The time-dependent health and biochemical effects in rats exposed to stainless steel welding dust and its soluble form.

Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. The principal objective of this study was to determine the dynamics of toxic effects of inhalation exposure to morphologically rated welding dust from stainless steel welding and its soluble form in TSE System with a dynamic airflow. We assessed the pulmonary toxicity of welding dust in Wistar rats exposed to 60.0 mg/m3 of respirable-size welding dust (mean diameter 1.17 µm) for 2 weeks (6 h/day, 5 days/week); the aerosols were generated in the nose-only exposure chambers (NOEC). An additional aim included the study of the effect of betaine supplementation on oxidative deterioration in rat lung during 2 weeks of exposure to welding dust or water-soluble dust form. The animals were divided into eight groups (n = 8 per group): control, dust, betaine, betaine + dust, soluble-form dust, soluble-form dust + betaine, saline and saline + betaine groups. Rats were euthanized 1 or 2 weeks after the last exposure for assessment of pulmonary toxicity. Differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase-LDH) activities were determined in bronchoalveolar lavage (BAL) fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) concentrations were assessed in serum. The increase in polymorphonuclear (PMN) leukocytes in BAL fluid (a cytological index of inflammatory responses of the lung) is believed to reflect pulmonary toxicity of heavy metals. Biomarkers of toxicity assessed in bronchoalveolar fluids indicate that the level of the toxic effect depends mainly on the solubility of studied metal compounds; biomarkers that showed treatment effects included: total cell, neutrophil and lymphocyte counts, total protein concentrations, and cellular enzyme (lactate dehydrogenase) activity. Betaine supplementation at 250 mg/kg/day in all study rats groups attenuated stress indices, and corticosterone and TBARS serum levels, and simultaneously stimulated increase of polymorphonuclear cells in BALF of rats. The study confirmed deleterious effect of transitory metals and particles during experimental inhalation exposure to welding dusts, evidenced in the lungs and brain by increased levels of total protein, higher cellular influx, rise of LDH in BALF, elevated TBARS and increased corticosterone in serum of rats. Our result confirm also the hypothesis about the effect of the welding dusts on the oxidative stress responsible for disturbed systemic homeostasis and impairment of calcium regulation.

Health effects and arsenic species in urine of copper smelter workers.

The aim of this study was to compare indices of exposure in workers employed at different work posts in a copper smelter plant using neurophysiological tests and to evaluate the relationship between urinary arsenic species with the aid of sensitive respiratory and renal biomarkers. We have attempted to elucidate the impact of different arsenic speciation forms on the observed health effects. We focused on the workers (n = 45) exposed to atmospheres containing specific diverse mixtures of metals (such as those occurring in Departments of Furnaces, Lead and Electrolysis) compared to controls (n = 16). Subjective symptoms from the central (CNS) and the peripheral (PNS) nervous system were recorded and visual evoked potential (VEP), electroneurography (ENeG) and electroencephalography (EEG) curves were analysed. Levels of airborne lead (PbA), zinc (ZnA) and copper (CuA) and Pb levels in blood (PbB) and the relationships between airborne As concentrations (AsA) and the urinary levels of the inorganic (iAs); As(+3), As(+5) and the organic; methylarsonate (MMA(V)), dimethylarsinate (DMA(V)) and arsenobetaine (AsB) arsenic species were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Effects of exposure were expressed in terms of biomarker levels: Clara cell protein (CC16) in serum as early pulmonary biomarker and ß2-microglobulin (ß2M) in urine and serum, retinol binding protein (RBP) as renal markers, measured by sensitive latex-immunoassay (LIA). Abnormal results of neurophysiological tests, VEP, EEG and ENeG showed dominant subclinical effects in CNS and PNS of workers from Departments of Lead and Furnace. In group of smelters from Departments of Furnace exposed to arsenic above current TLV, excreted arsenic species As(+3) and As(+5) seemed to reduce the level of Clara cell protein (CC16), thereby reducing anti-inflammatory potential of the lungs and increasing the levels of renal biomarker (ß2M) and copper in urine (CuU). The study confirmed deleterious arsenic effects to the kidney by increased levels of low-molecular weight protein in urine and the extent of the renal copper accumulation/excretion. The results of our work also support the usefulness of application of the sensitive neurophysiologic tests, such as VEP, EEG and ENeG, for the detection of early subclinical effects of the exposure of the nervous system in copper smelters.

