Organisation For Economic Co-operation And Development Guidelines Research Articles

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.

Predicting aquatic toxicities of chemical pesticides in multiple test species using nonlinear QSTR modeling approaches

In this study, we established nonlinear quantitative-structure toxicity relationship (QSTR) models for predicting the toxicities of chemical pesticides in multiple aquatic test species following the OECD (Organization for Economic Cooperation and Development) guidelines. The decision tree forest (DTF) and decision tree boost (DTB) based QSTR models were constructed using a pesticides toxicity dataset in Selenastrum capricornutum and a set of six descriptors. Other six toxicity data sets were used for external validation of the constructed QSTRs. Global QSTR models were also constructed using the combined dataset of all the seven species. The diversity in chemical structures and nonlinearity in the data were evaluated. Model validation was performed deriving several statistical coefficients for the test data and the prediction and generalization abilities of the QSTRs were evaluated. Both the QSTR models identified WPSA1 (weighted charged partial positive surface area) as the most influential descriptor. The DTF and DTB QSTRs performed relatively better than the single decision tree (SDT) and support vector machines (SVM) models used as a benchmark here and yielded R2 of 0.886 and 0.964 between the measured and predicted toxicity values in the complete dataset (S. capricornutum). The QSTR models applied to six other aquatic species toxicity data yielded R2 of >0.92 (DTF) and >0.97 (DTB), respectively. The prediction accuracies of the global models were comparable with those of the S. capricornutum models. The results suggest for the appropriateness of the developed QSTR models to reliably predict the aquatic toxicity of chemicals and can be used for regulatory purpose.

Exploring simple, transparent, interpretable and predictive QSAR models for classification and quantitative prediction of rat toxicity of ionic liquids using OECD recommended guidelines

The present study explores the chemical attributes of diverse ionic liquids responsible for their cytotoxicity in a rat leukemia cell line (IPC-81) by developing predictive classification as well as regression-based mathematical models. Simple and interpretable descriptors derived from a two-dimensional representation of the chemical structures along with quantum topological molecular similarity indices have been used for model development, employing unambiguous modeling strategies that strictly obey the guidelines of the Organization for Economic Co-operation and Development (OECD) for quantitative structure–activity relationship (QSAR) analysis. The structure–toxicity relationships that emerged from both classification and regression-based models were in accordance with the findings of some previous studies. The models suggested that the cytotoxicity of ionic liquids is dependent on the cationic surfactant action, long alkyl side chains, cationic lipophilicity as well as aromaticity, the presence of a dialkylamino substituent at the 4-position of the pyridinium nucleus and a bulky anionic moiety. The models have been transparently presented in the form of equations, thus allowing their easy transferability in accordance with the OECD guidelines. The models have also been subjected to rigorous validation tests proving their predictive potential and can hence be used for designing novel and “greener” ionic liquids. The major strength of the present study lies in the use of a diverse and large dataset, use of simple reproducible descriptors and compliance with the OECD norms.

Comparative toxicity of rac- and S-tebuconazole to Daphnia magna

Tebuconazole is a chiral triazole fungicide used as raceme in a variety of agricultural applications. Earlier studies showed that tebuconazole is toxic to many non-target aquatic organisms but relative data for tebuconazole enantiomers are lacking. Thus, goal of this study was to evaluate and compare the toxicity of rac- and S-tebuconazole with Daphnia magna at both acute and chronic levels according to Organization for Economic Cooperation and Development (OECD) guidelines 202 and 211 respectively, to provide some guidelines for optimizing chiral pesticides application and management. The exposure concentrations were 0.1, 0.5, 1, 2, 4, 8, 10 mg L−1 for both rac- and S-tebuconazole and their 48-h EC50 values to D. magna were 3.53 (3.32–3.78) and 2.74 (2.33–3.10) mg L−1 respectively, indicating that these both are medium toxic to D. magna with no significant toxicity difference at acute level. In chronic test, <24-h old D. magna were exposed to 0.01, 0.05, 0.10, 0.20, and 0.40 mg L−1 of rac- and S-tebuconazole with one blank and one solvent control for 21 days according to OECD guideline 211. Four developmental (molting rate, days to the 1st and 3rd brood, and body length) and five reproductive (size of the 1st and 3rd brood, number of broods, and number of neonates) parameters for each D. magna were determined. Results showed that both rac- and S-tebuconazole significantly reduced the reproduction and impacted the development of D. magna at concentrations of 0.05 mg L−1 or higher. Furthermore, S-tebuconazole was more toxic than raceme, and the difference between effects on the same parameters induced by rac- and S-tebuconazole was statistically significant. These results demonstrated that the chronic toxicity of S-tebuconazole might be underestimated in general use, and further studies should focus more on the biological behaviors of enantiomers and not just the raceme of tebuconazole and other chiral pesticides in the environment.

