Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene

A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins alpha 1-microglobulin and glutathione-S-transferase alpha (GST alpha) as biomarkers for damage of the proximal tubule and glutathione-S-transferase pi (GST pi) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers alpha 1-microglobulin, GST alpha, and GST pi consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.     

Urinary α<Subscript>1</Subscript>-microglobulin excretion as biomarker of renal toxicity in trichloroethylene-exposed persons

Objectives Concern on human renal toxicity and carcinogenicity of trichloroethylene is based on findings of increased incidences of renal cell cancers in persons with long-lasting and high occupational exposures to this solvent. The full tumour development is likely to require promotional stimuli, by repetitive episodes of high peak exposures to trichloroethylene, leading to nephrotoxicity. This process is visualised by the excretion of tubular marker proteins in the urine of exposed persons. For this purpose, surveillance of ₁-microglobulin excretion is being suggested by the Deutsche Forschungsgemeinschaft.Methods The present study assessed the applicability of ₁-microglobulin as a biomarker of proximal tubule damage in the prevention of nephrotoxicity by trichloroethylene exposures. For this purpose, ₁-microglobulin excretions were assessed in trichloroethylene-exposed and non-exposed subgroups of both cases (diseased with renal cancer) and controls (not diseased with renal cancer) of a recent case–control study.Results The median of ₁-microglobulin excretions in non-exposed persons was below the detection limit, but it was clearly elevated in exposed persons. The Wilcoxon rank sum test showed a significant difference (P=0.0090). Consistent with the underlying concept, renal cell cancer cases who had been exposed to trichloroethylene had higher ₁-microglobulin excretions than non-exposed cases (P=0.0005) and also had higher ₁-microglobulin excretions than exposed controls (P=0.0004). Of 20 trichloroethylene-exposed renal cell cancer cases only three (15%) displayed a normal ₁-microglobulin excretion of <5 mg/l. By contrast, 41 (52%) out of 79 non-exposed renal cancer cases showed normal excretions of the biomarker.Conclusion The present data are in agreement with the concept of pathogenesis of renal cell cancers developing under high (suggested: >500 ppm peak exposures) and long-term (several years) exposure to trichloroethylene. They also visualise the potential value of ₁-microglobulin excretion as a routine biomarker of renal toxicity that may be used in the medical surveillance of trichloroethylene-exposed persons.     

镉作业观察对象尿镉和肾小管损伤效应标志物6年追踪观察

目的 观察职业性镉作业观察对象尿镉及肾小管损伤效应标志物水平的变化, 比较脱离镉作业6年后镉作业观察对象尿肾小管损伤分子-1(KIM-1)的水平。
方法 选取8例职业性镉作业观察对象, 对2009-2014年度的尿镉、尿β₂-微球蛋白及尿维生素A结合蛋白(即视黄醇结合蛋白)水平进行跟踪观察。2014年用ELISA法检测观察对象及正常对照组尿肾小管损伤分子-1(KIM-1)的水平。
结果 停止镉作业后, 观察组的尿镉平均水平略有下降趋势, 但各年度间差异无统计学意义(P>0.05)。停止镉接触后, 观察组尿β₂-MG水平和尿视黄醇结合蛋白水平一直维持在正常范围。观察组各年度尿β₂-MG水平、尿视黄醇结合蛋白水平差异均无统计学意义(P>0.05)。停止镉接触6年后, 观察组尿KIM-1的水平(1.37 ±0.61) ng/mL, 对照组为(0.62 ±0.35) ng/mL, 两组差异有统计学意义(P < 0.05)。
结论 镉作业观察对象脱离镉接触后, 尿镉水平下降不明显, 传统的肾小管功能损害标志物尿β₂-MG及尿视黄醇结合蛋白水平无明显变化, 但尿KIM-1仍存在异常。
     

Studies of trichloroethylene-induced glycosuria: blood glucose and renal glucose reabsorption in rats exposed to trichloroethylene

