Assessment of occupational exposure to stainless steel welding fumes - A human biomonitoring study.

The aim of the study was to determine the concentration of hexavalent and trivalent chromium, nickel, manganese, and iron in welding fumes (WFs) and to evaluate the significant association between the concentration of metals in the biological material of welders. The studies were conducted in welders (n = 67) and controls (n = 52). Stainless steel WFs were continuously collected in the workers' breathing zone during a shift. The serum and urine concentrations of Cr and Ni were determined by ICP-MS. The content of Mn in the whole blood was determined using ET-AAS. The content of Cr in the erythrocytes was determined using ICP-MS. The Cr concentration in the welders' urine positively correlated with a work environment concentration of Cr (R = 0.59, p < 0.0001), Cr(VI) (R = 0.58, p < 0.0001), and Cr(III) (R = 0.64, p < 0.0001) in the inhalable fraction. The Ni concentration in the welders' urine positively correlated with the Ni concentration in the inhalable and respirable fraction (R = 0.34, p < 0.005 and R = 0.44, p < 0.002). The correlation between the Mn concentration in the work environment air and the Mn concentration in the welders' whole blood (R = 0.46, p < 0.0001) was observed.

Pulmonary response to methylcyclopentadienyl manganese tricarbonyl treatment in rats: injury and repair evaluation.

Methylcyclopentadienyl manganese tricarbonyl (MMT), an organometallic compound, used as an antiknock additive in fuels, may produce alveolar inflammation and bronchiolar cell injury. The aim of the experimental study on female rats was to determine by morphological examination and sensitive biomarkers, the course of the injury and repair process following a single i.p. injection of 5 mg/kg MMT. The animals were sacrificed 12, 24, 48 hours or 7 days post-exposure (PE). The first biochemical changes 12 h PE showed an increase in GSH-S-transferase (GST) activity in the lung parallel to the earliest observed morphological changes -vacuolation and swollen cytoplasm in type I pneumocytes. Alterations in type I pneumocytes were most prevalent in rat lung 24 h PE. Clara cells with dilated smooth endoplasmic reticulum membranes and cytoplasmic vacuolation could be observed. Compared to the values found for controls, Clara cell protein (CC16) in the bronchoalveolar lavage fluid (BALF) at 24 and 48 h PE decreased by 58% and 55%, respectively. At the same time (at 24 and 48 h), the total protein concentration in BALF increased 5 and 7 times, respectively. A significant rise in hyaluronic acid (HA) level was observed 24 and 48 h PE. Divided type II pneumocyte cells and Clara cells in their mitotic phase were observed in immunocytochemistry (detecting BrdU binding into DNA) 48 h PE. Seven days after MMT administration, fibroblasts, macrophages, collagen and elastin fibres could be seen in the alveolar walls as well as neutrophils, lymphocytes, and alveoli macrophages in the alveolar lumen. We conclude that injury and repair of bronchial epithelium cells, especially of Clara cells and type II pneumocyte cells, play an important part in MMT toxicity, probably depending on the antioxidant status of these cells. The sensitive biomarkers of CC16 and hyaluronic acid in BALF and serum reflect lung injury and indicate the time course of pulmonary damage and repair processes.

Serum clara-cell protein and beta2-microglobulin as early markers of occupational exposure to nitric oxides.

