Application of Covalent Binding Body Burden in the HµREL Human Hepatocyte Coculture Model for Reactivity Risk Assessment of Metabolically Low Turnover Drugs.

The human hepatocyte suspension model has been a valuable tool to study covalent binding (CVB) for compounds that form reactive metabolites. However, accurately measuring CVB values with the suspension model becomes challenging for metabolically low turnover compounds. In this study, we evaluated the HµREL human hepatocyte coculture model relative to existing literature using human hepatocyte suspension for drugs of known drug-induced liver injury category. Our results indicate that this coculture model provides ample metabolic turnover to reproducibly measure CVB. It is sufficiently robust to apply a predefined 1 mg/day CVB body burden threshold for risk assessment to guide our discovery programs, allowing for expanded coverage to include metabolically low turnover compounds.

Total body burden of neurotoxicant Hg in Chinese mitten crab (Eriocheir sinensis) - Considerations of distribution and human risk assessment.

The Chinese mitten crab (Eriocheir sinensis) is considered one of the 100 most invasive alien species in the world. Despite this, its role in ecosystems, among others, in the trophodynamics of pollutants including mercury, is still not fully understood. Becoming an increasingly important and widespread element of the trophic chain in new areas arouses interest from humans as consumers. Hence it is important to determine the level of contaminants (including Hg) in alien species. In the present study, great attention was paid separately to the soft tissues and hard tissues of the exoskeleton, which may play an important role in the detoxification of the crab's body from toxic Hg. The study was conducted on crabs collected in 2011-2021 in the Vistula Lagoon. Concentrations of total mercury and its forms were carried out using a Direct Mercury Analyzer, DMA-80 (Milestone, Italy). The present study showed that mercury accumulation of the crab's body largely occurred through the gills, followed by the oral route. The distribution of Hg in the crab's organs was related to the trophic origin of the mercury, while halide-bound mercury and semilabile forms from the respiration (filtration) process were redistributed into the crab's exoskeleton. Male crabs, compared to females, had a higher Hg burden on internal organs such as their hepatopancreas and gonads. Hg concentration in hard tissues was closely related to the type of mineralization of the carapace. The elimination of Hg from the muscles and from the hepatopancreas into the carapace was one of the important detoxification processes of the crab's body. Thus, moulting crabs effectively remove Hg protecting its body from the neurotoxin. As a result, a smaller Hg load is biomagnified, making the crab's muscle tissue fit for human consumption. The observed decrease in Hg concentrations from 2011 to 2021, as well as the spatial variability of Hg in the crab's muscles, testify that the crab can serve as a biomonitor for ecosystem changes.

An impact-based environmental risk assessment model toolbox for offshore produced water discharges.

We present a novel approach to environmental risk assessment of produced water discharges based on explicit impact and probability, using a combination of transport, fate and toxicokinetic-toxicodynamic models within a super-individual framework, with a probabilistic element obtained from ensemble simulations. Our approach is motivated by a need for location and species specific tools which also accounts for the dynamic nature of exposure and uptake of produced water components in the sea. Our approach is based on the well-established fate model DREAM, and accounts for time-variable exposure, considers body burden and effects for specific species and stressors, and assesses the probability of impact. Using a produced water discharge in the Barents Sea, with early life stages of spawning haddock, we demonstrate that it is possible to conduct a model-based risk assessment that highlights the effect of natural variations in environmental conditions. The benefits, limitations and potential for further improvements are discussed.

Arsenic and toxic metals in meat and fish consumed in Niger delta, Nigeria: Employing the margin of exposure approach in human health risk assessment.