In our previous experiments, a remarkable increase in urinary excretion of glucose was found in rats exposed to 821 ppm trichloroethylene for 12 wk. This was not accompanied with proteinuria, aminoaciduria, phosphaturia and definite histological changes in renal tubular structure. In order to ascertain the mechanism of the increase in urinary glucose excretion, blood glucose level and renal glucose reabsorption were studied in 10 male rats exposed to 783 ppm trichloroethylene for more than 3 wk. Another 10 male rats were studied as control. The following results were obtained: 1. Urine glucose of the trichloroethylene group increased after exposure for 2 wk. All the rats showed glycosuria (above 250 mg/dl) by the 4th week of exposure. 2. Plasma glucose levels were depressed by trichloroethylene to as low as 77% of that of the control group. Glycohemoglobin was similarly decreased. 3. Intravenous glucose tolerance tests (0.5 g/kg load) revealed that decreasing constant of plasma glucose (K value) was elevated by trichloroethylene, suggesting that induced hyperglycemia in the exposed rats improved more rapidly than in the controls. Trichloroethylene did not modify the secretion of insulin after glucose load, regardless of the depression in plasma insulin level before load. 4. Glucose titration tests revealed that tubular transport maximum for glucose (TmG) was decreased by trichloroethylene to as low as 46% of that of the control group. The ratio of TmG to glomerular filtration rate (the theoretical renal threshold for glucose) was also depressed to as low as 55% of that of the control group. The foregoing results indicate that trichloroethylene-induced glycosuria is attributable to deteriorated tubular reabsorption of glucose, and not to hyperglycemia. However, the mechanism for the selective disturbance of renal reabsorption of glucose is yet unknown.     

Renal carcinogenicity of trichloroethylene: update, mode of action, and fundamentals for occupational standard setting

Mechanistic data must be incorporated into the assessment of the human risks of chemical carcinogens, for trichloroethylene in particular. The total weight of evidence compiled from data on the genotoxicity of trichloroethylene indicates that systemic mutagenic activity is not expressed in vivo. New epidemiologic data on trichloroethylene generated in Denmark showed a steady decline of occupational exposure to trichloroethylene since 1947, but with occasions of high exposures before 1980. Earlier exposures were related to a slight increase in risk of non-Hodgkin's lymphoma, renal carcinoma, and esophageal carcinoma. Such confounders as coexposure to other industrial solvents (non-Hodgkin's lymphoma) and alcohol drinking (esophageal cancer) must be discussed. In Germany, a new consecutive case-control study on kidney cancer confirmed that the risk of renal cell cancer is significantly elevated in persons reporting long-term (several years) exposure to trichloroethylene. The results of all these studies indicate that low exposure (not higher than the current Occupational Exposure Limits) is not associated with increased risk of malignancy. In the kidney, trichloroethylene can act as a complete carcinogen at the stages of both tumor induction and tumor promotion/progresssion in a in a dose-dependent manner. Different types of kidney cancer can be triggered by different genes. Clear-cell renal carcinoma, preferentially induced by trichloroethylene, is linked with the homozygous inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. In highly exposed subjects, the local genotoxic effect of trichloroethylene results from bioactivation pathways leading to renal VHL gene damage and renal cell carcinomas. The view that renal cell cancer development after long-term (several years) and high (with prenarcotic episodes) occupational exposure to trichloroethylene is due to chronic damage of the proximal tubule of the kidney as a key step argues for the existence of a practical threshold. Prolonged and unusually high-dose exposure to trichloroethylene is deemed a strong risk factor for the development of renal cell cancer. The findings of experimental, mechanistic, and epidemiologic studies lead to the conclusion that trichloroethylene can be considered a human carcinogen for which a practical threshold appears likely and below which no relevant carcinogenic effect is to be expected.     

