Organisation For Economic Co-operation And Development Guidelines Research Articles

Evaluation of the Genotoxicity of Almond Hull: Implications for Its Use as a Novel Food Ingredient.

Almond hull, a substantial byproduct comprising more than half of almond fresh weight, has recently gained attention due to its functionality and sustainability benefits. Despite heightened interest, information regarding its toxicity remains limited. In order to assess its genotoxic potential, we conducted Good Laboratory Practice-compliant in vitro and in vivo studies following Organization for Economic Co-operation and Development (OECD) guidelines. No evidence of toxicity or mutagenicity was observed in a bacterial reverse mutation assay using five tester strains, evaluating almond hull at concentrations up to 5 mg/plate, with or without metabolic activation. Almond hull did not induce chromosome structural damage in a chromosome aberration assay using Chinese hamster ovary cells, nor did it cause any spermatogonial chromosomal aberration in tested male BALB/c mice. To evaluate its ability to induce DNA damage in rodents, a combined micronucleus assay was conducted in KM mice of both sexes. Almond hull was administered at doses of 1250, 2500, and 5000 mg/kg/day via gavage once daily for 2 days. No adverse effects of almond hull were observed in the micronucleus assay. Our results indicate no evidence of the genotoxic potential of almond hull administered up to the maximum concentrations of 5 g/kg, as recommended by OECD guidelines.

Exploring the anti-inflammatory, sedative, antidiabetic, and antioxidant potential in in-vitro and in-vivo models and phenolic profiling of Atractylis aristata Batt.

Ethnopharmacological relevanceAtractylis aristata batt., as an endemic plant from the Asteraceae family, holds a significant position in the Ahaggar region of southern Algeria's traditional medicine. The aerial parts of Atractylis aristata was used to cure inflammation, fever, and stomach disorders. Aim of the studyThe objective of the present investigation was to ascertain the overall bioactive components and phytochemical components and examine the antioxidant, antidiabetic, anti-inflammatory, acute toxicity, and sedative properties of the crude extract obtained from the aerial portions of Atractylis aristata (AaME). Materials and methodsThe AaME's antioxidant activity was assessed by the use of pyrogallol autoxidation, (1,1 diphenyl-2-picrylhydrazyl) (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and reducing power (RP) techniques. 1 mg/mL of AaME was used to evaluate the antidiabetic activity by applying the enzyme α-amylase inhibitory power test. At the same time, the bovine serum albumin (BSA) denaturation method was employed to quantify the in vitro anti-inflammatory activity at different concentrations (1.5625, 0.78125, 0.390625, 0.1953125 and 0.09765625 mg/mL). In contrast, following the Organization for Economic Co-operation and Development (OECD) guideline No. 423, which covers acute oral toxicity testing protocols, the limit dosage test was employed to assess in vivo acute toxicity. At the dose of 0.08 mg/mL, the carrageenan-induced paw edema approach was used to assess the anti-inflammatory efficacy in vivo, and the sedative activity was carried out at the dose of 0.08 mg/mL using the measurement of the locomotor method. Different bioactive compounds were identified within AaME using LC-MS/MS and HPLC-UV analysis. ResultsThe acute toxicity study showed no fatalities or noticeable neurobehavioral consequences at the limit test; this led to their classification in Globally Harmonized System (GHS) category Five, as the OECD guideline No 423 recommended. At a concentration of 0.08 mg/mL (2000 mg/kg), AaME showed apparent inhibition of paw edema and a significant (p = 0.01227) reduction in locomotor activity compared to the control animals. Our findings showed that AaME exhibited considerable antioxidant (IC50 = 0.040 ± 0.003 mg/mL (DPPH), IC50 = 0.005 ± 5.77 × 10-5 mg/mL (ABTS), AEAC = 91.15 ± 3.921 mg (RP) and IR% = 23.81 ± 4.276 (Inhibition rate of pyrogallol) and rebuts antidiabetic activities (I% = 57.6241% ± 2.81772). Our findings revealed that the maximum percentage of BSA inhibition (70.84 ± 0.10%) was obtained at 1.562.5 mg/mL. Thus, the AaME phytochemical profile performed using phytochemical screening, HPLC-UV, and LC-MS/MS analysis demonstrated that A. aristata can be a valuable source of chemicals with biological activity for pharmaceutical manufacturers. ConclusionThe phytochemical profiling, determined through HPLC-UV and LC-MS/MS applications, reveals this plant's therapeutic value. The aerial parts of Atractylis aristata contain bioactive molecules such as gallic acid, ascorbic acid, and quercetin, contributing to its significant antioxidant capabilities. Furthermore, identifying alizarin, the active compound responsible for its anti-inflammatory properties, could provide evidence supporting the anti-inflammatory capabilities of this subspecies.

