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At least 235 records · Page 13

NASA Space Radiation Protection Strategies: Risk Assessment and Permissible Exposure Limits

Permissible exposure limits (PELs) for short-term and career astronaut exposures to space radiation have been set and approved by NASA with the goal of protecting astronauts against health risks associated with ionizing radiation exposure. Short term PELs are intended to prevent clinically significant deterministic health effects, including performance decrements, which could threaten astronaut health and jeopardize mission success. Career PELs are implemented to control late occurring health effects, including a 3% risk of exposure induced death (REID) from cancer, and dose limits are used to prevent cardiovascular and central nervous system diseases. For radiation protection, meeting the cancer PEL is currently the design driver for galactic cosmic ray and solar particle event shielding, mission duration, and crew certification (e.g., 1-year ISS missions). The risk of cancer development is the largest known long-term health consequence following radiation exposure, and current estimates for long-term health risks due to cardiovascular diseases are approximately 30% to 40% of the cancer risk for exposures above an estimated threshold (Deep Space one-year and Mars missions). Large uncertainties currently exist in estimating the health risks of space radiation exposure. Improved understanding through radiobiology and physics research allows increased accuracy in risk estimation and is essential for ensuring astronaut health as well as for controlling mission costs, optimization of mission operations, vehicle design, and countermeasure assessment. We will review the Space Radiation Program Element's research strategies to increase accuracy in risk models and to inform development and validation of the permissible exposure limits.

Huff, J. L.↗

Cardiopulmonary Inflammatory Response to Meteorite Dust Exposures - Implications for Human Health on Earth and Beyond

This year marks the 50th anniversary of Apollo 11, the first time humans set foot on the Moon. The Apollo missions not only help answer questions related to our solar system, they also highlight many hazards associated with human space travel. One major concern is the effect of extraterrestrial dust on astronaut health. In an effort to expand upon previous work indicating lunar dust is respirable and reactive, the authors initiated an extensive study evaluating the role of a particulate’s innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. To allow for a broader planetary and geochemical assessment, seven samples were evaluated: six meteorites from either the Moon, Mars, or Asteroid 4 Vesta and a terrestrial basalt analogue. Even with the relatively small geochemical differences (all samples basaltic in nature), significant difference in cardiopulmonary inflammatory markers developed in both single exposure and multiple exposure studies. More specifically: 1) the single exposure studies reveal relationships between toxicity and a meteorite sample’s origin, its pre-ejected state (weathered versus un-weathered), and geochemical features (e.g. bulk iron content) and 2) multiple exposure studies reveal a correlation with particle derived reactive oxygen species (ROS) formation and neutrophil infiltration. Extended human exploration will further increase the probability of inadvertent and repeated exposures to extraterrestrial dusts. This comprehensive dataset allows for not only the toxicological evaluation of extraterrestrial materials but also clarifies important correlations between geochemistry and health. The utilization of an array of extraterrestrial samples from Moon, Mars, and asteroid 4Vesta will enable the development of a geochemical based toxicological hazard model that can be used for: 1) mission planning, 2) rapid risk assessment in cases of unexpected exposures, and 3) evaluation of the efficacy of various in situ techniques in gauging surface dust toxicity. Furthermore, by better understanding the importance of geochemical features on exposure related health outcomes in space, it is possible to better understand of the deleterious nature of dust exposure on Earth.

Harrington, A. D.↗

Space Environmental Exposure of the MISSE 9-15 Polymers and Composites Experiment 1-4 (PCE 1-4)

