Bioassay Data Research Articles

ICRP Publication 141: Occupational Intakes of Radionuclides: Part 4.

The 2007 Recommendations (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979a,b, 1980a, 1981, 1988) and Publication 68 (ICRP, 1994b). In addition, new data are now available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1989a, 1997) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2 and its task groups. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. OIR Part 1 (ICRP, 2015) describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. OIR Part 2 (ICRP, 2016), OIR Part 3 (ICRP, 2017), this current publication, and the final publication in the OIR series (OIR Part 5) provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic models; and data on monitoring techniques for the radioisotopes most commonly encountered in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv per Bq intake) for inhalation and ingestion, tables of committed effective dose per content (Sv per Bq measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The online electronic files that accompany the OIR series of publications contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. This fourth publication in the OIR series provides the above data for the following elements: lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), promethium (Pm), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), lutetium (Lu), actinium (Ac), protactinium (Pa), neptunium (Np), plutonium (Pu), americium (Am), curium (Cm), berkelium (Bk), californium (Cf), einsteinium (Es), and fermium (Fm).

Comparisons of outlier tests for potency bioassays.

Potency bioassays are used to measure biological activity. Consequently, potency is considered a critical quality attribute in manufacturing. Relative potency is measured by comparing the concentration-response curves of a manufactured test batch with that of a reference standard. If the curve shapes are deemed similar, the test batch is said to exhibit constant relative potency with the reference standard, a critical requirement for calibrating the potency of the final drug product. Outliers in bioassay potency data may result in the false acceptance/rejection of a bad/good sample and, if accepted, may yield a biased relative potency estimate. To avoid these issues, the USP<1032> recommends the screening of bioassay data for outliers prior to performing a relative potency analysis. In a recently published work, the effects of one or more outliers, outlier size, and outlier type on similarity testing and estimation of relative potency were thoroughly examined, confirming the USP<1032> outlier guidance. As a follow-up, several outlier detection methods, including those proposed by the USP<1010>, are evaluated and compared in this work through computer simulation. Two novel outlier detection methods are also proposed. The effects of outlier removal on similarity testing and estimation of relative potency were evaluated, resulting in recommendations for best practice.

3,5–Bis(2–Hydroxyphenyl)–1H–1,2,4–Triazole Derivatives: Synthesis, Crystal Structure and Insecticidal Activity

AbstractIn an effort to discover new molecules with good insecticidal activities, a series of 3,5‐bis (2‐hydroxyphenyl)‐1H‐1,2,4‐triazole derivatives were synthesized. The X–ray crystallographic and Hirshfeld surface calculation study of compound 4 c reveal the structural characteristics and strong intermolecular interactions and also evaluated for it's insecticidal activity. The bioassays data demonstrate that all the target compounds possess remarkable activities against broad bean aphid with the mortalities ranging from 98.12% to 100% at the concentration of 100 mg/L. In particular, methyl 4‐[3,5‐bis(2–hydroxyphenyl)‐1H‐1,2,4‐triazol‐1‐yl] benzoate (85.53%) shows higher activity than dinotefuran (85.25%) at the concentration of 10 mg/L whereas other compounds display low activity at the same concentration. The docking model of compound 4a shows possible mechanism of insecticidal action of target compounds. These results indicate that 3,5−bis (2−hydroxyphenyl) ‐1H‐1,2,4–triazole derivatives could be developed as novel and promising insecticides.

Bioactivity Profiling of Small-Volume Samples by Nano Liquid Chromatography Coupled to Microarray Bioassaying Using High-Resolution Fractionation.

