The European Union (EU) Chemicals Strategy for Sustainability regards chemicals that affect the immune system among the most harmful ones. The Extended One-Generation Reproductive Toxicity study (EOGRTS; Organisation for Economic Co-Operation and Development (OECD) Test Guideline (TG) 443), addresses, among others, potential effects of chemicals on development. In specific cases, the EOGRTS is performed with addition of a so-called cohort 3, that addresses potential effects on the developing immune system, by means of a central assay measuring the T-cell dependent antibody response (TDAR). This assay is based on an interplay of antigen presentation, T-cell help and antibody production by B-cells, and together comprises a functional immune response. In the context of the EOGRTS review project of the European Chemicals Agency (ECHA), we evaluated 15 available TDARs for compliance with conduct and reporting requirements. Collectively, the majority of the TDAR studies were considered to be adequately conducted. We however observed: (i) the protocols differed by the antigen used (sheep red blood cells (SRBC) or KLH), the route of administration (intravenous, intraperitoneal, or subcutaneous), prime or prime/boost immunizations, and whether IgG was measured. (ii) There was major variation in the effects of the positive control for immunosuppression, cyclophosphamide. (iii) Proficiency was not always shown. (iv) Statistical analysis was not always done or reported. (v) Results of effects on lymphocyte populations or other immunotoxicity observations obtained in cohort 1 (or 2) of the EOGRTS were not always discussed together with results of the TDAR. Taken together, next to an improved quality of reporting, this may suggest a need to better define the conduct of the TDAR in OECD TG 443 and OECD Guidance Document (GD) 151, at least for certain aspects.

Salvadora oleoides is used in Pakistani traditional medicine to treat inflammatory conditions, piles, boils, and ulcers. To evaluate the anti-inflammatory potential of S. oleoides (a mixture of aerial branches, leaves, and stem bark), we prepared crude extracts in Soxhlet apparatus by successively using different solvents and found the methanolic extract (OLM) to significantly inhibit the LPS-induced expression of pro-inflammatory cytokines and enzymes in J774 macrophages, at 50 µg/mL concentration. We also analysed the chemical constituents of OLM by dereplication, performed by HPLC-MS/MS and molecular networking. The major detected constituents were flavonoids and phenolic acids glycosides, most of them identified for the first time in S. oleoides. We also evaluated the toxicity of OLM against five cell lines, namely Caco-2, HepG2, HeLa, J774, and WI-38 by MTT assay. The IC50 was found to be higher than 100 µg/mL against these five cell lines after 72 h treatment. Furthermore, OLM was tested in mice for acute and sub-acute oral toxicity according to the guidelines of the Organisation for Economic Co-operation and Development (OECD). OLM was found non-toxic, except for some fibrosis observed in the spleens of treated mice in the sub-acute oral toxicity test. Our results confirm the anti-inflammatory potential of OLM and that it could be tested in in vivo inflammatory models, but its effect on the spleen should be considered before designing the experiments.

There are many risk factors associated with the spread of the COVID-19 pandemic, including low wind speed, fossil fuel energy production, air pollution, and smoking. Several studies argue that smoking is not a risk factor for COVID-19 morbidity among males or any other sub-group. The study aims to analyze the following research questions: (1) can smoking prevalence explain COVID-19 indicators (cases, mortality, and recovery)? Are these relationships monotonically increasing or decreasing? In an attempt to test the counter-intuitive possibility of a non-linear relationship, the proposed empirical model relaxes the assumption of monotonic change by applying the quadratic design and testing which one of the two competing models (quadratic or linear) better fits the data. Findings suggest more complex relationships between corona indices and prevalence of smoking than previously thought. These patterns might be explained by several conditions such as the attenuation of hypercytokinemia for mild levels of smoking prevalence compared with non-smokers, elevated social distancing of smokers in countries with lower smoking prevalence, and unidentified factors that should be examined in future research.

OBJECTIVE: Numerous pre-clinical and clinical studies have recently demonstrated the significant role of phage therapy in treating multidrug-resistant bacterial infections. However, only a few researchers have focused on monitoring the phage-mediated adverse reactions during phage therapy. The present study aimed to demonstrated the oral acute and sub-acute toxicity of bacteriophages (Klebsiella pneumoniae XDR strain) in Charles Foster rats with special reference to immunological response and adverse effects.
RESULTS: Bacteriophages were orally administered in dosages of 1010  PFU/ml and a 1015  PFU/ml to Charles Foster rats as a single dose (in acute toxicity study) and daily dosage for 28 days (in sub-acute toxicity study). One millilitre suspension of bacteriophages was administered through the oral gavage feeding tube. No adverse effect was observed in any of the experimental as well as in the control animals. Furthermore, an insignificant change in food and water intake and body weight was observed throughout the study period compared with the control group rats. On the 28th day of phage administration, blood was collected to estimate haematological, biochemical and cytokines parameters. The data suggested no difference in the haematological, biochemical and cytokine profiles compared to the control group. No significant change in any of the treatment groups could be observed on the gross and histopathological examinations. The cytokines estimated, interleukin-1 beta (IL-1β), IL-4, IL-6 and IFN-gamma, were found within the normal range during the experiment.
CONCLUSIONS: The results concluded that no adverse effect, including the severe detrimental impact on oral administration of high (1010  PFU/ml) and very high dose (1015  PFU/ml) of the bacteriophages cocktail.
CONCLUSIONS: The high and long-term oral administration of bacteriophages did not induce noticeable immunological response as well.

BACKGROUND: This study aimed to measure the efficiency and productivity of tobacco control policies across 16 selected Organization for Economic Co-operation and Development (OECD) countries from 2008 to 2014.
METHODS: A panel-data study.
METHODS: Data envelopment analysis was used in this study. Taxation on tobacco products and pictorial warning labels were chosen as the inputs. Percentage of the population of daily smokers above 15 years old and the number of cigarettes used per smoker per day were output variables. Additionally, the Malmquist total factor productivity (TFP) was used to analyze the panel data and measure productivity change and technical efficiency changes over time.
RESULTS: The highest technical efficiency score (1.05) was attributed to Norway, while the lowest (0.91) belonged to the UK. Technological change with a total mean of 1.06 implied that the technology and creativity have increased, while countries have been able to promote their creativity over the studied period. Norway with the TFP score of 1.15 was the most productive country, while the UK and Turkey with TFP scores of 0.95 and 0.98, respectively, were the least productive countries in terms of the implementation of the tobacco control policies.
CONCLUSIONS: Most OECD countries have productively implemented tax and pictorial warning policies to reduce tobacco use. To achieve the optimum outcome of the tobacco control policies and overcome the challenges of smoking use, countries need to tackle the difficult underlying factors, i.e. tobacco industry opposition and lobbyists, smuggling, and low socioeconomic status.

Both economic globalization and population aging have given rise to changes in environmental quality, but the research that integrates these two crucial factors into the same environment policy framework is still a blank. Therefore, using panel data of the Organization for Economic Cooperation and Development (OECD) over the period 1971-2016, this study examines the long-term impact of economic globalization and population aging on CO2 emissions. First, second-generation panel regression approaches are employed to verify the panel data, including unit root tests, cointegration tests and causality tests. Next, Fully Modified Ordinary Least Squares (FMOLS) and Dynamic Ordinary Least Squares (DOLS) are respectively used for empirical analysis of the long-term impact between variables. The augmented mean group (AMG) is also applied to ascertain the robustness results of the estimation coefficients. Finally, using Dumitrescu and Hurlin non-causality test to examine the causal associations between variables to avoid the contingency of the results. The overall results show that economic globalization and population aging decrease the long-term CO2 emissions. The inverted U-shaped relationship between economic growth and environmental pollution confirms the effectiveness of the Environmental Kuznets Curve (EKC) in OECD countries. In addition, unidirectional causal relationships have been found from economic globalization and population aging to CO2 emissions in this study. Policy suggestions in response to these findings are discussed.