Acute and Sub-chronic Toxicity Evaluation of the Ethanolic Extract of Coula edulis B., (Olacaceae) Stem Bark

Aims: Coula edulis Baill., (Olacaceae) is a non-lignified forest product not well known and widely used in sub-Saharan Africa as a phytomedicine or food additive. However, the toxicity of this plant remains unknown. This study aimed to assess the safety of the ethanolic extract of C. edulis stem bark (CEE).
 Study Design: Pharmacological study.
 Place and Duration of Study: Laboratory of Nutrition and Nutritional Biochemistry, Department of Biochemistry, University of Yaounde 1 (Cameroon), between June 2018 and July 2022.
 Methodology: Studies on the assessment of acute and subchronic toxicity were carried out by guidelines 423 of the Organization for Economic Co-operation and Development (OECD). Subacute toxicity of the sample was assessed over 28 days using repeated doses by OECD Guideline 407.
 Results: No cases of death and clinical signs of toxicity were observed in the treated rats, suggesting that the LD50 of C. edulis ethanolic extract is greater than 2000 mg/kg bw. Regarding the subacute toxicity study, the administration of CEE also did not result in any changes in the course of body weight. Only a significant decrease in the relative weight of the ovaries in females at the highest dose of 600 mg/kg was observed. In males and females, CEE did not affect lipid profile markers or transaminase levels (AST, ALT). In addition, a small but non-significant (p> 0.05) increase in creatinine was observed without kidney dysfunction. In males, CEE induced an increase in mean corpuscular volume number at 600 mg/kg, while at the same time, mean corpuscular hemoglobin concentration decreased at the 300 mg/kg dose. In females, a significant increase in the number of monocytes, red blood cells, and hemoglobin level were observed. No difference in the levels of urea, glucose, and lipid markers was observed nor histological changes in the organs studied.
 Conclusion: As would be expected, exposure to CEE did not cause significant toxic effects in treated rats. Therefore, this plant extract can be safely recommended for therapeutic use.

Development of a Lymnaea stagnalis embryo bioassay for chemicals hazard assessment

The validation of high-throughput toxicity tests with invertebrate species is a key priority to improve hazard assessment of new chemicals and increase the available test guidelines with organisms from a representative set of taxa. This work aimed to contribute to the validation of an embryo test with the freshwater gastropod Lymnaea stagnalis, which has been identified by Organization for Economic Co-operation and Development (OECD) as a potential invertebrate test model, and provide the basis for such an endeavor. Recently, a L. stagnalis reproductive test was standardized by the OECD. However, to encompass the entire life cycle, it is crucial to addresses embryogenic development — a phase highly susceptible to various anthropogenic chemicals, which is covered in the proposed methodology. The approach used in the present study is in line with the OECD guidelines and other published studies, namely the Detailed Review Paper (DRP) on Mollusks life-cycle toxicity testing.Here, the assay quality criteria such as basal mortality and abnormality rates, development, growth and hatching rates, the appropriated testing media, and the optimal assay duration were investigated. Cadmium was chosen as the positive test substance, due to the available data and the verified model sensitivity to this compound, namely in the OECD reproductive test validation process.The obtained data demonstrate that L. stagnalis embryogenesis using the developed methodology is highly sensitive to cadmium. High concentration-response correlation was observed using this reference compound, the EC10 and EC50 for growth are 13.57 and 21.84 μg/L, respectively, after 168 h of exposure. The development EC's 10 and 50 were 15.75 and 38.66 μg/L, respectively, after 240 h. This demonstrates the model sensitivity to this compound when compared with other embryo test models, as well as the model sensitivity during the embryogenesis, if compared with the adult stage. Further, given the determined sensitivity parameters, and incubation times, the test can be performed at 240 h as over 95 % of the control embryos were hatched and no further significant changes in the exposure groups were determined.Overall, the findings of the present study demonstrate that the embryo test with L. stagnalis has potential to high-throughput testing and the model has a high sensitivity to cadmium during this life cycle period. The background data provide by this study will be essential to foster the future standardization of this assay.