High-throughput screening platforms for the identification of bioactive compounds in mixtures have become important tools in the drug discovery process. Miniaturization of such screening systems may overcome problems associated with small sample volumes and enhance throughput and sensitivity. Here we present a new screening platform, coined picofractionation analytics, which encompasses microarray bioassays and mass spectrometry (MS) of components from minute amounts of samples after their nano liquid chromatographic (nanoLC) separation. Herein, nanoLC was coupled to a low-volume liquid dispenser equipped with pressure-fed solenoid valves, enabling 50-nL volumes of column effluent (300 nL/min) to be discretely deposited on a glass slide. The resulting fractions were dried and subsequently bioassayed by sequential printing of nL-volumes of reagents on top of the spots. Unwanted evaporation of bioassay liquids was circumvented by employing mineral oil droplets. A fluorescence microscope was used for assay readout in kinetic mode. Bioassay data were correlated to MS data obtained using the same nanoLC conditions in order to assign bioactives. The platform provides the possibility of freely choosing a wide diversity of bioassay formats, including those requiring long incubation times. The new method was compared to a standard bioassay approach, and its applicability was demonstrated by screening plasmin inhibitors and fibrinolytic bioactives from mixtures of standards and snake venoms, revealing active peptides and coagulopathic proteases.

Status of insecticide resistance and its biochemical and molecular mechanisms in Anopheles stephensi (Diptera: Culicidae) from Afghanistan

BackgroundInsecticide resistance of Anopheles stephensi, the main malaria vector in eastern Afghanistan, has been reported previously. This study describes the biochemical and molecular mechanisms of resistance to facilitate effective vector control and insecticide resistance management.MethodsMosquito larvae were collected from the provinces of Kunar, Laghman and Nangarhar from 2014 to 2017. The susceptibility of the reared 3–4 days old adults was tested with deltamethrin 0.05%, bendiocarb 0.1%, malathion 5%, permethrin 0.75% and DDT 4%. Cytochrome P450 content and general esterase, glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities were measured in the three field populations and the results were compared with those of the laboratory susceptible An. stephensi Beech strain. Two separate allele-specific PCR assays were used to identify L1014, L1014F and L1014S mutations in the voltage gated sodium channel gene of An. stephensi. Probit analysis, ANOVA and Hardy–Weinberg equilibrium were used to analyse bioassay, biochemical assay and gene frequency data respectively.ResultsThe population of An. stephensi from Kunar was susceptible to bendiocarb, apart from this, all populations were resistant to all the other insecticides tested. The differences between all values for cytochrome P450s, general esterases, GSTs and AChE inhibition rates in the Kunar, Laghman and Nangarhar populations were statistically significant when compared to the Beech strain, excluding GST activities between Kunar and Beech due to the high standard deviation in Kunar. The three different sodium channel alleles [L1014 (wild type), L1014F (kdr west) and L1014S (kdr east)] were all segregated in the Afghan populations. The frequencies of kdr east mutation were 22.9%, 32.7% and 35% in Kunar, Laghman and Nangarhar populations respectively. Kdr west was at the lowest frequency of 4.44%.ConclusionsResistance to different groups of insecticides in the field populations of An. stephensi from Kunar, Laghman and Nangarhar Provinces of Afghanistan is caused by a range of metabolic and site insensitivity mechanisms, including esterases, cytochrome P450s and GSTs combined with AChE and sodium channel target site insensitivity. The intensity and frequency of these mechanisms are increasing in these populations, calling for urgent reorientation of vector control programmes and implementation of insecticide resistance management strategies.

Quantitative in vitro-to-in vivo extrapolation (QIVIVE) of estrogenic and anti-androgenic potencies of BPA and BADGE analogues

The goal of the present study was to obtain an in vivo relevant prioritization method for the endocrine potencies of different polycarbonate monomers, by combining in vitro bioassay data with physiologically based kinetic (PBK) modelling. PBK models were developed for a selection of monomers, including bisphenol A (BPA), two bisphenol F (BPF) isomers and four different bisphenol A diglycidyl ethers (BADGEs), using in vitro input data. With these models, the plasma concentrations of the compounds were simulated, providing means to estimate the dose levels at which the in vitro endocrine effect concentrations are reached. The results revealed that, whereas the in vitro relative potencies of different BADGEs (predominantly anti-androgenic effects) can be up to fourfold higher than BPA, the estimated in vivo potencies based on the oral equivalent doses are one to two orders of magnitude lower than BPA because of fast detoxification of the BADGEs. In contrast, the relative potencies of 2,2-BPF and 4,4-BPF increase when accounting for the in vivo availability. 4,4-BPF is estimated to be fivefold more potent than BPA in humans in vivo in inducing estrogenic effects and both 2,2-BPF and 4,4-BPF are estimated to be, respectively, 7 and 11-fold more potent in inducing anti-androgenic effects. These relative potencies were considered to be first-tier estimates, particularly given that the potential influence of intestinal metabolism on the in vivo availability was not accounted for. Overall, it can be concluded that both 2,2-BPF and 4,4-BPF are priority compounds.

