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Official websites use. Share sensitive information only on official, secure websites. This article was submitted to Environmental Health, a section of the journal Frontiers in Public Health. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Ida-Viru County, in Eastern Estonia, features industrially contaminated sites—where oil shale has been mined and used for electricity generation, and shale oil extraction. Higher prevalence of respiratory and cardiovascular disease has been found in the region due to high quantities of air pollution. Altogether, three studies have been conducted among residents: first, among adults in the 's; second, among children in the 's; and third, among employees, with a focus on workers and miners in the oil shale chemistry industry in the late 's and 's. In some of those studies, increased levels of biomarkers in blood and urine heavy metals, 1-OHP have appeared; nevertheless, in last 20 years, there has been no population-wide HBM in Estonia. According to air pollution monitoring and emission analysis, the pollutants of concern are benzene, PM 10 , PM 2. In general, there is a decreasing trend in air pollutant levels, with the exception of a slight increase in One of the aims of HBM is to be analyzed if this trend can be identified in HBM, using similar biomarkers as applied earlier. The future perspective HBM could be divided into two Tiers. In Estonia, mining, and use of mineral resource oil shale for generating electricity generation and producing shale oil, is concentrated in Ida-Viru County— a large-scale industrial area in Eastern-Estonia. Oil shale is a fine-grained sedimentary rock containing organic matter, in the form of kerogen, which yields substantial amounts of oil and combustible gas. Oil shale industry activities have led to various environmental problems in the region, the most important of which is ambient air pollution. Ambient air quality affects health, as toxic substances entering the respiratory tract can also reach other organs through the bloodstream, and cause various health problems and diseases 3. Health effects, related to the oil shale sector, have been studied in Estonia; studies suggest poorer health indicators, including increased respiratory and cardiovascular disease prevalence and a decrease in life expectancy 4. In addition, children living in the area have a higher risk of developing asthma 5 , 6. Also a recent study has found the lung cancer age-standardized incidence rate being higher in Ida-Viru County compared to Estonia overall 7. One of the weaknesses in epidemiological studies has been poor exposure data, as discussed by Orru et al. We believe the implementation of human biomonitoring HBM , would help to specify data on exposures in the population and advantage to refine the results. HBM is a methodology for assessing human exposure to natural and man-made compounds from living or working environments. Typically, specific substances or their degradation products, called metabolites, are measured in blood, urine, breast milk, and other body fluids or human tissues. The most commonly used and preferred biological matrix for HBM is blood, as it is in contact with organs and tissues where many chemicals are deposited 8 , 9. However, there is a growing interest in non-invasive biomarkers, e. Accordingly, previous studies of the health effects of the oil shale sector have used fractional exhaled nitric oxide FeNO , which is a biomarker of airway inflammation 5 , 6. Compared to environmental monitoring, HBM has several advantages. For example, biological samples can characterize repeated exposure and the interaction of different exposures. HBM directly describes contaminants that have entered the body from all routes of exposure—inhalation, dermal absorption, and ingestion— and reflects individual differences due to different exposure levels, metabolism, and excretion rates. HBM data also refers to human physiological variations such as bioavailability, bioaccumulation, and persistence, which may increase the levels of some environmental chemicals e. Nevertheless, different matrixes blood, urine, hair, breast milk, etc. If chemical substances, or their metabolites, are released rapidly from the human organism, repeated sampling at the individual level— to indicate a long-term exposure pattern— is needed The generally accepted classification of biomarkers divides them into two main categories: 1 exposure biomarkers and 2 effect biomarkers. Exposure biomarkers detect and measure chemical residues, or metabolites, in tissues or body fluids. It has been found that the advantage of utilizing exposure biomarkers is the so-called integrated measurement exposure, which is especially important in the case of substances with large differences in absorption depending on the time and location of exposure 9. An important group of effect biomarkers is genotoxicity biomarkers in workers or, to a lesser extent, in the population exposed to mutagens or genotoxic carcinogens. Many tests are used for the