Organisation For Economic Co-operation And Development Guidelines Research Articles

Acute oral toxicity studies of methanolic extract and chloroform fraction of methanolic extract of seeds of muricata

Background: Natural products are considered to be safe and efficacious. Adequate proof of the safety of these herbal drugs is lacking. Objectives: The present study was undertaken to evaluate the acute oral toxicity of methanolic extract of seeds of Annona muricata (MAM) and chloroform fraction of MAM and to derive the lethal dose 50 (LD50) of chloroform fraction of methanol extract of seeds of A. muricata (CMAM). Materials and Methods: Acute toxicity studies of MAM and CMAM were conducted as per the Organisation for Economic Co-operation and Development (OECD) guidelines 420. LD50 of CMAM in rats and mice was estimated as per OECD guidelines 425. The toxic response was evaluated in vitro using hemolytic assay in rat and human erythrocytes. Results: The acute toxicity study done using OECD 420 guideline revealed that MAM and CMAM were safe at 300 mg/kg and produced mortality at 2000 and 5000 mg/kg. On gross examination, congestion of cranial, mesenteric, and uterine blood vessels was observed. As per OECD guidelines 425, CMAM was safe up to 980 mg/kg in rats and up to 175 mg/kg in mice and LD50 value was estimated to be 1310 mg/kg in rats and 310 mg/kg in mice. In vitro hemolytic assay showed that the plant fraction produced hemolysis. Conclusion: The present study concluded the toxicity produced by A. muricata seeds in the vascular system might be due to oxidative injury caused by the phytochemical constituents and it is essential to derive the safe pharmacological dose whenever the plant material is tested for efficacy studies.

Effects of ethanol extract of the resin exudate of boswellia dalzielii hutch on pain in mice

This study aimed to determine the analgesic properties and the acute toxicity of Ethanol Extract of the Resin Exudate of Boswellia dalzielii (EERBD) in mice animal model. We used the writhing or acetic acid abdominal constriction, tail-immersion, and hot plate tests to assess the analgesic effect of EERBD at three doses (100, 200, and 400 mg/kg). To study the acute toxicity of EERBD, 24 female mice were divided into four groups (n=6) and were orally treated with EERBD at the doses of 0, 2000, 4000, and 5000 mg/kg, as per OECD (Organization for Economic Co-operation and Development) guidelines No. 420. In the acetic acid-induced writhing reflex model, the EERBD ministration decreased the mean total number of writhes at the two doses (100 and 400 mg/kg), which were found highly significant (P < 0.001) compared to control group. In the tail immersion model, the EERBD administration at the dose of 400 mg/kg significantly increased the pain reaction time (P < 0.001 as compared to control) at 30 min, but another tested sample had no significant latency. In the hot-plate model, the drug extract created significant (P < 0.001) increase in the latency period compared to the control group at oral doses of 100 and 400 mg/kg when compared to initial time and control group (4.5 ± 1.29 s) with protective effect from 4.25 ± 1.50 s after 30 min. Administration of EERBD at the dose of 200 mg/kg showed no significant analgesic activity based on writing, tail immersion, and hot-plate tests. The extract did not show toxicity signs or death at dose of less than 5000 mg/kg per oral. The results suggest that EERBD contain bioactive substances with analgesics effects; hence, it might be a better alternative to conventional drug therapy for pain management.

Skin sensitizing effects of sulfur mustard and other alkylating agents in accordance to OECD guidelines