The Legal Aspects of Corporate Social Responsibility: Interview with Ursula Wynhoven

The Global Compact (UNGC) represents the world’s largest corporate citizenship initiative today. Created under the auspices of the United Nations (UN) to encourage companies around the world to adopt sustainable and socially responsible policies, the UNGC brings together businesses, UN agencies and labour groups in search of compromises. In a phone interview with the Journal’s team, Ursula Wynhoven, General Counsel and Head of the UN Global Compact, shared her views on current issues and challenges of the field. Before joining the UN, she was engaged with the Organisation for Economic Co-operation and Development (OECD) on the development of the OECD Guidelines for Multinational Enterprises (MNEs). Ursula Wynhoven has also worked as a lawyer in governmental human rights agencies and private practices in the United Kingdom, the United States and Australia, and is an adjunct professor at the University of Reykjavik’s School of Law in human rights and business.

Transfer Pricing: Un Practical Manual China

Any contemporary Chinese transfer pricing assessment needs to consider the United Nation (UN) Practical Manual on Transfer Pricing for Developing Countries released in May 2013. In particular, Chapter 10 discusses Country Practices and presents China’s most up to date transfer pricing policy statement. China is not an Organization for Economic Cooperation and Development (OECD) member nor has it formally adopted the OECD’s Transfer Pricing Guidelines for Multinational Enterprises and Tax Administrations. Chapter 10 makes it very clear that China is charting a different transfer pricing course in at least nine important areas. China believes that: 1. significant comparability adjustments are needed when comparable sets are drawn from developed countries; 2. the transactional net margin (TNMM) is considered overused and inaccurate; 3. location savings must be reflected in the costs; 4. toll manufacturers will be converted into contract manufacturers; 5. limited risk distributor status is denied for brand building distributors; 6. market premiums must be reflected in Chinese profits; 7. tax haven based IP ownership can be “looked through” or denied; 8. cost-plus methodology is rejected for “high and new technology status” (HNTS) entities; 9. royalty adjustments over time are necessary.The Chinese approach to transfer pricing or at least the approach presented in the Practical Manual uses familiar OECD terminology but it places a very different emphasis on some basic concepts in the OECD Guidelines. Thus, the Chinese market economics strengthens the State Administration of Taxation’s hand and encourages more forceful transfer pricing policies. This is the case even though these policies diverge from OECD norms. This paper considers the nine major areas where the Chinese position in the UN Practical Manual differs from positions in the OECD Guidelines.

Evaluation of electric arc furnace‐processed steel slag for dermal corrosion, irritation, and sensitization from dermal contact

