Read-across is a well-established data gap-filling technique applied for regulatory purposes. In US Environmental Protection Agency's New Chemicals Program under TSCA, read-across has been used extensively for decades, however the extent of application and acceptance of read-across among U.S. federal agencies is less clear. In an effort to build read-across capacity, raise awareness of the state of the science, and work towards a harmonization of read-across approaches across U.S. agencies, a new read-across workgroup was established under the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). This is one of several ad hoc groups ICCVAM has convened to implement the ICCVAM Strategic Roadmap. In this article, we outline the charge and scope of the workgroup and summarize the current applications, tools used, and needs of the agencies represented on the workgroup for read-across. Of the agencies surveyed, the Environmental Protection Agency had the greatest experience in using read-across whereas other agencies indicated that they would benefit from gaining a perspective of the landscape of the tools and available guidance. Two practical case studies are also described to illustrate how the read-across approaches applied by two agencies vary on account of decision context.
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http://dx.doi.org/10.1016/j.yrtph.2019.05.011 | DOI Listing |
Part Fibre Toxicol
December 2024
Health Effects Laboratory, Department of Environmental Chemistry and Health Effects, NILU, 2007, Kjeller, Norway.
Background: Hazard and risk assessment of nanomaterials (NMs) face challenges due to, among others, the numerous existing nanoforms, discordant data and conflicting results found in the literature, and specific challenges in the application of strategies such as grouping and read-across, emphasizing the need for New Approach Methodologies (NAMs) to support Next Generation Risk Assessment (NGRA). Here these challenges are addressed in a study that couples physico-chemical characterization with in vitro investigations and in silico similarity analyses for nine nanoforms, having different chemical composition, sizes, aggregation states and shapes. For cytotoxicity assessment, three methods (Alamar Blue, Colony Forming Efficiency, and Electric Cell-Substrate Impedance Sensing) are applied in a cross-validation approach to support NAMs implementation into NGRA.
View Article and Find Full Text PDFChemosphere
December 2024
Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India. Electronic address:
Regulatory authorities frequently need information on a chemical's capacity to produce acute systemic toxicity in humans. Due to concerns about animal welfare, human relevance, and reproducibility, numerous international initiatives have centered on finding a substitute for using animals in acute systemic lethality testing. These substitutes include the more current in-silico and in vitro techniques.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
December 2024
Lhasa Limited, Granary Wharf House, 2 Canal Wharf, Leeds, United Kingdom.
The carcinogenic potency categorisation approach (CPCA) has recently been introduced by health authorities. In this model, structural features from recent literature, industry proposals, and analyses performed by health authorities, provide a rapid assessment of the potential acceptable intake (AI) for a nitrosamine impurity. As with other screening regulatory values (such as the ICH M7 Threshold of Toxicological Concern), the CPCA is conservative and can be considered a de minimis risk management framework.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
December 2024
GSK, Health Hazard Assessment, Environment Health Safety (EHS), Munich, Germany.
Availability of toxicological data for pharmaceutical intermediates (IMs) used in the manufacture of small molecules is often limited. Scarcity of data - in particular, repeat-dose toxicity (RDT) - renders the calculation of health-based exposure limits (HBELs) problematic. Establishment of HBELs, including occupational exposure limits (OELs) and permitted daily exposures (PDEs) facilitating worker and patient safety respectively, is however essential.
View Article and Find Full Text PDFMol Divers
December 2024
Deparment of Microbiology, Assam University, Silchar, 788011, Assam, India.
Leishmaniasis, a neglected tropical disease caused by various Leishmania species, poses a significant global health challenge, especially in resource-limited regions. Visceral Leishmaniasis (VL) stands out among its severe manifestations, and current drug therapies have limitations, necessitating the exploration of new, cost-effective treatments. This study utilized a comprehensive computational workflow, integrating traditional 2D-QSAR, q-RASAR, and molecular docking to identify novel anti-leishmanial compounds, with a focus on Glycyl-tRNA Synthetase (LdGlyRS) as a promising drug target.
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