Vesicants cause a multitude of cutaneous reactions like erythema, blisters and ulcerations. After exposure to sulfur mustard (SM) and related compounds, patients present dermal symptoms typically known for chemicals categorized as skin sensitizer (e.g. hypersensitivity and flare-up phenomena). However, although some case reports led to the assumption that SM and other alkylating compounds represent sensitizers, a comprehensive investigation of SM-triggered immunological responses has not been conducted so far. Based on a well-structured system of in chemico and in vitro test methods, the Organization for Economic Co-operation and Development (OECD) established procedures to categorize agents on their skin sensitizing abilities. In this study, the skin sensitizing potential of SM and three related alkylating agents (AAs) was assessed following the OECD test guidelines. Besides SM, investigated AAs were chlorambucil (CHL), nitrogen mustard (HN3) and 2-chloroethyl ethyl sulfide (CEES). The methods are described in detail in the EURL ECVAM DataBase service on ALternative Methods to animal experimentation (DB-ALM). In accordance to OECD recommendations, skin sensitization is a pathophysiological process starting with a molecular initiating step and ending with the in vivo outcome of an allergic contact dermatitis. This concept is called adverse outcome pathway (AOP). An AOP links an adverse outcome to various key events which can be assayed by established in chemico and in vitro test methods. Positive outcome in two out of three key events indicates that the chemical can be categorized as a skin sensitizer. In this study, key event 1 “haptenation” (covalent modification of epidermal proteins), key event 2 “activation of epidermal keratinocytes” and key event 3 “activation of dendritic cells” were investigated. Covalent modification of epidermal proteins measured by using the DPRA-assay provided distinct positive results for all tested substances. Same outcome was seen in the KeratinoSens assay, investigating the activation of epidermal keratinocytes. The h-CLAT assay performed to determine the activation of dendritic cells provided positive results for SM and CEES but not for CHL and HN3. Altogether, following OECD requirements, our results suggest the classification of all investigated substances as skin sensitizers. Finally, a tentative AOP for SM-induced skin sensitization is suggested.

Acute and sub-acute toxicity study of bacterial signaling inhibitor Solanum torvum root extract in Wister rats

BackgroundSolanum torvum root extract is used to treat Asthma, Diabetes, and hypertension by Garo tribal healers of India and Bangladesh. Root tea is used to treat cough and fever by Attapadi tribal people of Kerala, India. The in vivo toxicological effects of Solanum torvum root extract was assessed by acute and sub-acute toxicity studies according to the OECD (Organisation for Economic Co-operation and Development) guidelines and per the guidance of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Environment and Forest, government of India.ResultsA single dose of Solanum torvum root extract (300 mg/kg, 600 mg/kg and 1200 mg/kg) was administrated daily for 14 days to estimate acute toxicity whereas subjects were treated for 28 days to assess the sub-acute toxicity. General functional behaviors, Physiological, histological, biochemical and hematological parameters were observed to understand the effect of extract upon study animal. All the study subjects were alive after the study period after acute and sub-acute toxicity assay. Functional and behavioral characteristics such as body position, respiration, clonic involuntary movement, tonic involuntary movement, palpebral closure, approach response, touch response, pinna reflex and tail pinch response; palpebral closure, lacrimation, salivation, piloerection, pupillary reflex, abdominal tone, limb tone, when held in hand were also found to be normal. Histological, biochemical and hematological parameters were also normal compared that with untreated group.ConclusionsThe acute and sub-acute toxicological analysis of Solanum torvum root extracts up on Wister rats suggested that there are no any dose response relation between extract administrated and toxicity, therefore there are no toxic effect by STRE, however more enlightenment regarding toxicity due to prolonged exposure can only be understood from chronic toxicity analysis.

Micronucleus Analysis by Flow Cytometry.

