OECD 414 supplementary prenatal developmental toxicity study of sodium molybdate dihydrate in the rat and benchmark dose evaluation.

In a continuing investigation of the potential for reproductive and developmental toxicity of molybdenum (Mo), consequent to the previous published OECD studies [1,2] and as directed by the European Chemicals Agency [3], a supplemental rat GLP-compliant Prenatal Developmental Toxicity (PNDT) study was conducted to investigate higher dose levels of sodium molybdate dihydrate (SMD) in an identical study design (OECD 414)[4] to Murray et al. 2014a [1], at dietary concentrations calculated to provide target Mo levels of 80 and 120 mg/kg bw/day (the maximum-tolerated dose). There was no effect on post-implantation loss, litter size, sex ratio or the incidence of external, visceral or skeletal fetal malformations or variations. Fetal weight was reduced proportionate to maternal dose. Minimal differences observed in the ossification status of some extremities of fetuses from females receiving 120 mg Mo/kg bw/day were confirmed as transient by skeletal examination of PND 21 pups from a further group of females receiving the same dose regime. There was no evidence of copper depletion in serum, placenta or liver. A benchmark dose evaluation using continuous and dichotomous approaches by combining the fetal body weight data from this study and the previous study determined that the BMD05 ranged from 47 to 57 mg Mo/kg bw/day, depending on the modelling approach and the BMDL05 estimates ranged from 37 to 47 mg Mo/kg bw/day. These levels are considered a more statistically robust point of departure for risk assessment for reproductive effects than the established NOAEL of 40 mg Mo/kg bw/day.

The non-use of evidence in the adoption of a sugar-sweetened beverage tax in OECD countries.

BACKGROUND: Studies confirm the positive effect of sugar-sweetened beverage (SSB) taxation on public health. However, only a few countries in Europe adopt SSB taxes. From a public policy perspective, we investigate the conditions under which countries do or do not follow this evidence. METHODS: Crisp-set Qualitative Comparative Analysis (QCA) of 26 European Organization of Economic Cooperation and Development countries with and without an SSB tax. We test which configurations of conditions (problem pressure, governmental composition, strategic planning, health care system, public health policies, inclusion of expert advice in policymaking) emerge as relevant in determining adoption and non-adoption between the years 1981 and 2021. Pathways that lead to the presence and absence of SSB taxes are identified separately. RESULTS: At least one of the following configurations of conditions is present in countries that introduced taxation: (i) high financial problem pressure, low regulatory impact assessment activity; (ii) high public health problem pressure, a contribution-financed health care system, no holistic strategy for combatting non-communicable diseases (NCDs); (iii) a tax-financed health care system, a holistic NCD strategy, high strategic and executive planning capacity. In countries that did not adopt SSB taxes, we find (i) high regulatory impact assessment activity, high levels of sugar export; (ii) no holistic NCD strategy, high spending on preventive care; (iii and iv) a lack of strategic planning capacity and either a high share of spending on preventive care or inclusion of expert advice. DISCUSSION: Evidence inclusion requires clear policy priorities in terms of strategy and resources to promote public health.

Scientific concepts and methods for moving persistence assessments into the 21st century.

