2018 Lush Science Prize

2020 ◽  
Vol 48 (1_suppl) ◽  
pp. 18S-25S
Author(s):  
Jenny McCann ◽  
Terry McCann
Keyword(s):  
Public Awareness ◽  
Relevant Literature ◽  
Toxicity Testing ◽  
In Vitro Assays ◽  
Adverse Outcome Pathway ◽  
Annual Conference ◽  
Animal Testing ◽  
Safety Testing ◽  
Animal Replacement

The Lush Prize supports animal-free testing by awarding money prizes of up to £350,000 per year to the most effective projects and individuals who have been working towards the goal of replacing animals in product or ingredient safety testing. Since its inception in 2012, the Lush Prize has distributed almost £2 million. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. In 2015, the judges also awarded a Black Box prize for the development of the skin sensitisation Adverse Outcome Pathway and its associated in vitro assays. The Science Prize is awarded to researchers whose work the judging panel believe to have made the most significant contribution, in the preceding year, to the replacement of animal testing. This 2018 Science Background paper outlines the research projects that were presented to the Prize judges as potential candidates for the 2018 Lush Science Prize award. To obtain an overview of developments in the field of animal replacement in toxicity research, recent work by the relevant scientific institutions and projects in this area, including the OECD, CAAT, ECVAM, UK NC3Rs, US Tox21 Programme, the ToxCast programme and EU-ToxRisk, was reviewed. Recent developments in toxicity testing research were investigated by searching the relevant literature. Abstracts from conferences focusing on animal replacement in toxicity testing that were held in the preceding 12 months, were also analysed, including those from the 2017 10th World Congress on Alternatives and Animals in the Life Sciences and the 2018 Society of Toxicology annual conference.

2017 Lush Science Prize

2018 ◽  
Vol 46 (4) ◽  
pp. 199-207
Author(s):  
Jenny McCann ◽  
Terry McCann
Keyword(s):  
Significant Contribution ◽  
Public Awareness ◽  
Toxicity Testing ◽  
Annual Conference ◽  
Animal Testing ◽  
Safety Testing ◽  
Scientific Institutions ◽  
Recent Developments ◽  
Animal Replacement ◽  
Annual Fund

Now in its sixth year, the Lush Prize supports animal-free testing by awarding money prizes of up to £350,000 to the most effective projects and individuals who have been working towards the goal of replacing animals in product or ingredient safety testing. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. In the event of a major breakthrough leading to the replacement of animal tests in the area of 21st Century Toxicology, a Black Box Prize (equivalent to the entire annual fund) is awarded. The Science Prize is awarded to the researchers whose work the judging panel believe has made the most significant contribution to the replacement of animal testing in the preceding year. This Background Paper outlines the research projects that were shortlisted and presented to the judging panel as potential candidates for the 2017 Lush Science Prize. This process involved reviewing recent work of the relevant scientific institutions and projects in this area, such as the OECD, Human Toxome Project, UK NC3Rs, US Tox21 programme, ToxCast programme and the Human Toxicology Project Consortium. Recent developments in toxicity testing research were also identified by searching for relevant published papers in the literature, and analysing abstracts from conferences focusing on animal replacement in toxicity testing that had been held in the preceding 12 months — for example, the 2016 EUSAAT-Linz conference and the 2017 Society of Toxicology annual conference.

Characterization of Serratia species and qualitative detection of Serratia marcescens in raw and pasteurized milk by an analytical method based on polymerase chain reaction

2021 ◽  
Vol 67 (2) ◽  
pp. 3453-3464
Author(s):  
Evelin Korcz ◽  
László Varga ◽  
Zoltán Kerényi
Keyword(s):  
Serratia Marcescens ◽  
Bacterial Species ◽  
Relevant Literature ◽  
Inhibitory Effect ◽  
Test Methods ◽  
In Vitro Assays ◽  
Pasteurized Milk ◽  
Milk Samples ◽  
Microbiological Methods

