Veterinary medicines are widely used across Europe to treat farm animals. Once administered to an animal they may be adsorbed and partially metabolised before being excreted in urine and faeces. The resulting manure or slurry can then be released directly to the environment or collected and stored before being applied to land.
Once released to land, the medicines may be washed off into surface waters or leach to groundwaters where they may impact environmental and human health. Consequently, under EU Directive 81/852/EEC, an environmental risk assessment is now required on veterinary medicines.
Unlike pesticides, nutrients and other priority pollutants, the behaviour and effects of veterinary medicines in the environment has not been extensively studied. Moreover, differences in the characteristics of veterinary medicines in relation to other chemical classes, mean that methodologies that have been developed for other chemical classes may not be appropriate for veterinary medicines. Guidelines and approaches have been developed for performing these assessments (e.g. CVMP, 1996; Spaepen et al., 1997; Montforts, 1999). Due to a lack of background data, these approaches are generally very simple and have been developed to predict 'worst case' concentrations. Moreover, the methodologies may not adequately consider leaching to groundwaters or runoff to surface waters and extrapolation across member states is problemmatic.
Cranfield University are therefore co-ordinating a European Framework V project to develop improved approaches for assessing the environmental impact of veterinary medicines released to the environment. The specific aims of the project are to:
a. identify those factors and processes controlling the degradability of veterinary medicines in manure, slurry, soil, sediment and water
b. identify those factors and processes controlling the leaching of veterinary medicines in the environment
c. assess the effects of veterinary medicines on soil fauna and flora
d. assess the environmental distribution of a range of veterinary medicines at the semi-field and field scales
e. develop exposure assessment models and associated scenarios for use by regulators and industry
Three compounds have been selected for the study based on available data on metabolism, degradation and usage, namely: oxytetracycline, sulfachloropyridazine and valnemulin. This paper describes initial work to assess the environmental risk associated with each of these compounds and outlines future work.
Environmental Risk Assessment of Study Compounds
Data was collated on the metabolism of each of the study compounds by animals. Tetracyclines are excreted predominantly in the urine and the faeces as the parent compound, corresponding to between 40-70% of the applied dose. Whilst the metabolism of sulfachloropyridazine has not been investigated, a number of other sulphonamides have been investigated. These studies indicate that a significant proportion (i.e. 30-95%) of the applied dose of a sulphonamide may be excreted unchanged. Valnemulin is extensively metabolised and around 2% of the administered valnemulin is excreted unchanged.
Properties and Persistence
Data was available on the sorption behaviour and biodegradability of oxytetracycline (Table 1). No data were available on the degradability of valnemulin or sulfachloropyridazine. The sorption coefficient for oxytetracycline was high, indicating that it is likely to partition extensively to soils and that it has a low potential to leach. Moreover, the degradation rates in water indicate that oxytetracycline will persist. In contrast, the properties of sulfachloropyridazine indicate that it will readily leach.
Table 1. Properties and persistence of study compounds
Prediction of Environmental Concentrations
The concentrations of each of the study compounds in soil water and soil were predicted using the uniform approach developed by Spaepen et al (1997). the input values for the approach are shown in Table 2. Predicted concentrations, assuming no degradation during storage, in soil ranged from 0.035 mg kg-1 (valnemulin) to 1.55 mg kg-1 (sulfachloropyridazine). Due to it's very low Log Koc, predicted concentrations of sulfachloropyridazine in soil water were high (i.e. 5.2 mg l-1) whereas concentrations on oxytetracycline and valnemulin were less than 4 μg l-1.
Table 2. Input data used to predict concentrations of study compounds in soil and water following treatment of pigs.
Table 3. Predicted concentrations of the study compound in soil (mg kg-1) or soil water (mg l-1)
Effects on organisms
A wide range of data was available on the effects of the study compounds on aquatic organisms (Table 4). Generally all of the study compounds were of low toxicity to the organisms studied.
Table 4. Effects of study compounds on aquatic and terrestrial organisms.
Risk assessment of study compounds
Predicted concentrations of the study compounds in soil and water were compared with lowest effective concentration to assess the likely environmental risk posed by each compound (Table 5). Generally, the ratios of predicted concentrations to effects concentrations were all well below 1, indicating that the compounds probably pose a low risk to terrestrial and aquatic organisms.
The exception to this was sulfachloropyridazine in soil water where the ratio was 31. This was determined using a toxicity data predicted using QSARs, experimental studies would be required to confirm these predictions. Moreover, predicted concentrations are 'worst case' and probably provide an overestimate of actual concentrations in the environment.
Table 5. Ratio's of predicted environmental concentrations to lowest observed effect concentrations for each of the study compounds.
The work to date has focused on collating available data on metabolism, properties, degradadability and effects of the study compounds. A number of experimental investigations are currently underway to generate information on: 1) actual concentrations of the compounds in the environment; 2) the degradability of the study compounds in slurry, water, soil and sediment; 3) the sorption behaviour of the study compounds in a slurry, sediment and soil; and 4) the effects of the compounds on terrestrial communities. These studies will be completed in the next 2-3 years.
On the basis of these investigations, the current risk assessment methodologies will be assessed and refined where appropriate.
Committee for Veterinary Medicinal Products. 1996. Note for guidance: environmental risk assessment for veterinary medicinal products other than GMO-containing and immunological products EMEA/CVMP/055/96-Final. European Agency for Evaluation of Medicinal Products, London, UK.
Montforts MHMM. Environmental Risk Assessment for Veterinary Medicinal Products. 1. Other than GMO-containing and Immunological Products. First update. RIVM, Report 603100001, Bilthoven, The Netherlands, 1999.
Spaepen, K.R.I., Van Leemput, L.J.J., Wislock, P.G., and C. Verscheuren, C., 1997. A uniform approach to estimate the predicted environmental concentrations of the residues of veterinary medicines in soil. Environmental Toxicology and Chemistry 16(9), 1977-1982.