Lowest Effect Level Research Articles

Corporate Income Tax: Effectiveness in the Context of Public Fiscal Policy and Entrepreneurship Support

The article analyzes the approaches to the definition of the essence and quantitative assessment of the fiscal effectiveness of the income tax. According to the results of the study, it was found out that the fiscal effectiveness of the income tax can be estimated through the indicators of fiscal importance of the tax in the tax revenues of the state (consolidated) budget; tax burden of the tax (in relation to GDP); elasticity of income tax; effective tax rate and tax productivity, etc. The analysis of the dynamics of these indicators over the past few years in Ukraine has allowed us to confirm the low level of fiscal effectiveness and regulatory potential of this tax for Ukraine. One of the possible ways to improve the fiscal effectiveness of the income tax is to use indirect channels of influence, which are represented by the general state of the country's economic development, labor market efficiency, level of welfare of the population, investment attractiveness, and performance of enterprises. The empirical study of determining the most significant channels of influence on the indicators of fiscal effectiveness of the income tax has made it possible to find out: 1) growth of absolute amounts of income tax revenue can be achieved through the use of the investment channel, budget channel and labor market channel; 2) increase in the tax burden on income tax is contributed by the increase in the revenues of the Consolidated Budget, index of industrial producer prices and consumer price index, and increase of the employment rate, while the improvement of the indicators of the overall economic development of the state and investment climate leads to reduction of the tax burden; 3) increase in the fiscal significance of the income tax is contributed by the increase in growth rate of direct investment, level of employment and real wages. Thus, the analysis conducted allowed to identify the channels through which authorities can influence the fiscal effectiveness of the income tax.

Detection and Prioritization of Developmentally Neurotoxic and/or Neurotoxic Compounds Using Zebrafish.

The standard methods for toxicity testing using rodent models cannot keep pace with the increasing number of chemicals in our environment due to time and resource limitations. Hence, there is an unmet need for fast, sensitive, and cost-effective alternate models to reliably predict toxicity. As part of Tox21 Phase III's effort, a 90-compound library was created and made available to researchers to screen for neurotoxicants using novel technology and models. The chemical library was evaluated in zebrafish in a dose-range finding test for embryo-toxicity (ie, mortality or morphological alterations induced by each chemical). In addition, embryos exposed to the lowest effect level and nonobservable effect level were used to measure the internal concentration of the chemicals within the embryos by bioanalysis. Finally, considering the lowest effect level as the highest testing concentration, a functional assay was performed based on locomotor activity alteration in response to light-dark changes. The quality control chemicals included in the library, ie, negative controls and replicated chemicals, indicate that the assays performed were reliable. The use of analytical chemistry pointed out the importance of measuring chemical concentration inside embryos, and in particular, in the case of negative chemicals to avoid false negative classification. Overall, the proposed approach presented a good sensitivity and supports the inclusion of zebrafish assays as a reliable, relevant, and efficient screening tool to identify, prioritize, and evaluate chemical toxicity.

КРОК УПЕРЕД І ДВА НАЗАД – ДЕКЛАРАЦІЇ ТА РЕАЛЬНІСТЬ ДЕРЖАВНОЇ ПОЛІТИКИ РОЗВИТКУ НАУКИ, ІННОВАЦІЙ ТА ВИСОКОТЕХНОЛОГІЧНОГО ВИРОБНИЦТВА В УКРАЇНІ

Сформульовано особливості здійснюваної в Україні політики розвитку науки, інновацій та високотехнологічного виробництва. Визначено, що пролонгація фінансово-економічних умов до відтворення власного виробництва без активізації інноваційної діяльності чи придбання інноваційних технологій зумовлює скорочення вітчизняними підприємствами випуску інноваційної продукції. Сьогодні впровадження нових науково-технічних розробок і технологічних рішень, які базуються на результатах вітчизняних наукових досліджень, відбувається в умовах домінування в Україні звуженого формату відтворення сфери науки та інновацій.Виконано міжнародний порівняльний аналіз результативності України протягом 1996–2016 рр. з аналогічними параметрами розбудови науки і високих технологій у країнах Східної та Західної Європи, Східної та Південно-Східної Азії, Північної Америки. Обгрунтовано, що Україна є єдиною серед цих країн, яка використала попередній 20-річний період власної розбудови не для збільшення фінансових асигнувань у розвиток вітчизняної науки і посилення її кадрового потенціалу, а навпаки – для їх зменшення. Встановлено, що пріоритетні напрями розбудови вітчизняних високих технологій – авіабудування та фармацевтика, на які у структурі українського високотехнологічного виробництва припадає, відповідно, 48,7% і 43,7%, – на світовому ринку вимірюються 0,1% і 0,04%. Це однозначно свідчить про реальний невисокий рівень дієвості статусу інноваційного пріоритету як у державній політиці інноваційного розвитку економіки, так і в економічній політиці держави в цілому.На підставі результатів порівняльного аналізу динаміки розвитку наукової галузі, сектору високих технологій, знаннєвих послуг і переробної промисловості зроблено висновок про те, що пройдений країною попередній етап національного економічного становлення на сьогодні призвів до ситуації, коли бажаними орієнтирами перспективного періоду розбудови України стають показники інноваційного розвитку економіки 1990-х років.