Serratia species are opportunistic pathogenic microorganisms primarily known as nosocomial infectious agents, which can also cause food quality problems. The appearance of the extracellular pigment-producing Serratia marcescens in cow’s milk causes its red discoloration, posing a challenge to the dairy industry and food certification laboratories. The detection of the bacterium by conventional procedures based on microbiological methods is time-consuming and labor-intensive, and in many cases does not lead to satisfactory results due to the competitive inhibitory effect of the accompanying microflora. Following the analysis of the relevant literature, the published endpoint PCR methods and the primers used for the detection of S. marcescens were evaluated in in silico and in vitro assays, and then the procedure was tested on farm milk samples. Using the method, a total of 60 raw and pasteurized milk samples were analyzed, more than half of which (i.e., 32) were identified as S. marcescens positive. The significance of our work is mainly represented by the application of the published test methods in food industry practice. Our results highlight to the importance of detecting this bacterial species.

Research on the development of alternatives to animal testing for pharmaceutical products and international standardisation

Impact ◽  
2021 ◽  
Vol 2021 (8) ◽  
pp. 44-45
Author(s):  
Hajime Kojima
Keyword(s):  
Research Group ◽  
Pharmaceutical Products ◽  
In Vitro Assays ◽  
Animal Testing ◽  
3 Dimensional ◽  
Alternatives To Animal Testing ◽  
Gene Assay ◽  
Innovative Work ◽  
Regulatory Acceptance

Scientists are working to develop new and innovative alternatives to animal testing that don't rely on the use of animals. Takao Ashikaga, Hajime Kojima and Yoko Hirabayashi are part of JaCVAM which works to promote the use of alternatives to animal testing. The goal is to replace, reduce or refine (3Rs) the use of animal under International harmonization. Hirabayashi is also the representative of a research group that is funded by the AMED and the representative of a research group funded by the MHLW. A challenge the researchers are facing in their quest to ensure the welfare of experimental animals and also ensure the safety of various pharmaceutical and chemicals is the lack of biomarkers to more accurately predict toxicity for regulatory acceptance. This means that without animal testing more costly and complex non-animal methods are required and presents a barrier to the adoption of non-animal methods for international standerisation. As such, there is a need to develop an easy way to obtain a lot of information. Hirabayashi and the team are working on the development of AI that can be used to evaluate the safety of different compounds. The researchers are developing in vitro assays such as ordinary 2-dimensional culture, 3-dimensional culture including organoids or spheroids, reporter gene assay and organ-on-a chip; and in silico assays such as computer toxicology using QSAR and Read Across. The researchers hope that their innovative work will contribute to the 3Rs, benefiting animal welfare for regulatory use.

scholarly journals A Next-Generation Risk Assessment Case Study for Coumarin in Cosmetic Products

2020 ◽  
Vol 176 (1) ◽  
pp. 236-252 ◽  
Author(s):  
Maria T Baltazar ◽  
Sophie Cable ◽  
Paul L Carmichael ◽  
Richard Cubberley ◽  
Tom Cull ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Biological Effects ◽  
In Vitro Assays ◽  
Next Generation ◽  
Animal Testing ◽  
Immunomodulatory Effects ◽  
Margin Of Safety