This study provides information on the health risk of As, Cd, Hg, Pb and V exposure from Nigerian foods consumption (fish, cow, goat and chicken meat) in different age-groups (children, adolescent, adult, senior) and six areas of Niger Delta, Nigeria (Choba, Khana, Eleme, TransAmadi, Uyo, and Yenogoa). The health risk assessment was performed by estimating the weekly or monthly intake of metals from foods and Margin of Exposure (MOE) approach by using established benchmark dose levels (BMDLs). Regarding As, cow and chicken meat products contributed to As exposure intake especially in children resulting in values higher than BMDL0.1 for cancer risk in TransAmadi and Uyo areas. Cadmium exposure was due to cow, chicken and goat meat ingestion mostly in adolescent above the tolerable monthly intake limit in TransAmadi and Uyo areas. Concerning Hg and V, the exposure from Nigerian food did not constitute a potential health hazard. Lead exposure in children were above or close to BMDL0.1 for developmental neurotoxicity by ingestion of cow and goat meat in all the Nigerian areas. In adult and senior the Pb dietary exposure were above the BMDL10 providing a low to negligible risk for kidney effects. The potential concern for health effects in Niger Delta population needs further efforts to decrease As, Cd and Pb dietary exposure especially for children and adolescent, who are more vulnerable to adverse life events.

Exposure Assessment of Multiple Mycotoxins and Cumulative Health Risk Assessment: A Biomonitoring-Based Study in the Yangtze River Delta, China.

The extensive exposure to multiple mycotoxins has been demonstrated in many countries; however, realistic assessments of the risks related to cumulative exposure are limited. This biomonitoring study was conducted to investigate exposure to 23 mycotoxins/metabolites and their determinants in 227 adults (aged 20-88 years) in the Yangtze River Delta, China. Eight mycotoxins were detected in 110 urine samples, and multiple mycotoxins co-occurred in 51/227 (22.47%) of urine samples, with deoxynivalenol (DON), fumonisin B1 (FB1), and zearalenone (ZEN) being the most frequently occurring. For single mycotoxin risk assessment, FB1, ZEN, aflatoxin B1 (AFB1), and ochratoxin A (OTA) all showed potential adverse effects. However, for the 12 samples containing DON and ZEN, in which none had a hazard risk, the combination of both mycotoxins in two samples was considered to pose potential endocrine disrupting risks to humans by hazard index (HI) method. The combined margin of exposure (MOET) for AFB1 and FB1 could constitute a potential health concern, and AFB1 was the main contributor. Our approach provides a blueprint for evaluating the cumulative risks related to different types of mycotoxins and opens a new horizon for the accurate interpretation of epidemiological health outcomes related to multi-mycotoxin exposure.

EXPOSURE LEVELS OF UKRAINIAN POPULATION IN THE CONTEXT OF AN ACTION PLAN TO REDUCE INDOOR RADON LEVELS. / RIVNI OPROMINENNIa NASELENNIa UKRAÏNY V KONTEKSTI PLANU DII ShchODO ZMENShENNIa RIVNIV RADONU V POVITRI PRYMIShchEN'.

OBJECTIVE: To analyze and evaluate the available information to indoor radon concentration in the context of theimplementation of the radon action plan. OBJECT OF STUDY: indoor radon-222 in dwellings by area and corresponding radiation risks of the population. Measurements were performed using passive track radonometry. The exposure time of the radonometers is atleast 30 days during heating season. Radiation risk calculations were performed according to the dose coefficientsand mathematical models of the ICRP. RESULTS: It was found that for the whole country, reference level 300 Bq/m3 (radon gas) is exceeded in 16 % ofcases. It was found that geometric mean of radon gas levels was 120 Bq/m3 and varies from 35 to 265 Bq/m3 bydifferent area, namely the difference between radon levels in different territories of the country can be up to 7.5times. Variability of radon levels at the district level is also significant. It was found, radon activity concentrationdiffering by almost 10 times by districts with lognormal distribution and a geometric mean of 75 Bq/m3. The analy-sis of radiation risks of the population has established that estimated annual number of lung cancer deaths due toradon in Ukraine is almost 8,900 cases; and а direct economic loss for the country are estimated at more than $450 million a year. CONCLUSIONS: Surveys of radon levels demonstrated significant variation in radon concentrations between different regions. For the whole country, reference level (300 Bq/m3) is exceeded on above 16 % of the dwellings, butpercentage of exceeding varies from 0.1 to 43.0 % by different area. Information on indoor radon concentrationsin almost a third of the country is non-available. For an effective implementation of the Action plan, it makes sense to introduce radon risk mapping.

INTEGRATED ASSESSMENT OF THE DEMOGRAPHIC STATE OF RADIOLOGICALLY CONTAMINATED AREAS OF UKRAINE. / INTEGRAL'NE OTsINIuVANNIa DEMOGRAFIChNOGO STANU RADIOAKTYVNO ZABRUDNENYKh TERYTORII UKRAÏNY.

