Environmental Assessment of Veterinary Medicinal Products in Denmark
1. Introduction
| 1.1 | Grouping of veterinary medicinal products in Denmark |
| 1.2 | Danish legislation on veterinary medicinal products |
| 1.3 | The structure of the report |
Veterinary medicinal products (VMP) are used in order to increase the health and well-fare
of our animals. Veterinary medicinal products are authorised for use by regulatory
authorities if they comply with scientific criteria on quality, efficacy, and safety. The
authorities consider occupational health during production and handling and safety to the
treated animal, to the consumer and to the environment. The environmental risk of
veterinary medicinal products has recently become a matter of increasing public scrutiny
and legal requirements. This report is focusing on the potential environmental risk of
veterinary medicines. Other aspects of the use of veterinary medicinal products have been
dealt with in different reports from the Danish authorities, e.g. the risk of increasing
resistance of bacteria to antibiotics (Miljøstyrelsen 1997).
The environmental risk of veterinary medicines is assessed according to different regulations depending on whether the application is therapeutic or non-therapeutic. The legislation in the European Union (EU) on the environmental risk assessment of veterinary medicines is contained in Commission Directive 92/18/EEC. This directive outlines the basic requirements for conducting an environmental risk assessment of veterinary medical products. A detailed guidance on environmental risk assessment is given in a Technical Guidance Document, EMEA/CVMP/055/96. The procedure for environmental risk assessment of VMP only concerns products sold after the 1st of January 1998. There is currently no European initiative to assess environmental risk of already marketed veterinary medicinal products.
Directive No. 94/40/EEC lays down a guidance for assessing the effects of food additives (frequently used as medicinal products as well, e.g. antibiotics) to animals. This guidance is currently being revised by the Commission.
Residues of veterinary medicinal products may be deposited on arable land or pastures as a constituent of manure and slurry. The use of manure/slurry as fertilisers on arable land may thus involve a risk for the environment. On the other hand the use of manure/slurry is desirable to recycle nutrients and hence an important part of the concept of a self-sustainable agriculture.
The main objective of the report is to :
- quantify the use of veterinary medicines in Denmark,
- estimate the environmental release of active substances and residues,
- identify groups of veterinary medicines that may pose a risk to the environment,
- identify groups of veterinary medicines that are unlikely to cause environmental risk, and to
- discuss the EU Technical Guidance Document on risk assessment of veterinary medicinal products (EMEA/CVMP/055/96) in relation to the existing EU Technical Guidance Document on risk assessment of new and existing substances.
Delimination
A few hundred papers concerning the environmental fate and impact of veterinary medicines were found in databases such as Medline, Biological Abstract, Analytical Abstract, Agricultural Abstract and Toxline. Conclusions and recommendations of this report are based on these studies and data of consumption of veterinary medicinal products in Denmark. No conclusions in the report have been related to specific products. Veterinary medicines used only for pets and horses are not considered in this report.
1.1 Grouping of veterinary medicinal products in Denmark
ATC and CAS code system
All veterinary medicines are internationally registered under ATC codes. The ATC code system is similar to the CAS code system. However, antimicrobial growth promoters are only registered under CAS codes as they are not considered to be medicines. Appendix A gives a list of the ATC and CAS codes for substances found in this report. Box 1.1 gives examples on some of the definitions and terms used in this report.
Veterinary medicines may be divided into therapeutic groups as follows. Compounds used for diseases associated with the alimentary tract and metabolism (group QA), the cardiovascular system (QC). Compounds used as dermatological products (QD), as sex hormones (QG) or as systemic hormones (QH). Compounds for anti-inflammatory systemic uses (QJ01+QJ51). Compounds used for diseases associated with the musculo-skeletal system (QM) or the central nerveous system (QN). Compounds used as antiparasitics (QP) and a group compounds with miscellaneous uses (QV). The group codes refers to the ATC code system and has been used for analysing the consumption of veterinary medicines in Denmark (Veterinærmedicinsk Produktkatalog, 1997).
