Peer review of validation studies: an assessment of the role of the OECD by reference to the validation of the uterotrophic assay for endocrine disruptors

The involvement of the OECD in managing the validation of the rat uterotrophic assay for endocrine disruptors, and in organising the peer review of the results of this study, has been assessed and compared with the many conclusions and recommendations in several published reports of international workshops on validation, and information in guidance documents, produced by the European Centre for the Validation of Alternative Methods (ECVAM), the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the OECD itself. It is concluded that the OECD has not followed the recommendations for full transparency and independence of the peer-review process. This is based on the fact that it has published a draft guidance document that differs from the report of a recent OECD workshop on validation, in such a way as to give the OECD the flexibility to fully control the peer-review process and, in so doing, to avoid full transparency. Comparison of the timing of the organisation of workshops by the OECD and the progression of the validation study, together with the fact that a draft test guideline for the assay was written before completion of the peer review, suggest that the OECD has given a higher priority to the expedition of the validation and regulatory acceptance of the uterotrophic assay than it has to good scientific and logistical practice. This severely undermines its credibility in the validation process, so, in order for the OECD to be rightly perceived as an honest broker, it is recommended that the OECD should play no role in the validation of new or revised tests, until after they have been successfully validated, peer reviewed, and endorsed by the appropriate authorities, and are ready for test guideline development. With regard to the on-going OECD validation studies of other in vivo assays for endocrine disruptors, the OECD should take immediate steps to ensure full independence and transparency of their peer review.     

Gender, culture, and sex-typed cognitive abilities

Although gender differences in cognitive abilities are frequently reported, the magnitude of these differences and whether they hold practical significance in the educational outcomes of boys and girls is highly debated. Furthermore, when gender gaps in reading, mathematics and science literacy are reported they are often attributed to innate, biological differences rather than social and cultural factors. Cross-cultural evidence may contribute to this debate, and this study reports national gender differences in reading, mathematics and science literacy from 65 nations participating in the 2009 round of the Programme for International Student Assessment (PISA). Consistently across all nations, girls outperform boys in reading literacy, d = −.44. Boys outperform girls in mathematics in the USA, d = .22 and across OECD nations, d = .13. For science literacy, while the USA showed the largest gender difference across all OECD nations, d = .14, gender differences across OECD nations were non-significant, and a small female advantage was found for non-OECD nations, d = −.09. Across all three domains, these differences were more pronounced at both tails of the distribution for low- and high-achievers. Considerable cross-cultural variability was also observed, and national gender differences were correlated with gender equity measures, economic prosperity, and Hofstede’s cultural dimension of power distance. Educational and societal implications of such gender gaps are addressed, as well as the mechanisms by which gender differences in cognitive abilities are culturally mediated.     

Estimates of the number of patients with high cumulative doses through recurrent CT exams in 35 OECD countries

PurposeTo estimate the number of patients in OECD (Organization for Economic Co-operation and Development) countries who receive a cumulative effective dose (CED) ≥ 100 mSv from recurrent computed tomography (CT) exams.MethodsTaking into account recently published data on the number of CTs per patient and the fraction of patients with CED ≥ 100 mSv as well as country-specific data for the number of CT exams/1,000 population from OECD publication, this paper makes estimations for 35 OECD countries.ResultsThe estimated total number of patients with CED ≥ 100 mSv for all 35 OECD countries combined in a 5-year period is around 2.5 million (2,493,685) in a population of 1.2 billion (1,176,641,900), i.e., 0.21% of the population. Expressed per 1,000 population, the range is from 0.51 for Finland to 2.94 for the US, a nearly six-fold difference. Countries with more than 2 patients with CED ≥ 100 mSv in a 5-yr period per 1,000 population are: Belgium, France, Iceland, Japan, Korea, Luxembourg, Portugal, Turkey, and US.ConclusionsThe first estimates of the number of patients likely receiving CED ≥ 100 mSv through recurrent CT exams in 35 OECD countries indicate that 2.5 million patients reach this level in a 5-year period. There is an urgent need for various stakeholders including medical physicists, referring physicians, health policy makers, manufacturers of CT equipment and epidemiologists to attend to the issue in the interest of patient radiation safety.     

