Virus-like particles (VLPs) induce strong humoral and cellular responses and have formed the basis of some currently licensed vaccines. Here, we present the method used for the production of R21, a VLP-based anti-sporozoite malaria vaccine, under current Clinical Good Manufacturing Practice regulations (cGMP). Previous preclinical studies in BALB/c mice showed that R21 produced almost complete protection against sporozoite challenge with transgenic Plasmodium berghei parasites.
View Article and Find Full Text PDFWater is used in petroleum oil refineries in significant volumes for cooling, steam generation and processing of raw materials. Effective water management is required at refineries to ensure their efficient and responsible operation with respect to the water environment. However, ascertaining the potential environmental risks associated with discharge of refinery effluents to receiving waters is challenging because of their compositional complexity.
View Article and Find Full Text PDFIntegr Environ Assess Manag
November 2021
Significant progress has been made in the scientific understanding of factors that influence the outcome of biodegradation tests used to assess the persistence (P) of chemicals. This needs to be evaluated to assess whether recently acquired knowledge could enhance existing regulations and environmental risk assessments. Biodegradation tests have limitations, which are accentuated for "difficult-to-test" substances, and failure to recognize these can potentially lead to inappropriate conclusions regarding a chemical's environmental persistence.
View Article and Find Full Text PDFRefinery effluents represent an emission source of hydrocarbons (HCs) and other constituents to the environment. Thus, characterisation of effluent quality in terms of concentrations of key parameters relative to permitted standards is important and for total petroleum hydrocarbons (TPH), the specific composition of the HC mixture can affect its toxicity to aquatic organisms. Therefore, this study was designed to analyse TPH, benzene, toluene, ethyl benzene, xylenes (BTEX), polycyclic aromatic hydrocarbons (PAHs), (bio) chemical oxygen demand, total nitrogen, total suspended solids and selected metals before, and after, treatment steps to demonstrate removal efficiencies across 13 refineries with variable wastewater treatment systems.
View Article and Find Full Text PDFAssessment and management of effluent discharges are key to avoiding environmental deterioration. Often compliance with discharge regulations and permits is based on a limited set of chemical parameters, while information on whole effluent hazardous properties (toxicity, bioaccumulation potential, persistence) and environmental risks is lacking. The need to collect those data and to become more effective in quickly identifying high-risk activities, without extensive laboratory testing, has led to the development of screening tools to complement information on chemical composition.
View Article and Find Full Text PDFThe assessment of substances of Unknown or Variable composition, Complex reaction products or Biological materials (UVCBs) presents significant challenges when determining biodegradation potential and environmental persistence for regulatory purposes. An example of UVCBs is the gas-to-liquid (GTL) products, which are synthetic hydrocarbons produced from natural gas using a catalytic process known as the Fischer-Tropsch process. These synthetic hydrocarbons are fractionated into a wide array of products equivalent in function to their petroleum-derived analogues.
View Article and Find Full Text PDFCurrent biodegradation screening tests are not specifically designed for persistence assessment of chemicals, often show high inter- and intra-test variability, and often give false negative biodegradation results. Based on previous studies and recommendations, an international ring test involving 13 laboratories validated a new test method for marine biodegradation with a focus on improving the reliability of screening to determine the environmental degradation potential of chemicals. The new method incorporated increased bacterial cell concentrations to better represent the microbial diversity; a chemical is likely to be exposed in the sampled environments and ran beyond 60 days, which is the half-life threshold for chemical persistence in the marine environment.
View Article and Find Full Text PDFGrowth and extensive urbanisation of the human population has been accompanied by increased manufacture and use of chemical compounds. To classify the fate and behaviour of these compounds in the environment, a series of international standardised biodegradation screening tests (BSTs) were developed over 30 years ago. In recent years, regulatory emphasis (e.
View Article and Find Full Text PDFHazard assessment of refinery effluents is challenging because of their compositional complexity. Therefore, a weight-of-evidence approach using a combination of tools is often required. Previous research has focused on several predictive tools for sophisticated chemical analyses: biomimetic extraction to quantify the potentially bioaccumulative substances, 2-dimensional gas chromatography, modeling approaches to link oil composition to toxicity (PETROTOX), and whole-effluent toxicity assessments using bioassays.
View Article and Find Full Text PDFObjective: V565 is a novel oral anti-tumor necrosis factor (TNF)-α domain antibody being developed for topical treatment of inflammatory bowel disease (IBD) patients. Protein engineering rendered the molecule resistant to intestinal proteases. Here we investigate the formulation of V565 required to provide gastro-protection and enable optimal delivery to the lower intestinal tract in monkeys.
View Article and Find Full Text PDFSince the 1940s, effluent toxicity testing has been used to assess potential ecological impacts of effluents and help determine necessary treatment options for environmental protection prior to release. Strategic combinations of toxicity tests, analytical tools, and biological monitoring have been developed. Because the number of vertebrates utilized in effluent testing is thought to be much greater than that used for individual chemical testing, there is a new need to develop strategies to reduce the numbers of vertebrates (i.
View Article and Find Full Text PDFreticulocyte-binding protein homolog 5 (PfRH5) is a leading asexual blood-stage vaccine candidate for malaria. In preparation for clinical trials, a full-length PfRH5 protein vaccine called "RH5.1" was produced as a soluble product under cGMP using the ExpreS platform (based on a S2 stable cell line system).