Acute Toxicity of Two Detergents on the Juvenile Climbing Perch (Anabas Testudineus) And Stinging Catfish (Heteropneustes Fossilis)

The two commercial household synthetic detergents were used to investigate the mortality and behavioural changes of juvenile Climbing perch (Anabas testudineus) and Stinging catfish (Heteropneustes fossilis). Average weight 2.83 ± 0.10 g and 3.93 ± 0.09g for A. testudineus and average length 3.85 ± 0.12cm and 4.33 ± 0.09cm were recorded for H. fossilis respectively. Acute toxicity tests were determined according to OECD (The Organization for Economic Cooperation and Development) guidelines for 72 hours exposure. Lethal Concentrations (LC10, LC50 and LC95) of both of the test materials were ascertained using probit analysis software (SPSS version 25) at 95% confidence limit. The LC50 values of detergent 1 were 120.4, 87.3, 59.7 mg/L for A. testudineus and 55.5, 31.6 and 24.5 mg/L for H. fossilis at 24h, 48h and 72h respectively. On the other hand, LC50 values of detergent 2 were 173.3, 90.2, 54.2 mg/L for A. testudineus and 44.8, 31.7, 22.0 mg/L for H. fossilis at 24h, 48h and 72h respectively. Toxicity was significantly increased along with exposure period for both fishes under two aquas conditions. H. fossilis was more susceptible than A. testudineus for both detergents. Comparative toxicity studies showed that detergent two was more effective than detergent one (detergent 2 ≥ detergent1). Physical changes such as discoloration in body and gill, damaged fin were also observed after 72h exposure of the both detergents. Behavioural responses in treated group were erratic swimming, restlessness, aggression, hyperactivity, more frequent movements at the bottom. Thus, adverse eco-toxicological impacts of synthetic detergents on fish mortality, behavioural pattern are suspected and suggested more elaborate research on physiological aspects for better understand the environmental impact in future. Bangladesh J. Zool. 51(1): 87-98, 2023

Acute and Sub-acute Oral Toxicity Assessment of Ferrum phosphoricum in Rats.

Ferrum phosphoricum (FP) has been used by traditional medicine practitioners for various ailments since ancient times. However, scientific evidence on the safety of FP is still unavailable. Thus, the current study aimed to investigate the acute and sub-acute oral toxicity of homeopathic FP in experimental rats. In an acute toxicity investigation, a single dose of 2,000 µL/kg of FP 6c, 30c and 200c was administered to female Wistar rats, which were monitored for up to 14 days according to the Organization for Economic Cooperation and Development (OECD) guideline 423. For a sub-acute toxicity study, FP 6c, 30c and 200c (200 µL/kg) were administered to male and female rats for 28 days as per the OECD guideline 407. All the animals were observed for mortality, clinical signs and body weight during the study. At the end of the experiment, hematological, biochemical and histopathological assessments were performed. During the acute toxicity study, no mortality was observed in rats administered with FP, and thus the median lethal dose (LD50) was identified as >2,000 µL/kg. In the sub-acute study, no mortality or adverse clinical signs were noticed with FP treatment. Moreover, weekly body weight gain was normal. Hematological and biochemical investigations revealed no abnormalities. Furthermore, histological analysis of FP-treated rats' vital organs revealed no pathological changes. Overall, our findings imply that FP 6c, 30c and 200c potencies are safe and do not cause toxicity when given orally to Wistar albino rats for an extended period at a dose of 200 µL/kg.

