Urinary phthalate monoesters and endometriosis in infertile Japanese women

Phthalates may act as an estrogen and are a potential risk factor for estrogen-related diseases such as endometriosis. We assessed the association between phthalate exposure and endometriosis in 166 consecutive women who presented at a university hospital for consultation regarding infertility. The subjects were interviewed and provided a urine specimen prior to a laparoscopic diagnosis of endometriosis. They were then categorized by the severity of endometriosis as controls (stages 0-I) and cases (stages II-IV). Urinary concentrations of the phthalate metabolites monoethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate were measured in 57 cases and 80 controls using high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Adjusted odds ratios for endometriosis in relation to dichotomized individual phthalate metabolites (standardized for creatinine) were calculated. No significant association between endometriosis and any urinary creatinine-adjusted phthalate monoester was seen. Adjusted odds ratio (95% confidence interval) for higher dichotomized MEHP by endometriosis was 1.57 (0.74-3.30). No monotonic trend was seen in urinary creatinine-adjusted concentration of phthalate metabolites by endometriosis stage (p = 0.23-0.90). Our results do not support the hypothesis that higher urinary concentrations of phthalate metabolites are associated with the risk of endometriosis in infertile Japanese women.     

Case-control study of toenail cadmium and prostate cancer risk in Italy

A role of cadmium exposure in prostate cancer etiology has been suggested by epidemiologic and laboratory studies, but conclusive evidence on this topic is still lacking. We investigated the relation between cadmium exposure, estimated by determining toenails cadmium levels, and prostate cancer risk in forty patients newly diagnosed with prostate cancer and fifty-eight hospital controls recruited in two provinces from southern and northern Italy. We found an excess cancer risk in subjects in the third and fourth (highest) quartiles of toenail cadmium concentration (odds ratio 1.3 and 4.7, respectively) compared with subjects in the bottom quartile. Results were basically unchanged when limiting the analysis to each province or entering toenail cadmium concentrations as continuous values in the regression model (P=0.004). Despite the limited statistical stability of the point estimates, these findings appear to support the hypothesis that cadmium exposure increases prostate cancer risk.     

Low ratio of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol-glucuronides (NNAL-Gluc)/free NNAL increases urothelial carcinoma risk

Cigarette smoking is the most important risk factor for bladder cancer. The compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are viewed as biomarkers for cigarette smoking exposure. Therefore, we wanted to explore the effects of these urinary metabolites on urothelial carcinoma (UC) risk. We recruited 127 pairs of UC cases and matched healthy participants for a hospital-based case-control study. Participants completed questionnaires of medical and social information, including smoking history, and provided 50 mL urine samples. Urine samples were analyzed for free NNAL and NNAL-Gluc using the liquid chromatography-tandem mass spectrometry method. Nonparametric analysis and multivariate logistic regression were applied to compare the differences in NNK-related metabolites between UC cases and controls, and to estimate the UC risk associated with certain risk factors. Overall, controls with higher cumulative cigarette smoking exposure had higher total NNAL, free NNAL and NNAL-Gluc. In addition, a decreased NNAL-Gluc/free NNAL ratio corresponded to a significantly increased UC risk. The association between the NNAL-Gluc/free NNAL ratio and UC risk was significant in a dose-response manner. Furthermore, cumulative cigarette smoking exposure was found to interact significantly with low NNAL-Gluc/free NNAL ratio to affect UC risk in this study. This is the first study to conclude that the metabolic products of total NNAL, free NNAL and NNAL-Gluc might be measured as biomarkers of cigarette smoking exposure. Furthermore, the NNAL-Gluc/free NNAL ratio was a better biomarker to evaluate UC risk than total NNAL.     

Cytochrome P450 1B1 mRNA levels in peripheral blood cells and exposure to polycyclic aromatic hydrocarbons in Chinese coke oven workers