During the last two decades the micronucleus (MN) test has been extensively used as a genotoxicity screening tool of chemicals and in a variety of exploratory and mechanistic investigations. The MN is a biomarker for chromosomal damage or mitotic abnormalities since it can originate from chromosome fragments or whole chromosomes that fail to be incorporated into daughter nuclei during mitosis (Fenech et al., Mutagenesis 26: 125-132, 2011; Kirsch-Volders et al., Arch Toxicol 85: 873-899, 2011). The simplicity of scoring, accuracy, amenability to automation by image analysis or flow cytometry and the readiness to be applied to a variety of cell types either in vitro or in vivo made it a versatile tool that contributed to a large extent in our understanding of key toxicological issues related to genotoxins and their effects at the cellular and organism levels. Recently, the final acceptance of the in vitro MN test Organization for Economic Cooperation and Development (OECD) guideline 487 (OECD, Guideline for testing of chemicals: in vitro mammalian cell micronucleus test 487: in vitro mammalian cell micronucleus test (MNVIT). Organization for Economic Cooperation and Development, Paris, 2010) together with the standard in vivo MN test OECD guideline 474 (OECD, Guideline for the testing of chemicals no. 474 mammalian erythrocyte micronucleus test. Organization for Economic Cooperation and Development, Paris, 1997) further positioned the assay as a key driver in the determination of the genotoxicity potential in exploratory research as well as in the regulatory environment. This book chapter covers to some extent the protocol designs and experimental steps necessary for a successful performance of the MN test and an accurate analysis of the MN by the flow cytometry technique.

«Soft law» in the system of regulation of corporate relations

In modern terms, «soft law» is turning into an effective tool for regulating corporate and, in general, economic relations at the national level. International corporate governance standards serve as a benchmark for the development of corporate law in all countries of the world. The subject of «lawmaking» in this case is not a state, but an international organization that formulates and adopts recommendation acts.The problem of «soft law» in modern legal science is very popular; it is devoted to a considerable number of works of foreign and domestic scientists, in particular, G. M. Velyminov, T. M. Neshataeva, J. B. Fogelson, T. Matveeva and others. For the first time in the post-Soviet space the problem of «soft» corporate law was raised by S. O. Chekhovskaja in 2012.The purpose of the article is to define the role of «soft law» in the system of regulation of corporate relations.There are three basic approaches to understanding «soft law» in the legal science:1) «soft law» is reduced to recommendatory acts of international intergovernmental organizations;2) «soft law» covers both documents of international intergovernmental organizations, as well as non-governmental organizations, in particular, Principles of international commercial agreements of UNIDROIT, ICC acts, etc .;3) the most widespread approach, in which «soft law» is considered instruments of non-state regulation, both international and national.The greatest influence of soft law acts has been such a part of corporate relations as corporate governance relations. The «soft law» acts in the field of corporate governance include: The G20 / Organization for Economic Cooperation and Development (OECD) Principles of Corporate Governance 2015, Declaration on International Investments and Multinational Enterprises 1976 and the OECD Guidelines for Multinational Enterprises 2011 as a component of the latter.The «soft» standards of corporate governance, which are legally non-binding in nature, due to the authority of the organization they have developed, are used by the states to reform corporate law. The paper proposes to distinguish between «soft law» acts and normative legal acts of recommendation nature, such as those approved by the decisions of the National Securities and Stock Market Commission dated July 24, 2014 No. 955 Principles of Corporate Governance.Soft law recommendations of international organizations, and OECD, in particular, have an impact both on the member states of the organization and on all other states and their private entities. Attention is drawn to the practice of voluntarily taking States' international obligations to comply with soft law. So, Ukraine is in accordance with Clause «c» of Part 1 of Art. 387 of the Association Agreement with the EU has committed itself to further developing corporate governance policies in line with international standards, namely the OECD Principles.Voluntary compliance with international corporate governance standards of corporations interested in good business reputation and increasing its competitiveness leads to the formation of corporate business practices in corporate relations.Today «soft law» defines the vector of development of corporate relations at the national level, and also serves as a tool for harmonization of national laws of different countries of the world. Soft law regulates corporate relations indirectly - through the influence on the development of national legislation, as well as directly - through the voluntary introduction by corporations of international standards in local regulations statutes, regulations, principles (codes) of corporate governance, as well as the formation of international commercial usages.

