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.

[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.

[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.

Bladder cancer documentation of causes: multilingual questionnaire, 'bladder cancer doc'.

There is a considerable discrepancy between the number of identified occupational-related bladder cancer cases and the estimated numbers particularly in emerging nations or less developed countries where suitable approaches are less or even not known. Thus, within a project of the World Health Organisation Collaborating Centres in Occupational Health, a questionnaire of the Dortmund group, applied in different studies, was translated into more than 30 languages (Afrikaans, Arabic, Bengali, Chinese, Czech, Dutch, English, Finnish, French, Georgian, German, Greek, Hindi, Hungarian, Indonesian, Italian, Japanese, Kannada, Kazakh, Kirghiz, Korean, Latvian, Malay, Persian (Farsi), Polish, Portuguese, Portuguese/Brazilian, Romanian, Russian, Serbo-Croatian, Slovak, Spanish, Spanish/Mexican, Tamil, Telugu, Thai, Turkish, Urdu, Vietnamese). The bipartite questionnaire asks for relevant medical information in the physician's part and for the occupational history since leaving school in the patient's part. Furthermore, this questionnaire is asking for intensity and frequency of certain occupational and non-occupational risk factors. The literature regarding occupations like painter, hairdresser or miner and exposures like carcinogenic aromatic amines, azo dyes, or combustion products is highlighted. The questionnaire is available on www.ifado.de/BladderCancerDoc.

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.

Assessment of the protective effects of selected dietary anticarcinogens against DNA damage and cytogenetic effects induced by benzo[a]pyrene in C57BL/6J mice.

The protective action in C57BL/6J mice from orally administered ellagic acid (EA), benzyl isothiocyanate (BITC), an extract of epigallocatechins (Tegreen®) as well as chlorophyllin (CHL) against benzo[a]pyrene (B[a]P)-induced DNA damage and cytogenetic effects was investigated. In pilot experiment the comet assay indicated protective effects for all compounds, while such activity was confined to EA and CH with respect to B[a]P-DNA adducts and micronuclei. EA and CH were chosen for the main study where the levels of DNA adducts in liver after injection of 30 mg B[a]P/kg b.w. did not differ from those found for animals exposed to B[a]P and treated with the protective substances. In leukocytes no significant protective effect of CHL was detected while a 2-fold increase of adduct concentrations was observed after co-administration of EA. In the comet assay CHL or EA caused a 3-fold decrease of SSB, and a 2-fold decrease of FPG sites in comparison to animals treated with B[a]P. CHL or EA showed a significant protective effect against B[a]P-induced MN in polychromatic erythrocytes in bone marrow. In contrast, flow cytometry measurements in peripheral blood indicated the MN frequency after treatment with CHL or EA almost twice as high as that recorded for B[a]P alone.

Fate and effects of CeO2 nanoparticles in aquatic ecotoxicity tests.

Cerium dioxide nanoparticles (CeO2 NPs) are increasingly being used as a catalyst in the automotive industry. Consequently, increasing amounts of CeO2 NPs are expected to enter the environment where their fate in and potential impacts are unknown. In this paper we describe the fate and effects of CeO2 NPs of three different sizes (14, 20, and 29 nm) in aquatic toxicity tests. In each standard test medium (pH 7.4) the CeO2 nanoparticles aggregated (mean aggregate size approximately 400 nm). Four test organisms covering three different trophic levels were investigated, i.e., the unicellular green alga Pseudokirchneriella subcapitata, two crustaceans: Daphnia magna and Thamnocephalus platyurus, and embryos of Danio rerio. No acute toxicity was observed for the two crustaceans and D. rerio embryos, up to test concentrations of 1000, 5000, and 200 mg/L, respectively. In contrast, significant chronic toxicity to P. subcapitata with 10% effect concentrations (EC10s) between 2.6 and 5.4 mg/L was observed. Food shortage resulted in chronic toxicity to D. magna, for wich EC10s of > or = 8.8 and < or = 20.0 mg/L were established. Chronic toxicity was found to increase with decreasing nominal particle diameter and the difference in toxicity could be explained by the difference in surface area. Using the data set, PNEC(aquatic)S > or = 0.052 and < or = 0.108 mg/L were derived. Further experiments were performed to explain the observed toxicity to the most sensitive organism, i.e., P. subcapitata. Toxicity could not be related to a direct effect of dissolved Ce or CeO2 NP uptake or adsorption, nor to an indirect effect of nutrient depletion (by sorption to NPs) or physical light restriction (through shading by the NPs). However, observed clustering of NPs around algal cells may locally cause a direct or indirect effect.

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).

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.

Reproducible comet assay of amorphous silica nanoparticles detects no genotoxicity.

Genotoxicity of commercial colloidal and laboratory-synthesized silica nanoparticles was tested using the single cell gel electrophoresis or Comet assay. By using a carefully developed protocol and careful characterization of the nanoparticle dispersions, Comet assays were performed on 3T3-L1 fibroblasts with 3, 6, and 24 h incubations and 4 or 40 microg/ml of silica nanoparticles. No significant genotoxicity was observed for the nanoparticles tested under the conditions described, and results were independently validated in two separate laboratories, showing that in vitro toxicity testing can be quantitatively reproducible.

Early neurotoxic effects of inhalation exposure to aluminum and/or manganese assessed by serum levels of phospholipid-binding Clara cells protein.

Little is known on the disturbances of lung epithelium function in aluminum casting smelters and shipyard welders exposed by inhalation to irritant occupational pollutants, dust and fumes. The exact mechanism of aluminum and manganese toxicity is not known, but it is thought that they may potentiate oxidative and inflammatory stress, leading to impaired neurological function. The aim of the study was to investigate the subclinical effects of aluminum and manganese exposure on the nervous system and to assess their relationship to the biomarkers of exposure and effect in workers exposed to neurotoxic fumes. The relationship between the neurological and respiratory effects was investigated in 50 workers at aluminum casting smelters exposed to x(GM) = 0.29 Al(2)O(3) mg m(-3), and 59 shipyard welders exposed to x(GM) = 0.16 Mn mg m(-3), and the reference group. Serum anti-inflammatory, phospholipid-binding Clara cell protein (CC16) as a peripheral marker of the bronchiolar epithelium function measured. The lowest CC16 concentrations were found in workers showing subjective CNS symptoms and abnormal neurophysiological findings: EEG and visual evoked potentials. A strong inverse relationship was found between serum Al (Al-S) and CC16 concentrations (p = 0.006). Younger smelter workers and welders, with a shorter exposure duration, presented a higher number of VEPs than the workers employed for a longer period of time. The sub-clinical neurological symptoms (VEP) and low CC16 level can be associated with an internalization of Al ions with lipid fractions of the lung epithelium, which in turn may help Al ions overcome the blood-brain barrier. The inhibited secretion of anti-inflammatory Clara cell protein and low respiratory performance in younger Mn welders was found to enhance subclinical neurotoxic symptoms, especially VEPs, related to exposure to airborne Mn and Mn-B.