer (IARC). The most relevant biological index exposure is the urinary cadmium. According to literature, no chelating agent can be still used in human cadmium poisonings. In France, some diseases caused by occupational exposure to cadmium may be compensated.

The incidence of serious poisoning caused by occupational cadmium exposure has declined over the past four decades due to improvements in the work environment. However, long-term low-level exposure to cadmium needs to be addressed. For workers in industries that handle cadmium, it is necessary to consider the daily cadmium intake from contaminated foods such as cereals and rice in addition to the occupational exposure, since workers might be exposed to higher levels of cadmium from a combination of these sources. Cadmium accumulates in the renal cortex by the long-term exposure along with increased concentrations of metallothionein, an important protein for protection from cadmium toxicity. However, some individuals have lower metallothionein levels despite increased cadmium accumulation in the kidneys. This article describes the strategy method for analyzing individual susceptibility to cadmium toxicity and genetic polymorphisms of metallothionein, with reference to the current status of occupational cadmium exposure.

This study was undertaken to estimate the amount of cadmium (Cd) exposure needed for the development of Itai-itai disease and the influence of using Jinzu River water for drinking and/or cooking on its development. The subjects comprised 38 Itai-itai disease patients admitted both for questionnaire survey and medical testing. The period when the patients started to perceive leg/back pain was defined as 'mild disease onset' and that when they experienced the most severe manifestations such as ambulatory disturbance as 'severe disease onset'. In a comparison of non-users/users of river water, mean age and lifetime Cd intake (LCd) estimated from the daily consumption of rice and other foods at the onset of mild or severe disease showed smaller values in the users than non-users. LCd in non-users/users of river water for drinking and/or cooking were estimated as 3.46-3.60 g/2.58-2.63 g at mild disease onset and 4.24-4.44 g/3.50-3.54 g at severe disease onset. A portion of the differences in LCd in non-users/users is attributable to the influence of Cd consumption from the use of river water, although it was suggested that LCd estimated from eating Cd-polluted rice exerted a greater influence on the development of Itai-itai disease than drinking and/or cooking with Cd-polluted river water.

Background: Chronic inflammation and malnutrition are associated with increased risk of cardiovascular death, and may cause protein-energy wasting in individuals with chronic kidney disease. Raised blood cadmium (Cd) levels were observed in maintenance haemodialysis (HD) patients in previous studies. However, the correlation of Cd exposure with inflammation and malnutrition remains uncertain. This study examined the possible adverse effects of environmental Cd exposure in maintenance HD patients., Methods: A total of 954 maintenance HD patients were enrolled and divided into four equal-sized groups based on blood Cd levels. Geographic, haematological, biochemical and dialysis-related data were obtained. The analysis included values for nutritional and inflammatory markers., Results: Abnormal blood Cd levels (> or =1 microg/L) were exhibited in 26.8% (256/954) of studied subjects. More subjects in the highest quartile group were malnourished (chi- square = 23.27; P < 0.0001) and had inflammatory changes (chi-square = 13.99; P = 0.0029) than in the lowest quartile group. Stepwise multiple regression analysis revealed a significant inverse correlation between serum albumin and blood Cd levels. Notably, a 10-fold increase in blood Cd levels was associated with a 0.06 g/dL decrease in serum albumin levels (P = 0.0060). Multivariate regression analysis also demonstrated a positive correlation between inflammatory risk (high-sensitivity C-reactive protein >3 mg/L) and blood Cd levels. The risk ratio of inflammation with a 10-fold increase in blood Cd levels was 1.388 (95% CI: 1.025-1.825, P = 0.0336)., Conclusions: Environmental Cd exposure is significantly associated with malnutrition, inflammation and even protein-energy wasting in maintenance HD patients. It is important for this population to avoid diets with high Cd concentrations and smoking.