Time-dependent behavioral data from zebrafish reveals novel signatures of chemical toxicity using point of departure analysis

High-content imaging of larval zebrafish behavior can be used as a screening approach to rapidly evaluate the relative potential for chemicals to cause toxicity. However, most statistical methods applied to these data transform movement values to incidence-based “hits” and calculate lowest effect levels (LELs), which loses individual fish resolution of behavior and defies hazard ranking due to reliance on applied dose levels. We developed a parallelizable workflow to calculate benchmark dose (BMD) values from dynamic, high-content zebrafish behavior data that scales for high-throughput chemical screening. To capture the zebrafish movement response from light to dark stimulus, we summarized time-dependent data using both area under the curve and the immediate change at the transition point into two novel metrics that characterized abnormal behavior as a function of chemical concentration. The BMD workflow was applied to calculate BMD10 values of 1060 ToxCast chemicals for 24 zebrafish endpoints, including behavior, mortality and morphology. The BMD10 values provided better precision and separation than LELs for clustering chemicals since they were derived from models that best-fit their concentration-response curves. Analysis of BMD10 values revealed behavioral signatures as the most sensitive endpoints. High concordance in chemical activity was observed between ToxCast in vitro data and zebrafish in vivo behavioral data, however ToxPi analysis indicated that rankings based on in vitro data were not a reliable predictor of in vivo rankings for lower potency chemicals. This analysis method will enable the use of high-content zebrafish behavioral screening data for BMD analysis in toxicological hazard assessment.

ОРГАНИЗАЦИЯ ПЕДАГОГИЧЕСКОГО ВЗАИМОДЕЙСТВИЯ УЧАСТНИКОВ ОБРАЗОВАТЕЛЬНОГО ПРОЦЕССА В КОМПЬЮТЕРНО ОРИЕНТИРОВАННОЙ УЧЕБНОЙ СРЕДЕ УЧРЕЖДЕНИЯ ВЫСШЕГО ОБРАЗОВАНИЯ

The article proves the relevance and topicality of creating a computer-oriented learning environment at a higher education institution. The problems of modern scientific researches dealing with the peculiarities of computer-oriented learning environment at the higher education institutions to develop the pedagogical interaction have been studied, as well as determined the main research areas and trends of this scientific issue. Some pedagogical conditions, including the creativity of teacher pedagogical activity; information competence of education process participants; pedagogical monitoring for the quality of professional specialist training; arranging the socio-psychological comfort for educational activities are considered essential to increase the effective pedagogical interaction among the educational process participants in a computer-centered educational environment of the higher education institutions. The results of modelling pedagogical experiment reveal the potential ways of implementing the examined pedagogical and educational conditions in the process of educational and professional communication. The peculiarities for developing the educational and methodical complex of academic course and training material are determined. The attention is focused on the possibilities for computer monitoring the student knowledge using software MyTestX. The study allows determining some efficiency criteria such as motivating, cognitive, and cooperative criteria required for the effective pedagogical interaction among education process participants in the computer-oriented learning environment at the higher education institutions with the corresponding high, sufficient and low levels of effectiveness within pedagogical interaction, as well as their relevant indicators. Methods for diagnosing the level of pedagogical interaction of education process participants under the conditions of a computer-oriented learning environment are analysed and chosen. The results of the pedagogical experiment confirming the effectiveness of the suggested pedagogical conditions to improve the effective arrangement of pedagogical interaction among education process participants in the computer-oriented learning environment of higher education institutions are presented.