Confronting Challenges to Substantive Remedy for Victims: Opportunities for OECD National Contact Points under a Due Diligence Regime Involving Civil Liability

Abstract This article examines the under-researched, inter-connected issues of substantive remedy and a role for Organization for Economic Cooperation and Development (OECD) National Contact Points (NCPs) to complement judicial remedy regimes involving civil liability for companies in home-state jurisdictions. Even where access to judicial procedural remedy exists, it need not ensure substantive remedy. Legal and economic resource-based power-disparities between parties can reduce victims’ opportunities to present and argue their case; and courts offer limited substantive remedy options compared with the types listed by the United Nations Guiding Principles on Business and Human Rights. The article argues that combining access to NCPs and judicial remedy offers important opportunities to address well-recognized challenges for victims’ access to substantive remedy, especially with strong NCPs. NCPs can operate in ways that courts normally cannot, to help give victims voice and a choice of substantive outcome. The European Union’s Corporate Sustainability Due Diligence Directive (CSDDD) proposal serves as a cue for the analysis. However, the issue is relevant for any OECD member or the OECD Guidelines adherent state.

Toxicological and pharmacological effects of Eugenia brasiliensis Lam. (Myrtaceae) leaves in mice.

Eugenia brasiliensis Lam., popularly known as "grumixama" or "Brazilian cherry", is widely used in folk medicine with astringent, diuretic, energizing, anti-rheumatic, and anti-inflammatory properties. Despite its traditional use, detailed toxicological studies of Eugenia brasiliensis are few. Thus, in the current study, we evaluate the toxicological effects of hydroalcoholic extract of Eugenia brasiliensis (HEEb) and its antinociceptive and anti-inflammatory activity. We used male, and female Swiss mice. Acute toxicity study was performed following the Organization for Economic Cooperation and Development (OECD) guideline 425, and subacute toxicity was assessed following OECD guideline 407. We observed behavioral responses, in addition to hematological, biochemical, and histological evaluations. The antinociceptive and anti-inflammatory activity of HEEb were assessed using the Carrageenan-induced mechanical allodynia and paw edema model. Mechanical allodynia, levels of inflammatory cytokines, and oxidative damage were evaluated. The treatment with HEEb was not able to generate important toxicological alterations. Moreover, doses of 100 and 300mg/kg of HEEb were able to reduce mechanical allodynia, paw edema, and inflammatory cytokines (TNF-α, IL-1β, and IL-6), decrease malondialdehyde and increase superoxide dismutase enzyme activity in the paw. This study demonstrated that HEEb does not present important toxic effects. Additionally, an important antinociceptive, anti-inflammatory, and antioxidant potential were observed.

A Study of the Antihyperlipidemic and Antioxidant Activities of Ethanolic Extracts of Leaves of Houttuynia cordata Thunb . (EELHC) in Albino Rats

The present study was designed to evaluate the antihyperlipidemic and antioxidant activities of leaves of Houttuynia cordata Thunb. The ethanolic extract was obtained by percolation method and acute oral toxicity tests were performed according to OECD (Organization for Economic Cooperation and Development) guidelines. Hyperlipidaemia was induced by feeding the rats with a high-fat diet consisting of coconut oil and vanaspati ghee, in a ratio of 2:3 v/v at a dose of 10 ml/Kg body weight. The extract was given at a dose of 500mg/kg body weight. Lipid profile, Malondialdehyde (MDA), Catalase (CAT), and Superoxide Dismutase (SOD) were measured using standard methods. The extract showed a significant decrease in total cholesterol, triglycerides, LDL, and MDA in the blood. On the other hand, HDL, CAT, and SOD increased significantly. The study demonstrates that the ethanolic extract of leaves of Houttuynia cordata Thunb., decreases blood lipid levels and lipid peroxidation. Keywords: Antihyperlipidemic, Antioxidant, Houttuynia cordata Thunb, EELHC

Acute and Repeated Dose 28-Day Oral Toxicity Study of the Aqueous Extracts from the Leafy Stem and Fruit of Pedalium murex D.Royen EX.L in Wistar Rats.