OBJECTIVE: Basing on the integrated assessment to conduct a comparative statistical analysis as of 2016 of thedemographic state of the areas of Ukraine that are recognized as those with the most intensive radiological con-tamination due to the Chornobyl NPP accident.Study object. The population of the regions of Ukraine with the most intensive radiological contamination due tothe Chornobyl NPP accident and the population of Ukraine as a whole (control). MATERIALS AND METHODS: The data of the State Statistics Service of Ukraine and its regional offices were used asinformation base in this study. Integrated assessment of the demographic situation in a oblast was conducted basedon the calculations of the territorial indices and multidimensional average variable on each region. Demographic,mathematical-statistical, graphic, software-technological methods were used in this study. RESULTS AND CONCLUSION: Radiologically contaminated regions of Ukraine differ significantly: both by the number ofpopulation (from 5800 people in the Poliske region to 105100 people in the Sarny region), and by the variability inthemedical and demographic indicators; bothone from another and compared to data for the country.The results of the calculations of 10 medical and demographic («positive¼ and «negative¼) territorial indices andmultidimensional average variable (P) as integrative assessment of the demographic state have revealed that thebest indicators of the demographic situation in 2016 were in Rokytne (P = 1.249) and Sarny (P = 1.112) regions ofthe Rivne oblast, while the worse indicators were in Kozelets (P = 0.363) and Ripky regions of the Chernihiv oblast.The demographic situation of the Olevsk region of the Zhytomyr oblast (P = 0.947)was the closest to the nationalaverage one. Poliske, Narodychi, Ovruch, Ivankiv and Korosten regions take intermediate position as comparedto theregions of Rivne and Chernihiv oblasts (P = 0.618-0.742).

Human biomonitoring initiative (HBM4EU) - Strategy to derive human biomonitoring guidance values (HBM-GVs) for health risk assessment.

The European Joint Program "HBM4EU" is a joint effort of 30 countries and the European Environment Agency, co-funded under the European Commission's Horizon 2020 program, for advancing and implementing human biomonitoring (HBM) on a European scale and for providing scientific evidence for chemical policy making. One important outcome will be a Europe-wide improvement and harmonization of health risk assessment following the coordinated derivation or update of health-related guidance values referring to the internal body burden. These guidance values - named HBM guidance values or HBM-GVs - can directly be compared with HBM data. They are derived within HBM4EU for priority substances identified by the HBM4EU chemicals prioritization strategy based on existing needs to answer policy relevant questions as raised by national and EU policy makers. HBM-GVs refer to both the general population and occupationally exposed adults. Reports including the detailed reasoning for the values' proposals are subjected to a consultation process within all partner countries of the consortium to reach a broad scientific consensus on the derivation approach and on the derived values. The final HBM-GVs should be applied first within the HBM4EU project, but may also be useful for regulators and risk assessors outside this project. The subsequent adoption of derived HBM-GVs at EU-level needs to be discussed and decided within the responsible EU bodies. Nevertheless, the establishment of HBM-GVs as part of HBM4EU is already a step forward in strengthening HBM-based policy efforts for public and occupational health. The strategy for deriving HBM-GVs which is based on already existing approaches from the German HBM Commission, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) as well as from the US-based scientific consultant Summit Toxicology, the allocation of a level of confidence to the derived values, and the consultation process within the project are comprehensively described to enlighten the work accomplished under the HBM4EU initiative.

Liposome-mediated delivery of challenging chemicals to aid environmental assessment of Bioaccumulative (B) and Toxic (T) properties.