Spacecraft in low Earth orbit (LEO) are subjected to harsh environmental conditions, including radiation (cosmic rays, ultraviolet (UV), x-ray and charged particle radiation), micrometeoroids and orbital debris, temperature extremes, thermal cycling, and atomic oxygen (AO). These environmental exposures can result in erosion, embrittlement and optical property degradation of susceptible materials threatening spacecraft performance and durability. To increase our understanding of effects such as AO erosion and radiation induced embrittlement of spacecraft materials, NASA Glenn Research Center has developed a series of experiments that were flown as part of the Materials International Space Station Experiment (MISSE) missions on the exterior of the International Space Station (ISS). These experiments have provided critical space environmental durability data such as AO erosion data of polymers and composites, and radiation induced mechanical property degradation of spacecraft insulation materials, after long term space exposure. Recently, four Glenn experiments with 365 flight samples were flown on ISS’s MISSE-Flight Facility (MISSE-FF). These experiments are the Polymers and Composites Experiment-1 (PCE-1) flown as part of the MISSE-9 mission, the PCE-2 flown as part of the MISSE-10 mission, the PCE-3 flown as part of the MISSE-12 and MISSE-15 missions, and the PCE-4 flown as part of the MISSE-13 mission. This paper provides details on the space environment exposure of Glenn’s PCE 1-4 flight samples. Passive samples were flown in each flight orientation for post-flight AO fluence determination and on-orbit contamination analyses. Solar exposure estimates were computed by Aegis Aerospace, Inc. The environment exposure details include the total space vacuum duration, time on the MISSE-FF, the direct space exposure duration, the AO fluence and the computed mission Equivalent Sun Hours (ESH) solar exposure. Typical on-orbit temperatures are also provided along with a summary of analyses of PCE 1-4 contamination witness samples. Knowledge of the space environmental exposure of the PCE 1-4 flight samples is crucial for flight data interpretation.

Atomic oxygen↗

Exposure Assumptions Underlying Cleanups to Industrial Versus Unrestricted Uses: Comparison of State and Federal Approaches - 17228

The Environmental Protection Agency (EPA) and various states have designated a variety of cleanup levels ranging from restricted (too much residual contamination to allow any use) to unrestricted or residential. Although there are many potential exposure scenarios, the States of Washington and New Jersey identify only two levels for cleanup of chemical contaminants in soil: 'unrestricted' and 'industrial' (Washington) and 'residential' vs 'non-residential' (New Jersey). Other agencies such as EPA and DOE recognize several levels of recreational use, between unrestricted and industrial, and likewise there are several levels of residential use as well. Cleanup criteria may allow or preclude the use of ground water for drinking, swimming pools, gardens, or lawns. Tribal unrestricted scenarios include the use of water (probably surface water in most scenarios) for sweat lodges, and have calculated high level exposure pathways for both dermal and inhalation pathways as well as ingestion. For residential scenarios, inadvertent ingestion of soil, drinking of ground water, and consumption of local foods represent the highest exposure pathways. Intermediate, recreational pathways may be non-consumptive (hiking, bird watching, photography) or consumptive (hunting, fishing, harvesting plants and medicines), the latter entailing much higher potential exposures. For each land-use there is a corresponding exposure scenario, with different assumptions about the maximally exposed individual, their age, and the amounts of air, water, soil, and foods they consume. For each exposure pathway one can compute the ratio between the exposure assumptions for any two scenarios. The product of the ratios comprises a Vulnerability Index. The index is higher for children than adults. For Washington this Index is reflected in the 'industrial' vs 'unrestricted' soil cleanup levels, which are 43.7 times lower for 'unrestricted'. This paper explores the similarities and differences in the exposure scenarios and vulnerability of the maximally exposed individuals and the consequences of a mismatch between current cleanup levels and possible future land uses. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Impacts of environmental exposure on thermal and mycological characteristics of insulation wools

Highlights: • Insulation materials (IM) suffer expositions to weather on energy efficient buildings. • Induced exposure to weather of IM reveals differences in ATR-FTIR spectra. • Mycological analysis shows a significant effect of exposure condition on IM. • Mold species detected may induce human health risk and degradation of IM. • Thermal conductivity of IM according humidity of air may impact energy performance. - Abstract: Fieldwork was conducted on 138 energy efficient buildings, to check if building site practices induced exposure to weather of thermal insulation. In nearly 80% of cases, insulation was exposed to weather due to insufficient protection. Therefore insulating wools were exposed, divided into three parts (control, exposure under shelter, exposure to weather). After the exposure period these samples were submitted to thermal conductivity measurements and infrared spectroscopy. A numerical study was carried out to evaluate the influence of weather conditions on thermal performance. Identifications of molds were realized by direct cultures of each sample. Mycological analyses provided the most significant results, showing a significant effect of exposure condition, with possible consequences in human health (toxinogenic, allergenic or pathogenic species) and material properties (cellulolytic species). Infrared spectrometry also showed some changes in sensitivity to water. These results show the interest to study in more detail the variations in the sensitivity, to moisture and mold, of insulation material throughout its ageing on site, and the interactions with the practices of the building process.