detection of DNA damage, such as micronucleus counting, Comet Assays single cell gel electrophoresis , chromosomal aberrations, DNA adducts, etc However, effect biomarkers have been found to be effective only when people exposed to high levels of contaminants e. Toxicological studies have shown that individuals' responses to chemical exposure can often vary significantly Ladeira and Viegas 14 consider that such differences between individuals may be genetically mediated or caused by some environmental stressor, disease process, or other epigenetic factor. Thus, effect biomarkers are currently recommended to be used as group indicators—they are sensitive, but not contaminant-specific and often difficult to interpret. Effect biomarkers have been used in earlier studies among oil shale sector workers see chapter HBM Among Employees in the Oil Shale Sector for details. Many countries have established national HBM programs. HBM can also identify spatial and temporal trends in human exposure as well as provide information on risk assessment. On the basis of risk assessments, decision-makers can be informed about chemical risks and policy measures can be initiated in order to protect population with the special focus on susceptible groups such as children and pregnant women 9 , 11 , Successful examples of the impact of HBM include the banning of lead in petrol, avoiding mercury-containing amalgam teeth fillings, restricting the use of phthalates in plastics, and several other initiatives It is now a joint project of 30 countries Estonia joined in , the European Environment Agency, and the European Commission for the period of — The harmonization of biomarkers collection and analysis— as well as the selection of which biomarkers to use— should make studies more comparable and give valuable reference material. Besides this, several other tools, such as questionnaires, have been developed which can be used in further HBM studies, i. Previous studies have shown that the most important oil shale sector pollutants— that cause toxic and allergic reactions— are benzene, formaldehyde, phenol, particulate matter PM 10 , fine particles PM 2. However, several studies have indicated that the health effects of PM 10 and PM 2. Annual average concentrations of benzene, particulate matter PM 10 , fine particles PM 2. In the case of PM 10 and PM 2. Concentrations of B a P have been on a slight upward trend in —, then decreased sharply in , and then started to increase again Figure 1. In our analysis, we conducted three larger HBM studies among residents and three among employees. The residents' studies were country-wide incl. The largest HBM program took place in —, where the content of heavy metals in the blood and hair of adults was studied in nine different regions in Estonia Table 1. The study included residents aged 20—60 who had lived in the area for at least 5 years and were born, or lived, in Estonia for at least 20 years In addition, later the data of residents from Maardu and Kostivere was analyzed The other two surveys were conducted among children in — and — In the first study 25 , an increase in the concentration of some microelements in blood of oil shale region children was found according to the contamination of the external environment. The cadmium concentration was 1. Compared to Tartu, the blood heavy metal concentrations were higher in all three Ida-Viru County cities. The second study 26 showed higher levels of lead and cadmium in children's hair in North-Eastern Estonia and higher levels of mercury in Western Estonia in the hair of island and coastal residents. The higher levels of mercury are most likely related to the consumption of fish caught in the Baltic Sea. In that study, the values were also compared to limit values at that time. The occupational studies have focused on miners and coke oven, and benzene plant workers. Due to weak ventilation systems and diesel-powered machinery, miners had a significantly higher exposure to benzene than oil shale sector's surface workers. Furthermore, mine workers are exposed to elevated levels of PM 2. The workers were highly exposed, as the average amount of B a P in the air inhaled by workers was 5. Though 1-OHP levels correlated with the number of DNA adducts, coke oven workers did not differ significantly compared to the controls from nearby Iisaku village The subsequent analysis found that genotype might have played an important role regarding both biomarkers 1-OHP and DNA adducts , as evidenced by significant differences in number of adducts by genotypes among coke oven workers The second study compared benzene plant and coke oven workers. Higher benzene concentrations were observed at the benzene plant, which was confirmed with personal monitoring of benzene in the exhaled air The same study also found higher levels of benzene in the workers' blood and elevated levels of the metabolite t,t-muconic acid MA in the workers' urine. The later analysis of effect biomarkers did not indicate an increase in the number of micronuclei in buccal cells 36 or increased