Standard aquatic toxicity tests of chemicals are often limited by the chemicals' water solubility. Liposomes have been widely used in the pharmaceutical industry to overcome poor pharmacokinetics and biodistribution. In this work, liposomes were synthesized and used in an ecotoxicological context, as a tool to assure stable dosing of technically challenging chemicals to zooplankton. Three chemicals with distinctly different characteristics were successfully incorporated into the liposomes: Tetrabromobisphenol A (TBBPA, log Kow 5.9, pKa1 7.5, pKa2 8.5), chlorinated paraffin CP-52 (log Kow 8-12) and perfluorooctanoic acid (PFOA, pKa 2.8). The size, production yield and stability over time was similar for all blank and chemical-loaded liposomes, except for when the liposomes were loaded with 10 or 100 mg g-1 PFOA. PFOA increased the size and decreased the production yield and stability of the liposomes. Daphnia magna were exposed to blank and chemical-loaded liposomes in 48 hour incubation experiments. A dose-dependent increase in body burden in D. magna and increased immobilization (LD50 = 7.6 ng CPs per individual) was observed. This confirms not only the ingestion of the liposomes but also the successful internalization of chemicals. This study shows that liposomes can be a reliable alternative to aid the study of aquatic toxicity of challenging chemicals.

Internal exposure rate conversion coefficients and absorbed fractions of mouse for 137Cs, 134Cs and 90Sr contamination in body.

The aim of this study was to determine parameters for estimating the internal exposure of all organs in mouse experiments from the radioactivity concentration in organs. The estimation of internal exposure rate conversion coefficients and absorbed fractions for 137Cs, 134Cs and 90Sr by the Particle and Heavy Ion Transport code System (PHITS) with a voxel-based mouse phantom is presented. The geometry of the voxel phantom is constructed from computer tomography images of a mouse 9 cm in length weighing 23.9 g. The voxel-based mouse phantom has the following organs: brain, skull, heart, lungs, liver, stomach, spleen, kidneys, bladder, testis and tissue (tissue and other organs). Gamma- and beta-rays from 137Cs, 134Cs and 90Sr sources in each source organ are generated and scored for every target organ. The internal exposure rate conversion coefficients and absorbed fractions are calculated from deposition energies in each target organ from each source organ and are used to generate an internal exposure rate conversion coefficient matrix and an absorbed fraction matrix. The absorbed fractions of beta-rays in the source organs are roughly 0.5-0.8 for 137Cs and 134Cs, and the absorbed fractions of gamma-rays are <0.04 for 137Cs and <0.03 for 134Cs. The internal exposure rate conversion coefficient matrix is defined using the absorbed fractions. The calculated internal exposure rate coefficient matrix is tested under a uniform radioactivity concentration of 1 Bq/kg for 137Cs, 134Cs and 90Sr. The estimated internal exposure rates in the mouse whole body for 137Cs, 134Cs and 90Sr are 3.28 × 10-3, 2.55 × 10-3 and 1.20 × 10-2 µGy/d, respectively. These values are very similar to those for an ellipsoid frog (31.4 g) and an ellipsoid crab egg mass (12.6 g) reported in ICRP Publication 108.

Multi-media biomarkers: Integrating information to improve lead exposure assessment.

Exposure assessment traditionally relies on biomarkers that measure chemical concentrations in individual biological media (i.e., blood, urine, etc.). However, chemicals distribute unevenly among different biological media; thus, each medium provides incomplete information about body burden. We propose that machine learning and statistical approaches can create integrated exposure estimates from multiple biomarker matrices that better represent the overall body burden, which we term multi-media biomarkers (MMBs). We measured lead (Pb) in blood, urine, hair and nails from 251 Italian adolescents aged 11-14 years from the Public Health Impact of Metals Exposure (PHIME) cohort. We derived aggregated MMBs from the four biomarkers and then tested their association with Wechsler Intelligence Scale for Children (WISC) IQ scores. We used three approaches to derive the Pb MMB: one supervised learning technique, weighted quantile sum regression (WQS), and two unsupervised learning techniques, independent component analysis (ICA) and non-negative matrix factorization (NMF). Overall, the Pb MMB derived using WQS was most consistently associated with IQ scores and was the only method to be statistically significant for Verbal IQ, Performance IQ and Total IQ. A one standard deviation increase in the WQS MMB was associated with lower Verbal IQ (ß [95% CI] = -2.2 points [-3.7, -0.6]), Performance IQ (-1.9 points [-3.5, -0.4]) and Total IQ (-2.1 points [-3.8, -0.5]). Blood Pb was negatively associated with only Verbal IQ, with a one standard deviation increase in blood Pb being associated with a -1.7 point (95% CI: [-3.3, -0.1]) decrease in Verbal IQ. Increases of one standard deviation in the ICA MMB were associated with lower Verbal IQ (-1.7 points [-3.3, -0.1]) and lower Total IQ (-1.7 points [-3.3, -0.1]). Similarly, an increase of one standard deviation in the NMF MMB was associated with lower Verbal IQ (-1.8 points [-3.4, -0.2]) and lower Total IQ (-1.8 points [-3.4, -0.2]). Weights highlighting the contributions of each medium to the MMB revealed that blood Pb was the largest contributor to most MMBs, although the weights varied from more than 80% for the ICA and NMF MMBs to between 30% and 54% for the WQS-derived MMBs. Our results suggest that MMBs better reflect the total body burden of a chemical that may be acting on target organs than individual biomarkers. Estimating MMBs improved our ability to estimate the full impact of Pb on IQ. Compared with individual Pb biomarkers, including blood, a Pb MMB derived using WQS was more strongly associated with IQ scores. MMBs may increase statistical power when the choice of exposure medium is unclear or when the sample size is small. Future work will need to validate these methods in other cohorts and for other chemicals.

