Abstract
As part of the risk assessment of veterinary pharmaceuticals, the potential impact of these chemicals on soil ecosystems has to be determined according to European law. However, almost no data from standardized laboratory tests are available. Therefore, in the EU FP6 ERAPharm, the effects of the widely used veterinary pharmaceutical ivermectin, an anthelminthic, were studied in chronic laboratory tests performed according to OECD (Organisation for Economic Co-operation and Development) and ISO (International Organization for Standardization) guidelines. In detail, three soil invertebrate species—the earthworm Eisenia fetida, the springtail Folsomia candida, and the predatory mite Hypoaspis aculeifer—were tested. The nominal concentrations of ivermectin mixed into the test substrate artificial soil was verified using residue analysis, which indicated that the test substance is persistent for at least up to 28 days. As expected when considering the mode of action of this substance, survival and reproduction of collembolans were clearly affected [LC50 = 8.4 mg/kg soil dry weight (dw); NOECrepro = 0.3 mg/kg soil (dw)]. Predatory mites reacted less sensitively [LC50 ≥ 31.6 mg/kg soil (dw); NOECrepro = 3.2 mg/kg soil (dw)]. Earthworm survival and reproduction were affected in the same order of magnitude as the predatory mites [LC50 ≥ 10 mg/kg soil (dw); NOECrepro = 2.5 mg/kg soil (dw)]. These results are in good agreement with the few data known from nonstandardized tests for the same or related soil invertebrate species. The results of these tests indicate that the effects of ivermectin on soil invertebrates—in particular, collembolans—cannot be excluded at field-relevant concentrations, as determined in a risk assessment according to VICH guidelines. More sophisticated higher-tier tests (e.g., in multispecies or semifield test systems) are recommended in order to assess the potential risk more accurately.
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References
Bloom RA, Matheson JC III (1993) Environmental assessment of avermectins by the US Food and Drug Administration. Vet Parasitol 48:281–294
Campbell WC, Fisher MH, Stapley EO, Albers-Schonberg G, Jacob TA (1983) Ivermectin: a potent new antiparasitic agent. Science 221:823–828
Duce IR, Scott RH (1985) Actions of dihydroavermectin B1a on insect muscle. Br J Pharmacol 85:395–401
Edwards CA, Atiyeh RM, Römbke J (2001) Environmental impact of avermectins. Rev Environ Contam Toxicol 171:111–137
EMEA (European Medicines Evaluation Agency) (2008) Revised guideline on environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 and GL38. EMEA/CVMP/ERA/418282/2005-Rev.1. Committee for Medicinal Products for Veterinary Use (CVMP), London
EU (European Union) (1991) Council directive concerning the placing of plant protection products on the market (91/414/EEC). European Union, Brussels
Finney DJ (1971) Probit analysis, 3rd edn. Cambridge University Press, London
Floate KD (1998) Off-target effects of ivermectin on insects and on dung degradation in southern Alberta, Canada. Bull Entomol Res 88:25–35
Floate KD, Wardhaugh KG, Boxall AB, Sherratt TN (2005) Fecal residues of veterinary parasiticides: nontarget effects in the pasture environment. Annu Rev Entomol 50:153–179
Gunn A, Sadd JW (1994) The effect of ivermectin on the survival, behaviour and cocoon production of the earthworm Eisenia fetida. Pedobiologia 38:327–333
Halley BA, Jacob TA, Lu AYH (1989) The environmental impact of the use of ivermectin: environmental effects and fate. Chemosphere 18:1543–1563
Hofman J, Hovorková I, Machát J (2009) Comparison and characterisation of OECD artificial soils. In: Moser H, Römbke J (eds) Ecotoxicological characterisation of waste. Results and experiences from an European ring test. Springer, New York, pp 223–229
ISO (International Organization for Standardization) (1999) Soil quality—inhibition of reproduction of Collembola (Folsomia candida) by soil pollutants. ISO 11267. ISO, Geneva
ISO (International Organization for Standardization) (2004) Soil quality—effects of pollutants on Enchytraeidae (Enchytraeus sp.). Determination of effects on reproduction and survival. ISO 16387. ISO, Geneva
Jensen J, Krogh PH, Sverdrup LE (2003) Effects of the antibacterial agents tiamulin, olanquindox and metronidazole and the anthelmintic ivermectin on the soil invertebrate species Folsomia fimetaria (Collembola) and Enchytraeus crypticus (Enchytraeidae). Chemosphere 50:437–443