The aim of this study was to clarify whether consumption of cadmium (Cd)-polluted rice or Jinzu River water exerted any influence on the occurrence of renal tubular dysfunction and/or Itai-itai disease. From the participants of health examinations conducted in 1967 and 1968, 3,078 subjects who had resided for >30 years in the present hamlet and were aged >50 years were selected as the target population and were divided according to their residence in 55 hamlets. In a multiple regression analysis, the regression coefficients between rice-Cd concentration and prevalence of abnormal urinary findings (proteinuria, glucosuria, or proteinuria with glucosuria) or patients with Itai-itai disease were statistically significant between both sexes. The correlation between the prevalence of users of Jinzu River water and the occurrence of glucosuria in men as well as abnormal urinary findings in women was not statistically significant. We surmise that eating Cd-polluted rice and drinking and/or cooking with Jinzu River water influenced the occurrence of Itai-itai disease. The occurrence of renal tubular dysfunction is likely to have also been influenced by both factors, with eating Cd-polluted rice having a greater impact on the occurrence of renal tubular dysfunction as compared to drinking and/or cooking with Jinzu River water.

No comprehensive data on sources or risk factors of cadmium exposure in Ukrainian children are available. In this we measured the blood levels of cadmium among 80 Ukrainian children and evaluated sources of exposure. A nested case-control study from a prospective cohort of Ukrainian 3-year-old children was conducted. We evaluated predictors of elevated blood cadmium using a multivariable logistic regression model. The model included socioeconomic data, parent occupation, environmental tobacco smoke, hygiene, body-mass index, and diet. Dietary habits were evaluated using the 1992 Block-NCI-HHHQ Dietary Food Frequency survey. Elevated cadmium was defined as blood levels in the upper quartile (0.25 microg/L). The mean age for all 80 children was 36.6 months. Geometric mean cadmium level was 0.21 microg/L (range = 0.11-0.42 microg/L; SD = 0.05). Blood cadmium levels were higher among children taking zinc supplements (0.25 vs 0.21 microg/L; P = 0.032), children who ate sausage more than once per week (0.23 vs 0.20; P = 0.007) and children whose fathers worked in a by-product coking industry (0.25 vs 0.21; P = 0.056). In the multivariable model, predictors of elevated blood cadmium levels included zinc supplementation (adjusted OR = 14.16; P < 0.01), father working in a by-product coking industry (adjusted OR = 8.50; P = 0.03), and low body mass index (<14.5; adjusted OR = 5.67; P = 0.03). This is the first study to indicate a strong association between elevated blood cadmium levels and zinc supplementation in young children. Whole-blood cadmium levels observed in this group of Ukrainian children appear to be similar to those reported in other Eastern European countries.

This study was undertaken to estimate the amount of cadmium (Cd) exposure needed for the development of Itai-itai disease. The investigated subjects comprised 82 Itai-itai disease patients and 11 persons requiring observation who were admitted in 1977 and 1978 for medical testing. With the period when the Itai-itai disease patients started to perceive leg/back pain defined as the 'mild disease onset', and the period when they experienced the most severe manifestations such as ambulatory disturbance and bone fractures defined as 'severe disease onset'. Relative cumulative person number distribution according to life time cadmium intake (LCD) at mild disease onset, severe disease onset, and time of death was depicted as an sigmoid curve and the establishment of probit regression lines was demonstrated between them. LCD at the time when mild disease onset and severe disease onset were recognized in half of the Itai-itai disease patients was 3.1 and 3.8 g, respectively. Furthermore, LCD at the time when mild disease onset and severe disease onset were recognized in 5% of the Itai-itai disease patients was calculated to be 2.6 and 3.3 g, respectively. The present results clarify that Itai-itai disease, the most severe stage of chronic Cd poisoning, occurs at levels of Cd consumption amounting to approximately three-fold of those currently seen in Japan.

This study investigated the associations among prevalence of patients with Itai-itai disease, and prevalence of abnormal urinary findings and cadmium (Cd) concentrations in rice in individual hamlets of the Jinzu River basin. From the 13,183 participants of the 1967 and 1968 health examinations, we selected 3,094 subjects as the target population who had resided in the current hamlet for a total of 30 years or longer and aged >/=50 years, and in the hamlet both the Cd concentration in rice and prevalence of patients with Itai-itai disease were known. When the inhabitants were divided into four groups according to the Cd concentration in rice or prevalence of abnormal urinary findings, significant relationships among three factors (Cd concentration in rice, prevalence of abnormal urinary findings and prevalence of patients with Itai-itai disease) were demonstrated clearly using the Cochran-Armitage test. Correlation coefficients among the three factors in 55 hamlets showed that the prevalence of the patients with Itai-itai disease increased according to increases in the mean Cd concentration in rice and increasing prevalence of urinary findings. This study demonstrated that Itai-itai disease is induced by exposure to environmental Cd and that renal dysfunction plays an important role in its development.

