Dataset Information

Developmental neurotoxicity - challenges in the 21st century and in vitro opportunities.

ABSTRACT: In recent years neurodevelopmental problems in children have increased at a rate that suggests lifestyle factors and chemical exposures as likely contributors. When environmental chemicals contribute to neurodevelopmental disorders developmental neurotoxicity (DNT) becomes an enormous concern. But how can it be tackled? Current animal test- based guidelines are prohibitively expensive, at $ 1.4 million per substance, while their predictivity for human health effects may be limited, and mechanistic data that would help species extrapolation are not available. A broader screening for substances of concern requires a reliable testing strategy, applicable to larger numbers of substances, and sufficiently predictive to warrant further testing. This review discusses the evidence for possible contributions of environmental chemicals to DNT, limitations of the current test paradigm, emerging concepts and technologies pertinent to in vitro DNT testing and assay evaluation, as well as the prospect of a paradigm shift based on 21st century technologies.

SUBMITTER: Smirnova L

PROVIDER: S-EPMC4778747 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Developmental neurotoxicity - challenges in the 21st century and in vitro opportunities.

Smirnova Lena L Hogberg Helena T HT Leist Marcel M Hartung Thomas T

ALTEX 20140101 2

In recent years neurodevelopmental problems in children have increased at a rate that suggests lifestyle factors and chemical exposures as likely contributors. When environmental chemicals contribute to neurodevelopmental disorders developmental neurotoxicity (DNT) becomes an enormous concern. But how can it be tackled? Current animal test- based guidelines are prohibitively expensive, at $ 1.4 million per substance, while their predictivity for human health effects may be limited, and mechanist ...[more]

PMID: 24687333

Similar Datasets

Project description:There is no good science in bad models. Cell culture is especially prone to artifacts. A number of novel cell culture technologies have become more broadly available in the 21st century, which allow overcoming limitations of traditional culture and are more physiologically relevant. These include the use of stem-cell derived human cells, cocultures of different cell types, scaffolds and extracellular matrices, perfusion platforms (such as microfluidics), 3D culture, organ-on-chip technologies, tissue architecture, and organ functionality. The physiological relevance of such models is further enhanced by the measurement of biomarkers (e.g., key events of pathways), organ specific functionality, and more comprehensive assessment cell responses by high-content methods. These approaches are still rarely combined to create microphysiological systems. The complexity of the combination of these technologies can generate results closer to the in vivo situation but increases the number of parameters to control, bringing some new challenges. In fact, we do not argue that all cell culture needs to be that sophisticated. The efforts taken are determined by the purpose of our experiments and tests. If only a very specific molecular target to cell response is of interest, a very simple model, which reflects this, might be much more suited to allow standardization and high-throughput. However, the less defined the end point of interest and cellular response are, the better we should approximate organ- or tissue-like culture conditions to make physiological responses more probable. Besides these technologic advances, important progress in the quality assurance and reporting on cell cultures as well as the validation of cellular test systems brings the utility of cell cultures to a new level. The advancement and broader implementation of Good Cell Culture Practice (GCCP) is key here. In toxicology, this is a major prerequisite for meaningful and reliable results, ultimately supporting risk assessment and product development decisions.

Project description:The Commonwealth Scientific and Industrial Research Organisation (CSIRO) cotton breeding program is the sole breeding effort for cotton in Australia, developing high performing cultivars for the local industry which is worth∼AU$3 billion per annum. The program is supported by Cotton Breeding Australia, a Joint Venture between CSIRO and the program's commercial partner, Cotton Seed Distributors Ltd. (CSD). While the Australian industry is the focus, CSIRO cultivars have global impact in North America, South America, and Europe. The program is unique compared with many other public and commercial breeding programs because it focuses on diverse and integrated research with commercial outcomes. It represents the full research pipeline, supporting extensive long-term fundamental molecular research; native and genetically modified (GM) trait development; germplasm enhancement focused on yield and fiber quality improvements; integration of third-party GM traits; all culminating in the release of new commercial cultivars. This review presents evidence of past breeding successes and outlines current breeding efforts, in the areas of yield and fiber quality improvement, as well as the development of germplasm that is resistant to pests, diseases and abiotic stressors. The success of the program is based on the development of superior germplasm largely through field phenotyping, together with strong commercial partnerships with CSD and Bayer CropScience. These relationships assist in having a shared focus and ensuring commercial impact is maintained, while also providing access to markets, traits, and technology. The historical successes, current foci and future requirements of the CSIRO cotton breeding program have been used to develop a framework designed to augment our breeding system for the future. This will focus on utilizing emerging technologies from the genome to phenome, as well as a panomics approach with data management and integration to develop, test and incorporate new technologies into a breeding program. In addition to streamlining the breeding pipeline for increased genetic gain, this technology will increase the speed of trait and marker identification for use in genome editing, genomic selection and molecular assisted breeding, ultimately producing novel germplasm that will meet the coming challenges of the 21st Century.

Project description:Globally, the livelihoods of over a billion people are affected by changes to marine ecosystems, both structurally and systematically. Resources and ecosystem services, provided by the marine environment, contribute nutrition, income, and health benefits for communities. One threat to these securities is ciguatera poisoning; worldwide, the most commonly reported non-bacterial seafood-related illness. Ciguatera is caused by the consumption of (primarily) finfish contaminated with ciguatoxins, potent neurotoxins produced by benthic single-cell microalgae. When consumed, ciguatoxins are biotransformed and can bioaccumulate throughout the food-web via complex pathways. Ciguatera-derived food insecurity is particularly extreme for small island-nations, where fear of intoxication can lead to fishing restrictions by region, species, or size. Exacerbating these complexities are anthropogenic or natural changes occurring in global marine habitats, e.g., climate change, greenhouse-gas induced physical oceanic changes, overfishing, invasive species, and even the international seafood trade. Here we provide an overview of the challenges and opportunities of the 21st century regarding the many facets of ciguatera, including the complex nature of this illness, the biological/environmental factors affecting the causative organisms, their toxins, vectors, detection methods, human-health oriented responses, and ultimately an outlook towards the future. Ciguatera research efforts face many social and environmental challenges this century. However, several future-oriented goals are within reach, including digital solutions for seafood supply chains, identifying novel compounds and methods with the potential for advanced diagnostics, treatments, and prediction capabilities. The advances described herein provide confidence that the tools are now available to answer many of the remaining questions surrounding ciguatera and therefore protection measures can become more accurate and routine.

Dataset Information

Developmental neurotoxicity - challenges in the 21st century and in vitro opportunities.

Publications

Developmental neurotoxicity - challenges in the 21st century and in vitro opportunities.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets