Adverse Outcome Pathway on inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment

Abstract

This Adverse Outcome Pathway (AOP) on Inhibition of Na+/I-symporter (NIS) leads to learning and memory impairment, has been developed under the auspices of the OECD AOP Development Programme, overseen by the Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST), which is an advisory group under the Working Group of the National Coordinators for the Test Guidelines Programme (WNT). The AOP has been reviewed internally by the EAGMST, externally by experts nominated by the WNT, and has been endorsed by the WNT and the Working Party on Hazard Assessment (WPHA) in May 2019. Through endorsement of this AOP, the WNT and the WPHA express confidence in the scientific review process that the AOP has undergone and accept the recommendation of the EAGMST that the AOP be disseminated publicly. Endorsement does not necessarily indicate that the AOP is now considered a tool for direct regulatory application. The Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology agreed to declassification of this AOP on 26 June 2019. This document is being published under the responsibility of the Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology. The outcome of the internal and external reviews are publicly available respectively in the AOP Wiki and the eAOP Portal of the AOP Knowledge Base at the following links: [internal review] [external review].

Towards a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – part II: how can key events of relevant adverse outcome pathways be addressed in toxicological assessments?

“…However, to date, only AOPs 42 and 54 (presenting direct MoAs) have been endorsed by the OECD (Crofton et al 2019;Rolaki et al 2019), whereas AOP 8, 134, and 152 (with the latter two presenting indirect MoAs) are denoted as "under development" (Table 1). Therefore, the sequence of events described in these AOPs, up to their adverse outcomes, should not be considered conclusive yet.…”

“…AOP 42: Inhibition of thyroid peroxidase (TPO) and subsequent adverse neurodevelopmental outcomes in mammals Supporting evidence is mostly derived from in vitro studies and rodent studies, while indicating that "it is well accepted" that specific key events also occur in humans; the main body of experimental evidence stems from studies with the very potent pharmaceutical TPO inhibitors propylthiouracil and methimazole. Crofton et al (2019) and Rolaki et al (2019). By comparison, AOP 8, AOP 134, and AOP 152 are research drafts, and AOP 8 has the author status "not under active development" indicating that it has been dormant since an early draft stage.…”

New approach methods to improve human health risk assessment of thyroid hormone system disruption–a PARC project

“…A limited number of AOPs have been developed to the level where they have been endorsed by the OECD Working Party on Hazard Assessment and the Working Group of National Coordinators of the Test Guidelines Programme (WPHA/WNT). This includes the AOP initiated by inhibition of thyroperoxidase (TPO) and leading to adverse neurodevelopmental outcomes in mammals ( Crofton et al, 2019 ) and the AOP leading from inhibition of the Na+/I- symporter (NIS) to learning and memory impairment in mammals ( Rolaki et al, 2019 ). Five AOPs linking TPO and deiodinase inhibition to impaired swim bladder inflation in fish have recently been endorsed ( Vergauwen et al, 2022a ; Vergauwen et al, 2022b ; Vergauwen et al, 2022c ; Vergauwen et al, 2022d ; Vergauwen et al, 2022e ).…”