Organisation For Economic Co-operation And Development Research Articles

First report on regression-based QSAR addressing pesticide dissipation half-life in plants: A step towards sustainable public health

The excessive use of pesticides (an important group of chemicals) in the agricultural as well as public sectors raises a health concern. Pesticides affect humans and other living organisms via the food chain. Therefore, it is very necessary to calculate the dissipation half-life of pesticides in plants. Experimental prediction of pesticide dissipation half-lives requires complex environmental conditions, high cost, and a long time. Thus, in-silico half-life predictions are suitable and the best alternative. Herein, a total of six PLS (partial least squares) models namely, M1 (overall), M2 (fruit), M3 (plant interior), M4 (leaf), M5 (plant surface), and M6 (whole plant) alongside two MLR (multiple linear regression) models i.e. M7 (fruit surface) and model M8 (straw) were generated using dissipation half-lives (log10(T1/2)) of pesticides in plants and their different parts. Models were constructed in strict accordance with the guidelines outlined by the Organization for Economic Co-operation and Development (OECD) and extensively validated using globally accepted validation metrics (determination coefficient (R2) = 0.610–0.795, leave-one-out (LOO) cross-validated correlation coefficient (Q2LOO) = 0.520–0.660, MAE-FITTED TRAIN (mean absolute error fitted train) = 0.119–0.148, MAE-LOOTRAIN = 0.132–0.177, predictive R2 or Q2F1 = 0.538–0.567, Q2F2 = 0.500–0.565, MAETEST = 0.122–0.232), confirming their accuracy, reliability, predictivity, and robustness. Lipophilicity, the presence of a cyclomatic ring, suphur, aromatic amine fragments, and chlorine atom fragments are responsible (+ve contribution) for high dissipation half-lives of pesticides in plants. In contrast, hydrophilicity, pyrazine fragments, and rotatable bonds reduce (−ve negative contribution) the dissipation half-lives of pesticides in plants. To address the real-world applicability, the models were employed to screen the PPDB (Pesticide Properties Database) database, which revealed the top 10 pesticides with the highest log(T1/2) in the whole plant and respective parts of the plant body. The present work will aid in developing safer and novel pesticides, regulatory risk assessment, various risk assessments for the sustenance of public health, screening of databases, and data-gap filling.

Testing the sensitivity of the medaka Transgenic Eleuthero-embryonic THYroid-Specific assay (TETHYS) to different mechanisms of action

There are many concerns about the impacts of Endocrine-Disrupting Chemicals on both wildlife and human populations. A plethora of chemicals have been shown to interfere with the Hypothalamic–Pituitary–Thyroid (HPT) axis in vertebrates. Disruption of the HPT axis is one of main endocrine criteria considered for the regulation of chemicals, along with the estrogen axis, androgen axis and steroidogenesis (EATS). In response to these concerns, the Organization for Economic Cooperation and Development (OECD) initiated the validation of test guidelines (TGs) covering the EATS modalities. Regarding thyroid activity and/or disruption assessment, three OECD TGs are validated, all of them using amphibians. To date, no OECD TGs based on fish are available for the detection of Thyroid Active Chemicals (TACs). To fill this gap, we developed a new test for the detection of TACs, the TETHYS assay (Transgenic Eleuthero-embryonic THYroid-Specific assay). This assay uses a medaka (Oryzias latipes) transgenic line Tg(tg:eGFP) expressing Green Fluorescent Protein in the thyroid follicles, under the control of the thyroglobulin promoter. This assay is performed at eleuthero-embryonic life-stages with an exposure length of 72 h. In the present study, the following reference chemicals with known thyroid hormone system mechanism of action have been tested: methimazole, sodium perchlorate, sodium tetrafluoroborate, diclofenac, iopanoic acid, sobetirome, NH-3 and 1–850. Except for the thyroid receptor antagonists, all chemicals tested were identified as thyroid active, modifying the total fluorescence and the size of the thyroid follicles. To investigate the test specificity, we tested three chemicals presumed to be inert on the HPT axis: cefuroxime, abamectin and 17α-ethinylestradiol. All were found to be inactive in the TETHYS assay. This promising New Approach Methodology can serve as a foundation for the development of a new OECD TG in the frame of regulatory assessment of chemicals for thyroid activity.