Antibiotic body burden of elderly Chinese population and health risk assessment: A human biomonitoring-based study.

Recently, the widespread use of antibiotic has raised concerns about the potential health risks associated with their microbiological effect. In the present study, we investigated 990 elderly individuals (age ≥ 60 years) from the Cohort of Elderly Health and Environment Controllable Factors in West Anhui, China. A total of 45 representative antibiotics and two antibiotic metabolites were monitored in urine samples through liquid chromatography electrospray tandem mass spectrometry. The results revealed that 34 antibiotics were detected in 93.0% of all urine samples and the detection frequencies of each antibiotic varied between 0.2% and 35.5%. The overall detection frequencies of seven human antibiotics (HAs), 10 veterinary antibiotics (VAs), three antibiotics preferred as HAs (PHAs), and 14 preferred as VAs (PVAs) in urines were 27.4%, 62.9%, 30.9% and 72.7%, respectively. Notably, the samples with concentrations of six PVAs (sulfamethoxazole, trimethoprim, oxytetracycline, danofloxacin, norfloxacin and lincomycin) above 5000 ng/mL accounted for 1.7% of all urine samples. Additionally, in 62.7% of urine samples, the total antibiotic concentration was in the range of the limits of detection to 20.0 ng/mL. Furthermore, the elderly individuals with the sum of estimated daily intakes of VAs and PVAs more than 1 µg/kg/day accounted for 15.2% of all participants, and a health risk related to change in gut microbiota under antibiotic stimulation was expected in 6.7% of the elderly individuals. Especially, ciprofloxacin was the foremost contributor to the health risk, and its hazard quotient value was more than one in 3.5% of all subjects. Taken together, the elderly Chinese people were extensively exposed to VAs, and some elderly individuals may have a health risk associated with dysbiosis of the gut microbiota.

Multicenter biomonitoring of polybrominated diphenyl ethers (PBDEs) in colostrum from China: Body burden profile and risk assessment.

Polybrominated diphenyl ethers (PBDEs) were listed in the Stockholm Convention due to their persistent and toxic nature. In utero exposure to PBDEs might affect fetal development as it is sensitive when exposed to even low dose of xenobiotic substances during the pregnancy. In this study, a multi-centre human biomonitoring study of tri-to hexa-BDEs was conducted in three Chinese cities using 60 colostrum samples from local residents. The patterns and influencing factors, correlation with the birth outcome, and potential health risks during the breastfeeding of tri-to hexa-BDEs in the colostrum samples were assessed. The median concentration of tri-to hexa-BDEs was 9.1 (Interquartile range: 3.1-19.5) ng g-1 lipid weight, and BDE-153 contributed 68% of the detected PBDEs. The PBDE levels were mostly associated with maternal age and drinking water sources, while correlations with other factors including weight gain, BMI, parity and the number of aborted pregnancies was not significant. The level of BDE-28 was positively correlated with the birth weight, while the BDE-99 was positively correlated with the head circumference, using multilinear regression. For the total hazard quotients, 60% of the infants have an estimated value higher than 1, showed potential chronic hazard for future development and possible adverse health effects to the babies from the exposure to PBDE congeners. Alternative food source seems to have a lower risk for neonates than the colostrum, but the advantages of breastfeeding undoubtedly outweigh the risks and potential adverse health effects caused by environmental PBDEs and other xenobiotic chemical exposure.