Cytochrome P450 1B1 (CYP1B1) is induced through the Ah receptor and is involved in the activation of polycyclic aromatic hydrocarbons (PAHs). To determine the validity of a quantitative analysis of CYP1B1 mRNA in peripheral human blood cells for the estimation of PAH exposure, a real-time quantitative polymerase chain reaction method was used to measure the relative levels of CYP1B1 mRNA in 37 Chinese coke oven workers and 13 control workers. A large inter-individual difference in the levels was observed. The average level of the CYP1B1 mRNA in workers at the top work site, where the PAH exposure level from the coke ovens was highest, was significantly higher than in workers at the middle site (P<0.01) or the controls (P=0.02). A non-significant positive correlation was found between the CYP1B1 mRNA levels and urinary 1-hydroxypyrene (R=0.22, P=0.13), and a significant correlation between these mRNA levels and urinary cotinine (R=0.33, P=0.02). It was interesting that a significant positive correlation between CYP1B1 mRNA and 1-hydroxypyrene was observed in subjects with the Leu/Leu type of CYP1B1 Leu432Val polymorphism (R=0.33, P=0.02, n=38) and a non-significant correlation in subjects with the Leu/Val and Val/Val types (R=-0.36, P=0.25, n=12), although the number of subjects in this strata analysis was small. Our preliminary study suggests that PAH exposure in coke ovens and smoking maybe associated with CYP1B1 mRNA levels in peripheral blood cells although mRNA is generally unstable and could be expressed following exposure to other agents.     

Cadmium in blood and urine after cessation of exposure.

A plant for the synthesis and packaging of cadmium oxide was operated for 32 months (1982-84) in a small chemical factory producing zinc and copper oxide. The cumulative exposure of 6 workers was from 12 to 190 days. Five years after cessation of exposure the blood cadmium levels in the exposed were, on average, 4-10 times higher than those of a reference group and the urinary cadmium levels were 1-6-times higher. In view of the long half-life of cadmium in the human body, the choice of normal reference values requires particular care since brief and sometimes forgotten exposures to cadmium may be a confounding factor to set reference values.     

Assessment of endotoxin levels in the home and current asthma and wheeze in school-age children

The relationship between household endotoxin and asthma in children is not clear. To further investigate the relationship between sources of endotoxin and childhood asthma, we conducted a case-control study of children with and without asthma and examined their more frequent household exposures in the home. Children ages 6-13 years with current asthma (n = 70) or wheeze only (n = 19) were sex and age matched (+/-1 year) to 107 controls. Play area and mattress dust were collected for endotoxin analysis. Atopic status was determined by skin prick testing for allergies. A family size of >4 per household was associated with higher endotoxin levels (EU/mg) in the bed dust (P < 0.05). Passive smoking (P < 0.05) and the presence of a cat were associated with higher levels of endotoxin in mattress dust. Endotoxin levels in either the play dust or the bed dust did not differ between cases and controls. Within atopic cases, those with higher endotoxin loads (EU/m2) in bed or play areas were more likely to miss school for chest illness (P < 0.05). In this study, household endotoxin is not a risk factor for current asthma overall but may be associated with increased severity in children with atopic asthma. PRACTICAL IMPLICATIONS: This study did not find that household sources of endotoxin were associated with asthma. However, within atopic asthmatics, asthma severity (as measured by a history of being kept home from school because of a chest illness in the past year) was associated with higher levels of endotoxin in dust from the child's bed. There is a need to further investigate the nature of the relationship between household endotoxin and asthma severity in children which could lead to better management of childhood asthma.     

Determination of cadmium in whole blood and scalp hair samples of Pakistani male lung cancer patients by electrothermal atomic absorption spectrometer

A large number of epidemiologic studies have been undertaken to identify potential risk factors for cancer, amongst which the association with cadmium has received considerable attention. There is compelling evidence in support of positive associations between cadmium and risk of lung cancer. In present study we measured the concentration of Cd in whole blood and scalp hair samples of 120 male lung cancer patients (smokers) and 150 controls or referents (smokers and nonsmokers) from different cities of Pakistan. Both referents and patients were of same age group (ranged 40-70 years), socio-economic status, localities and dietary habits. The scalp hair and whole blood samples were oxidized by 65% nitric acid: 30% hydrogen peroxide (2:1) ratio in microwave oven. To check the validity of the proposed method, a conventional wet acid digestion method was used to obtain total Cd concentration in certified samples of human hair BCR 397 and Clincheck control-lyophilized human whole blood. All digests were analyzed for Cd concentration by electrothermal atomic absorption spectrometer (ETAAS). The results of this study showed that the average Cd concentration was higher in the blood and scalp hair of lung cancer patients at different stages as compared to controls (p<001). The smoker referents have high level of Cd in both biological samples as compared to nonsmoker subjects. These results illustrate that the patients who continued smoking after confirmed diagnosis of lung cancer have 34.2-67.26 and 22.4-57.3% more Cd in blood samples and scalp hair than lung cancer patients who cease smoking. This study is compelling evidence in support of positive associations between cadmium, cigarette smoking and lung cancer risk.     

