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This necessitates a fundamental shift towards a proactive safe-and-sustainable-by-design (SSbD) framework, where considerations of ecological safety and lifecycle sustainability are not an afterthought, but are integral components of the material innovation process from its inception.185,186 The SSbD framework defined by the European Commissions Joint Research Centre (JRC) 2023 report, which integrates safety assessment into the earliest stages of innovation, is advocated

Development and optimisation of alternative methods and approaches Main gaps identified: high rate of misleading/false genotoxic positives Existing in vitro methods, whilst having a high sensitivity (and thus low false negative rate), have a relatively low specificity and thus high rate of false (misleading) positive results, which typically has led to unnecessary follow-up testing in vivo for the confirmation of these results

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The reasoning of the use of kidney cells in the experiments is generally attributed to the formation of cysteine-conjugates in liver followed by transport to the kidney (Correia et al

At the metabolic input level, the System Xc transporter, composed of solute carrier family 7 member 11 (SLC7A11) and solute carrier family 3 member 2, mediates cystine uptake, providing essential precursors for GSH synthesis (147,153155)