Harmonisation of environmental exposure assessment for veterinary pharmaceuticals and biocides

The spread of veterinary medicinal products and biocides onto agricultural land is an important path of entry into the environment. For this reason, experimental studies on transformation of veterinary medicinal products and biocides in manure are required according to current guidance (e.g. EMA/CVMP/ERA/430327/2009). To allow for a consistent assessment of studies within the registration process, a harmonised internationally accepted and validated test method is needed. However, such a test guideline is still missing. A draft test guideline was developed within a previous project (‘Development of test guidance for transformation of veterinary pharmaceuticals and biocides in liquid manure’, [read more]). The aim of the present project was to further develop this draft test guideline for an experimental method to study the transformation of veterinary pharmaceuticals and biocides in cattle and pig liquid manure, and to validate it in an international inter-laboratory comparison (ring test). A supplementary literature review was carried out as described below.

(1) Influence of different experimental set-ups on observed mineralisation

To further develop the draft test guideline, the influence of different test-setups on observed mineralisation (expressed as CO2 and CH4 formation) was evaluated. Specifically, the following issues were addressed:

  • Does the use of a flow-through (i.e. continuously passing nitrogen over the manure samples) or, alternatively, semi-static system (i.e. intermittently passing nitrogen over the manure samples) influence the formation rate of CO2 and CH4 and the CH4/CO2-ratio?
  • Does the flow rate of nitrogen influence the formation rate of CO2 and CH4, and the CH4/CO2-ratio?
  • Do the amount of incubated manure and the dry matter content of the manure have an influence on the mineralisation rate?

For further information, see the report on this subproject.

(2) Literature review of studies on occurrence and transformation of veterinary pharmaceuticals and biocides in manure

Within this literature review, publicly available studies with liquid manure were evaluated, e.g. with regard to the transformation fate of the veterinary pharmaceuticals and biocides, the origin and characteristics of the used manure, and the experimental setup. Transformation strongly depended on the test conditions, especially the temperature, redox potential and dry matter content of the manure. Unfortunately, information on the critical parameters is not provided in all studies. Furthermore, the characterisation of the liquid manure is in many cases insufficient due to missing parameters such as dry matter content, pH and TOC.

Additionally, publicly available monitoring data of veterinary medicinal products in manure were collected and evaluated concerning e.g. the origin and characteristics of the manure, the identified compounds and the measured concentrations. Most data are available for sulphonamides, tetracyclines and fluoroquinolones.

For both transformation studies and monitoring studies, a standardised guidance would improve applicability in regulatory contexts and enhance the scientific outcome of these studies.

Further information is provided in the report on this subproject.

(3) Ring test for validation of a draft test protocol for studies on transformation in manure

The ring test was conducted with the purpose to validate the test protocol and to derive criteria for quality and reproducibility of the test results. Two test compounds – a veterinary medicinal product (florfenicol) in pig manure and a biocide (imidacloprid) in cattle manure – were investigated. Based on the experimental results of the ring test as well as discussions and conclusions of two workshops (one at the beginning, and one at the end of the project), a revised draft test guideline was prepared.

For further information, see the report on this subproject.

This work was funded by the German Environment Agency (FKZ 3712 65 420).