The total body burden of chromium associated with skin disease and smoking among cement workers

BACKGROUND: Hand eczema and other skin diseases have been associated with the exposure of chromium among cement workers. Studies on skin disease and other factors associated with the body burden of chromium are limited. OBJECTIVE: The present study investigated the role of skin disease and smoking in the association with body burden of chromium among cement workers. METHODS: Forty-five workers (38 men and 7 women) were recruited for this study and interviewed to obtain information on demographic status, lifestyle, employment history, and affecting factors. Urine samples were collected to measure the urinary chromium concentration to represent the body burden of chromium. RESULTS: The average urinary chromium concentration was approximately 6 times higher in non-smoking workers with hand eczema than in non-smoking workers with no skin disease (45.5 vs. 7.6 microg/L). The average chromium level increase to 87.0 microg/L for smokers with the disease. Compared with workers with no hand eczema, the odds ratio of having urinary chromium concentration exceeding the biological exposure index level significantly increased to 11.6 (95% CI=1.3-102.2) for non-smoking workers with skin disease, and to 48.0 (95% CI=4.5-510.8) for smoking workers with skin disease. The multiple regression analysis showed that the use of gloves may reduce significantly the chromium exposure. CONCLUSIONS: Inadequate protection and personal behavior increase the internal dose of chromium in cement workers. Total body burden of chromium are higher among cement workers with skin disease and smoking habit. These workers deserve intervention education on personal hygiene to reduce the exposure of chromium.     

Sources of cadmium exposure among healthy premenopausal women

Background

Cadmium, a persistent and widespread environmental pollutant, has been associated with kidney function impairment and several diseases. Cigarettes are the dominant source of cadmium exposure among smokers; the primary source of cadmium in non-smokers is food. We investigated sources of cadmium exposure in a sample of healthy women.

Methods

In a cross-sectional study, 191 premenopausal women completed a health questionnaire and a food frequency questionnaire. The cadmium content of spot urine samples was measured with inductively-coupled plasma mass spectrometry and normalized to urine creatinine content. Multivariable linear regression was used to estimate the strength of association between smoking habits and, among non-smokers, usual foods consumed and urinary cadmium, adjusted for age, race, multivitamin and supplement use, education, estimated total energy intake, and parity.

Results

Geometric mean urine creatinine-normalized cadmium concentration (uCd) of women with any history of cigarette smoking was 0.43 μg/g (95% confidence interval (CI): 0.38-0.48 μg/g) and 0.30 μg/g (0.27-0.33 μg/g) among never-smokers, and increased with pack-years of smoking. Analysis of dietary data among women with no reported history of smoking suggested that regular consumption of eggs, hot cereals, organ meats, tofu, vegetable soups, leafy greens, green salad, and yams was associated with uCd. Consumption of tofu products showed the most robust association with uCd; each weekly serving of tofu was associated with a 22% (95% CI: 11-33%) increase in uCd. Thus, uCd was estimated to be 0.11 μg/g (95% CI: 0.06-0.15 μg/g) higher among women who consumed any tofu than among those who consumed none.

Conclusions

Cigarette smoking is likely the most important source of cadmium exposure among smokers. Among non-smokers, consumption of specific foods, notably tofu, is associated with increased urine cadmium concentration.     

Sodium retention in rats with cadmium-induced hypertension

Chronic feeding of non-toxic doses of cadmium induces an average increase of 15 to 20 mm Hg in indirectly measured systolic pressure of lightly anaesthetized rats. The mechanism of this increase is not known, but cadmium has several potentially pressor effects, including increased sodium retention. This report describes both sodium balance and blood pressure in a pair of experiments where cadmium was fed and in a pair where it was injected. All four cadmium challenges induced sodium retention and also induced hypertension. Thus, rats with either low or moderate chronic exposure to fed cadmium (well below the exposures required to induce toxicity) retained more intraperitoneally injected radiosodium than controls and at the same time developed higher systolic pressures than controls. Immediately following intraperitoneally injected cadmium, rats lost a radiosodium load more slowly than controls or alternately accumulated dietary radiosodium more rapidly than controls; in both situations the blood pressure was higher than in controls. These data indicate that some of the pressor effect associated with cadmium exposure could result from its concomitant antinatriuretic effect.     