cancer-specific ras p21 proteins in plasma The third study compared 50 underground mine workers exposed to diesel exhaust with 50 above-ground oil shale sector workers. It was found that miners had a higher degree of DNA damage Comet assay data compared to the control group Muzyka et al. Based on the analysis of pollutants, emission and monitoring, the pollutants characterizing the environmental pollution of the oil shale sector would be PM 10 , and PM 2. Elvidge et al. The most common of these are the markers of inflammation: C-reactive protein CRP , interleukin 6 IL-6 , and fibrinogen. However, more than half of the studies using these markers have shown no effect. Less commonly used, but more robust biomarkers have been oxidized low-density lipoprotein ox LDL , lipoprotein receptor-1, TBARS, which characterize lipid hyperperoxidation, and malondialdehyde MDA , a marker of oxidative stress. However, the limitation is that these biomarkers are also elevated with cardiovascular diseases, so they are not specific for the contamination. Even more robust biomarkers are heavy metals bound to particles The update of the temporal and spatial trends, should be encompassed. This should certainly include heavy metals from the earlier HBM in Estonia lead, cadmium, mercury, copper, zinc , as well as arsenic and chromium. In the case of benzene, we recommend to determine it as the BTEX benzene, toluene, ethylbenzene, and xylene metabolite complex, which has been used as a biomarker found in urine in petroleum distribution facilities It has been earlier used among oil shale sector workers Another important metabolite would be 1-hydroxypyrene glucuronide 1-OHP-G , which allows better determination of low exposure to PAH It is a sensitive methodology that can be used to determine low levels biomarkers. This is especially crucial among those less exposed, such as children HBM is valuable tool in indicating exposures as well as early effects in a large number of studies 9 , The information on human exposure can then be linked to data on sources and epidemiological surveys in order to inform research on exposure-response relationships in humans However, there are also several limitations in the interpretation of HBM results. One of the main limitations is that in many cases it may be difficult to confirm from which source the measured effects have been induced. This can be refined by using HBM and environmental monitoring data in parallel, where we can ultimately identify the sources of the pollutants. Other major limitations are the confounding factors that could induce similar effects, e. One of the possibilities to collect data on confounding factors is through questionnaires. Often, HBM is very costly and resource intensive. Tan et al. Tier 2, in a later stage, could focus on effect biomarkers, e. Collecting blood samples in Tier 1 for Tier 2 could be beneficial. Applying the described approached and taking into account the limitations, would warrant the solid ground for HBM in Estonia. Though, besides the exposed population, e. We support including the areas that have been analyzed earlier: Tallinn as capital area, Southern-Estonia as reference area and Western-Estonian coastal areas with somewhat different dietary habits like higher consumption of Baltic-Sea fish. In the current analysis we could identify several HBM studies in the oil shale industry area in Estonia; however, all of those have been made in , , and 's. During the last two decades there has been change in environmental quality, so the update of HBM data is essential. Publicly available datasets were analyzed in this study. This data can be found here: Data is available in the reports referred in the article. Ethical approval was not provided for this study on human participants because the current study only reviews earlier studies. The original studies had been approved by local ethics committees. HO and ML contributed conception of the study. HO and TV compiled the database of earlier studies. HO and AV contributed interpretation of the study findings. AV and KH reviewed the methodology used for chemical analysis in human biomonitoring. All authors contributed to writing the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We would like to express the gratitude to the family of Prof. Silla for bringing his original, largely unpublished, materials to Estonian Health Board. The study was supported by the Estonian Environmental Research Center with the project: Implementation of biomonitoring among population exposed to the oil shale sector workers and residents , preliminary study—Identification of biomarkers. The open access publication was supported by Umea University. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Front Public Health. Find articles by Hans Orru. Find articles by Anu Viitak. Find articles by Koit Herodes. Find articles by Triin Veber. Received Jul 10; Accepted Sep 22; Collection date Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Country-side affected by cement production.

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