Abstract Next-Generation Risk Assessment is defined as an exposure-led, hypothesis-driven risk assessment approach that integrates new approach methodologies (NAMs) to assure safety without the use of animal testing. These principles were applied to a hypothetical safety assessment of 0.1% coumarin in face cream and body lotion. For the purpose of evaluating the use of NAMs, existing animal and human data on coumarin were excluded. Internal concentrations (plasma Cmax) were estimated using a physiologically based kinetic model for dermally applied coumarin. Systemic toxicity was assessed using a battery of in vitro NAMs to identify points of departure (PoDs) for a variety of biological effects such as receptor-mediated and immunomodulatory effects (Eurofins SafetyScreen44 and BioMap Diversity 8 Panel, respectively), and general bioactivity (ToxCast data, an in vitro cell stress panel and high-throughput transcriptomics). In addition, in silico alerts for genotoxicity were followed up with the ToxTracker tool. The PoDs from the in vitro assays were plotted against the calculated in vivo exposure to calculate a margin of safety with associated uncertainty. The predicted Cmax values for face cream and body lotion were lower than all PoDs with margin of safety higher than 100. Furthermore, coumarin was not genotoxic, did not bind to any of the 44 receptors tested and did not show any immunomodulatory effects at consumer-relevant exposures. In conclusion, this case study demonstrated the value of integrating exposure science, computational modeling and in vitro bioactivity data, to reach a safety decision without animal data.

Integrated Decision-tree Testing Strategies for Environmental Toxicity with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1_suppl) ◽  
pp. 29-42 ◽  
Author(s):  
Christina Grindon ◽  
Robert Combes ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Risk Assessment ◽  
Decision Tree ◽  
Aquatic Toxicity ◽  
Toxicity Testing ◽  
Threshold Concentration ◽  
Alternative Methods ◽  
The European Union ◽  
Animal Testing ◽  
Testing Strategies

Liverpool John Moores University and FRAME recently conducted a research project sponsored by Defra on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This paper focuses on the prospects for using alternative methods (both in vitro and in silico) for environmental (aquatic) toxicity testing. The manuscript reviews tests based on fish cells and cell lines, fish embryos, lower organisms, and the many expert systems and QSARs for aquatic toxicity testing. Ways in which reduction and refinement measures can be used are also discussed, including the Upper Threshold Concentration — Step Down (UTC) approach, which has recently been retrospectively validated by ECVAM and subsequently endorsed by the ECVAM Scientific Advisory Committee (ESAC). It is hoped that the application of this approach could reduce the number of fish used in acute toxicity studies by around 65–70%. Decision-tree style integrated testing strategies are also proposed for acute aquatic toxicity and chronic toxicity (including bioaccumulation), followed by a number of recommendations for the future facilitation of aquatic toxicity testing with respect to environmental risk assessment.

scholarly journals Commentary on ‘‘Toxicity Testing in the 21st Century: A vision and a Strategy’’

2010 ◽  
Vol 29 (1) ◽  
pp. 11-14 ◽  
Author(s):  
Robert F Phalen
Keyword(s):  
21St Century ◽  
Toxicity Testing ◽  
In Vitro Testing ◽  
Chemical Toxicity ◽  
Animal Testing ◽  
In Vitro Techniques ◽  
Human Monitoring ◽  
Animal Tests ◽  
In Silico Methods

Toxicity Testing in the 21st Century: A Vision and a Strategy (NRC, 2007) presents a bold plan for chemical toxicity testing that replaces whole-animal tests with cell-culture, genetic, other in-vitro techniques, computational methods, and human monitoring. Although the proposed vision is eloquently described, and recent advances in in-vitro and in-silico methods are impressive, it is difficult believe that replacing in-vitro testing is either practical or wise. It is not clear that the toxicity-related events that occur in whole animals can be adequately replicated using the proposed methods. Protecting public health is a serious endeavor that should not be limited by denying animal testing. Toxicologists and regulators are encouraged to read the report, carefully consider its implications, and share their thoughts. The vision is for too important to ignore.

scholarly journals Kidney-based in vitro models for drug-induced toxicity testing

2019 ◽  
Vol 93 (12) ◽  
pp. 3397-3418 ◽  
Author(s):  
João Faria ◽  
Sabbir Ahmed ◽  
Karin G. F. Gerritsen ◽  
Silvia M. Mihaila ◽  
Rosalinde Masereeuw
Keyword(s):  
Adverse Effects ◽  
Drug Disposition ◽  
Drug Effects ◽  
Toxicity Testing ◽  
Cell Types ◽  
In Vitro Assays ◽  
Vascular Effects ◽  
Drug Induced

