Endpoint sensitivity in fish endocrine disruption assays: regulatory implications.

Area of Science:

• Environmental Toxicology
• Chemical Risk Assessment
• Endocrinology

Background:

• Endocrine disrupting chemicals (EDCs) require screening for mode of action (MOA) and toxicity.
• Risk assessment typically relies on apical endpoints, not biomarker endpoints indicating MOA.
• The 21-day fish assay (OECD TG229) incorporates both biomarker and apical endpoints.

Purpose of the Study:

• To evaluate the utility of the 21-day fish assay for risk assessment of EDCs.
• To compare endpoint sensitivity and lowest observed effect concentrations (LOECs) between the 21-day fish assay and the fish sexual development test (FSDT).

Main Methods:

• Compiled 142 datasets for the 21-day fish assay and 38 for the FSDT.
• Included 62 chemicals with diverse MOAs.
• Analyzed endpoint sensitivity and LOECs across species like fathead minnow, medaka, and zebrafish.

Main Results:

• Vitellogenin (VTG), fecundity, and gonad histology are the most sensitive endpoints in the 21-day fish assay.
• Secondary sex characteristics (SSC) are less sensitive and may miss some MOAs.
• LOECs from the 21-day fish assay generally align with FSDT, supporting its use in risk assessment.

Conclusions:

• Biomarker (VTG) and apical (fecundity) endpoints from the 21-day fish assay are valuable for EDC risk assessment.
• The 21-day fish assay provides comparable LOECs to the FSDT for most chemicals.
• A weight of evidence approach is crucial for interpreting 21-day fish assay results, considering chemical-specific effects.