Comparison of neurobehavioral and biochemical effects in rats exposed to dusts from copper smelter plant at different locations.

Mixed exposure to metals (including arsenic and lead) associated with the neurological and respiratory effects constitute one of the major health problems of copper smelting. Chemical composition of the dust, and the expected health effect of inhalation can be very diverse at different parts of the smelter plant. The aims of this study were to compare lung responses and behavioral effects in female Wistar rats after instillation of dust collected from different production processes at the same smelter department. Dusts collected at two different locations of furnace hall were sifted through 25-µm-mesh sieve. Obtained dust fractions, P-25(I) collected near stove, rich in heavy metals and arsenic, and P-25(II) collected near anode residue storage site, rich in aluminium, were instilled to rats. At 1, 7 and 30 days after dusts instillation, lung injury and inflammation were measured by analyzing sings of lung permeability in the bronchoalveolar lavage fluid (BALF), cell differentiation in BALF sediment and lung morphology. The behavioral studies were done 30 days after exposure. Results of biochemical tests showed a strong pro-inflammatory effect of P-25(I) fractions. Mostly characteristic effects after instillation of P-25(I) samples were 10× increased protein leakages in BALF. Both P-25(I) and P-25(II) fractions caused a reduction of Clara-cell 16 protein concentration (CC16) in BALF and activation of serum butyrylcholinesterase (BChE) at all time points. The morphological studies after exposure to P-25(I) fractions showed multi-focal infiltrations in the alveoli. The behavioral results, especially P-25(II) group rats (in open filed, passive avoidance and hot plate tests), indicated adverse effects in the nervous system, which may be related to changes in the dopaminergic and cholinergic pathway. The symptoms were noted in the form of persistent neurobehavioral changes which might be associated with the content of neurotoxic metals. e.g. Al, Mn and/or As. Decrease of CC16 concentration that occurred immediately after instillation of both dust samples, point out impaired anti-inflammatory potential, resulted in early harmful effect not only to the respiratory tract but also to the whole body, including the nervous system.

Clara Cell protein and myeloperoxidase levels in serum of subjects after exposure to fire smoke.

INTRODUCTION: Fire smoke inhalation is a well-recognized aetiological factor of airway injuries. The objective of this study was evaluation of Clara cell protein (CC16) and myeloperoxidase (MPO) concentrations in serum of patients after exposure to uncontrolled fire smoke. METHODS: The study group consisted of 40 consecutive patients admitted to the Toxicology Unit after exposure to fire smoke. CC16 and MPO concentrations in their serum samples was measured on the day of admission to hospital and rechecked at the 2nd day and on the day of discharge. Patients also underwent routine toxicological diagnostic procedures applied in case of exposures, such as carboxyhaemoglobin (COHb) levels and blood lactate and urinary thiocyanate concentrations. The same diagnostic tests were performed in the control group consisting of 10 healthy subjects not exposed to fire smoke. RESULTS: The average concentration of CC16 in the serum of subjects exposed to toxic factors was significantly higher at the day of admission in comparison with the respective values recorded on the 2nd day and on the day of discharge. The mean level of CC16 in the serum of the exposed group was also significantly higher than that in the control group. Tests for MPO concentrations in the serum did not reveal any significant changes in patients exposed to fire smoke. CONCLUSIONS: As indicated, acute exposure to smoke induces injury at the alveolar level, which results in a transient increase of CC16 in serum of exposed subjects.

Assessment of neurobehavioral and biochemical effects in rats exposed to copper smelter dusts.

