Tracing thyroid hormone-disrupting compounds: database compilation and structure-activity evaluation for an...

Area of Science:

• Environmental Chemistry
• Toxicology
• Endocrinology

Background:

• Anthropogenic compounds can disrupt endocrine systems, with thyroid hormone disruption gaining attention.
• Thyroid hormone transport protein (TTR) binding is a key mechanism for disruption.

Purpose of the Study:

• To review and chemically characterize compounds tested for TTR binding.
• To develop a database of TTR binders to aid in identifying thyroid hormone-disrupting compounds (THDCs).

Main Methods:

• Principal component analysis for chemical characterization.
• Compilation of a database of 250 compounds and mixtures tested for TTR binding.
• Application of the database in an effect-directed analysis (EDA) of a sediment sample.

Main Results:

• Identified 144 TTR binders, with 52 being more potent than thyroxine (T4).
• Confirmed triclosan and nonylphenol as contributors to TTR binding in sediment, but accounting for <1% of total potency.
• Highlighted challenges in identifying unknown THDCs and the need for comprehensive databases.

Conclusions:

• Databases with compound-specific toxicological properties are crucial for identifying THDCs.
• EDA combined with such databases can effectively pinpoint causative agents of thyroid hormone disruption.
• Further research is needed to understand the full spectrum of THDCs and their environmental impact.