ACUTE AND SUB CHRONIC TOXICITY STUDIES OF PURIFIED WITHANIA SOMNIFERA EXTRACT IN RATS

Objective: The objective of the present study was to evaluate the acute and sub-chronic (90 d; repeated dose) toxicity of Withania somnifera (ashwagandha) extract in rats.Methods: The acute toxicity was evaluated as per OECD (Organisation for Economic Co-operation and Development) guidelines 423. Purified ashwagandha extract (PAE) was fed at 2000 mg/kg body weight (bw) to overnight fasted female rats. The animals were observed daily for clinical signs of abnormality/mortality. After 14 d, animals were sacrificed and gross pathological changes were recorded. Sub-chronic toxicity of PAE was studied by feeding the extract at 100, 500 and 1000 mg/kg bw daily to rats as per OECD guidelines 408. After 90 d feeding, heamatological and biochemical parameters of treated rats were compared with control animals. Histopathology of all the major organs was also studied.Results: In the acute toxicity study, no mortality or clinical signs of toxicity were observed in any of the animals at maximum recommended dose level of 2000 mg/kg bw; therefore the LD50 is>2000 mg/kg bw in rats. The repeated administration of PAE for 90 d in rats at the maximum dose level of 1000 mg/kg bw did not induce any observable toxic effects, when compared to its corresponding control animals. The hematology and biochemistry profile of treated rats was similar to control animals and difference was non-significant (p>0.05). The histopathology of major organs of all the control and treated animals was normal. In this study the NOAEL (No Observed Adverse Effect Level) was calculated as 1000 mg/kg bw daily for rats.Conclusion: The present study clearly indicates that PAE does not have any toxic effects in animals at the dose evaluated as evidenced by acute and sub chronic toxicity studies in rats.

Subchronic Toxicity Evaluation of Ethanol Extract of Picria fel-terrae Lour. Leaf in Wistar Rats.

Picria fel-terrae extract has been investigated for its hepatoprotective activity. This current study was conducted to evaluate the subchronic toxic effect of Picria fel-terrae Lour. leaf extract. The subchronic toxicity of ethanol extract of P. fel-terrae leaf was evaluated by OECD (Organization for Economic Cooperation and Development) guidelines. The extract at doses of 125, 250, 500, 1000 mg/kg body weight (BW) were orally administered to the test animals for 90 days. Signs of toxicity and mortality were observed for 90 days and 118 days. The biochemistry, hematology, macropathology, relative organ weight and histopathology examination was also performed. The macroscopic and microscopic examinations of liver, lung, kidney, spleen and heart displayed normal color and texture after treatment, with ethanol extract P. fel-terrae leaf at doses of 125 and 250 mg/kg BW. The signs of toxicity, mortality, macroscopic and microscopic changes, as well as increasing biochemistry parameters were observed after treatment, with extract at the dose of 500 and 1000 mg/kg BW. However, the abnormal value of biochemistry parameters was returned to normal when the treatment was stopped. There was no effect on hematological parameters at all doses of extract. The ethanol extract P. fel-terrae leaf is untoxic for long-term use at dose 125 and 250 mg/kg BW. The toxic effect of P. fel-terrae at 500 and 1000 mg/kg BW was reversible.

Safety and Toxicology of Magnolol and Honokiol.

Magnolia officinalis and Magnolia obovata bark extracts have been used for thousands of years in Chinese and Japanese traditional medicines and are still widely employed as herbal preparations for their sedative, antioxidant, anti-inflammatory, antibiotic, and antispastic effects. Neolignans, particularly magnolol and honokiol, are the main substances responsible for the beneficial properties of the magnolia bark extract (MBE). The content of magnolol and honokiol in MBE depends on different factors, including the Magnolia plant species, the area of origin, the part of the plant employed, and the method used to prepare the extract. The biological and pharmacological activities of magnolol and honokiol have been extensively investigated. Here we review the safety and toxicological properties of magnolol and honokiol as pure substances or as components of concentrated MBE, including the potential side-effects in humans after oral intake. In vitro and in vivo genotoxicity studies indicated that concentrated MBE has no mutagenic and genotoxic potential, while a subchronic study performed according to OECD (Organisation for Economic Co-operation and Development) guidelines established a no adverse effect level for concentrated MBE > 240 mg/kg b.w/d. Similar to other dietary polyphenols, magnolol and honokiol are subject to glucuronidation, and despite a relatively quick clearance, an interaction with pharmaceutical active principles or other herbal constituents cannot be excluded. However, intervention trials employing concentrated MBE for up to 1 y did not report adverse effects. In conclusion, over the recent years different food safety authorities evaluated magnolol and honokiol and considered them safe.