Female Wistar rats were instilled per os by gavage with different copper dust samples: P-25 obtained by passing the test material through a 25 µmsieve, and P-0.1 containing soluble matter and ultra-fine, non-soluble<100 nm particulate matter (PM) fraction. The control group received sterile saline. The effects were studied at day 1, 7, and 30 post-exposure, focusing on bronchoalveolar lavage fluid (BALF) analysis (including biochemistry, cell morphology, cell viability, and Clara cell 16 protein concentration) and pathomorphology of lung. Results of biochemical tests showed a strong pro-inflammatory effect of both particulate fractions. The morphological studies after exposure to P-25 and P-0.1 fractions showed multi-focal infiltrations in the alveoli. Changes in behavioral (radial maze and passive avoidance tests) have shown that memory in groups exposed to dust was impaired. Our findings indicate that both samples of dust from Copper Smelter cause greater and lesser intensity (P-25 > P-0.1) of the symptoms of acute inflammatory reaction immediately 24 h after instillation to rats. Exposure results in dropping CC16 protein level in serum of rats. After one month, previous acute inflammation was resolved and transformed in persistent low-grade inflammation. The low-grade inflammation resulted in induction of neurobehavioral effects probably by changes in "cholinergic anti-inflammatory pathway" in which acetylcholine modulates neurotransmission.

The inflammatory response in lungs of rats exposed on the airborne particles collected during different seasons in four European cities.

Epidemiological studies have reported associations of ambient particulate air pollution, especially particulate matter (PM) less than 10 µm with exacerbations of asthma and chronic obstructive pulmonary disease. In an in vivo model, we have tested the toxicity of urban airborne particles collected during spring, summer, and winter seasons in four cities (Amsterdam, Lodz, Oslo, and Rome) spread across Europe. The seasonal differences in inflammatory responses were striking, and almost all the study parameters were affected by PM. Coarse fractions of the urban particle samples were less potent per unit mass than the fine fractions in increasing cytokine [macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)-α] levels and in reducing Clara-cell secretory protein (CC16) levels. This study shows that PM collected at 4 contrasting sites across Europe and during different seasons have differences in toxic potency. These differences were even more prominent between the fine and coarse fractions of the PM.

Association between occupational exposure to arsenic and neurological, respiratory and renal effects.

Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n=16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and beta(2)-microglobulin (beta(2)M) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m(3)). The contents of lead did not exceed the TLV (0.05 mg/m(3)). Low CC16 levels in serum (12.1 microg/l) of workers with SNS and VEP symptoms and highest level As-U (x(a) 39.0 microg/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum beta(2)M and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system.

Pulmonary irritation after inhalation exposure to benzalkonium chloride in rats.

BACKGROUND: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) with a C8 to C18 chain length of alkyl groups. Since BAC exerts toxic effects on microorganisms, it has been used as an effective germicide and preservative, mostly in cosmetic industry and medicine. However, the toxic potential of BAC may be hazardous to humans, due to the common use of preparations containing BAC as a preservative. MATERIAL AND METHODS: To assess the possible toxic effects of BAC, two-stage experiments were performed on female Wistar rats. At first, LC50 after a single exposure to BAC aerosol was determined. Then, the animals were exposed to BAC aerosol at 30 mg/m3 for 6 h, and for 3 days (6 h/day). The controls were unexposed rats. Directly after BAC exposure and 18 h afterwards, BALF concentrations were measured of total protein, Clara cell protein, matrix metalloproteinase-9 (MMP-9), hyaluronic acid (HA), immunoglobulin E (IgE) and cytokines (TF-alpha, IL-6 and MIP-20), lactate dehydrogenase (LDH) and GSH-S-transferase (GST). RESULTS: The LC50 value for exposed rats was ca. 53 mg BAC in m3 air for 4 h. All the rats survived single and repeated inhalation exposure to 30 mg/m3 BAC. After single and repeated exposure, lung weight, total protein, HA and LDH activity in BALF of exposed rats were higher than in controls while CC16 levels were decreased. A significantly higher BALF concentration of IL-6 and IgE was noted in animals exposed to single and repeated doses. BALF concentrations of MMP-9, TNF-alpha, and MIP-2 in exposed rats were similar to those in control animals. CONCLUSION: BAC may be classified to class I acute inhalation toxicity. It showed a strong inflammatory and irritant activity on the lungs after 6h inhalation and stimulated dynamic patterns of IL-6 and IgE production and protein infiltration from blood vessels to BALF. Continued exposure resulted in cellular destruction, a statistically significant increase in LDH activity and a continuous decrease in CC16 concentration in BALF.

