Environmental Risk Assessment of Pharmaceuticals

Current status of ERAPharm

In the second year of the project, a considerable amount of work focussed on the human case study compound atenolol and the veterinary case study compound ivermectin. For these two pharmaceuticals, complete environmental risk assessments (case studies) are performed within ERAPharm. An additional human case study compound, fluoxetine, was selected. Further test pharmaceuticals are investigated in the individual work packages.

Fate work packages
In year 2, additional analytical methods were developed for quantifying pharmaceuticals in sediments and soils. Some analytical methods were adapted to allow the analysis of invertebrate tissues and fish plasma. Interlaboratory comparison studies were performed to validate the established analytical methods for different matrices. Sorption studies were carried out with sediment, soil and sludge, and studies were started to investigate the biodegradation of various pharmaceuticals in freshwater and marine sediment and in sewage treatment plants. Excretion and fate of ivermectin were investigated in field studies. Furthermore, runoff simulation experiments and tile drain studies were conducted in Canada to assess dissipation characteristics and mobility of a range of human pharmaceuticals.

The scenario selection for the environmental risk assessment of veterinary pharmaceuticals was finalised and the identified scenarios were compared to existing FOCUS and VetCalc scenarios. Mechanistic models for transport of pesticides from soil into water bodies were evaluated for their applicability to veterinary pharmaceuticals. In addition, a survey was carried out on usage of parasiticides in U.K. cattle farms to derive realistic input concentrations for fate and transport models. All available literature data on ivermectin and atenolol and a range of other pharmaceuticals were collected and work was started to evaluate existing models for their ability to predict adsorption and biodegradation of pharmaceuticals.

Effects work packages
The parasiticides ivermectin, albendazole and morantel were screened using a mode-of-action based set of in vitro and low complexity bioassays. Two terrestrial microcosm experiments were performed, one with sulfamethoxazole and one with chlorotetracyline, to evaluate effects on structure and function of bacterial communities. The environmental relevance of the soil microorganism nitrogen transformation test for the assessment of pharmaceuticals was improved.

At the laboratory scale, studies on the effects of ivermectin on terrestrial invertebrates were completed. At the semi-field scale, work that had started in year 1 was continued using three test systems that differ in their complexity: terrestrial model ecosystem (TME) studies, MS-3-studies and SMS-studies. A field study was conducted in York, U.K., for investigating the effects of ivermectin on dung organisms and soil arthropods, along with the excretion profile and the persistence of ivermectin. A second field study has been started near Madrid, Spain.

The evaluation of the effects of ivermectin and atenolol on aquatic invertebrates was completed. In addition, long-term effects of fluoxetine on three invertebrate species were investigated. Two complex tests were performed with fluoxetine: a multi-species invertebrate test with three laboratory-reared invertebrate species and a microcosm test with natural plankton and benthos communities. Bioaccumulation of ivermectin in aquatic oligochaetes was investigated.

A review of available information on comparative physiology, pharmacology and toxicology of β-blockers was completed. Two long-term fish studies were carried out with the human case study pharmaceutical atenolol: a fish early life stage test and a reproduction test, both with the fathead minnow (Pimephales promelas). The molecular-sequences of the β1- and β2-adrenergic receptor of the fathead minnow were further identified.

Environmental risk assessment
Work of the four working groups that address different aspects of the environmental risk assessment of pharmaceuticals - (1) approaches to target the environmental risk assessment, (2) methods for assessing exposure to pharmaceuticals, (3) methods for assessing the effects of pharmaceuticals on the environment and (4) approaches for assessing transformation products - was continued. Further data on fate and effects of the case study pharmaceuticals atenolol and ivermectin were compiled and, as far as possible, environmental risk assessments were performed according to current guidance documents. An additional human case study with fluoxetine was started.

5th ERAPharm meeting, 02 - 05 October, 2006, Stoney Lake, Ontario, Canada