Unsafe herbal sex enhancement supplements in Nigerian markets: a human risk assessment.

High rates of irreversible oligo- or azoospermia are found among Nigerian men, leading many to consume herbal male sex enhancement products. The possibility of reproductive toxicity due to heavy metal contamination (Cr, As, Co, Hg, Cd, and Pb) of herbal products commonly used to boost libido or treat erectile dysfunction necessitated this study. In this study, herbal sex enhancement supplements were bought from pharmaceutical shops in Port Harcourt, Nigeria, and analyzed for heavy metals (Cr, As, Co, Hg, Cd, and Pb) contents using atomic absorption spectroscopy. The estimated daily metal intake (EDImetal), target hazard quotients (THQ), and total target hazard quotients (TTHQ) were determined. All the herbal sex enhancers used in this study contained heavy metals in these ranges: lead (0.032-0593), cobalt (0.025-0.075), cadmium (0.0011-0.048), and chromium (0.016-0.49) mg/kg. About 24.32% of the samples had TTHQ greater than 1. The EDImetal, THQ, and TTHQ of herbal sex enhancement supplements suggest that the use of some of these herbal sex enhancement supplements may not be risk-free after chronic exposure. Herbal sex enhancement supplements sold in Nigeria contain high levels of lead and cadmium. Since these metals are known to have male reproductive toxicity, these supplements may be adding to both the body burden of these metals and also implicated in the increasing incidence of male infertility in Nigeria.

INTERCOMPARISON ON INTERNAL DOSE ASSESSMENT FOR NUCLEAR POWER PLANTS IN KOREA.

The intercomparison test is a quality assurance activity performed for internal dose assessment. In Korea, the intercomparison test on internal dose assessment was carried out for nuclear facilities in May 2018. The test involved four nuclear facilities in Korea, and seven exposure scenarios were applied. These scenarios cover the intake of 131I, a uranium mixture, 60Co and tritium under various conditions. This paper only reviews the participant results of three scenarios pertinent to the operation of nuclear power plants and adopts the statistical evaluation method, used in international intercomparison tests, to determine the significance values of the results. Although no outliers were established in the test, improvements in the internal dose assessment procedure were derived. These included the selection of intake time, selection of lung absorption type according to the chemical form and consideration of the contribution of previous intake.

Novel risk assessment of reactive metabolites from discovery to clinical stage.

This study was aimed to predict drug-induced liver injury caused by reactive metabolites. Reactive metabolites covalently bind to proteins and could result in severe outcomes in patients. However, the relation between the extent of covalent binding and clinical hepatotoxicity is still unclear. From a perspective of body burden (human in vivo exposure to reactive metabolites), we developed a risk assessment method in which reactive metabolite burden (RM burden), an index that could reflect the body burden associated with reactive metabolite exposure, is calculated using the extent of covalent binding, clinical dose, and human in vivo clearance. The relationship between RM burden and hepatotoxicity in humans was then investigated. The results indicated that this RM burden assessment exhibited good predictability for sensitivity and specificity, and drugs with over 10 mg/day RM burden have high-risk for hepatotoxicity. Furthermore, a quantitative trapping assay using radiolabeled trapping agents ([35S]cysteine and [14C]KCN) was also developed, to detect reactive metabolite formation in the early drug discovery stage. RM burden calculated using this assay showed as good predictability as RM burden calculated using conventional time- and cost-consuming covalent binding assays. These results indicated that the combination of RM burden and our trapping assay would be a good risk assessment method for reactive metabolites from the drug discovery stage.

S VALUES FOR NEUROIMAGING PROCEDURES ON KOREAN PEDIATRIC AND ADULT HEAD COMPUTATIONAL PHANTOMS.