Toxicity profiling of flame retardants in zebrafish embryos using a battery of assays for developmental toxicity, neurotoxicity, cardiotoxicity and hepatotoxicity toward human relevance

Following the voluntary phase-out of brominated flame retardants (BFRs) due to their environmental persistence and toxicity, the organophosphorus flame retardants (OPFRs) are emerging replacements. However, there is limited information on the potential human health effects of the OPFRs. Zebrafish embryos are a viable vertebrate model organism with many advantages for high throughput testing toward human hazard assessment. We utilized zebrafish embryos to assess developmental toxicity, neurotoxicity, cardiotoxicity and hepatotoxicity, of eight replacement OPFRs: (triphenyl phosphate [TPHP], isopropylated phenyl phosphate [IPP], 2-ethylhexyl diphenyl phosphate [EHDP], tert-butylated phenyl diphenyl phosphate [BPDP], trimethyl phenyl phosphate [TMPP], isodecyl diphenyl phosphate [IDDP], tris(1,3-dichloroisopropyl) phosphate [TDCIPP], and tris(2-chloroethyl) phosphate [TCEP]) and two BFRs (3,3′,5,5′- tetrabromobisphenol A [TBBPA] and 2,2′4,4′-brominated diphenyl ether [BDE-47]). To determine potential effects on teratogenicity, embryos were exposed to flame retardants (FRs) at 4 h post fertilization (hpf) to 4 days post fertilization (dpf) and morphological alterations and corresponding survival were evaluated at 2 and 4 dpf. Internal concentrations were measured in larvae used in this assay by liquid chromatography-mass spectrometry. Locomotor activity was assessed in larvae treated for 48 h (from 3 dpf to 5 dpf), followed by hepatotoxicity evaluation. Finally, alterations in heart rate and rhythmicity were assessed to determine cardiotoxicity in 48 hpf embryos exposed to compounds for 3 h. Results suggest that several OPFRs (BPDP, EHDP; IPP, TMPP; TPHP and TDCIPP) produced adverse effects in multiple target organs at concentrations comparable to the two BFRs. As these OPFRs have the capacity to disrupt an integrated vertebrate model, they potentially have the capacity to affect mammalian biology. Then, we compared the lowest effective levels (LEL) in zebrafish with estimated or measured human plasma concentrations using biomonitoring data (human plasma, breast milk, handwipe samples and house dust) and a high throughput toxicokinetic (HTTK) model. Results indicate that for some compounds, the nominal LELs were within the range of human exposures, while internal LELs in zebrafish are above internal exposures in humans. These findings demonstrate the value of the zebrafish model as a relevant screening tool and support the need for further hazard characterization of the OPFRs.

Challenges of implementing an effective risk-based supervision on anti-money laundering and countering the financing of terrorism under the 2013 FATF methodology

PurposeThe purpose of this study is to assess whether level of income of a particular country affects the level of effectiveness in anti-money laundering (AML)/ countering the financing of terrorism (CFT) supervision to identify the most important recommendations in achieving high level of effectiveness and critically discuss the findings of the fourth round evaluations with the outcome of first two objectives.Design/methodology/approachThe level of effectiveness was rated in terms of a four-point Likert scale given 4 for high, 3 for substantial, 2 for moderate and 1 for low level of effectiveness. The countries were ranked using a four-point Likert scale given 4 for high income, 3 for upper middle income, 2 for lower middle income and 1 for low income countries as per the categorisation of World Bank list of economies (World Bank, 2017). For the purpose of estimation, level of effectiveness was rated in terms of a four-point Likert scale given 4 for high, 3 for substantial, 2 for moderate and 1 for low level of effectiveness. The level of technical compliance was ranked using a five-point Likert scale given 5 for compliant, 4 for largely compliant, 3 for partially compliant, 2 for non-compliant and 1 for not applicable as per the ratings given in FATF 2013 methodology (FATF, 2013).FindingsIt was observed that the level of income of a particular jurisdiction has a positive relationship with the level of effectiveness in AML/CFT supervision. Statistical analysis reveal that AML/CFT framework on regulation and supervision of financial institutions (Recommendation 26) and providing guidance and feed back to reporting entities (Recommendation 34) have significant impact on effectiveness level on AML/CFT supervision over the powers of supervisors (Recommendation 27), regulation and supervision of designated non-financial business and professions (Recommendation 28) and sanctions (Recommendation 35).Research limitations/implicationsThe research was limited to 36 fourth round mutual evaluation reports.Originality/valueThis paper is an original work done by the author as a result of the experience which the author received involving as an assessor in mutual evaluations.

