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Environmental Assessment of Veterinary Medicinal Products in Denmark

2. Use, consumption and environmental release of veterinary medicinal products in Denmark

Veterinary medicinal products sold in Denmark are authorised by the Danish Medicines Agency or the Danish Plant Directorate. The Danish Plant Directorate annually publish data on the consumption of antimicrobial growth promoters and feed administrated drugs. This report summarises both the data compiled by the Danish Medicines Agency and the Danish Plant Directorate .

2.1 Quantification of the use of single substances

This report focus primarily on the following therapeutic groups as they are used to a significant extent in the agricultural livestock production and hence are submitted for a potential environmental release;

	alimentary tract and metabolism (group QA),
	antibiotics (group QJ01 and QJ51),
	central nervous system (group QN)
	antiparasitic agents (group QP).

Furthermore,

hormones (group QG and QH)

are included in the evaluation, as this group of substances have a high and specific biological activity and hence are potential hazardous if released to the environment.

Antimicrobial growth promoters and feed administrated drugs are also included in this report. The following therapeutically groups of medicines are not considered; Cardiovascular system (group QC), Dermatological products (group QD), Musculo-skeletal system (group QM), Miscellaneous (group QV), as their environmental release most likely is small.

Data from 1996 and 1997 concerning the amount of Veterinary Medicinal Products prescribed (A and B labelled) for therapeutic use were obtained from the Danish Medicines Agency. The estimate of the amount of active substance used in Denmark in 1996 and 1997 is based on amount of active substance sold as calculated from the number of recorded A- or B-labelled prescriptions.

The sale of V- and H-labelled products, e.g. ivermectin and hydrocortisone, has not been recorded, therefore it has not been possible to obtain information on the sale of these products. Data for single substances of feed administrated drugs, i.e. antimicrobial growth promoters, coccidiostatics, and antibiotics were obtained from the Danish Plant Directorate and used without further processing. The data for the selected therapeutic groups, for feed administrated drugs, coccidiostatics, and antimicrobial growth promoters are briefly reviewed below and presented in more detail in Appendix C (Table C.1 to C.8).Table C 9 in Appendix C shows an example of the calculation applied to the data received from the Danish Medicines Agency.

2.1.1 Drugs for the alimentary tract and metabolism (group QA), Table C.1

The total consumption of this group of drugs was in 1997 approximately 14 tons. Neomycin, an antibiotic, accounts for 3.9 tons and the majority of the remaining use is made up by Boric acid, calciumglyconat and magnesiumhypophosphit. All other substances are used in quantities less 1 tons.

2.1.2 Hormones (group QG and QH), Table C.2

Hormones are generally divided into two therapeutic groups; sex hormones (QG) and systemic hormones (QH). A total of ca. 30 kg of active hormones, divided on twelve different substances, were used in 1997. In the EU, as opposed to the US, hormones may not be used as growth promoters. This most likely explains the relatively small amount used in Denmark.

2.1.3 Antibiotics (group QJ01 and QJ51) , Table C.3

In 1997 a total of 48.5 tons of active substance was used therapeutically divided on more than 30 different antibiotics. Some pre-mix substances may also be used as feed administrated drugs. Hence, some data may be registered both by the Danish Medicines Agency and the Danish Plant Directorate. Double counting may therefore occur. Several compounds are used in quantities exceeding 1.0 tons, e.g. benzylpenicillin, lincomycin, amoxillin, ampicillin and the tetracyclines. Many antibiotics are used in quantities less than 100 kg. The use of some of the antibiotics, e.g. benzylpenicillin and spiramycin, were found by translating IE units to mg by use of conversion units found in Martindale (1996).

2.1.4 Drugs for the Central Nervous System (CNS) (group QN), Table C.4

The group consists of 14 substances all used in small amounts. Totally 230 kg active substance was used in 1997, dominated by the use of metamizolnatrium (177 kg).

2.1.5 Antiparasitic agents (group QP), Table C.5

In 1997, an prescription of 236 kg of sulfaclozine was the only registered use of antiparasitic drugs. Antiparasitic drugs sold without prescription, e.g. ivermectin, are presumably used in relatively large amounts.

2.1.6 Antimicrobial growth promoters (non-therapeutic use), Table C.6

The use of growth promoters in Denmark from 1989-1998 is presented in Figure 2.1. Growth promoters are primarily used for production of pigs. The consumption of antimicrobial growth promoters according to animal species is presented in Table C.9. The use of microbial growth promoters has increased from about 65 tons in 1989 to around 120 tons in 1997. 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. Avoparcin was previous the most used antibiotic in Denmark. Due to the risk of inducing cross-resistance against antibiotics essential for treatment of serious human infectious diseases, the use of avoparcin was banned in 1995. In the following years, virginiamycin, tylosine, bacitracin, spiramycin, carbadox and olaquindox were banned as growth promoters in the EU. A voluntary agreement between the farmer organisations and the Ministry of Agriculture banned the use of antiobiotic growth promotors in the production of broilers, pigs and calves.