Pedalium murex (P. murex) is used in folk medicine for treatment of male infertility. However, scientific data on its safety are limited. This study was carried out to assess the acute and repeated dose 28-day oral toxicity of the aqueous extracts from P. murex leafy stem and fruit in Wistar rats. The acute toxicity test was performed according to the line 423 of the Organization for Economic Cooperation and Development (OECD) guidelines. The rats were randomly divided into three groups (n = 3). The control group received distilled water, while the experimental groups were given at a single dose, 5000 mg/kg of each extract. The repeated dose 28-day oral toxicity was performed according to the line 407 of the OECD guidelines. 35 rats divided into 7 groups of 5 male rats each were daily treated for 28 days with each extract at 200 mg/kg, 400 mg/kg, and 800 mg/kg, respectively. The in-life parameters were recorded during the follow-up. At the end of this study, organ weights, hematology, biochemistry, and histology parameters were analyzed. In the acute oral toxicity test, there was no morbidity or mortality related to the treatments. Both extracts belong therefore to category 5 of the globally harmonized system (GHS) of classification. In the repeated dose 28-day oral toxicity test, both extracts did not alter animal's behavior. However, both extract administration led to proteinuria and renal damages. P. murex leafy stem and fruit aqueous extracts exhibited potential nephrotoxicity. Therefore, care should be taken when they are used over an extended period.

Ethylated analogue of Zingerone: A new and eco-respectful preservative in cosmetics.

This article describes the eco-design of a new preservative in cosmetics based on bio-inspiration of natural extracts from traditional medicines. In order to reach the multiple specification targets, various structures have been synthesized and evaluated to select the one demonstrating broad antimicrobial spectrum with favorable environmental profile and application potential to a wide variety of formulas. In order to evaluate the antimicrobial activity of the synthesized structures, the method of the challenge test consisting in an artificial contamination of the sample with collection microbial strains and evaluation of the number of revivable microorganisms was used to select the most promising candidate. Validation of its antimicrobial potential was later confirmed on Gram positive and Gram negative bacteria, yeast and mold with measurement of its Minimum Inhibitory Concentration (MIC) in comparison with known preservatives. Environmental impact assessment of the selected candidate was achieved with the help of ready biodegradability and aquatic ecotoxicity tests performed according to appropriate Organization tes a strfor Economic Co-operation and Development (OECD) and European Union (EU) guidelinesy. Bio-inspired from turmeric and ginger extracts, an ethylated analog of Zingerone (EZ) with the chemical name 4-(3-ethoxy-4-hydroxyphenyl)butan-2-one demonstrates the strongest activity on Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans. Moreover, EZ shows a solubility in water two times higher than that of Zingerone thus increasing its interest as a potential preservative. Finally, its assessment of ready biodegradability and aquatic ecotoxicity in OECD-EU tests with a favorable environmental profile confirms its unique interest and fully justifies its use in cosmetic formulas as an eco-respectful preservative. Bio-inspiration based on technologies without noteworthy side effects but also on eco-design, particularly through the use of measures of potential environmental impact very upstream of a development, are two fundamental elements for the launching of new eco-friendly cosmetic ingredients. This approach has thus validated the strong potential of EZ as a preservative of eco-respectful formulas. The selection of EZ is also a very good example of the achievement of two key objectives targeted by cosmetic companies for the development of a novel active ingredient: environmental performance and technical performance.

Subchronic toxicity study of the characterized hydroalcoholic extract of Paederia foetida (L.) leaves in swiss albino mice

• Chemical characterization of hydroalcoholic extract of paederia foetida (Linn.). • HPTLC fingerprinting profile of hydroalcoholic extract of P. foetida. • Sub chronic toxicity profile of hydroalcoholic extract of P. foetida. • In vivo safety assessment of hydroalcoholic extract of P. foetida according to OECD guideline 408. Paederia foetida Linn. have long been used as traditional medicines in subtropical countries for various diseases such as treatment of rheumatism, diarrhoea, inflammation, piles, snake bites, toothaches and a variety of other ailments. Phytochemical investigations of P. foetida leaves suggest the presence of glycosides, flavonoids, alkaloids, carbohydrates, amino acids and volatile oils. HPTLC fingerprint of hydroalcoholic extract of P. foetida leaves (HAPF) was developed for the quality control. Since the toxicity of a plant following repeated exposure is of higher clinical significance, the present investigation was conducted to establish the subchronic toxicity profile of the HAPF. Sub-chronic oral toxicity study of HAPF was done according to the Organization for Economic Cooperation and Development (OECD) guideline, HAPF was administered to swiss albino mice at doses of 1000, 300 and 100 mg/kg b. w. per day for 90 days. There was no significant ( p < 0.05) difference observed in the consumption of food and water, body weight and relative organ weights in different treatment groups comparison with vehicle treated mice. Changes in haematological and serum biochemical levels were not significant ( p < 0.05), which showed that long-term oral consumption of HAPF had no adverse effects. The histopathology examination did not show any differences in the organs that are critical to life. Based on what we found, HAPF is safe for long-term oral consumption at doses up to 1000 mg/kg body weight.