Few studies have estimated the prevalence and mean urinary cadmium levels in U.S. workers and the factors associated with high cadmium exposure. In this study, urinary cadmium measurements were obtained on 11228 U.S. workers aged 18 to 64 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Urinary cadmium levels ranged from 0.01 to 15.57 microg/L, with a geometric mean of 0.30 microg/L (0.28 microg/g creatinine) for all U.S. workers. The prevalence of urinary cadmium levels >or=5 microg/L was 0.42% (551000) for U.S. workers aged 18 to 64 years. Among U.S. workers in the metal industry (two-digit Standard Industrial Classification or SIC codes 33 and 34), the geometric mean urinary cadmium level was 0.48 microg/L (0.39 microg/g creatinine), and 0.45% of these workers had urinary cadmium levels >or=10 microg/L. The prevalence of urinary cadmium levels >or=15 microg/L was 0.0028% (3907). The agriculture industry (two-digit SIC codes 01, 02, and 07-09) was associated with low urinary cadmium levels, compared with repair services industries (two-digit SIC codes 75 and 76). Results from ordinary least squares regression analyses indicated that smokers had significantly higher urinary cadmium levels than nonsmokers (p

The research was carried out concerning the contents of cadmium in breast cancer tissues in 52 women aged 35-81 years (x = 67.62 +/- 12.43) living in the Wielkopolska region. Particular concentrations of this metal in the range of 0.01-1.08 mg/g wet wt. (x = 0.13 +/- 0.18) were found in all the studied specimens. The obtained results were assessed regarding the women's place of residence--Kalisz, Leszno, Pila or Poznan voivodships--and a particular living area: an industrialised town, other towns or villages of the Wielkopolska region. A statistically significant difference in the content of cadmium in breast cancer tissues was found in women inhabiting the Poznan and Pila voivodships. Moreover, marked differences were observed between the average cadmium concentrations in the breast cancer tissue samples in women living in the remaining voivodships and the types of living areas.

Objective: To examine whether environmental exposure to cadmium has been inducing kidney dysfunction among middle-aged women in the general population in Japan., Methods: This study was conducted in 2000 and 2001. Morning spot urine samples were collected from 10,753 women (mostly aged 35 to 60 years) in ten prefectures all over Japan (thus about 1,000 women per site). Urine samples were analyzed for cadmium (Cd-U), calcium (Ca-U), magnesium (Mg-U), zinc (Zn-U), alpha(1)- and beta(2)-microglobulins (alpha(1)- and beta(2)-MG-U). The urinary analyte concentrations were corrected for creatinine (cr) concentration (i.e., Ucr). The data thus obtained were subjected to statistical evaluation by chi-square test, ANOVA, multiple comparison test, and simple regression analysis (SRA) as well as multiple regression analysis (MRA) including logistic regression analysis (LRA). Log-normal distribution was assumed for Cd-Ucr, alpha(1)-MG-Ucr and beta(2)-MG-Ucr, whereas normal distribution was considered for age, Ca-Ucr, Mg-Ucr and Zn-Ucr., Results: Geometric mean values (GM) of Cd-Ucr were distributed unevenly, depending on the sampling areas, with a grand GM of 1.3 microg/g cr, the highest (3.2 microg/g cr) and lowest GM values(0.8 microg/g cr) being significantly different from GMs of other areas. Correlation matrix analysis with subjects of all ages showed that log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr correlated significantly (r=0.272 and 0.202, respectively) with log Cd-Ucr, but they correlated also with age (r=0.280 and 0.213, respectively). The same analysis with the two selected age groups (41-50 and 51-60 years), however, failed to show close correlation of alpha(1)-MG-Ucr and log beta(2)-MG-Ucr with Cd-Ucr. Both MRA and LRA indicated that age was a confounding factor in the evaluation of the effect of Cd-U on the two MG levels. Whereas the LRA with the all-age group showed a positive influence of log Cd-Ucr on log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr, such effect disappeared in parallel with the disappearance of age effects when LRA was conducted with the two selected age groups. An exceptional observation was the influence of log Cd-Ucr on log alpha(1)-MG-Ucr (but not on log beta(2)-MG-Ucr) in LRA when a cut-off value of 5.00 mg for alpha(1)-MG-U/g cr was applied. Comparison between the low and high Cd-U groups showed that both alpha(1)-MG-Ucr and beta(2)-MG-Ucr were higher in the high Cd-U groups, but prevalence of cases with alpha(1)-MG-Ucr and beta(2)-MG-Ucr in excess of the cut-off values did not differ between the two groups except when a cut-off value of 5.00 mg/g cr was employed for alpha(1)-MG-U., Conclusions: In over-all evaluation, no clear-cut evidence was obtained in the present study to show that environmental exposure to Cd has induced tubule dysfunction among middle-aged women in the general population in Japan. It might be the case, however, that an increase in alpha(1)-MG-U was associated with Cd exposure. In this sense, it is apparently desirable from public health viewpoints to make further efforts to reduce the intensity of the general population's exposure to environmental Cd.

