bluuebunny/crossref_metadata_2025 huggingface dataset:
The EpiOcular Eye Irritation Test (EIT) for Hazard Identification and Labelling of Eye Irritating Chemicals: Protocol Optimisation for Solid Materials and the Results after Extended Shipment
Authors: Kaluzhny Yulia , Kandárová Helena , Handa Yuki , DeLuca Jane , Truong Thoa , Hunter Amy , Kearney Paul , d'Argembeau-Thornton Laurence , Klausner Mitchell
Published: April 2019

The 7th Amendment to the EU Cosmetics Directive and the EU REACH Regulation have reinforced the need for in vitro ocular test methods. Validated in vitro ocular toxicity tests that can predict the human response to chemicals, cosmetics and other consumer products are required for the safety assessment of materials that intentionally, or inadvertently, come into contact with the eye. The EpiOcular Eye Irritation Test (EIT), which uses the normal human cell-based EpiOcular™ tissue model, was developed to address this need. The EpiOcular-EIT is able to discriminate, with high sensitivity and accuracy, between ocular irritant/corrosive materials and those that require no labelling. Although the original EpiOcular-EIT protocol was successfully pre-validated in an international, multicentre study sponsored by COLIPA (the predecessor to Cosmetics Europe), data from two larger studies (the EURL ECVAM–COLIPA validation study and an independent in-house validation at BASF SE) resulted in a sensitivity for the protocol for solids that was below the acceptance criteria set by the Validation Management Group (VMG) for eye irritation, and indicated the need for improvement of the assay's sensitivity for solids. By increasing the exposure time for solid materials from 90 minutes to 6 hours, the optimised EpiOcular-EIT protocol achieved 100% sensitivity, 68.4% specificity and 84.6% accuracy, thereby meeting all the acceptance criteria set by the VMG. In addition, to satisfy the needs of Japan and the Pacific region, the EpiOcular-EIT method was evaluated for its performance after extended shipment and storage of the tissues (4–5 days), and it was confirmed that the assay performs with similar levels of sensitivity, specificity and reproducibility in these circumstances.
More Noise Does Not Mean More Precision: A Review of Aldenberg and Rorije (2013)
Authors: Fox David R.
Published: April 2019

This paper provides a critical review of recently published work that suggests that the precision of hazardous concentration estimates from Species Sensitivity Distributions (SSDs) is improved when the uncertainty in the input data is taken into account. Our review confirms that this counter-intuitive result is indeed incorrect.
SEARCHBreast Workshop Proceedings: 3D Modelling of Breast Cancer
Authors: Morrissey Bethny , Blyth Karen , Carter Phil , Chelala Claude , Holen Ingunn , Jones Louise , Speirs Valerie
Published: April 2019

SEARCHBreast, a UK initiative supported by the NC3Rs, organised a workshop entitled 3D Modelling of Breast Cancer. The workshop focused on providing researchers with solutions to overcome some of the perceived barriers to working with human-derived tumour cells, cell lines and tissues, namely: a) the limited access to human-derived material; and b) the difficulty in working with these samples. The workshop presentations provided constructive advice and information on how to best prepare human cells or tissues for further downstream applications. Techniques in developing primary cultures from patient samples, and considerations when preserving tissue slices, were discussed. A common theme throughout the workshop was the importance of ensuring that the cells are grown in conditions as similar to the in vivo microenvironment as possible. Comparisons of the advantages of several in vitro options, such as primary cell cultures, cell line cultures, explants or tissue slices, suggest that all offer great potential applications for breast cancer research, and highlight that it need not be a case of choosing one over the other. The workshop also offered cutting-edge examples of on-chip technologies and 3-D tumour modelling by using virtual pathology, which can contribute to clinically relevant studies and provide insights into breast cancer metastatic mechanisms.
On the Safety of E-cigarettes: “I can Resist anything except Temptation”1
Authors: Combes Robert D. , Balls Michael
Published: April 2019

Strategic policy decisions are being made about e-cigarettes, based on the plausibility of their greater safety, rather than on essential scientific evidence which would permit a proper risk assessment. If e-cigarettes are really ‘safer’, then their use should be recommended, but only after an intelligent analysis of their risk to human health, based on integrated in silico, in vitro and clinical studies for both scientific and logistical reasons
Non-human Primates in Neuroscience Research: The Case against its Scientific Necessity
Authors: Bailey Jarrod , Taylor Katy
Published: April 2019

Public opposition to non-human primate (NHP) experiments is significant, yet those who defend them cite minimal harm to NHPs and substantial human benefit. Here we review these claims of benefit, specifically in neuroscience, and show that: a) there is a default assumption of their human relevance and benefit, rather than robust evidence; b) their human relevance and essential contribution and necessity are wholly overstated; c) the contribution and capacity of non-animal investigative methods are greatly understated; and d) confounding issues, such as species differences and the effects of stress and anaesthesia, are usually overlooked. This is the case in NHP research generally, but here we specifically focus on the development and interpretation of functional magnetic resonance imaging (fMRI), deep brain stimulation (DBS), the understanding of neural oscillations and memory, and investigation of the neural control of movement and of vision/binocular rivalry. The increasing power of human-specific methods, including advances in fMRI and invasive techniques such as electrocorticography and single-unit recordings, is discussed. These methods serve to render NHP approaches redundant. We conclude that the defence of NHP use is groundless, and that neuroscience would be more relevant and successful for humans, if it were conducted with a direct human focus. We have confidence in opposing NHP neuroscience, both on scientific as well as on ethical grounds.
Statistics of Scientific Procedures on Living Animals 2014: A New Format, and Hopefully a New Era of Diminishing Animal Experimentation?
Authors: Hudson-Shore Michelle
Published: April 2019