Labelling and despensation of veterinary medicinal products (VMP)
Veterinary medicinal products have to be labelled with instructions concerning application, storage etc. in accordance with the laws. Veterinary Medicinal Products are dispensed as follows
| A: | May only be dispensed once with a prescription. |
| B: | May only be dispensed once with a prescription unless number and intervals of dosing are indicated the prescription. |
| H: | May be dispensed without prescription/requisition. |
| V: | May be sold by other suppliers than pharmacies. |
Following a special regulation dated the 15. December 1975, products sold as V-labelled medicine includes antiparasitic agents, iron and vitamins
VMP applied as feed additives are divided into three groups;
 | A: Antibiotics (pigs, ruminants and poultry) |
| D: Coccidiostatics and related drugs (poultry) |
| J: Growth promoting substances (pigs). |
The following products are used within each group :
| A: | Zinc Bacitrin, spiramycin, flavofosfolipol, tylosinfosfat, monensin natrium, salinomycin natrium and avilamycin. |
| D: | Amprolium, amprolium-etophat, dinitolmid, dimetridazol, metik lorpindol, decoquinat, monensin natrium, robenidin, ronidazol, ipronidazol, metiklorpindol metylbenzoat, arprinocid, lasalocid natrium, halofuginon, narasin, salinomycin natrium, nicarbazin, nifursol, maduramincinammonium, and diclaruzil. |
| J: | Carbadox and olaquindox |
Premix
The sale of mixtures as feed administrated drugs, the so-called premix, may cause some minor inaccuracy in the data compilation. Double counting may occasionally have occurred between the data on antibiotics used therapeutically (Table C.3) and antibiotics used as feed administered medicine (Table C.8). As an example, according to the data from the DMA more than 600 kg of the tylosin containing premix "TylanâVet. 2%" was sold in 1996. Although the mixture "TylanâVet. 2%" is a medicinal feed additive, only 0.6 kg was registered for this used by the Plant Directorate in 1996. The same is true for other "premix" products.
Box 1.1.
Definitions of terms as used in this report
Veterinary medicinal products Veterinary medicinal products are defined as substances applied to animals to avoid, relieve, treat or cure diseases or symptoms or to stimulate functions of the organisms. The use of veterinary medicinal products may be divided into the following categories: - therapeutic use (treatment of disease) Feed administrated drugs Feed administrated drugs are defined as medicines. These may only be dispensed following prescription from a veterinarian. Feed administrated drugs are pre-mixtures of drugs mixed with one or more feeds. Feed administrated drugs are applied to pigs, cattle and fish. The following antibiotics are used in pre-mixtures registered in Denmark; chlortetracycline, enrofloxacin, oxilic acid, lincomycin, and sulfadiazin in combination with trimetroprim, and tylosin. The annual consumption of feed administrated drugs is registered by the Danish Plant Directorate. Antimicrobial growth promoters Antimicrobial growth promoters are defined as feed additives. The sale of Antimicrobial growth promoters is regulated by the Danish Plant Directorate. These substances may only be used as additives to the feed, if they have a beneficial effect, either on the animal performance or on the feed conversion ratio. The substances are used non-therapeutically only. The active compounds may, however, sometimes be uses as veterinary medicines also. |
Veterinary Medicinal Products used in Danish husbandry may be authorised for use according to laws and regulations issued by the Ministry of Health and the Ministry of Food, Agriculture and Fisheries, e.g. ‘Lægemiddelloven’, ‘Bekendtgørelse om lægemidler til veterinær brug’, ‘Bekendtgørelser om foderlægemidler til dyr og fisk’, ‘Bekendtgørelse om tilsætningsstoffer’. The regulations may overlap, depending on the application of the product as the identical active substance may be used both therapeutically and non-therapeutically, i.e. as a veterinary medicine and as growth promoter. The annual use of the identical active substance may therefore be recorded by different authorities. Due to a complex regulation a short overview of regulatory issues of particular interest to this report is given in Appendix B.
1.3 The structure of the report
The first chapter includes besides a short general introduction to the background and main objectives of the report a definitions of terms and a summary of the Danish regulation of veterinary medicines. In chapter 2 a quantification, on single compound levels, of the use of veterinary medicines (A and B labelled), antimicrobial growth promoters, and feed administrated drugs are presented. An overview is given on the anticipated environmental release and exposure routes of veterinary medicines.
Chapter 3 describes the occurrence and fate of veterinary medicinal substances in the environment, and includes calculations of the predicted environmental concentration of a few selected veterinary medicines. Fertilisation of arable land and pastures with manure/slurry is a major source to the environmental release of veterinary medicines. Therefore, a brief description of the relevant Danish legislation regulating the load of manure/slurry on agricultural soil is included in chapter 3. Chapter 4 describes existing information dealing with effects of veterinary medicinal substances on organisms from aquatic and terrestrial environments. Chapter 5 discusses the Technical Guidance Gocument on environmental risk assessment of veterinary medicinal substance in relation to the technical guidance document used for environmental risk assessment of industrial chemicals in the EU. At the end of each chapter a summary is given and conclusions drawn. Finally, in chapter 6 and 7 the overall conclusions and recommendations are presented.