Electric arc furnace (EAF) steel slag is alkaline (pH of ~11-12) and contains metals, most notably chromium and nickel, and thus has potential to cause dermal irritation and sensitization at sufficient dose. Dermal contact with EAF slag occurs in many occupational and environmental settings because it is used widely in construction and other industrial sectors for various applications including asphaltic paving, road bases, construction fill, and as feed for cement kilns construction. However, no published study has characterized the potential for dermal effects associated with EAF slag. To assess dermal irritation, corrosion and sensitizing potential of EAF slag, in vitro and in vivo dermal toxicity assays were conducted based on the Organisation for Economic Co-operation and Development (OECD) guidelines. In vitro dermal corrosion and irritation testing (OECD 431 and 439) of EAF slag was conducted using the reconstructed human epidermal (RHE) tissue model. In vivo dermal toxicity and delayed contact sensitization testing (OECD 404 and 406) were conducted in rabbits and guinea pigs, respectively. EAF slag was not corrosive and not irritating in any tests. The results of the delayed contact dermal sensitization test indicate that EAF slag is not a dermal sensitizer. These findings are supported by the observation that metals in EAF slag occur as oxides of low solubility with leachates that are well below toxicity characteristic leaching procedure (TCLP) limits. Based on these results and in accordance to the OECD guidelines, EAF slag is not considered a dermal sensitizer, corrosive or irritant.

Toxicity Measurement of Imidazolium Ionic Liquids Using Acute Toxicity Test

Ionic liquids (ILs) can be considered as environmentally friendly solvent, but they have the ability to dissolve in water and accumulate in the environment. Therefore, the toxicity of ILs should be assessed in order to prevent their harm to human and environment. This study was carried out to investigate the toxicity of ILs towards marine and freshwater fish. Three ILs have been tested, which are 1-Butyl-3-methylimidazolium hydrogen sulfate and 1-Butyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide toward marine fish and 1-Hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide toward freshwater fish. Two different marine fish were employed, which are: Cephalopholis cruentata (grouper) and Lates calcarifer (barramundi). For freshwater fish, male Poecilia reticulate (guppy) was employed. The toxicity tests were conducted according to OECD (Organisation for Economic Cooperation and Development) guideline 203. For 1-Butyl-3-methylimidazolium hydrogen sulphate [BMIM][HSO4], the median lethal concentration (LC50) estimated toward Cephalopholis cruentatato be 199.98mg.L-1. For 1-Butyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide [BMIM][TFSI], LC50 estimated toward LatesCalcariferto be 374.11mg.L-1. While, for 1-Hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide, [HMIM][NTf2], LC50 estimated toward Poecilia Reticulate to be 207.49mg.L-1. All the LC50 values obtained can be identified as practically nontoxic liquids based on Acute Toxicity Rating Scale by Fish and Wildlife Service (FWS). As to our knowledge, there is no previous reported toxicity studies of [BMIM][HSO4] and [BMIM][TFSI] on marine fish and [HMIM] [NTf2] on freshwater fish. Thus, this paper can be used as a benchmark for researchers who are dealing with these three ILs.

Evaluation of safety profile of homoeopathic mother tinctures

Background: Mother tinctures are commonly prescribed in day to day practice as therapeutic agents by homoeopathic practitioners. However, being the base preparation of medicines, safety of mother tinctures still remains a challenge because of the high variability of chemical components involved.The present study investigated the acute and sub-acute oral toxicity of different homoeopathic mother tinctures (Bellis perennis, Curcuma longa, Rauwolfia serpentina, Ricinnus communis, Tribulus terrestris and Terminalia arjuna) in experimental models. Methods: Toxicity studies were conducted to assess the level to which substances are toxic for humans and animals. In acute oral toxicity study, different homoeopathic mother tinctures were administered orally (a single dose of 4 ml/kg)and animals were observed for toxic symptoms till 14 days as per OECD (Organisation for Economic Co-operation and Development) - 423 guidelines. For sub-acute toxicity study, 28 day oral toxicity of mother tinctures (4 ml/kg daily) was carried out according to the OECD guidelines for testing of chemicals - 407. At the end of 28 days, the animals were sacrificed and toxicity was assessed on parameters such as blood, biochemistry and histopathology. Results: Results indicate that there were no toxic symptoms observed in tested animals. Results of sub-acute toxicity study did not show any change in body weight, haematological and biochemical parameters as compared to control. The histopathological examination of kidney and liver also did not reveal any organ toxicities.