THE CURRENT LEARNING METHODOLOGY AND IT’S FUTURE TRENDS

The future of any country's development the main determining factor is education. The main goal of education is for student’s successful training, intellectual, moral, with appropriate physical capabilities and humaneness respect, study, work, and live independently is to develop into a capable individual. Nowadays, the development of technology changes people's lives technology while making it easier and easier of a person who wants to receive services based on progress arouses interest. It is also in education and depends. [1]Technological innovation fundamentally transforms education, reshaping the needs and skills required for present and future workplaces. Building a future-ready education system requires consistent delivery of 21st-century curriculum and inclusive models that provide a strong foundation for lifelong adaptation and new skills development, with specialized education focusing on skills that are in demand in the real world. This disconnect between employer needs and talent pools must be addressed.This study on where and how modern learning methods and trends are headed in today's Industry 4.0 transition is based on the predictions of a wide range of experts from the World Economic Forum's expert network and the Organization for Economic Co-operation and Development (OECD)'s Education and It was developed based on the initiative of the Future of Skills 2030 project.

THE IMPACT OF TAXATION ON INTERNATIONAL COMMERCE AND EXCHANGE RATE ON IMPORTS

The globalization of capital markets has accelerated capital movements, turning the world into one large marketplace. International trade has become an important tool in shaping the financial structure of countries. However, elements such as customs duties and import quotas play a decisive role in trade between countries. Taxes, which are a financial policy tool of countries, are used to influence foreign trade, particularly imports. One of the determining factors in foreign trade activities is the exchange rate. The purpose of this study is to examine the effect of taxes on imports and the change in the nominal exchange rate on the import volume of goods and services. In this study, which examined 20 Organization for Economic Co-Operation and Development (OECD) countries with data for the period 1999-2021 taken from the World Bank official website, the model was analyzed with the help of AR (1) Residual Random Effects Generalized Least Squares Regression Model Estimator. The analysis revealed that increases in international trade taxes and exchange rate increases reduce the import volume. This result empirically supports the conclusion that taxes on international trade and reductions in exchange rates increase import volume.

Evaluation of acute and subacute toxicity and sedative effect of Feretia apodanthera Delile (Rubiaceae) leaves

IntroductionMedicinal plants have experienced a resurgence in usage over recent decades. Indeed, they constitute a therapeutic resource for a considerable proportion of the world's population. Nevertheless, evaluating the safety of these plants remains a challenge in ensuring their secure utilisation. AimThe aim of this study was to assess the safety, tolerability and sedative effect of Feretia apodanthera MethodsA lyophilised aqueous infusion of Feretia apodanthera was prepared from dried leaf powder. The Organisation for Economic Co-operation and Development (OECD) guidelines 423 and 407 were employed. The initial assessment of acute toxicity was conducted by administering a single dose of 2,000 mg kg-1 of lyophilisate to female rats, after which the animals were observed for a period of 14 days. In a subsequent series of experiments, the subacute toxicity of the lyophilisate was evaluated through daily administrations of doses of 250 mg kg-1, 500 mg kg-1 and 1,000 mg kg-1 to both male and female rats over a period of 28 days. Furthermore, the potential sedative effect of the lyophilisate was investigated in mice. ResultsIn both single administration and repeated administration over 28 days in rats, the lyophilisate of the aqueous infusion of Feretia apodanthera did not induce mortality or significant changes in weight progression, water and food consumption, relative organ weights, or biochemical and haematological parameters, compared to the controls. However, it potentiated diazepam-induced sleep in mice. This sedative effect appears to involve an interaction with GABAA receptors. ConclusionAlthough the sedative effect should be taken into account during use, the aqueous leaf infusion of Feretia apodanthera appears to be relatively well tolerated in both single and repeated administrations.