The Annual Statistics of Scientific Procedures on Living Animals Great Britain 2014 reports a welcome decline in animal experimentation in the UK. However, caution has to be exercised when interpreting these most recent figures, due to the significant changes made to satisfy the requirements of Directive 2010/63/EU as to what information is reported and how it is reported. Comparisons to the figures and trends reported in previous years is difficult, so this paper focuses on the specifics of the current report, providing information on overall animal use and highlighting specific issues associated with genetically-altered animals, fish and primates. There is a detailed discussion of the extent of the changes, commenting on the benefits and disadvantages of the new format, in areas such as severity of procedures, legislation and techniques of special interest. It also considers the consequences of the changes on the effective monitoring of laboratory animal use, the openness and transparency regarding the impacts of animal use, and the implementation of Three Rs initiatives. In addition, suggestions for further improvements to the new format are made to the Home Office.
A Training Course on Laboratory Animal Science: An Initiative to Implement the Three Rs of Animal Research in India
Authors: Pratap Kunal , Singh Vijay Pal
Published: April 2019

There is a current need for a change in the attitudes of researchers toward the care and use of experimental animals in India. This could be achieved through improvements in the provision of training, to further the integration of the Three Rs concept into scientific research and into the regulations of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). A survey was performed after participants undertook the Federation of European Laboratory Animal Science Associations (FELASA) Category C-based course on Laboratory Animal Science (in 2013 and 2015). It revealed that the participants subsequently employed, in their future research, the practical and theoretical Three Rs approaches that they had learned. This is of great importance in terms of animal welfare, and also serves to benefit their research outcomes extensively. All the lectures, hands-on practical sessions and supplementary elements of the courses, which also involved the handling of small animals and procedures with live animals, were well appreciated by the participants. Insight into developments in practical handling and welfare procedures, norms, directives, and ethical use of laboratory animals in research, was also provided, through the comparison of results from the 2013 and 2015 post-course surveys.
Evaluation of Non-animal Methods for Assessing Skin Sensitisation Hazard: A Bayesian Value-of-Information Analysis
Authors: Leontaridou Maria , Gabbert Silke , Van Ierland Ekko C. , Worth Andrew P. , Landsiedel Robert
Published: April 2019

This paper offers a Bayesian Value-of-Information (VOI) analysis for guiding the development of non-animal testing strategies, balancing information gains from testing with the expected social gains and costs from the adoption of regulatory decisions. Testing is assumed to have value, if, and only if, the information revealed from testing triggers a welfare-improving decision on the use (or non-use) of a substance. As an illustration, our VOI model is applied to a set of five individual non-animal prediction methods used for skin sensitisation hazard assessment, seven battery combinations of these methods, and 236 sequential 2-test and 3-test strategies. Their expected values are quantified and compared to the expected value of the local lymph node assay (LLNA) as the animal method. We find that battery and sequential combinations of non-animal prediction methods reveal a significantly higher expected value than the LLNA. This holds for the entire range of prior beliefs. Furthermore, our results illustrate that the testing strategy with the highest expected value does not necessarily have to follow the order of key events in the sensitisation adverse outcome pathway (AOP).
Local Tolerance Testing under REACH: Accepted Non-animal Methods are Not on Equal Footing with Animal Tests
Authors: Sauer Ursula G. , Hill Erin H. , Curren Rodger D. , Kolle Susanne N. , Teubner Wera , Mehling Annette , Landsiedel Robert
Published: April 2019

In general, no single non-animal method can cover the complexity of any given animal test. Therefore, fixed sets of in vitro (and in chemico) methods have been combined into testing strategies for skin and eye irritation and skin sensitisation testing, with pre-defined prediction models for substance classification. Many of these methods have been adopted as OECD test guidelines. Various testing strategies have been successfully validated in extensive in-house and inter-laboratory studies, but they have not yet received formal acceptance for substance classification. Therefore, under the European REACH Regulation, data from testing strategies can, in general, only be used in so-called weight-of-evidence approaches. While animal testing data generated under the specific REACH information requirements are per se sufficient, the sufficiency of weight-of-evidence approaches can be questioned under the REACH system, and further animal testing can be required. This constitutes an imbalance between the regulatory acceptance of data from approved non-animal methods and animal tests that is not justified on scientific grounds. To ensure that testing strategies for local tolerance testing truly serve to replace animal testing for the REACH registration 2018 deadline (when the majority of existing chemicals have to be registered), clarity on their regulatory acceptance as complete replacements is urgently required.
Acute Oral Toxicity Testing: Scientific Evidence and Practicability Should Govern Three Rs Activities
Authors: Buesen Roland , Oberholz Uwe , Sauer Ursula G. , Landsiedel Robert
Published: April 2019