Biochemical effects of NOx on 60 workers (both genders) of nitric acid production were studied. The control group consisted of 61 nonexposed people employed elsewhere in the plant. Although the actual threshold limit valuetime weighted averages (TLV-TWA) were not exceeded in the specific conditions of our study, the subjects were exposed to NO2 and NO during several exposure episodes with peak maximal concentrations of 140 ppm and 515 ppm, respectively. Additional cross-week evaluation of several biochemical biomarkers in 15 NOx-exposed workers from one shift was performed. The objective of the study was to evaluate the value of serum Clara-cell protein (CC16) as a marker of bronchoalveolar epithelium activity. Antioxidant status was assessed by measuring activity of enzymes: glutathione peroxidase (GSH-Px), ceruloplasmin (Cp) in plasma, or superoxide dismutase (SOD), gluthatione S-transferase (GST), and nonenzymatic alpha-tocopherol in erythrocytes and thiobarbituric acid-reactive substances (TBARS) in plasma. Serum hyaluronic acid (HA) determining the connective tissue matrix status of airways, and beta2-microglobulin in serum (beta2M-S) and urine (beta2M-U) as a marker of renal function in occupational exposure to NOx were also employed. Exposure to NOx initiates peroxidative chain depleting of lipoprotein pool (alpha-tocopherol) in blood. Serum CC16 levels in NOx-exposed workers were found to be closely connected with alpha-tocopherol content. In NOx-exposed workers, the beta2M-S level was significantly higher than in the nonexposed ones, with the exception of smokers. Results of the cross-week study confirm cumulative systemic effects of NOx on several examined biomarkers. SOD and GST were found to be depleted. A transient higher level of HA after a 5-d shift significantly inversely correlated with CC16 level. The data imply that NOx-depleted levels of CC16 are detectable already after an 8-h shift. Our results demonstrate that even low NOx human exposure can cause characteristic changes in bronchiolar epithelium cells and renal effects. Serum CC16 level, although a nonspecific marker, was lowest in NOx-exposed subjects. The most sensitive parameters in exposed workers were beta2M-S and a-tocopherol. Spirometric assessment was not useful to describe low occupational exposure to NOx. In studying the effects of NOx on biomarkers, it is essential to carefully select suitable time of sampling. Screening of CC16, beta2M-S, and a-tocopherol can be successfully employed for biological monitoring of exposure to NOx.

The effects of environmental cadmium exposure on kidney function: the possible influence of age.

The study aimed to assess the possible influence of long-term environmental exposure to cadmium and age at the time of exposure on renal function. The study was a follow-up of the 1991-1994 project concerning 2000 inhabitants of a cadmium-contaminated area in the vicinity of a zinc smelter. Since the smelter was built in the late 1950s but was not operated until 1968, some of the inhabitants were not exposed to cadmium during childhood. For the follow-up, 308 persons who in 1993 presented with Cd-U levels > or = 0.5 microg/L adjusted for specific gravity (1.020) were selected in 2000. The study population included 136 people who were exposed to cadmium in childhood (former children) and 172 adults (unexposed adults) with no such exposure. These two groups were divided into subgroups according to Cd-U levels: < or =1 (group 1), 1-2 (group 2), and > or =2 microg/g creatinine (group 3). Urinary and blood cadmium and the markers of renal tubular dysfunction (beta2 M-U, RBP-U, NAG, NAG-A, NAG-B) and glomerular dysfunction (Alb-U and beta2 M-S) were measured. Persons with a history of occupational exposure to cadmium were excluded from this project. In group 3 of the unexposed adults, concentrations of RPB-U, NAG, NAG-B, and Alb-U were significantly higher than those in group 1. In former children, this could be observed only for RPB-U and Alb-U. Urine concentrations of these markers were higher in all of the subgroups of former children than in the groups of unexposed adults (except for NAG and its two forms). However, these differences were significant only for RBP-U in group 3. The findings indicate that early renal effects in the general population may occur at Cd-U concentrations above 2 microg/g creatinine and at lower levels for NAG-B. Moreover, cadmium exposure in childhood may have a stronger impact the renal function, particularly tubular reabsorption, than the exposure of a mature organism.

Glutaraldehyde inhalation exposure of rats: effects on lung morphology, Clara-cell protein, and hyaluronic acid levels in BAL.