The Changing Effect of Economic Development on the Consumption-Based Carbon Intensity of Well-Being, 1990–2008

Recent sustainability science research focuses on tradeoffs between human well-being and stress placed on the environment from fossil fuel consumption, a relationship known as the carbon intensity of well-being (CIWB). In this study we assess how the effect of economic development on consumption-based CIWB—a ratio of consumption-based carbon dioxide emissions to average life expectancy—changed from 1990 to 2008 for 69 nations throughout the world. We examine the effect of development on consumption-based CIWB for the overall sample as well as for smaller samples restricted to mostly high-income OECD nations, Non-OECD nations, and more nuanced regional samples of Non-OECD nations in Africa, Asia, and Latin America. We find that the effect of economic development on CIWB increased through time for the overall sample. However, analyses of the Non-OECD and OECD samples indicate that while the effect of development on CIWB increased from null to a moderate level for the Non-OECD nations, the effect of economic development was much larger, relatively stable through time, and more unsustainable for the OECD nations. Additional findings reveal important regional differences for Non-OECD nations. In the early 1990s, increased development led to a reduction in CIWB for Non-OECD nations in Africa, but in more recent years the relationship changed, becoming less sustainable. For the samples of Non-OECD nations in Asia and Latin America, we find that economic development increased consumption-based CIWB, and increasingly so throughout the 19 year period of study.     

Income inequality and obesity prevalence among OECD countries

Using recent pooled data from the World Health Organization Global Infobase and the World Factbook compiled by the Central Intelligence Agency of the United States, this study assesses the relation between income inequality and obesity prevalence among 31 OECD countries through a series of bivariate and multivariate linear regressions. The United States and Mexico well lead OECD countries in both obesity prevalence and income inequality. A sensitivity analysis suggests that the inclusion or exclusion of these two extreme cases can fundamentally change the findings. When the two countries are included, the results reveal a positive correlation between income inequality and obesity prevalence. This correlation is more salient among females than among males. Income inequality alone is associated with 16% and 35% of the variations in male and female obesity rates, respectively, across OECD countries in 2010. Higher levels of income inequality in the 2005-2010 period were associated with a more rapid increase in obesity prevalence from 2002 to 2010. These associations, however, virtually disappear when the US and Mexico have been excluded from the analysis. Findings from this study underscore the importance of assessing the impact of extreme cases on the relation between income inequality and health outcomes. The potential pathways from income inequality to the alarmingly high rates of obesity in the cases of the US and Mexico warrant further research.     

Guidance for understanding solubility as a limiting factor for selecting the upper test concentration in the OECD in vitro micronucleus assay test guideline no. 487

The OECD guideline for the in vitro mammalian cell micronucleus test (OECD 487) was recently adopted in July 22, 2010. Since its publication, it has become apparent that the guidance for testing chemicals where solubility is a limiting factor can be interpreted in a variety of ways. In this communication, we provide clarification for testing insoluble chemicals. The intent of the OECD 487 guideline is for the high dose to be the lowest precipitating concentration even if toxicity occurs above the solubility limit in tissue culture medium. Examination of precipitation can be done by the unaided eye or microscopically. Precipitation is examined at the onset or end of treatment, with the intent to identify precipitate present during treatment.     

In vitro genotoxicity testing strategy for nanomaterials and the adaptation of current OECD guidelines

There is a pressing requirement to define a hazard identification and risk management strategy for nanomaterials due to the rapid growth in the nanotechnology industry and their promise of life-style revolutions through the development of wide-ranging nano-containing consumer products. Consequently, a battery of well defined and appropriate in vitro assays to assess a number of genotoxicity endpoints is required to minimise extensive and costly in vivo testing. However, the validity of the established protocols in current OECD recognised genotoxicity assays for nanomaterials is currently being questioned. In this report, we therefore consider the in vitro OECD genotoxicity test battery including the Ames, micronucleus and HPRT forward mutation assays, and their potential role in the safety assessment of nanomaterial induced DNA damage in vitro.     