36 MATERIALS SCIENCE↗

Incidence of nephrolithiasis in relation to environmental exposure to lead and cadmium in a population study

Whether environmental exposure to nephrotoxic agents that potentially interfere with calcium homeostasis, such as lead and cadmium, contribute to the incidence of nephrolithiasis needs further clarification. We investigated the relation between nephrolithiasis incidence and environmental lead and cadmium exposure in a general population. In 1302 participants randomly recruited from a Flemish population (50.9% women; mean age, 47.9 years), we obtained baseline measurements (1985–2005) of blood lead (BPb), blood cadmium (BCd), 24-h urinary cadmium (UCd) and covariables. We monitored the incidence of kidney stones until October 6, 2014. We used Cox regression to calculate multivariable-adjusted hazard ratios for nephrolithiasis. At baseline, geometric mean BPb, BCd and UCd was 0.29 µmol/L, 9.0 nmol/L, and 8.5 nmol per 24 h, respectively. Over 11.5 years (median), nephrolithiasis occurred in 40 people. Contrasting the low and top tertiles of the distributions, the sex- and age-standardized rates of nephrolithiasis expressed as events per 1000 person-years were 0.68 vs. 3.36 (p=0.0016) for BPb, 1.80 vs. 3.28 (p=0.11) for BCd, and 1.65 vs. 2.95 (p=0.28) for UCd. In continuous analysis, with adjustments applied for sex, age, serum magnesium, and 24-h urinary volume and calcium, the hazard ratios expressing the risk associated with a doubling of the exposure biomarkers were 1.35 (p=0.015) for BPb, 1.13 (p=0.22) for BCd, and 1.23 (p=0.070) for UCd. In conclusion, our results suggest that environmental lead exposure is a risk factor for nephrolithiasis in the general population. - Highlights: • Prevalence and incidence rates of nephrolithiasis are increasing worldwide. • Lead and cadmium interfere with calcium homeostasis and might cause nephrolithiasis. • Environmental exposure to lead, not cadmium, predicts nephrolithiasis in the population. • Safety standards for environmental lead exposure need to account for nephrolithiasis. • Reducing environmental exposure to lead remains a priority.

54 ENVIRONMENTAL SCIENCES↗

Cadmium, lead, and arsenic contamination in paddy soils of a mining area and their exposure effects on human HEPG2 and keratinocyte cell-lines

A mining district in south China shows significant metal(loid) contamination in paddy fields. In the soils, average Pb, Cd and As concentrations were 460.1, 11.7 and 35.1 mg kg{sup −1} respectively, which were higher than the environmental quality standard for agricultural soils in China (GB15618-1995) and UK Clea Soil Guideline Value. The average contents of Pb, Cd and As in rice were 5.24, 1.1 and 0.7 mg kg{sup −1} respectively, which were about 25, 4.5 or 2.5 times greater than the limit values of the maximum safe contaminant concentration standard in food of China (GB 2762-2012), and about 25, 10 or 1 times greater than the limit values of FAO/WHO standard. The elevated contents of Pb, Cd and As detected in soils around the factories, indicated that their spatial distribution was influenced by anthropogenic activity, while greater concentrations of Cd in rice appeared in the northwest region of the factories, indicating that the spatial distribution of heavy metals was also affected by natural factors. As human exposure around mining districts is mainly through oral intake of food and dermal contact, the effects of these metals on the viability and MT protein of HepG2 and KERTr cells were investigated. The cell viability decreased with increasing metal concentrations. Co-exposure to heavy metals (Pb+Cd) increased the metals (Pb or Cd)-mediated MT protein induction in both human HepG2 and KERTr cells. Increased levels of MT protein will lead to greater risk of carcinogenic manifestations, and it is likely that chronic exposure to metals may increase the risk to human health. Nevertheless, when co-exposure to two or more metals occur (such as As+Pb), they may have an antagonistic effect thus reducing the toxic effects of each other. Capsule: Metal contaminations in paddy soils and rice were influenced by anthropogenic activity; metal co-exposure induced MT protein in human cells. - Highlights: • Pb, Cd and As in paddy soils and rice were higher than national and FAO standards. • Pb, Cd and As spatial distribution was mainly influenced by anthropogenic activity. • The HepG2 and KERTr cell viability decreased with increasing metal concentrations. • Co-exposure to heavy metals increased MT protein induction in HepG2 and KERTr cells. • Co-exposure to some metals (As+Pb) may have an antagonistic effect.