Evaluation and Optimization of Pharmacokinetic Models for in Vitro to in Vivo Extrapolation of Estrogenic Activity for Environmental Chemicals.

Background:To effectively incorporate in vitro data into regulatory use, confidence must be established in the quantitative extrapolation of in vitro activity to relevant end points in animals or humans.Objective:Our goal was to evaluate and optimize in vitro to in vivo extrapolation (IVIVE) approaches using in vitro estrogen receptor (ER) activity to predict estrogenic effects measured in rodent uterotrophic studies.Methods:We evaluated three pharmacokinetic (PK) models with varying complexities to extrapolate in vitro to in vivo dosimetry for a group of 29 ER agonists, using data from validated in vitro [U.S. Environmental Protection Agency (U.S. EPA) ToxCast™ ER model] and in vivo (uterotrophic) methods. In vitro activity values were adjusted using mass-balance equations to estimate intracellular exposure via an enrichment factor (EF), and steady-state model calculations were adjusted using fraction of unbound chemical in the plasma () to approximate bioavailability. Accuracy of each model-adjustment combination was assessed by comparing model predictions with lowest effect levels (LELs) from guideline uterotrophic studies.Results:We found little difference in model predictive performance based on complexity or route-specific modifications. Simple adjustments, applied to account for in vitro intracellular exposure (EF) or chemical bioavailability (), resulted in significant improvements in the predictive performance of all models.Conclusion:Computational IVIVE approaches accurately estimate chemical exposure levels that elicit positive responses in the rodent uterotrophic bioassay. The simplest model had the best overall performance for predicting both oral (PPK_EF) and injection (PPK_) LELs from guideline uterotrophic studies, is freely available, and can be parameterized entirely using freely available in silico tools. https://doi.org/10.1289/EHP1655

Antibiotic-driven escape of host in a parasite-induced Red Queen dynamics.

Winnerless coevolution of hosts and parasites could exhibit Red Queen dynamics, which is characterized by parasite-driven cyclic switching of expressed host phenotypes. We hypothesize that the application of antibiotics to suppress the reproduction of parasites can provide an opportunity for the hosts to escape such winnerless coevolution. Here, we formulate a minimal mathematical model of host–parasite interaction involving multiple host phenotypes that are targeted by adapting parasites. Our model predicts the levels of antibiotic effectiveness that can steer the parasite-driven cyclic switching of host phenotypes (oscillations) to a stable equilibrium of host survival. Our simulations show that uninterrupted application of antibiotic with high-level effectiveness (greater than 85%) is needed to escape the Red Queen dynamics. Interrupted and low level of antibiotic effectiveness are indeed useless to stop host–parasite coevolution. This study can be a guide in designing good practices and protocols to minimize the risk of further progression of parasitic infections.

Combining mouse embryonic stem cells and zebrafish embryos to evaluate developmental toxicity of chemical exposure

The assays in this study utilize mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured. In zebrafish embryos, lethality and the lowest effect level concentrations for morphological malformations were determined. Clustering of the assays based on frequency of affected assays resulted in a ranking of the test compounds that correlated to in vivo rodent data (R = 0.88, P < 0.001). We conclude that the combination of ESC- and zebrafish-based assays provides a valuable platform for the prioritization of pharmaceutical and industrial chemicals for further testing of developmental toxicity in rodents.

An assessment of the dynamic effects of monetary policy in Macedonia

ABSTRACTMacedonia, as a small emerging economy, is exposed to foreign risks such as: exchange rate volatility, trade distortions, and highly volatile capital flows. To ‘protect’ its economy, since 1995, the Macedonian Central Bank has applied the monetary strategy of exchange rate targeting, where the interest rate on Central Bank bills auctions is a basic monetary-policy instrument. This paper re-examined the effectiveness of the current monetary policy in Macedonia using the policy-oriented vector error correction model (VECM). We found that the Macedonian Central Bank demonstrates a low level of monetary-policy effectiveness and the existing monetary-policy strategy does not necessarily promote its ability to react countercyclically.

The advantages of linear concentration-response curves for in vitro bioassays with environmental samples.