Abstract The kidney is frequently involved in adverse effects caused by exposure to foreign compounds, including drugs. An early prediction of those effects is crucial for allowing novel, safe drugs entering the market. Yet, in current pharmacotherapy, drug-induced nephrotoxicity accounts for up to 25% of the reported serious adverse effects, of which one-third is attributed to antimicrobials use. Adverse drug effects can be due to direct toxicity, for instance as a result of kidney-specific determinants, or indirectly by, e.g., vascular effects or crystals deposition. Currently used in vitro assays do not adequately predict in vivo observed effects, predominantly due to an inadequate preservation of the organs’ microenvironment in the models applied. The kidney is highly complex, composed of a filter unit and a tubular segment, together containing over 20 different cell types. The tubular epithelium is highly polarized, and the maintenance of this polarity is critical for optimal functioning and response to environmental signals. Cell polarity is dependent on communication between cells, which includes paracrine and autocrine signals, as well as biomechanic and chemotactic processes. These processes all influence kidney cell proliferation, migration, and differentiation. For drug disposition studies, this microenvironment is essential for prediction of toxic responses. This review provides an overview of drug-induced injuries to the kidney, details on relevant and translational biomarkers, and advances in 3D cultures of human renal cells, including organoids and kidney-on-a-chip platforms.

scholarly journals Targeted Pathway-based In Vivo Testing Using Thyroperoxidase Inhibition to Evaluate Plasma Thyroxine as a Surrogate Metric of Metamorphic Success in Model Amphibian Xenopus laevis

2020 ◽  
Vol 175 (2) ◽  
pp. 236-250 ◽  
Author(s):  
Jonathan T Haselman ◽  
Jennifer H Olker ◽  
Patricia A Kosian ◽  
Joseph J Korte ◽  
Joseph A Swintek ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
In Vitro Assays ◽  
Adverse Outcome Pathway ◽  
Sodium Iodide Symporter ◽  
Chemical Safety ◽  
Compensatory Response ◽  
Amphibian Metamorphosis ◽  
In Vivo Testing

Abstract Chemical safety evaluation is in the midst of a transition from traditional whole-animal toxicity testing to molecular pathway-based in vitro assays and in silico modeling. However, to facilitate the shift in reliance on apical effects for risk assessment to predictive surrogate metrics having characterized linkages to chemical mechanisms of action, targeted in vivo testing is necessary to establish these predictive relationships. In this study, we demonstrate a means to predict thyroid-related metamorphic success in the model amphibian Xenopus laevis using relevant biochemical measurements during early prometamorphosis. The adverse outcome pathway for thyroperoxidase inhibition leading to altered amphibian metamorphosis was used to inform a pathway-based in vivo study design that generated response-response relationships. These causal relationships were used to develop Bayesian probabilistic network models that mathematically determine conditional dependencies between biochemical nodes and support the predictive capability of the biochemical profiles. Plasma thyroxine concentrations were the most predictive of metamorphic success with improved predictivity when thyroid gland sodium-iodide symporter gene expression levels (a compensatory response) were used in conjunction with plasma thyroxine as an additional regressor. Although thyroid-mediated amphibian metamorphosis has been studied for decades, this is the first time a predictive relationship has been characterized between plasma thyroxine and metamorphic success. Linking these types of biochemical surrogate metrics to apical outcomes is vital to facilitate the transition to the new paradigm of chemical safety assessments.

scholarly journals The Twin Children of Auschwitz–Birkenau: Conference on Nazi Medicine/Research: Genes and DZ Twinning; IVF Versus Spontaneous Twinning; Gender Identity Disorder; Royal Protector: Danish and Australian Twin Registries/Human Interest: MZ Twin Co-Principals; Twin Loss at Sandy Hook; Twin Documentaries; New Twin and Twin-Like Reunions; Prominent Twins’ Passing