Low level exposure to cadmium and early kidney damage: the OSCAR study

OBJECTIVES—To study the dose-response relation between cadmium dose and renal tubular damage in a population of workers and people environmentally or occupationally exposed to low concentrations of cadmium.
METHODS—Early kidney damage in 1021 people, occupationally or environmentally exposed to cadmium, was assessed from cadmium in urine to estimate dose, and protein HC (α₁-microglobulin) in urine to assess tubular proteinuria.
RESULTS—There was an age and sex adjusted correlation between cadmium in urine and urinary protein HC. The prevalence of tubular proteinuria ranged from 5% among unexposed people to 50% in the most exposed group. The corresponding prevalence odds ratio was 6.0 (95% confidence interval (95% CI) 1.6 to 22) for the highest exposure group, adjusted for age and sex. Multiple logistic regression analysis showed an increasing prevalence of tubular proteinuria with urinary cadmium as well as with age. After adjustment to the mean age of the study population (53 years), the results show an increased prevalence of 10% tubular proteinuria (taking into account a background prevalence of 5%) at a urinary cadmium concentration of 1.0 nmol/mmol creatinine.
CONCLUSION—Renal tubular damage due to exposure to cadmium develops at lower levels of cadmium body burden than previously anticipated.


Keywords: cadmium; environmental; tubular damage     

Markers of early renal changes induced by industrial pollutants. II. Application to workers exposed to lead.

The present study has been carried out in the framework of a collaborative research project on the development of new markers of nephrotoxicity. A battery of more than 20 potential indicators of renal changes has been applied to 50 workers exposed to lead (Pb) and 50 control subjects. After application of selection criteria 41 exposed and 41 control workers were eventually retained for the final statistical analysis. The average blood Pb concentration of exposed workers was 480 micrograms/l and their mean duration of exposure was 14 years. The battery of tests included parameters capable of detecting functional deficits (for example, urinary proteins of low or high molecular weight), biochemical alterations (for example, urinary eicosanoids, glycosaminoglycans, sialic acid) or cell damage (for example, urinary tubular antigens or enzymes) at different sites of the nephron or the kidney. The most outstanding effect found in workers exposed to Pb was an interference with the renal synthesis of eicosanoids, resulting in lower urinary excretion of 6-keto-PGF1 alpha and an enhanced excretion of thromboxane (TXB2). The health significance of these biochemical alterations, detectable at low exposure to Pb is unknown. As they were not associated with any sign of renal dysfunction, they may represent reversible biochemical effects or only contribute to the degradation of the renal function from the onset of clinical Pb nephropathy. The urinary excretion of some tubular antigens was also positively associated with duration of exposure to Pb. Another effect of Pb that might deserve further study is a significant increase in urinary sialic acid concentration.     

Renal cell carcinoma and occupational exposure to chemicals in Canada

This study assesses the effect of occupational exposure to specific chemicals on the risk of renal cell carcinoma in Canada. Mailed questionnaires were used to obtain data on 1279 (691 male and 588 female) newly diagnosed, histologically confirmed renal cell carcinoma cases and 5370 population controls in eight Canadian provinces, between 1994 and 1997. Data were collected on socio-economic status, smoking habit, alcohol use, diet, residential and occupational histories, and years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using unconditional logistic regression. The study found an increased risk of renal cell carcinoma in males only, which was associated with occupational exposure to benzene; benzidine; coal tar, soot, pitch, creosote or asphalt; herbicides; mineral, cutting or lubricating oil; mustard gas; pesticides; and vinyl chloride. Compared with no exposure to the specific chemical, the adjusted ORs were 1.8 (95% CI = 1.2-2.6), 2.1 (1.3-3.6), 1.4 (1.1-1.8), 1.6 (1.3-2.0), 1.3 (1.1-1.7), 4.6 (1.7-12.5), 1.8 (1.4-2.3) and 2.0 (1.2-3.3), respectively; an elevated risk was also associated with exposure to cadmium salts and isopropyl oil. The risk of renal cell carcinoma increased with duration of exposure to benzene, benzidine, cadmium, herbicides and vinyl chloride. Very few females were exposed to specific chemicals in this study; further research is needed to clarify the association between occupational exposure to chemicals and renal cell carcinoma in females.     