Over the past decades, the application of single-photon emission computed tomography and positron emission tomography in neuroimaging has markedly increased. In the current study, we used a series of Korean computational head phantoms with detailed cranial structures for 6-, 9-, 12-, 15-y-old children and adult and a Monte Carlo transport code, MCNPX, to calculate age-dependent specific absorbed fraction (SAF) for mono-energetic electrons ranging from 0.01 to 4 MeV and S values for seven radionuclides widely used in nuclear medicine neuroimaging for the combination of ten source and target regions. Compared to the adult phantom, the 6-y phantom showed up to 1.7-fold greater SAF (cerebellum < cerebellum) and up to 1.4-fold greater S values (vitreous body < lens) for 123I. The electron SAF data, combined with our previous photon SAF data, will facilitate absorbed dose calculations for various cranial structures in patients undergoing neuroimaging procedures.

CALIBRATION OF LOW ENERGY X-RAY EXPERIMENTAL SETUP WITH STRONGLY FILTERED BEAM USING DATA FROM A SEMICONDUCTOR AND A THERMOLUMINESCENT DETECTORS.

The calibration of low energy X-ray experimental setup with strongly filtered beam dedicated to radiobiological research was performed using the absorbed dose calculated from the data collected by two types detectors. For this purpose a semiconductor (Amptek, USA) and a thermoluminescent (Institute of Nuclear Physics, Krakow, Poland) detectors were applied. The absorbed dose in water values estimated by both detectors are in good agreement.

[Human Biomonitoring as a Useful Approach to Health Risk Assessment Compared with Occupational Exposure Assessment of Insecticide Intake: Fundamental Study Focused on Local Populations and Occupational Fields].

Human biomonitoring (HBM) is a technique to evaluate chemical exposure level by measuring the levels of chemicals or related substances such as their metabolites or adducts in biological samples (e.g., urine or blood). Compared with exposure assessment by an approach to estimate insecticide intake from diet or the environment, HBM can provide information more specific to an individual exposure dose and can reflect the exact body burden condition at the time of measurement. If the analytical sensitivities, completeness and cost-effectiveness of the method are improved further, HBM might be widely applicable to not only research fields such as epidemiological and occupational study but also routine analysis for effective prevention of the exposure of the human body to chemical substances. In this article, we provide an overview of HBM as a determination method for insecticide exposure markers in urine and its applications, and discuss future research perspectives in the field of environmental and occupational health.

Systematic developmental neurotoxicity assessment of a representative PAH Superfund mixture using zebrafish.

Superfund sites often consist of complex mixtures of polycyclic aromatic hydrocarbons (PAHs). It is widely recognized that PAHs pose risks to human and environmental health, but the risks posed by exposure to PAH mixtures are unclear. We constructed an environmentally relevant PAH mixture with the top 10 most prevalent PAHs (SM10) from a Superfund site derived from environmental passive sampling data. Using the zebrafish model, we measured body burden at 48 hours post fertilization (hpf) and evaluated the developmental and neurotoxicity of SM10 and the 10 individual constituents at 24 hours post fertilization (hpf) and 5 days post fertilization (dpf). Zebrafish embryos were exposed from 6 to 120 hpf to (1) the SM10 mixture, (2) a variety of individual PAHs: pyrene, fluoranthene, retene, benzo[a]anthracene, chrysene, naphthalene, acenaphthene, phenanthrene, fluorene, and 2-methylnaphthalene. We demonstrated that SM10 and only 3 of the individual PAHs were developmentally toxic. Subsequently, we constructed and exposed developing zebrafish to two sub-mixtures: SM3 (comprised of 3 of the developmentally toxicity PAHs) and SM7 (7 non-developmentally toxic PAHs). We found that the SM3 toxicity profile was similar to SM10, and SM7 unexpectedly elicited developmental toxicity unlike that seen with its individual components. The results demonstrated that the overall developmental toxicity in the mixtures could be explained using the general concentration addition model. To determine if exposures activated the AHR pathway, spatial expression of CYP1A was evaluated in the 10 individual PAHs and the 3 mixtures at 5 dpf. Results showed activation of AHR in the liver and vasculature for the mixtures and some individual PAHs. Embryos exposed to SM10 during development and raised in chemical-free water into adulthood exhibited decreased learning and responses to startle stimulus indicating that developmental SM10 exposures affect neurobehavior. Collectively, these results exemplify the utility of zebrafish to investigate the developmental and neurotoxicity of complex mixtures.