Effect of Chlorine and Temperature on Larvicidal Activity of Cuban Bacillus thuringiensis Isolates

The efficacy of biolarvicides may be influenced by species of mosquito, larval age and density, temperature, water quality, bacterial formulation, and others. The aim of this study was to evaluate the influence of temperature and chlorine on larvicidal activity of Bacillus thuringiensis Cuban isolates against Aedes aegypti. The influence of temperature (25, 30, 35 °C) and chlorine (2.25mg/L) on the larvicidal activity of eleven B. thuringiensis Cuban isolates (collected between 2007 and 2009) were tested under laboratory conditions following WHO protocols. Bioassay data were analyzed by Probit program. The effect of chlorine and temperature (25, 30, 35 and 40 °C) on the Cry and Cyt proteins of these isolates was determined by SDS-PAGE polyacrylamide gel electrophoresis. The pathogenicity of the isolates U81, X48 was affected at 35 °C. However, A21, A51, L910, and R89 isolates increase their entomopathogen activity at 35 °C. No differences were observed in toxicity of M29, R84, R85 and R87 isolates at different temperatures. The Cry 4, Cry 10 and Cry 11 proteins were reduced in A21, X48, R85 isolates at 35 and 40 °C. The Cyt proteins were reduced at 35 and 40 °C in A21, X48, R85, and A51 isolates. In L910 and R84 isolates, the Cyt toxin was degraded only at 40 °C. In chlorinated water, the lethal concentrations 50 and 90 in A21, A51, M29, R84, U81, and X48 isolates were increase. A21, A51, L910, R85, and X48 isolates have a strong larvicidal activity for the treatment of Ae. aegypti breeding's sites exposed to high temperature and chlorine.

The effect of quercetin and exercise in rat metabolic syndrome model

Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5-g]chromenones were synthesized featuring phenyl (7a-k) and chalcone (12a-k) bridge representing flavones or homoisoflavonoids core. New molecules are synthesized utilizing aldol condensation to inspect as antioxidants against DPPH and ABTS+ and antiproliferative agents toward selected human cancer cell lines. Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. The results concluded that both individual structures of 7 and 12 were vital for modulating pharmacological potencies and presence of different electron withdrawing and electron donating functional group(s) on the phenylsulfonyl entity yielded varied biological effects. Substituent h (OCF3) and j, k (OCH3) were found to play a crucial role scavenging DPPH and ABTS+ as well as inhibiting cancer cell lines SK-OV-3 and HT-29. Moreover, molecules bearing halogen atom(s) such as substituent b-g expressed excellent inhibitory potential against HeLa and A-549 cancerous cell lines. Bioassay data displayed some interesting structure-activity relationships which are discussed in this paper. The results justified that tested derivatives are promising antioxidants and cytotoxic agents and warrant further structural optimization and bioassay studies. Spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR and elemental analysis (CHN) were carried out to confirm the final structures.

Nonanimal Models for Acute Toxicity Evaluations: Applying Data-Driven Profiling and Read-Across.

