Advice to the European Commission as Regards Type and Criteria for Comprehensive Studies to Be Requested From Manufacturers: The Opinion of the Scientific Committee on Health, Environmental, and Emerging Risks (SCHEER).

The European Commission has established a priority list of 15 additives contained in cigarettes and roll-your-own tobacco subject to enhanced reporting obligations. The European Union (EU) Tobacco Products Directive (TPD) prescribes that Member States shall require manufacturers and importers of tobacco products to carry out comprehensive studies on these additives to assess their contribution to any of the properties listed in Article 6 of the TPD: toxicity or addictiveness, characterizing flavor, inhalation facilitation, nicotine uptake, and carcinogenic, mutagenic, or toxic for reproduction. The Scientific Committee on Health, Environmental, and Emerging Risks (SCHEER) has provided guidance on the type and criteria for comprehensive studies, and on the most suitable methodologies to test these 15 tobacco additives as well as additives on future updated lists. The SCHEER proposes a stepwise strategy as the most pragmatic and efficient way to assess the effects of tobacco additives. In addition to proposing specific steps and tests to be considered by industry, some general criteria were also identified such as no comparative testing (testing cigarettes with and without the additive) and no animal studies. As tobacco additives have no benefits for health, but rather may promote use of and addiction to an extremely toxic product, a risk-benefit analysis is not the appropriate paradigm for assessing the additive. When comprehensive studies confirm that additives have any of the properties listed in Article 6 of the TPD, regulatory actions should be considered. If uncertainties cannot be solved by comprehensive studies, the SCHEER recommends that the assessors consider the worst-case evaluation. IMPLICATIONS: In this article, the SCHEER proposes a stepwise strategy to assess (1) the toxic and addictive effects, (2) the characterizing flavor, and (3) facilitating inhalation properties of tobacco additives. The proposed steps and tests provide guidance to (1) Member State on which comprehensive studies should be requested and (2) tobacco industry on which strategy of testing should be applied to address the request and to prepare reports to be sent to the relevant authorities for the evaluation of tobacco additives "safety" to comply with the Tobacco Products Directive 2014/40/EU.

[Analysis of tasks of occupational health services accomplished in Poland, 1997-2014. Do we exploit the full potential of prophylactic examinations of workers?] / Analiza zadan sluzby medycyny pracy realizowanych w Polsce w latach 1997­2014. Czy w pelni wykorzystujemy potencjal badan profilaktycznych?

BACKGROUND: Mandatory medical reports can be used to evaluate the scope of activity of occupational health services (OHS), including the number and kind of services. MATERIAL AND METHODS: The analysis comprised data for the period 1997-2014, derived from mandatory reports MZ-35A submitted by OHS units. RESULTS: During the analyzed period the number of occupational medicine physicians decreased from 8507 to 6741, while the number of OHS units - responsible for prophylactic care - increased from 4967 to 6261. In the years under report 3,961 million mandatory health check-ups were performed, of which 99.3% resulted in issuing fitness for work certificates. Pre-employment examinations made 38.8%, while periodical ones - 52.8% and control ones - 6.7% of all check-ups. Moreover, 336 700 examinations of apprentices, students, vocational courses attendants and Ph.D. students were performed to evaluate any contradictions for vocational training. In 2014, there were 1871 workers provided with preventive care per 1 occupational physician. It was estimated that despite legal obligation, only 22.2% of employers had signed agreements with OHS units. CONCLUSIONS: The analysis of the number and kind of services provided by OHS units revealed high but not fully exploited potential for efficient prophylaxis of both directly occupational work-related and indirectly work-exacerbated diseases. Med Pr 2017;68(1):105-119.

[Challenges to occupational medicine in view of the problem of work-related diseases and the aging of workforce. Directions for further development and intentional changes in preventive care of employees in Poland]. / Wyzwania medycyny pracy wobec problemu chorób zwiazanych z praca oraz starzenia sie populacji osób pracujacych. Dalszy kierunek rozwoju i celowe zmiany w opiece profilaktycznej nad pracujacymi w Polsce.