The evaluation of a chemical substance's persistence is key to understanding its environmental fate, exposure concentration, and, ultimately, environmental risk. Traditional biodegradation test methods were developed many years ago for soluble, nonvolatile, single-constituent test substances, which do not represent the wide range of manufactured chemical substances. In addition, the Organisation for Economic Co-operation and Development (OECD) screening and simulation test methods do not fully reflect the environmental conditions into which substances are released and, therefore, estimates of chemical degradation half-lives can be very uncertain and may misrepresent real environmental processes. In this paper, we address the challenges and limitations facing current test methods and the scientific advances that are helping to both understand and provide solutions to them. Some of these advancements include the following: (1) robust methods that provide a deeper understanding of microbial composition, diversity, and abundance to ensure consistency and/or interpret variability between tests; (2) benchmarking tools and reference substances that aid in persistence evaluations through comparison against substances with well-quantified degradation profiles; (3) analytical methods that allow quantification for parent and metabolites at environmentally relevant concentrations, and inform on test substance bioavailability, biochemical pathways, rates of primary versus overall degradation, and rates of metabolite formation and decay; (4) modeling tools that predict the likelihood of microbial biotransformation, as well as biochemical pathways; and (5) modeling approaches that allow for derivation of more generally applicable biotransformation rate constants, by accounting for physical and/or chemical processes and test system design when evaluating test data. We also identify that, while such advancements could improve the certainty and accuracy of persistence assessments, the mechanisms and processes by which they are translated into regulatory practice and development of new OECD test guidelines need improving and accelerating. Where uncertainty remains, holistic weight of evidence approaches may be required to accurately assess the persistence of chemicals. Integr Environ Assess Manag 2022;18:1454-1487. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Comparative study of estrogenic activities of phytoestrogens using OECD in vitro and in vivo testing methods.

With growing scientific interest in phytoestrogens, a number of studies have investigated the estrogenic potential of phytoestrogens in a wide variety of assay systems. However, evaluations of individual phytoestrogens with different assay systems make it difficult for predicting their relative estrogenic potency. The objective of this study was to compare estrogenic properties of fifteen known phytoestrogens using an estrogen receptor-α (ER-α) dimerization assay and Organization for Economic Cooperation and Development (OECD) standardized methods including in vitro estrogen receptor (ER) transactivation assay using VM7Luc4E2 cells and in vivo uterotrophic assay using an immature rat model. Human ER-α dimerization assay showed positive responses of eight test compounds and negative responses of seven compounds. These results were consistently found in luciferase reporter assay results for evaluating ER transactivation ability. Seven test compounds exhibiting relatively higher in vitro estrogenic activities were subjected to uterotrophic bioassays. Significant increases in uterine weights were only found after treatments with biochanin A, 8-prenylnaringenin, and coumestrol. Importantly, their uterotrophic effects were lost when animals were co-treated with antagonist of ER, indicating their ER-dependent effects in the uterus. In addition, analysis of estrogen responsive genes revealed that these phytoestrogens regulated uterine gene expressions differently compared to estrogens. Test methods used in this study provided a high consistency between in vitro and in vivo results. Thus, they could be used as effective screening tools for phytoestrogens, particularly focusing on their interactions with ER-α.

Evaluation of Estrogen Receptor Agonistic Activity of Medicinal Herbs Using Organization for Economic Cooperation and Development Transactivation Assay with Rat Liver S9 Fraction.

A number of studies employing different in vitro assays have demonstrated the estrogen-like activity of natural substances. All assays have their advantages and limitations as a screening tool. No single in vitro assay is considered ideal for predicting estrogenic action in a complex in vivo system. To assess agonistic activities of several medicinal herbs on the estrogen receptor (ER) and their metabolic alteration, the Organization for Economic Cooperation and Development (OECD) Performance-Based Test Guideline No. 455 in vitro assay was performed in this study using recombinant VM7Luc4E2 cells in combination with rat liver S9 fractions. Ethanol extracts of medicinal herbs showed binding affinities for ER-α and ER-ß at different levels. However, luciferase reporter assay using VM7Luc4E2 cells revealed that only two test extracts [Pueraria lobata root extract (PLE); Glycyrrhiza glabra root extract (GGE)] exhibited ER transcriptional activity when their activities were compared with the response by 17ß-estradiol. Importantly, incubation of PLE or GGE with rat liver S9 fractions increased their ER transcriptional activities, in particular when phase I metabolic enzymes were activated. Puerarin and glabridin were the most abundant isoflavones found in PLE and GGE, respectively. The present results demonstrate that PLE and GGE possess potential as ER agonists with their metabolic activation. This study also suggests that the application of OECD in vitro assay with rat liver S9 fraction is an efficient screening tool to evaluate estrogenic activities of natural substances.

New insight into examining the role of financial development in economic growth effect on a composite environmental quality index.