Glutaraldehyde (GA) is a biocide widely used in hospital and laboratory practice. GA is a volatile substance and, under certain circumstances, significant airborne concentrations may be generated at room temperature. Occupational exposure to GA by inhalation is suspected of causing delayed irritating effects. In recent years, GA has emerged as the main cause of occupational asthma among health-care workers. The aim of the present study was to evaluate effects of GA inhalatory exposure (0.025 ppm or 0.1 ppm, for 28 days) in rats exposed corresponding to the occupational shift cycle, at time point 24 h, 48 h, and 7 days postexposure (PE). Numerous vacuoles and dilated spaces in epithelial cells in bronchioles showing a destructive effect of GA on the cellular membrane were observed at 24 h PE in 0.1 ppm exposed rats. Lipid vacuoles observed after 48 h PE in higher GA exposure, in the Clara cells of the bronchial epithelium, and in endothelial cells of the alveolar capillaries are probably attributable to disturbed lipid metabolism. Many foci of collagen fibers were observed already after 7 days postexposure. Monitoring of inflammatory response and repair was made possible by using two biomarkers: Clara-cell protein (CC16) and hyaluronic acid (HA). Our results show that the inflammatory repair response contributed to progenitor Clara cells and HA plays a role in the development of fibrotic changes in the lung of rats. Glutaraldehyde in rats causes fibrotic effects at the actual threshold limit value-time weighted average (TLV-TWA) level for GA as specified by current Polish and other national regulations.

Reversibility of microproteinuria in nickel-cadmium battery workers after removal from exposure.

OBJECTIVES: The study was aimed at assessing the reversibility of renal tubule dysfunction in workers exposed to cadmium according to the severity of microproteinuria, concentrations of cadmium in urine (Cd-U), and the time since removal from exposure. METHODS: The study was carried out in a nickel-cadmium battery factory. Exposure to cadmium was formerly very high. In 1983 and in 1986-1988, geometric mean concentrations of cadmium in blood (Cd-B) of workers amounted to 23.3 micro g/l and 55.7 microg/l, respectively. Workers with determinations of Cd-B, Cd-U and retinol binding protein in urine (RBP-U) in the past were eligible for the study. Fifty-eight workers who had met this profile and had been removed from exposure to cadmium before 1998 were investigated in 1998-1999. They were divided into three groups according to their RBP-U concentrations in 1986-1988: <300 ( n=26); 301-1,501 ( n=25) and >1501 microg/g creatinine ( n=7). RESULTS: In 1999, the RPB-U levels were below 300 microg/g creatinine in 85%, 64% and 42% of persons from groups 1, 2 and 3, respectively. Statistical analysis of the results by means of multi-parametric logistic regression analysis revealed that, from the viewpoint of reversibility of tubular proteinuria, its severity in 1986-1988 was most important. Also, the time since the removal from exposure to cadmium and Cd-U levels seemed to play some role, but the influence of these parameters was not statistically significant. Significant correlation between beta(2)-microglobulin in serum (beta(2)M-S) and RBP-U concentrations measured in 1998-1999 with apparent lack of correlation between beta(2)M-S and RBP-U concentrations in 1986-1988 supports the hypothesis that the glomerular impairment induced by cadmium may be secondary to the tubular lesion rather than independent from tubular effect. CONCLUSIONS: The results show that the tubular proteinuria, and maybe also the decline in glomerular filtration rate, may be reversible, even in the case of relatively high past exposure. The results confirm the necessity for monitoring urinary levels of low-molecular-weight proteins during periodic examination of workers exposed to cadmium.

Quantification of Clara cell protein in rat and mouse biological fluids using a sensitive immunoassay.