Ayapana triplinervis Vahl: Potential toxicity and therapeutic effects assessed in a zebrafish model

Background: In Reunion, 27 medicinal plants have recently been registered in the French Pharmacopoeia. Among them, Ayapana triplinervis Vahl (A. triplinervis) is traditionally used to combat inflammation and oxidative stress, as well as to promote healing and tissue regeneration. Purpose: This work aims to investigate the toxicity of A. triplinervis Aqueous Extract (AAE) using the zebrafish model, and to determine its Maximum Non-Toxic Concentration (MNTC). Then, using several pathological models established in zebrafish, the beneficial effects of AAE at its MNTC on inflammation, oxidative stress, tissue regeneration, and on lipid accumulation were investigated. Methods: AAE toxicity was evaluated according to the OECD (Organization for Economic Cooperation and Development) guidelines in the zebrafish eleutheroembryos (0 to 96 hpf) and by gene/transgene expression analyses of toxicity biomarkers. The impact of AAE on inflammation, oxidative stress and regeneration was studied by immunohistochemistry and reactive oxygen species staining methods in a caudal fin amputation model. Finally, the beneficial effects of AAE on lipid accumulation were investigated in high-fat diet (HFD)treated larvae. Results: AAE increased immune cell recruitment as well as tail regeneration after caudal fin amputation. It also reduced oxidative stress. In the HFD larva model, AAE showed interesting lipid reduction effects. Conclusion: Using rapid and robust zebrafish models, we demonstrated the beneficial properties of AAE, highlighting its pro-regenerative, antioxidant and lipid-lowering effects.

Standardisation and international adoption of defined approaches for skin sensitisation.

In the absence of stand-alone one-to-one replacements for existing animal tests, efforts were made to integrate data from in silico, in chemico and in vitro methods to ensure sufficient mechanistic coverage of the skin sensitisation Adverse Outcome Pathway (AOP) and generate predictions suitable for hazard identification and potency sub-categorisation. A number of defined approaches (DAs), using fixed data interpretation procedures (DIP) to integrate data from multiple non-animal information sources, were proposed and documented using a standard reporting template developed by the Organisation for Economic Co-operation and Development (OECD). Subsequent international activities focused on the extensive characterisation of three of these DAs with respect to the reference in vivo data, applicability domains, limitations, predictive performances and characterisations of the level of confidence associated with the predictions. The ultimate product of this project was an OECD Guideline that provides information equivalent to that provided by the animal studies and that can be used to satisfy countries’ regulatory data requirements for skin sensitisation. This Defined Approach Guideline was the first of its kind for the OECD, and provides an important precedent for regulatory adoption of human biology-relevant new approach methodologies with performances equivalent to, or better than, traditional animal tests. This mini review summarizes the principal features of the defined approaches described in OECD guideline 497.

Adverse outcome pathway from activation of the AhR to breast cancer-related death.

Adverse outcome pathways (AOPs) are formalized and structured linear concepts that connect one molecular initiating event (MIE) to an adverse outcome (AO) via different key events (KE) through key event relationships (KER). They are mainly used in eco-toxicology toxicology, and regulatory health issues. AOPs must respond to specific guidelines from the Organization for Economic Co-operation and Development (OECD) to weight the evidence between each KE. Breast cancer is the deadliest cancer in women with a poor prognosis in case of metastatic breast cancer. The role of the environments in the formation of metastasis has been suggested. We hypothesized that activation of the AhR (MIE), a xenobiotic receptor, could lead to breast cancer related death (AO), through different KEs, constituting a new AOP. An artificial intelligence tool (AOP-helpfinder), which screens the available literature, was used to collect all existing scientific abstracts to build a novel AOP, using a list of key words. Four hundred and seven abstracts were found containing at least a word from our MIE list and either one word from our AO or KE list. A manual curation retained 113 pertinent articles, which were also screened using PubTator. From these analyses, an AOP was created linking the activation of the AhR to breast cancer related death through decreased apoptosis, inflammation, endothelial cell migration, angiogenesis, and invasion. These KEs promote an increased tumor growth, angiogenesis and migration which leads to breast cancer metastasis and breast cancer related death. The evidence of the proposed AOP was weighted using the tailored Bradford Hill criteria and the OECD guidelines. The confidence in our AOP was considered strong. An in vitro validation must be carried out, but our review proposes a strong relationship between AhR activation and breast cancer-related death with an innovative use of an artificial intelligence literature search.

