Experiences with the OECD 308 transformation test: a human pharmaceutical perspective

Area of Science:

• Environmental Chemistry
• Ecotoxicology
• Pharmaceutical Science

Background:

• The Organisation for Economic Co-operation and Development (OECD) 308 water-sediment transformation test is crucial for environmental risk assessment (ERA) of pharmaceuticals in Europe since 2006.
• It's the primary transformation test for aquatic/sediment compartments, aiding in classifying drug persistence and environmental fate.

Purpose of the Study:

• To analyze 31 OECD 308 studies on pharmaceutical behavior in water-sediment systems.
• To evaluate the formation of nonextractable residues (NER) and the persistence of pharmaceuticals.
• To assess the feasibility of using a simplified 1-point analysis for estimating half-life.

Main Methods:

• Overview of 31 OECD 308 studies conducted by four companies.
• Analysis of geometric mean (gm) parent total system half-life and 10th/90th percentile values.
• Quantification of nonextractable residues (NER) as a percentage of applied radioactivity.
• Kinetic analysis of parent compound remaining in water and sediment extracts.

Main Results:

• The geometric mean parent total system half-life was 30 days (10th/90th percentile: 14.0/121.6 days).
• Cationic substances exhibited approximately twice the half-life of neutral and anionic substances.
• Considerable NER formation was observed (gm: 38%), with cationic substances forming the most (50.8%).
• A simplified 1-point analysis showed good agreement with measured total system half-life values.

Conclusions:

• Cationic pharmaceuticals demonstrate increased persistence and NER formation in water-sediment systems.
• A simplified 1-point analysis may be a viable screening tool for estimating pharmaceutical half-life in ERA.
• Recommendations include developing more relevant tests, standardizing terminology, and further investigating cationic drug behavior and bioavailability.