Use of Anthelmintics in Herbivores and Evaluation of Risks for the Non Target Fauna of Pastures

Vet. Res. 33 (2002) 547–562  INRA, EDP Sciences, 2002 547 DOI: 10.1051/vetres:2002038 Review article

Use of anthelmintics in herbivores and evaluation of risks for the non target fauna of pastures

Jean-Pierre LUMARET*, Faiek ERROUISSI

Laboratoire de Zoogéographie, Université Paul Valéry-Montpellier 3, route de Mende, 34199 Montpellier Cedex 5, France

(Received 14 January 2002; accepted 30 April 2002)

Abstract – The overall purpose of this paper was to review the major and most recent literature relat- ing the effects of anthelmintics on dung breeding invertebrates and dung degradation. Faecal residues or metabolites of drugs belonging to the benzimidazole and levamisole/morantel groups are relatively harmless to dung fauna, on the contrary to other anthelmintics such as coumaphos, dichlorvos, pheno- thiazine, piperazine, synthetic pyrethroids, and most macrocyclic lactones which have been shown to be highly toxic for dung beetles (abamectin, ivermectin, eprinomectin, doramectin), among which moxidectin was the less toxic for dung beetles. To date, the detrimental impact upon non-target organisms has been considered acceptable in eradicating the parasites because of their economic importance to commercial livestock production. The consequences of routine treatments are discussed with consideration of the long-term consequences for cow pat fauna and sustainable pastureland ecology. anthelmintic / residue / dung beetle / Diptera / sustainable parasite control

Résumé – Usage des anthelminthiques en élevage et évaluation des risques pour la faune non cible du pâturage. Cet article de synthèse passe en revue les travaux de la littérature les plus récents concernant les effets secondaires des principaux produits vétérinaires utilisés en routine sur la faune coprophage et sur la dégradation des excréments dans les pâturages. Les résidus (ou les métabolites) des groupes du benzimidazole et levamisole/morantel trouvés dans les excréments s’avèrent relative- ment peu toxiques pour la faune coprophage. Au contraire les anthelminthiques des groupes suivants s’avèrent hautement toxiques: coumaphos, dichlorvos, phénothiazine, pipérazine, pyréthroïdes de synthèse, et la plupart des lactones macrocycliques (abamectine, ivermectine, éprinomectine, dora- mectine), la moxidectine étant la moins toxique pour la faune coprophage. Jusqu’à présent, cet impact négatif a été considéré comme acceptable par les éleveurs et firmes pharmaceutiques en regard de l’importance économique du contrôle et/ou l’éradication des parasites. Les conséquences des trai- tements de routine sont discutées en considérant que l’absence de dégradation des bouses constatée

*Correspondence and reprints Tel.: (33) 4 67 14 23 16; fax: (33) 4 67 14 24 59; e-mail: [email protected] 548 J.P. Lumaret, F. Errouissi localement peut malgré tout s’accompagner d’une érosion silencieuse de la biodiversité, avec un dé- séquilibre à long terme du fonctionnement des pâturages. anthelminthique / résidus / coléoptère coprophage / diptère / contrôle raisonné des parasites

Table of contents

1. Introduction...... 548 2. Pharmacokinetics and routes of elimination...... 549 3. Concentration, stability and activity of anthelmintics in the faeces; effects on non-target dung-feeding fauna ...... 550 4. Influence of anthelmintics on dung degradation ...... 554 5. Indirect effects of antiparasitic use ...... 556 6. Conclusion ...... 556