Background:Low-cost, high-throughput in vitro bioassays have potential as alternatives to animal models for toxicity testing. However, incorporating in vitro bioassays into chemical toxicity evaluations such as read-across requires significant data curation and analysis based on knowledge of relevant toxicity mechanisms, lowering the enthusiasm of using the massive amount of unstructured public data.Objective:We aimed to develop a computational method to automatically extract useful bioassay data from a public repository (i.e., PubChem) and assess its ability to predict animal toxicity using a novel bioprofile-based read-across approach.Methods:A training database containing 7,385 compounds with diverse rat acute oral toxicity data was searched against PubChem to establish in vitro bioprofiles. Using a novel subspace clustering algorithm, bioassay groups that may inform on relevant toxicity mechanisms underlying acute oral toxicity were identified. These bioassays groups were used to predict animal acute oral toxicity using read-across through a cross-validation process. Finally, an external test set of over 600 new compounds was used to validate the resulting model predictivity.Results:Several bioassay clusters showed high predictivity for acute oral toxicity (positive prediction rates range from 62–100%) through cross-validation. After incorporating individual clusters into an ensemble model, chemical toxicants in the external test set were evaluated for putative acute toxicity (positive prediction rate equal to 76%). Additionally, chemical fragment–in vitro–in vivo relationships were identified to illustrate new animal toxicity mechanisms.Conclusions:The in vitro bioassay data-driven profiling strategy developed in this study meets the urgent needs of computational toxicology in the current big data era and can be extended to develop predictive models for other complex toxicity end points. https://doi.org/10.1289/EHP3614

Phenylsulfonyl piperazine bridged [1,3]dioxolo[4,5-g]chromenones as promising antiproliferative and antioxidant agents

Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5-g]chromenones were synthesized featuring phenyl (7a-k) and chalcone (12a-k) bridge representing flavones or homoisoflavonoids core. New molecules are synthesized utilizing aldol condensation to inspect as antioxidants against DPPH and ABTS+ and antiproliferative agents toward selected human cancer cell lines. Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. The results concluded that both individual structures of 7 and 12 were vital for modulating pharmacological potencies and presence of different electron withdrawing and electron donating functional group(s) on the phenylsulfonyl entity yielded varied biological effects. Substituent h (OCF3) and j, k (OCH3) were found to play a crucial role scavenging DPPH and ABTS+ as well as inhibiting cancer cell lines SK-OV-3 and HT-29. Moreover, molecules bearing halogen atom(s) such as substituent b-g expressed excellent inhibitory potential against HeLa and A-549 cancerous cell lines. Bioassay data displayed some interesting structure-activity relationships which are discussed in this paper. The results justified that tested derivatives are promising antioxidants and cytotoxic agents and warrant further structural optimization and bioassay studies. Spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR and elemental analysis (CHN) were carried out to confirm the final structures.

Baseline susceptibility of Bemisia tabaci MEAM1 (Hemiptera: Aleyrodidae) in Australia to spirotetramat, cyantraniliprole and dinotefuran, with reference to pyriproxyfen cross‐resistance

AbstractSilverleaf whitefly, Bemisia tabaci (Gennadius) Middle East‐Asia Minor 1 (MEAM1), previously known as B biotype, is an agricultural pest of global significance and has developed resistance to many commonly used insecticides. Toxicity of spirotetramat, cyantraniliprole and dinotefuran to B. tabaci MEAM1 populations from eastern Australia was determined by laboratory bioassay, using either a foliar leaf dip or systemic uptake methodology. All field‐collected populations tested were susceptible to spirotetramat (12 tested from 2011 to 2015), cyantraniliprole (23 tested from 2014 to 2017) and dinotefuran (16 tested from 2015 to 2017). Based on LC50 values, there was a 2.1‐fold difference in the response of field populations to spirotetramat, a threefold difference in response to cyantraniliprole, while the response to dinotefuran varied depending on assay used, 1.8 vs. 2.6 with a foliar assay and systemic uptake assay, respectively. Testing of spirotetramat and cyantraniliprole against a pyriproxyfen‐resistant strain, AY09‐1R demonstrated no evidence of cross‐resistance to pyriproxyfen. When tested against dinotefuran, AY09‐1R had a resistance factor of two indicating possible weak cross‐resistance to pyriproxyfen, although it is also possible that the strain carries other forms of resistance given its origin. Discriminating doses of 100 mg/L for spirotetramat, 1 mg/L for cyantraniliprole and 60 mg/L (systemic) and 600 mg/L (foliar) for dinotefuran were calculated from the bioassay data. All three insecticides demonstrated good efficacy against silverleaf whitefly, and for the Australian cotton industry, they add three modes of action to the insecticide resistance management strategy, providing greater flexibility in control options. This study has established baseline toxicity data and discriminating doses for spirotetramat, cyantraniliprole and dinotefuran, which will serve as a useful reference for future monitoring and management of B. tabaci MEAM1 insecticide resistance in Australian cotton.