Biodegradability and transformation of human pharmaceutical active ingredients in environmentally relevant test systems

Human pharmaceutical active ingredients that are orally or parenterally administered may be metabolised in the body and after excretion may be further transformed in the receiving environmental compartments. The optimal outcome from an environmental point of view—complete mineralisation—is rarely observed. Small molecule pharmaceuticals are commonly not readily biodegradable according to Organisation for Economic Cooperation and Development (OECD) 301 tests. However, primary transformation is often observed. To gain information on the transformation of active ingredients in the environment, long-term studies like transformation in aquatic water/sediment systems according to OECD guideline 308 are required for the environmental risk assessment for human active pharmaceutical ingredients. Studies received until mid 2010 as part of the dossiers for marketing authorisation applications were evaluated concerning transformation products. The evaluation revealed that in 70 % of the studies, at least one transformation product (TP) is formed above 10 % of the originally applied dose, but in only 26 % of the studies are all TP identified. The evaluation also revealed that some TP of pharmaceutical active ingredients show a considerably longer DT50 compared to the parent compound. An example is the TP (val)sartan acid that is formed from an antihypertensive compound.

Acute and subchronic dermal toxicity of Vitex negundo essential oil

Vitex negundo is a common herb in different herbal formulation. The potential acute and sub-chronic dermal toxicities were evaluated as per OECD (Organization for Economic Cooperation and Development) guidelines 402 and 411, respectively. Both sexes of Wistar rats were exposed to Vitex negundo oil of 2000 mg/kg body weight for acute dermal toxicity, whereas in the dermal sub-chronic toxicity study, rats were exposed to Vitex negundo oil 250, 500 and 1000 mg/kg body weight, respectively, for five times a week for 90 d. In acute and sub-chronic toxicity studies, all animals were normal without any behavioral, serum biochemistry, hematology, necroscopical and histopathological changes. The no observed effect level (NOEL) and no observed adverse effect level (NOAEL) of Vitex negundo oil were 250 and 1000 mg/kg/day, respectively. Vitex negundo oil is under the category 5 (Unclassified) according to the Globally Harmonized System, with an LD50 value of over 2000 mg/kg.

Incorporating the OECD Guidelines in International Investment Agreements: Turning a Soft Law Obligation into Hard Law?

This article has been written as a response to two recent developments. First, as a response to the recent update of the Organisation for Economic Co-operation and Development (OECD) Guidelines on 25 May 2011, which seem to have taken a form based on human rights due diligence. Second, as a response to the resolution by the European Parliament of 6 April 2011 on the future EU international investment policy in which it asks the Commission to include, in all future agreements, a reference to the updated OECD Guidelines. This article examines how human rights due diligence, as enshrined in the OECD Guidelines, could be incorporated in international investment agreements (IIAs). Therefore, the concept of human rights due diligence as introduced in the UN Guiding Principles and the OECD Guidelines was explored. It includes empirical research as to how multinationals (MNEs) currently incorporate the concept of human rights due diligence in their policies in order to facilitate investors and policymakers with the knowledge necessary to give an adequate response to this concept. It continues by providing several options as to how the OECD Guidelines could be incorporated in investment agreements, including the advantages and disadvantages of these options.

Dermal and ocular irritation and skin sensitization studies of fullerene C60 nanoparticles