We investigated the association between the Cd concentration in rice and renal dysfunction in individuals living in the Cd-polluted Jinzu River basin, using a logistic regression analysis. In the cases of logistic regression analysis for people (1) who had either resided in the present hamlet since birth or who had moved there from a non-polluted area and for those (2) who had resided in the present hamlet since birth, except for glucosuria in males, all partial correlation coefficients between the Cd concentration in rice and occurrence of abnormal urinary findings were statistically significant in both sexes. The allowable level of Cd concentration in rice was calculated by substituting the abnormality rates of urinary findings of the controls in the 40-49, 50-59 and 60-69 year age groups into the logistic regression formula for people (3). The value for subjects aged 50 years was 0.13 and 0.17 ppm for males and females, respectively, with regard to proteinuria and 0.15 and 0.10 ppm for males and females, respectively, with regard to proteinuria+glucosuria.

Serum cadmium levels at delivery were measured in a consecutive sample of 100 mother-infant pairs in Egypt using venous blood from mothers and umbilical cord blood from neonates. The serum cadmium levels of mothers ranged from 0.4 to 2.2 microg/L (mean 0.73 microg/L) and of infants from 0.2 to 1.5 microg/L (mean 0.66 microg/L). Infant cadmium levels were about 70% of maternal levels in most pairs. Serum cadmium was significantly higher in mothers and babies passively exposed to tobacco smoke. Five-minute Apgar scores were negatively correlated with cord blood cadmium levels. The cadmium levels did not differ between subjects from Cairo and Giza or according to urban, suburban or rural areas. Thus, in utero exposure to cadmium was evident and wider-scale studies on its long-term effects are recommended.

Objectives: The purpose of this study was to determine the impact of iron status on cadmium dose among pregnant women., Methods: Iron status and cadmium concentration in blood, urine, and placenta were determined among women followed for 2 years from early pregnancy., Results: Blood cadmium and urinary cadmium were correlated with iron status throughout the study period. Urinary cadmium increased longitudinally among women with exhausted iron stores during their pregnancy. The increase in urinary cadmium with age was more pronounced in multiparous than in nulliparous women., Conclusions: Iron deficiency during pregnancy leads to increased cadmium absorption and body burden. Multiparous women exhibit additional increases with increasing age.

This report covers part of the assessment of a site in northern France polluted by industrial metal emissions. Our objectives were to assess the cadmium burden in children aged 8 to 11 years and look for factors that affected it. A cross-sectional population-based study took place in 1996-1997 and included 400 children (200 in the metal-polluted area). The geometric mean of the blood cadmium (CdB) levels of children living on the polluted site was 0.51 microg/L (95% CI=[0.49-0.53]); that of the nonexposed children was 0.47 microg/L (95% CI=[0.45-0.49]) (P<0.01). The geometric mean of the urinary cadmium (CdU) levels of children living on the polluted site was 1.16 microg/g creatinine (95% CI=[1.01-1.34]); that of the nonexposed children was 0.99 microg/g creatinine (95% CI=[0.86-1.14]) (P=0.10). Mean CdB was higher among children within 4 km of a zinc smelter and consuming > or =500 ml of tap water daily (x1.34; 95% CI=[1.14-1.51]) compared with children living more than 4 km away and consuming <500 ml of tap water daily. Independently of this association, consumption of fish and shellfish (> or =once a week vs. or =once daily vs.

