Inhalation cancer risk assessment for environmental exposure to hexavalent chromium: Comparison of margin-of-exposure and linear extrapolation approaches.

Hexavalent chromium [Cr(VI)] exists in the ambient air at low concentrations (average upperbound ~0.1 ng/m3) yet airborne concentrations typically exceed EPA's Regional Screening Level for residential exposure (0.012 ng/m3) and other similar benchmarks, which assume a mutagenic mode of action (MOA) and use low-dose linear risk assessment models. We reviewed Cr(VI) inhalation unit risk estimates developed by researchers and regulatory agencies for environmental and occupational exposures and the underlying epidemiologic data, updated a previously published MOA analysis, and conducted dose-response modeling of rodent carcinogenicity data to evaluate the need for alternative exposure-response data and risk assessment approaches. Current research supports the role of non-mutagenic key events in the MOA, with growing evidence for epigenetic modifiers. Animal data show a weak carcinogenic response, even at cytotoxic exposures, and highlight the uncertainties associated with the current epidemiological data used in risk assessment. Points of departure from occupational and animal studies were used to determine margins of exposure (MOEs). MOEs range from 1.5 E+3 to 3.3 E+6 with a median of 5 E+5, indicating that current environmental exposures to Cr(VI) in ambient air should be considered of low concern. In this comprehensive review, the divergent results from default linear and MOE assessments support the need for more relevant and robust epidemiologic data, additional mechanistic studies, and refined risk assessment strategies.

Premature mortality due to air pollution in European cities: a health impact assessment.

BACKGROUND: Ambient air pollution is a major environmental cause of morbidity and mortality worldwide. Cities are generally hotspots for air pollution and disease. However, the exact extent of the health effects of air pollution at the city level is still largely unknown. We aimed to estimate the proportion of annual preventable deaths due to air pollution in almost 1000 cities in Europe. METHODS: We did a quantitative health impact assessment for the year 2015 to estimate the effect of air pollution exposure (PM2·5 and NO2) on natural-cause mortality for adult residents (aged ≥20 years) in 969 cities and 47 greater cities in Europe. We retrieved the cities and greater cities from the Urban Audit 2018 dataset and did the analysis at a 250 m grid cell level for 2015 data based on the global human settlement layer residential population. We estimated the annual premature mortality burden preventable if the WHO recommended values (ie, 10 µg/m3 for PM2·5 and 40 µg/m3 for NO2) were achieved and if air pollution concentrations were reduced to the lowest values measured in 2015 in European cities (ie, 3·7 µg/m3 for PM2·5 and 3·5 µg/m3 for NO2). We clustered and ranked the cities on the basis of population and age-standardised mortality burden associated with air pollution exposure. In addition, we did several uncertainty and sensitivity analyses to test the robustness of our estimates. FINDINGS: Compliance with WHO air pollution guidelines could prevent 51 213 (95% CI 34 036-68 682) deaths per year for PM2·5 exposure and 900 (0-2476) deaths per year for NO2 exposure. The reduction of air pollution to the lowest measured concentrations could prevent 124 729 (83 332-166 535) deaths per year for PM2·5 exposure and 79 435 (0-215 165) deaths per year for NO2 exposure. A great variability in the preventable mortality burden was observed by city, ranging from 0 to 202 deaths per 100 000 population for PM2·5 and from 0 to 73 deaths for NO2 per 100 000 population when the lowest measured concentrations were considered. The highest PM2·5 mortality burden was estimated for cities in the Po Valley (northern Italy), Poland, and Czech Republic. The highest NO2 mortality burden was estimated for large cities and capital cities in western and southern Europe. Sensitivity analyses showed that the results were particularly sensitive to the choice of the exposure response function, but less so to the choice of baseline mortality values and exposure assessment method. INTERPRETATION: A considerable proportion of premature deaths in European cities could be avoided annually by lowering air pollution concentrations, particularly below WHO guidelines. The mortality burden varied considerably between European cities, indicating where policy actions are more urgently needed to reduce air pollution and achieve sustainable, liveable, and healthy communities. Current guidelines should be revised and air pollution concentrations should be reduced further to achieve greater protection of health in cities. FUNDING: Spanish Ministry of Science and Innovation, Internal ISGlobal fund.

Reflections on the OECD guidelines for in vitro skin absorption studies.

At the 8th conference of Occupational and Environmental Exposure of the Skin to Chemicals (OEESC) (16-18 September 2019) in Dublin, Ireland, several researchers performing skin permeation assays convened to discuss in vitro skin permeability experiments. We, along with other colleagues, all of us hands-on skin permeation researchers, present here the results from our discussions on the available OECD guidelines. The discussions were especially focused on three OECD skin absorption documents, including a recent revision of one: i) OECD Guidance Document 28 (GD28) for the conduct of skin absorption studies (OECD, 2004), ii) Test Guideline 428 (TGD428) for measuring skin absorption of chemical in vitro (OECD, 2004), and iii) OECD Guidance Notes 156 (GN156) on dermal absorption issued in 2011 (OECD, 2011). GN156 (OECD, 2019) is currently under review but not finalized. A mutual concern was that these guidance documents do not comprehensively address methodological issues or the performance of the test, which might be partially due to the years needed to finalize and update OECD documents with new skin research evidence. Here, we summarize the numerous factors that can influence skin permeation and its measurement, and where guidance on several of these are omitted and often not discussed in published articles. We propose several improvements of these guidelines, which would contribute in harmonizing future in vitro skin permeation experiments.

Bayesian deprivation index models for explaining variation in elevated blood lead levels among children in Maryland.

Lead exposure adversely affects children's health. Exposure in the United States is highest among socioeconomically disadvantaged individuals who disproportionately live in substandard housing. We used Bayesian binomial regression models to estimate a neighborhood deprivation index and its association with elevated blood lead level (EBLL) risk using blood lead level testing data in Maryland census tracts. Our results show the probability of EBLL was spatially structured with high values in Baltimore city and low values in the District of Columbia suburbs and Baltimore suburbs. The association between the neighborhood deprivation index and EBLL risk was statistically significant after accounting for spatial dependence in probability of EBLL. The percent of houses built before 1940, African Americans, and renter occupied housing were the most important variables in the index. Bayesian models provide a flexible one-step approach to modeling risk associated with neighborhood deprivation while accounting for spatially structured and unstructured heterogeneity in risk.

A new criterion for the health risk assessment of Se and Pb exposure to residents near a smelter.

There is an increasing evidence linking protective effect of selenium (Se) against Pb toxicology; however, Pb exposure risk assessments usually consider only the environmental Pb contamination and dietary intake. Based on the current understanding of mechanisms of SePb interactions, the physiological function/toxicology of Se and the toxicology of Pb, a new criterion for Se and Pb exposure assessment is developed. Additionally, seven existing criteria were also used to assess the resident health risks around a smelter in China. The Pb concentrations in locally-produced foods exceeded the national tolerance limits of China and the Se in the foods were similar to those in areas with adequate Se levels. In accordance with the illustrated assessments of the new criterion and seven existing criteria, we found a large knowledge gap between the new and traditional assessments of exposure to Pb and/or Se. The new assessment criteria suggested that almost all the residents were facing the Se deficiency and 58% of the residents not only had the adverse health of Se deficiency, but also had the health risks of Pb toxicity. The Pb and Se in the hair and urine may partly support the new criterion. This study suggested that the process of Se counteracting the Pb toxicity may result in Se deficiency. Pb exposure combined Se intake should be considered in future assessments of Pb exposure (or Se intake).

Explaining variation in elevated blood lead levels among children in Minnesota using neighborhood socioeconomic variables.

BACKGROUND: Childhood lead exposure is linked to numerous adverse health effects and exposure in the United States is highest among people living in substandard housing, which is disproportionately inhabited by socioeconomically disadvantaged individuals. In this paper, we compared the Vox lead exposure risk score and concentrated disadvantage based on principal component analysis (PCA) to weighted quantile sum (WQS) regression to determine which method was best able to explain variation in elevated blood lead levels (EBLLs). METHODS: We constructed indices for census tracts in Minnesota and used them in Poisson regression models to identify the best socioeconomic measure for explaining EBLL risk. RESULTS: All indices had a significant association with EBLL in separate models. The WQS index had the best goodness-of-fit, followed next by the Vox index, and then the concentrated disadvantage index. Among the most important variables in the WQS index were percent of houses built before 1940, percent renter occupied housing, percent unemployed, and percent African American population. CONCLUSIONS: The WQS approach was best able to explain variation in EBLL risk and identify census tracts where targeted interventions should be focused to reduce lead exposure.

Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution.

This article reviews the current legislative requirements for risk assessment of combined exposure to multiple chemicals via multiple exposure routes, focusing on human health and particularly on food-related chemicals. The aim is to identify regulatory needs and current approaches for this type of risk assessment as well as challenges of the implementation of appropriate and harmonized guidance at international level. It provides an overview of the current legal requirements in the European Union (EU), the United States and Canada. Substantial differences were identified in the legal requirements for risk assessment of combined exposure to multiple chemicals and its implementation between EU and non-EU countries and across several regulatory sectors. Frameworks currently proposed and in use for assessing risks from combined exposure to multiple chemicals via multiple routes and different durations of exposure are summarized. In order to avoid significant discrepancies between regulatory sectors or countries, the approach for assessing risks of combined exposure should be based on similar principles for all types of chemicals. OECD and EFSA identified the development of harmonized methodologies for combined exposure to multiple chemicals as a key priority area. The Horizon 2020 project "EuroMix" aims to contribute to the further development of internationally harmonized approaches for such risk assessments by the development of an integrated test strategy using in vitro and in silico tests verified for chemical mixtures based on more appropriate data on potential combined effects. These approaches and testing strategies should be integrated in a scientifically based weight of evidence approach to account for complexity and uncertainty, to improve risk assessment.

Risk Assessment of Benzene, Toluene, Ethyl Benzene, and Xylene Concentrations from the Combustion of Coal in a Controlled Laboratory Environment.

A D-grade type coal was burned under simulated domestic practices in a controlled laboratory set-up, in order to characterize the emissions of volatile organic compounds (VOCs); namely, benzene, toluene, ethylbenzene, and xylenes (BTEX). Near-field concentrations were collected in a shack-like structure constructed using corrugated iron, simulating a traditional house found in informal settlements in South Africa (SA). Measurements were carried out using the Synspec Spectras GC955 real-time monitor over a three-hour burn cycle. The 3-h average concentrations (in µg/m³) of benzene, toluene, ethylbenzene, p-xylene, and o-xylene were 919 ± 44, 2051 ± 91, 3838 ±19, 4245 ± 41 and 3576 ± 49, respectively. The cancer risk for adult males and females in a typical SA household exposure scenario was found to be 1.1 and 1.2 respectively, which are 110- and 120-fold higher than the U.S. Environmental Protection Agency (EPA) designated risk severity indicator (1 × 10-6). All four TEX (toluene, ethylbenzene, p-xylene and o-xylene) compounds recorded a Hazard Quotient (HQ) of less than 1, indicating a low risk of developing related non-carcinogenic health effects. The HQ for TEX ranged from 0.001 to 0.05, with toluene concentrations being the lowest, and ethylbenzene the highest. This study has demonstrated that domestic coal burning may be a significant source of BTEX emission exposure.

Association of Short-term Exposure to Air Pollution With Mortality in Older Adults.

Importance: The US Environmental Protection Agency is required to reexamine its National Ambient Air Quality Standards (NAAQS) every 5 years, but evidence of mortality risk is lacking at air pollution levels below the current daily NAAQS in unmonitored areas and for sensitive subgroups. Objective: To estimate the association between short-term exposures to ambient fine particulate matter (PM2.5) and ozone, and at levels below the current daily NAAQS, and mortality in the continental United States. Design, Setting, and Participants: Case-crossover design and conditional logistic regression to estimate the association between short-term exposures to PM2.5 and ozone (mean of daily exposure on the same day of death and 1 day prior) and mortality in 2-pollutant models. The study included the entire Medicare population from January 1, 2000, to December 31, 2012, residing in 39 182 zip codes. Exposures: Daily PM2.5 and ozone levels in a 1-km × 1-km grid were estimated using published and validated air pollution prediction models based on land use, chemical transport modeling, and satellite remote sensing data. From these gridded exposures, daily exposures were calculated for every zip code in the United States. Warm-season ozone was defined as ozone levels for the months April to September of each year. Main Outcomes and Measures: All-cause mortality in the entire Medicare population from 2000 to 2012. Results: During the study period, there were 22 433 862 million case days and 76 143 209 control days. Of all case and control days, 93.6% had PM2.5 levels below 25 µg/m3, during which 95.2% of deaths occurred (21 353 817 of 22 433 862), and 91.1% of days had ozone levels below 60 parts per billion, during which 93.4% of deaths occurred (20 955 387 of 22 433 862). The baseline daily mortality rates were 137.33 and 129.44 (per 1 million persons at risk per day) for the entire year and for the warm season, respectively. Each short-term increase of 10 µg/m3 in PM2.5 (adjusted by ozone) and 10 parts per billion (10-9) in warm-season ozone (adjusted by PM2.5) were statistically significantly associated with a relative increase of 1.05% (95% CI, 0.95%-1.15%) and 0.51% (95% CI, 0.41%-0.61%) in daily mortality rate, respectively. Absolute risk differences in daily mortality rate were 1.42 (95% CI, 1.29-1.56) and 0.66 (95% CI, 0.53-0.78) per 1 million persons at risk per day. There was no evidence of a threshold in the exposure-response relationship. Conclusions and Relevance: In the US Medicare population from 2000 to 2012, short-term exposures to PM2.5 and warm-season ozone were significantly associated with increased risk of mortality. This risk occurred at levels below current national air quality standards, suggesting that these standards may need to be reevaluated.

The air of Europe: where are we going?

Air pollution constitutes one of the main threats to public health in Europe. Significant impacts on the health of Europeans in terms of morbidity and mortality have been observed, even in cases of low exposure and where pollutant levels are within limits set by the European Union (EU). The respiratory system is a primary target of the harmful effects of key air pollutants. Emissions of many air pollutants have decreased substantially over the past decades in Europe, resulting in diminished concentrations and improved air quality. However, in several European cities concentrations still exceed EU reference values and, more often, the stricter World Health Organization air quality guidelines for all regulated air pollutants (particles with 50% cut-off aerodynamic diameters of 10 and 2.5 µm, nitrogen dioxide (NO2), benzo[a]pyrene and ozone (O3)) except sulfur dioxide. In addition, current trends indicate that in the absence of substantial changes, particulate matter, NO2 and O3 will still exceed limits in 2020. Additional efforts must be made to comply with current standards and guidelines. These should include a more accurate and detailed monitoring of air pollutants, reduction of emissions and individual behaviour changes.

Air Pollution and Mortality in the Medicare Population.

BACKGROUND: Studies have shown that long-term exposure to air pollution increases mortality. However, evidence is limited for air-pollution levels below the most recent National Ambient Air Quality Standards. Previous studies involved predominantly urban populations and did not have the statistical power to estimate the health effects in underrepresented groups. METHODS: We constructed an open cohort of all Medicare beneficiaries (60,925,443 persons) in the continental United States from the years 2000 through 2012, with 460,310,521 person-years of follow-up. Annual averages of fine particulate matter (particles with a mass median aerodynamic diameter of less than 2.5 µm [PM2.5]) and ozone were estimated according to the ZIP Code of residence for each enrollee with the use of previously validated prediction models. We estimated the risk of death associated with exposure to increases of 10 µg per cubic meter for PM2.5 and 10 parts per billion (ppb) for ozone using a two-pollutant Cox proportional-hazards model that controlled for demographic characteristics, Medicaid eligibility, and area-level covariates. RESULTS: Increases of 10 µg per cubic meter in PM2.5 and of 10 ppb in ozone were associated with increases in all-cause mortality of 7.3% (95% confidence interval [CI], 7.1 to 7.5) and 1.1% (95% CI, 1.0 to 1.2), respectively. When the analysis was restricted to person-years with exposure to PM2.5 of less than 12 µg per cubic meter and ozone of less than 50 ppb, the same increases in PM2.5 and ozone were associated with increases in the risk of death of 13.6% (95% CI, 13.1 to 14.1) and 1.0% (95% CI, 0.9 to 1.1), respectively. For PM2.5, the risk of death among men, blacks, and people with Medicaid eligibility was higher than that in the rest of the population. CONCLUSIONS: In the entire Medicare population, there was significant evidence of adverse effects related to exposure to PM2.5 and ozone at concentrations below current national standards. This effect was most pronounced among self-identified racial minorities and people with low income. (Supported by the Health Effects Institute and others.).

A quantitative screening-level approach to incorporate chemical exposure and risk into alternative assessment evaluations.

As the general public and retailers ask for disclosure of chemical ingredients in the marketplace, a number of hazard screening tools were developed to evaluate the so-called "greenness" of individual chemical ingredients and/or formulations. The majority of these tools focus only on hazard, often using chemical lists, ignoring the other part of the risk equation: exposure. Using a hazard-only focus can result in regrettable substitutions, changing 1 chemical ingredient for another that turns out to be more hazardous or shifts the toxicity burden to others. To minimize the incidents of regrettable substitutions, BizNGO describes "Common Principles" to frame a process for informed substitution. Two of these 6 principles are: "reduce hazard" and "minimize exposure." A number of frameworks have emerged to evaluate and assess alternatives. One framework developed by leading experts under the auspices of the US National Academy of Sciences recommended that hazard and exposure be specifically addressed in the same step when assessing candidate alternatives. For the alternative assessment community, this article serves as an informational resource for considering exposure in an alternatives assessment using elements of problem formulation; product identity, use, and composition; hazard analysis; exposure analysis; and risk characterization. These conceptual elements build on practices from government, academia, and industry and are exemplified through 2 hypothetical case studies demonstrating the questions asked and decisions faced in new product development. These 2 case studies-inhalation exposure to a generic paint product and environmental exposure to a shampoo rinsed down the drain-demonstrate the criteria, considerations, and methods required to combine exposure models addressing human health and environmental impacts to provide a screening level hazard and exposure (risk) analysis. This article informs practices for these elements within a comparative risk context to improve alternatives assessment evaluation and decision making. Integr Environ Assess Manag 2017;13:1007-1022. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Requirements for Notification, Evaluation and Reduction of Lead-Based Paint Hazards in Federally Owned Residential Property and Housing Receiving Federal Assistance; Response to Elevated Blood Lead Levels. Final rule.

This final rule amends HUD's lead-based paint regulations to reduce blood lead levels in children under age six (6) who reside in federally-owned or -assisted pre-1978 housing, formally adopting a revised definition of "elevated blood lead level" (EBLL) in children under the age of six (6), in accordance with Centers for Disease Control and Prevention (CDC) guidance. It also establishes more comprehensive testing and evaluation procedures for the housing where such children reside. This final rule also addresses certain additional elements of the CDC guidance pertaining to assisted housing and makes technical corrections and clarifications. This final rule, which follows HUD's September 1, 2016, proposed rule, takes into consideration public comments submitted in response to the proposed rule.

Comparison of Points of Departure for Health Risk Assessment Based on High-Throughput Screening Data.

BACKGROUND: The National Research Council's vision for toxicity testing in the 21st century anticipates that points of departure (PODs) for establishing human exposure guidelines in future risk assessments will increasingly be based on in vitro high-throughput screening (HTS) data. OBJECTIVES: The aim of this study was to compare different PODs for HTS data. Specifically, benchmark doses (BMDs) were compared to the signal-to-noise crossover dose (SNCD), which has been suggested as the lowest dose applicable as a POD. METHODS: Hill models were fit to > 10,000 in vitro concentration-response curves, obtained for > 1,400 chemicals tested as part of the U.S. Tox21 Phase I effort. BMDs and lower confidence limits on the BMDs (BMDLs) corresponding to extra effects (i.e., changes in response relative to the maximum response) of 5%, 10%, 20%, 30%, and 40% were estimated for > 8,000 curves, along with BMDs and BMDLs corresponding to additional effects (i.e., absolute changes in response) of 5%, 10%, 15%, 20%, and 25%. The SNCD, defined as the dose where the ratio between the additional effect and the difference between the upper and lower bounds of the two-sided 90% confidence interval on absolute effect was 1, 0.67, and 0.5, respectively, was also calculated and compared with the BMDLs. RESULTS: The BMDL40, BMDL25, and BMDL18, defined in terms of extra effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. Similarly, the BMDL25, BMDL17, and BMDL13, defined in terms of additional effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. CONCLUSIONS: The SNCD may serve as a reference level that guides the determination of standardized BMDs for risk assessment based on HTS concentration-response data. The SNCD may also have application as a POD for low-dose extrapolation.

Evaluation of air quality zone classification methods based on ambient air concentration exposure.

Air quality zones are used by regulatory authorities to implement ambient air standards in order to protect human health. Air quality measurements at discrete air monitoring stations are critical tools to determine whether an air quality zone complies with local air quality standards or is noncompliant. This study presents a novel approach for evaluation of air quality zone classification methods by breaking the concentration distribution of a pollutant measured at an air monitoring station into compliance and exceedance probability density functions (PDFs) and then using Monte Carlo analysis with the Central Limit Theorem to estimate long-term exposure. The purpose of this paper is to compare the risk associated with selecting one ambient air classification approach over another by testing the possible exposure an individual living within a zone may face. The chronic daily intake (CDI) is utilized to compare different pollutant exposures over the classification duration of 3 years between two classification methods. Historical data collected from air monitoring stations in Kuwait are used to build representative models of 1-hr NO2 and 8-hr O3 within a zone that meets the compliance requirements of each method. The first method, the "3 Strike" method, is a conservative approach based on a winner-take-all approach common with most compliance classification methods, while the second, the 99% Rule method, allows for more robust analyses and incorporates long-term trends. A Monte Carlo analysis is used to model the CDI for each pollutant and each method with the zone at a single station and with multiple stations. The model assumes that the zone is already in compliance with air quality standards over the 3 years under the different classification methodologies. The model shows that while the CDI of the two methods differs by 2.7% over the exposure period for the single station case, the large number of samples taken over the duration period impacts the sensitivity of the statistical tests, causing the null hypothesis to fail. Local air quality managers can use either methodology to classify the compliance of an air zone, but must accept that the 99% Rule method may cause exposures that are statistically more significant than the 3 Strike method. IMPLICATIONS: A novel method using the Central Limit Theorem and Monte Carlo analysis is used to directly compare different air standard compliance classification methods by estimating the chronic daily intake of pollutants. This method allows air quality managers to rapidly see how individual classification methods may impact individual population groups, as well as to evaluate different pollutants based on dosage and exposure when complete health impacts are not known.

[Actual problem of methodology and development of evidence-based health risk assessment associated with chemical exposure].

Paramount problems of the development of the assessment of population health risks associated with the chemical exposure in Russia are considered on the ground of critical analysis of reports devoted to methodological issues of the risk assessment and guidelines published since 2010. Causes of the lack in progress of risk assessment are discussed. The information of executed research revealed the significant retardation number of Russian publications devoted to the evidence-based health risk assessment compare to worldwide trend. The analysis of publications according to evidence-based health risk assessment in Russia in 1998 - 2012 demonstrated methodical problems to be leading to the underestimation of the real risk to population's health. There are demonstrated directions in the renewal of methodology and practice of hygienic standardization on the basis of the risk assessment. The comparative analysis of values of uncertainty factors (modifying factors, conversion factors) used for extrapolation and accepted in different countries and organizations was made. The system of extrapolation coefficients of DNEL (Derive No-Effect Level) is presented. The leading principles of modern toxicology and risk assessment based on strict scientific proofs are showed. Criteria of evidence-based toxicology and risk assessment are presented.Among actual problems which demand their decision there are considered: the assessment of combined action in regulatory toxicology; expansion of spheres of the application of health risk assessment methodology; the improvement ofpreparation and certification of experts in the field of health risk assessment; need of check of dispersion models and their replacement by more modern models; the improvement of exposure assessment with taking into account the international requirements; the assessment of regional exposure factors; expansion of atmospheric air monitoring in all the large cities of Russia.

[Cytogenetic status of the residents of the Gydansky Peninsula (Gydan)].

The relevance of the study on the Gydansky Peninsula lies in poor knowledge and inaccessibility of the territory, planned intensive industrial development of the Gydansky Peninsula, in 2011 there were received licenses for the exploration of license areas at the peninsula up to 2031. Industrial development will inevitably lead to certain environmental shifts, emission of the harmful substances into biosphere, the accumulation of anthropogenic pollutants in soil and water sources. The proposed development of the territory of the Peninsula Gydan sets the task of assessment of the impact of gas and oil production in conditions of the far North on health, as well indigenous persons as employees recruited to this of the region. One of the informative approaches to the assessment of population health is the assessment of the cytogenetic status with the use of noninvasive analysis of buccal epithelium. The aim of the study is to determine the cytogenetic status of the inhabitants of the village of Antipayuta of the Yamal-Nenets Autonomous Okrug for the assessment of the impact of environmental factors on the health of the population at the present stage of the industrial development of the territory. Samples of buccal epithelium of 81 alien and indigenous people of the Yamal-Nenets Autonomous district were the object of the investigation. There was performed the analysis of indices of cells of buccal epithelium of the residents living in the village in comparison with the control group. The analysis of samples was performed on a Nikon Eclipse E100 microscope. For the assessment of the cytogenetic status of the individual there was used the proposed by Sycheva L. P. (2012-Index of accumulation of cytogenetic damages (Iac). It is shown that the frequency of occurrence of micronucleus and nuclear protrusions does not exceed the performance of the control group. The index of accumulation of cytogenetic damage for the population of the village is 0.78±0.07% and corresponds to a low level. The analysis of indices of buccal epithelial cells of residents living in rural areas was performed in the comparison with the control group The prevalence rate of cells with micronuclei and protrusions were shown to account of 14.6% andfail to exceed indices in the control group. Accumulation index of cytogenetic damages for the village population is 0.78 ± 0.07 % and corresponds to the low level. The amount of cells with micronuclei and protrusions in the current study is by 14.6% lower than the average of the control group. The intensity of proliferative processes and apoptosis in the comparison groups occurs evenly.

[Tracing for arsenic exposure--a differentiation of arsenic compounds is essential for the health assessment]. / Der Arsenbelastung auf der Spur.

Arsenic is ubiquitous and harmful to health in occupation and environment. Arsenic exposure is measured through analysis of arsenic compounds in urine. The identification of several arsenic species is necessary to understand the hazardous potential of the arsenic compounds which differ highly in their toxicity. To estimate the extent of an occupational exposure to arsenic, arsenic species were evaluated for the first time by the working group "Setting of Threshold Limit Values in Biological Material" of the DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area and Biologische Arbeitsstoffreferenzwerte (BAR) of 0.5 µg / L urine for arsenic (III), 0.5 µg / L urine for arsenic (V), 2 µg / L urine for monomethylarsonic acid (MMA) and 10 µg / L urine for dimethylarsinic acid (DMA) were set. If the reference value for total arsenic is exceeded, a further differentiation of arsenic species now enables to estimate the individual health risks taking into account special influences such as seafood consumption.

[Novosibirsk Research Hygiene Institute - 85 years serving sanitary epidemiologic well-being of Siberia population].

The authors present review ot themes covered by Novosibirsk Research Hygiene Institute and the study results obtained over recent years. Evidences are that industrial Siberian centers demonstrate general positive changes in environmental pollution decrease and better health state of children and adolescents, but the situation remains warning about medical and sanitary care for workers engaged into hazardous work conditions, about lower diagnostic coverage of occupational diseases in periodic medical examinations. Facts are that qualified early diagnosis of primary signs of workers' disablement and opportune rehabilitation and preventive treatment enable to stop occupational diseases formation.

Risk assessment on the use of herbal medicinal products containing pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PA) are common plantal toxins directed against insect herbivores. Unsaturated PAs are known to be hepatotoxic. Many of the PAs are in addition mutagenic and some may possibly be carcinogenic for humans. The risk of an exposure to PAs associated with their occurrence in herbal medicinal products and in foodstuff is under current discussion. The present risk assessment for herbal medicinal products containing PAs is based on a margin of safety derivation for foodstuff indicating that a life-long exposure to maximally 0.007 µg/kg bw/day is not expected to be associated with safety concerns. This approach offers a possibility to estimate the potential risk of PA-containing herbal medicinal products irrespective of the route of administration. It assumes PA levels in the final herbal medicinal product below 0.01 ppm and considers for dermal administration a 100% skin penetration of the PAs reflecting a worst-case scenario. As a result, the calculated margins of safety show a potential exposure using herbal medicinal products 70-, 45.5-, and 19.3-fold lower on a one-day base and 608-, 396-, and 168- fold lower on a one-year base for adults, children aged 12 years, and children aged 4 years, respectively, than the thresholds considered acceptable for foodstuff.