The inclusion of an index, which can be the representative of environmental quality from different aspects, seems to be of paramount significance. This issue is a major challenging one in the economic-environmental literature. This study investigates the role of financial development in economic growth effect on the composite environmental quality index (CEQI) in two groups of selected Organization of the Petroleum Exporting Countries (OPEC) and Organization for Economic Co-operation and Development (OECD) countries. In this regard, System Generalized Method of Moment (SYS-GMM) is applied to fit the research models. According to the findings, in the selected OPEC countries, financial development reinforces negative impacts of economic growth on environmental quality. In the selected OECD countries, economic growth has negative effect on the environmental quality and financial development weakens this effect. The effect of financial development on the CEQI is respectively negative and positive in OPEC and OECD countries. Moreover, in both groups of selected countries, energy consumption and economic growth have a negative impact on the CEQI; nonetheless, trade openness has a positive effect. Accordingly, some policy suggestions and new recommendations are presented for future studies, which would contribute to the better implementation of economic-environmental policies. Graphical abstract.

Agricultural nitrogen and phosphorus balances of Korea and Japan: Highest nutrient surplus among OECD member countries.

Excessive nutrient balance is a very crucial issue for environmental hazards. The constant addition of high-amounts of nutrient sources in agricultural production generates negative environmental conditions in Korea and Japan yet to be resolved. Therefore, it is obligatory to comprehend the nutrient (nitrogen (N) and phosphorus (P)) balance that is assessed by the difference between nutrient input and output in the soil surface in Korea and Japan. Among 34 Economic Co-operation and Development (OECD) countries, Korea and Japan had the highest N and P balances and thus both countries are primarily responsible for severe environmental pollution via nutrient release. The cultivable land area in both countries has constantly decreased during 1990-2017 at approximately 20 and 15% in Korea and Japan, respectively. Even N and P use efficiency sharply decreased with increasing N and P balance in both targeted countries. Japanese P balance, Korean N and P balances were decreased after the mid-1990s whereas, Japanese N balance almost unchanged for the last 28 years. Unlike chemical fertilizer input, Korean manure input level significantly increased from 78 kg N ha-1 in 1990 to 157 kg N ha-1 in 2017. Japanese manure input level was higher than that of chemical fertilizer without any big change for the last 28 years. The lion share of high N and P balance in both countries could generate from manure inputs, therefore, the number of livestock and their produced debris need to be used with more cautious for the reduction of national N and P surpluses at a benchmark level. These findings ensure to make a more environment friendly policy that can further reduce nutrient balance as well as improve soil health.

Role of nurses and midwives in improving patient safety during childbirth: Evidence from obstetric trauma in OECD countries.

OBJECTIVES: To measure the role of nurses and midwives in reducing obstetric trauma as a proxy for safety failures during childbirth in member countries of Organization for Economic Co-operation and Development (OECD). METHODS: The number of practicing nurses' and midwives' density per 1000 population and the proportion of third- and fourth-degree obstetric trauma during vaginal delivery with instrument (OT1) and without instrument (OT2) in crude rates per 100 vaginal deliveries for patients aged 15 and over collected from World Development Indicators and OECD Health Statistics in 17 OECD countries during 2010-2017 period. The statistical technique of panel data analysis was applied to estimate the impact of nurses and midwives on improving patient safety during childbirth. The number of physicians per 1000 population, health care expenditure (HCE) per capita and total number of hospital beds per 1000 population were added in data analysis as control variables. RESULTS: The results of panel co-integration test and dynamic long-run models confirm that there were meaningful relationships from the level of nursing and midwifery staff to reducing OECD's obstetric trauma indicators with long-run magnitudes of -15.8614 for OT1 and -0.0519 for OT2. In addition, the results of panel error-correction model argue that if the long-run relationships between nursing and midwifery staff and obstetric trauma indicators are disturbed by the shortage in the needed nurses and midwives, then it takes at least 25 years for OT1 and 18 years for OT2 to reduce and restore back to equilibrium; that is quite a long time. CONCLUSION: A higher proportion of nursing and midwifery staff is associated with higher patient safety during childbirth in OECD countries. Overall, our findings alert policy makers to consider the deleterious impacts of shortage in the level of nursing and midwifery staff on declining patient safety during childbirth as well as quality of acute care in OECD.