Jensen J, Diao X, Hansen AD (2009) Single- and two-species tests to study effects of the anthelmintics ivermectin and morantel, and the coccidiostatic monensin on soil invertebrates. Environ Toxicol Chem 28:316–323
Krogh PH, Axelsen JA (1998) Test on the predatory mite Hypoaspis aculeifer preying on the collembolan Folsomia fimetaria. In: Løkke H, Van Gestel CAM (eds) Handbook of soil invertebrate toxicity tests. Wiley, Chichester, UK, pp 131–156
Krogh KA, Søeborg T, Brodin B, Halling-Sørensen B (2008) Sorption and mobility of ivermectin in different soils. J Environ Qual 37:2202–2211
Krogh KA, Jensen GG, Schneider MK, Fenner K, Halling-Sørensen B (2009) Analysis of the dissipation kinetics of ivermectin at different temperatures and in four different soils. Chemosphere 75:1097–1104
Liebig M, Alonso Fernandez A, Blübaum-Gronau E, Boxall A, Brinke M, Carbonell G, Egeler P, Fenner K, Fernandez C, Fink G, Garric J, Halling-Sørensen B, Jensen J, Knacker T, Krogh KA, Küster A, Löffler D, Porcel Cots MA, Pope L, Prasse C, Römbke J, Rönnefahrt I, Schneider MK, Schweitzer N, Tarazona JV, Ternes TA, Traunspurger W, Wehrhan A, Duis K (submitted) Environmental risk assessment of ivermectin: a case study. Integr Environ Assess Manag
Lumaret J-P, Errouissi F (2002) Use of anthelminthics in herbivores and evaluation of risks for the non target fauna of pastures. Vet Res 33:547–562
OECD (Organisation for Economic Co-operation and Development) (1984) OECD-guideline for testing of chemicals No. 207. Earthworm acute toxicity test. OECD, Paris
OECD (Organisation for Economic Co-Operation and Development) (2002) OECD-guideline for testing of chemicals No. 307. Aerobic and anaerobic transformation in soil. Paris, France
OECD (Organisation for Economic Co-Operation and Development) (2004) OECD-guideline for testing of chemicals No. 222. Earthworm reproduction test. OECD, Paris
OECD (Organisation for Economic Co-Operation and Development) (2006a) Guidance document for the statistical analysis of ecotoxicity data. No. 54. OECD, Paris
OECD (Organisation for Economic Co-operation and Development) (2006b) OECD series on testing and assessment No. 56. Guidance document on the breakdown of organic matter in litterbags. OECD, Paris
OECD (Organisation for Economic Co-Operation and Development) (2008) OECD-guideline for testing of chemicals No. 226. Predatory mite reproduction test in soil (Hypoaspis (Geolaelaps) aculeifer). OECD, Paris
Õmura S (2002) Mode of action of avermectin. In: Õmura S (ed) Macrolide antibiotics: chemistry, biology and practice. Academic Press, New York, pp 571–576
Õmura S (2008) Ivermectin: 25 years and still going strong. Int J Antimicrob Agents 31:91–98
Raich-Montiu J, Krogh KA, Granados M, Jönsson JÅ, Halling-Sørensen B (2008) Determination of ivermectin and transformation products in environmental waters using hollow fibre-supported liquid membrane extraction and liquid chromatography–mass spectrometry/mass spectrometry. J Chromatogr A 1187:275–280
Rohrer SP, Arena JP (1995) Ivermectin interactions with invertebrate ion channels. In: Marshall Clark J (ed) Molecular action of insecticides on ion channels. American Chemical Society, Washington, DC, pp 264–283
Römbke J, Moser T (2002) Validating the enchytraeid reproduction test: organisation and results of an international ringtest. Chemosphere 46:1117–1140
Römbke J, Heimbach F, Hoy S, Kula C, Scott-Fordsmand J, Sousa P, Stephenson G, Weeks J (eds) (2003) Guidance document: effects of plant protection products on functional endpoints in soil (EPFES). SETAC Publishing, Pensacola, FL
ToxRat® (2003) Software for the statistical analysis of biotests. ToxRat® Solutions GmbH, Alsdorf, Germany
VICH (International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products) (2004) GL38. Environmental impact assessments (EIAs) for veterinary medicinal products—Phase II. CVMP/VICH/790/03. European Medicines Evaluation Agency, London
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This work was funded by the European Union under the 6th framework program in the STREP ERAPharm (SSPI-CT-2003-511135). The views expressed herein by the authors do not necessarily reflect the views or policies of their respective agencies.
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Römbke, J., Krogh, K.A., Moser, T. et al. Effects of the Veterinary Pharmaceutical Ivermectin on Soil Invertebrates in Laboratory Tests. Arch Environ Contam Toxicol 58, 332–340 (2010). https://doi.org/10.1007/s00244-009-9414-8
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DOI: https://doi.org/10.1007/s00244-009-9414-8