Influence of pH-dependent aquatic toxicity of ionizable pharmaceuticals on risk assessments over environmental pH ranges.

Due to variation in pH, ionizable pharmaceuticals entering aquatic environments experience different degrees of ionization, which may affect toxicity. Using data from toxicity testing at only neutral pH may potentially under- or overestimate actual toxicity at pH ranges found in natural aquatic environments. Here we show relative pH-dependent acute toxicity to Daphnia magna for the pharmaceutical weak bases fluoxetine and sertraline, as well as the weak acids naproxen, diclofenac, ibuprofen and ketoprofen. A probabilistic modelling approach using the pH-dependent toxicity data for D. magna and an environmental pH distribution based on over 4000 European running waters from 21 countries predicted that environmental toxicity for the weak bases may be underestimated if pH 7 was assumed. The model predicted median underestimation by a factor of 3, with 90% of the model results ranging from 1 to 6. Consequently, due to the slightly basic nature of the European running waters, weak acid toxicity may be overestimated by a factor of 2. Predicted median toxicity was 0.5 of that assuming pH 7 with 90% of the results ranging from 0.03 to 5. Because aquatic pH exhibits large variation both within and between countries, we advise the use of site-specific risk assessments for ionizable pharmaceuticals in making informed water management decisions.