Mechanistic Analysis of Chemically Diverse Bromodomain-4 Inhibitors Using Balanced QSAR Analysis and Supported by X-ray Resolved Crystal Structures.

Bromodomain-4 (BRD-4) is a key enzyme in post-translational modifications, transcriptional activation, and many other cellular processes. Its inhibitors find their therapeutic usage in cancer, acute heart failure, and inflammation to name a few. In the present study, a dataset of 980 molecules with a significant diversity of structural scaffolds and composition was selected to develop a balanced QSAR model possessing high predictive capability and mechanistic interpretation. The model was built as per the OECD (Organisation for Economic Co-operation and Development) guidelines and fulfills the endorsed threshold values for different validation parameters (R2tr = 0.76, Q2LMO = 0.76, and R2ex = 0.76). The present QSAR analysis identified that anti-BRD-4 activity is associated with structural characters such as the presence of saturated carbocyclic rings, the occurrence of carbon atoms near the center of mass of a molecule, and a specific combination of planer or aromatic nitrogen with ring carbon, donor, and acceptor atoms. The outcomes of the present analysis are also supported by X-ray-resolved crystal structures of compounds with BRD-4. Thus, the QSAR model effectively captured salient as well as unreported hidden pharmacophoric features. Therefore, the present study successfully identified valuable novel pharmacophoric features, which could be beneficial for the future optimization of lead/hit compounds for anti-BRD-4 activity.

Hypericum lanceolatum Lam. Medicinal Plant: Potential Toxicity and Therapeutic Effects Based on a Zebrafish Model.

Hypericum lanceolatum Lam. (H. lanceolatum) is a traditional medicinal plant from Reunion Island used for its pleiotropic effects mainly related to its antioxidant activity. The present work aimed to 1) determine the potential toxicity of the plant aqueous extract in vivo and 2) investigate its putative biological properties using several zebrafish models of oxidative stress, regeneration, estrogenicity, neurogenesis and metabolic disorders. First, we characterized the polyphenolic composition by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and identified chlorogenic acid isomers, quercetin and kaempferol derivatives as the major compounds. We then evaluated for the first time the toxicity of an aqueous extract of H. lanceolatum and determined a maximum non-toxic concentration (MNTC) in zebrafish eleutheroembryos from 0 to 96 hpf following OECD (Organization for Economic Cooperation and Development) guidelines. This MNTC test was also determined on hatched eleutheroembryos after 2 days of treatment (from 3 to 5 dpf). In our study, the anti-estrogenic effects of H. lanceolatum are supported by the data from the EASZY assay. In a tail amputation model, we showed that H. lanceolatum at its MNTC displays antioxidant properties, favors immune cell recruitment and tissue regeneration. Our results also highlighted its beneficial effects in metabolic disorders. Indeed, H. lanceolatum efficiently reduces lipid accumulation and body mass index in overfed larva- and adult-models, respectively. In addition, we show that H. lanceolatum did not improve fasting blood glucose levels in a hyperglycemic zebrafish model but surprisingly inhibited neurogenesis impairment observed in diabetic conditions. In conclusion, our study highlights the antioxidant, pro-regenerative, anti-lipid accumulation and pro-neurogenic effects of H. lanceolatum in vivo and supports the use of this traditional medicinal plant as a potential alternative in the prevention and/or treatment of metabolic disorders.

Towards Standardization for Determining Dissolution Kinetics of Nanomaterials in Natural Aquatic Environments: Continuous Flow Dissolution of Ag Nanoparticles.