The role of education in moderating the impact of development on environmental sustainability in OECD countries

This study explores the interconnections among industrialization, urbanization, Foreign Direct Investment (FDI), and carbon emissions (CO2e) across 31 OECD (Organization for Economic Cooperation and Development) countries from 1998 to 2020. In addition, it analyzes how education moderates these relationships. This study employs CO2e as the explained variable, while industrialization, urbanization, and FDI serve as explanatory variables, with education as a moderator. This research utilized Hierarchical regression analysis to examine how education moderates the associations among industrialization, urbanization, FDI, and CO2e. Additionally, to validate the reliability of our results, we utilized the Generalized Method of Moments (GMM). The results of this study imply that CO2e levels increase with the level of industrialization and urbanization. The pursuit of education also contributed to the increase in CO2e. Moreover, education and industrialization have detrimental effects on CO2e. To fill this gap in the existing literature, this study investigates the relationship between industrialization, urbanization, FDI, and CO2e, a domain with scarce empirical investigations. Furthermore, this study contributes uniquely to the literature by investigating the moderating influence of education on the relationships between independent variables and CO2e. This original aspect of this research aims to enhance our understanding of the complex connections between these factors.

Foreign Direct Investment and Its Impact on India's Economic Growth

One of the most important ways for nations to integrate into the global economy and promote economic growth and development is through foreign direct investment, or FDI. It means that an organization or individual from one nation invests resources into the assets or commercial ventures of another nation. Foreign direct investment (FDI) denotes a long-term stake and a substantial amount of control or influence over the management of the foreign firm, in contrast to foreign portfolio investments, which consist of passive ownership of securities. Intra-company loans, reinvestment of earnings, and ownership of equity are ways to attain this control. FDI is so more than just a cash investment; it's a calculated action that has the power to influence the host nation's economic environment. Three main components make up foreign direct investment (FDI) according to the International Monetary Fund (IMF) and the Organisation for Economic Co-operation and Development (OECD): equity capital, reinvested earnings, and intra-company loans. Acquiring shares in a foreign company signifies ownership and control through equity capital. The investor's portion of profits that are reinvested in the overseas business to support development and expansion, as opposed to being sent home as dividends, is known as reinvested earnings. Funds borrowed or lent between the parent business and its overseas affiliates are referred to as intra-company loans, and they reflect continuing financial exchanges inside the corporate network. FDI may be divided into two primary categories: vertical FDI, which involves a company investing in a host nation to move upstream or downstream in different stages of production, and horizontal FDI, which involves a company replicating its home country-based activities at the same point of the value chain in a host country.

Effects of Berberis asiatica, Withania somnifera, and Their Combination on Body Weight in Streptozotocin-Nicotinamide-Induced Type 2 Diabetes in Wistar Rats.

Introduction Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, impaired insulin secretion, and beta cell dysfunction, often leading to chronic hyperglycemia and associated complications. Berberis asiatica (BA) and Withania somnifera (WS) are ancient medicinal plants with a reputation for having potential therapeutic effects in diabetes management. The purpose of this study was to look into how body weight (BW) was affected in streptozotocin-nicotinamide (STZ-NIC) induced T2DM in Wistar rats by BA, WS, and their polyherbal combination (PHC). Materials and methods Seventy-eight Wistar rats of both sexes were divided into 13 groups, with six rats in each group, including normal and diabetic controls, and treated with varying doses of BA, WS, and PHC. The rats were under observation over the course of 35 days for any change in BW. The Organization for Economic Co-operation and Development (OECD) rules and guidelines were followed in the conduct of acute toxicity tests. One-way analysis of variance (ANOVA), followed by Tukey-Kramer post hoc tests, was used for statistical analysis. Results The findings indicated that the highest dose of BA (1000 mg/kg) significantly improved BW in diabetic rats, approaching that of the normal control group. The combination of BA and WS also demonstrated significant improvements in BW, suggesting a synergistic effect. The standard antidiabetic drugs, metformin and glimepiride, were effective in increasing BW in diabetic rats. Conclusion The study concludes that BA, WS, and their combination have a positive impact on BW management in T2DM rats, with the combination therapy showing enhanced effects. These findings support the potential utilization of these herbs in managing BW and other T2DM-associated metabolic disturbances and abnormalities.

