The REACH Regulation 1907/2006/EC aims to improve knowledge of the potential risks to humans and the environment of the large number of chemicals produced and used in the EU. The testing requirements are likely to trigger numerous toxicological studies, potentially involving millions of experimental animals, despite the professed goal of REACH to reduce vertebrate testing. It may be necessary therefore to shift emphasis away from animal studies towards more pragmatic strategies, reserving animal tests for the substances of greatest concern. One approach is to waive certain tests based on levels of exposure to the substance. This review explores application of 'Exposure-Based Waiving' (EBW) of toxicity studies, with a particular focus on inhalation where possible, considering the potential qualitative and quantitative supporting arguments that might be made, including the use of thresholds of toxicological concern. Incorporating EBW into intelligent testing strategies for substance registration could advance the goals of REACH and the 3Rs (reduction, replacement and refinement of animals in research) by reducing the usage of animals in toxicity tests, whilst maintaining appropriate protection of human health and the environment. However greater regulatory evaluation, acceptance and guidance are required for EBW to achieve its full impact.
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http://dx.doi.org/10.1016/j.fct.2011.03.050 | DOI Listing |
Alzheimers Dement
December 2024
Institut de recherches cliniques de Montréal (IRCM), Montréal, QC, Canada.
Background: Soluble Aβ oligomers (AβOs) induce synapse dysfunction, leading to cognitive impairment and memory deficits in Alzheimer's disease (AD). Our laboratory and several research groups characterized neurexin family members' physiological roles, pivotal synaptic adhesion molecules for development, plasticity, and maintenance. Beyond their normal functions, we found neurexins binding to AβOs causes AβO-induced neurexin dysregulation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Case Western Reserve Universit, CLEVELAND, OH, USA.
Background: Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer's disease (AD). Mitochondrial proteostasis regulated by chaperones and proteases in each compartment of mitochondria is critical for mitochondrial function, and it is suspected that mitochondrial proteostasis deficits may be involved in mitochondrial dysfunction in AD.
Method: An unbiased screening of intraneuronal Aβ42 protein-interactome was perfumed in AD cell culture.
Alzheimers Dement
December 2024
Edith Cowan University, Perth, Western Australia, Australia.
Background: Our research group is currently exploring the potential of Butyric acid (NaB), a Short Chain Fatty Acid (SCFA), as a novel therapeutic agent for Alzheimer's disease (AD).
Methods: In our investigation using the 5xFAD mouse model of AD, we observed that NaB had significant effects on Aβ levels, as well as on associative learning and cognitive functioning. Notably, we recorded a 40% reduction in brain Aβ and a 25% increase in fear response during both cued and contextual testing.
J Appl Lab Med
January 2025
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Background: The US healthcare system is complex and includes a number of entities and systems that provide services to patients and to pay for them. While improving health and well-being are accepted goals of healthcare, the 3 stakeholder groups relevant to healthcare-patients, providers, and payers-often have different perspectives on how care should be utilized, performed, and paid for. These differing perspectives are discussed as they relate to clinical laboratory testing.
View Article and Find Full Text PDFNat Commun
January 2025
Grid Therapeutics, Durham, NC, USA.
GT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a "3 + 3" schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!