In vitro assays and high-throughput screening (HTS) tools are increasingly being employed as replacements for animal testing, but most concentration-response curves are still evaluated with models developed for animal testing. We argue that application of in vitro assays, particularly reporter gene assays, to environmental samples can benefit from a different approach to concentration-response modeling. First, cytotoxicity often occurs at higher concentrations, especially for weakly acting compounds and in complex environmental mixtures with many components. In these cases, specific effects can be masked by cytotoxicity. Second, for many HTS assays, low effect levels can be precisely quantified because of the low variability of controls in cell-based assays and the opportunity to run many concentrations and replicates when using high-density well-plate formats (e.g., 384 or more wells per plate). Hence, we recommend focusing concentration-response modeling on the lower portion of the concentration-response curve, which is approximately linear. Effect concentrations derived from low-effect level linear concentration-response models facilitate simple derivation of relative effect potencies and the correct application of mixture toxicity models in the calculation of bioanalytical equivalent concentrations. Environ Toxicol Chem 2018;37:2273-2280. © 2018 SETAC.

Multigenerational effects of nickel on Daphnia magna depend on temperature and the magnitude of the effect in the first generation.

Ecological risk assessment is commonly based on single-generation ecotoxicological tests that are usually performed at one standard temperature. We investigated the effects of nickel (Ni) on Daphnia magna reproduction at 15, 20, and 25 °C over 4 generations. Multigenerational Ni effects on D. magna reproduction depended on the magnitude of the effect in the first generation (F0) and showed very different patterns at different temperatures. At low effect level concentrations (<10% effect concentration [EC10] in F0), chronic Ni toxicity at 15 and 20 °C did not increase over 4 generations, and the increase in Ni toxicity at 25 °C observed in F1 and F2 in some Ni treatments did not persist into F3, where complete recovery of reproduction was observed. At higher effect level concentrations, the multigenerational Ni effects depended on the test temperature. In F0, Ni toxicity was 6.5-fold lower at 25 °C than at 15 °C (based on the median effect concentration), but the temperature effect on Ni toxicity was not explained by differences in Ni accumulation. At a lower temperature, lower internal Ni concentrations in D. magna were necessary to induce the same Ni toxicity as at a higher temperature. Overall, our results indicate that low single-generation chronic effect concentrations of Ni in D. magna (EC10 in the present study) are also protective in a long-term, multigenerational context and that temperature should be taken into account in the ecological risk assessment of Ni. Environ Toxicol Chem 2018;37:1877-1888 © 2018 SETAC.

CORPORATE INCOME TAX: EFFECTIVENESS IN THE CONTEXT OF PUBLIC FISCAL POLICY AND ENTREPRENEURSHIP SUPPORT

The article analyzes the approaches to the definition of the essence and quantitative assessment of the fiscal effectiveness of the income tax. According to the results of the study, it was found out that the fiscal effectiveness of the income tax can be estimated through the indicators of fiscal importance of the tax in the tax revenues of the state (consolidated) budget; tax burden of the tax (in relation to GDP); elasticity of income tax; effective tax rate and tax productivity, etc. The analysis of the dynamics of these indicators over the past few years in Ukraine has allowed us to confirm the low level of fiscal effectiveness and regulatory potential of this tax for Ukraine. One of the possible ways to improve the fiscal effectiveness of the income tax is to use indirect channels of influence, which are represented by the general state of the country's economic development, labor market efficiency, level of welfare of the population, investment attractiveness, and performance of enterprises. The empirical study of determining the most significant channels of influence on the indicators of fiscal effectiveness of the income tax has made it possible to find out: 1) growth of absolute amounts of income tax revenue can be achieved through the use of the investment channel, budget channel and labor market channel; 2) increase in the tax burden on income tax is contributed by the increase in the revenues of the Consolidated Budget, index of industrial producer prices and consumer price index, and increase of the employment rate, while the improvement of the indicators of the overall economic development of the state and investment climate leads to reduction of the tax burden; 3) increase in the fiscal significance of the income tax is contributed by the increase in growth rate of direct investment, level of employment and real wages. Thus, the analysis conducted allowed to identify the channels through which authorities can influence the fiscal effectiveness of the income tax

Corporate Income Tax: Effectiveness in The Context of Public Fiscal Policy and Entrepreneurship Support