54 ENVIRONMENTAL SCIENCES↗

Phthalate esters on urban airborne particles: Levels in PM10 and PM2.5 from Mexico City and theoretical assessment of lung exposure

Highlights: • Phthtalates esters were found in PM{sub 10} and PM{sub 2.5} collected in Mexico City. • DEHP and DnBP were the phthalates esters in higher concentration. • The exposure to DEHP was estimated as high as 18 ng/8 h. • Age and gender are variables that must be considered when evaluating exposure by inhalation. Endocrine disrupting chemicals (EDCs) from the environment are associated with reproductive abnormalities (i.e. decreased sperm concentration; increased endometriosis) and alterations of the cardiovascular system (i.e. increased blood pressure and risk of coronary disease). Some phthalates esters have been identified as EDCs, for which inhalation is considered as one of the routes of exposure. However, only little is known regarding inhalational exposure to EDCs via urban airborne particles. In the present study, we report the monthly concentration of 8 phthalate esters measured in PM{sub 10} and PM{sub 2.5} collected and recovered during 7 months in a highly populated area of Mexico City. Using the levels of PM{sub 10} and PM{sub 2.5} reported by the automatized network of environmental monitoring of Mexico City for the sampling site, we estimated exposure levels for people of different ages and gender. Two endocrine disrupting compounds, the phthalate esters DEHP and DnBP, were found on the particles in higher concentrations during the warmer months of the year. The highest concentration was reported for DEHP (229.7 μg/g of particles) in PM{sub 2.5} collected in May 2013. After calculations of the DEHP concentration in the atmosphere, and using the respiratory flow rate, we determined males were potentially exposed to larger quantities of DEHP, reaching up to 18 ng/8 h in April 2013. Despite the concentrations of phthalates seem to be rather small, a comprehensive characterization of its presence is necessary in order to evaluate the overall exposure to these compounds, providing a clear view of exposure on children, adolescents and pregnant women.

54 ENVIRONMENTAL SCIENCES↗

mRNA Transcript Abundance during Plant Growth and the Influence of Li + Exposure

Lithium (Li) toxicity in plants is, at a minimum, a function of Li + concentration, exposure time, species and growth conditions. Most plant studies with Li + focus on short-term acute exposures. This study examines short- and long-term effects of Li + exposure in Arabidopsis with Li + uptake studies and measured shoot mRNA transcript abundance levels in treated and control plants. Stress, pathogen-response and arabinogalactan protein genes were typically more up-regulated in older (chronic, low level) Li + -treatment plants and in the much younger plants from acute high-level exposures. The gene regulation behavior of high-level Li + resembled prior studies due to its influence on: inositol synthesis, 1-aminocyclopropane-1-carboxylate synthases and membrane ion transport. In contrast, chronically-exposed plants had gene regulation responses that were indicative of pathogen, cold, and heavy-metal stress, cell wall degradation, ethylene production, signal transduction, and calcium-release modulation. Acute Li + exposure phenocopies magnesium-deficiency symptoms and is associated with elevated expression of stress response genes that could lead to consumption of metabolic and transcriptional energy reserves and the dedication of more resources to cell development. In contrast, chronic Li + exposure increases expression signal transduction genes. The identification of new Li + -sensitive genes and a gene-based “response plan” for acute and chronic Li + exposure are delineated.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Prenatal cadmium exposure alters postnatal immune cell development and function

Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can result in long term detrimental effects on the immune system of the offspring and these effects are to some extent sex-specific. -- Highlights: ► Prenatal exposure to Cd causes no thymocyte phenotype changes in the offspring ► Analysis of the splenocyte phenotype demonstrates a macrophage-specific effect only in male offspring ► The cytokine profiles suggest an effect on peripheral Th1 cells in female and to a lesser degree in male offspring ► There was a marked increase in serum anti-streptococcal antibody levels after immunization in both sexes ► There was a marked decrease in the numbers of splenic CD8{sup +}CD223{sup +} cells in both sexes.

60 APPLIED LIFE SCIENCES↗

Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation. - Highlights: • An acute exposure to ROFA triggers the occurrence of systemic oxidative stress. • Changes in plasmatic oxidative stress markers appear as early as 1 h after exposure. • ROFA induces proinflammatory cytokines release and intravascular leukocyte activation. • PMN activation is a relevant source of reactive oxygen species in this model. • These findings may account for previously described cardiopulmonary alterations.

60 APPLIED LIFE SCIENCES↗

Blood morphology and the levels of selected cytokines related to hematopoiesis in occupational short-term exposure to lead

The aim of the study was to investigate the influence of a short-term exposure to lead on the blood morphology and the levels of selected cytokines related to hematopoiesis in occupationally exposed workers. The study population included 37 males occupationally exposed to lead for 36 to 44 days. Their blood lead level raised from 10.7 ± 7.67 μg/dl at baseline to the level of 49.1 ± 14.1 μg/dl at the end of the study. The level of hemoglobin and values of MCH and MCHC were decreased due to a short-term exposure to lead by 2%, 2%, and 1%, respectively. The counts of WBC, LYM, and MXD increased significantly by 5%, 7%, and 35%. Similarly, the count of PLT increased by 7%, while PDW, MPV, and P-LCR decreased by 6%, 3%, and 9%, respectively. The levels of IL-7, G-CSF, HGF, PDGF AB/BB, SCF, and PECAM-1, decreased significantly by 30%, 33%, 8%, 30%, 25%, and 20%, respectively. A short-term occupational exposure to lead results in a decreased hemoglobin level and increased counts of WBC and PLT. Changes in counts and proportions of different types of leukocytes and decreased values of PLT indices, such as PDW, MPV, and P-LCR, due to the subacute lead-exposure may be associated with lead-induced decreased levels of cytokines related to hematopoiesis, including SCF, G-CSF, IL-7, and PDGF. - Highlights: • Subacute exposure to lead results in a decreased hemoglobin level. • Subacute exposure to lead results in increased counts of WBC and PLT. • Subacute exposure to lead decreases the levels of SCF, G-CSF, IL-7, and PDGF.

60 APPLIED LIFE SCIENCES↗

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. - Highlights: • Prenatal exposure to a phthalate mixture disrupts F1 estrous cyclicity. • Prenatal exposure to a phthalate mixture induces F1 ovarian cysts. • Prenatal exposure to a phthalate mixture decreases F1 female fertility-related indices. • Prenatal exposure to a phthalate mixture induces F1 breeding complications.

60 APPLIED LIFE SCIENCES↗

Estimating the Acute Health Impacts of Fire-Originated PM 2.5 Exposure During the 2017 California Wildfires: Sensitivity to Choices of Inputs