1. INTRODUCTION affect the development and survival of non-target organisms in estuarine and ma- Over the past decade, concerns have rine ecosystems [17, 18, 23, 36, 37]. been increasingly expressed by the scien- The development of anthelmintics and tific community regarding the possible un- latterly endectocides with a broad range of intended side effects of chemicals used in target pathogens has provided more effi- veterinary and agricultural practices and, cient and economic options for the treat- more particularly, in the widespread use of ment and control of parasitic disease both in the macrocyclic lactone class of chemicals ruminant and monogastric animals. In pas- such as anthelmintics used to control gas- tures, most antiparasitic agents are ex- trointestinal parasites of grazing livestock creted, to some extent, in the faeces of and companion animals. In the scientific treated animals, creating a concern for their community there is a lack of consensus effect on the organisms that feed and/or over the potential of macrocyclic lactone breed in animal excrements. As the spec- residues, excreted in the dung of treated an- trum of activity of the antiparasitic agents imals, to harm dung beetles that utilise this has enlarged, the potential for affecting dung. Scientists do not agree on the extent non-target organisms has increased equally of such risks, mainly because of the com- [81]. Many of the non-target organisms plex dynamics of insect populations that play a vital role in the processes of dung fluctuates widely according to factors such dispersal. They are crucial for maintaining as climatic fluctuations, rainfall, cattle pasture hygiene, nutrient cycling, soil aera- management and pasture quality [6, 98]. tion, humus content, water percolation and This situation has raised concerns not only pasture productivity. In addition, they also for the possible impact on dung degradation ensure that the livestock grazing area is not but also for the consequences on pastu- drastically reduced by an accumulation of reland insect communities and ecosystem dung [50]. In the cow dung community, stability and on the sustainability of pasture dung feeder flies [42], coprophagous bee- fertility [8, 41, 50, 64, 68, 81, 107, 115, tles [43, 44, 53] and annelid worms [54, 55, 117]. At the same time, it has been shown 85] are the most important organisms. Un- that modern anthelmintics also adversely der warm and dry climate conditions, dung Use of anthelmintics and risks for the fauna 549 beetles appear the most important organ- some anthelmintics on non-target inverte- isms to degrade dung pats, while earth- brates. Faecal residues or metabolites of worms predominate both in activity and drugs belonging to the benzimidazole and biomass under temperate and more mesic levamisole/morantel groups are thought to conditions [85]. Earthworms aggregate un- be relatively harmless to dung fauna [81, der dung pats [15] and it has been demon- 110], on the contrary to other anthelmintics strated that dung is readily eaten and such as coumaphos, dichlorvos, phenothi- removed from the surface by these organ- azine, piperazine [12, 64], synthetic isms which are therefore presumed to play pyrethroids [10, 115], and most macrocyclic an important role in the decay and disap- lactones [25, 50, 99, 100, 102] which have pearance of dung [38]. However, it has been been shown to be highly toxic for dung bee- shown that earthworm activity in pats may tles. strongly depend on beetle occurrence and Several factors can modify the environ- activity. Beetles rapidly colonise and mental risks: (i) The amount of the active oviposite in dung pats in the first few days agent which enters the environment; this after they are dropped, facilitating the ini- amount depends on the route or delivery tial breakdown of dung and allowing the system of administration [50], and on the subsequent entry of earthworms which physiology of the treated animals [3, 4]; continue to degrade the dung [15, 38, 55, (ii) The concentration and persistence of 107]. The occurrence of many species is fa- the drug in the faeces, and the total amount cilitated by the activities of other species of droppings from treated animals com- which colonise droppings earlier. When pared to the total faecal deposits in the pas- beetles utilise dung pats, they dig small tun- ture [30, 81]; (iii) Environmental factors nels which weaken the pats and, at the same (light, rainfall, temperature…) and the co- time, beetles inoculate the heart of pats with incidence of deposits with activity of microorganisms as they carry spores of tel- non-target organisms [30, 41]; (iv) The sus- luric fungi and microorganisms on their in- ceptibility of organisms, some taxa are tegument. Consequently, the presence of more susceptible than others, and some are beetles stimulates the microbial activity. highly resistant [24, 25, 28, 29, 35, 39, 41, Normally, about 80% of the ammonia re- 112, 113]. lease from dung pats is lost during the first five days, but when sufficient numbers of In the present paper, the environmental beetles are present for quick burial, the loss effects and fates of anthelmintics are re- is reduced to 5–15% and permits the use of viewed from data collected for the registra- this N by plants for up to two years. Under tion of some compounds and from scientific such conditions, pats become progressively literature. soil annexes, with the network of tunnels making colonisation of pats by edaphic fauna easier [25]. Tunnels made by beetles 2. PHARMACOKINETICS improve the oxygen supply to copro- AND ROUTES OF ELIMINATION phagous flies but also provide runways so predatory Staphylinids can get at the flies In a recent and exhaustive report, [105]. Dung burial by beetles decreases Wardhaugh [110] reviewed the parasiti- wastage of herbage through the rejection of cides registered for use in cattle in Austra- fouled herbage and smothering of pasture lia. The author gave information on the leaf area [68]. excretion route and insecticidal activity of particular chemicals and cites literature that There is now a considerable amount of contains relevant information. The main data on the risks of the adverse effects of delivery routes of these parasiticides are 550 J.P. Lumaret, F. Errouissi oral, pour-on, injectable, sustained-release higher ivermectin concentration has been bolus, back-liner, back-rubber, back-spray, reported in cattle dung, when a topical and ear tag. Endectocides (e.g. abamectin, pour-on formulation was used as compared moxidectin, doramectin, ivermectin, and with an injectable formulation; however eprinomectin) are mostly delivered through both formulations showed comparable per- injectable, sustained-release bolus and sistency [95]. Sustained-release bolus pour-on, while the delivery routes of mostly concerns ivermectin, morantel and ectocides are more diverse. benzimidazoles. According to the manu- facturer, each bolus of ivermectin given to a Levamisole and albendazole are mainly 150–450 kg calf contains 1.72 g of the ac- eliminated in the urine [12, 47, 86], while tive molecule which is released by an os- the principal elimination route of motic pump at a rate of about 12 mg·day–1 oxfendazole, fenbendazole, and morantel over 135 days. The high levels of concerns the faeces, without significant in- ivermectin recovered in cattle faeces indi- secticidal activity on non-target fauna [46, cate that a large proportion of the dose re- 48, 64, 82, 103]. Macrocyclic lactones are leased by the bolus (80 to 90%) is excreted primarily excreted in the faeces, with no- in the faeces [4]. This route of administra- ticeable insecticidal activity on non-target tion and elimination is potentially more dis- organisms. This concerns abamectin [56, ruptive to the pasture ecosystem than any 86, 88], ivermectin [14, 29, 59, 68, 88, 96, other formulation because of their slow re- 103, 107, 112], eprinomectin [109, 117], lease and extended period activity [53]. doramectin [32, 93, 98] and moxidectin Ivermectin is not metabolised in the rumen [28, 58, 98, 101, 109, 114, 120]. Insecti- and a significant part of the drug may pass cidal activity in the faeces was noticed with down the gastrointestinal tract into the fae- synthetic pyrethroids (alpha-cypermethrin ces without absorption into the systemic [10, 11], flumethrin [10], cypermethrin [10, circulation [5]. Oral formulations (oral 11, 61], deltamethrin [10, 33, 106, 115], paste or drench formulations) of ivermectin cyhalothrin [10, 11], permethrin [33], for sheep and horses have less fenvalerate [91]) and organo-phosphates, bioavailability and persistence than the in- e.g. dichlorvos [64]. Other chemicals used jectable formulation for cattle [50, 65, 76]. in cattle also showed insecticidal activity in Herd [50] estimated that this formulation faeces, e.g. diflubenzuron [26], clorsulon had fewer environmental effects, although [104], triflumuron [83] and methoprene the use of an oral paste for horses still re- [26]. sulted in a significant delay in dung degra- Injectable or subcutaneous formulations dation rates [52]. of endectocides promote a slow absorption of the drug from the subcutaneous injection site to produce an effective controlled re- 3. CONCENTRATION, STABILITY lease formulation [63] and to extend the pe- AND ACTIVITY riod of high plasma concentration [50]. OF ANTHELMINTICS Intramuscular injection of ivermectin is an IN THE FAECES; EFFECTS oil-based formulation, which increases the ON NON-TARGET lipophilicity of the drug and promotes a DUNG-FEEDING FAUNA slow release from the injection site and a longer mean residence time in the animal In laboratory studies, dung from sheep when compared to other formulations. Top- treated with an oral mixture of oxfendazole ical pour-on formulations of endectocides andlevamisolewasshowntobetoxicto are alcohol-based formulations and they are both fly and beetle larvae [113]. The mor- mainly administered using a high dosage. A tality was thought to be associated with the Use of anthelmintics and risks for the fauna 551 oxfendazole component since levamisole is [115] showed that residues of deltamethrin rapidly absorbed following oral, subcuta- (pour-on formulation) in cattle dung were neous or topical administration, and is rap- excreted in concentrations sufficient to in- idly and largely excreted unchanged in the hibit survival of larvae of the dung-breed- urine. However in field studies, using a ing fly Musca vetustissima for 7–14 days pulse release formulation delivering after treatment. Peak concentrations of 750 mg of oxfendazole, no evidence of any 0.4 mg deltamethrin·kg–1 dry weight of fae- effects of oxfendazole on the rate of dung ces occurred three days after treatment and degradation or on the numbers or weight of were sufficient to kill adult beetles earthworms in the pasture were found (Onthophagus binodis and Euoniticellus [119]. According to McKellar [81], the fulvus) for at least twice this period. benzimidazoles have relatively short residence times following single oral adminis- Studies on the potential ecotoxic effects tration and very low concentrations are of endectocides in the environment showed passed in the faeces within 36 h that these effects depend on animals (cattle, (thiabendazole), 96 h (albendazole) or 168 h horses, sheep), the formulation or delivery (oxfendazole, fenbendazole) after adminis- system in which endectocides are administration [73–75, 118]. The fenbendazole bolus tered, and the stages of the non-target or- delivers 67–103 mg of fenbendazole per ani- ganisms (either adults or larvae). Ivermectin mal per day with prophylactic activity for concentrations in faeces decline with time 140 days [89]. from approximately day 2 after subcutaneous or pour-on administration. Following The relative daily doses of morantel are the administration of 300 µg·kg–1 by the sub- 680–2300 mg per animal (oral drench) and cutaneous route, concentrations of ivermectin 50–150 mg per animal (sustained-release in the faeces declined from 8 µg·g–1 on day 2 bolus) [13]. Twenty-four hours after oral post-administration to approximately administration of morantel tartrate (which 2.5 µg·g–1 by day 7 post-administration [19]. is poorly absorbed following oral adminis- Following administration to cattle of a sus- tration) at 10 mg·kg–1 bodyweight, the con- tained-release bolus prepared to deliver centration of morantel in the faeces ivermectin at a low daily dosage for collected from cattle were > 10 µg·g–1 (dry 135 days, the faecal ivermectin concentra- weight) [82]. Morantel did not affect the de- tion dropped to a steady-state concentration velopment of the yellow dung fly in the fae- of around 1.18 µg·g–1 which was main- ces from treated cattle [82]. tained up to 120 days post-treatment [4]. Ivermectin was detected in both plasma When cattle were treated with the (0.05 ng·mL–1) and faeces (2.67 ng·g–1)up pyrethroid flumethrin pour-on at the rec- –1 to 160 days. This faecal excretion of high ommended dose (1 mL·10 kg ), the results ivermectin concentrations for prolonged indicate that flumethrin did not affect the periods after bolus administration to cattle degradation of the dung pats exposed in the may represent a special threat to the ecosys- field 1–28 days after treatment compared tem. with the pats of the control group [60]. However this result is not consistent with In horses, the comparison of the faecal the findings of Bianchin et al. [10] on the le- excretion profile of moxidectin and thal effects of flumethrin residues in faeces ivermectin after oral administration showed on adult dung beetles of Onthophagus that ivermectin remained above the detect- gazella, a species also present in the previ- able level for 40 days (0.6 ± 0.3 ng·g–1), ous trial area: field observations made by whereas moxidectin remained detectable farmers showed beetles dying after applica- for 75 days (4.3 ± 2.8 ng·g–1)[84].Ivermectin tion of the parasiticide [60]. Wardaugh et al. presented a faster elimination rate than 552 J.P. Lumaret, F. Errouissi moxidectin, reaching 90% of the total drug the main differences between moxidectin and excreted in the faeces at four days post-treat- ivermectin are related to physicochemical ment, whereas moxidectin reached similar differences that explain their pharma- levels at eight days post-treatment. No signif- cokinetic and metabolic characteristics [84]. icant differences were observed for the val- The differences observed in anthel- ues of maximum faecal concentration mintic efficiency between both drugs can (C max) and time of C max between both be extrapolated to their environmental im- groups of horses, demonstrating similar pact on dung fauna. According to Herd [50] patterns of drug transference from the the experiments reported in several coun- plasma to the gastrointestinal tract. The val- tries indicate that moxidectin is ecologi- ues of the area under the faecal concentra- cally safer than ivermectin. It has been tion time curve were slightly higher in the reported that 200 µg·kg–1 b.w. of moxidectin treatment group (7 104 ± –1 moxidectin in cattle had no adverse effects 2 277 ng·day·g ) but were not significantly on adult emergence of the dung beetles different from those obtained in the ± Onthophagus gazella and Euoniticellus ivermectin treatment group (5 642 intermedius, whereas ivermectin residues 1 122 ng·day·g–1). The concentration in the ± in the faeces significantly reduced the adult faeces only represented 44.3 18.0% of the emergence [28]. Moreover, a comparative total parental drug administered compared ± study carried out on steers [114] demon- to 74.3 20.2% for ivermectin. This sug- strated that dung residues in the faeces col- gests a higher level of metabolization for lected 3–35 days after treatment with an moxidectin in horses [84]. injectable formulation of moxidectin Studies on the potential ecotoxic effects (200 µg·kg–1) had no significant effects on of endectocides led intense interest in eluci- the survival of larvae of Musca vetustissima dating the fate of these drugs in the faeces or M. domestica. In contrast, ivermectin [4, 25, 28, 50, 66, 107, 112, 113]. The envi- treated steers produced dung that inhibited ronmental impact of antiparasitic chemo- larval development of both M. vetustissima therapy depends on the deleterious effects and M. domestica for a period of 14 days af- which the agent or its metabolites have on ter treatment. an organism in the locus of excreta, the In horses, Lumaret [66] demonstrated amount of the active agent excreted, the significant adverse effects on the fly temporal nature of excretion and the stabil- Neomyia cornicina for five days after oral ity of the ecotoxic residues [81]. The faecal treatment with moxidectin administered in concentration levels of ivermectin found in doses of 400 µg·kg–1 whereas the adminis- horse droppings [84] were all above con- tration of a dose of 200 µg·kg–1 of centrations that are lethal or sublethal to ivermectin had effects for 21 days. These many dung breeding invertebrates of bene- differences could explain why moxidectin fit to the ecosystem [50, 100]. It has been can attain prolonged and persistent concen- demonstrated that ivermectin concentra- trations in faeces although its environmen- tions as low as 0.001 µg·g–1 (1 ng·g–1)wet tal effects may be shorter than those weight are toxic to some dung breeding in- observed in ivermectin treated animals. sects [101]. In sheep, the oral administration of Although greater persistence of faecal moxidectin results in initial faecal concen- excretion was obtained in the horses treated trations that are 10 times higher than those with moxidectin, these results do not neces- observed in cattle after subcutaneous injec- sarily signify that moxidectin is more tion, but by seven days the levels in both ecotoxic than ivermectin, particularly on sheep and cattle are similar. At this stage, the dung degradation fauna [50]. Probably, the cumulative excretion accounts for 43% Use of anthelmintics and risks for the fauna 553 of the dose and parent moxidectin com- activity and females had a greatly reduced prises 25% of the total residues in sheep fat accumulation and distended guts with faeces [1]. The faecal excretion of orally unusual contents after feeding for 43 days administered ivermectin by sheep is more on dung collected after ivermectin treat- rapid. By seven days, the faecal residues ac- ment [112]. Ivermectin residues in sheep count for 69% of the dose and 61–69% of dung also increased the mortality of newly these residues are present as the parent drug emerged Euoniticellus fulvus when feeding [40, 76]. Other studies have shown 95% re- for 10 days on faeces voided during the covery of the total dose in the faeces of first day after drenching, but not subse- sheep seven days after intra-ruminal ad- quently [113]. Conversely, sexually ma- ministration [2], two-thirds of this being re- ture adults of Anoplotrupes stercorosus covered during the first two days [98]. The (Col. Geotrupidae) feeding on horse drop- presence of ivermectin residues in sheep pings collected immediately following oral droppings after oral administration influ- ivermectin treatment showed no apparent enced the survival of fly and beetle larvae toxicological effect [65]. for less than a week after treatment, but such transient effects were unlikely to have On the contrary to adults, the larval a major impact on insect populations [113]. stages of dung beetles are highly suscepti- However, the recent introduction of con- ble to avermectin residues in cattle and trolled-release capsules of ivermectin for sheep dung. An increased larval mortality, sheep have modified previous conclusions in many instances up to 100%, has been ob- [116]. The capsule releases a measured served in dung collected during the first amount of ivermectin each day and oper- weeks or months after treatment [98]. De- ates for 100 days. No fly larvae and almost layed larval development has been re- no beetle larvae survived in sheep faeces corded in Onthophagus gazella [27, 86, collected up to 39 days after capsule admin- 94], whilst the morphology of the head cap- istration. Newly emerged Onthophagus sules of dead larvae indicated that toxicity taurus (Coleoptera: Scarabaeidae) also suf- occurred at the first instar stage; the exami- fered significant mortality whereas those nation of surviving third-stage instars from who survived underwent delayed sexual day seven dung indicated sub-lethal effects maturation [116]. Ivermectin residues had of ivermectin residues [94]. The effects of no effect on the survival of sexually mature cattle treatment (two trials) with ivermectin beetles, but reduced the fecundity of slow-release (SR) bolus were monitored on O. taurus. the larval development of the dung beetle Aphodius constans Duft. (Col. Aphodiidae) In most cases, the mortality of sexually [25]. In the first trial, faecal ivermectin con- mature adults was unaffected although an centration reached a peak at 63 days increased mortality and a slower rate of post-treatment (1 427 ng·g–1) and ivermectin ovarian development were recorded in the was detected up to 147 days post-treatment newly emerged dung beetle Onthophagus (7.2 ng·g–1). In this trial, ivermectin prevented binodis feeding for an extended period of the development of larvae A. constans (100% eight weeks on the dung of cattle treated mortality) until day 105, while at day 135 the with abamectin [86]. Similarly, an in- rate of emergence was still significantly creased mortality of newly-emerged Copris lower than the control. In the second trial, hispanus and Onitis belial adults has been the difference between the control and the recorded after feeding for 14 days on dung treated series remained significant until containing ivermectin residues collected up 143 days post-treatment, with no emergence to eight days after treatment [112]. Copris until 128 days post-administration of the hispanus displayed a suppressed feeding SR bolus to cattle [25]. 554 J.P. Lumaret, F. Errouissi

