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Environmental Assessment of Veterinary Medicinal Products in Denmark

4. Ecotoxicological effects of veterinary medicinal products

Assessments of environmental effects of veterinary medicinal products have only recently been required prior to the marketing of new products. This has contributed to the relatively low number of published studies dealing with environmental effects of veterinary medicinal products (van Gool, 1993 and Halling-Sørensen et al. 1998). Ecotoxicological effects of veterinary medicines are summarised in Table G, Appendix G, and briefly reviewed below.

Bacteria

One of the most widely used groups of veterinary medicinal products, the antibiotics, is specifically designed to control bacteria in animals. Obviously this makes them potentially hazardous to bacteria and other microorganisms in the environment (Warman 1980, Pursell et al. 1995). Antibiotics may have a broad spectrum of activity or designed to be either specifically active against gram negative or gram positive bacteria. Processes affected may therefore include more specific but environmentally important processes like the nitrification, which is driven solely by a few gram-negative bacteria species, or more general processes such as decomposition of organic matter, which is a co-operation between a conglomerate of different types of micro-organisms. When evaluating the effect of antibiotics towards the microbial community it is hence important to keep in mind that the type of target organisms vary between antibiotics. The types of veterinary antibiotics used in Denmark and the target bacteria for each group of substances are given in Box 4.1 and Table 4.1.

4.1 The aquatic environment

Phytoplankton

Streptomycin prevented growth of six blue-green algae species at concentrations from 0.09 to 0.86 mg/l (Harrass et al. 1985). The blue-green algae was generally more sensitive than the green algae tested. Chlorella vulgaris, Scenedesmus obliquus and Ulothrix sp. grew in active streptomycin concentrations less than 21 mg/l, while Chlamydomonas reinhardtii growth was prevented at concentrations of 0.66 mg/l. Algae growth in sublethal concentrations of streptomycin was slowed or delayed, and the maximum density attained by several species was decreased. Result published by Lanzky and Halling-Sørensen (1997) showed that Chlorella sp. are sensitive (EC₁₀ = 2.03 mg/l and EC₅₀ = 12.5 mg/l ) to metronidazole (which is used in fish farms).

Crustaceans/copopods

The acute toxicity of furazolidone, 3-[(5-Nitrofurfurylidene)amino]-2-oxazolidinone, which are largely used in medicated fish feed, have been investigated by Macrì et al (1988). The authors found a significant toxicity of the compound to Daphnia magna, while Artemia salina proved to be the less sensitive. Migliore et al. (1997) showed a toxicity of several agricultural antibiotics to Artemia. Acute toxicity studies showed that the four antibiotics; aminosidine, bacitracin, erythromycin and lincomycin, all used as feed additive or mass therapy in intensive farming, were only slightly toxic to Dapnia magna (Dojmi di Delupis et al. 1992). EC₅₀ values after 48 hours was found in the range of 30 mg/l to 500 mg/l with bacitracin as the mosttoxic.

Fish

Only very little information are outlined in the literature concerning the effects of medicines on fish species. Acute test on Bradio rerio with metronidazole showed no effect on the survival (Lanzky and Halling-Sørensen 1997).

Box 4.1.
Types of veterinary antibiotics used in Denmark.

Table 4.1.
The target bacteria and the most common use of different groups of antibiotics in Denmark. Brackets () indicates that only a few substances within the group is affecting the indicated group of bacteria.

Tabel 4.1.
Virkningsspekter for antibiotika anvendt i Danmark. Bakterietyper i parentes () betyder at det kun er et begrænset antal bakteriearter i gruppen som påvirkes.

Group of antibiotic	Therapeu-tic use	Growth promotor	Gram negative	Gram positive
Aminoglycosides	X		X
Beta-lactam	X		(X)	X
Flavomycins		X		X
Ionophors		X		X
Lincosamides	X		(X)	X
Macrolides	X	X		X
Oligosaccharides		X		X
Polypeptides	X	X		X
Quinolones	X		X	(X)
Quinoxalines		X	X
Sulfonamides	X		X	X
Tetracyclines	X		X	X