Acute oral toxicity is determined for regulatory hazard classification or non-classification. The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) recommends the following modules for acute oral toxicity testing: a) the use of the in vitro 3T3 Neutral Red Uptake (NRU) test to identify substances not requiring classification and to estimate starting doses for in vivo acute oral toxicity studies; and b) the use of data from sub-acute toxicity studies to identify substances not requiring classification. However, the application of these modules in a regulatory context would require a predefined, validated and formally accepted testing strategy and data interpretation procedure, which are not available. Furthermore, the application of the 3T3 NRU assay for starting dose estimations could in fact increase the number of animals used. Finally, only very few substances exist for which data from sub-acute or other repeated dose studies are available, but data from acute studies are not. Therefore, in practice, the prediction of acute toxicity by using sub-acute toxicity data is generally irrelevant. It could even lead to a risk of overdosing in the range-finding study, which may result in the death of many or all of the animals used.
Expectations for the Methodology and Translation of Animal Research: A Survey of the General Public, Medical Students and Animal Researchers in North America
Authors: Joffe Ari R. , Bara Meredith , Anton Natalie , Nobis Nathan
Published: April 2019

To determine what are considered acceptable standards for animal research (AR) methodology and translation rate to humans, a validated survey was sent to: a) a sample of the general public, via Sampling Survey International (SSI; Canada), Amazon Mechanical Turk (AMT; USA), a Canadian city festival (CF) and a Canadian children's hospital (CH); b) a sample of medical students (two first-year classes); and c) a sample of scientists (corresponding authors and academic paediatricians). There were 1379 responses from the general public sample (SSI, n = 557; AMT, n = 590; CF, n = 195; CH, n = 102), 205/330 (62%) medical student responses, and 23/323 (7%, too few to report) scientist responses. Asked about methodological quality, most of the general public and medical student respondents expect that: AR is of high quality (e.g. anaesthesia and analgesia are monitored, even overnight, and ‘humane’ euthanasia, optimal statistical design, comprehensive literature review, randomisation and blinding, are performed), and costs and difficulty are not acceptable justifications for lower quality (e.g. costs of expert consultation, or more laboratory staff). Asked about their expectations of translation to humans (of toxicity, carcinogenicity, teratogenicity and treatment findings), most expect translation more than 60% of the time. If translation occurred less than 20% of the time, a minority disagreed that this would “significantly reduce your support for AR”. Medical students were more supportive of AR, even if translation occurred less than 20% of the time. Expectations for AR are much higher than empirical data show to have been achieved.
Attitudes toward the use of Animals in Chronic versus Acute Pain Research: Results of a Web-based Forum
Authors: Ormandy Elisabeth H. , Griffin Gilly
Published: April 2019

When asked about the use of animals in biomedical research, people often state that the research is only acceptable if pain and distress are minimised. However, pain is caused when the aim is to study pain itself, resulting in unalleviated pain for many of the animals involved. Consequently, the use of animals in pain research is often considered contentious. To date, no research has explored people's views toward different types of animal-based pain research (e.g. chronic or acute pain). This study used a web-based survey to explore people's willingness to support the use of mice in chronic versus acute pain research. The majority of the participants opposed the use of mice for either chronic (68.3%) or acute (63.1%) pain research. There was no difference in the levels of support or opposition for chronic versus acute pain research. Unsupportive participants justified their opposition by focusing on the perceived lack of scientific merit, or the existence of non-animal alternatives. Supporters emphasised the potential benefits that could arise, with some stating that the benefits outweigh the costs. The majority of the participants were opposed to pain research involving mice, regardless of the nature and duration of the pain inflicted, or the perceived benefit of the research. A better understanding of public views toward animal use in pain research may provide a stronger foundation for the development of policy governing the use of animals in research where animals are likely to experience unalleviated pain.
The Adverse Outcome Pathway Concept: A Basis for Developing Regulatory Decision-making Tools
Authors: Delrue Nathalie , Sachana Magdalini , Sakuratani Yuki , Gourmelon Anne , Leinala Eeva , Diderich Robert
Published: April 2019