Clara cell protein is a 16-17 kDa protein (CC16) secreted by Clara cells in the bronchiolar lining fluid of the lung. In order to investigate the potential of this protein as a pulmonary marker in animals, CC16 was isolated from rat bronchoalveolar lavage fluid (BALF) and a sensitive latex immunoassay applicable to both rat and mouse CC16 was developed. The pattern of CC16 concentrations in rat biological fluids determined by the immunoassay was consistent with the hypothesis of a passive diffusion of the protein across the bronchoalveolar/blood barriers showing a difference of more than 5,000 fold between the concentration in the epithelial lining fluid (mean, 140 mg x L(-1)) and that in serum (20 microg x L(-1)) or urine (3 microg x L(-1)). In BALF, the CC16 concentration averaged 5,500 microg x L(-1) and was of the same magnitude as that determined on lung and trachea homogenates. CC16 was also detectable in amniotic fluid with a mean value of 800 microg x L(-1) before delivery. Damage of Clara cells produced by methylcyclopentadienyl manganese tricarbonyl resulted in a significant decrease of CC16 in BALF but did not affect the serum levels of the protein. The nephrotoxicant sodium chromate by contrast had no influence on the CC16 content of BALF but markedly increased CC16 levels in both serum and urine as a result of impaired glomerular filtration and tubular reabsorption, respectively. In conclusion, mouse or rat Clara cell protein of 16-17 kDa can easily be quantified, not only in bronchoalveolar lavage fluid, but also in extrapulmonary fluids such as serum or urine. Thus, in rodents, Clara cell protein of 16-17 kDa follows the same metabolic pathway as in humans, diffusing from the respiratory tract into serum where it is eliminated by the kidneys. This serum Clara cell protein of 16-17 kDa may be useful as a peripheral marker of events taking place in the respiratory tract.

Urinary excretion of copper bound to low molecular weight proteins in the population exposed to cadmium in community and occupational environments.

People living in Cd-polluted areas excrete increased amounts of copper with urine. A substantial quantity of this is eliminated with metallothionein the concentration of which in urine increases in people exposed to cadmium. Therefore, the measurement of metallothionein in urine is applied as a marker of renal function in people exposed to cadmium in addition to other low molecular weight proteins, beta 2-microglobulins (beta 2MG) and retinol binding proteins (RBP). In this study copper bound to metallothionein-like proteins of low molecular weight (CuBP)--a newly proposed marker of cadmium nephrotoxicity, as well as beta 2MG and RBP, were evaluated in those exposed to cadmium in the community and in occupational environments. The results obtained indicated that people exposed to cadmium in both polluted environments excreted greater amount of CuBP in urine than people not exposed to cadmium. In groups excreting cadmium in urine in amounts ranging from 1 to 10 micrograms/l the urinary level of CuBP was closely associated with the levels of beta 2MG and RBP. A considerable increase in the excretion of urinary CuBP began when Cd concentration in urine exceeded 4 micrograms/l. The amount of CuBP excreted was higher in people with renal disfunction than in those with a normal renal function. It is suggested that urinary excretion of CuBP may be considered as a specific marker of renal function in people exposed to cadmium.

[Nephrotoxic action of cadmium]. / Nefrotoksyczne dzialanie kadmu.

Functional state of kidney in persons exposed to cadmium (Cd) is estimated mostly by determination of low molecular proteins in urine (beta 2MG, RBP) they are sensitive but not specific indicators of Cd exposure effects. The usefulness of a new indicator of renal functional disorders which is similar to metallothionein was studied. The test involved the determination of the urinary excretion of cadmium bound to low molecular specific protein. It was assessed in population exposed to cadmium in industry (high cadmium concentration) and in population limited to the conditions of residential area (low cadmium concentrations). It was found, that CdBP excretion in urine was higher in a group of persons exposed to cadmium with renal dysfunction (regardless of level of exposure). This was closely correlated with beta 2MG and levels in urine. People with renal dysfunction,-unexposed to cadmium have not excreted any CdBP in urine.

Integrated index of occupational exposure to cadmium as a predictor of kidney dysfunction.

In a study carried out in an alkaline battery factory, the study group consisted of 141 factory workers exposed to cadmium, while 206 workers in the textile industry constituted the control group. Cadmium in blood (Cd-B), cadmium in urine (Cd-U) as well as beta 2-microglobulin and retinol-binding protein (RBP) in urine were determined. Exposure to cadmium in the factory was high. In 1988, Cd-B concentrations in different departments averaged 11.2-29.9 micrograms/l. To evaluate the admissible period of occupational exposure to cadmium, an integrated exposure index [Cd-B (micrograms/l) x years of exposure] is proposed. According to the dose-response relationship, an increase in low molecular weight protein excretion in urine can be expected in 10% of subjects at an integrated exposure index of about 300 micrograms/l x years of exposure. The data obtained confirmed the validity of the recommended health-based limits for occupational exposure of 10 micrograms/l and 10 micrograms/g creatinine for Cd-B and Cd-U respectively.