Is a Water Content of 60% Maximum Water Holding Capacity Suitable for Folsomia candida Reproduction Tests? A Study with Silver Nanoparticles and AgNO₃.

Silver nanoparticles (AgNP) are increasingly emitted to the environment due to a rise in application in various products; therefore, assessment of their potential risks for biota is important. In this study the effects of AgNP at environmentally relevant concentrations (0.6–375 µg kg−1 soil) on the soil invertebrate Folsomia candida in OECD (Organisation for Economic Co-operation and Development) soil was examined at different soil water contents. Animals were retrieved by heat extraction, which had an efficiency of about 90% compared with the floatation method. The tested water content range is set by OECD Guideline 232 (40–60% of the maximum water holding capacity, WHC), and we detected significant differences in toxicity due to these. With AgNO3, used as an ionic control, the number of juveniles significantly decreased only at 40% WHC, which might be due to dilution of the toxicant at higher soil water content. In turn, at 60% WHC, the reproduction of F. candida significantly increased in the presence of AgNP compared with in the control. However, at this water content, the required number of juveniles in the control treatment was not reached in three independent tests. The fact that the OECD validity criterion is not met indicates that the soil conditions are not suitable for reproduction at 60% WHC.

Toxicity characteristics of sewage treatment effluents and potential contribution of micropollutant residuals

BackgroundA typical sewage treatment plant is designed for organic and nutrient removal from municipal sewage water and not targeted to eliminate micropollutants such as pesticides, pharmaceuticals, and nano-sized metals which become a big concern for sustainable human and ecological system and are mainly discharged from sewage treatment plant. Therefore, despite contaminant removal by wastewater treatment processes, there are still remaining environmental risks by untreated pollutants in STP (sewage treatment plant) effluents. This study performed aquatic toxicity tests of raw wastewater and treated effluents in two sewage treatment plants to evaluate toxicity reduction by wastewater treatment process and analyze concentration of contaminants to reveal potential toxic factors in STP effluents.MethodsWater samples were collected from each treatment steps of two STPs, and acute and chronic toxicity tests were conducted following USEPA (United States Environmental Protection Agency) and OECD (Organization for Economic Cooperation and Development) guidelines. Endpoints were immobility for mortality and reproduction effect for estrogenicity.ResultsAcute EC50s (median effective concentration) of influents for Seungki (SK) and Jungnang (JN) STPs are 54.13 ± 32.64% and 30.38 ± 24.96%, respectively, and reduced to 96.49 ± 7.84% and 100%. Acute toxicity reduction was clearly correlated with SS (suspended solids) concentration because of filter feeding characteristics of test organisms. Chronic toxicity tests revealed that lethal effect was reduced and low concentration of influents showed higher number of neonates. However, toxicity reduction was not related to nutrient removal. Fecundity effect positively increased in treated wastewater compared to that in raw wastewater, and no significant differences were observed compared to the control group in JN final effluent implying potential effects of estrogenic compounds in the STP effluents.ConclusionsConventional wastewater treatment process reduced some organics and nutritional compounds from wastewater, and it results in toxicity reduction in lethal effect and positive reproductive effect but not showing correlation. Unknown estrogenic compounds could be a reason causing the increase of brood size. This study suggests that pharmaceutical residues and nanoparticles in STP effluents are one of the major micropollutants and underline as one of estrogenic effect factors.