Assessment and management of risks arising from exposure to cadmium in fertilisers--II

A preliminary, illustrative human health risk assessment of exposure to cadmium in phosphate fertilisers was performed using typical UK data and a protocol previously developed for application by individual Member States in the European Union. The risk assessment indicated that the for the most pessimistic population exposures characterised by both extreme (97th percentile) cereal and potato consumption and high susceptibility to cadmium uptake, the estimated dose was under the WHO Provisional Tolerable Weekly Intake (PTWI) for fertiliser cadmium concentrations ranging from 15 to 100 mg Cd/kg P2O5 applied over 100 years. However, the low margin of safety for high risk groups and the uncertainties inherent in the overall risk assessment suggested that a prudent risk management strategy would involve maintenance of low levels of cadmium in fertilisers and/or conditions that permitted low accumulation of cadmium in soils. On this basis, two main risk reduction measures were developed and assessed: (a) imposition of limits on cadmium concentration in fertilisers; and (b) imposition of charges on levels of cadmium in phosphate fertilisers. An assessment of the economic impact of these risk reduction measures indicated that, at all price elasticities, the most significant impact in terms of changes in demand and changes in consumer expenditure on phosphate fertilisers will be seen with cadmium charges where no thresholds are defined. The impact on the consumer (i.e. farmer) will be an increase in spending of approximately US $4000 per year, which is considered significant, accompanied by a decrease in demand above 20%. If a threshold is set at 60 mg Cd/kg P2O5, the impact is significantly reduced, but stays relatively high compared to the other options. The analysis also indicates that the use of low-cadmium rock is the low cost option. At a likely rock price increase of approximately 5% and assuming a likely price elasticity of -0.2, the yearly costs to farmers will be approximately US $82 which is considered a minimal impact. In the worst case scenario (elasticity of -0.6 and a 10% increase in rock prices), the increase in spending by farmers will be of 3.9% or US $221 which is also considered to represent a minimal impact. At similar price elasticities, the use of decadmation technologies is predicted to be more costly than the use of low-cadmium rock but this option can still be considered as having a minimal impact on the consumer (increase in expenditure of 1.9-13.3% or US $106-748).     

慢性肾脏病4-5期非透析患者死亡的危险因素分析

目的 探讨慢性肾脏病（CKD）4-5期非透析患者死亡的主要原因、临床特点及其危险因素.方法 收集萍乡市人民医院2010年5月至2013年5月201例CKD4-5期非透析患者的一般资料,其中CKD4期125例,CKD5期76例.对CKD4-5期非透析患者死亡的危险因素进行多因素Logistic回归分析.结果 201例患者中,死亡69例（34.3%）,其中CKD4期31例,CKD5期38例.主要死亡原因：心血管疾病21例（30.4%）,脑血管疾病18例（26.1%）,感染16例（23.2%）,其他14例（20.3%）.多因素Logistic回归分析结果显示,低肾小球滤过率（eGFR,OR=0.206,P=0.029）、高C反应蛋白（CRP,OR=3.624,P=0.017）、高血尿酸（OR=2.158,P=0.018）、低白蛋白（OR=0.509,P=0.032）及高血磷（OR=1.479,P=0.021）均为CKD4-5期非透析患者死亡的危险因素.结论 CKD4-5期非透析患者病死率较高,心血管疾病是最常见的死因,低eGFR、高CRP、高血尿酸、低白蛋白水平及高磷血症是患者死亡的独立危险因素.     

The role of metals in autoimmune vasculitis: epidemiological and pathogenic study