As part of the representative Environmental Survey in Germany in 1990-1992, investigators determined cadmium levels in blood provided by 3,965 subjects aged 25-69 yr. The investigators considered approximately 150 variables (i.e., demographics, household and occupational characteristics, environmental exposures, smoking habits, frequency of food consumption, and additional life-style features) as potential predictors in multivariate regression analysis. On the basis of the results of multivariate regression analysis, the authors derived 2 slightly different models for the prediction of blood cadmium levels in populations from West and East Germany. Both models included 3 primary predictors of blood cadmium levels. The 2 models explained 51.3% and 61.2% of the observed variance in blood cadmium levels in West and East Germany, respectively. The most important predictor was a specific indicator for smoking habits, which was determined from a separate mathematical model. In this model, the effect of smoking was considered, and the model accounted for the biological half-life of cadmium in blood.

Using as an index of exposure the Cd concentration in rice and as an index of health effect the urinary abnormality rate (proteinuria, glycosuria, and proteinuria with glycosuria) in the most systematic and extensive health screening examination conducted in 1967 and 1968 in the Jinzu River basin, Japan (a total of 13,183 subjects), we investigated whether a dose-response relationship exists between the two indices. For subjects that lived in the same hamlet since birth, with low Cd concentrations in rice it was confirmed that renal dysfunction does not develop unless the length of residence is prolonged, whereas with high Cd concentrations in rice renal dysfunction develops even when the length of residence is short. For subjects that lived in the same hamlet for over 30 years and that were aged over 50 years, the urinary abnormality rate in individual hamlets showed significant increases with increases in the mean Cd concentration in rice, demonstrating that a dose-response relationship existed. The allowable values of Cd concentration in rice were estimated to be in the range of 0.05-0.20 ppm, representing values lower than the 0.4 ppm provisionally adopted by the Japanese government., (Copyright 2001 Academic Press.)

It is well known that cadmium (Cd) causes renal dysfunction such as increase of beta(2)-microglobulin excretion into urine. Although Cd in rice seems to be one of the largest sources of total Cd intake in Japan, there are very few studies that have epidemiologically clarified the relationship between Cd concentration in rice (Cd-R) and renal dysfunction, because such studies are basically ecological studies, in which confounding factors are difficult to take into consideration. To derive safety levels for foodstuff from Cd-R, it is essential to evaluate the effect of confounding factors. Thus, we investigated the dose-response relationship between renal dysfunction and not only Cd-R but also confounding factors, and we tried to determine whether Cd-R is an adequate indicator of "dose" in the dose-response relationship between Cd intake and renal dysfunction. In 1971, Cd-R data were obtained from rice samples collected by the Environment Agency, Government of Japan in the Fuchu area of Toyama Prefecture, which is known as a place where many itai-itai disease patients were found, and medical data were collected during 1979-1984 by Toyama Prefecture. First, the dose-response relationship between Cd-R and renal dysfunction was analyzed using the data from the Fuchu area. Second, to investigate the effect of confounding factors, analysis using the data from both the Fuchu area and an unpolluted area with environmental factors different from those of the Fuchu area was performed. The results showed that the cause of renal dysfunction could not be explained by Cd-R alone, and confounding factors were not negligible. Although it is difficult to clarify precisely the confounding factors from the available data, it is concluded that deriving a safety level for foodstuffs using only the Cd-R level as a reference is not appropriate., (Copyright 2000 Academic Press.)