Rate accelerations with zeolite Y in the synthesis of octahydro xanthenes and benzoxanthenes and their simple bio assay data

Abstract Zeolite Y (CBV-720) has been accomplished as an efficient, easily available and eco-friendly catalyst for one pot synthesis of 1, 8-Dioxo-octahydroxanthene and 14-aryl -14H dibenzo [a, j] xanthenes with 5, 5-dimethyl-1, 3- cyclohexanedione or 2-OH naphthol with different substituted aryl aldehydes under neat (solvent free) at 110 0C and microwave conditions. This protocol offers simple cyclocondensation, excellent yields, low reaction time, low amount reusable catalyst and simple operational procedures and free from adverse solvents.

High-throughput analysis of insecticides on malaria vectors using liquid chromatography tandem mass spectrometry.

BackgroundDifferent setups and protocols have been developed for investigating insecticide effects on Anopheles (An.) mosquitoes, vectors of malaria. However, chemical uptake resulting from their tarsal contact with insecticide-treated material has seldom been investigated. To address the challenges encountered in the interpretation of bioassay data, a high throughput method for chemical analysis on malaria vectors was developed and validated for five selected insecticides including alpha-cypermethrin (aCYP), deltamethrin (DM), etofenprox (EPX), permethrin (PM), pirimiphos-methyl (PPM).MethodsThe method includes a single chemical extraction step via an ultrasound probe on mosquito samples and analysis via liquid chromatography coupled to high-resolution tandem mass spectrometry (UHPLC-MS/MS). The protocol was established for two malaria vector species, Anopheles gambiae senso stricto (s.s.) and An. stephensi, both males and females. Recovery rates ranged from 70 to 100% without any influence of sex or species. The method was efficiently applied to female An. gambiae s.s. of the KISUMU1 reference strain, after susceptibility tests using the World Health Organization’s standard protocol.ResultsSusceptibility tests revealed 13.4–18.4 minutes knockdown times for 50% mosquitoes during exposure to EPX and pyrethroids. The mortality rates 24 hours post-exposure to insecticides were mostly 99–100%, except in two PM and three PPM assays suggesting possible or confirmed resistance to these insecticides. The mean insecticide uptake in dead mosquitoes ranged from 23 pg (aCYP) to 1812 pg (EPX) per specimen. However, the mean uptake in survivors to PM and PPM was reduced by at least 25%, suggesting that acute doses were not achieved in these specimens during bioassays.ConclusionsThe developed and validated UHPLC-MS/MS method could be used to address some limitations of bioassays or to assess the penetration of insecticides in mosquito matrix with reference to cuticle thickness and other insecticide resistance mechanisms.

Biokinetics of 238Pu oxides: inferences from bioassay data

The bioassay data collected from several workers involved in 238Pu inhalation incidents have been analysed using the most recent biokinetic models described in the Occupational Intakes of Radionuclides (OIR) series of publications. Although all exposures were thought to be to 238Pu oxides, the observed urinary excretion patterns differed in different inhalation incidents. The urinary excretion from individuals involved in one of the incidents increased steadily with time, peaking around two to three years before decreasing. This pattern is described in Part 4 of the OIR series using the ‘238PuO2, ceramic’ model. This non-monotonic behaviour, explained as being due to fragmentation and dissolution, was not specific to the incident, but observed in other incidents. The urinary excretion data collected from individuals involved in another incident showed dissolution behaviour between Type M and Type S. Finally, the bioassay data from yet another incident showed a pattern that appears to represent behaviour more insoluble than Type S, which is possibly a result of self-heating due to the decay heat from 238Pu. The urinary excretion patterns and corresponding dose coefficients have been calculated and compared.