The system of occupational health care in Poland, based on occupational medicine service, takes care of almost 12.5 million employees subjected to over 4.5 million obligatory periodic medical check ups. This form of providing prophylactic care comes down to examinations dictated by legal regulations, whose scope is not oriented towards a comprehensive workers' health assessment, but to the examination of the systems and organs critical to work-related dangers. Simultaneously, epidemiological data indicate a large number of chronic diseases, which may influence the professional activity, like hypertension or diabetes and a high percentage of patients not aware of their illness. Since patients participating in obligatory examinations usually feel healthy and do not use health care services on a daily basis, an occupational medicine physician has a unique opportunity to detect health disorders at an early stage, which can prevent the development of health complications affecting the condition of the patient, limiting their professional activity, but also causing additional costs of the health care system. The authors have proven the need to involve occupational medicine services in the prevention of chronic diseases and the need to introduce additional sources of financing for procedures enabling early detection of diseases the patient may not be aware of or control of the effectiveness of already diagnosed illnesses. They addressed the need to change the current legal form of establishing and announcing the range of examinations and directives for certifying the lack or presence of health contraindications to work to the specified and updated standards prepared by scientific research institutes and occupational medicine societies. Med Pr 2016;67(5):691-700.

Rad51C: a novel suppressor gene modulates the risk of head and neck cancer.

We conducted a case-control study to investigate the possible association between the head and neck cancer (HNC) and genetic variability of Rad51C tumor suppressor gene. Eight polymorphic sites spanning over non-coding regions of Rad51C promoter, exon 1 and intron 1 were genotyped in 81 HNC cases and 156 healthy controls using the real-time PCR technique. One investigated site turned out to be not polymorphic, while among the remaining seven sites a significant HNC risk-increasing effect was found for rs16943176 (c.-118G>A), rs12946397 (c.-26C>T) and rs17222691 (c.145+947C>T) on both allelic (OR=1.8; p<0.05) and genotypic (OR=2.0; p<0.05) level. Furthermore, our data seem to provide marginal evidence, that this effect might possibly be confined to women only (OR=2.8; p=0.05 for allelic and OR=3.7; p=0.05 for genotypic comparisons). These SNPs were found to co-segregate together forming two distinct, HNC risk-modulating haplotypes. The genetic variability of Rad51C might thus be of relevance with respect to HNC risk.

Exposure to polycyclic aromatic hydrocarbons in women from Poland, Serbia and Italy--relation between PAH metabolite excretion, DNA damage, diet and genotype (the EU DIEPHY project).

Exposure of the general population to polycyclic aromatic hydrocarbons (PAH) is ubiquitous. The aim of this study was to analyze biomarkers associated with the uptake of PAH in 428 non-smoking women from Lodz (Poland), Viterbo (Italy), Belgrade (Serbia) and from the Pancevo area, where the petrochemical complex was destroyed by the air raids in 1999. Urinary excretion of PAH metabolites was lowest in Italian women, intermediary for Serbian and highest in Polish women, who predominantly excreted hydroxy phenanthrenes as metabolites of phenanthrene. Bulky DNA adduct levels were highest in Italian and Polish women. Genotype or PAH ambient air levels could not explain the dissimilarities between the study groups with respect to biomarker patterns, which probably reflected differences in life style-associated factors.

Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles.

The potential toxic effects in murine (3T3-L1) and human (WI-38) fibroblast cell lines of commercially available silica nanoparticles (NPs), Ludox CL (nominal size 21 nm) and CL-X (nominal size of 30 nm) were investigated with particular attention to the effect over long exposure times (the tests were run after 72 h exposure up to 7 days). These two formulations differed in physico-chemical properties and showed different stabilities in the cell culture medium used for the experiments. Ludox CL silica NPs were found to be cytotoxic only at the higher concentrations to the WI-38 cells (WST-1 and LDH assays) but not to the 3T3-L1 cells, whereas the Ludox CL-X silica NPs, which were less stable over the 72 h exposure, were cytotoxic to both cell lines in both assays. In the clonogenic assay both silica NPs induced a concentration dependent decrease in the surviving fraction of 3T3-L1 cells, with the Ludox CL-X silica NPs being more cytotoxic. Cell cycle analysis showed a trend indicating alterations in both cell lines at different phases with both silica NPs tested. Buthionine sulfoximine (γ-glutamylcysteine synthetase inhibitor) combined with Ludox CL-X was found to induce a strong decrease in 3T3-L1 cell viability which was not observed for the WI-38 cell line. This study clearly indicates that longer exposure studies may give important insights on the impact of nanomaterials on cells. However, and especially when investigating nanoparticle effects after such long exposure, it is fundamental to include a detailed physico-chemical characterization of the nanoparticles and their dispersions over the time scale of the experiment, in order to be able to interpret eventual impacts on cells.

Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N(2)O).

OBJECTIVES: Occupational exposure to nitrous oxide (N(2)O) and/or halogenated hydrocarbons has been suggested to induce damage of genetic material, but the underlying mechanisms remain obscure. This study investigated the role of oxidative processes in the genotoxicity associated with exposure to waste anaesthetic gases. METHODS: The study was performed in 36 female nurses and in 36 unexposed female health care workers matched for age and employment duration. Genotoxic effects were examined by Comet test modification employing formamidopyrimidine glycosylase (FPG) that allows assessment of oxidative DNA damage. Reactive oxygen species (ROS) in leukocytes were investigated by fluorescence spectroscopy with 2',7'-dichlorofluorescin diacetate. Oxidative stress markers including 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), thiobarbituric acid-reacive substances (TBARS), α-tocopherol, and glutathione peroxidise (GPX) activity were measured immuno- or colorimetrically. N(2)O, sevoflurane and isoflurane were monitored by gas chromatography and mass spectrometry. RESULTS: The study documents for the first time the positive correlation between the oxidative DNA damage and the N(2)O levels in the ambient air. By contrast, no association was observed between genotoxic effects and sevoflurane or isoflurane. In addition, ROS generation and plasma and urine concentrations of TBARS and 8-iso-PGF(2α), respectively, were elevated, while GPX activity was reduced in nurses exposed to waste anaesthetic gases. Path analysis pointed to a causal relationship between N(2)O exposure, oxidative stress and DNA damage. CONCLUSION: Occupational exposure to N(2)O is associated with increased oxidative DNA damage and the level of exposure plays a critical role in this regard. Increased oxidative stress may represent a mechanistic link between chronic N(2)O exposure and genotoxicity.

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.

[Conditionings of population exposure to electromagnetic fields associated with the rational use of 5G radiocommunication networks in Poland]. / Uwarunkowania ekspozycji ludnosci na pole elektromagnetyczne zwiazane z uzytkowaniem radiokomunikacyjnych sieci w technologii 5G w Polsce.

In 2017, preparations were made in Poland to provide all citizens with access to the Internet at a speed of at least 30 Mb/s, and at a speed of at least 100 Mb/s for 50% of households. This goal is to be realized, among others, by means of the fifth generation (5G) radio-communication networks. This work presents the assumptions of the 5G network structure and estimates of the level of population exposure toelectromagnetic fields related to their rational use. It was also analyzed whether, from the technical point of view, 5G networks could be implemented while respecting the currently acceptable level of electromagnetic field intensity in Poland (7 V/m), taking into account the current environmental exposure caused by antennas of cellular base stations. This is a contribution to the ongoing discussion on the need to change the requirements in Poland in order to limit the level of population exposure to electromagnetic fields. Based on the available documentation of the proposed technical standards, the theoretical analysis of environmental exposure to the electromagnetic field emitted by 5G systems shows that, with rational power management, obtaining the expected (compatible with 5G standards) quality of connections via base stations installed outside of buildings and using intelligent antenna systems with controlled beams, it will be possible to maintain the electric field strength and power density below the current limit values in places accessible to the public (<7 V/m, <0.1 W/m2). Med Pr. 2020;71(2):245-53.

[Protection of the population health from electromagnetic hazards - challenges resulting from the implementation of the 5G network planned in Poland]. / Ochrona zdrowia ludnosci przed zagrozeniami elektromagnetycznymi − wyzwania wynikajace z planowanego w Polsce wdrozenia systemu radiokomunikacji standardu 5G.