The bovine corneal opacity and permeability test in routine ocular irritation testing and its improvement within the limits of OECD test guideline 437

Data on eye irritation are generally needed for the hazard identification of chemicals. As the Bovine Corneal Opacity and Permeability (BCOP) test has been accepted by many regulatory agencies for the identification of corrosive and severe ocular irritants since September 2009 (OECD Test Guideline 437, TG 437), we evaluated this alternative method for routine testing at BASF. We demonstrated our technical proficiency by testing the reference standards recommended in TG 437, and 21 additional materials with published BCOP and in vivo data. Our results matched the published in vitro data very well, but with some intentionally selected false negatives (FNs) and false positives (FPs), the concordance was 77% (24/31), with FN and FP rates of 20% (2/10) and 24% (5/21), respectively. In addition, we tested 21 in-house materials, demonstrating the utility of the BCOP assay for our own test material panel. Histopathological assessment of the corneas by light microscopy was also conducted, as this was suggested as a means of improving the identification of FNs. The histopathology corrected the classification of some FNs, but also increased the number of FPs. Parallel to the test method evaluation, we compared three new opacitometer models with the current standard device. We recommend the use of an opacitometer developed in our BASF laboratory, which has certified components and electronic data storage, resulting in what we consider to be excellent sensitivity, stability and reproducibility.     

Regulations and the European scene

The environment does not recognize national boundaries. Nor, increasingly, does trade. There is, therefore, a need to harmonize the regulation of the planned release of organisms containing recombinant DNA. This is particularly important for the geographically and economically interdependent countries in Europe. The various nations within the European Community have responded differently to proposals for planned release. An important step towards harmonization has been made with the OECD report on recombinant DNA. Yet there is still scope for a Community-wide framework of regulation.     

Deaths rise in good economic times: Evidence from the OECD

This study uses aggregate data for 23 Organization for Economic Cooperation and Development (OECD) countries over the 1960-1997 period to examine the relationship between macroeconomic conditions and deaths. The main finding is that total mortality and deaths from several common causes rise when labor markets strengthen. For instance, controlling for year effects, location fixed-effects (FE), country-specific time trends and demographic characteristics, a 1% point decrease in the national unemployment rate is associated with growth of 0.4% in total mortality and the following increases in cause-specific mortality: 0.4% for cardiovascular disease, 1.1% for influenza/pneumonia, 1.8% for liver disease, 2.1% for motor vehicle deaths, and 0.8% for other accidents. These effects are particularly pronounced for countries with weak social insurance systems, as proxied by public social expenditure as a share of GDP. The findings are consistent with evidence provided by other recent research and cast doubt on the hypothesis that economic downturns have negative effects on physical health.     

Testing environmental Kuznets curve hypothesis: The role of renewable and non-renewable energy consumption and trade in OECD countries

This paper investigates the causal relationships between per capita CO₂ emissions, gross domestic product (GDP), renewable and non-renewable energy consumption, and international trade for a panel of 25 OECD countries over the period 1980–2010. Short-run Granger causality tests show the existence of bidirectional causality between: renewable energy consumption and imports, renewable and non-renewable energy consumption, non-renewable energy and trade (exports or imports); and unidirectional causality running from: exports to renewable energy, trade to CO₂ emissions, output to renewable energy. There are also long-run bidirectional causalities between all our considered variables. Our long-run fully modified ordinary least squares (FMOLS) and dynamic ordinary least squares (DOLS) estimates show that the inverted U-shaped environmental Kuznets curve (EKC) hypothesis is verified for this sample of OECD countries. They also show that increasing non-renewable energy increases CO₂ emissions. Interestingly, increasing trade or renewable energy reduces CO₂ emissions. According to these results, more trade and more use of renewable energy are efficient strategies to combat global warming in these countries.     