BACKGROUND: A possible relationship between Silica (Si) exposure and antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis has been reported. Furthermore, tuberculosis (TBC) has been frequently described in patients with silicosis, and TBC infection shares with ANCA-associated vasculitis the formation of granulomas. Therefore, an intriguing network including Silica, Vasculitis, TBC and ANCA might be hypothesized. The aim of this work was to further investigate these correlations using both epidemiological and pathogenic approaches. METHODS: Study I--epidemiological study. A case-control study to compare the occupational histories of 31 cases of biopsy proven vasculitis (18 pauci-immune crescentic glomerulonephritis, 9 microscopic polyangitis, 4 Wegener's granulomatosis) with those of 58 age, sex and residence-matched controls (affected by other kidney diseases), was performed. Occupational Health physicians designed an appropriate questionnaire in order to evaluate a wide spread of exposures and calculate their entity by the product of Intensity x Frequency x Duration. Study II--tuberculosis association. A case-control study to evaluate the frequency of a previous history of tuberculosis (TBC) in 45 patients with vasculitis and 45 controls were performed. Study III--ANCA positivity. A case-control study to evaluate the presence of ANCA was performed by testing blood samples of 64 people with previous professional exposure and 65 sex/age matched patients hospitalized in a General Medicine Unit. Furthermore, the same evaluation was made in a pilot study in 16 patients with ongoing or previous TBC. Study IV--experimental study. The oxygen free radicals (OFR) and IL-12 production (both involved in the pathogenesis of vasculitis) from human phagocytic cells stimulated with an amorphous (diatomaceous earth) and a crystalline (quartz) form of Si at the doses of 10 and 100 microg ml(-1) was evaluated. RESULTS: Study I--a positive history of exposure to Si resulted in significantly more present in cases (14/31 = 45%) than in controls (14/58 = 24%, P = 0.04, OR = 2.4) and no other significant exposure association was found (including asbestos, mineral oil, formaldehyde, diesel and welding fumes, grain and wood dust, leather, solvents, fungicides, bitumen, lead and paint). Study II--past TBC infection was significantly more present in patients with vasculitis (12/45 = 26%) than in controls (4/45 = 8%, P < 0.05). Study III--ANCA was present in 2/64 exposed people (vs. 0/65 controls, P = NS) and 0/16 patients with TBC. Study IV--both amorphous and crystalline Si forms represented a stimulus for OFR and IL-12 production, but quartz resulted as a greater inductor. CONCLUSIONS: We conclude that Si exposure might be a risk factor for ANCA-associated vasculitis, possibly enhancing endothelial damage by phagocyte generation of oxygen free radicals and Th1 differentiation by an excessive IL-12 phagocyte production. Frequency of TBC was significantly higher in vasculitis patients. ANCA was not frequent in the preliminary examination of people with previous professional exposure or patients with TBC, but the number of samples evaluated is too small to allow conclusions.     

24小时尿钠排泄与难治性高血压患者血压达标状态的相关性:单中心横断面研究

目的分析24 h尿钠排泄与难治性高血压(resistant hypertension,RH)患者诊室血压及家庭自测血压(home blood pressure monitoring,HBPM)达标状态的关系。方法通过北京协和医院心内科门诊RH数据库,收集2017年10月至2018年3月间在北京协和医院心内科门诊就诊的RH患者临床资料,进行横断面调查。检测患者24 h尿钠,记录患者同期诊室血压、HBPM水平及临床用药情况,以所有患者24 h尿钠水平四分位数为分界点,将研究对象分为低尿钠、低-中尿钠、中-高尿钠及高尿钠4组。采用多因素Logistic回归,分析影响RH血压达标状态的危险因素。结果共202例RH患者入选本研究,男性107例,女性95例,平均年龄(59. 87±16. 30)岁。24 h尿钠平均水平为(198. 92±96. 59) mmol,年轻患者及体质量指数高者尿钠水平更高(P均<0. 001)。随尿钠升高,降压药物的服用种类显著增多(P=0. 001),早晨及上午的HBPM达标率低(P=0. 040,0. 032)。多因素Logistic回归分析显示,24 h尿钠水平与诊室血压(OR=2. 356,95%CI:1. 004～5. 533,P=0. 049),HBPM早晨血压(OR=2. 408,95%CI:1. 026～5. 650,P=0. 030)及HBPM上午血压(OR=2. 299,95%CI:1. 031～5. 129,P=0. 033)达标状态独立相关,而与下午及夜间HBPM血压达标状态无显著相关(P均>0. 05)。结论 24 h尿钠是RH患者诊室血压及HBPM早晨及上午血压达标的独立相关因素,限制钠盐摄入对减少RH患者血压波动、促进血压达标有重要作用。     

Histological and toxicological responses of the mummichog, Fundulus Heteroclitus (L.) to combinations of levels of cadmium and dissolved oxygen in a freshwater

Impact of dissolved oxygen concentration (D.O.) on toxicity of cadmium to mummichogs in a freshwater medium and histological changes associated with exposure were determined. Levels of mortality were related to duration of exposure, cadmium concentration, and levels of dissolved oxygen. Median tolerance concentrations, at 96h, ranged upward from 1.3 to about 3.0 mg Cd 1⁻¹ at 2.3 and 8.5 mg DO 1⁻¹, respectively. Statistical analyses of mortality data showed factors examined were interdependent and that Cd × DO and Cd × time interactions were significant (P < 0.01). No histopathology was evident at 3 mg Cd 1⁻¹, although histopathology was evident in gills from fish exposed to 28 mg Cd 1⁻¹ for 6 1/2 h.