The article analyzes the approaches to the definition of the essence and quantitative assessment of the fiscal effectiveness of the income tax. According to the results of the study, it was found out that the fiscal effectiveness of the income tax can be estimated through the indicators of fiscal importance of the tax in the tax revenues of the state (consolidated) budget; tax burden of the tax (in relation to GDP); elasticity of income tax; effective tax rate and tax productivity, etc. The analysis of the dynamics of these indicators over the past few years in Ukraine has allowed us to confirm the low level of fiscal effectiveness and regulatory potential of this tax for Ukraine. One of the possible ways to improve the fiscal effectiveness of the income tax is to use indirect channels of influence, which are represented by the general state of the country's economic development, labor market efficiency, level of welfare of the population, investment attractiveness, and performance of enterprises. The empirical study of determining the most significant channels of influence on the indicators of fiscal effectiveness of the income tax has made it possible to find out: 1) growth of absolute amounts of income tax revenue can be achieved through the use of the investment channel, budget channel and labor market channel; 2) increase in the tax burden on income tax is contributed by the increase in the revenues of the Consolidated Budget, index of industrial producer prices and consumer price index, and increase of the employment rate, while the improvement of the indicators of the overall economic development of the state and investment climate leads to reduction of the tax burden; 3) increase in the fiscal significance of the income tax is contributed by the increase in growth rate of direct investment, level of employment and real wages. Thus, the analysis conducted allowed to identify the channels through which authorities can influence the fiscal effectiveness of the income tax.

Leadership Style and Job Effectiveness of Librarians in South-West Nigerian Universities

Job effectiveness of academic librarians in today's information age is important as they are expected to be the vanguard of acquiring, processing, storing and disseminating information to users. It is of utmost importance for academic librarians to provide quality information to support teaching, learning, research and community service. However, the general opinion among professional members and studies revealed low level of job effectiveness of librarians which could be due to certain factors in their work environment like leadership style. The study investigated the extent to which leadership style influenced job effectiveness of librarians in universities in South-West, Nigeria. The study adopted the survey research design. Population of study consisted of 373 librarians from 35 university libraries in South-West, Nigeria. Total enumeration was used. A validated questionnaire was used as the instrument for data collection. The Cronbach's alpha reliability coefficients for each of the variables ranged from 0.96 to 0.98. Response rate was 80.96%. Data analysis was done using correlation and multiple regression The findings showed that Leadership style in terms of transformational, transactional and laissez-faire had a significant positive relationship with job effectiveness (r =.704, p <.05). The study concluded that a positive relationship existed between leadership style and job effectiveness. This study made recommendations to improve job effectiveness and leadership styles, one of which is that academic librarians should use a leadership style that encourages effective performance from academic librarians at any given time.

Benzalkonium Chloride and Anticancer Drugs in Binary Mixtures: Reproductive Toxicity and Genotoxicity in the Freshwater Crustacean Ceriodaphnia dubia.

Benzalkonium chloride (BAC) is a cationic surfactant commonly used as a disinfectant. Its ubiquitous nature is the result of high usage and frequent discharge into the environment and evidence of interaction with numerous contaminants, such as pharmaceutical active compound residues. Anticancer drugs, among these compounds, are able to exert eco-genotoxic effects at sub ng-µg/L. The purpose of this study was to assess the reproductive toxicity and the genotoxicity of 5-fluorouracil (5-FU), cisplatin (CDDP), etoposide (ET), and imatinib mesylate (IM)-binary mixtures combined with BAC in Ceriodaphnia dubia. The effects of the mixtures were assessed under the assumption of independent action in experiments that applied two effect levels. The type of interaction was not the same over the range of effect sizes. The combined action experiment on reproduction showed an antagonistic effect at higher effect levels for all binary combinations, except for BAC/IM, whereas independent action was observed in all mixtures at a low effect level. The results of binary combinations on genotoxicity showed antagonistic effects for BAC+ET and BAC+CDDP, whereas independence was expressed in BAC+IM and BAC+5-FU. The antagonistic interactions still led to higher effects than those observed after single exposures at the same doses in most cases. The effects of mixtures of drugs should be taken into account for environmental risk assessment.

