Exposure Assessment of Pharmaceuticals and Their Metabolites in the Aquatic Environment: Application to the French Situation and Preliminary Prioritization

ABSTRACT

Low levels of pharmaceuticals have been detected in many countries in surface waters. As a wide range of pharmaceuticals can reach aquatic environments, a selection of molecules to survey is the first step before implementing a monitoring program. We used a simple equation to calculate Predicted Environmental Concentrations (PECs), adapted from the European Medicine Agency model used for the Environmental Risk Assessment (ERA) of human pharmaceutical. Excretion fractions for pharmaceuticals were determined for 76 compounds. Using year 2004 French drug consumption data, we determined aquatic PECs for 112 parent molecules and several metabolites. Considering excretion fractions of pharmaceuticals can lead to drastically reduce predicted concentrations reaching the aquatic environment and help to target environmentally relevant pharmaceuticals and metabolites. Calculated PECs using the described methodology are consistent with French field measurements. The simple model for calculating PECs can be used as a valuable estimation of the exposure. Risk quotient ratios were also calculated. Due to the lack of ecotoxicological data, the use of PEC/PNEC ratios is not enough informative to prioritize pharmaceuticals likely to pose a risk for surface waters. Alternative ways to prioritize risk to pharmaceuticals, combining PEC, pharmacological, and ecotoxicological data available from the literature, should be implemented.

Key Words:

• pharmaceuticals
• metabolites
• exposure assessment
• aquatic environment
• prioritization

ACKNOWLEDGMENTS

The authors thank the AFSSAPS (Cavalié Philippe, Rouleau Alice, and Castot Anne), for kindly sharing consumption data of pharmaceuticals. The authors also thank Tatiana Boucard (UK Environment Agency) for kindly proofreading the former manuscript. The authors also thank the Agence de l'Eau Rhône Méditerrannée & Corse for financially supporting this project. Finally, the authors are grateful to the two anonymous reviewers for their helpful comments that allowed us to improve this article.

Notes

*Indicates a prodrug.

**Data from Carlsson et al. 2006. Underlined metabolites are considered to be of environmental concern (see section about environmental relevance of active metabolites for further details).

*Removal fraction determined in winter (Castiglioni et al. 2006).

**Removal fraction determined in summer (Castiglioni et al. 2006).

^a distribution of PEC calculated using minimal and maximal WWTP removal rates reviewed (see Table 3 for details),

^b PEC calculated using WWTP removal rates calculated by Paffoni et al. 2006,

*PECc are considered negligible considering the very low Fexcreta values of 0.01 assumed for diazepam and simvastatin,

**PECc is considered negligible as Paffoni et al. (2006) reports a WWTP removal fraction of 1. WWTP measured concentrations from Paffoni et al. (2006) are mean concentrations.

*active metabolite of simvastatin.

^a mean values.

^b median values.

^c oxazepam PEC was calculated by summing different sources for this compound. ND: not detected or not already searched in the aquatic environment. NA: not applicable due to lack of data.

*Indicates that risk quotients for these compounds were calculated applying the EMEA methodology (three NOEC values from three different taxonomic groups). Other risk ratios were conducted using TGD (2003) recommendations (with only one or two NOEC values). When three NOEC values for three different taxonomic groups were available, a factor of 10 was applied to the lowest NOEC value; when two NOECs were available, a factor of 50 was applied; a factor of 100 was applied when only one NOEC value was available. **Quoted by Webb 2001, in Kummerer 2001. NA: not available.