There is an ongoing discussion about electromagnetic hazards in the context of the new wireless communication technology - the fifth generation (5G) standard. Concerns about safety and health hazards resulting from the influence of the electromagnetic field (EMF) emitted by the designed 5G antennas have been raised. In Poland, the level of the population's exposure to EMF is limited to 7 V/m for frequencies above 300 MHz. This limitation results from taking into account the protective measures related not only to direct thermal hazards, but also to diversified indirect and long-term threats. Many countries have not established legal requirements in this frequency range, or they have introduced regulations based on recommendations regarding protection against direct thermal risks only (Council Recommendation 1999/519/EC). For such protection, the permissible levels of electric field intensity are 20-60 V/m (depending on the frequency). This work has been created through an interdisciplinary collaboration of engineers, biologists and doctors, who have been for many years professionally dealing with the protection of the biosphere against the negative effects of EMF. It presents the state of knowledge on the biological and health effects of the EMF emitted by mobile phone devices (including millimeter waves which are planned to be used in the 5G network). A comparison of the EU recommendations and the provisions on public protection being in force in Poland was made against this background. The results of research conducted to date on the biological effects of the EMF radiofrequency emitted by mobile telecommunication devices, operating with the frequencies up to 6 GHz, do not allow drawing any firm conclusions; however, the research evidence is strong enough for the World Health Organization to classify EMF as an environmental factor potentially carcinogenic to humans. At the moment, there is a shortage of adequate scientific data to assess the health effects of exposure to electromagnetic millimeter waves, which are planned to be used in the designed 5G devices. Nevertheless, due to the fact that there are data indicating the existence of biophysical mechanisms of the EMF influence that may lead to adverse health effects, it seems necessary to use the precautionary principle and the ALARA principle when creating environmental requirements for the construction and exploitation of the infrastructure of the planned 5G system. Med Pr. 2020;71(1):105-13.

DNA damage induced by nitrous oxide: study in medical personnel of operating rooms.

Occupational exposure to anaesthetics such as nitrous oxide (N(2)O) and halogenated hydrocarbons has been suggested to increase risk of genetic damage. However, the dose-dependency of genotoxic effects has not been unequivocally established and their relation to occupational exposure limit (OEL) remain obscure. In this study, the genotoxicity associated with occupational exposure to anaesthetics has been investigated in a group of 55 female nurses and 29 male anaesthesiologists active for at least 5 years in a working environment containing variable concentrations of N(2)O and halogenated hydrocarbons. 83 unexposed health care workers (52 female nurses and 31 male doctors) matched for age, gender, smoking habit and employment duration were included in the control group. Genotoxicity has been assessed using comet test. Concentrations of nitrous oxide, sevoflurane and isoflurane monitored by gas chromatography and mass spectrometry made possible to relate the extent of DNA damage to the level of exposure. Our results for the first time document a positive correlation between the DNA damage and the N(2)O levels in the ambient air. By contrast, no correlation has been observed between genotoxic effects and concentrations of sevoflurane and isoflurane. The extent of genetic injury was especially aggravated among nurses and anaesthesiologists exposed to N(2)O in concentrations exceeding OEL (180 mg/m(3)). We conclude that occupational exposure to N(2)O is associated with increased DNA damage and that the level of exposure plays a critical role in this regard.

Carcinogenic effect of arsenate in C57BL/6J/Han mice and its modulation by different dietary selenium status.

In this study, carcinogenic effects of arsenate in female C57BL/6J/Han mice exposed in drinking water to 50, 200 or 500microgAs/L for 24 months were investigated. All animals were fed low-selenium diet, however half of them were supplemented with sodium selenite in drinking water (200microgSe/L) to ensure the normal dietary level of selenium. Glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma after 3, 6, 12 and 18 months in satellite groups showed considerable decrease in animals from non-selenium supplemented groups in comparison to supplemented groups. A clear arsenic concentration-dependent increase in the number of malignant lymphoma associated with increase in the risk of death was observed (hazard ratio=0.91, 1.46, and 2.24, for 50, 200 and 500microgAs/L, respectively). No significant influence of selenium dietary status on arsenic carcinogenicity was shown. A significant association between selenium supplementation status and increased risk of death of the animals from causes other than malignant tumors was found (HR=1.79, p=0.04).

Genotoxic effects in C57Bl/6J mice chronically exposed to arsenate in drinking water and modulation of the effects by low-selenium diet.