IN VIVO ANTI-DIABETIC ACTIVITY EVALUATION OF THE BARK OF CASCABELA THEVETIA L. IN STREPTOZOTOCIN INDUCED DIABETIC RATS

Objective: In this study, the plant Cascabela thevetia L. was selected based on ethnomedicinal documentation reports for evaluation of the antidiabetic activity. The aim of this study was to carry out acute toxicity study and in vivo evaluation of antidiabetic activity in an animal model.Methods: Firstly direct extraction of the dried bark powder was done with methanol using soxhlet apparatus. After collecting the extract, acute toxicity study was performed according to OECD (Organization for Economic Cooperation and Development) guideline 425. For in vivo evaluation of antidiabetic activity, streptozotocin (STZ) and nicotinamide induced type 2 diabetic male rat model was used. Six groups containing six animals in each were taken for the in vivo study and marked as normal control, standard control, negative control and test controls. For all the animals body weight, body temperature, blood glucose levels were determined at an interval of 5 d. After 15 d of treatment different biochemical parameters like triglyceride, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), alkaline phosphatase level (ALP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total protein were determined and the results were evaluated by statistically using one-way analysis of variance (ANOVA). On the 15th day, all the animals were sacrificed and histopathological study of pancreases tissue was done.Results: The effects of the test extracts in lowering the blood glucose level and maintaining other biochemical parameters in the test groups were compared with the effect of standard drug metformin hydrochloride, 10 mg/kg body weight treated group and negative control group. The data were statistically evaluated using one-way analysis of variance (ANOVA) followed by Dunnet comparison all vs control method and taking significant at p<0.01. By comparing different biochemical parameters and histoarchitecture of the different test groups of animals, it was found that group V treated with 200 mg/kg body weight shows a significant effect.Conclusion: After performing the experiment it was found that the bark of Cascabela thevetia L. has the potential for blood glucose lowering activity and able to control abnormal lipids and enzymes level in blood. Further isolation of the compounds can lead to finding out the exact compound responsible for the activity.

Anticholangiocarcinoma activity and toxicity of the Kaempferia galanga Linn. Rhizome ethanolic extract

BackgroundCholangiocarcinoma (CCA) is an important public health problem in several tropical and subtropical parts of the world particularly Thailand. Chemotherapy of CCA is largely ineffective and discovery and development of effective alternative drugs is urgently needed. The objective of the study was to confirm the anti-CCA potential as well as toxicity of the crude extract of Kaempferia galangal Linn. (rhizome) both in vitro and in animal models.MethodsThe ethanolic extract of K. galanga Linn. rhizome, ethyl-p-methoxycinnamate (EPMC) and 5-fluorouracil (5-FU) were evaluated for their cytotoxic activities against CCA cell line (CL-6) using MTT cell proliferation assay. Acute and subacute toxicity of the extract were evaluated in ICR (Imprinting Control Region) mice according to the OECD (International Organization for Economic Co-operation and Development) Guideline. Anti-CCA activity was evaluated in CCA- xenografted nude mice.ResultsResults of cytotoxicity test showed moderate activity of the extract and EPMC with median (95% confidence interval: 95% CI) 50% inhibitory concentration (IC50) of 64.2 (57.76–72.11) and 49.19 (48.16–52.29) μg/ml, respectively. The IC50 of 5-FU was 107.1 (103.53–109.64) μg/ml. The selectivity index (SI) values for the extract, EPMC and 5-FU against human normal cell line (OUMS) and cancer cell line (CL-6) were 2.2, 2.09 and 1.31, respectively. Toxicity testing revealed no overt toxic effect up to the maximum single oral dose of 5000 mg/kg body weight and up to daily dose of 1000 mg/kg body weight for 30 days. The extract at the maximum tolerated dose level of 1000 mg/kg body weight for 30 days exhibited promising anti-CCA activity in CL6-xenografted nude mice as determined by inhibitory activity on tumor growth (58.41%) and lung metastasis (33.3%), as well as prolongation of survival time (62 days).ConclusionThe K. galangal Linn. rhizome extract and its bioactive compound EPMC exhibited moderate cytotoxic activity against human CCA tumor (CL-6) cell line. Results of toxicity testing suggest that the extract was well tolerated up to the maximum single oral dose of 5000 mg/kg body weight and daily dose of 1000 mg/kg body weight for 30 days. The extract exhibited promising anti-CCA activity in CL6-xenografed nude mice as determined by significant inhibitory activity on tumor growth and lung metastasis, as well as prolongation of survival time.

