Utilising in silico, in vitro and ‘omics New Approach Methodologies (NAMs)

Descriptions

A supplier needs to carry out a range of project delivery options, to deliver against stages 1, 2 and 3 as described below:

Stage 1:
This case study is to support the UK FSA’s policy need to determine which TAs are the most potent (neuro)toxicants so as to prioritise specific substances and inform decisions on the UK’s monitoring of these alkaloids in foods. An integral part of this aim is to confirm that neurotoxicity is the primary mode of action of these alkaloids. This aim will be achieved using a tiered-testing strategy of in silico, in vitro and ‘omics NAMs. This will then be extended to other plant alkaloids such as glycoalkaloids and pyridazine alkaloids.

Stage 2:
To derive a HBGV for human exposure for the top priority, i.e. most potent substance within the class of TAs. This will utilise physiologically-based kinetic (PBK) modelling and quantitative in vitro to in vivo extrapolation (QIVIVE). This will then be extended to other plant alkaloids such as glycoalkaloids and pyridazine alkaloids.

Stage 3:
From a methodological perspective, a broader third objective of the case study is to evaluate and attempt to build confidence within the FSA in the application of a series of relevant NAMs that have been integrated in a manner to address policy needs. These NAMs are tiered and incorporate existing human in vivo data as well as new testing on human in vitro cell lines, to maximise the relevance and accuracy to human food safety.