The Adverse Outcome Pathway (AOP) concept is expected to guide risk assessors in their work to use all existing information on the effects of chemicals on humans and wildlife, and to target the generation of additional information to the regulatory objective. AOPs will therefore be used in the Organisation for Economic Co-operation and Development (OECD) chemical safety programme, as underlying scientific rationales for the development of alternative methods for hazard assessment, such as read-across, in vitro test methods or the development of integrated testing strategies that have the potential to replace animal tests. As a proof-of-concept, the OECD has developed an AOP for skin sensitisation, and as a follow-up has: a) implemented the AOP into the OECD QSAR Toolbox, so that information related to the Key Events (KEs) in the AOP can be used to group chemicals that are expected to act by the same mechanism and hence have the same skin sensitisation potential; b) developed alternative test methods for the KEs, so that ultimately chemicals can be tested for skin sensitisation without the use of animal tests. The development of integrated testing strategies based on the AOP is ongoing. Building on this proof-of-concept, the OECD has launched an AOP development programme with a first batch of AOPs published in 2016. A number of IT tools, which together form an AOP Knowledge Base, are at various stages of development, and support the construction of AOPs and their use in the development of integrated approaches for testing and assessment. Following the publication of the first batch of AOPs, OECD member countries will decide on priorities for their use in supporting the development of tools for regulatory use.
Establishment of a Tumour–Stroma Airway Model (OncoCilAir) to Accelerate the Development of Human Therapies against Lung Cancer
Authors: Mas Christophe , Boda Bernadett , Futy Mireille Caul , Huang Song , Wisniewski Ludovic , Constant Samuel
Published: April 2019

This paper highlights the work for which OncoTheis, a Swiss biotechnology company, engaged in the development of innovative bioengineered tissues and organoids for cancer research, was co-awarded the 2015 Lush Science Prize. Noting that the use of animal models failed to lead to the design of effective treatments for cancer, OncoTheis has opted to develop in vitro models based exclusively on human cells. The company currently focuses on lung cancer, which is the leading cause of cancer-related deaths worldwide, with more than one million deaths per year. To address this public health concern, we developed OncoCilAir™, a new 3-D model that mimics in vitro the progression of the disease as it happens in patients. In this system, bronchial and lung tumour cells obtained from discarded surgical tissue are co-cultured in a Petri dish to reconstitute a fragment of the human lung. After appropriate differentiation, the culture closely reproduces malignant pulmonary nodules invading a small piece of functional airway tissue. As OncoCilAir includes both healthy and cancerous tissues, it can be used to test tumour-killing activity and the adverse effects of chemotherapies and other anti-cancer drugs. Moreover, a single culture can be maintained for up to three months, which permits studies of longer-term effects, including the assessment of drug resistance and tumour recurrence. OncoCilAir heralds a new generation of integrated in vitro models, which is expected to increase the quality of preclinical research while replacing animal testing.
It Takes a Village: Stakeholder Participation is Essential to Transforming Science
Authors: Sullivan Kristie
Published: April 2019

Efforts toward replacing the use of animals in toxicology testing have begun to make significant headway in the last several years, due to co-operative and pragmatic efforts on the part of many stakeholders, and the public pressure that non-governmental advocacy organisations represent. Science-focused advocacy organisations have a unique role to play in these efforts, as they often have flexibility to adapt quickly to keep a project going and forge connections among different kinds of stakeholders to help encourage buy-in. This year, meaningful progress has been made, especially in regulatory laws and policies, which will lead to the replacement of animals in toxicology testing. In order to keep this momentum, we need to measure progress — but this requires improved transparency and regular reporting of animal use. In addition, we should consider how strategies that have successfully reduced and replaced animal use in toxicology can be applied to basic biomedical research practices.
The Use of Neurocomputational Models as Alternatives to Animal Models in the Development of Electrical Brain Stimulation Treatments
Authors: Beuter Anne
Published: April 2019

Recent publications call for more animal models to be used and more experiments to be performed, in order to better understand the mechanisms of neurodegenerative disorders, to improve human health, and to develop new brain stimulation treatments. In response to these calls, some limitations of the current animal models are examined by using Deep Brain Stimulation (DBS) in Parkinson's disease as an illustrative example. Without focusing on the arguments for or against animal experimentation, or on the history of DBS, the present paper argues that given recent technological and theoretical advances, the time has come to consider bioinspired computational modelling as a valid alternative to animal models, in order to design the next generation of human brain stimulation treatments. However, before computational neuroscience is fully integrated in the translational process and used as a substitute for animal models, several obstacles need to be overcome. These obstacles are examined in the context of institutional, financial, technological and behavioural lock-in. Recommendations include encouraging agreement to change long-term habitual practices, explaining what alternative models can achieve, considering economic stakes, simplifying administrative and regulatory constraints, and carefully examining possible conflicts of interest.
In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products: Workshop Proceedings, Conclusions and Paths Forward for In Vitro Model Use
Authors: Behrsing Holger , Hill Erin , Raabe Hans , Tice Raymond , Fitzpatrick Suzanne , Devlin Robert , Pinkerton Kent , Oberdörster Günter , Wright Chris , Wieczorek Roman , Aufderheide Michaela , Steiner Sandro , Krebs Tobias , Asgharian Bahman , Corley Richard , Oldham Michael , Adamson Jason , Li Xiang , Rahman Irfan , Grego Sonia , Chu Pei-Hsuan , McCullough Shaun , Curren Rodger
Published: April 2019