The toxicity of macrocyclic lactone resi- ers of the soil, where climatic conditions influ- dues to the development of eggs and larvae ence the activity of dung-breeding insects of dung breeding flies has been extensively (Scarabaeidae, Hydrophilidae, Staphylinidae, examined, since many species are consid- larvae of Diptera) [67]. When beetles exploit ered as pests. The larval development of the dung pats, they dig small tunnels, which house fly Musca domestica and the bush fly weaken the pats and, at the same time, beetles Musca vetustissima are significantly affected inoculate the heart of pats with microorgan- for up to four weeks after subcutaneous isms as they carry spores of telluric fungi and ivermectin treatment of cattle (0.2 mg·kg–1) microorganisms on their integument. Conse- [70, 86, 113, 114]. Adult females of the quently, the presence of beetles stimulates sheep blowfly Lucilia cuprina exhibited the microbial activity [16, 69]. It is also impaired ovarian development, reduced fe- well known that the dung-breeding Diptera cundity and reduced survival when fed con- assists in breaking down cattle dung pats tinuously on sheep dung collected within [45]. Under such conditions, pats progres- 24 hours of oral treatment with ivermectin, sively become soil annexes, the network of whereas adult males showed aberrant mat- tunnels making the colonisation of pats by ing behaviour [20, 21, 71, 72]. The face fly edaphic mesofauna easier. The artificial ex- Musca autumnalis showed a 14–46 day pe- clusion of both flies and beetles from fresh riod of reduced larval development [70, cattle dung pats for only one month after the 96], on the contrary to the stable fly deposition of pats considerably lowers the Stomoxys calcitrans where less toxic ef- rate of decay [67]. fects were observed after subcutaneous ivermectin treatment of cattle [90]. The ef- The alteration in the rate of degradation fects of ivermectin on Neomyia cornicina, has not been reported for faeces from ani- an obligate dung feeder, show similar dif- mals treated with benzimidazole, levami- ferences between cattle and sheep faecal sole and oxibendazole [52]. Krüger et al. residues, with larval development being re- [60] indicated that the fluomethrin did not ducedforupto32daysand7days,respec- affect the degradation of dung pats exposed tively, and with physiological modifications in the field 1–28 days after treatment of cat- [34, 35, 96, 112]. By contrast, dung col- tle compared with pats of a control group. lected as early as three days after the subcu- By comparison, Lumaret [64] investigated taneous treatment of cattle with moxidectin the impact of dichlorvos treatment of had no effect on the development of M. horses on dung degradation. Artificial fae- domestica and M. vetustissima larvae [24, cal copromes using dung collected two 114]. In addition, following oral moxidectin days after treatment disintegrated more treatment, residues in sheep faeces were slowly than those from untreated horses toxic to N. cornicina development for a (57% and 0% remanence respectively, after shorter period than those following oral an eight-month exposure in the field). Herd ivermectin treatment [66]. et al. [52] also reported a significant delay in dung dispersal when horses were treated with ivermectin. By the end of their study 4. INFLUENCE (eight months), there was a 24.7% reduc- OF ANTHELMINTICS ON DUNG tion in ivermectin copromes compared with DEGRADATION 59.1% and 59.9% for control and oxibendazole copromes, respectively. In The recycling of faeces is a complex addition, there were significantly more linkage of slow processes in which micro- copromes showing complete dispersal in organisms and the edaphic fauna intervene oxibendazole or control plots than in at the soil surface as well as in the upper lay- ivermectin plots. Use of anthelmintics and risks for the fauna 555