Figure 2.1.
Annual use in tons of antimicrobial growth promoters during the period 1989-1998. (Data for 1998 is calculated on the basis of the use during the first six months). Source: Danish Plant Directorate.

Figur 2.1.
Forbruget af antimikrobielle vækstfremmeer (tons pr. år) i perioden 1989 til 1998. (Tal for 1998 er baseret på de første seks måneders forbrug) Kilde: Plantedirektoratet.

2.1.7 Coccidiostatics used in poultry production, Table C.7

The report includes data from the period 1989-1998. Approximately 17 tons coccidiostatics were used in 1997 and an estimated 16 tons have been used during 1998. In 1997 12 different substances have been used with Salomycin and Metichlorpindo/Methylbenzoquat taking up half of the total consumption.

2.1.8 Veterinary medicine used as feed administrated drugs, Table C.8.

The total use of feed administrated drugs was 1.720 kg in 1996, which was approximately a 30% decrease compared to 1995. Approximately 99 % of the total amount of feed administrated drugs are antibiotics. Approximately 20% of the total use in 1995 were used in poultry production. The remaining 80 % were used in fish farming, including 100 kilo of antibiotics (oxytetracycline and amoxcillin) that was used therapeutically.

2.1.9 Summary of the use of veterinary medicinal products in Denmark.

The use of Veterinary Medicinal Products in Denmark during 1997 is illustrated in Figure 2.2. Veterinary Medicinal Products prescribed by veterinarians constituted (in 1997) 14 tons of active substances used for the treatment of alimentary tract and metabolism, 29 kg of active hormones, 230 kg of CNS-active substances , and 236 kg of antiparasitic substances and 48.5 tons of antibiotics. 1.7 tons of antibiotics were used in 1996 as feed administrated drugs. Non-therapeutic use included more than 107 tons of antibiotics and 17 tons of active substances used as coccidiostatics in poultry production. The total therapeutic and non-therapeutic use of antibiotics exceeds 170 tons. Antibiotics are hence by far the dominating group of veterinary medicinal products used in Denmark. A significant reduction is, however, observed during the first half of 1998. No information about the sale of V- and H-labelled drugs was available. These groups include a number of commonly used antiparasitic substances, e.g. ivermectin, and are most likely also sold in large quantities.

Figure 2.2.
Use of veterinary antibiotics in Denmark during 1997 as a) therapeutics, b) microbial growth promoters, c) coccidiostatics, and d) feed administrated drugs (1996 data).

Figur 2.2
Forbruget af veterinært anvendt antibiotica i Danmark i 1997 a) terapeutisk, b)som mikrobielle vækstfremmere, c) coccidiostatika, og d) foderlægemidler (1996 data).

2.2 Environmental Release

Compared to industrial chemicals, the exposure routes of veterinary medicinal products to the environment is relatively easy to identify and related to specific field scenarios. Veterinary medicines may be spread to the environment, either directly when using the drugs or by subsequent excretion from the animals. The dominating pathway of environmental release in the terrestrial compartment is by amendment of arable soil with manure or slurry. In fish farms, an unknown part of food-pellets coated with or containing the medical compound (most often an antibacterial drug) will not be eaten hence reach the sediment unchanged. If taken up, the medication may be excreted as unchanged compounds or as metabolites and finally reaches the sediment. Figure 2.3 shows the anticipated exposure routes for veterinary medicines to the environment.
  

Figure 2.3.
Environmental release scenarios for veterinary medicinal products used in aquaculture (top) and in livestock production (bottom). The scenario for livestock covers all species of animals. However, not all routes of exposure is equal important. For example is the total environmental release from field going pigs and poultry insignificant in comparison to the release from animals in stables.

Figur 2.3.
Eksponeringsveje af miljøet for veterinære lægemidler anvendt i aquakulturer (top) og i husdyrproduktionen (bund). Scenariet for husdyr dækker alle typer. Ikke alle eksponeringsveje er lige vigtige for alle dyr. For eksempel er det totale miljøudslip fra fritgående grise og høns minimalt i forhold til dyr i stalde.

Veterinary medicines are widely used for therapeutically treatment of all groups of animals. The group of antibiotics used non-therapeutic is used as growth promoters to especially pigs, but also cattle and poultry. Coccidiostatics is only used as growth promoters in poultry production. The medicinal mixtures sold as "premixed" drugs are used for therapeutic treatment of pigs, cattle and poultry. The approximately number of animals in Danish livestock production is shown in Table 2.1. A detailed list on single substance level divided in animal species is found for therapeutic and non-therapeutic uses of antibiotics in Appendix D, Table D1 and D2. Box 2.1 includes a short description of exposure scenarios for application of medicines to different types of animals.