Responses of mummichogs to cadmium in freshwater are compared with results of a previous study involving exposure of the species to cadmium in seawater and with responses of freshwater fishes subjected to various heavy metals. Differences and similarities in patterns of response are discussed in terms of water balance.     

The Iowa radon lung cancer study--phase I: Residential radon gas exposure and lung cancer

Exposure to high concentrations of radon (222Rn) progeny produces lung cancer in both underground miners and experimentally-exposed laboratory animals. The goal of the study was to determine whether or not residential radon exposure exhibits a statistically significant association with lung cancer in a state with high residential radon concentrations. A population-based, case-control epidemiologic study was conducted examining the relationship between residential radon gas exposure and lung cancer in Iowa females who occupied their current home for at least 20 years. The study included 413 incident lung cancer cases and 614 age-frequency-matched controls. Participant information was obtained by a mailed-out questionnaire with face-to-face follow-up. Radon dosimetry assessment consisted of five components: (1) on-site residential assessment survey; (2) on-site radon measurements; (3) regional outdoor radon measurements; (4) assessment of subjects' exposure when in another building; and (5) linkage of historic subject mobility with residential, outdoor, and other building radon concentrations. Histologic review was performed for 96% of the cases. Approximately 60% of the basement radon concentrations and 30% of the first floor radon concentrations of study participants' homes exceeded the US Environmental Protection Agency action level of 150 Bq m(-3) (4 pCi l(-1)). Large areas of western Iowa had outdoor radon concentrations comparable to the national average indoor value of 55 Bq m(-3) (1.5 pCi l(-1)). Excess odds of 0.24 (95% CI = -0.05-0.92) and 0.49 (95% CI = 0.03-1.84) per 11 WLM(5-19) were calculated using the continuous radon exposure estimates for all cases and live cases, respectively. Slightly higher excess odds of 0.50 (95% CI = 0.004-1.80) and 0.83 (CI = 0.11-3.34) per 11 WLM(5-19) were noted for the categorical radon exposure estimates for all cases and the live cases. A positive association between cumulative radon gas exposure and lung cancer was demonstrated using both categorical and continuous analyses. The risk estimates obtained in this study indicate that cumulative radon exposure presents an important environmental health hazard.     

Review of toxicity test results submitted in support of pesticide tolerance petitions.

A long term-low level exposure (LLE) experiment was conducted on rats to determine the metabolic patterns for realistic environmental dietary levels of cadmium. Male rats fed with 61 ppb of cadmium ad libitum, 50 labelled with ¹⁰⁹Cd radiotracer as cadmium chloride via drinking mineral water and 11 unlabelled via food for 2 years. The diet was characterized in its metal content by neutron activation analysis to obtain the total dietary intake of different elements.The kidney was found to be the tissue with the major concentration of cadmium which accumulated continuously during the experiment.The variation of the accumulation pattern of Cd concentration in the liver and intestine indicated an initial rapid increase of Cd during the first 100 days. After this period an apparent equilibrium was attained in both these tissues until the end of the study.The intracellular distribution of cadmium in kidneys, liver, intestine and pancreas were similar, the cytosol fractions containing about 80% of the cellular cadmium. Dialysis experiments indicated that significant amounts of cadmium were able to be associated with cellular organelles, the mitochondria representing the most important organelle capable of binding cadmium.The cytoplasmatic Cd-profiles obtained at various stages of the experiment showed that the metal was only bound to a low-molecular-weight component, cadmium-binding protein (CdBP), which represents the specific cellular-binding component for cadmium under the long term-low level exposure (LLE) conditions.No significant variations in the concentrations of the elements in different organs were observed in animals supplemented with ¹⁰⁹Cd in respect to ¹⁰⁹Cd untreated controls.     