In Great Britain, in one trial in which of dung fly larvae plays a major role in dis- cattle were dosed with an experimental sus- rupting the integrity of dung during the first tained-release bolus delivering eight mg of weeks [98]. ivermectin daily, the faeces were shown to be highly toxic to dung feeding insects, the absence of which significantly retarded the In many countries farmers have adopted rate of dung pat degradation [107]. Dung strategic worm control programs and from cattle treated with ivermectin was anthelmintic usage tends to be seasonally solid and intact after 100 days due to non synchronous [108]. A model simulating the dung beetle activity. In Denmark, Madsen effects of drug residues on dung beetle pop- et al. [70] showed that the decomposition of ulations indicates that controlled-release dung pats from recently ivermectin treated capsules of ivermectin have the potential to heifers was delayed within the first three cause substantial declines in beetle num- weeks when compared with a control. bers, particularly if the treatment coincides However no adverse effects of treatment with the spring emergence of beetles [110]. were recorded on earthworms and the re- In the same way, a model of the effect of tarded decomposition rate was ascribed to deltamethrin on the breeding success of the adverse effects on the primary dipteran dung beetles in the field suggests that a sin- decomposing fauna. Similarly in Canada, gle pour-on treatment of this drug may re- Floate [29] reported that insect activity was duce beetle activity in the next generation significantly reduced in dung from cattle by more than 70% if the time of application treated with a recommended dose coincides with peak beetle emergence in (500 µg·kg–1) of ivermectin. Reduced in- spring. Two or more successive treatments sect activity was associated with slower at three weekly intervals had the potential to drive beetle populations towards local dung pat degradation. When ivermectin extinction unless there is significant immi- was added directly to the dung, at levels gration from surrounding untreated areas previously reported to occur in dung from [115]. A similar situation was described in treated cattle, the treated dung was not ap- Mexico with a herbicide widely used to preciably degraded after 340 days in the control weeds in pastures, which drove lo- field. In contrast, untreated dung pats de- cal dung beetle populations towards extinc- posited at the same time and place were tion (due to drastic reduction in female largely degraded after 80 days in the field fecundity) when the herbicide was applied [29]. In Australia a field study confirmed during the beetle breeding period [77]. the above observations [22]. However, the Forbes [30] reasoned that, at any one time potential of ivermectin use to affect pasture in the field, only a small proportion of dung quality has been the subject of consider- pats would contain residues of ivermectin, able, and ongoing, debate [31, 50, 51], hence beetles can easily move to an un- since other experiments were unable to de- treated pat. However this does not discount tect any significant change in degradation the possibility of sublethal effects due to rate or in the long-term accumulation of short-term exposure of ivermectin residues dung in the field following treatment with [22]. During the warmer months of the year, ivermectin [7, 8, 119]. The differences in beetles move from pat to pat every two to the results may reflect the diversity of the four days, particularly when they are abun- dung-feeding fauna of the various coun- dant and/or immature [87]. Thus in situations tries. The high sensitivity of many Diptera in which the whole herd may be treated, the to avermectins may explain the negative ef- chance that beetles will contact toxic faeces fects of residues in faeces, since the activity will be very high. 556 J.P. Lumaret, F. Errouissi