No information is available on the fate of veterinary medicinal products during storage of manure/slurry. If the substance in question is hydrophilic it will be dissolved in the aqueous fraction of the manure/slurry. Opposite, if the substance is hydrophobic, it will mainly adsorb on the particulate matter. If the substances are used therapeutically for field animals, these substances, e.g. hormones, antibiotics or antiparasitic drugs, will be urinated or defecated directly on the field and the exposure might be of a high local concentration. Both spreading of manure/slurry and dropping of excreta by field animals may lead to a run-off of especially hydrophilic substances in cases of subsequent heavy rain. However, the legislation aims at reducing this risk by having restrictions on where, when and how to apply manure and slurry to the soil.

Veterinary medicinal products used in fish farms may enter adjacent ecosystems either directly by water flow or they may accumulate in sediments, which at a later stage may be spread on arable land for fertilising purposes.

Table 2.1.
The approximate number of animals in Denmark in 1997. Data from Statistics Denmark 1997/1998.

Tabel 2.1.
Det omtrentlige antal dyr i Danmark i 1997. Data fra Danmarks Statistik 1997/1998.

Box 2.1.
Exposure scenarios following veterinarian drug application(s)

Six different scenarios for environmental release of veterinary drugs have been identified. These include release from: a) pigs, b) cattle, c)sheep, d) horses, e) poultry and f) fish in aquaculture Within each group of animals the fate and environmental release of a particular drug vary with a number of parameters, including time of use relative to the production cycle of the animal(s) and excretion pathway. The excretion pathway is among other things depending on water solubility of the substance. Most antibiotics are water soluble, whereas the groups of aver-/ivermectins are more lipohilic. Scenarios for cattle, sheep and horses The scenarios of cows, sheep and horses are similar. (Figure 2.3.) Faeces and urine from stabled animals may be stored and used as fertiliser on arable land. Drugs released both by the urine and the faeces will be stored together and released simultaneous. Hence, the major exposure pathway and the excretion rates is less important. VMP administered to livestock will follow the manure/slurry ending up on arable land . Livestock on pastures will deposit their excreta directly to the fields. The drugs present in dung will, depending on its chemical properties, stay there during dung degradation or leach to the soil in cases of rain. Drugs released via the urine will immediately reach the soil and if water soluble leach further down to groundwater or adjacent water systems with the soil water. Most drugs excreted by the urine is by nature relatively water soluble, whereas drugs excreted via faeces in general is less soluble. The quantity of manure/slurry produced by the three groups of animals differ, with cattle as the far most important, followed by sheep and horses. Scenarios for pigs and poultry The scenarios of pigs and poultry are similar (Figure 2.3). In both cases the animals in stables counts by far the highest numbers. Although the numbers of pigs and chickens kept on open land currently are increasing in Denmark, deposition by livestock directly on fields is insignificant in comparison to the amount produced by animals in stables. Scenario for fish farms Drugs are usually added with feeding tablets both for therapeutic and non-therapeutic use in fish farms. The drugs may be ingested by the fish or lost to the detritus or directly to the sediments. The non-ingested part may be as high as 80-90%. Depending on the solubility of the drug it will be associated with different pools. Water soluble VMPs are mainly associated with the the water phase, and generally have a high mobility in the system. Lipophilic compounds on the other hand are connected to the organic pools of the system, i.e. in the lipids of fish, in detritus or in sediments.

2.3 Summary and conclusions

No public available database exists with information on the therapeutically use of veterinary medicines in Denmark. This report estimates the amount used based on data from 1996 and 1997 received by the Danish Medicines Agency (DMA).

The Danish Plant Directorate (DPD) has since 1986 calculated the annual consumption of growth promoters and medicines for feed additives on single active substance level as kg active substance per year. This register is available for the public, but includes only the total quantity of growth promoters in Denmark. It would improve the usefulness if data was divided into species level and post boundary practise.

Data for A and B labelled therapeutically used substances is included in this report. The sale of V labelled substances, such as antiparasitic drugs and H labelled compounds, such as acetylicaceticacid, are not registered. The quantity of antiparasitic drugs used is most likely significant.

Data from the DMA showed the following use for therapeutic applications in 1997: 14 tonnes of active substances for diseases associated with the alimentary tract and metabolism, 29 kg of active hormones, 230 kg of CNS-active substances, 236 kg of antiparasitic drugs and 48.5 tons of antibiotics.

Data from the DPD showed that in 1997 more than 107 tons of antibiotics were used non-therapeutically. Another 1.7 tons were used as feed administrated drugs in 1997.

17 tons of active substance was used as coccidiostatic in the production of poultry.

The total therapeutic and non-therapeutic application of antibiotics thus exceeded 170 tons in 1997. This amount also includes, although considered as a minor part, application for pets.

The main environmental route of exposure for veterinary medicines entering the environment is through the faeces and urine of treated animals.

 

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