Effects of low-dose cadmium exposure on biological examinations

We conducted an epidemiological study to investigate the effects of low-dose cadmium (Cd) exposure on human health in a specific area of a town in Japan where low Cd concentration was detected in rice. We compared clinical findings, urinary and whole blood Cd concentrations, and indicators of renal dysfunction between the polluted area and the control area. The study employed 44 men and 54 women from the polluted area and 21 men and 29 women from the control area. In urine analysis, as indicators of Cd exposure and possible related renal dysfunction, Cd, beta(2)-microglobulin (beta(2)-MG), alpha(1)-microglobulin (alpha(1)-MG), N-acetyl-beta-D-glucosaminidase (NAG), total protein, inorganic phosphorus, lysozyme and creatinine were quantitatively measured. In blood analysis, serum IP and creatinine and whole blood Cd were measured. No case of renal dysfunction due to Cd exposure was confirmed. However, both the urinary and whole blood Cd of the polluted area were significantly higher than those of the control area for both sexes. Urinary beta(2)-MG did not differ between the two areas. For women, urinary alpha(1)-MG was significantly higher in the polluted area than in the control area. In correlation analysis, beta(2)-MG, alpha(1)-MG and NAG, were positively correlated with both of urinary and whole blood Cd for men and women in the polluted area except for between urinary beta(2)-MG and urinary Cd for men. In the control area, the sole positive correlation observed was between urinary beta(2)-MG and whole blood Cd for men. We then examined the determinants of variations of parameters in urinary and blood tests. Potential determinants were age, sex, body mass index, an indicator of smoking habits (cigarette index) and the index of estimated Cd intake from rice (Cd-rice-index). Cd-rice-index was expressed as the product of Cd concentrations in homegrown rice multiplied by daily frequency multiplied by duration (years) of residence in the polluted area. In multiple regression analysis, whole blood Cd was independently associated with Cd-rice-index, age and gender. Variations in whole blood Cd accounted for a substantial portion of the variations in urinary Cd, although they were less influential in older individuals. Whole blood Cd was the sole independent variable related to variations in urinary beta(2)-MG. Cd-rice-index accounted for a portion of the variance in urinary NAG, while age was a more powerful determinant. It was thus revealed that the consumption of homegrown rice polluted with Cd in low concentration resulted in an elevation of whole blood Cd level and consequent increase in urinary Cd level. However, it was not clearly elucidated that the excretion of urinary low-molecular microglobulins could increase significantly in response to slight elevation of Cd body load.     

A case-control study of childhood leukemia in Woburn,Massachusetts: the relationship between leukemia incidence and exposure to public drinking water

A 1981 Massachusetts Department of Public Health study confirmed a childhood leukemia cluster in Woburn, Massachusetts. Our follow-up investigation attempts to identify factors potentially responsible for the cluster. Woburn has a 130-year industrial history that resulted in significant local deposition of tannery and chemical manufacturing waste. In 1979, two of the city's eight municipal drinking water wells were closed when tests identified contamination with solvents including trichloroethylene. By 1986, 21 childhood leukemia cases had been observed (5.52 expected during the seventeen year period) and the case-control investigation discussed herein was begun. Nineteen cases and 37 matched controls comprised the study population. A water distribution model provided contaminated public water exposure estimates for subject residences. Results identified a non-significant association between potential for exposure to contaminated water during maternal pregnancy and leukemia diagnosis, (odds ratio = 8.33, 95% CI 0.73-94.67). However, a significant dose-response relationship (P < 0.05) was identified for this exposure period. In contrast, the child's potential for exposure from birth to diagnosis showed no association with leukemia risk. Wide confidence intervals suggest cautious interpretation of association magnitudes. Since 1986, expected incidence has been observed in Woburn including 8 consecutive years with no new childhood leukemia diagnoses.     

Assessment and management of risk to wildlife from cadmium

Cadmium, a nonessential heavy metal that comes from natural and anthropogenic sources, is a teratogen, carcinogen, and a possible mutagen. Assessment of potential risk from cadmium requires understanding environmental exposure, mainly from ingestion, although there is some local exposure through inhalation. Chronic exposure is more problematic than acute exposure for wildlife. There is evidence for bioaccumulation, particularly in freshwater organisms, but evidence for biomagnification up the food chain is inconsistent; in some bird studies, cadmium levels were higher in species that are higher on the food chain than those that are lower. Some freshwater and marine invertebrates are more adversely affected by cadmium exposure than are birds and mammals. There is very little experimental laboratory research on the effects of cadmium in amphibians, birds and reptiles, and almost no data from studies of wildlife in nature. Managing the risk from cadmium to wildlife involves assessment (including ecological risk assessment), biomonitoring, setting benchmarks of effects, regulations and enforcement, and source reduction.