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract.

Objective:To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek (Trigonella foenum-graecum L) seed extract in laboratory rats.Materials and Methods:The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively.Results:The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture.Conclusions:IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity.SUMMARY Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without mutagenicity or genotoxicity potetial. Abbreviations Used: 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control. 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control

Retraction Note to: “Global Assessment in the World Bank Education Strategy 2020”

This article published in Volume 2, Issue 1, pages 29-41 (DOI 10.5195/ehe.2011.41) has been retracted at the request of the editors. The editors became aware of the issue on 21 March 2016 and quickly began investigating the situation. Several locations in the article contain plagiarized texts from various authors, either with inadequate or no attribution. Specifically, these include: excerpts from Marilee J. Bresciani’s 2006 book Outcomes-Based Academic and Co-Curricular Program Review: A Compilation of Institutional Practices appearing on page 30; excerpts from Tom Schuller and Stéphan Vincent-Lancrin’s chapter in the 2009 book International Organizations and Higher Education Policy: Thinking Globally, Acting Locally? appearing on page 31; excerpts from the Organisation for Economic Co-operation and Development (OECD) website “UNESCO, OECD guidelines for quality provision in cross-border higher education” appearing on page 31; excerpts from David H. Kamens and Connie L. McNeely’s 2010 article, “Globalization and the Growth of International Education Testing and National Assessment” published in the Comparative Education Review appearing on page 31, and; excerpts from E. J. K. McKellar’s conference paper “Change our assessment practices? Why should we? The theory behind assessment practices” appearing on pages 32-33. The author apologizes to the journal and to its readers for the errors noted above.

Safety evaluation (acute and sub-acute studies) of the aqueous extract of the leaves of Myrianthus arboreus P. Beauv. (Cecropiaceae) in Wistar rats

Ethnopharmacological relevanceMyrianthus arboreus P. Beauv (Cecropiaceae) is a medicinal plant distributed in forests and damp places of tropical Africa. Its leaves are widely used as food and/or for the treatment of various ailments including dysmenorrhoea, female infertility, tumors and diarrhea. However, to the best of our knowledge, no safety assessment of this plant has been reported yet. Aim of studyThe present study aimed at evaluating the safety of the aqueous extract of leaves of Myrianthus arboreus (MAA) in Wistar rats through an acute and sub-acute oral administration. Material and methodsIn acute oral toxicity, the test was performed according to the Organization for Economic Cooperation and Development (OECD) guidelines Nr. 423 (acute toxicity class method, ATC) with slight modifications. Female Wistar rats were orally treated with the aqueous extract of M. arboreus at the doses of 2000 and 5000mg/kg. In sub-acute toxicity study, using the OECD guidelines Nr. 407, the extract was administered by gavage at the doses of 20, 110 and 200mg/kg/day for 28 consecutive days. ResultsA single oral administration of 2000 or 5000mg/kg of the extract induced neither mortality nor exterior signs of toxicity indicating a LD50 >5000mg/kg. In sub-acute study, the extract decreased triglycerides, total cholesterol/high density lipoproteins ratio and atherogenic index of plasma in both sexes at all tested doses. Alanine transaminase decreased in both sexes at 200mg/kg and serum creatinine levels decreased at all tested doses in females. Moreover, significant increases in ovarian and uterine wet weights, red blood cell count, hematocrit, mean corpuscular hemoglobin and hemoglobin were observed at 200mg/kg in females. In males, this extract decreased white blood cell count, lymphocytes and relative weight of seminal vesicles and ventral prostate at 200mg/kg. ConclusionThe aqueous extract of Myrianthus arboreus leaves was non-toxic in acute administration and exhibited a relatively low toxicity potential on accessory sex organs in both sexes, and leukocytes in males following the repeated 28-days oral administration of the dose 200mg/kg.