In 2009, the passing of the Family Smoking Prevention and Tobacco Control Act facilitated the establishment of the FDA Center for Tobacco Products (CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed ‘modified risk’. On 4–6 April 2016, the Institute for In Vitro Sciences, Inc. (IIVS) convened a workshop conference entitled, In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products, to bring together stakeholders representing regulatory agencies, academia and industry to address the research priorities articulated by the FDA CTP. Specific topics were covered to assess the status of current in vitro smoke and aerosol/vapour exposure systems, as well as the various approaches and challenges to quantifying the complex exposures in in vitro pulmonary models developed for evaluating adverse pulmonary events resulting from tobacco product exposures. The four core topics covered were: a) Tobacco Smoke and E-Cigarette Aerosols; b) Air–Liquid Interface- In Vitro Exposure Systems; c) Dosimetry Approaches for Particles and Vapours/ In Vitro Dosimetry Determinations; and d) Exposure Microenvironment/Physiology of Cells. The 2.5-day workshop included presentations from 20 expert speakers, poster sessions, networking discussions, and breakout sessions which identified key findings and provided recommendations to advance these technologies. Here, we will report on the proceedings, recommendations, and outcome of the April 2016 technical workshop, including paths forward for developing and validating non-animal test methods for tobacco product smoke and next generation tobacco product aerosol/vapour exposures. With the recent FDA publication of the final deeming rule for the governance of tobacco products, there is an unprecedented necessity to evaluate a very large number of tobacco-based products and ingredients. The questionable relevance, high cost, and ethical considerations for the use of in vivo testing methods highlight the necessity of robust in vitro approaches to elucidate tobacco-based exposures and how they may lead to pulmonary diseases that contribute to lung exposure-induced mortality worldwide.
New Animal-free Concepts and Test Methods for Developmental Toxicity and Peripheral Neurotoxicity
Authors: Leist Marcel
Published: April 2019

The complex toxicological fields of repeat dose organ toxicity (RDT) and developmental and reproductive toxicity (DART) still require new concepts and approaches to achieve a fully animal-free safety assessment of chemicals. One novel approach is the generation of relevant human cell types from pluripotent stem cells, and the use of such cells for the establishment of phenotypic test methods. Due to their broad endpoints, such tests capture multiple types of toxicants, i.e. they are a readout for the activation of many adverse outcome pathways (AOPs). The 2016 Lush Science Prize was awarded for the development of one such assay, the PeriTox test, which uses human peripheral neurons generated from stem cells. The assay endpoints measure various cell functions, and these give information on the potential neurotoxicity and developmental neurotoxicity hazard of test compounds. The PeriTox test method has a high predictivity and sensitivity for peripheral neurotoxicants, and thus addresses the inherent challenges in pesticide testing and drug development. Data from the test can be obtained quickly and at a relatively high-throughput, and thus, the assay has the potential to replace animal-based safety assessment during early product development or for screening potential environmental toxicants.
The Use of Animals in Contemporary Medical Research — If Not Animals, then who or What?
Authors: Zwolińska Jolanta
Published: April 2019

Contemporary science provides a range of opportunities for improving research methods and for eliminating animals from experiments
Questionable Progress in the Application of the Three Rs to Improve Science, Human Well-being and Animal Welfare
Authors: Balls Michael , Combes Robert D.
Published: April 2019

While the standard of animal experimentation in the UK is generally very high, the aim of the Home Office appears to be to maintain the status quo, rather than to achieve significant Replacement and Reduction, and ensure Refinement
Murine Alveolar Epithelial Cells and Their Lentivirus-mediated Immortalisation
Authors: Sapich Sandra , Hittinger Marius , Hendrix-Jastrzebski Remi , Repnik Urska , Griffiths Gareth , May Tobias , Wirth Dagmar , Bals Robert , Schneider-Daum Nicole , Lehr Claus-Michael
Published: April 2019

In this study, we describe the isolation and immortalisation of primary murine alveolar epithelial cells (mAEpC), as well as their epithelial differentiation and barrier properties when grown on Transwell® inserts. Like human alveolar epithelial cells (hAEpC), mAEpC transdifferentiate in vitro from an alveolar type II (ATII) phenotype to an ATI-like phenotype and exhibit features of the air–blood barrier, such as the establishment of a thin monolayer with functional tight junctions (TJs). This is demonstrated by the expression of TJ proteins (ZO-1 and occludin) and the development of high transepithelial electrical resistance (TEER), peaking at 1800ω•cm2. Transport across the air–blood barrier, for general toxicity assessments or preclinical drug development, is typically studied in mice. The aim of this work was the generation of novel immortalised murine lung cell lines, to help meet Three Rs requirements in experimental testing and research. To achieve this goal, we lentivirally transduced mAEpC of two different mouse strains with a library of 33 proliferation-promoting genes. With this immortalisation approach, we obtained two murine alveolar epithelial lentivirus-immortalised (mAELVi) cell lines. Both showed similar TJ protein localisation, but exhibited less prominent barrier properties (TEERmax ~250Ω•cm2) when compared to their primary counterparts. While mAEpC demonstrated their suitability for use in the assessment of paracellular transport rates, mAELVi cells could potentially replace mice for the prediction of acute inhalation toxicity during early ADMET studies.
Electronic Cigarettes: Can Dependable Public Health Policies be Developed and Applied without Relevant and Reliable Risk Assessments?
Authors: Balls Michael , Combes Robert
Published: April 2019