A critical assessment of the OECD collaborative study to validate the uterotrophic assay for the detection of oestrogenic and anti-oestrogenic chemicals

The design and execution of a recently completed validation study on the rat uterotrophic assay for detecting oestrogens and anti-oestrogens, managed by the OECD, are critically assessed with respect to internationally agreed criteria for the validation of new in vitro and in vivo toxicity test methods. It is concluded that, while the design of the study did not take account of several important criteria for validation, the uterotrophic assay appears to reliably detect the strong and weak oestrogenic substances used in the study, which act via binding to the oestrogen receptor in vivo. However, the reliability of the assay has not been substantiated for detecting anti-oestrogens that act as antagonists, due to the involvement of an insufficient number of experiments and test chemicals. Moreover, the data do not permit an assessment of the accuracy of the prediction of oestrogenicity, and the protocols have not been sufficiently optimised with regard to controlling variables. This problem has been exacerbated by a wish to introduce as much flexibility as possible into the protocols during the formal validation phase of the study, rather than during a separate prevalidation stage. In addition, the choice between surgically treated and/or immature animals, and details of housing and husbandry conditions that are necessary for increasing the sensitivity and efficiency of the assay, need to be clarified. The assay also lacks a well-defined prediction model by which the overall relevance of the data to toxicity, and especially to human hazard, can be assessed, and no performance criteria have been established. The results of this analysis of the study indicate that it would be premature to produce an OECD test guideline for the uterotrophic assay at this time, before some of the above issues have been satisfactorily resolved.     

Population genetics of the HRAS1 minisatellite locus.

Several years ago it was reported that rare HRAS1 VNTR alleles occurred more frequently in U.S. Caucasian cancer patients than in unaffected controls. Such an association, in theory, could be caused by undetected population heterogeneity. Also, in a study clearly relevant to this issue, it was recently reported that significant deviations from Hardy-Weinberg equilibrium exist at this locus in a sample of U.S. Caucasians. These considerations motivate our population genetic analysis of the HRAS1 locus. From published studies of the HRAS1 VNTR locus, which classified alleles into types, we found only small differences in the allele frequency distributions of samples from various European nations, although there were larger differences among ethnic groups (African American, Caucasian, and Oriental). In an analysis of variation of rare-allele frequencies among samples from four European nations, most of the variance was attributable to molecular methodology, and very samples from four European nations, most of the variance was attributable to molecular methodology, and very little of the variance was accounted for by nationality. In addition, we showed that mixture of European subpopulations should result in only minor deviations from expected genotype proportions in a Caucasian database and demonstrated that there was no significant deviation from Hardy-Weinberg equilibrium in our HRAS1 data.     

Incidence,prevalence, mortality,disability-adjusted life years and risk factors of cancer in Australia and comparison with OECD countries, 1990–2015: findings from the Global Burden of Disease Study 2015

BackgroundComparative evidence on the burden, trend, and risk factors of cancer is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to assess cancer burden – incidence, prevalence, mortality, disability-adjusted life years (DALYs) – and attributable risk factors for Australia between 1990 and 2015, and to compare them with those of 34 members of the Organisation for Economic Co-operation and Development (OECD).MethodsThe general GBD cancer estimation methods were used with data input from vital registration systems and cancer registries. A comparative risk assessment approach was used to estimate the population-attributable fractions due to risk factors.ResultsIn 2015 there were 198,880 (95% uncertainty interval [UI]: 183,908–217,365) estimated incident cancer cases and 47,562 (95% UI: 46,061–49,004) cancer deaths in Australia. Twenty-nine percent (95% UI: 28.2–29.8) of total deaths and 17.0% (95% UI: 15.0–19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the trachea, bronchus and lung, colon and rectum, and prostate were the most common causes of cancer deaths. Thirty-six percent (95% UI: 33.1–37.9) of all cancer deaths were attributable to behavioral risks. The age-standardized cancer incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34 other OECD countries Australia ranked first (highest) and 24^th based on ASIR and ASDR, respectively.ConclusionThe incidence of cancer has increased over 25 years, and behavioral risks are responsible for a large proportion of cancer deaths. Scaling up of prevention (using strategies targeting cancer risk factors), early detection, and treatment of cancer is required to effectively address this growing health challenge.     

