Environmental Assessment of Veterinary Medicinal Products in Denmark
Summary
A Technical Guidance Document, EMEA/CVMP/055/96 outlines a detailed evaluation procedure to assess the environmental risk of new veterinary medical products used in husbandry. Despite a relative high usage of some veterinary medical product very little information on consumption, release, fate and effects of this group of substances is generally available. Therefore, the Danish Environmental Protection Agency and the Danish Medicines Agency in co-operation have initiated the work described in this report.
The main objectives of the report have been:
 | to quantify the use of veterinary medicinal products in Denmark, |
| to estimate the environmental release of active substances and residues, |
| to identify groups of veterinary medicinal products that may pose a risk to the environment, and |
| to discuss the EU Technical Guidance Document on risk assessment of veterinary medical products in relation to existing EU Technical Guidance Document on risk assessment of new and existing substances. |
This report focuses primarily on the following therapeutic groups: antibiotics, antiparasitic compounds, and substances used for treatment of the alimentary tract, the central nerve system (CNS) and problems with metabolisms. These compounds are all used in significant quantities. Furthermore, hormones are included as they are a group of substances with a very high biological activity.
The use of antibiotics used therapeutically was 48.5 tons in 1997. Another 1.7 tons of antibiotics were used as feed administrated drugs in 1996 (no data available for 1997). Other therapeutically uses of veterinary medicinal products (VMP) included in 1997 14 tonnes of active substances for the alimentary tract and metabolism , 236 kg of antiparasitic compounds, 230 kg of for CNS-active products and 29 kg of active hormones.
In 1997 more than 105 tons of antibiotics were used non-therapeutically as antimicrobial growth promoters. The total quantity of antibiotics used thus exceeds 170 tons (including coccidiostatics). However, the data for the first six months of 1998, where only 28.9 tons were used, indicate a significant reduction in the annual use of antibiotics as feed additives in Denmark. No information is available on another widely used group of drugs, the antiparasitic compounds, as these are sold outside pharmaceutics without prescription.
The environmental release of a number of substances is estimated in realistic worst case scenarios. The main route of environmental exposure for all drugs is via manure or slurry. On the basis of the information on recommended doses of veterinary medical products and the normal application of manure in Denmark, Predicted Environmental Concentrations (PECs) was estimated. For antibiotics PECs were found in the range of 0.2 to 9 mg / kg soil depending on compound and application. For hormones PECs were found between 0.01 and 0.05 mg/kg soil and for substances used in connection with the alimentary tract PECs between 0.04 and 5.7 mg / kg soil were estimated. For substances used for CNS disorders in cows, PECs between 0.1 and 28 mg / kg soil were found. PECs are generally somewhat higher when soil is amended with cow manure than with pig manure, as the higher nitrogen content in pig manure prescribes a lower load of manure according to the legislation that regulates the maximum load of nitrogen per hectare. In cases of direct deposition on the soil with no subsequent tilling, the concentration may locally be higher.
These results are all worst case scenarios, as no degradation during storage is incorporated in the calculations. Half-lives for antibiotics varies from a few days to years depending of the conditions, but information about the fate of these compounds during storage in the manure tank and in the soil is limited.
Very little is known about the ecotoxicological effects of most veterinary medicines. Best information is available for antibiotics and antiparasitic compounds. Even for these substances, it is not possible to conclude or exclude whether serious unwanted side-effects in the environment may occur as a result of normal use. The information is also too sparse to conclude whether specific types of substances are more harmful than others. However, it is generally assumed that the broad spectrum antibiotics and antiparasitic drugs may affect a broader range of organisms than more specific acting drugs.
It is not possible to conclude from the data available whether the current normal veterinary use of hormones or substances used for diseases associated to the CNS or the metabolism may have effects on the environment.
The risk assessment procedure for new and existing substances (chemicals) have briefly been reviewed and compared with the risk assessment of veterinary medicinal substances (drugs). The comparison reveals a number of differences in the evaluation procedure. Environmental concentrations of veterinary medicinal substances below certain cut-off values, e.g. 10 µg/kg in dung or soil, do not warrant an environmental risk assessment. The uncertainty of the predicted environmental concentration for veterinary medicinal products is significantly less than that of certain uses of existing chemicals. Furthermore in the calculation of the Predicted No Effect Concentrations (PNEC-values) for drugs, the recommended use of application (safety) factors on comparable data is often 10-100 times lower than for industrial chemicals. Finally, there is not, as in the case of existing chemicals, a national or international strategy of how and when to assess already existing VMP. On the basis of national priority list among the approximately 100,000 existing chemicals in the EU database EINECS and priority indicated by a European priority method (EURAM) a comprehensive risk assessment is produced by competent authorities in the European member states.