Building a fuzzy model for determining the level of social well-being of the population

This paper considers objects that affect the social security of the country. The complexity of such objects makes the development of computer systems in sociological research a difficult algorithmic task because of information uncertainty. Human thinking is based on inaccurate, approximate data, the analysis of which makes it possible to formulate clear decisions. In practice, there are usually no precise mathematical models that describe social objects. In such cases, it is advisable to use fuzzy mathematics as a tool for solving this problem. The main advantage of this approach compared to other artificial intelligence methods is the ability to interpret the results obtained. To assess the level of social well-being of the population, we used the mathematical apparatus of fuzzy set theory and fuzzy inference. The study is based on the OECD Better Life Index, which was developed by the Organization for Economic Cooperation and Development (OECD) to help countries assess and improve the quality of life of their citizens. In the course of the study, a fuzzy inference system was built to measure the social well-being of the population based on the indicators of the OECD Better Life Index. Since determining the level of social well-being is a complex task, a hierarchical structure with two main groups of social well-being indicators was constructed to simplify it. The resultant system evaluates each social indicator included in the OECD’s Better Life Index. Using the fuzzy inference model built, it was possible to assess the social well-being of the country’s population in a simple and transparent way in comparison with the OECD member countries. The results of the study make it possible to understand which indicators of social well-being of the country’s population are desirable or need to be improved in the future

The Impact of the Global Minimum Tax Reform on China and Its Countermeasures

Abstract Significant corporate tax reform was agreed upon by more than 140 nations in 2021, with implementation set for 2023 and beyond. Many people throughout the globe are discussing the possible effects of the Organization for Economic Cooperation and Development (OECD) planned adjustment to the global minimum tax (GMT) on their respective economies. The OECD has formulated a “two-pillar” scheme for international tax rules for 137 countries and regions within the overall framework. Pillar 2 is to set the tax rate at 15%, the world’s lowest corporate tax. The GMT is a reclassification of the taxing authority mechanism for the profits of multinational corporations, which has made significant adjustments to the global tax coordination and governance mechanism. People living in China and earning money from China must pay university fees, which are all of a nationality. Progressive rates ranging from 3 to 45% apply to the complete income. Therefore, taking the initiative in policy is crucial to address this challenge actively. This article makes an in-depth assessment and prediction of the impact of the GMT reform on China’s tax system and enterprises and proposes countermeasures. However, approximately 20% of the earnings can be exposed to the 15% tax rate that governments can apply. If the entire process is mixed in tandem, the tax rate equals 0.2%. Hence, an important amount of tax revenue can proceed down the drain. From the numerical outcomes, the minimum tax with jurisdictional blending was set at 12.5% under Pillar 2; the disparity between the sample’s top and lowest EATRs would decrease by 2.8% points.

The Origins of a Fiscal Outlier: The Abandonment of a Federal VAT in the Nixon Presidency

Abstract Richard Nixon was the first president who examined the possibility of introducing a value-added tax (VAT) at the federal level in the late twentieth century. By 1970, his administration had considered recommending it alongside other domestic programs to overcome the criticism against the VAT’s regressivity, potential conflict in the federal–state tax authority, and the fragmented decision-making authority between the executive and legislative branches of the government. However, in 1971, the Nixon administration shifted their policy priority toward gaining the middle-class political support by linking local property tax relief to a federal VAT. Although they combined the two measures with a rebate to obtain consent to and confidence in them from the “opponents” among the “internalists” of policymaking and societal actors, their attempt failed to accomplish it. As a result, Nixon abandoned the federal VAT. This abandonment was a missed opportunity to introduce a federal VAT, leading the United States to become a fiscal outlier among Organisation for Economic Co-operation and Development (OECD) countries: it has not yet implemented a national/federal VAT. Furthermore, this outcome marked the origin of certain historical characteristics of the American fiscal state: the use of tax expenditures, “fend-for-yourself federalism,” weak extractive capacity, and fiscal inflexibility.