Clara cells protein, prolactin and transcription factors of protein NF-ĸB and c-Jun/AP-1 levels in rats inhaled to stainless steel welding dust and its soluble form.

OBJECTIVES: Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese, and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. Bronchiolar epithelium Clara cells/club cells, coordinate these inflammatory responses. Clara cells secretory protein (CC16) with ant-inflammatory role. MATERIAL AND METHODS: The pulmonary toxicity of welding dust (WD) was assessed for Wistar rats exposed to 60 mg/m3 of respirable-size welding dust (mean diameter 1.17 µm for 1 and 2 weeks (6 h/day, 5 days/week)) or the aerosols of soluble form (SWD) in the nose-only exposure chambers. Additionally the effect of antiinflammatory betaine supplementation was assessed. Clara cells secretory protein, differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase - LDH) activities were determined in bronchoalveolar lavage fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) and prolactin concentrations were assessed in serum. Histopathology examination of lung, brain, liver, kidney, spleen was done. Additionally slices of brain and lung were exanimated in laser ablation inductively coupled plasma mass spectrometry. RESULTS: Both WD and SWD exposure evoked large bronchiolar infiltration shoved in histopathology examination. In this study, TBARS inversely correlated with a significant decrease of CC16 concentration that occurred after instillation of both WD and SWD indicating decreased anti- inflammatory potential in the lung. In WD exposed rats prolactin correlated with nuclear factor-kappa B (NF-κB), LDH, TBARS and serum levels Cr, Ni and inversely with c-Jun. In SWD exposed rats prolactin correlated with CC16 indicated effect of prolactin on the population of epithelial cells. CONCLUSIONS: In the current study, deleterious effects of repeated inhalation stainless steel welding dust form on club (Clara) cell secretory protein (CC16) were demonstrated. Clara cells secretory protein relation with prolactin in exposed rats to welding dust were shown and explored whether the NF-κB and c-Jun/activator protein 1 related pathway was involved. Int J Occup Med Environ Health 2018;31(5):613-632.

[Toxic effect of benzalkonium chloride on animals and humans]. / Toksyczne dzialanie chlorku benzalkoniowego na zwierzeta i ludzi.

Benzalkonium chloride (BAC) exerts toxic effects on microorganisms. This property has been utilized in the cosmetic industry and medicine, where it is used as effective germicide and preservative agents. Various BAC-containing preparations used by people may induce a number of adverse effects on the human body. Bearing in mind that BAC is widely used in different branches of the national economy, its toxic effect may cause a health problem of significant importance to humans. The authors describe BAC toxic effects exerted on humans and laboratory animals as well as relevant hazards resulting from the use of BAC-contained preparations.

Relation between sources of particulate air pollution and biological effect parameters in samples from four European cities: an exploratory study.

Given that there are widely different prevalence rates of respiratory allergies and asthma between the countries of Europe and that exposure to ambient particulate matter (PM) is substantial in urban environments throughout Europe, an EU project entitled "Respiratory Allergy and Inflammation Due to Ambient Particles" (RAIAP) was set up. The project focused on the role of physical and chemical composition of PM on release of cytokines of cells in vitro, on respiratory inflammation in vivo, and on adjuvant potency in allergy animal models. Coarse (2.5-10 microm) and fine (0.15-2.5 microm) particles were collected during the spring, summer and winter in Rome (I), Oslo (N), Lodz (PL), and Amsterdam (NL). Markers within the same model were often well correlated. Markers of inflammation in the in vitro and in vivo models also showed a high degree of correlation. In contrast, correlation between parameters in the different allergy models and between allergy and inflammation markers was generally poor. This suggests that various bioassays are needed to assess the potential hazard of PM. The present study also showed that by clustering chemical constituents of PM based on the overall response pattern in the bioassays, five distinct groups could be identified. The clusters of traffic, industrial combustion and/or incinerators (TICI), and combustion of black and brown coal/wood smoke (BBCW) were associated primarily with adjuvant activity for respiratory allergy, whereas clusters of crustal of material (CM) and sea spray (SS) are predominantly associated with measures for inflammation and acute toxicity. The cluster of secondary inorganic aerosol and long-range transport aerosol (SIALT) was exclusive associated with systemic allergy. The present study has shown that biological effect of PM can be linked to one or more PM emission sources and that this linkage requires a wide range of bioassays.