Effects of exposure to low concentrations of chlorinated hydrocarbons on the kidney and liver of industrial workers.

An assessment has been made of biochemical alterations in renal and hepatic functions of 73 male operators employed for an average of 8.2 years (range 0.5-23 years) in a chemical plant producing chlorinated hydrocarbons. Exposure to allyl chloride (AC), 1,3-dichloropropene (DCP), epichlorohydrin (ECH), and hexachlorocyclopentadiene (HEX) has regularly been determined by personal air monitoring since 1980. Although exposures to DCP and ECH were well below currently accepted maximum allowable concentrations (MACs), relatively high exposures to AC and HEX, occasionally exceeding the MAC, have been measured. The results of the kidney and liver function tests were compared with those of a control group comprising 35 men employed at the materials division and not occupationally exposed to chemicals. Biochemical alterations of liver function were assessed by determination in serum of alanine and aspartate aminotransferases (ALAT, ASAT), alkaline phosphatase (AP), total bilirubin (BIL), gamma-glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), and total bile acids (SBA). No differences between the exposed group and the control group were found. Nor were differences found in biochemical tests for renal tubular damage (urinary alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) and renal tubular function (urinary retinol binding protein (RBP). Total urinary protein and albumin excretion were measured to assess the integrity of the glomerulus. Urinary total protein did not differ between the groups, but urinary albumin, although within normal limits in both groups, was significantly higher (p < 0.02) in the exposed group. This difference in urinary albumin could not simply be explained by exposure to chlorinated hydrocarbons because albumin concentrations did not correlate with the duration of employment. It is concluded that long term exposure to concentrations of AC, DCP, ECH, or HEX below or near the current limit threshold value does not lead to clinically significant effects on kidney and liver.     

Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene: new aspects to be considered

Technical dinitrotoluene (DNT) is a mixture of 2,4- and 2,6-DNT. In humans, industrial or environmental exposure can occur orally, by inhalation, or by skin contact. The classification of DNT as an 'animal carcinogen' is based on the formation of malignant tumors in kidneys, liver, and mammary glands of rats and mice. Clear signs of toxic nephropathy were found in rats dosed with DNT, and the concept was derived of an interrelation between renal toxicity and carcinogenicity. Recent data point to the carcinogenicity of DNT on the urinary tract of exposed humans. Between 1984 and 1997, 6 cases of urothelial cancer and 14 cases of renal cell cancer were diagnosed in a group of 500 underground mining workers in the copper mining industry of the former GDR and having high exposures to explosives containing technical DNT. The incidences of both urothelial and renal cell tumors in this group were 4.5 and 14.3 times higher, respectively, than anticipated on the basis of the cancer registers of the GDR. The genotyping of all identified tumor patients for the polymorphic enzymes NAT2, GSTM1, and GSTT1 identified the urothelial tumor cases as exclusively 'slow acetylates'. A group of 161 miners highly exposed to DNT was investigated for signs of subclinical renal damage. The exposures were categorized semi-quantitatively into 'low', 'medium', 'high', and 'very high'. A straight dose-dependence of the excretion of urinary biomarker proteins with the ranking of exposure was seen. Biomarker excretion (alpha1-microglobulin, glutathione S-transferases alpha and pi) indicated that DNT-induced damage was directed toward the tubular system. New data on DNT-exposed humans appear consistent with the concept of cancer initiation by DNT isomers and the subsequent promotion of renal carcinogenesis by selective damage to the proximal tubule. The differential pathways of metabolic activation of DNT appear to apply to the proximal tubule of the kidney and to the urothelium of the renal pelvis and lower urinary tract as target tissues of carcinogenicity.     

