Environmental Risk Assessment of Active Human Pharmaceutical Ingredients in Urban Rivers in Japan.

Area of Science:

• Environmental Chemistry
• Ecotoxicology
• Pharmaceutical Science

Background:

• Active pharmaceutical ingredients (APIs) pose potential risks to aquatic ecosystems.
• Japan's Ministry of Health, Labor and Welfare (MHLW) established Environmental Risk Assessment (ERA) guidance in 2016 for new pharmaceutical development.
• Phase 1 of the MHLW's ERA guidance uses predicted environmental concentrations (PECs) to assess environmental risk.

Purpose of the Study:

• To evaluate the effectiveness of Phase 1 in the MHLW's ERA guidance.
• To compare measured environmental concentrations (MECs) of approved APIs with predicted environmental concentrations (PECs) in Japanese aquatic environments.

Main Methods:

• Collected seasonal water samples from seven urban rivers and three sewage treatment plants (STPs) in Japan.
• Analyzed 51 APIs and sucralose using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Compared MECs with MHLW's PEC values (PECjapan), using an action limit of 10 ng/L.

Main Results:

• 44 APIs detected in rivers and 42 in STPs, with concentrations from nanograms to micrograms per liter.
• Most APIs had median MECs below their respective PECjapan values.
• Ketoprofen was the only API with a PECjapan below 10 ng/L and a MECmax greater than or equal to 10 ng/L.

Conclusions:

• The PECjapan values in Phase 1 of the MHLW's ERA guidance are generally appropriate for risk assessment.
• Discrepancies in MECmax values for some APIs suggest potential overestimation of river dilution or underestimation of API production.
• Further refinement of dilution factors and production estimations may be needed for specific APIs.