View Article and Find Full Text PDFThe advent of adverse outcome pathways (AOPs) has provided a new lexicon for description of mechanistic toxicology, and a renewed enthusiasm for exploring modes of action resulting in adverse health and environmental effects. In addition, AOPs have been used successfully as a framework for the design and development of non-animal approaches to toxicity testing. Although the value of AOPs is widely recognised, there remain challenges and opportunities associated with their use in practise.
View Article and Find Full Text PDFGas-to-liquid (GTL) products are synthetic hydrocarbons produced from natural gas using a catalytic process known as the Fischer-Tropsch process. This process yields a synthetic crude oil that consists of saturated hydrocarbons which can subsequently be refined to a range of products analogous to those obtained from petroleum refining. However, in contrast to their petroleum-derived analogs, GTL products are essentially free of unsaturated or aromatic compounds and do not contain any sulfur-, oxygen-, or nitrogen-containing compounds.
View Article and Find Full Text PDFManometric test systems, adapted from those used to measure biochemical oxygen demand (BOD), and the OxiTop test system in particular, are being increasingly used to determine the biodegradability of chemicals in accordance to OECD 301F guidelines. In this study, the suitability of the OxiTop test system for determining the biodegradability of volatile hydrophobic substances has been explored. Experiments in biotic and abiotic systems were conducted with readily biodegradable complex aliphatic hydrocarbons covering a range of volatilities.
View Article and Find Full Text PDFUrban regions of the world are expanding rapidly, placing additional stress on water resources. Urban water bodies serve many purposes, from washing and sources of drinking water to transport and conduits for storm drainage and effluent discharge. These water bodies receive chemical emissions arising from either single or multiple point sources, diffuse sources which can be continuous, intermittent, or seasonal.
View Article and Find Full Text PDFTo enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement). In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART).
View Article and Find Full Text PDFClearly defined protection goals specifying what to protect, where and when, are required for designing scientifically sound risk assessments and effective risk management of chemicals. Environmental protection goals specified in EU legislation are defined in general terms, resulting in uncertainty in how to achieve them. In 2010, the European Food Safety Authority (EFSA) published a framework to identify more specific protection goals based on ecosystem services potentially affected by plant protection products.
View Article and Find Full Text PDFGas-to-liquid (GTL) products are synthetic hydrocarbons produced from natural gas using a Fischer-Tropsch process. This process yields a synthetic crude oil that consists of saturated hydrocarbons, primarily linear alkanes, with increasing amounts of branched (methyl-groups) alkanes as the chains get longer. In addition, small amounts of cycloalkanes (branched cyclopentanes and cyclohexanes) may be formed as the polymerization reaction prolongs.
View Article and Find Full Text PDFThis critical review examines the definition and implementation of environmental protection goals for chemicals in current European Union (EU) legislation, guidelines, and international agreements to which EU countries are party. The European chemical industry is highly regulated, and prospective environmental risk assessments (ERAs) are tailored for different classes of chemical, according to their specific hazards, uses, and environmental exposure profiles. However, environmental protection goals are often highly generic, requiring the prevention of "unacceptable" or "adverse" impacts on "biodiversity" and "ecosystems" or the "environment as a whole.
View Article and Find Full Text PDFIntegr Environ Assess Manag
July 2016
The ecotoxicity testing of chemicals for prospective environmental safety assessment is an area in which a high number of vertebrates are used across a variety of industry sectors. Refining, reducing, and replacing the use of animals such as fish, birds, and amphibians for this purpose addresses the ethical concerns and the increasing legislative requirements to consider alternative test methods. Members of the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Ecotoxicology Working Group, consisting of representatives from academia, government organizations, and industry, have worked together over the past 6 y to provide evidence bases to support and advance the application of the 3Rs in regulatory ecotoxicity testing.
View Article and Find Full Text PDFThe trend in discharges of petroleum-related substances from refineries in Europe shows a consistent picture of declining emissions, since first measured in 1969. This decline coincides with enhanced internal capture or recycling procedures and increasing use of physical and biological treatments. At the same time, and partly in response to legislative drivers, there has been an increase in the use of chronic (long-term) toxicity tests and alternative methods for assessing the quality of effluent discharges.
View Article and Find Full Text PDFTests with vertebrates are an integral part of environmental hazard identification and risk assessment of chemicals, plant protection products, pharmaceuticals, biocides, feed additives and effluents. These tests raise ethical and economic concerns and are considered as inappropriate for assessing all of the substances and effluents that require regulatory testing. Hence, there is a strong demand for replacement, reduction and refinement strategies and methods.
View Article and Find Full Text PDFWhole effluent assessments (WEA) are being investigated as potential tools for controlling aqueous industrial discharges and minimizing environmental impact. The present study investigated how toxicity and the presence of potentially bioaccumulative substances altered when refinery effluents were subjected to biodegradation tests. Three petrochemical effluents were assessed, two freshwater and one saline, and subjected to two different types of biodegradation tests, resembling either a ready style (dissolved organic carbon (DOC)-die away) or an inherent style (Zahn-Wellens) test and the toxicity and potential to bioaccumulate parameters were re-analysed during and after biodegradation.
View Article and Find Full Text PDFIntegr Environ Assess Manag
July 2010
Animal alternative tests are gaining serious consideration in an array of environmental sciences, particularly as they relate to sound management of chemicals and wastewater discharges. The ILSI Health and Environmental Sciences Institute and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test in March, 2008. This relatively young discipline is following advances in animal alternatives for human safety sciences, and it is advisable to develop a broad comparison of how animal alternative tests involving fish are viewed in a regulatory context over a wide array of authorities or advising bodies.
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