Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstuffs and Cigarette Smoke

Cadmium is a cumulative nephrotoxicant that is absorbed into the body from dietary sources and cigarette smoking. The levels of Cd in organs such as liver and kidney cortex increase with age because of the lack of an active biochemical process for its elimination coupled with renal reabsorption. Recent research has provided evidence linking Cd-related kidney dysfunction and decreases in bone mineral density in nonoccupationally exposed populations who showed no signs of nutritional deficiency. This challenges the previous view that the concurrent kidney and bone damage seen in Japanese itai-itai disease patients was the result of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and calcium. Further, such Cd-linked bone and kidney toxicities were observed in people whose dietary Cd intakes were well within the provisional tolerable weekly intake (PTWI) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives of 1 μg/kg body weight/day or 70 μg/day. This evidence points to the much-needed revision of the current PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is accumulating and Cd effects on reproductive outcomes have begun to emerge

The Validity of Benchmark Dose Limit Analysis for Estimating Permissible Accumulation of Cadmium

Cadmium (Cd) is a toxic metal pollutant that accumulates, especially in the proximal tubular epithelial cells of kidneys, where it causes tubular cell injury, cell death and a reduction in glomerular filtration rate (GFR). Diet is the main Cd exposure source in non-occupationally exposed and non-smoking populations. The present study aimed to evaluate the reliability of a tolerable Cd intake of 0.83 μg/kg body weight/day, and its corresponding toxicity threshold level of 5.24 μg/g creatinine. The PROAST software was used to calculate the lower 95% confidence bound of the benchmark dose (BMDL) values of Cd excretion (ECd) associated with injury to kidney tubular cells, a defective tubular reabsorption of filtered proteins, and a reduction in the estimated GFR (eGFR). Data were from 289 males and 445 females, mean age of 48.1 years of which 42.8% were smokers, while 31.7% had hypertension, and 9% had chronic kidney disease (CKD). The BMDL value of ECd associated with kidney tubular cell injury was 0.67 ng/L of filtrate in both men and women. Therefore, an environmental Cd exposure producing ECd of 0.67 ng/L filtrate could be considered as Cd accumulation levels below which renal effects are likely to be negligible. A reduction in eGFR and CKD may follow when ECd rises from 0.67 to 1 ng/L of filtrate. These adverse health effects occur at the body burdens lower than those associated with ECd of 5.24 µg/g creatinine, thereby arguing that current health-guiding values do not provide a sufficient health protection

Time Course of the Response of Myofibrillar and Sarcoplasmic Protein Metabolism to Unweighting of the Soleus Muscle

Contributions of altered in vivo protein synthesis and degradation to unweighting atrophy of the soleus muscle in tail-suspended young female rats were analyzed daily for up to 6 days. Specific changes in myofibrillar and sarcoplasmic proteins were also evaluated to assess their contributions to the loss of total protein. Synthesis of myofibrillar and sarcoplasmic proteins was estimated by intramuscular (IM) injection and total protein by intraperitoneal (IP) injection of flooding doses of H-3-phenylaianine. Total protein loss was greatest during the first 3 days following suspension and was a consequence of the loss of myofibrillar rather than sarcoplasmic proteins. However, synthesis of total myofibrillar and sarcoplasmic proteins diminished in parallel beginning in the first 24 hours. Therefore sarcoplasmic proteins must be spared due to a decrease in their degradation. In contrast, myofibrillar protein degradation increased, thus explaining the elevated degradation of the total pool. Following 72 hours of suspension, protein synthesis remained low, but the rate of myofibrillar protein loss diminished, suggesting a slowing of degradation. These various results show acute loss of protein during unweighting atrophy is a consequence of decreased synthesis and increased degradation of myofibrillar proteins, and sarcoplasmic proteins are spared due to slower degradation, likely explaining the sparing of plasma membrane receptors. Based on other published data, we propose that the slowing of atrophy after the initial response may be attributed to an increased effect of insulin

Evidence for Concurrent Effects of Exposure to Environmental Cadmium and Lead on Hepatic CYP2A6 Phenotype and Renal Function Biomarkers in Nonsmokers

We examined the interrelationships between phenotype of hepatic cytochrome P450 2A6 (CYP2A6), nephropathy, and exposure to cadmium and lead in a group of 118 healthy Thai men and women who had never smoked. Their urinary Cd excretion ranged from 0.05 to 2.36 μg/g creatinine, whereas their urinary Pb excretion ranged from 0.1 to 12 μg/g creatinine. Average age and Cd burden of women and men did not differ. Women, however, on average showed a 46% higher urinary Pb excretion (p < 0.001) and lower zinc status, suggested by lower average serum Zn and urinary Zn excretion compared with those in men. Cd-linked nephropathy was detected in both men and women. However, Pb-linked nephropathy was seen only in women, possibly because of higher Pb burden coupled with lower protective factors, notably of Zn (p < 0.001), in women compared with men. In men, Pb burden showed a negative association with CYP2A6 activity (adjusted β= −0.29, p = 0.003), whereas Cd burden showed a positive association with CYP2A6 activity (adjusted β= 0.38, p = 0.001), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. The weaker correlation between Cd burden CYP2A6 activity in women despite similarity in Cd burden between men and women is consistent with opposing effects of Pb and Cd on hepatic CYP2A6 phenotypic expression. A positive correlation between Cd-linked nephropathy (urinary N-acetyl-β-d-glucosaminidase excretion) and CYP2A6 activity in men (r = 0.39, p = 0.002) and women (r = 0.37, p = 0.001) suggests that Cd induction of hepatic CYP2A6 expression and Cd-linked nephropathy occurred simultaneously