2013 ◽  
Vol 16 (3) ◽  
pp. 751-757 ◽  
Author(s):  
Nancy L. Segal
Keyword(s):  
Gender Identity ◽  
Gender Identity Disorder ◽  
Relevant Literature ◽  
Annual Conference ◽  
Vitro Fertilization ◽  
Human Interest ◽  
Medicine Research ◽  
Twin Children ◽  
Sandy Hook

The twin children who survived the Holocaust and the horrific medical experiments conducted by Nazi doctors are sometimes overlooked in the relevant literature. This topic and more were discussed as part of an annual conference hosted by students from Yeshiva University's Medical Ethics Society in October 2012. A selective summary of this meeting is followed by summaries of recent twin studies concerning genetic influences on twinning, in vitro fertilization versus spontaneous twin pregnancies, gender identity disorder, and royal support for twin registries. Several human interest stories are also worth noting. They include identical twin school principals, twin loss at Sandy Hook Elementary School, timely twin documentaries, new twin and twin-like reunions, and the passing of two prominent twins.

scholarly journals SCREENED: A Multistage Model of Thyroid Gland Function for Screening Endocrine-Disrupting Chemicals in a Biologically Sex-Specific Manner

2020 ◽  
Vol 21 (10) ◽  
pp. 3648
Author(s):  
Lorenzo Moroni ◽  
Fulvio Barbaro ◽  
Florian Caiment ◽  
Orla Coleman ◽  
Sabine Costagliola ◽  
...  
Keyword(s):  
Stem Cell ◽  
Thyroid Gland ◽  
Thyroid Function ◽  
In Vitro Assays ◽  
Human Thyroid ◽  
Adverse Outcome Pathway ◽  
Thyroid Cells ◽  
Cellular Assays ◽  
Specific Manner

Endocrine disruptors (EDs) are chemicals that contribute to health problems by interfering with the physiological production and target effects of hormones, with proven impacts on a number of endocrine systems including the thyroid gland. Exposure to EDs has also been associated with impairment of the reproductive system and incidence in occurrence of obesity, type 2 diabetes, and cardiovascular diseases during ageing. SCREENED aims at developing in vitro assays based on rodent and human thyroid cells organized in three different three-dimensional (3D) constructs. Due to different levels of anatomical complexity, each of these constructs has the potential to increasingly mimic the structure and function of the native thyroid gland, ultimately achieving relevant features of its 3D organization including: (1) a 3D organoid based on stem cell-derived thyrocytes, (2) a 3D organoid based on a decellularized thyroid lobe stromal matrix repopulated with stem cell-derived thyrocytes, and (3) a bioprinted organoid based on stem cell-derived thyrocytes able to mimic the spatial and geometrical features of a native thyroid gland. These 3D constructs will be hosted in a modular microbioreactor equipped with innovative sensing technology and enabling precise control of cell culture conditions. New superparamagnetic biocompatible and biomimetic particles will be used to produce “magnetic cells” to support precise spatiotemporal homing of the cells in the 3D decellularized and bioprinted constructs. Finally, these 3D constructs will be used to screen the effect of EDs on the thyroid function in a unique biological sex-specific manner. Their performance will be assessed individually, in comparison with each other, and against in vivo studies. The resulting 3D assays are expected to yield responses to low doses of different EDs, with sensitivity and specificity higher than that of classical 2D in vitro assays and animal models. Supporting the “Adverse Outcome Pathway” concept, proteogenomic analysis and biological computational modelling of the underlying mode of action of the tested EDs will be pursued to gain a mechanistic understanding of the chain of events from exposure to adverse toxic effects on thyroid function. For future uptake, SCREENED will engage discussion with relevant stakeholder groups, including regulatory bodies and industry, to ensure that the assays will fit with purposes of ED safety assessment. In this project review, we will briefly discuss the current state of the art in cellular assays of EDs and how our project aims at further advancing the field of cellular assays for EDs interfering with the thyroid gland.

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