Context: Widespread production and use of nanomaterials have caused the release of increasing amounts of nanomaterials into the environment. The introduction of novel materials into industry requires safety evaluations as well as an understanding of the impact of the nanomaterials on human health, because the unique properties and size of nanomaterials may also result in unique health risks. Skin and eyes have the highest risk of exposure to nanomaterials, because deposition to the superficial organs has the potential to be a major route of exposure during the manufacturing, use, and disposal of nanomaterials. However, information on the dermal and eye irritation and sensitization of fullerene C60 nanoparticles is still lacking.Objectives: This study was performed to examine the potential irritating and sensitizing effects of fullerenes on the skin and eyes.Methods: The dermal and eye irritation study was performed using rabbits according to the Organisation for Economic Co-operation and Development (OECD) Guidelines 404 and 405, respectively. The skin sensitization study was carried out in accordance to the OECD Guideline 406 using guinea pigs. The concentrations of the fullerenes in the test substances were the maximum allowable for administration. Fullerenes were applied at 50 mg in dermal irritation, 40 mg in skin sensitization, and 100 mg in eye irritation studies.Results: No dermal responses, including erythema/eschar or edema, were found in rabbits treated with fullerenes. No rabbits exhibited corneal opacity, abnormality of the iris, or chemosis eye at any time point after the application of fullerenes. Fullerenes caused conjunctival redness and blood vessel hyperemia at 1 h, but not at 24 h. No erythema or edema was observed after the challenge with fullerenes in the fullerene-treated guinea pigs.Conclusion: Reversible minimal potential for acute irritation of the eyes was induced by fullerenes, but neither irritation nor sensitization was caused on the skin. Although the present study provided initial information on the acute irritation and acute sensitization of highly purified C60 fullerenes, information on the toxicological effects of fullerenes and their derivatives is still limited. Further information is needed to clarify the potential for toxicity given the complex nature of fullerenes and their derivatives.

Developmental neurotoxicity guideline study: Issues with methodology, evaluation and regulation*

Recently social concerns have been increasing about the effects of environmental factors on children's health, especially on their nervous systems. The U.S. Environmental Protection Agency (EPA) and the Organisation for Economic Co-operation and Development (OECD) have published testing guidelines for developmental neurotoxicity (DNT). Approximately 110 guideline studies have been conducted to date. Importantly, information from these studies has provided data critical for regulatory decisions for a number of chemicals. However, the DNT guidelines do not always satisfy all stakeholders because of some uncertainties in their methodology, evaluation, and regulation. Methodological issues include incomplete harmonization between EPA and OECD guidelines, criticisms of the methodology for learning and memory testing, and unspecified positive control substances. Potential artifacts in morphometric neuropathological measures, criteria for observation measures, uncertainty of postnatal offspring exposure, especially in feeding studies, and extrapolation of data from rats to humans are major evaluation issues. In addition, there is some uncertainty in the use of an additional safety factor for susceptibility of infants and children. Moreover, the DNT guidelines have extensive time and cost requirements, use large numbers of animals, and there is a limited set of laboratories that can conduct the study. This paper reviews some of these issues and summarizes discussions from the symposium 'Developmental neurotoxicity testing: Scientific approaches towards the next generation to protecting the developing nervous system of children' held at the 2011 annual meeting of the Japanese Teratology Society.

Business, social responsibility, and corruption

This paper explores the role of corporate social responsibility and the reporting thereof in the fight against corruption. A special focus is laid on the international endeavors to improve transparency through reporting, and the paper elaborates extensively on the United Nations Global Compact (UNGC), the Organisation for Economic Co‐operation and Development (OECD) Guidelines for Multinational Enterprises and the Global Reporting Initiative's (GRI) Sustainability Reporting Guidelines. Voluntary initiatives, such as the UNGC, the OECD guidelines, and the GRI guidelines, are considered to play an important role in providing the trust‐based informal social norms, without which markets and societies cannot function. Copyright © 2012 John Wiley &amp; Sons, Ltd.

First report on development of quantitative interspecies structure–carcinogenicity relationship models and exploring discriminatory features for rodent carcinogenicity of diverse organic chemicals using OECD guidelines

Different regulatory agencies in food and drug administration and environmental protection worldwide are employing quantitative structure–activity relationship (QSAR) models to fill the data gaps related with properties of chemicals affecting the environment and human health. Carcinogenicity is a toxicity endpoint of major concern in recent times. Interspecies toxicity correlations may provide a tool for estimating sensitivity towards toxic chemical exposure with known levels of uncertainty for a diversity of wildlife species. In this background, we have developed quantitative interspecies structure–carcinogenicity correlation models for rat and mouse [rodent species according to the Organization for Economic Cooperation and Development (OECD) guidelines] based on the carcinogenic potential of 166 organic chemicals with wide diversity of molecular structures, spanning a large number of chemical classes and biological mechanisms. All the developed models have been assessed according to the OECD principles for the validation of QSAR models. Consensus predictions for carcinogenicity of the individual compounds are presented here for any one species when the data for the other species are available. Informative illustrations of the contributing structural fragments of chemicals which are responsible for specific carcinogenicity endpoints are identified by the developed models. The models have also been used to predict mouse carcinogenicities of 247 organic chemicals (for which rat carcinogenicities are present) and rat carcinogenicities of 150 chemicals (for which mouse carcinogenicities are present). Discriminatory features for rat and mouse carcinogenicity values have also been explored.