Serum Clara cell protein as an indicator of pulmonary impairment in occupational exposure at aluminum foundry.

OBJECTIVES: Although some of the exposures in aluminum (Al) smelting have been well characterized, and respiratory disorders in aluminum production workers are well known, the relationship between internal aluminum loads and appropriate lung biomarkers have not been elucidated. The aim of our work was to carry out a comprehensive investigation in workers employed in the Aluminum Foundry Casting Department with special reference to currently existing hygiene standards, known as threshold limit values (TLV) based on aluminum effects on the respiratory system. The measurement of serum anti-inflammatory Clara cell protein (CC16) was employed as a peripheral marker of the lung epithelium function. MATERIALS AND METHODS: A group of 50 casting smelters, 5 locksmiths, 11 sawyers and auxiliary workers exposed to dust containing 14% of aluminum, and a group of 42 controls were examined. Respiratory function tests were performed and forced volume capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory volume in the first percent (FEV1%), forced expiratory flows in 50% VC (FEV50), and markers of foundry workers' exposure and body burden, Al concentration in the breathing zone, blood and urine, biomarkers of the effects of exposure, concentration of CC16 and hyaluronic acid (HA) in serum were determined in all examined workers. Additional measurements comprised determinations of serum iron (Fe) levels, myeloperoxidase (MPO), eosinophil cationic protein (ECP), immunoglobulin E (IgE), glutathione S-transferase (GST), and superoxide dismutase (SOD) activity in erythrocytes. RESULTS: The group of casting smelters was characterized by the highest levels of aluminum in urine (Al-U) (43.7 microg L(-1)), high levels of MPO, ECP and IgE, high SOD activity, low CC16 levels, and low activity of GST. Lower Al-U excretion was observed in locksmiths (35.2 microg L(-1)) and sawyers (21.7 microg L(-1)). Serum CC16 proved to be the most sensitive biomarker, showing high inverse relationship with serum Al (Al-S) concentrations in casting smelters (p = 0.006). CONCLUSIONS: The study showed that in conditions of occupational exposure, dusts containing Al2O3 < 1 mg m(-3) cause changes in the respiratory system and biomarkers in serum, especially in CC16, connected with altered functioning of this system. Changes in concentrations of the examined biomarkers and also in respiratory parameters of the study subjects were observed when Al-U concentration was > 40 microg L (-1).

Prognostic significance of low serum levels of Clara cell phospholipid-binding protein in occupational aluminium neurotoxicity.

The relationship between respiratory and neurological effects of exposure to aluminium (Al) was investigated in a group of foundry workers exposed to Al at concentrations below the threshold limit value (TLV) binding in Poland (2.0 mg Al2O3 m(-3)). Neurological and neurophysiological parameters indicated subclinical effects of Al exposure on the nervous system. The measurement of serum anti-inflammatory Clara cell protein (CC16) was employed as a peripheral marker of the lung epithelium function. There was a strong inverse relationship between serum Al (Al-S) and CC16 concentrations (p = 0.006). The lowest CC16 concentrations were found in serum of workers characterised by subjective symptoms of the central nervous system (CNS) and abnormal results of neurophysiological examinations (EEG and VEP). Low serum CC16 concentrations and enhanced Al and iron (Fe) levels were also observed in the younger age group of workers with the subjective CNS symptoms and abnormal VEP results, which suggests that Fe is implicated in strengthening of the neurotoxic Al potential. The results of our study support the hypothesis that subclinical neurological symptoms (especially abnormal VEP) are most likely associated with internalisation of Al ions with lipid fractions of the lung epithelium, which in turn may help Al ions overcome the blood-brain barrier. Low serum CC16 concentrations (<10 microg L(-1)) were noted in workers with the abnormal results of neurological (CNS) and neurophysiological (EEG and VEP) examinations as well as with Al body burden manifested by urinary excretion (Al-U) below 60 microg L(-1) and Al-S concentration of 2 microg L(-1). This concentration may be considered as a threshold allowable biological concentration of aluminium.