Interactions between Financial and Environmental Networks in OECD Countries

We analysed a multiplex of financial and environmental networks between OECD countries from 2002 to 2010. Foreign direct investments and portfolio investment showing the flows in equity securities, short-term, long-term and total debt, these securities represent the financial layers; emissions of NO _x, PM10, SO ₂, CO ₂ equivalent and the water footprint associated with international trade represent the environmental layers. We present a new measure of cross-layer correlations between flows in different layers based on reciprocity. For the assessment of results, we implement a null model for this measure based on the exponential random graph theory. We find that short-term financial flows are more correlated with environmental flows than long-term investments. Moreover, the correlations between reverse financial and environmental flows (i.e. the flows of different layers going in opposite directions) are generally stronger than correlations between synergic flows (flows going in the same direction). This suggests a trade-off between financial and environmental layers, where, more financialised countries display higher correlations between outgoing financial flows and incoming environmental flows than from lower financialised countries. Five countries are identified as hubs in this finance-environment multiplex: The United States, France, Germany, Belgium-Luxembourg and United Kingdom.     

OECD guidelines on open access: commercialization in disguise?

The Organisation for Economic Co-operation and Development (OECD) has published a new set of principles and guidelines to promote open access to datasets and results from publicly funded research. However, there is reason to think twice about the implications of making demands for transparency and open access for publicly funded research only. How will such demands affect incentives and research agendas? Might this new regulation of publicly funded research have undesirable effects on the quality and value of research? Placing the OECD guidelines in a broader context of research regulation, we argue that they might provide a further push toward collaboration with commercially sponsored research and reinforce incentive structures that favour the creation of commercial value.     

2-Aminoanthracene, diethylstilboestrol and vinblastine tested in the in vitro mammalian cell micronucleus test at British American Tobacco UK in support of the OECD draft Test Guideline 487

Reference genotoxic compounds 2-aminoanthracene, diethylstilboestrol and vinblastine were tested in the in vitro micronucleus assay using Chinese hamster V79 derived cells in the laboratories of British American Tobacco in the UK. The work was conducted in support of the cytotoxicity measures recommended in the 2007 version of the OECD Test Guideline 487. The three compounds were positive in the assay in the presence and absence of the cytokinesis blocking agent cytochalasin B at concentrations that did not exceed the recommended cytotoxic limits determined by relative population doubling, relative increase in cell counts, relative cell counts and cytokinesis block proliferation index. Consequently, this work supports the hypothesis that relative population doubling, relative increase in cell counts and relative cell counts are appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay.     

The biological monitoring of toxic impacts on the environment.

The monitoring of the environment, for a long time confined to the analysis of some chemical products, today opens itself up to biological methods. The evaluation of the structure and functioning of the living communities within the ecosystem, the amount of pollution given off by the reactions of biochemical systems, and the toxic effects of chemical substances which allow biologists to estimate the diagnosis of the situation of the ecosystem. These tools are only now imposed to the member nations of the European Union through the water framework directive which has recently been published. This convergence between scientific advances and the needs of the environmental management opens the way for the development of biomonitoring technologies.     

Study on the long-term and short-term effects of globalization and population aging on ecological footprint in OECD countries

Population aging has become a global phenomenon. Whereas, the ecological consequences of population aging are rarely addressed in current research. In this context, this study contributes to the existing literature by providing new empirical evidence on how population aging along with globalization, economic growth, energy consumption, natural resource rent, and human capital affect ecological footprint for selected 27 Organization for Economic Cooperation and Development (OECD) countries during 1970–2017. This study utilizes an advanced econometric approach, Pooled Mean Group (PMG) estimator for empirical estimation, that allows heterogeneity in the slope parameters and dependencies across countries. The long-term results disclose that globalization (overall) decreases the ecological footprint. On the other hand, financial and political globalization poses a favorable impact on environmental quality, while economic and social globalization is found to increase environmental degradation. Population aging has a statistically significant negative effect on the ecological footprint, but its non-linear term increases the ecological footprint. Additionally, economic growth, energy consumption, and natural resource rent exacerbate environmental deterioration. In contrast, human capital decreases ecological footprint. Based on the empirical results, important policy implications have been provided.