The NOAEL Equivalent of Environmental Cadmium Exposure Associated with GFR Reduction and Chronic Kidney Disease

Cadmium (Cd) is a highly toxic metal pollutant present in virtually all food types. Health guidance values were established to safeguard against excessive dietary Cd exposure. The derivation of such health guidance figures has been shifted from the no-observed-adverse-effect level (NOAEL) to the lower 95% confidence bound of the benchmark dose (BMD), termed BMDL. Here, we used the PROAST software to calculate the BMDL figures for Cd excretion (ECd) associated with a reduction in the estimated glomerular filtration rate (eGFR), and an increased prevalence of chronic kidney disease (CKD), defined as eGFR ≤ 60 mL/min/1.73 m2. Data were from 1189 Thai subjects (493 males and 696 females) mean age of 43.2 years. The overall percentages of smokers, hypertension and CKD were 33.6%, 29.4% and 6.2%, respectively. The overall mean ECd normalized to the excretion of creatinine (Ecr) as ECd/Ecr was 0.64 µg/g creatinine. ECd/Ecr, age and body mass index (BMI) were independently associated with increased prevalence odds ratios (POR) for CKD. BMI figures ≥24 kg/m2 were associated with an increase in POR for CKD by 2.81-fold (p = 0.028). ECd/Ecr values of 0.38–2.49 µg/g creatinine were associated with an increase in POR for CKD risk by 6.2-fold (p = 0.001). The NOAEL equivalent figures of ECd/Ecr based on eGFR reduction in males, females and all subjects were 0.839, 0.849 and 0.828 µg/g creatinine, respectively. The BMDL/BMDU values of ECd/Ecr associated with a 10% increase in CKD prevalence were 2.77/5.06 µg/g creatinine. These data indicate that Cd-induced eGFR reduction occurs at relatively low body burdens and that the population health risk associated with ECd/Ecr of 2.77–5.06 µg/g creatinine was not negligible

A GIS-Aided Assessment of the Health Hazards of Cadmium in Farm Soils in Central Taiwan

A geostatistical method was developed to examine the correlation, or lack of it, between the levels of cadmium (Cd) detected in farm soils and those detected in the human specimens collected from residents around the contaminated areas in Changhua County where cadmium contamination of staple rice has been documented. We used the Taiwan EPA environment data in 2002 and human data which were generated by the National Health Research Institutes during 2003–2005. Kriging interpolation methods were used to determine soil Cd concentrations. A Zonal statistical function was performed to assess the individual exposure. Soil Cd levels and tissue Cd levels in residents were analyzed for contamination hotspots and other areas to determine correlation between the two variables. Three Cd contamination hotspots were identified, in which no correlation was found between soil Cd levels and tissue Cd levels in residents. Our results demonstrate how GIS spatial modeling technique can be used to estimate distribution of pollutants in an area using a limited number of data points. Results indicated no association between the soil contamination and the exposure of residents to Cd, suggesting that both the soils and the residents are receptors of Cd as a pollutant from as yet unidentified sources

The association of urinary cadmium with sex steroid hormone concentrations in a general population sample of US adult men

<p>Abstract</p> <p>Background</p> <p>Studies investigating the association of cadmium and sex steroid hormones in men have been inconsistent, but previous studies were relatively small.</p> <p>Methods</p> <p>In a nationally representative sample of 1,262 men participating in the morning examination session of phase I (1998–1991) of the third National Health and Nutrition Examination Survey, creatinine corrected urinary cadmium and serum concentrations of sex steroid hormones were measured following a standardized protocol.</p> <p>Results</p> <p>After adjustment for age and race-ethnicity, higher cadmium levels were associated with higher levels of total testosterone, total estradiol, sex hormone-binding globulin, estimated free testosterone, and estimated free estradiol (each p-trend < 0.05). After additionally adjusting for smoking status and serum cotinine, none of the hormones maintained an association with urinary cadmium (each p-trend > 0.05).</p> <p>Conclusion</p> <p>Urinary cadmium levels were not associated with sex steroid hormone concentrations in a large nationally representative sample of US men.</p

Toxicological Assessment of Toxic Element Residues in Swine Kidney and Its Role in Public Health Risk Assessment

In order to ensure the safety of consumers in Serbia the prevalence of toxic elements (As, Cd, Hg, Pb) in swine kidney collected from three different areas in Serbia (n = 90) was determined by atomic absorption spectrometry. Also, in order to find information on the effects of accumulation of toxic elements on swine kidney, pathohistological examination of the kidneys was performed. The presence of mercury was found in 33.3% of kidney samples in the range of 0.005–0.055 mg/kg, while the presence of cadmium was detected less often (27.7%) but in larger amounts (0.05–1.23 mg/kg). The presence of arsenic was found only in one sample, while no lead was found. The results of the metal-to-metal correlation analysis supported there were the result of different sources of contamination. Pathohistological examination of kidneys confirms tubulopathies with oedema and cell vacuolization. In addition, haemorrhages and necrosis of proximal kidney tubule cells were found. This study demonstrates that toxic elements in Serbian slaughtered pigs are found at levels comparable to those reported in other countries, and consequently the levels reported in this study do not represent a concern from a consumer safety point of view. The lack of a strong correlation between histopathological changes and the incidence of toxic elements found in this study might be explained as the result of synergism among toxic elements and other nephrotoxic compounds which enhance the toxicity of the individual toxins even at the relatively low mean concentrations observed in this study