Urinary protein excretion in workers exposed to low doses of cadmium

Conclusions There was evidence of mild renal dysfunction in three of the cadmium-exposed individuals out of the total of 39. However, in none of them did we find a fully developed tubular proteinuria in which moderate increases of total proteinuria, increased lysozymuria and beta-2 microglobulinuria, and excretion of low molecular weight proteins by SDS-PAGE would also be found.Out of the four parameters determined, only one patient had three of them in the abnormal range, but this patient showed predominant elimination of high molecular weight proteins, compatible with glomerular damage, an unexpected finding in cadmium poisoning. Renal dysfunction was detected in one control subject who had increased total protein classified as tubular. There were two abnormal SDS-PAGE patterns found in the control group in which the other parameters measured were normal as was the case in the cadmium exposed patients.     

Lack of nephrotoxicity of styrene at current TLV level (50 ppm)

Summary Biochemical markers of kidney damage were examined in 37 female workers exposed to an average concentration of 225 mg/m³ of styrene. The concentration of mandelic acid in urine was on the average 759 mg/g creatinine. The mean duration of employment of the exposed subjects was 11 years. The results were compared to those obtained in 35 control female workers matched for age and a number of demographic and lifestyle factors and with no history of exposure to organic solvents. No difference was found in the urinary excretion of albumin, beta₂-microglobulin, retinol-binding protein, total proteins, glucose, lysozyme, lactate dehydrogenase and beta-N-acetyld-glucosaminidase. The present study provides thus further evidence that exposure to styrene at the current TLV (215 mg/m³) does not entail any detectable risk for the renal function.     

Occupational exposure to toluene and its possible causative role in renal damage development in shoe workers

Objectives: An important, although, unprecise number of shoe workers in Leon, Mexico, are in continuous contact with toluene-based glues. The induction of renal glomerular and/or tubular lesions as a result of toluene exposure is still being discussed controversially. Our objective was to evaluate the extent of occupational exposure, assessing urinary o-Cresol excretion as a measure for toluene exposure in a population at risk as compared to a control population. Urinary albumin excretion (UAE) and N-acetyl-β-D-glucosaminidase (NAG) enzymatic activity were tested to assess renal dysfunction. Methods: A cross-sectional study was performed comparing 50 toluene-exposed shoe workers and 25 control subjects. Urinary o-cresol was assessed on first and last day of labor week from exposed subjects. A single urine sample was obtained from control subjects. Urinary Albumin excretion (UAE) and (NAG) activity were examined in 12 h urine samples in all subjects. Urine and serum creatinine were measured to asses renal function. Results: At the end of the labor week, urinary o-cresol levels were higher in samples obtained from exposed subjects. Albumin excretion was similar in the exposed and control groups. NAG activity was greater in the exposed group compared to control group (median 3.5 U/g creatinine vs 1.9 U/g creatinine, z=2.6, P=0.009). An inverse relationship was found between schooling years and the NAG enzymatic activity for the two studied groups (r= −0.27, P=0.02), Conclusions: Our findings support the hypothesis that toluene may be a factor associated with the presence of renal damage in exposed shoe workers. As NAG activity is increased, we believe the lesion initiates in the renal tubular cells.     