Exposure to wildfire smoke increases the risk of respiratory and cardiovascular hospital admissions. Health impact assessments, used to inform decision-making processes, characterize the health impacts of environmental exposures by combining preexisting epidemiological concentration–response functions (CRFs) with estimates of exposure. These two key inputs influence the magnitude and uncertainty of the health impacts estimated, but for wildfire-related impact assessments the extent of their impact is largely unknown. We first estimated the number of respiratory, cardiovascular, and asthma hospital admissions attributable to fire-originated PM 2.5 exposure in central California during the October 2017 wildfires, using Monte Carlo simulations to quantify uncertainty with respect to the exposure and epidemiological inputs. We next conducted sensitivity analyses, comparing four estimates of fire-originated PM 2.5 and two CRFs, wildfire and nonwildfire specific, to understand their impact on the estimation of excess admissions and sources of uncertainty. We estimate the fires accounted for an excess 240 (95% CI: 114, 404) respiratory, 68 (95% CI: -10, 159) cardiovascular, and 45 (95% CI: 18, 81) asthma hospital admissions, with 56% of admissions occurring in the Bay Area. Although differences between impact assessment methods are not statistically significant, the admissions estimates' magnitude is particularly sensitive to the CRF specified while the uncertainty is most sensitive to estimates of fire-originated PM 2.5 . Not accounting for the exposure surface's uncertainty leads to an underestimation of the uncertainty of the health impacts estimated. Employing context-specific CRFs and using accurate exposure estimates that combine multiple data sets generates more certain estimates of the acute health impacts of wildfires.

58 GEOSCIENCES↗

RECONSTRUCTION OF INDIVIDUAL DOSES DUE TO MEDICAL EXPOSURES FOR MEMBERS OF THE TECHA RIVER COHORT

Purpose: To describe a methodology for reconstruction of doses due to medical exposures for members of the Techa River Cohort (TRC) who received diagnostic radiation at the clinic of the Urals Research Center for Radiation Medicine (URCRM) in 1952–2005. To calculate doses of medical exposure for the TRC members and compare with the doses that resulted from radioactive contamination of the Techa River. Material and Methods: Reconstruction of individual medical doses is based on data on x-ray diagnostic procedures available for each person examined at the URCRM clinics and values of absorbed dose in 12 organs per typical x-ray procedure calculated with the use of a mathematical phantom. Personal data on x-ray diagnostic examinations have been complied in the computerized “Registry of x-ray diagnostic procedures.” Sources of information are archival registry books from the URCRM x-ray room (available since 1956) and records on x-ray diagnostic procedures in patient-case histories (since 1952). The absorbed doses for 12 organs of interest have been evaluated per unit typical x-ray procedure with account taken of the x-ray examination parameters characteristic for the diagnostic machines used at the URCRM clinics. These parameters have been evaluated from published data on technical characteristics of the x-ray diagnostic machines used at the URCRM clinics in 1952–1988 and taken from the x-ray room for machines used at the URCRM in 1989–2005. Absorbed doses in the 12 organs per unit typical x-ray procedure have been calculated with use of a special computer code, EDEREX, developed at the Saint-Petersburg Research Institute of Radiation Hygiene after Professor P.V. Ramzaev. Individual accumulated doses of medical exposure have been calculated with a computer code, MEDS (Medical Exposure Dosimetry System), specifically developed at the URCRM. Results: At present, the “Registry of x-ray diagnostic procedures” contains information on individual x-ray examinations for over 9,500 persons including 6,415 TRC members. Statistical analysis of the Registry data showed that the more frequent types of examinations were fluoroscopy and radiography of the chest and fluoroscopy of the stomach and the esophagus. Average absorbed doses accumulated by year 2005 calculated for the 12 organs varied from 4 mGy for testes to 40 mGy for bone surfaces. Maximum individual medical doses could reach 500–650 mGy and in some cases exceeded doses from exposure at the Techa River. Conclusions: For the first time the doses of medical exposure were calculated and analyzed for members of the Techa River Cohort who received diagnostic radiation at the URCRM clinics. These results are being used in radiation-risk analysis to adjust for this source of confounding exposure in the TRC.

dose reconstruction↗

Repetitive diacetyl vapor exposure promotes ubiquitin proteasome stress and precedes bronchiolitis obliterans pathology