4.2 The terrestrial environment

Plants

Batchelder has tested the effects of the antibiotics chlortetracycline and oxytetracycline on plants when grown in both a nutrient solution media (Batchelder 1981) and in soils (Batchelder 1982). Two greenhouse studies were conducted to evaluate the effects on pinto bean plants (Phaseolus vulgaris) grown in aerated nutrient media and in soil. Root growth and development were markedly decreased by both antibiotics as their concentrations were increased from 0 to 160 ppm in solution. Top dry weights were reduced 71 - 87 % by the antibiotic concentrations, and root dry weight were decreased 66 - 94%. Plant mortality increased as the antibiotic concentration were increased and all plants died at the 160 mg L^-1 treatment level. The results showed that relatively low antibiotic concentrations can markedly affect pinto bean plant growth and development in nutrient solution. In the study using soil as growth media Batchelder (1982) found a large variation of the sensitivity among plant species. The most sensitive plant species was pinto beans when grown on sandy loam soil. Pinto beans were severely affected by antibiotics when the soil was watered with solution containing up to 160 mg tetracyclines L^-1. Phenothiazine has been implicated in deleterious changes in the botanical composition of pastures (Southcott 1988).

Insects

Since the 1970s is has been known that antiparasitic drugs excreted by animals could adversely affect the development and survival of non-target organisms, important in the process of dung degradation and nutrient cycling. Whereas drugs such as piperazine, thiabendazole and levamisole has little or no effect on beetles breeding in dung, formulations of coumaphos, dichlorvos and phenothiazine adversely affected their survival and reproduction for at least 4 to 5 days after treatment (Blume et al. 1976). Residues of dichlorvos has been shown to delay dung degradation (Lumaret 1986). The 1980´s saw the introduction of a new class of compounds known as macrocyclic lactones. This group, which includes avermectins (doramectin, abamectin and ivermectin) and milbemycins (moxidectin), are to a large extend excreted in the faeces of treated livestock as unaltered drug. Abamectin and ivermectin have been reported to have effects on a wide range of arthropods. In the late 80´s Wall and Strong (1987) discovered that residues of ivermectin in cattle dung had lethal effects on beneficial dung degrading insects and hence delayed the dung degradation. The environmental effects of ivermectin has later been investigated by others, e.g. Sommer C. (1992a; 1992b;1992c), Madsen et al. (1990) and Holter (1993). Research have shown that the duration of effects after treatment of ivermectin on dung degrading organisms is depended on the non-target species (beetles, flies, earthworms), form of drug application, and livestock species. By studying the number and development of immature dung beetles (Onthophagus gazella), Sommer & Nielsen (1992) showed a nearly 100% larvicidal effect of ivermectin (1.6 mg kg^-1, d.w.) in dung collected one week after treatment. In dung voided 17 days after treatment only half of the larvae were able to survive, although the ivermectin concentration had dropped to 0.3 mg kg^-1 (d.w.). Madsen et al. (1990) observed the effects of ivermectin on two species of flies in dung from treated heifers. No chemical analysis of the dung was performed, but results from the laboratory studies showed that the face fly Musca autumnalis was more sensitive to ivermectin than the house fly Musca domestica, and that dung excreted 40 days after treatment still killed 50% of the fly larvae.

Mosquito Larvea

Macrì et al. (1988) showed that furazolidone had a significant toxic effect on the mosquito larvae Culex pipiens.

4.3 Summary and conclusions on environmental effects of veterinary medicines

The literature primarily includes effect studies on acute toxicity of antibiotics in the aquatic environment and effects of antiparasitic agents on dung/soil fauna.

Antibiotics are generally toxic to algae, but less toxic to crustaceans and fish. Especially the blue-green algae seems very sensitive to some antibiotics

Many studies have shown that antiparasitic drugs may be lethal for beneficial insects living in dung voided several weeks after treatment of cattle. Only a single study has investigated effects of ivermectin on earthworms.

Information is generally lacking on the long term ecotoxicological effects and on the ecological consequences of a continuous environmental exposure, e.g. in the cases of boli slowly releasing antiparasitic drugs during an entire grazing season.

The environment will often be exposed to many drugs and/or other hazardous chemicals simultaneous. However, generally very little is known about the resulting total environmental hazard, risk and impact of simultaneous occurring chemicals, including veterinary drugs.

Compared to industrial chemicals which often have a general narcotic mode of action, veterinary medicines generally have a specific mode of action. In the light of the limitations of the existing standardised test battery for evaluating the environmental hazard and risk of veterinary drugs, new and more appropriate test methods may be needed. Such new tests should, however, be validated and standardised before widely employed.

 

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