Background: Official development assistance (ODA) is one of the most important means for donor countries to foster diplomatic relations with low- and middle-income countries and contribute to the welfare of the international community.Objective: This study estimated the sectoral allocation of gross disbursements of ODA of the 29 Development Assistance Committee (DAC) member countries of the Organisation for Economic Co-operation and Development (OECD) for the duration of 2011 to 2018, by aid type (bilateral, multilateral, and both aids).Methods: Data from the OECD iLibrary were used. The sector definition was based on the OECD sector classification. For core funding to multilateral agencies that do not specialize in each aid sector, we estimated ODA and its flows based on the OECD methodology for calculating imputed multilateral ODA.Results: For all 29 countries, during the period of 2014-2018 where data were available for all the countries, the sector with the highest average annual ODA contribution was health at 20.34 billion USD (13.21%), followed by humanitarian aid at 18.04 billion (11.72%). Humanitarian aid has increased in the sectoral share rankings in both bilateral and multilateral aid, and the sectoral share for refugees in donor countries has increased in bilateral aid. While the 29 countries show relatively similar trends for sectoral shares, some countries and sectors display unique trends. For instance, infrastructure and energy sectors in bilateral aid of Japan are particularly high accounts for 48.48% of the total bilateral ODA of the country in 2018.Conclusions: This paper evaluated ODA trends by major donors of DAC countries in the pre-COVID-19 pandemic periods. We hope that our estimates will contribute to the review of the strategic decision-making and the effective implementation of future ODA policy discussions in the DAC countries while ensuring transparency.

Protection and restoration of different endangered bird species from pesticide exposure is crucial from the point of safety assessment of ecosystem. Toxicity predictions or risk assessment of pesticides by chemometric tools is one of the challenging fields in recent era. In the present study, classification-based quantitative structure toxicity relationship (QSTR) models were developed for a large dataset (516) of diverse pesticides on multiple avian species mallard duck, bobwhite quail, and zebra finch according to the Organization for Economic Co-operation and Development guidelines. The QSTR models were developed by linear discriminant analysis method with genetic algorithm for feature selection from 2D descriptors using QSAR-Co software. Different statistical metrics assured the reliability and robustness of the developed models. External compound prediction highlighted predictive nature of the models. The mechanistic interpretation suggested that presence of phosphate, halogens (Cl, Br), ether linkage, and NCOO influence the avian toxicity. Furthermore, model reliability was checked by the application of the standardization approach of the applicability domain (AD). Finally, the developed models provided a priori toxic and non-toxic classification for unknown pesticides (inside AD), with particular emphasis on organophosphate pesticides. The interspecies toxicity correlation and predictions encouraged for their further applicability for the fulfilment of data gaps in vital missing species.

The objective is to evaluate the relations between gender health inequalities and economic prosperity in the Organisation for Economic Co-operation and Development (OECD) countries. The groups included health indicators in the specification of men, women and gender inequalities: life expectancy, causes of mortality and avoidable mortality. The variable determining the economic prosperity was represented by the Gross Domestic Product (GDP). The analytical processing included descriptive analysis, analysis of differences and analysis of relationships. The regression analysis was presented as the main output of the research. Most of the significant gender differences in health showed a more positive outcome for women. It is possible to identify a certain relation between gender health inequalities and economic prosperity. If there is some reduction in gender inequalities in health, the economic prosperity will increase. The reduction seems to be more effective on the part of men than women. The output of the cluster analysis showed the relations of indicators evaluating the inequalities and the prosperity. The countries such as Luxembourg, Norway or Switzerland showed very positive outputs, on the other hand, the countries with a potential for the improvement are Lithuania, Latvia or Estonia. Overall, the policies should focus on reducing the inequalities in avoidable mortality as well as reducing the frequent diseases in younger people.

UNASSIGNED: Ursolic acid (UA) has been used in alternative medicine for decades, and there has been a great interest in its medicinal properties. Despite this increased interest, a detailed long-term toxicity study has not been performed. The objective of this study was to determine the long-term toxic effect of UA on clinical chemistry, haematology, coagulation, pathology/morphology, behaviour and motor skills in rats.
UNASSIGNED: A solution was made by dissolving UA in a mixture of 0.1% Tween 80 and 0.5% hydroxypropyl methylcellulose in Milli-Q Water. The control group received the vehicle, and the test groups received a dose up to 1000 mg/kg/day via oral gavage. The solution was administered to both male and female (Han-Wistar) rats for 90 consecutive days.
UNASSIGNED: UA did not cause any deaths, abnormal body weights or abnormal pathology at all test doses. In addition to that, no toxicological changes were observed in behaviour, neurotoxicity, coagulation, haematology or clinical chemistry that are related to the administration of UA.
UNASSIGNED: This study indicates that oral dosing of UA for 90 consecutive days does not lead to toxic effects at any of the doses. Therefore, the NOAEL for UA is likely to be higher than 1000 mg/kg/day.