The use of electronic cigarettes is being encouraged as a way of escaping from the harm resulting from conventional tobacco smoking, while scant attention is being paid to the long-term risks of inhaling electronic cigarette vapour. More information is needed for an acceptable risk assessment, from integrated non-animal testing and sound clinical investigations
The Use of Human Keratinocytes in the EU/COLIPA International In Vitro Phototoxicity Test Validation Study and the ECVAM/COLIPA Study on UV Filter Chemicals
Authors: Clothier Richard , Willshaw Angie , Cox Helen , Garle Michael , Bowler Helen , Combes Robert
Published: April 2019

The EU/COLIPA in vitro phototoxicity study involved the testing of 30 chemicals in Phase II, and the ECVAM/COLIPA study on UV filter chemicals involved the testing of 20 chemicals, for which in vivo human and/or animal data were available. Primary human keratinocytes, from four separate male donors, were not found to be sensitive to the 5J/cm2 UVA produced by the SOL500 lamp when assayed by using the neutral red uptake endpoint, as employed with the 3T3 cells used in these international interlaboratory validation studies. The primary human keratinocytes tested in one laboratory alongside the 3T3 fibroblasts gave consistent indications of phototoxicity with all the phototoxicants tested in the Phase II and UV filter studies. The one exception was bithionol, which was predicted to be non-phototoxic in both studies. None of the non-phototoxic chemicals resulted in a positive reaction with the Photo-irritation Factor (PIF) version of the prediction model. However, when the Mean Photo Effect (MPE) prediction model version was applied (with a cut-off point of 0.1), one sunscreen agent, octyl salicylate, was deemed to have phototoxic potential. The entire set of negative rated chemicals included in Phase II and in the UV filter study were also rated as non-phototoxic by the MPE prediction model.
Can Cytotoxic Effects Induced by Industrial Chemicals be Time-dependent?
Authors: Kuchowicz Ewa , Rydzynski Konrad
Published: April 2019

Short-term and delayed cytotoxic effects of selected water-soluble and water-insoluble industrial chemicals (dimethyl sulphoxide, ethyl alcohol, methyl alcohol, ammonium nitrate, benzalkonium chloride, butoxyethanol and propylene glycol) were tested on confluent 3T3-L1 mouse fibroblasts by using the neutral red uptake (NRU) assay and the MTT assay. The NRU and MTT assays were performed after exposure to a chemical for 10 minutes and 3 hours and then again 7 days later. The results indicate that the system of testing used permits the assessment of both early and delayed cytotoxic effects of different classes of chemicals. Our experiments revealed that three out of the seven substances tested (butoxyethanol, dimethyl sulphoxide and propylene glycol) exhibited similar cytotoxic effects when assessed after exposure for 10 minutes and 7 days later. The results for ammonium nitrate, ethyl alcohol and methyl alcohol, tested after exposure for 10 minutes and 7 days later, did not significantly differ from each other. However, we noted that the cytotoxic effects observed 7 days after exposure were more pronounced than those found for the same concentration, after exposure for 3 hours. One chemical tested (benzalkonium chloride) had almost no cytotoxic effect after exposure for 10 minutes and 3 hours, but showed a strong cytotoxic effect 7 days after exposure. Our study indicated that the cytotoxic effect might be time-dependent in some chemicals, thus inducing a delayed effect in vitro. In our opinion, it is advisable to assess the cytotoxicity of a chemical after exposure for 3 hours (for immediate effects) and again 7 days later (for delayed effects).
Oxidative DNA Damage in Human Cells Induced by Paraquat
Authors: Petrovská Helena , Dušinská Mária
Published: April 2019

Oxidative DNA damage was studied after exposing two human transformed cell lines (HeLa and Hep G2) and freshly isolated human peripheral lymphocytes to the herbicide, paraquat. We used the alkaline comet assay, modified by incubating nucleoid DNA with endonuclease III to detect oxidised pyrimidines, and with formamidopyrimidine glycosylase to detect 8-oxo-guanine and ring-opened purines. Paraquat induces both strand breaks and oxidised bases, the amounts of each being dependent on the concentration of paraquat and the cell type exposed. Exposure to lower concentrations of paraquat for 1 hour induced dose-dependent DNA damage in Hep G2 cells and in human peripheral lymphocytes. DNA damage was reduced at higher concentrations. Our results support the finding that paraquat induces oxidative stress but, over a certain concentration range, also stimulates antioxidant protection. Reduction of DNA damage was not found in HeLa cells after exposure for 1 hour or 24 hours. Short-term exposure to paraquat induced a moderate amount of oxidative DNA damage (mainly oxidized pyrimidines) in HeLa cells. Exposure for 24 hours induced a high proportion of oxidised bases and strand breaks. Hep G2 cells showed the greatest number of DNA strand breaks, with no sign of base oxidation.
Time-courses of Growth Inhibition and Recovery for Narcotic Chemicals and 2,6-Dinitrophenol in Pollen Suspensions of Nicotiana sylvestris
Authors: Sichtling Stefan , Quader Hartmut , Kristen Udo
Published: April 2019