Refinement of an OECD test guideline for evaluating the effects of endocrine disrupting chemicals on aromatase gene expression and reproduction using novel transgenic cyp19a1a-eGFP zebrafish.

Transgenic fish are powerful models that can provide mechanistic information regarding the endocrine activity of test chemicals. In this study, our objective was to use a newly developed transgenic zebrafish line expressing eGFP under the control of the cyp19a1a promoter in the OECD Fish Short Term Reproduction Assay (TG 229) to provide additional mechanistic information on tested substances. For this purpose, we exposed adult transgenic zebrafish to a reference substance of the TG 229, i.e. prochloraz (PCZ; 1.7, 17.2 and 172.6 µg/L). In addition to "classical" endpoints used in the TG 229 (reproductive outputs, vitellogenin), the fluorescence intensity of the ovaries was monitored at 4 different times of exposure using in vivo imaging. Our data revealed that 172.6 µg/L PCZ significantly decreased the number of eggs laid per female per day and the concentrations of vitellogenin in females, reflecting the decreasing E2 synthesis due to the inhibition of the ovarian aromatase activities. At 7 and 14 days, GFP intensities in ovaries were similar over the treatment groups but significantly increased after 21 days at 17.2 and 172.6 µg/L. A similar profile was observed for the endogenous cyp19a1a expression measured by qPCR thereby confirming the reliability of the GFP measurement for assessing aromatase gene expression. The overexpression of the cyp19a1a gene likely reflects a compensatory response to the inhibitory action of PCZ on aromatase enzymatic activities. Overall, this study illustrates the feasibility of using the cyp19a1a-eGFP transgenic line for assessing the effect of PCZ in an OECD test guideline while providing complementary information on the time- and concentration-dependent effects of the compound, without disturbing reproduction of fish. The acquisition of this additional mechanistic information on a key target gene through in vivo fluorescence imaging of the ovaries was realized without increasing the number of individuals.

Systemic Therapy for Advanced and Metastatic Colon Cancer / 대한소화기학회지

Colon cancer is one of the three most common cancers in both men and women in Organization for Economic Cooperation and Development countries. Approximately one-quarter of colon cancer patients have a metastasis at the time of diagnosis, and systemic therapy is used in many of them as a first line therapy. In addition to existing cytotoxic drugs, target therapy has been introduced in colon cancer and immunotherapy has shown clinical benefits in the treatment of metastatic colon cancer. The purpose of this review was to briefly summarize the National Comprehensive Cancer Network guidelines for systemic therapy in colon cancer with special reference to targeted agents and novel agents.

Preclinical safety assessment of Angelica acutiloba using a 13-week repeated dose oral toxicity study in rats / 한국실험동물학회지

Angelica acutiloba (AA), a Japanese species of Danggui, has been used worldwide as a traditional herbal medicine with several bioactivities including anti-diabetic, anti-allergic, anti-inflammatory, anti-tumor, and anti-obesity. However, there is lack of toxicological data available to evaluate potential long-term toxicity and the no-observed-adverse-effect level (NOAEL) of AA extract in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In the 14-day repeat-dose toxicity study, no adverse effects on mortality, body weight change, clinical signs, and organ weights was found following repeat oral administration to rats for 14 days (125, 250, 500, 1000, and 2000 mg/kg body weight), leading that 2000 mg/kg is the highest recommended dose of AA extract for the 13-week repeat-dose oral toxicity study. In the 13-week repeat-dose oral toxicity study, the AA extract was orally administered to groups of rats for 13 weeks (125, 250, 500, 1000, and 2000 mg/kg body weight) to compare between control and AA extract groups. The administration of AA extract did not produce mortality or remarkable clinical signs during this 13-week study. And, the data revealed that there were no significant differences in food/water consumption, body weight, hematological parameters, clinical chemistry parameters, gross macroscopic findings, organ weight and histopathology in comparison to the control group. On the basis of these results, the subchronic NOAEL of the AA extract was more than 2000 mg/kg/day when tested in rats. And, the AA extract is considered safe to use orally as a traditional herbal medicine.

