AOP Report: Thyroperoxidase Inhibition Leading to Altered Visual Function in Fish Via Altered Retinal Layer Structure

Area of Science:

• Endocrinology and toxicology
• Environmental science
• Developmental biology

Background:

• Thyroid hormones (THs) regulate critical physiological and developmental processes, including vertebrate eye development.
• Thyroid hormone system-disrupting chemicals (THSDCs) pose risks to wildlife survival by impairing visual system function.
• The specific sequence of events from TH system disruption (THSD) to altered fish eye development requires further elucidation.

Approach:

• Developed an adverse outcome pathway (AOP) based on an extensive literature review (approx. 120 studies up to 2021).
• Focused on studies investigating THSD impacts on fish eye development.
• Linked inhibition of thyroperoxidase (TPO), a key enzyme in TH synthesis, to retinal structure and visual function effects in fish (AOP-Wiki, AOP 363).

Key Points:

• Weight-of-evidence evaluation indicates moderate confidence in the link between reduced TH levels and altered retinal structure.
• Mechanisms underlying these effects require further investigation.
• The AOP, while based on fish, is plausibly applicable to other vertebrate classes.

Conclusions:

• Established an AOP (AOP 363) detailing the effects of TPO inhibition on fish eye development.
• Connected this AOP to existing pathways concerning TPO and deiodinase inhibition, forming an AOP network for THSD in fish.
• This network addresses the need for thyroid-related endpoints in fish test guidelines for THSDC evaluation.