In a previous structure-activity analysis of chlorophenol and nitrophenol toxicity, the pollen tube growth test was shown to discriminate between oxidative uncoupling and narcotic mechanisms of action. To examine the suitability of the use of pollen tubes in screening for narcotic chemicals, we used tobacco pollen suspensions and performed time-course experiments on pollen tube growth inhibition and recovery after exposure to 1-butanol, 2-chloroaniline, 2,4-dichlorophenol and 2,6-dinitrophenol, during pollen culture for 22 hours. After exposure to the chemicals for 2 hours, pollen tubes exposed to 1-butanol and 2,6-dinitrophenol were able to recover, whereas recovery was poor after exposure to 2-chloroaniline and 2,4-dichlorophenol. Dilution experiments to remove the narcotics from the pollen suspension indicated that 2-chloroaniline and 2,4-dichlorophenol accumulated in the pollen grain wall, presumably due to their high octanol/water partition coefficients. Therefore, we suggest that the pollen tube growth test is not suitable for correctly predicting the narcotic potencies of highly lipophilic compounds. In the presence of 1-butanol, pollen grains did not germinate, but became characteristically enlarged. This observation suggests that 1-butanol inhibits the establishment of the cell polarity necessary for initiating pollen tube outgrowth.
Evaluation of PVA/dextran/chitosan hydrogel for wound dressing
Authors: Lin Shin-Ping , Lo Kai-Yin , Tseng Tien-Ni , Liu Jui-Ming , Shih Ting-Yu , Cheng Kuan-Chen
Published: April 2019

Developing a multiple functional wound dressing suitable for different stages of wound healing is important for patients with special wound such as burn or decubital ulcers. In this study, poly (vinyl alcohol) (PVA), dextran, and chitosan are integrated to produce ideal wound dressing where glutaraldehyde (GA) is used as the cross-linker. The result demonstrated that 6% PVA hydrogel with 0.25% chitosan was found to provide antimicrobial ability. The PVA/chitosan hydrogel combined with 4% dextran utilizing GA cross-linking also presents the high cell proliferation ability, which suggests that the hydrogel is potential as a wound dressing. In the following physical analyses, the addition of chitosan and dextran appeared to promote the thermostability, mechanical properties, water retention, and moisturizing ability in the PVA hydrogel. In conclusion, the PVA/chitosan/dextran hydrogel has promising potential such as high water content, antimicrobial property, and well cell proliferation, which can be applied to wound healing application.
The Voyage Perilous
Authors: Znagie Bechir
Published: April 2019

Europe too has its boat people: a tragic tide flowing from North Africa and further south
Hi-Tech Terror
Authors: Hesse Genevieve
Published: April 2019

Threats from neo-Nazis are forcing German journalists to choose self-defence or self-censorship
Apartheid and Censorship
Authors: Gordimer Nadine
Published: April 2019

Written in 1972 following the South African government's plans to abolish the right of appeal against decisions brought by the State Publications Control Board
The subjective well-being of homeworkers across life domains
Authors: Reuschke Darja
Published: April 2019

This paper extends the view of homeworking as a type of flexible working by employees in organisations aimed at improving work–life balance and job satisfaction, to a type of work that encapsulates significant changes of work towards increased self-employment and casual work, high proportions of which are performed in people’s homes. Such changes to work represent a reconfiguration of the spatial separation and relationship between place of work and place of residence. Through homeworking, this paper studies how changing geographies of work and workplaces impact on workers’ life satisfaction overall and across various aspects of their lives. Using a large representative longitudinal dataset for the United Kingdom, findings reveal that workers’ satisfaction with their job, income and leisure time is significantly shaped by homeworking and that the employment status (employee versus self-employed) and gender are important elements for understanding how homeworking is related to subjective well-being. Homeworking is positively related with leisure time satisfaction of men and women. Job satisfaction advances of homeworking are only observed for employees, but not the self-employed. Men’s income satisfaction is decreased when they work as self-employed without employees in their homes. Future policies and research concerning workers’ subjective well-being need to pay attention to the continued trend towards individualised work in people’s own homes.
Classics Revisited: “The evolution of nests and nest-building in birds”, by Dr Nicholas E Collias (1964) American Zoologist 4(2): 175–190
Authors: McLendon Aidan K
Published: April 2019

Although one of the most studied organisms in other disciplines, the role of birds as zoogeomorphic agents has been somewhat overlooked in geography literature. Bird nests serve as a manifestation of the reciprocal relationships that birds have with their environment. Dr Nicholas E. Collias’s “The evolution of nests and nest-building in birds”, published in American Zoologist (1964), was one of the first to hypothesize the intimate connection between bird nests and their landscapes. Researchers interested in understanding the role birds have as zoogeomorphic agents should view Collias (1964) as an essential resource for information and inspiration for further exploration.
Association of migraine with calcification in major vessel beds: The Rotterdam Study
Authors: Wen Ke-xin , Ikram Mohammad Arfan , Franco Oscar H , Vernooij Meike , MaassenVanDenBrink Antoinette , Bos Daniel , Kavousi Maryam
Published: April 2019

Background

To explore the role of large-artery atherosclerosis in migraine, we investigated the association between migraine and arterial calcification in different intracranial and extracranial vessels.

