Nonclinical Immunotoxicity Testing in the Pharmaceutical World: The Past, Present, and Future

Baldrick, Paul

doi:10.1007/s43441-019-00091-5

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…Furthermore, there can even be separate NOAELs: one based on an interpretation that the ADA finding is adverse to the monkey, and another acknowledging that immunogenicity is an expected consequence in nonhuman primates and therefore may be deemed "non-adverse" with respect to assessing risk in humans. 8 Thus, for some companies, immune complex disease is not included within the NOAEL assignment but instead is categorized as adverse in animals specifically, but not relevant for evaluating human outcomes. In such cases, predictions of human risk are built around an integrated safety assessment that is not focused mainly on an NOAEL derived from nonclinical toxicity testing.…”

Section: Setting An Noael-examplesmentioning

confidence: 99%

Toxicology Paradise: Sorting Out Adverse and Non-adverse Findings in Animal Toxicity Studies

Baldrick

Cosenza²,

Alapatt

et al. 2020

Int J Toxicol

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A challenge for all toxicologists is defining what study findings are actually adverse versus non-adverse in animal toxicity studies, and which ones are relevant for generating a no observed adverse effect level (NOAEL) to assess human risk. This article presents views on this challenge presented by toxicologists, toxicologic pathologists, and regulatory reviewers at the 2019 annual meeting of the American College of Toxicology during a workshop entitled “Toxicology Paradise: Sorting Out Adverse and Non-adverse Findings.” The speakers noted that setting a NOAEL is not always straightforward, not only for small molecules but also for biopharmaceuticals, and that a “weight of evidence” approach often is more useful than a rigid threshold-setting algorithm. Regulators from the US Food and Drug Administration and European Union told how assessment of adverse nonclinical findings is undertaken to allow clinical studies to commence and drug marketing approvals to succeed, along with the process that allows successful dialogs with regulators. Nonclinical case studies of findings judged to be adverse versus non-adverse were presented in relation to the many factors that might halt or delay clinical development. The process of defining adverse findings and the NOAEL in final study reports was discussed, as well as who should be involved in the process.

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Section: Setting An Noael-examplesmentioning

confidence: 99%

Toxicology Paradise: Sorting Out Adverse and Non-adverse Findings in Animal Toxicity Studies

Baldrick

Cosenza²,

Alapatt

et al. 2020

Int J Toxicol

Self Cite

View full text Add to dashboard Cite

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Integrated approaches for immunotoxicity risk assessment: challenges and future directions

Chandrasekar,

Panicker,

Dey

et al. 2024

Discov Toxicol

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Unveiling the anticancer potential of the ethanolic extract from Pometia pinnata: Molecular dynamics targeting CHK1 and cytotoxicity study on MCF-7 cells

Wahyuni,

Marianne,

Nugraha

et al. 2024

PHAR

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Cancer remains one of the most lethal diseases globally, with CHK1 being a critical pathway frequently altered in cancer progression. This study evaluated the anticancer and cytotoxic properties of the ethanol extract of Matoa (Pometia pinnata) leaves in silico and in vitro. Maceration was conducted to obtain the ethanol extract with physicochemical, pharmacokinetic, and toxicity predictions conducted using Lipinski’s Rule of Five, pkCSM, and Pro-Tox II. Molecular docking was performed using Autodock Vina and DOCK6.2, followed by molecular dynamic simulations using GROMACS. Cytotoxicity assays on MCF-7 cells were carried out using the MTT methods. The results demonstrated that the extract tested positive for flavonoids, alkaloids, tannins, saponins, glycosides, and steroids. The extract also shows potential inhibitory activity against CHK1, supported by favorable binding affinities and critical amino acid interactions. Additionally, the extract exhibited a moderate cytotoxic effect on cell MCF-7 with an IC50 of 139 µg/mL.

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Nonclinical Immunotoxicity Testing in the Pharmaceutical World: The Past, Present, and Future

Cited by 3 publications

References 46 publications

Toxicology Paradise: Sorting Out Adverse and Non-adverse Findings in Animal Toxicity Studies

Toxicology Paradise: Sorting Out Adverse and Non-adverse Findings in Animal Toxicity Studies

Integrated approaches for immunotoxicity risk assessment: challenges and future directions

Unveiling the anticancer potential of the ethanolic extract from Pometia pinnata: Molecular dynamics targeting CHK1 and cytotoxicity study on MCF-7 cells

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