5. INDIRECT EFFECTS which the damage influences pastureland OF ANTIPARASITIC USE ecology, with often a lack of consideration of long-term consequences for cow pat insects [100]. The second problem concerns cow pat Insects which breed exclusively in the breakdown and the possibility of pasture dung of herbivores, in which anthelmintics fouling. The sub-lethal responses of are used, are liable to suffer adverse effects. non-target fauna are induced at drug con- Common species could suffer local extinc- centrations below those measured several tion but would be able to recolonise any days after a standard absorption of the such area [79]. However rare species may anthelmintic, but the use of a sustained-re- not have this recolonisation potential and leased bolus will considerably increase the therefore could be put at risk by the use of sub-lethal responses. If the reproductive avermectins, and particularly when a performance of the surviving adults is im- slow-release bolus is used. As well as influ- paired, the full consequences will not be ap- encing the dung-inhabiting invertebrate parent until the next generation. Some fauna, the use of some parasiticides could models predict that even a single treatment also indirectly affect some species of verte- has the capacity to cause real reduction in brates by depleting the quantity of an im- beetle numbers and the effect is greater portant food resource. The effects of such when there are several successive treat- invertebrate food reduction would be ex- ments over a period of weeks [115]. It has pected to be especially severe if it occurs at been estimated that, in 1991, sufficient critical times for the vertebrates, such as avermectins were sold to treat 15% of the during the breeding season or when the world population of 1.3 billion cattle. This young animals have to forage and feed for is undoubtedly an over-estimate since themselves. This concerns many birds [9, many cattle are treated more than once in a 62, 80, 105], a number of species of bats single season, thus the proportion of cattle which feed on Aphodius beetles and the yel- not treated with avermectin would be low dung fly Scathophaga stercoraria greater than reported [30, 81]. However adults [57, 78, 92], and terrestrial mammals many farmers have adopted strategic worm such as hedgehogs, shrews and badgers, control programs and anthelmintic usage which feed on a wide range of invertebrates tends to be seasonally synchronous, [79]. avermectins being used routinely together with other parasiticides. Wardhaugh and Ridsdill-Smith [111] summarised one fu- 6. CONCLUSION ture challenge: are there really untreated refugia in the modern pastoral ecosystem This review of available data published and, if so, how confident can we be that in the scientific literature shows that resi- these are sufficiently extensive in both time dues of many antiparasitics currently regis- and space to adequately compensate for any tered for the control of internal and external losses that may occur in treated areas? parasites of cattle and other animals are There are two ways to consider the fairly or highly toxic to egg-laying adults or long-term consequences of the use of para- to developing larvae of many non-target siticides. Either we try to protect the eco- dung-breeding invertebrates. It is very diffi- system function, i.e. dung degradation, or cult to recognize the importance of delayed we try to protect the ecosystem structure, reactions to non-lethal doses of antiparasitics. i.e. individual species or populations. If the This concerns all anthelmintics, but function is favoured, we have to accept the avermectin is one of the most concerned. The loss of rare species or large reductions in vital question concerns the full extent to the populations of dung fauna provided that Use of anthelmintics and risks for the fauna 557 dung decomposition is unaffected. If our sary year round treatment, the use of eco- concern is structure, then the challenge will logically safe drugs during insect breeding be to protect the majority of dung insect seasons, keeping avermectin-treated ani- species populations, e.g. to protect 95% of mals off the pasture when dung is the most the diversity of dung insects (C. Long, pers. toxic, and selective chemotherapy of ani- comm). mals with high faecal egg counts will provide added safety [50]. These practices The part played by anthelmintics in could be easily done, even with a pastureland fouling much depends on the one-month excretion of environmental nature of drug administration. Measuring toxic drugs (e.g. subcutaneous injection, the drug concentration in faeces while pour-on). Conversely, the use of slow-re- studying insect demography would go a lease bolus which deliver avermectins long way in helping to understand what is within 4–5 months appears poorly compati- really happening in the various experiments ble with sustainable pastureland ecology. [100]. Most results were obtained after only a several week exposition of pats from treated and untreated animals. Long-term ACKNOWLEDGEMENTS experiments are needed, as a persistent reduction in beetle abundance and species diversity can be observed without immediate We are grateful to Wendy Brand-Williams who revised the English version of the manu- and notable influence on dung degradation script. The helpful criticism of the manuscript in the field. Cattle, horses, sheep, swine, to by the two anonymous referees and the editor is varying degrees are all utilised by humans gratefully acknowledged. for economic gain. To date, the detrimental impact upon non-target organisms has been considered acceptable in eradicating para- REFERENCES sites because of their economic importance to commercial livestock production. Pro- duction will increase when these parasites [1] Afzal J., Stout S.J., daCunha A.R., Miller P., Moxidectin: absorption, tissue distribution, ex- are suppressed but we remain oblivious to cretion and biotransformation of 14 C-labelled the long-term consequences of this action moxidectin in sheep, J. Agric. Food Chem. 42 [97]. Anthelmintics are of considerable (1994) 1767-1773. value in agriculture, but possibly at an [2] Ali D.N., Hennessy D.R., The effect of level of unevaluated cost to the greater environ- feed intake on the pharmacokinetic disposition and efficacy of ivermectin in sheep, J. Vet. ment. The serious challenge is to seek to de- Pharmacol. Ther. 19 (1996) 89-94. termine the ecological limits to rural [3] Alvinerie M., Tardieu D., Sutra J.F., Bojensen activities, to assess much more critically G., Galtier P., Metabolic profile of ivermectin in the inadvertent by-products of controlling goats: an in vitro evaluation, in: Lees P. (Ed.), parasites and pests, and the long-term con- Proceedings of the 6th International Congress of European Association for Veterinary Pharma- sequences of these by-products to our com- cology and Toxicology (EAVPT), Edinburgh mercial animal production systems. Herd 7–11 August, Abstract No S10 P6, Blackwell [49] pointed out that, in many parts of the Scientific Publications, Edinburgh, 1996, p. 262. world, irrational parasite control programs [4] Alvinerie M., Sutra J.F., Galtier P., Lifschitz tend to be the rule rather than the exception A., Virkel G., Sallovitz J, Lanusse C., Persis- and livestock owners are pressured into tence of ivermectin in plasma and faeces following administration of a sustained-release bolus to damaging over-use of antiparasitic drugs. cattle, Res. Vet. Sci. 66 (1998) 57-61. Sustainable parasite control practices have [5] Andrew N.W., Halley B.A., Stability of already been summarised [49]. These prac- ivermectin in rumen fluids, J. Vet. Pharmacol. tices include the elimination of unneces- Ther. 19 (1996) 295-299. 558 J.P. Lumaret, F. Errouissi