Influence of Rurality on Oral Cancer Trends among Organisation for Economic Co-Operation and Development (OECD) Member Countries-A Scoping Review.

Oral cancer is the general term used to describe cancers of the oral cavity and oropharyngeal region. These cancers are one of the leading causes of death in elderly residents within the Organisation for Economic Co-operation and Development (OECD) member countries in the 21st century. This scoping review was carried out to assess the influence of rurality on oral cancer trends and patterns among OECD member countries. Four online databases (Medline, PubMed, Scopus, and CINAHL) were searched for studies that reported on oral cancer trends in rural and remote areas in OECD member countries. A total of 1143 articles were obtained initially; among them, 995 papers were screened to include 18 articles for this scoping review. Studies have reported increasing incidence and prevalence in the United States, Australia, Canada, and European countries wherein risk factors such as tobacco, alcohol, and human papilloma virus (HPV) infections were associated with oral and oropharyngeal cancers. Awareness among people living in rural areas about HPV-related cancers was very low, while rates of tobacco and alcohol abuse were noted to be rising more rapidly than among their urban counterparts. Furthermore, the ageing population was most affected compared to the younger age groups of people with oral and oropharyngeal cancer that are prevalent in these regions. Overall, despite living in developed countries, rurality was noted to be a significant factor in the lower life expectancy of oral cancer patients, mainly due to the limited accessibility to tertiary cancer care centres and advanced medical care.

Cultivating Political Efficacy: Facilitation as a Catalyst for Democratic Education and Civic Competence

ABSTRACT Participation in democratic processes is a cornerstone for good governance and societal trust. The Organization for Economic Co-operation and Development (OECD) and academic literature emphasize enhancing civic engagement to foster democracy, shape policies, and build societal trust. Within this context, the concept of facilitation gains prominence as a vital mechanism that enhances participatory inclusivity and better decision-making through capacity-building. However, the current scope of facilitation is limited, mainly emphasizing its role as a skill for democratic engagement but neglecting its capacity to confront declining political efficacy. To address this oversight, this study aims to provide a comprehensive understanding of facilitation in the context of democratic participation and political efficacy. Conducting a systematized review of 54 publications, the paper contributes significantly to the largely underexplored domain of facilitation theory. The study's findings offer a nuanced understanding of facilitation's role in democratic engagement. Far from just serving as a tool for managing interpersonal relations, the data demonstrate that facilitation is primarily employed to navigate process conflicts concerning agency, power, and responsibility. Furthermore, the data highlights a significant link between facilitation practice and increased internal and external political efficacy. These insights position facilitation as a crucial catalyst for democratic education, playing a key role in fostering a more engaged and resilient democratic society.

Development of the Patient-Reported Indicator Surveys (PaRIS) conceptual framework to monitor and improve the performance of primary care for people living with chronic conditions

BackgroundThe Organisation for Economic Co-operation and Development (OECD) Patient-Reported Indicator Surveys (PaRIS) initiative aims to support countries in improving care for people living with chronic conditions by collecting information on...

Advancing Soil Risk Assessment: A Novel Earthworm Cocoon Test with a Complementary Toxicokinetic-Toxicodynamic Modeling Approach.