Evaluation of in vitro and in vivo genotoxicity of Angelica acutiloba in a standard battery of assays / 한국실험동물학회지

Among three representative species of Angelica found in Asian countries, including Korea, China, and Japan, Angelica acutiloba (AA) has been used as traditional herbal medicine with antitumor, anti-inflammatory, anti-obesity, and anti-diabetes activities. In this study, the potential genotoxicity and mutagenicity of the AA extract were examined in a battery of in vitro and in vivo tests (bacterial reverse mutation assay, in vitro chromosomal aberrations assay, and in vivo micronucleus assay) in accordance with the test guidelines for toxicity testing developed by the Organization for Economic Cooperation and Development. Upon testing in the bacterial mutation assay (Ames test) using five Salmonella typhimurium TA98, TA100, TA102, TA1535 and TA1537, no significant increase the number of revertant colonies in the metabolic activation system and non-activation system was noted in the AA extract groups. Also, in the chromosome aberration test, the AA extract did not cause chromosomal aberration with or without metabolic activation by S9 mix. A bone marrow micronucleus test of mice demonstrated that the incidence of micronucleated polychromatic erythrocytes in the AA extract groups (500, 1000 and 2000 mg/kg BW) was equivalent to that of the negative control group. Based on these results from a standard battery of assays, the AA extract was concluded to have no genotoxic at the proper dose.

The Effect of Geographic Units of Analysis on Measuring Geographic Variation in Medical Services Utilization.

OBJECTIVES: We aimed to evaluate the effect of geographic units of analysis on measuring geographic variation in medical services utilization. For this purpose, we compared geographic variations in the rates of eight major procedures in administrative units (districts) and new areal units organized based on the actual health care use of the population in Korea. METHODS: To compare geographic variation in geographic units of analysis, we calculated the age-sex standardized rates of eight major procedures (coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, surgery after hip fracture, knee-replacement surgery, caesarean section, hysterectomy, computed tomography scan, and magnetic resonance imaging scan) from the National Health Insurance database in Korea for the 2013 period. Using the coefficient of variation, the extremal quotient, and the systematic component of variation, we measured geographic variation for these eight procedures in districts and new areal units. RESULTS: Compared with districts, new areal units showed a reduction in geographic variation. Extremal quotients and inter-decile ratios for the eight procedures were lower in new areal units. While the coefficient of variation was lower for most procedures in new areal units, the pattern of change of the systematic component of variation between districts and new areal units differed among procedures. CONCLUSIONS: Geographic variation in medical service utilization could vary according to the geographic unit of analysis. To determine how geographic characteristics such as population size and number of geographic units affect geographic variation, further studies are needed.

Financial impact of the GFC: health care spending across the OECD.

Since the onset of the global financial crisis (GFC), health spending has slowed markedly or fallen in many OECD countries after years of continuous growth. However, health spending patterns across the 34 countries of the OECD have been affected to varying degrees. This article examines in more detail the observed downturn in health expenditure growth, analysing which countries and which sectors of health spending have been most affected. In addition, using more recent preliminary data for a subset of countries, this article tries to shed light on the prospects for health spending trends. Given that public sources account for around three-quarters of total spending on health on average across the OECD, and, in an overall context of managing public deficits, the article focuses on the specific areas of public spending that have been most affected. This study also tries to link the observed trends with some of the main policy measures and instruments put in place by countries. The investigation finds that while nearly all OECD countries have seen health spending growth decrease since 2009, there is wide variation as to the extent of the slowdown, with some countries outside of Europe continuing to see significant growth in health spending. While all sectors of spending appear to have been affected, initial analysis appears to show the greatest decreases has been experienced in pharmaceutical spending and in areas of public health and prevention.