The dissolution of metal-based engineered nanomaterials (ENMs) in aquatic environments is an important mechanism governing the release of toxic dissolved metals. For the registration of ENMs at regulatory bodies such as REACH, their dissolution behavior must therefore be assessed using standardized experimental approaches. To date, there are no standardized procedures for dissolution testing of ENMs in environmentally relevant aquatic media, and the Organisation for Economic Co-operation and Development (OECD) strongly encourages their development into test guidelines. According to a survey of surface water hydrochemistry, we propose to use media with low concentrations of Ca2+ and Mg2+ for a better simulation of the ionic background of surface waters, at pH values representing acidic (5 < pH < 6) and near-neutral/alkaline (7 < pH < 8) waters. We evaluated a continuous flow setup adapted to expose small amounts of ENMs to aqueous media, to mimic ENMs in surface waters. For this purpose, silver nanoparticles (Ag NPs) were used as model for soluble metal-bearing ENMs. Ag NPs were deposited onto a 10 kg.mol−1 membrane through the injection of 500 µL of a 5 mg.L−1 or 20 mg.L−1 Ag NP dispersion, in order to expose only a few micrograms of Ag NPs to the aqueous media. The dissolution rate of Ag NPs in 10 mM NaNO3 was more than two times higher for ~2 µg compared with ~8 µg of Ag NPs deposited onto the membrane, emphasizing the importance of evaluating the dissolution of ENMs at low concentrations in order to keep a realistic scenario. Dissolution rates of Ag NPs in artificial waters (2 mM Ca(NO3)2, 0.5 mM MgSO4, 0–5 mM NaHCO3) were also determined, proving the feasibility of the test using environmentally relevant media. In view of the current lack of harmonized methods, this work encourages the standardization of continuous flow dissolution methods toward OECD guidelines focused on natural aquatic environments, for systematic comparisons of nanomaterials and adapted risk assessments.

Convergence of corporate governance in state-owned enterprises: A case study in an emerging market using OECD Guidelines

This article investigates an under-researched area of government activity and corporate governance reform, namely, corporate governance in state-owned enterprises. State-owned enterprises (SOEs) form a significant part of the economy in many countries and particularly in Asia. This article contributes to the larger corporate governance convergence debate by investigating whether arrangements originally conceptualised in the private sector prior to going global have indeed gone global and extended into the public sector. The article approaches the problem by investigating three interrelated questions posed by Clarke (2011): whether convergence could occur, whether it is occurring and whether such convergence is a good thing. Using a combination of DiMaggio and Powell’s (1983) institutional framework, convergence theory and doctrinal methods, the article sets the Organisation for Economic Co-operation and Development (OECD) Guidelines on Corporate Governance of State-Owned Enterprises as a benchmark and assesses Philippine state-owned enterprise law and practices. The analysis revealed a high level of convergence. We find evidence that convergence was occurring by a series of high-level dialogues, that it was open and sufficiently non prescriptive to allow selective adoption and adaptation to local context. In evaluating the convergence, we believe that the benefit to the overall welfare of the Philippines outweighed the drawbacks

Integrated skin sensitization assessment based on OECD methods (I): Deriving a point of departure for risk assessment_suppl2

Three guidelines covering key events in the skin sensitization adverse outcome pathway are endorsed by the Organisation for Economic Co-operation and Development (OECD). A recent guideline covers defined approaches (DA) to combine data from these tests for regulatory (sub)classification. The guideline methods provide continuous data that could characterize the sensitization potency on a more granular scale beyond (sub)classifications. We assembled a comprehensive database of in vitro and in vivo results from OECD guideline tests. Building on a previous approach using regression models, we provide quantitative models using input data from the kinetic direct peptide reactivity assay (kDPRA), the KeratinoSens™ (KS) assay, and the human cell line activation test (h-CLAT) to calculate a point of departure (PoD) in the form of a predicted local lymph node assay (LLNA) EC3 value for use in risk assessment. Predictive models include results from either two or all three assays. Detailed analysis versus in vivo data estimates redundancy between different tests and helps guide model selection. All models were tested on a set of case studies selected for their availability of multiple LLNA reference data in the OECD database. The predicted PoDs were within or close to the range of the variation of the historical LLNA data for most of these cases studies, and overall, the models predicted the in vivo value with a median fold-misprediction factor of around 2.5. The robustness of the models was characterized by comparing a comprehensive historical database versus the curated dataset provided by the OECD working group on DA.