In the current European Union pesticide risk assessment for soil organisms, effect endpoints from laboratory studies (Tier 1) and field studies (higher-tier risk assessment) are compared with predicted environmental concentrations in soil, derived from the proposed use pattern. The simple but conservative initial Tier 1 risk assessment considers a range of worst-case assumptions. In contrast, the higher-tier assessment focuses on specific conditions tested in the corresponding field study. Effect modeling, such as toxicokinetic-toxicodynamic (TKTD) modeling, is considered a promising future tool to address uncertainties in soil risk assessment, such as extrapolation to different ecological, pedo-climatical, or agronomical situations, or to serve as an intermediate tier for potential refinement of the risk assessment. For the implementation of TKTD modeling in soil organism risk assessment, data on earthworm growth and reproduction over time are required, which are not provided by the standard Organisation for Economic Co-operation and Development (OECD) 222 laboratory test. The underlying study with carbendazim presents a new earthworm cocoon test design, based on the OECD 222 test, to provide the necessary data as input for TKTD modeling. This proposed test design involves destructive samplings at days 7, 14, 21, and 28, enabling the determination of growth, cocoon number, and the number of juveniles hatched per cocoon in 7-day intervals. The new cocoon test allowed the disentanglement of the toxic effect of carbendazim in earthworms: At the highest concentration prominent effects on growth and reproductive output were observed, and the number of cocoons was significantly reduced compared to control. The results highlighted different physiological modes of action: effect on growth via higher maintenance costs as a primary mode of action as well as a reduced number of cocoons (effect on reproduction) and a lower number of juveniles hatching from each cocoon (hazard during oogenesis) as a secondary mode of action. We provide an example of how this new test's data can be used to feed a dynamic energy budget theory-TKTD model of Eisenia fetida. We also validate it against the original OECD 222 test design, outlining its potential future use in soil risk assessment. Environ Toxicol Chem 2024;43:2377-2386. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Bacillus subtilis ZB423: 90-Day repeat dose oral (gavage) toxicity study in Wistar rats.

The novel genetically modified probiotic Bacillus subtilis ZB423 was assessed in a 90-day repeated-dose oral toxicity study adhering to Good Laboratory Practice (GLP) and Organization for Economic Cooperation and Development (OECD) guidelines. Spray-dried spores at a concentration of 1.1E12 CFU/g were administered at doses of 130, 260, and 519 mg/kg body weight/day correlating to 1.43 × 1011, 2.86 × 1011, and 5.71 × 1011 CFU/kg/day, respectively, by oral gavage to Wistar rats for a period of 90 consecutive days. Results showed no toxicologically relevant findings for B. subtilis ZB423 from measured parameters. The no observed adverse effect level (NOAEL) of B. subtilis ZB423 is 519 mg/kg body weight/day corresponding to 5.71 × 1011 CFU/kg/day for lyophilized B. subtilis ZB423 spores under the test conditions employed.

Developing a sustainable development goals index for OECD countries: An effectiveness-based hierarchical data envelopment analysis

The Sustainable Development Goals (SDGs) consist of a set of multidimensional indicators comprising 17 goals and 169 targets from various perspectives. The use of a composite index is crucial for assessing the overall performance of each country in relation to the SDGs, given the extensive range of indicator measures involved. However, different weight schemes may lead to different results. Therefore, incorporating an objective weight is required to ensure the comparability and accuracy of the index. The main objective of this paper is to construct an SDG index for Organisation for Economic Co-operation and Development (OECD) countries using an effectiveness-based hierarchical data envelopment analysis (H-DEA) model and apply it to assess SDG effectiveness in OECD countries. The results of this study provide countries with more valuable insights based on the weights of the goals (indicators) that are endogenous to the dataset, assisting them in identifying priorities and strategies to improve future SDG performance.

Identifying Influential Variables on Health Expenditure of the Organisation for Economic Co-Operation and Development (OECD) Countries.

Health expenditures of countries have an increasing trend in general and identifying variables affecting health expenditure is an important step toward budget planning for financial sustainability. This study aimed to examine the health expenditure of the Organisation for Economic Co-operation and Development (OECD) countries and identify influential variables. The data for the years 2000-2018 of OECD countries' current health expenditure (% of GDP) and economic, demographic, and health variables, considered to affect the health expenditure, to include in the analysis were extracted using the World Bank database (World Bank 2021). Data analys using Chi-Squared Automatic Interaction Detection (CHAID) decision tree technique. Fifteen variables in economic, demographic, and health categories are selected to build the CHAID decision tree. As a result of CHAID analysis, five variables are identified as influential on current health expenditure, which are gross domestic product per capita, life expectancy at birth, death rate, out-of-pocket expenditure, and fertility rate. Thirty-seven OECD countries are classified into eleven groups by the decision rules in terms of the current health expenditure. The high value of the correlation coefficient between the predicted values and the actual values of health expenditure of countries indicates good prediction performance. Moreover, the regression models built using the identified influential variables as explanatory variables give good forecast accuracy. As an effective tool, the CHAID decision tree technique provides a rule-based model in the form of a tree with nodes and branches, illustrating the splitting process graphically with identified variables and their cut-off points for classification and prediction.