Renal effects of low doses of mercury

OBJECTIVES: The present study was aimed at investigating early markers of renal damage and dysfunction in subjects exposed to low doses of mercury from different sources. Different groups of subjects were examined with urinary Hg excretion (HgU) ranging from 0.1 to 35.0 micrograms/g creatinine: 122 occupationally exposed workers, 22 subjects living in a non-polluted area, but consuming large amounts of tuna and sword fish, and 197 controls. METHODS: Several markers of renal changes were measured in urine (albumin, fibronectin, beta 2-microglobulin, retinol-binding protein, tubular antigens, N-acetyl-beta-D-glucosaminidase activity) and serum (beta 2-microglobulin and cystatin C). Serum autoantibodies towards collagen, laminin and tubular antigens were assessed in subjects with abnormal renal markers. The role of glutathione-S-tranferases GSTT1 and GSTM1 polymorphisms in the inter-individual variability of biological response to Hg was also investigated. RESULTS: Renal markers were not correlated with HgU. None of such markers differed significantly between exposed workers and controls, except for urinary beta 2-microglobulin, which was decreased in Hg-exposed workers (GM = 55.8 vs 86.6 micrograms/g creatinine), in the absence of any changes in serum concentration. Subjects usually eating tuna and sword fish showed an increased urinary excretion of beta 2-microglobulin, albumin and fibronectin. Serum titres of auto-antibodies did not differ between the groups. Neither in controls nor in exposed workers were the observed differences modified by the GSTM1 and GSTT1 genotypes. CONCLUSION: The present study did not provide evidence of any changes in kidney integrity and function in subjects exposed to very low levels of inorganic Hg resulting in urinary Hg lower than 35 micrograms/g creatinine. Nor did we obtain evidence of Hg-induced autoimmunity towards kidney components. The potential modifying role of GST polymorphisms could not be clarified in the absence of effects associated with exposure to the risk factor, i.e., to inorganic Hg. Preliminary data suggesting nephrotoxic effects of organic Hg from a diet rich in large fish resulting in increased levels of both blood and urinary Hg--which however did not exceed 20 micrograms/g creatinine--deserves further investigation.     

A cross-sectional survey of kidney function in refinery employees

We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.     

Cancer risk among workers at Danish companies using trichloroethylene: a cohort study

Trichloroethylene is an animal carcinogen with limited evidence of carcinogenicity in humans. Cancer incidence between 1968 and 1997 was evaluated in a cohort of 40,049 blue-collar workers in 347 Danish companies with documented trichloroethylene use. Standardized incidence ratios for total cancer were 1.1 (95% confidence interval (CI): 1.04, 1.12) in men and 1.2 (95% CI: 1.14, 1.33) in women. For non-Hodgkin's lymphoma and renal cell carcinoma, the overall standardized incidence ratios were 1.2 (95% CI: 1.0, 1.5) and 1.2 (95% CI: 0.9, 1.5), respectively; standardized incidence ratios increased with duration of employment, and elevated standardized incidence ratios were limited to workers first employed before 1980 for non-Hodgkin's lymphoma and before 1970 for renal cell carcinoma. The standardized incidence ratio for esophageal adenocarcinoma was 1.8 (95% CI: 1.2, 2.7); the standardized incidence ratio was higher in companies with the highest probability of trichloroethylene exposure. In a subcohort of 14,360 presumably highly exposed workers, the standardized incidence ratios for non-Hodgkin's lymphoma, renal cell carcinoma, and esophageal adenocarcinoma were 1.5 (95% CI: 1.2, 2.0), 1.4 (95% CI: 1.0, 1.8), and 1.7 (95% CI: 0.9, 2.9), respectively. The present results and those of previous studies suggest that occupational exposure to trichloroethylene at past higher levels may be associated with elevated risk for non-Hodgkin's lymphoma. Associations between trichloroethylene exposure and other cancers are less consistent.     

Urinary beta2 microglobulin related to chronic low level exposure to metallic cadmium dust in Finnish cadmium processing workers.

The determination of urinary beta2 microglobulin is a sensitive method for screening groups which run the risk of developing renal tubular damage due to cadmium exposure. In this study, the urinary beta2 microglobulin excretion of 78 male workers who had been exposed to cadmium dust levels of 6.3-11.0 microgram/m3 from 0.5 to 4 h daily for an average of four years was compared to 35 nonexposed male workers. Possible effects of smoking on renal beta2 micorglobulin excretion were controlled. The results indicate that the levels of cadmium to which the workers were exposed have no measurable renal effects on the health of workers.     