Preclinical safety evaluation of low molecular weight galactomannans based standardized fenugreek seeds extract.

The objective of the present study was to evaluate acute oral toxicity, subchronic toxicity, and mutagenic potential of low molecular weight galactomannans based standardized fenugreek seeds extract (LMWGAL-TF) in laboratory animals rats as per Organization for Economic Co-operation and Development (OECD) guidelines. For the acute toxicity (AOT) study, LMWGAL-TF was orally administered to Sprague-Dawley (SD) rats at a dose of 2000 mg/kg with vehicle control (VC) group (n = 5 per sex per group) as per OECD guideline no. 423. For the repeated dose toxicity study, the SD rats were orally administered with a daily oral dose of LMWGAL-TF 250, 500 and 1000 mg/kg/day with VC group (n = 15 per sex) for a period of 90 days followed by a recovery period of 28 days as per OECD guideline no. 408. The effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenic potential of LMWGAL-TF was tested using reverse mutation assay (AMES test, OECD guideline No. 471). The LMWGAL-TF did not show mortality or treatment-related adverse signs during acute (dose 2000 mg/kg) and subchronic (90-days repeated dose 250, 500 and 1000 mg/kg) administration. The LMWGAL-TF showed oral lethal dose (LD50) more than 2000 mg/kg during AOT study. The dose of 1000 mg/kg was found as no observed adverse effect level (NOAEL) in rats during subchronic toxicity study. Furthermore, LMWGAL-TF did not show mutagenic potential in vitro. In conclusion, LMWGAL-TF was found safe during acute and subchronic (90 days repeated dose) toxicity studies in rats with no mutagenicity.

In vitro steroid profiling system for the evaluation of endocrine disruptors

Endocrine disruptors (ED) are chemicals that affect various aspects of the endocrine system, often leading to the inhibition of steroidogenesis. Current chemical safety policies that restrict human exposure to such chemicals describe often time-consuming and costly methods for the evaluation of ED effects. We aimed to develop an effective tool for accurate phenotypic chemical toxicology studies. We developed an invitro ED evaluation system using gas chromatography/mass spectrometry (GC/MS/MS) methods for metabolomic analysis of multi-marker profiles. Accounting for sample preparation and GC/MS/MS conditions, we established a screening method that allowed the simultaneous analysis of 17 steroids with good reproducibility and a linear calibration curve. Moreover, we applied the developed system to H295R human adrenocortical cells exposed to forskolin and prochloraz in accordance with the Organization for Economic Cooperation and Development (OECD) guidelines and observed dose-dependent variations in steroid profiles. While the OECD guidelines include only testosterone and 17β-estradiol, our system enabled a comprehensive and highly sensitive analysis of steroid profile alteration due to ED exposure. The application of our ED evaluation screen could be economical and provide novel insights into the hazards of ED exposure to the endocrine system.

Outcome of the pesticides peer review meeting on general recurring issues in ecotoxicology

Outcome of the pesticides peer review meeting on general recurring issues in ecotoxicology

Evaluation of the in vivo genotoxicity of Allura Red AC (Food Red No. 40)

Allura Red AC (Food Red No. 40) is a red azo dye that is used for food coloring in beverage and confectionary products. However, its genotoxic properties remain controversial. To clarify the in vivo genotoxicity, we treated mice with Allura Red AC and investigated the induction of DNA damage (liver, glandular stomach), clastogenicity/anuegenicity (bone marrow), and mutagenicity (liver, glandular stomach) using Comet assays, micronucleus tests, and transgenic gene mutation assays, respectively. All studies were conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guideline. Although Allura Red AC was administered up to the maximum doses recommended by the OECD guideline, no genotoxic effect was observed in any of the genotoxic endpoints. These data clearly show no evidence of in vivo genotoxic potential of Allura Red AC administered up to the maximum doses in mice.