Determination of Trichothecenes in Cereal Matrices Using Subcritical Water Extraction Followed by Solid-Phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry

Subcritical water extraction followed by solid-phase extraction and ultra-high performance liquid chromatography coupled with tandem mass spectrometry detection is reported for the first time for the determination of 6 trichothecenes (deoxynivalenol, deoxynivalenol-3-glucoside, 3-acetyl-deoxynivalenol, 15-acetyl-deoxynivalenol, HT-2 toxin, and T-2 toxin) from different cereals. Water with 1% formic acid was used as the extraction solvent followed by a solid-phase extraction clean-up, achieving good performance with acceptable extraction recoveries, method detection limits between 0.05 μg kg−1 and 4.0 μg kg−1, and method quantification limits between 0.4 μg kg−1 and 20 μg kg−1. The use of water as the extraction solvent allowed a selective extraction affording low matrix effect levels and the detection and quantification of natural target trichothecenes at very low concentration levels. This extraction method was applied to different cereals, a pseudocereal and an oilseed sample, of which maize, millet, and oat were contaminated by at least one trichothecene.

Preliminary ecotoxicity hazard evaluation of DOPO-HQ as a potential alternative to halogenated flame retardants

Recent regulatory and environmental pressures have led to increasing demands for environmentally friendly flame retardants as alternatives to halogenated flame retardants (HFRs). A new flame retardant alternative, 10-(2, 5-dihydroxyl phenyl)-9, 10-dihydro-9-oxa-10- phosphaphenanthrene-10-oxide (DOPO-HQ), was applied due to its high thermal stability and glass transition temperature. However, there is little information available for its ecotoxicology.For this purpose, the preliminary ecotoxicity of DOPO-HQ was investigated and evaluated, using aquatic, terrestrial and microorganism toxicity according to Organization for Economic Co-operation and Development (OECD) guidelines under the framework of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. No effect was observed on Pseudokirchneriella subcapitata, Daphnia magna and Gobiocypris rarus at the saturation water solubility. For active sludge, Eisenia foetida and seedling emergence, no effect was observed at the limited highest concentration of 1000 mg/L or 1000 mg kg−1 dw. However, moderate effect on the shoot weight is observed with the maximum inhibition rate of 46.3% when exposed to 1000 mg kg−1 dw.Comparing the ecotoxicity of DOPO-HQ with that of HFRs and their typical alternatives, the toxicity of DOPO-HQ is markedly lower than those of triphenyl phosphate (TPP) and HFRs such as tris(2-chloro-1-methylethyl) phosphate (TCPP), tris(1,3-dichloro-2-propyl) phosphate (TDCCP), tris(2-chloroethyl) phosphate (TCEP) and tetrabromobisphenol A (TBBPA). Similar low effect levels were observed for resorcinol bis (biphenyl) phosphate (RDP), bisphenol A bis (biphenyl) phosphate (BDP) and its parent chemical 9, 10-dihydro-9-oxa-10-phosphaphenanthrene −10-oxide (DOPO). DOPO-HQ could be a potential alternative to HFRs from an environmental perspective.

Effects of Polar Bear and Killer Whale Derived Contaminant Cocktails on Marine Mammal Immunity.

Most controlled toxicity studies use single chemical exposures that do not represent the real world situation of complex mixtures of known and unknown natural and anthropogenic substances. In the present study, complex contaminant cocktails derived from the blubber of polar bears (PB; Ursus maritimus) and killer whales (KW; Orcinus orca) were used for in vitro concentration-response experiments with PB, cetacean and seal spp. immune cells to evaluate the effect of realistic contaminant mixtures on various immune functions. Cytotoxic effects of the PB cocktail occurred at lower concentrations than the KW cocktail (1 vs 16 μg/mL), likely due to differences in contaminant profiles in the mixtures derived from the adipose of each species. Similarly, significant reduction of lymphocyte proliferation occurred at much lower exposures in the PB cocktail (EC50: 0.94 vs 6.06 μg/mL; P < 0.01), whereas the KW cocktail caused a much faster decline in proliferation (slope: 2.9 vs 1.7; P = 0.04). Only the KW cocktail modulated natural killer (NK) cell activity and neutrophil and monocyte phagocytosis in a concentration- and species-dependent manner. No clear sensitivity differences emerged when comparing cetaceans, seals and PB. Our results showing lower effect levels for complex mixtures relative to single compounds suggest that previous risk assessments underestimate the effects of real world contaminant exposure on immunity. Our results using blubber-derived contaminant cocktails add realism to in vitro exposure experiments and confirm the immunotoxic risk marine mammals face from exposure to complex mixtures of environmental contaminants.