Pneumotoxicity of dust from aluminum foundry and pure alumina: a comparative study of morphology and biomarkers in rats.

OBJECTIVES: The overall objective was to assess the role of aluminum dust and fumes in the aluminum foundry (Al-F) in generating local inflammation in the respiratory tract, which may lead to induction and elicitation of occupational asthma and fibrosis. To understand the underlying mechanisms of involving particles from foundry, a long-term study was performed on rats. MATERIALS AND METHODS: Pure alpha-alumina (Al-P) or (Al-F) was intratracheally instillated to rats in doses of 20 mg suspended in 0.5 ml of saline. After 3, 6 and 9 months since instillation, the following biomarkers were assessed in lung tissues: Clara cell protein (CC16), hyaluronic acid (HA), total protein, metaloproteinases (MMP) in bronchoalveolar lavage fluid (BALF), and GSH-S-transferase (GST). Morphological study of lungs and cells in BALF sediment was also performed. RESULTS: In the long-term study, Al-F dust induced marked changes in both epithelial cells and lung tissues, leading to important remodeling in collagen deposit and elastase fibres after 6 and 9 months. By contrast, the same dose of Al-P caused an increase in the number of polymorphonuclear leukocytes in the lung and fibrosis, but the latter was manifested by only slight signs. The lung BALF showed a decreasing level of Clara cell protein and a markedly increased expression of MMP-2 and MMP-9. These findings suggest that there is an upregulation of MMP and an increase in epithelial cell death and Clara cells proliferation, which may contribute to the respiratory symptoms through remodeling of airways and alveolar structures. CONCLUSIONS: In conclusion, it must be said that CC16 is the most sensitive biomarker. Decreasing levels of this biomarker in BALF was observed in an early phase (3 months PE) of our study with serum aluminum (Al-S) concentration not exceeding 30 microg/L(-1). Foundry dust causes marked irritation and inflammation in the rat lung. In occupational exposure it may therefore be active in the human lung, and thus contribute to the chronic obturative pulmonary disease (COPD).

Neurological and respiratory symptoms in shipyard welders exposed to manganese.

OBJECTIVE: The nervous system is the major target of the toxic effect of manganese (Mn) and its compounds in welding fumes. In humans, inhalation is the most frequent route of Mn access, therefore, the respiratory tract and lungs are usually involved in the process of translocation of inhaled noxius agent by blood to the brain. This study was performed to assess whether it is possible to use neurophysiological tests for the detection of early effects of exposure to low Mn concentrations. It is also known that irritating welding fumes affect distal bronchioles of nonciliated, epithelial Clara cells, which secret anti-inflammatory and immunossupresive Clara cell protein (CC16) into the respiratory tract. The examination of usefulness of CC16 as early pulmonary biomarker for neurophysiological abnormal results of welding fumes exposure was performed. MATERIALS AND METHODS: The study group comprised 59 welders employed at different workposts in a shipyard, matched for age and smoking habits with the control group composed of 23 mechanicians and electricians not exposed to welding fumes. Subjective neurological symptops (CNS), visual evoked potentials (VEP) and electroencephalography (EEG) were examined in welders and the relationships between Mn concentrations in the air, blood and urine as well as between cummulative exposure index (CEI) (Mn mg/m3 x years of exposure) were investigated. Effects of exposure were expressed in the form of biomarkers of the body burden, and CC16 as early pulmonary biomarker in welding exposure was examined by sensitive latex-immunoassay. RESULTS: Abnormal results of VEP and EEG and the lowest CC16 levels were found in the youngest welders exposed to welding fumes. Those changes were related to the highest Mn airborne levels (xg > 0.3 mg/m3) and high blood Mn concentrations (approximately 14.0 microg/dL). The highest values of correlation coefficients were found only in welders characterized by abnormal neurophysiological results, VEP (r = 0.83) and VEP and VEP+EEG (r = 0.82). The multiple linear regression analysis from all analyzed subgroups, indicated that those with only abnormal neurophysiological tests, VEP and EEG, showed the highest values of partial correlation. It also revealed partial correlation cofficiants between Mn in the air, CEI (Mn mg/m3 x years) and CC16, Mn-B and Mn-U in VEP and VEP+EEG groups. It was found that the highest partial correlations were between the magnitude of exposure--Mn mg/m3, CEI and Mn-B concentration (R2 = 0.72, R2 = 0.66) as well as between CC16 pulmonary biomarker effects and Mn-B concentration (R2 = 0.51). CONCLUSIONS: The subclinical effects revealed in neurological endpoints and abnormal results of neurophysiological tests, VEP and EEG, confirmed that those sensitive tests could be used for the detection of early effect of exposure to low manganese concentration. Inhibition of Clara cell protein secretion in younger welders not adapted to the Mn environment suppresses anti-inflammatory effect in the respiratory tract and probably enhances the absorption and thus the incidence of subclinical neurotoxic symptoms related to airborne Mn and Mn-B levels.