MPS dose reconstruction for internal emitters: some site-specific issues and approaches

Background As part of the Million Person Study (MPS), dose reconstructions for internal emitters have been performed for several U.S. facilities where large quantities of radionuclides were handled. The main challenges and dominant sources of potential error in retrospective dose estimates for internally exposed workers have been found to vary from site to site. This article discusses some important issues encountered in dose reconstructions performed for selected MPS sites and the approaches used to address those issues. The focus is on some foundational components of retrospective dose assessments that have received little attention in the literature. Methods The discussion is built around illustrative exposure data and dose reconstructions for workers at selected facilities addressed in the MPS. Related findings at some non-MPS sites are also discussed. Results Each of the following items has been found to be a major source of potential error in reconstructed tissue doses for some MPS sites: identification of all dosimetrically important internal emitters; the time pattern of intake; the mode(s) of intake; reliability of bioassay measurements; application of surrogate (coworker) information in lieu of, or in conjunction with, worker-specific monitoring data; the chemical and physical forms of inhaled radionuclides; and the relation of air monitoring data to actual intake. Conclusions (1) Much of the dose reconstruction effort for internal emitters should be devoted to development of best feasible exposure scenarios. (2) Coworker data should be used to assign exposure scenarios or dose estimates to workers with missing exposure data only if there is compelling evidence of similar coworker exposure. (3) Bioassay data for some radionuclides and periods of operation at MPS sites are of questionable reliability due to sizable uncertainties associated with contamination, recovery, or background issues. (4) Dose estimates derived solely from air monitoring data should be treated as highly uncertain values in the absence of site-specific information demonstrating that the data are reasonably predictive of intake. (5) For intakes known or assumed to be via inhalation, the uncertainty in lung dose typically is much greater than the uncertainty in dose to systemic tissues, when dose estimates are based on urinary excretion data. (6) The lung dose estimate often can be improved through development of site-specific respiratory absorption parameter values. (7) There is generally insufficient site-specific information to justify development of site-specific systemic models.

Validation of a system of models for plutonium decorporation therapy.

A recently proposed system of models for plutonium decorporation (SPD) was developed using data from an individual occupationally exposed to plutonium via a wound [from United States Transuranium and Uranium Registries (USTUR) Case 0212]. The present study evaluated the SPD using chelation treatment data, urine measurements, and post-mortem plutonium activities in the skeleton and liver from USTUR Case 0269. This individual was occupationally exposed to moderately soluble plutonium via inhalation and extensively treated with chelating agents. The SPD was linked to the International Commission on Radiological Protection (ICRP) Publication 66 Human Respiratory Tract Model (HRTM) and the ICRP Publication 30 Gastrointestinal Tract model to evaluate the goodness-of-fit to the urinary excretion data and the predictions of post-mortem plutonium retention in the skeleton and liver. The goodness-of-fit was also evaluated when the SPD was linked to the ICRP Publication 130 HRTM and the ICRP Publication 100 Human Alimentary Tract Model. The present study showed that the proposed SPD was useful for fitting the entire, chelation-affected and non-affected, urine bioassay data, and for predicting the post-mortem plutonium retention in the skeleton and liver at time of death, 38.5years after the accident. The results of this work are consistent with the conclusion that Ca-EDTA is less effective than Ca-DTPA for enhancing urinary excretion of plutonium.

Topsoil and urban dust pollution and toxicity in Taranto (southern Italy) industrial area and in a residential district.