Procedural Rules for the Implementation of the OECD Guidelines for Multinational Enterprises — a Public International Law Perspective

Since the 1990s it is possible to witness, in the multiplication of inter- and transnational actors, an increasing diversity in international norm-making processes as well as a growing variation in enforcing these norms, generically labeled under the term “global governance.” The actions of these private, hybrid or intergovernmental actors on the global level are increasingly seen as equivalent to the exercise of political authority formerly reserved for the state. As in the domestic context, the exercise of such authority raises questions about the procedural guarantees that anyone affected by this action should enjoy. The Organization for Economic Cooperation and Development (OECD) has evaded intensive scholarly attention from the global governance perspective thus far, although by now it is evident that it strongly contributes to this phenomenon through its various activities. The OECD Guidelines for Multinational Enterprises (Guidelines) are but one area in which the OECD is said to assume global governance functions by strongly influencing corporate behavior.

Evaluation of the genotoxicity of the food additive, gum ghatti

Gum ghatti is a food additive in some parts of the world, serving as an emulsifier, a stabilizer, and a thickening agent. To evaluate its genotoxic potential, we conducted Good Laboratory Practice compliant in vitro and in vivo studies in accordance with the Organisation for Economic Co-operation and Development (OECD) guidelines. No evidence of toxicity or mutagenicity was detected in a bacterial reverse mutation assay using five tester strains evaluating gum ghatti at up to 6mg/plate, with or without metabolic activation. Gum ghatti also did not induce chromosome structural damage in a chromosome aberration assay using Chinese hamster ovary cells. To assess the ability to induce DNA damage in rodents, a combined micronucleus/Comet assay was conducted in male B6C3F1 mice. Gum ghatti was administered at 1000, 1500, and 2000mg/kg/day by gavage once daily for 4days and samples were collected 4h after the final dosing. No effect of gum ghatti was measured on micronucleated reticulocyte (MN-RET) frequency in peripheral blood, or DNA damage in blood leukocytes or liver as assessed by the Comet assay. Our results show no evidence of genotoxic potential of gum ghatti administered up to the maximum concentrations recommended by OECD guidelines.

Toxicity of sodium tungstate to earthworm, oat, radish, and lettuce.

Due to unknown effects of the potential exposure of the terrestrial environment to tungsten substances, a series of toxicity studies of sodium tungstate (Na(2) WO(4) ) was conducted. The effect on earthworm (Eisenia fetida) survival and reproduction was examined using Organisation for Economic Co-operation and Development (OECD) Guideline 222. No effect on either endpoint was seen at the highest concentration tested, resulting in a 56-d no-observed-effect concentration (NOEC) of ≥586 mg tungsten/kg dry soil (nominal concentrations). The effect of sodium tungstate on emergence and growth of plant species was examined according to OECD Guideline 208: oat (Avena sativa), radish (Raphanus sativus), and lettuce (Lactuca sativa). No effects on emergence, shoot height, and dry shoot weight were observed in oats exposed to the highest concentration, resulting in a 21-d NOEC of ≥586 mg tungsten/kg dry soil. The NOECs for radish and lettuce were 65 and 21.7 mg tungsten/kg dry soil (nominal concentrations), respectively. Respective 21-d median effective concentration values (EC50) for radish and lettuce were >586 and 313 mg tungsten/kg dry soil (based on shoot height) (confidence level [CL] -8.5-615); EC25 values were 152 (CL 0-331) and 55 (CL 0-114) mg tungsten/kg dry soil. Results are consistent with the few other tungsten substance terrestrial toxicity studies in the literature.