Long-term exposure to cadmium (Cd) causes renal damage in the general population. The maximum allowable urinary Cd concentration, which was calculated from our previous study performed in a Cd-polluted area, was almost the same as the mean urinary Cd concentration of people living in nonpolluted areas. We assessed whether environmental Cd exposure is related to renal dysfunction of people in nonpolluted areas in Japan. Blood and urine samples were collected from 2753 subjects (1105 men and 1648 women) ages over 50 years old in three nonpolluted areas. Blood was analyzed for Cd and urine was analyzed for Cd, total protein, beta(2)-microglobulin (beta(2)-mg), and N-acetyl-beta-D-glucosaminidase (NAG). Cd in blood or urine was employed as indicators of internal dose; and urinary total protein, beta(2)-mg, and NAG were used as an indicator of renal dysfunction. Multiple regression analysis and logistic regression analysis were performed to clarify the dose-effect and dose-response relationship between blood or urinary Cd concentration and indicators of renal dysfunction. Multiple regression analysis demonstrated a significant dose-effect relationship between Cd in blood and urine and indicators of renal dysfunction. Logistic regression analysis also showed that the probability that individual subjects would have abnormal values of the renal variables was significantly related to Cd in blood and urine., (Copyright 2000 Academic Press.)

Concentrations of lead and cadmium were estimated in blood samples of 43 healthy dogs from urban India. Concentrations were 19.5+/-2.1 microg lead/dL and 0.74+/-0.13 microg cadmium/dL, which were considerably higher for rural dogs. Sex, age, and diet had no significant effect on lead and cadmium blood concentrations, yet male and adult dogs had higher levels than females and young dogs. The use of dogs as sentinels for environment quality in India was indicated by this study.

To provide new leads regarding occupational prostate cancer risk factors, we linked 36,269 prostate cancer cases reported to the Swedish National Cancer Registry during 1961 to 1979 with employment information from the 1960 National Census. Standardized incidence ratios for prostate cancer, within major (1-digit), general (2-digit), and specific (3-digit) industries and occupations, were calculated. Significant excess risks were seen for agriculture-related industries, soap and perfume manufacture, and leather processing industries. Significantly elevated standardized incidence ratios were also seen for the following occupations: farmers, leather workers, and white-collar occupations. Our results suggest that farmers; certain occupations and industries with exposures to cadmium, herbicides, and fertilizers; and men with low occupational physical activity levels have elevated prostate cancer risks. Further research is needed to confirm these findings and identify specific exposures related to excess risk in these occupations and industries.

Background: A patient with unexplained minor behavioural changes associated with an axonal sensorimotor polyneuropathy had a history of chronic occupational exposure to cadmium (Cd). Although animal studies have shown that Cd is a potent neurotoxicant, little is known about its toxicity for the human central nervous system. The aim of this study was to investigate the toxic potential of chronic occupational exposure to Cd on neurobehavioural functions., Methods: A cross sectional epidemiological study was conducted ina group of Cd workers and an age matched control group. Eighty nine adult men (42 exposed to Cd and 47 control workers) were given a blinded standardised examination that consisted of computer assisted neurobehavioural tests (neurobehavioural examination system), a validated questionnaire to assess neurotoxic complaints (neurotoxicity symptom checklist--60, NSC-60), and a standardised self administered questionnaire to detect complaints consistent with peripheral neuropathy and dysfunction of the autonomic nervous system. Historical and current data on biomonitoring of exposure to Cd, either the highest value of Cd in urine (CdU in microgram Cd/g creatinine) of each Cd worker during work (CdUmax) or the current value (CdUcurrent) of each control, were available as well as data on microproteinuria., Results: Cd workers (CdUmax: mean (range), 12.6 (0.4-38.4)) performed worse than the controls (CdUcurrent: mean (range), 0.7 (0.1-2.0)) on visuomotor tasks, symbol digit substitution (p = 0.008), and simple reaction time to direction (p = 0.058) or location (p = 0.042) of a stimulus. In multiple linear regression analysis, symbol digit substitution, simple direction reaction time test, and simple location reaction time test were significantly related to CdUmax, (beta = 0.35 (p < 0.001), beta = 0.25 (p = 0.012), and beta = 0.23 (p = 0.021) respectively). More complaints consistent with peripheral neuropathy (p = 0.004), complaints about equilibrium (p = 0.015), and complaints about concentration ability (p = 0.053) were found in the group exposed to Cd than in the control group, and these variables correlated positively with CdUmax (peripheral neuropathy: beta = 0.38, p < 0.001; equilibrium: beta = 0.22, p = 0.057; concentration ability: beta = 0.27, p = 0.020)., Conclusion: Slowing of visuomotor functioning on neurobehavioural testing and increase in complaints consistent with peripheral neuropathy, complaints about equilibrium, and complaints about concentration ability were dose dependently associated with CdU. Age, exposure to other neurotoxicants, or status of renal function could not explain these findings. The present study also indicates that an excess of complaints may be detected in Cd workers before signs of microproteinuria induced by Cd occur.