Cadmium and lead in blood in relation to low bone mineral density and tubular proteinuria

Long-term exposure to cadmium may cause kidney and bone damage. Urinary cadmium is commonly used as the dose estimate for the body burden of cadmium. However, elevated levels of cadmium in the urine may reflect not only high levels of cadmium dose but also renal dysfunction. In this study we used blood cadmium as the dose estimate. In addition, we analyzed blood lead. We examined 479 men and 542 women, ages 16-81 years, who were environmentally or occupationally exposed to cadmium and lead. We used urinary protein alpha 1-microglobulin as a marker for tubular proteinuria and measured forearm bone mineral density using dual-energy X-ray absorptiometry. The relationship between blood cadmium and tubular proteinuria was strong, even when we excluded occupationally exposed participants. The subgroup with the highest blood cadmium levels had a 4-fold risk of tubular proteinuria compared to the subgroup with the lowest blood cadmium levels. In the older age group (age > 60), the risk of low bone mineral density (z-score < -1) for the subgroup with the highest blood cadmium levels was almost 3-fold compared to the group with lowest blood cadmium levels. We found no similar associations for lead. The observed effects may be caused by higher cadmium exposure in the past. This study strengthens previous evidence that cadmium exposure may affect both bone mineral density and kidney function.     

Oxidative damage in foundry workers occupationally co-exposed to PAHs and metals

Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) has been reported in foundries. A higher risk for DNA damage or oxidative damage lesions was also found in occupationally PAH-exposed groups. The aim of this study was to assess PAH exposure by urinary excretion of 1-hydroxypyrene (1-OHP), a biological exposure marker. Furthermore, we aimed to evaluate the oxidative damage of foundry workers with different job tasks and the association between 1-OHP, metal exposure and oxidative damage in foundry workers exposed to pervasive carcinogens.     

Biological monitoring and exposure to mercury

Occupational health professionals' interest in controlling mercury (Hg) exposure, and the use of biological monitoring in this context, has been ongoing for a number of years. Evidence from urinary Hg results in a number of UK firms who have undertaken some form of biological monitoring or occupational health surveillance suggest that exposure has decreased over the last 10-15 years. This decrease precedes the establishment in the UK of an advisory biological monitoring guidance value (HGV) for urinary Hg and the production of updated medical guidance from the Health & Safety Executive on Hg exposure (MS12 1996). This latter document recommends a urinary sampling interval for urinary Hg of between 1 and 3 months, which is consistent with the reported toxicokinetics of Hg excretion, but we highlight that urinary Hg represents integrated exposure over many previous months. Mercury is a recognized nephrotoxin and MS12 1996 mentions the use of regular dipstick protein estimations. We review our experience of investigating proteinuria and enzymuria in a large-scale cross-sectional occupational study. The incidence of Hg-induced renal disease is probably very rare at current exposure levels. Therefore acceptance of a high false-positive rate of proteinuria not related to Hg exposure needs to be considered in any urinary protein testing regime of Hg workers. The establishment of an HGV for urinary Hg has raised questions about the uncertainty associated with a urinary Hg result, including factors such as diurnal variation, whether urine correction by creatinine or specific gravity is preferable and the possibility of non-occupational sources of Hg contributing significantly towards breaching the HGV. Correction of urinary Hg results by creatinine or specific gravity and the use of a fixed sampling time, such as the beginning or end of the day, substantially reduce the uncertainty in a urinary Hg measurement. But even with good laboratory precision, an individual with a true urinary Hg excretion of 20 nmol/mmol creatinine could supply urine samples of between 14 and 26 nmol/mmol creatinine. The influence of dietary sources in the UK contributing to urinary Hg values approaching or exceeding the HGV is unlikely. The use of tribal or ethnic cosmetics and remedies needs to be considered if a urinary Hg result looks inappropriately high, as some such preparations have been found to contain Hg and can be absorbed through the skin. The ability of excessive chewers or teeth grinders who have a large number of dental amalgam fillings to breach the urinary HGV in the absence of substantial occupational Hg exposure has been reported in a few Scandanavian studies. We report here a likely case of this phenomenon. Since the establishment of the HGV, our biological monitoring Hg data from a number of industry sectors using inorganic or metallic Hg have suggested that a minority of samples (13%) are still greater than the HGV.