Scintigraphic assessment of renal function in steel plant workers occupationally exposed to lead.

OBJECTIVES: Occupational exposure to lead may produce kidney damage, but existing data on the dose range associated with nephrotoxicity are inconclusive. We here assessed renal function under conditions of low to moderate lead exposure using renal scintigraphy. METHODS: Fifty-three male foundrymen (exposed group) and fourty male office workers (control group) from a steel plant were included in the study. Glomerular and tubular renal function were assessed by means of (99m)Tc-DTPA and (99m)Tc-EC clearance, respectively. Urinary markers of glomerular dysfunction (albumin) and tubular damage (α1-microglobulin (α1M), ß2-microglobulin (ß2M), retinol-binding protein (RBP), N-acetyl-ß-glucosaminidase (NAG) activity) were determined using latex beads tests or colorimetry. The lead concentration in blood was measured with atomic absorption spectrometry. RESULTS: The blood lead concentrations were 145.8 (121.3-175.3) and 39.3 (35.1-44.1) µg/l (geometric mean, 95(th) CI, p<0.001) in the exposed and control groups, respectively. Subjects exposed to lead presented with increased (99m)Tc-DTPA clearance (158.3 (148.4-168.8) vs. 135.9 (127.9-144.4) ml/min; p<0.01) and urinary albumin excretion (7.61 (6.28-9.22) vs. 4.78 (4.05-5.65) mg/g creatinine; p<0.001). (99m)Tc-EC clearance and excretion of α1M, ß2M, RBP and NAG were not significantly different between the groups. Significant correlations between (99m)Tc-DTPA clearance and blood lead concentrations (r=0.45; p<0.01) and between urinary albumin excretion and blood lead concentrations (r=0.71; p<0.001) were noted. CONCLUSIONS: Use of renal scintigraphy in present study revealed measurable alterations of renal function under the conditions of low-level lead exposure and suggest that increased glomerular filtration may be an early indicator of kidney damage in subjects occupationally exposed to lead.

Integrated indexes of occupational exposure as predictors of kidney dysfunction.

The aim of the study was to evaluate the dose-effect and dose-response relationships between the integrated indexes Cd-A x t (mg/m3 x years of exposure) and Cd-B x t (microg/l x years of exposure), and the increase in retinol binding protein excretion in urine (RBP-U) and beta2-microglobulin concentration in serum (beta2M-S). The study was carried out in the nickel-cadmium battery factory in 1998-1999. Exposure to cadmium was formerly very high. The study group consisted of 116 persons for whom the results of determinations of Cd-B were available during two former observation periods (1983 and 1986-1988). The mean age of the group was 49 years and the mean period of exposure was 17 years. The dose-effect relationship between Cd-B x t and RBP-U or beta2M-S was much better (r = 0.642 and 0.513) than between Cd-A x t and RBP-U or beta2M-S (r = 0.173 and 0.127). There was also correlation between Cd-U (microg/g creatinine), measured in 1998-1999, and RBP-U or beta2M-S (r = 0.343 and 0.198). Urinary cadmium should, however, be used with caution as a dose estimate because its excretion may increase as a result of renal damage. According to the dose-response relationship, an increase in RBP excretion above 300 microg/g creatinine can be expected in 10% of subjects at the integrated exposure index (Cd-B x t) of about 450 microg/l x years, and an increase in beta2M-S above the accepted cut-off point of 2.4 mg/l can be expected in 10 % of subjects at Cd-B x t of about 190 microg/l x years. The data obtained confirmed the validity of the recommended at present health-based limit for occupational exposure of 5 microg/l of blood, as well as the superiority of the biological monitoring of exposure to cadmium over the environmental monitoring.