[6] Barth D., Importance of the methodology in the tion, tissue distribution, and excretion of tritium interpretation of factors affecting degradation of labelled ivermectin in cattle, sheep, and rat, J. dung, Vet. Parasitol. 48 (1993) 99-108. Agr. Food Chem. 38 (1990) 2072-2078. [7] Barth D., Heinze-Mutz E.M., Roncalli R.A., [20] Cook D.F., Ovarian development in females of Schlüter D., Gross S.J., The degradation of dung the Australian sheep blowfly Lucilia cuprina produced by cattle treated with an ivermectin (Diptera: Calliphoridae) fed on sheep faeces and slow-release bolus, Vet. Parasitol. 48 (1993) the effect of ivermectin residues, Bull. Entomol. 215-227. Res. 81 (1991) 249-256. [8] Barth D., Heinze-Mutz E.M., Langholff W., [21] Cook D.F., Effect of avermectin residues in Roncalli R.A., Schlüter D., Colonisation and sheep dung on mating of the Australian sheep degradation of dung pats after sub-cutaneous blowfly, Lucilia cuprina, Vet. Parasitol. 48 treatment of cattle with ivermectin or (1993) 205-214. levamisole, Appl. Parasitol. 35 (1994) 277-293. [22] Dadour I.R., Cook D.F., Neesam C., Dispersal of [9] Beintema A.J., Thissen J.B., Tensen D., Visser dung containing ivermectin in the field by G.H., Feeding ecology of charadriiform chicks Onthophagus taurus (Coleoptera: Scarabaeidae), in agricultural grasslands, Ardea 79 (1991) Bull. Entomol. Res. 89 (1999) 119-123. 31-44. [10] Bianchin I., Honer M.R., Gomes A., Koller [23] Davies I.M., McHenery J.G., Rae G.H., Environ- W.W., Efeito de alguns arrapaticidas/inseticidas mental risk from dissolved ivermectin to marine sobre Onthophagus gazella, EMBRAPA Commu- organisms, Aquaculture 158 (1997) 263-275. nicado Técnico 45 (1992) 1-7. [24] Doherty W.M., Stewart N.P., Coob R.M., Keiran [11] Bianchin I., Alves R.G.O., Koller W.W., Effect P.J., In-vitro comparison of the larvicidal activ- of pour-on tickicides/insecticides on adults of ity of moxidectin and abamectin against the African dung beetle Onthophagus gazella Onthophagus gazella (F) (Coleoptera: Fabr. (Coleoptera: Scarabaeidae), An. Soc. Scarabaeidae) and Haematobia irritans exigua Entomol. Bras. 27 (1998) 275-279. De Meijere (Diptera: Muscidae), J. Aust. Entomol. Soc. 33 (1994) 71-74. [12] Blume R.R., Younger R.L., Aga A., Myers C.J., Effects of residues of certain anthelmintics in [25] Errouissi F., Alvinerie M., Galtier P., Kerbœuf bovine manure on Onthophagus gazella,a D., Lumaret J.-P., The negative effects of the res- non-target organism, Southwest. Entomol. 1 idues of ivermectin in cattle dung using a sus- (1976) 100-103. tained-release bolus on Aphodius constans (Duft.) (Coleoptera: Aphodiidae), Vet. Res. 32 [13] Boettner W.A., Aguiar A.J., Cardinal J.R., The (2001) 421-427. morantel SR trilaminate: a device for the controlled ruminal delivery of morantel to cattle, J. [26] Fincher G.T., Sustained-release bolus for horn fly Control Release 8 (1988) 23-30. (Diptera: Muscidae) control: effects of methoprene and diflubenzuron on some nontarget species, En- [14] Bogan J.A., McKellar Q.A., The pharmacodynamics viron. Entomol. 20 (1991) 77-82. of ivermectin in sheep and cattle, J. Vet. Pharmacol. Ther. 11 (1988) 260-268. [27] Fincher G.T., Injectable ivermectin for cattle: effects on some dung-inhabiting insects, Environ. [15] Boyd J.M., The ecology of earthworms in cat- Entomol. 21 (1992) 871-876. tle-grazed machair in Tiree, Argyll, J. Anim. Ecol. 27 (1958) 147-157. [28] Fincher G.T., Wang G.T., Injectable moxidectin for cattle: effects on two species of dung-burying [16] Breymeyer A., Jakubczyk H., Olechowicz E., Influ- beetles, Southwest. Entomol. 17 (1992) ence of coprophagous arthropods on microorgan- 303-306. isms in sheep faeces – Laboratory investigations, Bull. Acad. Pol. Sci., Sér. Sci. Biol. 23 (1975) [29] Floate K.D., Off-target effects of ivermectin on 257-262. insects and on dung degradation in southern Al- berta, Canada, Bull. Entomol. Res. 88 (1998) [17] Burridge L.E., Haya K., The lethality of 25-35. ivermectin, a potential agent for treatment of salmonids against sea lice, to the shrimp [30] Forbes A.B., A review of regional and temporal Crangon septemspinosa, Aquaculture 117 use of avermectins in cattle and horses world- (1993) 9-14. wide, Vet. Parasitol. 48 (1993) 19-28. [18] Burridge L.E., Haya K., Waddy S.L., Wade J., [31] Forbes A.B., Environmental assessments in vet- The lethality of anti-sea lice formulations erinary parasitology: a balanced perspective, Int. Salmosan (Azamethiphos) and Excis J. Parasitol. 26 (1996) 567-569. (cypermethrin) to stage IV and adult lobsters [32] Galbiati C., Conceicao C.H.C., Florcovski J.L., (Homarus americanus) during repeated short- Calafiori M.H., Effect of anthelmintic injection term exposures, Aquaculture 182 (2000) 27-35. into cattle on the coprophagous beetle [19] Chiu S.H.L., Green M.L., Bayliss F.P., Eline D., Dichotomius anaglypticus (Mann., 1829), Rosegay A., Meriwether H., Jacob T.A., Absorp- Ecossistema 20 (1995) 100-108. Use of anthelmintics and risks for the fauna 559

[33] Gaughan L., Ackerman M.E., Unai T., Casida fenbendazole metabolites in sheep, J. Vet. J.E., Distribution and metabolism of trans- and Pharmacol. Ther. 16 (1993) 132-140. cis-permethrin in lactating dairy cows, J. Agric. [49] Herd R., Control strategies for ruminant and Food Chem. 26 (1978) 613-617. equine parasites to counter resistance, encyst- [34] Gover J., Strong L., Effects of ingested ivermectin ment, and ecotoxicity in the USA, Vet. Parasitol. on body mass and excretion in the dung fly, 48 (1993) 327-336. Neomyia cornicina, Physiol. Entomol. 20 (1995) [50] Herd R., Endectocidal drugs: ecological risks 93-99. and counter-measures, Int. J. Parasitol. 25 [35] Gover J., Strong S., Determination of the toxicity (1995) 875-885. of faeces of cattle treated with an ivermectin sustained-release bolus and preference trials using a [51] Herd R., Ecotoxicity of the avermectins: a reply dung fly, Neomyia cornicina, Entomol. Exp. to Forbes, Int. J. Parasitol. 26 (1996) 571-572. Appl. 81 (1996) 133-139. [52] Herd R., Stinner B.R., Purrington F.F., Dung dis- [36] Grant A., Briggs A.D., Toxicity of ivermectin to persal and grazing area following treatment of estuarine and marine invertebrates, Mar. Pollut. horses with a single dose of ivermectin, Vet. Bull. 36 (1998) 540-541. Parasitol. 48 (1993) 229-240. [37] Grant A., Briggs A.D., Use of ivermectin in ma- [53] Herd R., Strong L., Wardhaugh K., Research rec- rine fish farms: some concerns, Mar. Pollut. ommendations, Vet. Parasitol. 48 (1993) Bull. 36 (1998) 566-568. 337-340. [38] Guild W.J., Earthworms and soil structure, in: [54] Holter P., Effect of dung beetles (Aphodius spp.) Kevan D.K. (Ed.), Soil Zoology, Butterworths, and earthworms on the disappearance of cattle London, 1955. dung, Oikos 32 (1979) 393-402. [39] Gunn A., Sadd W., The effect of ivermectin on [55] Holter P., Effect of earthworms on the disappear- the survival behaviour and cocoon production of ance rate of cattle droppings, in: Satchell J.E. the earthworm Eisenia foetida, Pedobiologia 38 (Ed.), Earthworm Ecology, Chapman and Hall, (1994) 327-333. London, 1983, pp. 49-57. [40] Halley B.A., Nessel R.J., Lu A.Y.H., Environ- [56] Houlding B., Ridsdill-Smith T.J., Bailey W.J., mental aspects of ivermectin usage in livestock: Injectable abamectine causes delay in general considerations, in: Campbell W.C. (Ed.), Scarabaeine dung beetle egg-laying in cattle Ivermectin and Abamectin, Springer Verlag, dung, Aust. Vet. J. 68 (1991) 185-186. New York, 1989, pp. 162-172. [57] Jones G., Prey selection by the greater horseshoe [41] Halley B.A., VandenHeuvel W.J.A., Wislocki bat Rhinolophus ferrumequinum: optimal forag- P.G., Environmental effects of the usage of ing by echolocation, J. Anim. Ecol. 59 (1990) avermectins in livestock, Vet. Parasitol. 48 587-602. (1993) 109-125. [58] Kadiri N., Lumaret J.-P., Janati-Idrissi A., Lac- [42] Hammer O., Biological and ecological investiga- tones macrocycliques: leur impact sur la faune tions of flies associated with pasturing cattle and non-cible du pâturage, Ann. Soc. Entomol. Fr. their excrement, Vidensk. Medd. Naturhist. (N.S.) 35 (Suppl.) (1999) 222-229. Foren. Kobenhavn 5 (1941) 141-393. [59] Krüger K., Scholtz C.H., Lethal and sublethal ef- [43] Hanski I., Patterns in beetle succession in drop- fects of ivermectin on the dung-breeding beetles pings, Ann. Zool. Fenn. 17 (1980) 17-25. Euoniticellus intermedius (Reiche) and Onitis [44] Hanski I., The three coexisting species of alexis Klug (Coleoptera, Scarabaeidae), Agric. Sphaeridium (Coleoptera, Hydrophilidae), Ann. Ecosyst. Environ. 61 (1997) 123-131. Entomol. Fenn. 46 (1980) 39-48. [60] Krüger K., Scholtz C.H., Reinhardt K., Effects of [45] Hanski I., The dung insect community, in: the pyrethroid flumethrin on colonisation and Hanski I., Cambefort Y (Eds.), Dung Beetle degradation of cattle dung by adult insects, Ecology, Princeton University Press, Princeton, South Afr. J. Sci. 94 (1998) 129-133. New Jersey, 1991, pp. 5-22. [61] Krüger K., Luckhele O.M., Scholtz C.H., Sur- [46] Hennessy D.R., Steel J.W., Prichard R.K., Lacey vival and reproduction of Euoniticellus E., The effect of co-administration of parben- intermedius in dung following application of dazole on the disposition of oxfendazole in cypermethrin and flumethrin pour-ons to cattle, sheep, J. Vet.Pharmacol. Ther. 15 (1992) 10-18. Bull. Entomol. Res. 89 (1999) 543-548. [47] Hennessy D.R., Sangster N.C., Steel J.W., [62] Laurence B.R., The larval inhabitants of cow Collins G.H., Comparative pharmacokinetic be- pats, J. Anim. Ecol. 23 (1954) 234-260. haviour of albendazole in sheep and goats, Int. J. [63] Lo P.-K.A., Fink D.W., Williams J.B., Blodinger Parasitol. 23 (1993) 321-325. J., Pharmacokinetics studies of ivermectin: ef- [48] Hennessy D.R., Steel J.W., Prichard R.K., fects of formulation, Vet. Res. Commun. 9 Biliary secretion and enterohepatic recycling of (1985) 251-268. 560 J.P. Lumaret, F. Errouissi

