Environmental Risk Assessment of Pharmaceuticals

Pharmaceuticals provide immense societal benefits, but their environmental impact demands thorough evaluation. Regulatory agencies like the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) mandate comprehensive Environmental Risk Assessments (ERAs) for new medicinal products to ensure their safety for ecosystems and human health. This process involves both risk assessments and hazard assessments to identify and mitigate environmental risks effectively. Human health risk assessments are also required for a full evaluation of pharmaceutical toxicology.

Importance of Risk and Hazard Assessments

Both risk assessment and hazard assessment are integral to the environmental risk assessment (ERA) process:

• Risk Assessment: Evaluates the likelihood of adverse effects based on exposure levels.
• Hazard Assessment: Identifies substances with harmful properties, ensuring regulatory actions can minimize environmental accumulation and ecosystem damage.

Environmental Risk Assessment of Pharmaceuticals: Evaluating Potential Exposure

The ERA for pharmaceuticals consists of two distinct phases: Phase I (screening) and Phase II (detailed assessment).

Phase I: Screening and Triggering Phase II

This initial phase evaluates the likelihood of environmental exposure based on the pharmaceutical's intended use and properties.

• Key Evaluation: Predicted Environmental Concentration in Surface Water (PECSW):
  • PECSW estimates the concentration of a pharmaceutical in surface water.
  • If PECSW exceeds 0.01 µg/L, a Phase II assessment is triggered.
• Substance-Specific Considerations:
  • Endocrine-active substances (EAS) or antibacterials may require tailored evaluations, even at low PECSW values.
  • Natural substances or biodegradable compounds may be exempt if justified.

Outcome: Substances with minimal environmental concerns conclude ERA at Phase I, while others proceed to Phase II for further evaluation.

Phase II: Comprehensive Risk Assessment

Phase II is subdivided into Tier A (initial risk characterization) and Tier B (advanced testing and refinements).

Tier A: Initial Risk Assessment

• Physico-Chemical Properties: Assessment includes water solubility, biodegradability, and partition coefficients.
• Ecotoxicity Testing: Focuses on chronic effects across three trophic levels: algae, daphnia, and fish (e.g., OECD 210 Fish Early Life Stage test).
• Risk Quotient (RQ): Compares PECSW to the Predicted No-Effect Concentration (PNEC). An RQ ≥ 1 indicates further evaluation is needed.

Tier B: Advanced Testing and Refinements

• Refined PECSW: Accounts for patient metabolism, sewage treatment removal rates, and partitioning into environmental compartments using models like SimpleTreat.
• Additional Testing: Includes bioaccumulation (OECD 305) and sediment toxicity studies.

Outcome: Substances with persistent risks may require mitigation strategies or alternative recommendations.

Environmental Hazard Assessment of Pharmaceuticals: PBT/vPvB Evaluation

Hazard assessment identifies the intrinsic properties of a substance that may pose long-term environmental risks, independent of exposure levels. This process evaluates a substance's persistence (P), bioaccumulation (B), and toxicity (T) criteria, collectively referred to as PBT, or very Persistent and very Bioaccumulative (vPvB).

Criteria for PBT/vPvB Assessment

1. Persistence (P):
   • Substances with long degradation half-lives in water, sediment, or soil are considered persistent.
   • Non-biodegradable substances identified via OECD 301 tests are flagged for further evaluation.
2. Bioaccumulation (B):
   • Substances with a bioconcentration factor (BCF) > 2,000 are classified as bioaccumulative.
   • A BCF > 5,000 indicates very high bioaccumulation potential.
3. Toxicity (T):
   • Chronic toxicity tests identify substances harmful to aquatic organisms (e.g., OECD 201, OECD 211, and OECD 210).
   • Compounds classified as carcinogenic, mutagenic, or toxic for reproduction under CLP regulation also meet the T criteria.

Zebrafish in Environmental Risk Assessment: A Key Testing Model

Zebrafish (Danio rerio) are widely employed in ERA due to their unique biological traits:

• Transparency: Facilitates real-time observations of developmental and physiological impacts.
• Rapid Development: Enables quick assessments of acute and chronic toxicity.
• OECD Compliance: Zebrafish assays align with established guidelines, ensuring robust and reliable data.

Key Zebrafish Applications in Environmental Risk Assessment:

• Aquatic Toxicity Tests (OECD 236): Evaluate chemical impacts on zebrafish embryos.
• Bioaccumulation Studies (OECD 305): Measure the accumulation of substances in zebrafish tissues.
• Endocrine Disruption Tests: Detect hormonal interference in zebrafish systems.

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Conclusion

The environmental risk assessment of pharmaceuticals is essential for safeguarding ecosystems and human health. The dual approach of risk and hazard assessments ensures comprehensive evaluations of both exposure levels and intrinsic properties of medicinal substances. With tools like zebrafish, researchers can conduct efficient and ethical assessments, contributing to sustainable pharmaceutical innovation.

REFERENCES

European Medicine Agency - Environmental risk assessment of medicinal products for human use

By Miriam Martínez

Miriam is a Human Biologist with a strong background in neuropharmacology and a passion for bridging science and innovation. After earning a master’s degree in the Pharmaceutical and Biotech Industry, she completed her PhD in Biomedicine at Pompeu Fabra University (Barcelona), where her research focused on the behavioral analysis of animal models for neurophenotypical characterization. Following her doctoral studies, Miriam transitioned into the healthcare marketing and communication sector, where she played a key role in developing impactful marketing strategies and educational campaigns for leading pharmaceutical brands. She now leverages her scientific expertise, strategic thinking, and creative communication skills in her current role at ZeClinics.