Adverse environmental conditions in the Taranto area (southern Italy) were investigated in studies of air, marine sediment, and human health. The present study aimed at providing unprecedented information on soil pollution and toxicity in a set of sites around recognized pollution sources in the Taranto area, since previous studies were focused on marine or air pollution, or on human health effects. The investigated area included a steel foundry and a power plant, as well as some sites located in an adjacent neighborhood. Surface soil samples and urban dust were collected and submitted to inorganic and organic analyses and tested for toxicity in two invertebrate bioassay models; a sea urchin (Sphaerechinus granularis) and an annelid (Caenorhabditis elegans). Inorganic analysis was carried out using ICP-MS for elemental composition for a total of 34 elements, whose levels were evaluated as a function of bioassay data analyzed through principal component analysis (PCA). Other analyses included asbestos search by powder X-ray diffraction (PXRD) and organic analysis for polycyclic aromatic hydrocarbons (PAHs) and aliphatic compounds (C10-C40). Toxicity bioassays were carried out on a sea urchin (Sphaerechinus granularis), and an annelid (Caenorhabditis elegans). Sea urchin bioassays evaluated effects of topsoil or street dust sample exposures (0.1 to 0.5% dry wt/vol) on developing embryos and on sperm, and scored as (a) % developmental defects, (b) inhibition of fertilization success and offspring damage, and (c) frequencies of mitotic aberrations. C. elegans mortality assay displayed significant toxicity associated with soil samples. The overall effects of samples showed very high toxicity at four out of nine sites. These effects were consistent with the highest levels measured for metals and PAHs. Further studies of health effects related to dust exposures in residential areas are warranted. Graphical abstract ᅟ.

Improved Modeling of Plutonium-DTPA Decorporation.

Individuals with significant intakes of plutonium (Pu) are typically treated with chelating agents, such as the trisodium salt form of calcium diethylenetriaminepentaacetate (CaNa3-DTPA, referred to hereafter as Ca-DTPA). Currently, there is no recommended approach for simultaneously modeling plutonium biokinetics during and after chelation therapy. In this study, an improved modeling system for plutonium decorporation was developed. The system comprises three individual model structures describing, separately, the distinct biokinetic behaviors of systemic plutonium, intravenously injected Ca-DTPA and in vivo-formed Pu-DTPA chelate. The system was linked to ICRP Publication 100, "Human Alimentary Tract Model for Radiological Protection" and NCRP Report 156, Development of a Biokinetic Model for Radionuclide-Contaminated Wounds and Procedures for Their Assessment, Dosimetry and Treatment." Urine bioassay and chelation treatment data from an occupationally-exposed individual were used for model development. Chelation was assumed to occur in the blood, soft tissues, liver and skeleton. The coordinated network for radiation dosimetry approach to decorporation modeling was applied using a chelation constant describing the secondorder, time-dependent kinetics of the in vivo chelation reaction. When using the proposed system of models for plutonium decorporation, a significant improvement of the goodness-of-fit to the urinary excretion data was observed and more accurate predictions of postmortem plutonium retention in the skeleton, liver and wound site were achieved.

THE MAYAK WORKER DOSIMETRY SYSTEM (MWDS-2016): INTERNAL DOSIMETRY RESULTS AND COMPARISON WITH MWDS-2013

Differences in results from the new Mayak Worker Dosimetry System (MWDS-2016) vs the previous MWDS-2013 are described. Statistical characteristics are shown for the distribution of accumulated absorbed doses to organs for 8340 workers with bioassay data. Differences in mean values of accumulated doses and their relative standard uncertainties calculated by MWDS-2016 and MWDS-2013 were analysed separately for various types of industrial compounds of plutonium, specifically nitrates, mixtures and oxides. Within the range of accumulated doses >1 mGy, lung doses for nitrates and mixtures decreased by 41 and 15%, respectively, and remained at the same level for oxides. Accumulated liver doses within the range >1 mGy increased for nitrates and mixtures by 13 and 8%, respectively, and decreased for oxides by 7%.

ChEMBL: towards direct deposition of bioassay data.

ChEMBL is a large, open-access bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012, 2014 and 2017 Nucleic Acids Research Database Issues. In the last two years, several important improvements have been made to the database and are described here. These include more robust capture and representation of assay details; a new data deposition system, allowing updating of data sets and deposition of supplementary data; and a completely redesigned web interface, with enhanced search and filtering capabilities.