[64] Lumaret J.-P., Toxicité de certains anthelminthiques Acad. Sci. Paris, Life Sciences 324 (2001) vis-à-vis des insectes coprophages et conséquences 989-994. sur la disparition des excréments de la surface du [78] McAney C.M., Fairley J.S., Analysis of the diet of sol, Acta Oecol., Oecol. Appl. 7 (1986) 313-324. the lesser horseshoe Rhinolophus hipposideros in [65] Lumaret J.-P., Comparative effects of the West of Ireland, J. Zool. (London) 217 (1989) moxidectin 2% equine gel and ivermectin 1.87% 491-498. equine gel on dung non-target fauna when used [79] McCracken D.I., The potential for avermectins at the recommended dose in horse, Expt No. to affect wildlife, Vet. Parasitol. 48 (1993) 0876-E-FR-06-95, American Cyanamid Com- 273-280. pany, Princeton, NJ, 1996. [80] McCracken D.I., Foster G.N., Bignal E.M., [66] Lumaret J.-P., Ecological disturbance of Bignal S., An assessment of chough Pyrrhocorax endectocides on non-target fauna in pasture, pyrrhocorax diet using multivariate analysis Proceedings of 16th International Conference of techniques, Avocetta 16 (1992) 19-29. World Association for the Advancement of Vet- erinary Parasitology, Sun City, South Africa, [81] McKellar Q.A., Ecotoxicology and residues of 1997, p. 54. anthelmintic compounds, Vet. Parasitol. 72 (1997) 413-435. [67] Lumaret J.-P., Kadiri N., The influence of the first wave of colonisation insects on cattle dung [82] McKellar Q.A., Scott E.W., Baxter P., Anderson dispersal, Pedobiologia 39 (1995) 506-517. L.A., Bairden K., Pharmacodynamics, pharmacokinetics and faecal persistence of [68] Lumaret J.-P., Galante E., Lumbreras C., Mena morantel in cattle and goats, J. Vet. Pharmacol. C., Bertrand M., Bernal J.L., Cooper J.-F., Kadiri Ther. 16 (1993) 87-92. N., Crowe D., Field effects of antiparasitic drug ivermectin residues on dung beetles, J. Appl. [83] Miller R.W., Bay Vi 7533 tested in cattle and Ecol. 30 (1993) 428-436. poultry as a feed through compound against flies, Southwest Entomol. 72 (1992) 130-134. [69] Lussenhop J., Kumar R., Wicklow D.T., Elloyd J.E., Insect effects on bacteria and fungi in cattle [84] Pérez R., Cabezas I., Sutra J.F., Galtier P., dung, Oikos 34 (1980) 54-58. Alvinerie M., Faecal excretion profile of moxidectin and ivermectin after oral administra- [70] Madsen M., Nielsen B.O, Holter P., Pedersen tion in horses, Vet. J. 161 (2001) 85-92. O.C., Jespersen J.B, Vagn Jensen K.-M., Nansen P., Grønvold J., Treating cattle with ivermectin: [85] Putman R.J., Carrion and dung: the decomposi- effects on the fauna and decomposition of dung tion of animal wastes, Inst. Biol., Stud. Biol. 156, pats, J. Appl. Ecol. 27 (1990) 1-15. 1983, 62 p. [71] Mahon R.J., Wardhaugh K.G., Impact of dung [86] Ridsdill-Smith T.J., Survival and reproduction of from ivermectin-treated sheep on oogenesis and Musca vetustissima Walker (Diptera: Muscidae) survival of adult Lucilia cuprina, Aust. Vet. J. 68 and scarabaeine dung beetle in dung of cattle (1991) 173-177. treated with avermectin B1, J. Aust. Entomol. Soc. 27 (1988) 175-178. [72] Mahon R.J., Wardhaugh K.G., van Gerwen A.C.M., Whitby W.A., Reproductive develop- [87] Ridsdill-Smith T.J., Effects of avermectin resi- ment and survival of Lucilia cuprina dues in cattle dung on dung beetle (Coleoptera: Wiedemann when fed sheep dung containing Scarabaeidae) reproduction and survival, Vet. ivermectin, Vet. Parasitol. 48 (1993) 193-204. Parasitol. 48 (1993) 127-137. [88] Roncalli R.A., Environmental aspects of use of [73] Marriner S.E., Bogan J.A., Pharmacokinetics of Ivermectin and Abamectin in livestock: effects albendazole in sheep, Am. J. Vet. Res. 41 (1980) on cattle dung fauna, in: Campbell W.C. (Ed.), 483-491. Ivermectin and Abamectin, Springer Verlag, [74] Marriner S.E., Bogan J.A., Pharmacokinetics of New York, 1989, pp. 173-181. oxfendazole in sheep, Am. J. Vet. Res. 42 (1981) [89] Schmid K., Pharmacological properties of the 1143-1145. Panacur SR bolus. A device for sustained release [75] Marriner S.E., Bogan J.A., Pharmacokinetics of of fenbendazole in the reticulorumen of cattle, fenbendazole in sheep, Am. J. Vet. Res. 42 14th International Conference of the World (1981) 1146-1148. Association for the Advancement of Veterinary [76] Marriner S.E., McKinnon I, Bogan J.A., The Parasitology, Cambridge, UK, 1993, p. 231. pharmacokinetics of ivermectin after oral and [90] Schmidt C.D., Activity of an avermectin against subcutaneous administration to sheep and selected insects in aging manure, Environ. horses, J. Vet. Pharmacol. Ther. 10 (1987) Entomol. 12 (1983) 455-457. 175-179. [91] Schreiber E.T., Campbell J.B., Boxler D.J., [77] Martinez I.M., Lumaret J.-P., Cruz M.R., Sus- Petersen J.J., Comparison of beetles collected pected side effects of a herbicide on dung beetle from the dung of cattle untreated and treated populations (Coleoptera: Scarabaeidae), C.R. with fenvalerate ear tags and pastured on two Use of anthelmintics and risks for the fauna 561