Methods

1856 participants were included, mean age (standard deviation) 67.4 (5.8) years, from the population-based Rotterdam Study cohort. Migraine was assessed by validated questionnaire and vascular calcification was assessed by computed tomography (expressed in Agatston score for the coronary arteries and volume in mm3 for the aortic arch, intracranial, and extracranial carotid arteries). Per vessel, the association of migraine with calcification was investigated by linear regression, adjusted for age, sex, cardiovascular risk factors, and calcification in other vessels.

Results

Of the participants, 279 (15%) were identified as persons with lifetime migraine. In multivariable adjusted models, migraine was associated with smaller intracranial carotid artery calcification volume (difference in log-transformed calcification volume in persons with migraine compared to persons without migraine: −0.19[−0.29, −0.08]). While subjects with migraine also showed a lower calcification burden in the remaining arterial beds, those associations did not reach statistical significance.

Conclusions

Persons with migraine, compared to those without, had less arterial calcification in the intracranial carotid artery, but not in other arterial beds. Future studies are needed to confirm these findings.
Are White Women Showing Up for Racial Justice? Intergroup Contact, Closeness to People Targeted by Prejudice, and Collective Action
Authors: Tropp Linda R. , Uluğ Özden Melis
Published: April 2019

Although scholars have suggested that relationships with people of color can enhance White people’s commitment to racial justice, many women of color have questioned whether White people, and White women in particular, actually “show up” to protest for racial justice. Focusing on the contact experiences and closeness White women have with people from racial and ethnic groups different from their own, we tested how these relationships may predict their reported motivations to engage in protests for racial justice. With a broad online sample of White American women (Study 1), and White women who attended the 2017 Women’s March (Study 2), our results showed that both positive contact and closeness to people targeted by prejudice predicted White women’s willingness to participate in protests for racial justice (Studies 1 and 2). Only closeness to people targeted by prejudice significantly predicted actual participation in collective action for racial justice (Studies 1 and 2) and also predicted motivation for racial justice among those who attended the 2017 Women’s March (Study 2). Findings suggest that White women’s inclinations to protest for racial justice may be linked to the close relationships they have with people targeted by prejudice, while more general forms of positive contact may not be related to such action. Additional online materials for this article are available on PWQ ’s website at https://journals.sagepub.com/doi/suppl/10.1177/0361684319840269 . Online slides for instructors who want to use this article for teaching are available on PWQ' s website at http://journals.sagepub.com/page/pwq/suppl/index
Work Schedule Patching in Health Care: Exploring Implementation Approaches
Authors: Kossek Ellen Ernst , Rosokha Lindsay Mechem , Leana Carrie
Published: April 2019

The authors propose a typology of “work schedule patching,” the ongoing adjustments made to plug scheduling holes after employers post schedules. Patching occurs due to changes in employer work demands, or employee nonwork demands necessitating scheduling adjustments, which are reactive or proactive. Using qualitative data from eight health-care facilities, the authors identified three narratives justifying schedule patching implementation approaches (share-the-pain, work-life-needs, and reverse-status-rotation) with variation in formalization and improvisation. Exploratory analysis showed a suggestive link between improvised work–life scheduling and lower pressure ulcers. This article advances theory on balancing the “service triangle” of scheduling in-service economies including health care.
“Dreamers” or threat: Bilingual frame building of DACA immigrants
Authors: Rendon Hector , de Moya Maria , Johnson Melissa A.
Published: April 2019

This research analyzes Spanish- and English-language news discourses in the United States following the announcement of the Deferred Action for Childhood Arrivals (DACA) program. It identifies how sources quoted by journalists affected framing of stories in five ethnic and general market newspapers. Coverage of Dreamers and DACA was generally positive, especially compared to common representations of undocumented immigrants as criminals and as a threat to the United States. Certain sources were a strong predictor for some frames about DACA, and undocumented people who arrived in the United States when they were children could be analyzed in communication research as a different category of immigrants than other adults.
Attitudes about Care at the End of Life among Clinicians: A Quick, Reliable, and Valid Assessment Instrument
Authors: Bradley Elizabeth H. , Cicchetti Domenic V. , Fried Terri R. , Rousseau David M. , Johnson-Hurzeler Rosemary , Kasl Stanislav V. , Horwitz Sarah M.
Published: April 2019

Several initiatives to improve care at the end of life involve educational programs to influence clinicians’ attitudes about care for patients with terminal illnesses. The objective of this research was to develop and test a short and easily administered instrument for measuring physicians’ and nurses’ attitudes towards care at the end of life. The instrument was tested using a cross-sectional study of 50 clinicians (25 physicians and 25 nurses) from general medicine, cardiology, oncology, and geriatric medicine. Both reliability and validity were assessed, and the instrument was found to have acceptable test-retest reliability and construct validity. Such an assessment instrument may be useful in evaluating the impact of initiatives to modify attitudes towards terminal care and in improving the quality of care at the end of life.