Neurological and neurophysiological examinations of workers exposed to arsenic levels exceeding hygiene standards.

OBJECTIVES: The assessment of the neurotoxic effect of arsenic (As) and its inorganic compounds is still the subject of interest due to a growing As application in a large array of technologies and the need to constantly verify the principles of prevention and technological parameters. The aim of this study was to determine the status of the nervous system (NS) in workers exposed to As at concentrations exceeding hygiene standards (Threshold Limit Values (TLV) - 10 µg/m(3), Biological Exposure Index (BEI) - 35 µg/l) and to analyze the relationship between the NS functional state, species of As in urine and As levels in the workplace air. MATERIAL AND METHODS: The study group comprised 21 men (mean age: 47.43±7.59) employed in a copper smelting factory (mean duration of employment: 22.29±11.09). The control group comprised 16 men, matched by age and work shifts. Arsenic levels in the workplace air (As-A) ranged from 0.7 to 92.3 µg/m(3); (M = 25.18±28.83). The concentration of total arsenic in urine (As(tot)-U) ranged from 17.35 to 434.68 µg/l (M = 86.82±86.6). RESULTS: Syndrome of peripheral nervous system (PNS) was manifested by extremity fatigue (28.6%), extremity pain (33.3%) and paresthesia in the lower extremities (33.3%), as well as by neuropathy-type mini-symptoms (23.8%). Electroneurographic (ENeG) tests of peroneal nerves showed significantly decreased response amplitude with normal values of motor conduction velocity (MCV). Stimulation of sural nerves revealed a significantly slowed sensory conduction velocity (SCV) and decreased sensory potential amplitude. Neurophysiological parameters and the results of biological and environmental monitoring showed a relationship between As(tot), As(III) (trivalent arsenic), the sum of iAs (As(III)+As(V) (pentavalent arsenic))+MMA (monomethylarsonic acid) concentration in urine and As levels in the air. CONCLUSIONS: The results of the study demonstrate that occupational exposure to inorganic arsenic levels exceeding hygiene standards (TLV, BEI) generates disorders typical of peripheral neuropathy.

Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride.

BACKGROUND: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. MATERIALS AND METHODS: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m(3) for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m3 for 6 h. RESULTS: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. CONCLUSION: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs.

Application of cellular biosensors for analysis of bioactivity associated with airborne particulate matter.

Exposure to airborne particulate matter (PM) is a known risk factor for adverse health effects observed in many environmental and occupational settings. The pathological mechanisms involved in PM-mediated toxicity depend on the size and contents of particles that vary depending on the source of emission. Chemical compositions of PM show multiple components with different bioavailabilities that are capable of acting on multiple molecular and cellular targets, making it difficult to predict PM-associated toxicity based solely on chemical analysis. The aim of the study was to develop robust, sensitive and economical assays for environmental pollutants based on genetically modified mammalian cells. We tested the suitability of two biosensor assays, Fluorescent Cell Chip and Oxibios, developed in part in our laboratories, for assessment of the potential toxicity of airborne PM. Reference PM and PM obtained by sampling of diesel exhaust and indoor air in aluminum and copper facilities in Poland were tested with the two bioassays using unified experimental protocols. Resultant data showed complex patterns of stimulatory and inhibitory activities that were consistent with the origin of PM and might be correlated with their chemical composition. The analysis was informative with regard to type and extent of possible toxicity associated with specific PM and allowed for detection of significant differences between PM from different industrial sites and particular locations within the same industrial sites as well as overall ranking of toxicity risk based on chemical analysis.