“…The qualitative and quantitative evaluation demonstrated that several of the in vitro and in silico approaches used have “equivalent or superior performance to existing animal tests and were successful in predicting human skin sensitization outcomes for both hazard and potency” ( Kleinstreuer et al, 2018 ). Thanks to the high level of confidence in both the AOP and the methods, these alternative approaches may be integrated into regulatory processes ( EPA, 2018 ) and in the next-generation skin allergy risk assessment ( Gilmour et al, 2022 ). Moreover, recently, several AOPs for thyroid disruption have been developed and can be assembled into an AOP network whereby decreased thyroid hormone (TH) levels constitutes a KE shared with diverse MIEs and AOs, including neurodevelopmental defects ( Klose et al, 2021 ; Knapen et al, 2020 ; Noyes et al, 2019 ).…”
Section: Existing Case Studies Of Aop Application In Chemical Hazard ...mentioning
“…The qualitative and quantitative evaluation demonstrated that several of the in vitro and in silico approaches used have “equivalent or superior performance to existing animal tests and were successful in predicting human skin sensitization outcomes for both hazard and potency” ( Kleinstreuer et al, 2018 ). Thanks to the high level of confidence in both the AOP and the methods, these alternative approaches may be integrated into regulatory processes ( EPA, 2018 ) and in the next-generation skin allergy risk assessment ( Gilmour et al, 2022 ). Moreover, recently, several AOPs for thyroid disruption have been developed and can be assembled into an AOP network whereby decreased thyroid hormone (TH) levels constitutes a KE shared with diverse MIEs and AOs, including neurodevelopmental defects ( Klose et al, 2021 ; Knapen et al, 2020 ; Noyes et al, 2019 ).…”
Section: Existing Case Studies Of Aop Application In Chemical Hazard ...mentioning
“…In the LLNA assay, the test material is topically applied to the animal’s skin; this test is applicable to nanomaterials formulated as creams or lotions. In vitro assays myeloid U937 skin sensitization test (U-SENS also known as MUSST) and human cell line activation test (h-CLAT) were developed as surrogates for LLNA/LLNP and showed consistent performance in interlaboratory studies ( 241 – 243 ). However, when applied to nanomaterials testing, the results of these in vitro assays do not always correlate with that of the in vivo LLNP studies.…”
Section: Available Methods and Models To Study Immunotoxicitymentioning
Nanotechnology carriers have become common in pharmaceutical products because of their benefits to drug delivery, including reduced toxicities and improved efficacy of active pharmaceutical ingredients due to targeted delivery, prolonged circulation time, and controlled payload release. While available examples of reduced drug toxicity through formulation using a nanocarrier are encouraging, current data also demonstrate that nanoparticles may change a drug’s biodistribution and alter its toxicity profile. Moreover, individual components of nanoparticles and excipients commonly used in formulations are often not immunologically inert and contribute to the overall immune responses to nanotechnology-formulated products. Said immune responses may be beneficial or adverse depending on the indication, dose, dose regimen, and route of administration. Therefore, comprehensive toxicology studies are of paramount importance even when previously known drugs, components, and excipients are used in nanoformulations. Recent data also suggest that, despite decades of research directed at hiding nanocarriers from the immune recognition, the immune system’s inherent property of clearing particulate materials can be leveraged to improve the therapeutic efficacy of drugs formulated using nanoparticles. Herein, I review current knowledge about nanoparticles’ interaction with the immune system and how these interactions contribute to nanotechnology-formulated drug products’ safety and efficacy through the lens of over a decade of nanoparticle characterization at the Nanotechnology Characterization Laboratory.
“…Having published our skin allergy risk assessment (SARA) model in 2019, 19 we have subsequently published and widely presented case studies on the application of the NGRA framework for skin allergy decision-making. 20 Currently, Unilever is collaborating with the US government NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) to adapt the SARA model for regulatory use, and the new SARA-ICE (Integrated Chemical Environment) Defined Approach is being evaluated at OECD level.Figure 3.Unilever NGRA framework for decision-making on consumer safety: Skin allergy. NGRA workflow for a skin allergy risk assessment case study (0.1% coumarin in face cream, 1% coumarin in deodorant; Reynolds et al 18 ).…”
Section: Safety Science: Next Generation Risk Assessment (Ngra) Throu...mentioning
The decisions we make on chemical safety, for consumers, workers and the environment, must be based on the best scientific data and knowledge available. Rapid advances in biology, in cell-based technologies and assays, and in analytical and computational approaches, have led to new types of highly relevant scientific data being generated. Such data enable us to improve the safety decisions we make, whilst also enabling us to avoid animal testing. Stimulated by the UK and EU bans on animal testing for cosmetics, Next Generation Risk Assessment (NGRA) approaches, which integrate various types of non-animal scientific data, have been established for assessing the safety of chemical ingredients used in cosmetics and other consumer products. In stark contrast, the chemicals regulations in Europe and other parts of the world have not kept pace with modern safety science and regulators are now mandating even more animal testing. Urgently closing this science–regulation gap is essential to upholding the EU’s legislative requirement that any animal testing is a last resort. The ongoing revisions of UK and EU chemicals strategy and regulations provide an opportunity to fundamentally change the design and assessment paradigm needed to underpin safe and more sustainable innovation, through applying the best science and tools available rather than continuing to be anchored in animal tests dating back many decades. A range of initiatives have recently been launched in response to this urgent need, in the UK as well as in the EU.
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