In C57Bl/6J mice chronically exposed to arsenate in drinking water at 50, 200, or 500 microg As/L, genotoxic effects in bone-marrow cells using micronucleus test and in peripheral blood leukocytes using the comet assay were determined after 3, 6 or 12 mo. To assess the modulating role of selenium in development of the effects, the animals were fed a specially prepared low-selenium diet and were supplemented with sodium selenite (200 microg Se/L) in drinking water (supplemented groups) or were without Se supplementation (nonsupplemented groups). Measurements of glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma were performed after 3, 6, and 12 mo and showed a marked decrease in values in animals in non-Se supplemented compared to Se-supplemented groups. After 3 mo of arsenic exposure in the Se-supplemented animals the level of DNA fragmentation (without Endo III and Fpg enzymes) did not differ from the control; however, increased oxidative damage of purine and pyrimidine bases was observed. In groups not supplemented with Se, an increase of DNA fragmentation was observed; however, the levels of oxidative DNA damage in these groups did not differ from the control. None of the positive effects observed in the comet assay after 3 mo was related to arsenate concentration. The levels of DNA damage after 6 and 12 mo of exposure to arsenic as well as the frequency of micronuclei after 3, 6, and 12 mo did not differ significantly between exposed and control animals, irrespective of Se supplementation status.

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.

DNA damage in leukocytes of workers occupationally exposed to arsenic in copper smelters.

Inorganic arsenic (i-As) is a known human carcinogen; however, humans continue to be exposed to i-As in drinking water and in certain occupational settings. In this study, we used the Comet assay to evaluate DNA damage in the somatic cells of workers from three Polish copper smelters who were occupationally exposed to i-As. Blood samples were collected from 72 male workers and 83 unexposed male controls and used for the detection of DNA damage, oxidative DNA damage, and DNA damage after a 3-hr incubation in culture. Urine samples were collected to assess the level of exposure. The mean concentration of arsenic metabolites in urine [the sum of arsenite (AsIII), arsenate (AsV), monomethylarsenate (MMA) and dimethylarsenate (DMA)] and the concentrations of DMA (the main metabolite in urine) were higher in workers than in controls, but the differences were not statistically significant. By contrast, the level of DNA damage, expressed as the median tail moment, was significantly higher in the leukocytes of workers than in the controls. Comet assays conducted with formamidopyrimidine glycosylase (FPG) digestion to detect oxidative DNA damage indicated that oxidative lesions were present in leukocytes from both the exposed and control groups, but the levels of damage were significantly higher among the workers. Incubation of the cells in culture resulted in a significant reduction in the levels of DNA damage, especially among leukocytes from the workers, suggesting that the DNA damage was subject to repair. Our findings indicate that copper smelter workers have increased levels of DNA damage in somatic cells, suggesting a potential health risk for the workers. Although i-As was present in air samples from the smelters and in urine samples from workers, no clear association could be made between i-As exposure and the DNA damage.

Development of the "Cell Chip": a new in vitro alternative technique for immunotoxicity testing.

Predictive testing of immunotoxicity associated with chemical compounds is complicated and cannot be accomplished with a single test. As most of the existing tests for immunotoxicity employ experimental animals, there is an increasing need for alternative tests in vitro. We have developed a new system for in vitro immunotoxicity testing, which employs changes in cytokine expression observed in vitro as an endpoint indicating potential for perturbation of the immune system in vivo. This system named "fluorescent cell chip" (FCC) is based on a number of genetically modified cell lines that regulate the expression of a transgene coding for fluorescent protein enhanced green fluorescent protein (EGFP) in a similar way as they regulate expression of IL-1beta, IL-2, IL-4, IFN-gamma, IL-10, TNF-alpha, and beta-actin. Morphological and functional features of selected cell lines expressing EGFP under the control of cytokine promotors were compared with maternal cell lines and this comparison showed that critical functional features of the maternal cell lines were preserved in EGFP expressing cells. Two chemicals with known immunotoxic activities, cyclosporine A and potassium tetrachloro-platinate(II), mediated compound-specific pattern of inhibition and activation of reporter gene expression. Thus, the "fluorescent cell chip" has demonstrated potential for application as a predictive screening test for immunomodulatory activities of chemicals. The major advantage of this approach is the possibility to apply this test in high throughput screening of high number of compounds for their well defined biological activity.

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.