Uncovering the exact cause of polyneuropathies seems to be impossible in up to 24% of the cases. Experimental studies have shown that cadmium (Cd), which is a well-known occupational and environmental hazard, can be a potent neurotoxicant for the peripheral nervous system. Moreover, Cd has a half-life of more than 15 years in humans. We hypothesize that older workers may be more susceptible to an increased Cd body burden, and may develop a peripheral polyneuropathy (PNP) over time. A blinded epidemiological survey was performed in 13 retired, long-term Cd-exposed workers and 19 age-matched controls. Historical Cd biomonitoring data were available over the last two decades. A neurological clinical examination, nerve conduction studies, and needle EMG were performed, and a standardized questionnaire was given to evaluate polyneuropathy complaints. If two of the following four criteria, i.e. complaints of polyneuropathy, neurophysiological changes compatible with polyneuropathy, distal symmetrical areflexia, or distal symmetrical anesthesia for vibration sense, temperature or blunt-sharp discrimination were present, the diagnosis of PNP was made. Two (11%) of the control and seven (54%) of the retired Cd workers met the PNP criteria OR: 9.92 (95%CI 1.60-61.6), Fisher exact test p=0.015. The existence of a polyneuropathy was related to the level of the Cd body burden as reflected by urinary Cd multiple logistic regression p=0.016, OR=1.26, (95%CI, 1.04-1.51), but not to blood lead (p=0.352). Our findings favour the hypothesis of a promoting role of increased cadmium body burden in the development of PNP at older age.

A follow-up study on renal tubular dysfunction was carried out on 193 female inhabitants of the cadmium (Cd)-polluted Jinzu River basin and 40 reference subjects living in an adjacent area in 1994-95. They were 54 to 70 years old when the initial examination was conducted in 1983-84. In the Cd-polluted Jinzu River basin, extensive reclamation of polluted rice fields has been conducted since 1979; as a result, the average Cd concentrations in polished rice consumed by the subjects in the 1994-95 study (0.12 ppm in 1994, 0.14 ppm in 1995) were significantly lower than those in the 1983-84 study (0.26 ppm in 1983, 0.29 ppm in 1984). The average Cd levels in urine in the follow-up study (7.5 micrograms/g Cr. in 1994, 7.7 micrograms/g Cr. in 1995) were also significantly lower than those in the initial study (13.5 micrograms/g Cr. in 1983, 13.3 micrograms/g Cr. in 1984). However, the mean values for urinary excretion of beta 2-microglobulin (beta 2-m) (3.9 mg/g Cr. in 1994, 3.7 mg/g Cr. in 1995) and glucose (203 mg/g Cr. in 1994, 251 mg/g Cr. in 1995) in the follow-up study were significantly higher than those obtained at the initial examination (2.0 mg/g Cr. and 125 mg/g Cr. in 1983 and 1.1 mg/g Cr. and 78 mg/g Cr. in 1984 for beta 2-m and glucose excretion, respectively). The magnitude of increase in urinary excretion of beta 2-m and glucose in inhabitants of the Cd-polluted area was significantly higher than that of the inhabitants of the reference area. Moreover, an increase was observed in the prevalence of renal tubular dysfunction determined by urinary beta 2-m exceeding 10 mg/g creatinine and urinary glucose exceeding 150 mg/g creatinine only among inhabitants of the Cd-polluted area; it is noteworthy that 31 new cases of renal tubular dysfunction were observed in the follow-up study. These results indicate that renal tubular dysfunction among inhabitants of the Cd-polluted Jinzu River basin is irreversible and progressive, and many new cases of renal tubular dysfunction were also noted over a period of 11 years, despite the fact that Cd exposure had decreased over the past 11 years.