Preclinical evidence of the anti-inflammatory effect and toxicological safety of aryl-cyclohexanone in vivo.

Respiratory distress syndrome is a complex inflammatory condition defined by the presence of acute hypoxemia and cellular infiltration with diffuse alveolar injury following a tissue injury, such as acute lung injury. The inflammatory process involved in this pathology is a defense mechanism of the body against infectious agents and/or tissue injuries. However, when the condition is not reversed, it becomes a significant cause of tissue damage, sometimes leading to loss of function of the affected organ. Therefore, it is essential to understand the mechanisms underlying inflammation, as well as the development of new therapeutic agents that reduce inflammatory damage in these cases. Aryl-cyclohexanone derivatives have previously shown significant anti-inflammatory activity linked to an immunomodulatory capacity in vitro and may be good candidates for therapies in which inflammation plays a central role. Was evaluated the anti-inflammatory capacity of a synthesized molecule aryl-cyclohexanone in the murine model of lipopolysaccharide (LPS)-induced acute lung injury. The assessment of acute oral toxicity follows the Organization for Economic Co-operation and Development (OECD) guideline 423. The results demonstrated that the studied molecule protects against LPS-induced inflammation. We observed a decrease in the migration of total and differential leukocytes to the bronchoalveolar lavage fluid (BALF), in addition to a reduction in exudation, myeloperoxidase (MPO) activity, nitric oxide metabolites, and the secretion of pro-inflammatory cytokines (alpha tumor necrosis factors [TNF-α], interleukin-6 [IL-6], interferon-gamma [IFN-γ], and monocyte chemoattractant protein-1 [MCP-1]). Finally, aryl cyclohexanone did not show signs of acute oral toxicity (OECD 423). The results prove our hypothesis that aryl-cyclohexanone is a promising molecule for developing a new, safe anti-inflammatory drug.

Development of chemical categories for per- and polyfluoroalkyl substances (PFAS) and the proof-of-concept approach to the identification of potential candidates for tiered toxicological testing and human health assessment

Per- and Polyfluoroalkyl substances (PFAS) are a class of manufactured chemicals that are in widespread use and many present concerns for persistence, bioaccumulation and toxicity. Whilst a handful of PFAS have been characterized for their hazard profiles, the vast majority have not been extensively studied. Herein, a chemical category approach was developed and applied to PFAS that could be readily characterized by a chemical structure. The PFAS definition as described in the Toxic Substances Control Act (TSCA) section 8(a)(7) rule was applied to the Distributed Structure-Searchable Toxicity (DSSTox) database to retrieve an initial list of 13,054 PFAS. Plausible degradation products from the 563 PFAS on the non-confidential TSCA Inventory were simulated using the Catalogic expert system, and the unique predicted PFAS degradants (2484) that conformed to the same PFAS definition were added to the list resulting in a set of 15,538 PFAS. Each PFAS was then assigned into a primary category using Organisation for Economic Co-operation and Development (OECD) structure-based classifications. The primary categories were subdivided into secondary categories based on a chain length threshold (>=7 vs < 7). Secondary categories were subcategorized using chemical fingerprints to achieve a balance between total number of structural categories vs.level of structural similarity within a category based on the Jaccard index. A set of 128 terminal structural categories were derived from which a subset of representative candidates could be proposed for potential data collection, considering the sparsity of relevant toxicity data within each category, presence on environmental monitoring lists, and the ability to identify plausible manufacturers/importers. Refinements to the approach taking into consideration ways in which the categories could be updated by mechanistic data and physicochemical property information are also described. This categorization approach may be used to form the basis of identifying candidates for data collection with related applications in QSAR development, read-across and hazard assessment.