[Latex immunologic methods of determining micro-molecular proteins and albumins in urine. Part I. Description of the method]. / Lateksowo-immunologiczna metoda oznaczania bialek niskoczasteczkowych i albuminy w moczu. I. Opis metody.

The most frequent markers of early kidney dysfunction include determination of micromolecular proteins, such as beta 2-microglobulin (beta 2M), retinol-binding protein (RBP) and albumins (Alb), in urine. The determination of those proteins in urine is carried out by means of immunological methods. The latex-immunological methods (LIA), allowing to avoid the use of radioisotopes and relatively cheap one as compared with ready-made proprietary kits, may prove to be particularly useful in Polish laboratories. The LIA method in routine tests of protein content in urine was practically assessed. Reproducibility of the method was verified under the conditions of international quality control.

[A latex immunologic method of analysis of low-molecular proteins and albumin in urine. II. Beta 2-microglobulin, retinol-binding protein and albumin levels in the urine of general Polish population and workers exposed to cadmium]. / Lateksowo-immunologiczna metoda oznaczania bialek niskoczasteczkowych i albuminy w moczu. II. Poziomy beta 2mikroglobuliny, bialka wiazacego retinol i albuminy w moczu w populacji generalnej w Polsce oraz u osób narazonych zawodowo na kadm.

The aim of the work was to collect data about beta 2-microglobulin (beta 2M), retinol-binding protein (RBP) and albumin (Alb) levels in subjects not exposed to nephrotoxic agents in Poland. The data are necessary to interpret determination results in persons occupationally exposed to these chemicals. Concentrations of beta 2-microglobulin, retinol-binding protein and albumin in urine were determined using latex-immunological method. Examination of levels of low molecular proteins and albumin was made on population from agricultural regions of Poland (the Suwalki region) and on textile plant workers from Lódz not exposed to nephrotoxic agents. It was found that upper normal level of low molecular proteins in urine was 300 micrograms/l and of albumin 60 mg/l. The data obtained indicate that sex and age play an important role in beta 2-M and RBP excretion. In the workers of an alkaline accumulator plant who were occupationally exposed to cadmium, a statistically increased excretion of low molecular proteins in urine was observed compared to the controls from Lódz. In 20% of the subjects beta 2-M and RBP concentration in urine were higher than the accepted upper normal levels. Collected data make one aware of necessity to study the above determinations which lead to an early detection of renal function disorders.

Correlation of cadmium-induced nephropathy and the metabolism of endogenous copper and zinc in rats.

Female Wistar rats were injected (sc) every second day for 8 weeks with Cd (0.25 mg/kg) as CdCl2. After only a 2-week exposure, when cadmium (Cd) concentration in liver was about 13 micrograms/g, ultrastructural examinations revealed some irregular ergastoplasm systems and significant proliferation of smooth endoplasmic reticulum in the hepatocyte ultrastructure. The increase in Zn content occurred simultaneously with the increase in Cd concentration in the liver (Zn to Cd ratio was 1:1). In the kidneys after a 3-week exposure, when Cd concentration was 7 micrograms/g, the concentration of endogenous Cu increased. At the same time the urinary excretion of that metal was considerably higher than that of the control group. In the kidneys after a 4-week exposure, when Cd concentration in this organ exceeded 10 micrograms/g tissue, injured brush border microvilli and swollen mitochondria in the proximal convoluted tubular cells were seen. In renal corpuscules, fusion between the podocyte pedicles was also found. The changes in renal cortex ultrastructure became more pronounced when Cd concentration in kidney was increasing. Necrotic changes in the examined organ were observed when Cd concentration increased to about 30 micrograms/g tissue. The critical concentration in renal cortex of about 200 micrograms/g tissue should be revised. The present margin of safety with regard to risk of renal effects is small.