Bronchiolitis obliterans (BO) is a devastating lung disease seen commonly after lung transplant but also seen following severe respiratory tract infection or chemical inhalation exposure. Diacetyl (DA; 2,3-butanedione), highly reactive alpha-diketone is known to cause BO when inhaled, however, the mechanisms of how inhalation exposure leads to BO development remains poorly understood. In the current work, we combined two clinically relevant models for studying the pathogenesis of DA-induced BO: (1) an in vivo rat model of repetitive DA vapor exposures with recovery and (2) an in vitro model of primary human airway epithelial cells exposed to pure DA vapors. Rats exposed to 5 consecutive days 200 parts-per-million DA 6 hrs per day had worsening survival, persistent hypoxemia, poor weight gain, and histologic evidence of BO 14 days after DA exposure cessation. At the end of exposure, increased expression of the ubiquitin stress protein, ubiquitin-C, accumulated within DA-exposed rat lung homogenates, localized primarily to the airway epithelium, the primary site of BO development, and did not occur in air-exposed controls. Lung proteasome activity increased concurrently after DA exposure. In primary human airway cultures, global proteomics analysis identified 519 significantly modified proteins in DA-exposed samples relative to controls with the ubiquitin proteasome system, endosomal reticulum transport, and the response to unfolded protein pathways being upregulated while cell-cell adhesion and oxidation-reduction pathways being downregulated in DA-exposed samples. Altogether, repetitive DA vapor exposure resulted in abundant protein damage, accumulation of polyubiquinated proteins, and ubiquitin proteasome stress prior to the development of chemical-induced BO pathology.

59 BASIC BIOLOGICAL SCIENCES↗

Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin, cytokeratin 8 and 18 was reduced in NES2Y/DDT. • Expression of HNRH1 and cytokeratin 18 was reduced in NES2Y/DDE.

54 ENVIRONMENTAL SCIENCES↗

Tracing fetal and childhood exposure to lead using isotope analysis of deciduous teeth

We report progress in using the isotopic composition and concentration of Pb in the dentine and enamel of deciduous teeth to provide a high resolution time frame of exposure to Pb during fetal development and early childhood. Isotope measurements (total Pb and {sup 208}Pb/{sup 206}Pb, {sup 207}Pb/{sup 206}Pb ratios) were acquired by laser ablation inductively coupled mass spectrometry at contiguous 100 micron intervals across thin sections of the teeth; from the outer enamel surface to the pulp cavity. Teeth samples (n=10) were selected from two cohorts of children, aged 5–8 years, living in NE England. By integrating the isotope data with histological analysis of the teeth, using the daily incremental lines in dentine, we were able to assign true estimated ages to each ablation point (first 2–3 years for molars, first 1–2 years for incisors+pre-natal growth). Significant differences were observed in the isotope composition and concentration of Pb between children, reflecting differences in the timing and sources of exposure during early childhood. Those born in 2000, after the withdrawal of leaded petrol in 1999, have the lowest dentine Pb levels (<0.2 µg Pb/g) with {sup 208}Pb/{sup 206}Pb (mean ±2σ: 2.126–2.079) {sup 208}Pb/{sup 206}Pb (mean ±2σ: 0.879–0.856) ratios that correlate very closely with modern day Western European industrial aerosols (PM{sub 10}, PM{sub 2.5}) suggesting that diffuse airborne pollution was probably the primary source and exposure pathway. Legacy lead, if present, is insignificant. For those born in 1997, dentine lead levels are typically higher (>0.4 µgPb/g) with {sup 208}Pb/{sup 206}Pb (mean ±2σ: 2.145–2.117) {sup 208}Pb/{sup 206}Pb (mean ±2σ: 0.898–0.882) ratios that can be modelled as a binary mix between industrial aerosols and leaded petrol emissions. Short duration, high intensity exposure events (1–2 months) were readily identified, together with evidence that dentine provides a good proxy for childhood changes in the isotope composition of blood Pb. Our pilot study confirms that laser ablation Pb isotope analysis of deciduous teeth, when carried out in conjunction with histological analysis, permits a reconstruction of the timing, duration and source of exposure to Pb during early childhood. With further development, this approach has the potential to study larger cohorts and appraise environments where the levels of exposure to Pb are much higher. - Highlights: • Reconstructing a high resolution chronology of early childhood exposure to lead. • Combined laser ablation lead isotope – histological analysis of children's teeth. • Using dentine to recover information on the intensity, duration and source of lead. • Importance of industrial airborne lead pollution in a post-leaded petrol era.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