Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test

Area of Science:

• Environmental Toxicology
• Developmental Biology
• Alternative Testing Strategies

Background:

• Thyroid-active compounds pose risks to development.
• Existing zebrafish scoring systems have limitations in detecting these effects.
• Alternative methods are needed to reduce animal testing.

Purpose of the Study:

• To assess zebrafish developmental scoring systems for detecting thyroid-active compound toxicity.
• To evaluate the applicability of zebrafish as an alternative testing model.
• To develop an enhanced scoring system for developmental toxicity.

Main Methods:

• Zebrafish embryos were exposed to model thyroid-active compounds (T3, PTU, MMI, NaClO4, AMI).
• Exposure time windows included 48-120, 0-72, and 0-120 hours post fertilization (hpf).
• A General Developmental Score (GDS) was developed, extending the existing General Morphology Score (GMS) to 120 hpf and incorporating new parameters.

Main Results:

• All tested compounds induced developmental changes, with triiodothyronine (T3) being the most potent.
• Affected parameters included iridophores, swimming behavior, swim bladder inflation, and yolk sac resorption, evident by 120 hpf.
• The 0-120 hpf exposure window provided comprehensive data, with no added benefit from the 48-120 hpf window.

Conclusions:

• The zebrafish General Developmental Score (GDS) effectively detects developmental toxicity induced by thyroid toxicants.
• The GDS is a cumulative and sensitive scoring system applicable beyond 72 hpf.
• Zebrafish-based GDS offers a viable integrated testing strategy to reduce, refine, and replace animal testing for developmental toxicants.