range types in western Nebraska, Environ. sustained-release boluses, Vet. Parasitol. 62 Entomol. 60 (1987) 1135-1140. (1996) 253-266. [92] Shiel C.B., McAney C.M., Fairley J.S., Analy- [104] Sundlof S.F., Whitlock T.W., Clorsulon sis of the diet of Natterer’s bat Myotis nattereri pharmacokinetics in sheep and goats following and the common long-eared bat Plecotus oral and intravenous administration, J. Pharmacol. auritus in the West of Ireland, J. Zool. (London) Ther. 15 (1992) 282-291. 223 (1991) 299-305. [105] Valiela I., An experimental study of mortality [93] Silva Junior V.P.da, Borja G.E.M., Sanavria A., factors of larval Musca autumnalis DeGeer, Residual effect of doramectin and ivermectin Ecol. Monogr. 39 (1969) 199-225. on the development of Sarcopromusca pruna [106] Venant A., Belli P., Borrel S., Mallet J., Excre- (Shannon & Del Ponte, 1926) (Diptera: tion of deltamethrin in lactating dairy cows, Muscidae) in cattle faeces, Arquiv. Facult. Vet., Food Addit. Contam. 7 (1990) 535-543. Univ. Fed. Rio Grande do Sul 25 (1997) 85-91. [107] Wall R., Strong L., Environmental conse- [94] Sommer C., Overgaard N.B., Larvae of the quences of treating cattle with antiparasitic dung beetle Onthophagus gazella F. (Col., drug ivermectin, Nature 327 (1987) 418-421. Scarabaeidae) exposed to lethal and sublethal ivermectin concentrations, J. Appl. Entomol. [108] Waller P.J., Mahon R.J., Wardhaugh K.G., Re- 114 (1992) 502-509. gional and temporal use of avermectins for ru- [95] Sommer C., Steffansen B., Changes with time minants in Australia, Vet. Parasitol. 48 (1993) after treatment in the concentrations of 29-44. ivermectin in fresh cow dung and in cow pats [109] Wardhaugh K.G., Drug residues in the faeces aged in the field, Vet. Parasitol. 48 (1993) cattle treated with pour-on formulations of 67-73. eprinomectin and moxidectin and their effects [96] Sommer C., Steffansen B., Overgaard N., on the development and survival of the bush fly, Grønvold J., Vagn Jensen K.-M., Jespersen Musca vetustissima and a scarabaeine dung J.B., Springborg J., Nansen P., Ivermectin ex- beetle, Onthophagus taurus, CSIRO Contract o creted in cattle dung after subcutaneous injec- Report N 52, CSIRO Entomology, Canberra, tion or pour-on treatment: concentrations and Australia, 1999, pp. 1-29. impact on dung fauna, Bull. Entomol. Res. 82 [110] Wardhaugh K.G., Parasiticides registered for (1992) 257-264. use in cattle in Australia – an annotated bibliog- [97] Spratt D.M., Endoparasite control strategies: raphy and literature guide prepared for the Na- implications for biodiversity of native fauna, tional Dung Beetle Planning Forum, CSIRO Int. J. Parasitol. 27 (1997) 173-180. Entomology Contracted Report Series 56 (2000) 1-15. [98] Steel J.W., Assessment of the effects of the macrocyclic lactone class of chemicals on dung [111] Wardhaugh K.G., Ridsdill-Smith T.J., beetles and dung degradation in Australia, in: Antiparasitic drugs and the livestock industry – National Registration Authority for Agricul- cause for concern? Aust. Vet. J. 76 (1998) tural and Veterinary Chemicals (NRA), Special 259-261. Review of Macrocyclic Lactones, Australia, [112] Wardhaugh K.G., Rodriguez-Menendez H., 1998, 79 pp. The effects of the antiparasitic drug, [99] Steel J.W., Wardhaugh K.G., Ecological impact ivermectin, on the development and survival of of macrocyclic lactones on dung fauna, in: the dung-breeding fly, Orthelia cornicina (F) Vercruysse J., Rew R.S. (Eds.), Macrocyclic and the scarabaeinae dung beetles, Copris lactones: A revolution in antiparasitic therapy, hispanus L., Bubas bubalus (Oliver) and Onitis CABI Publishing, Wallingford, UK (in press). belial F., J. Appl. Entomol. 106 (1988) 381- 389. [100] Strong L., Avermectins: a review of their impact on insects of cattle dung, Bull. Entomol. [113] Wardhaugh K.G., Mahon R.J., Axelsen A., Res. 82 (1992) 265-274. Rowland M.W., Wanjura W., Effects of ivermectin residues in sheep dung on the devel- [101] Strong L., James S., Some effects of rearing the opment and survival of the bushfly, Musca yellow dung fly Scatophaga stercoraria in cat- vetustissima Walker and the scarabaeine dung tle dung containing ivermectin, Entomol. Exp. beetle, Euoniticellus fulvus Goeze, Vet. Appl. 63 (1992) 39-45. Parasitol. 48 (1993) 139-157. [102] Strong L., Wall R., Effects of ivermectin and [114] Wardhaugh K.G., Holter P., Whitby W.A., moxidectin on the insects of cattle dung, Bull. Shelley K., Effects of drug residues in the fae- Entomol. Res. 84 (1994) 403-409. ces of cattle treated with injectable formula- [103] Strong L., Wall R., Woolford A., Djeddour D., tions of ivermectin and moxidectin on larvae of The effect of faecally excreted ivermectin and the bush fly, Musca vetustissima and the house fenbendazole on the insect colonisation of cat- fly, Musca domestica, Aust. Vet. J. 74 (1996) tle dung following the oral administration of 370-374. 562 J.P. Lumaret, F. Errouissi

[115] Wardhaugh K.G., Longstaff B.C., Lacey M.J., pour-on formulations of eprinomectin or Effects of residues of deltamethrin in cattle fae- moxidectin, Vet.Parasitol. 99 (2001) 155-168. ces on the development and survival of three [118] Weir A.J., Bogan J.A., Thiabendazole and species of dung-breeding insects, Aust. Vet. J. 5-hydroxythiabendazole in the plasma of 76 (1998) 273-280. sheep, J. Vet. Pharmacol. Ther. 8 (1985) [116] Wardhaugh K.G., Holter P., Longstaff B., The 413-414. development and survival of three species of [119] Wratten S.D., Mead-Briggs M., Gettinby G., coprophagous insect after feeding on the faeces Ericsson G., Baggott D.G., An evaluation of the of sheep treated with controlled-release formu- potential effects of ivermectin on the decompo- lations of ivermectin or albendazole, Aust. Vet. sition of cattle dung pats, Vet. Rec. 133 (1993) J. 79 (2001) 125-132. 365-371. [117] Wardhaugh K.G., Longstaff B.C., Morton R., A [120] Zulalian J., Stout S.J., Da Cunha A.R., Garcés comparison of the development and survival of T., Miller P., Absorption, tissue distribution, the dung beetle, Onthophagus taurus (Schreb.) metabolism and excretion of moxidectin in cat- when fed on the faeces of cattle treated with tle, J. Agric. Food Chem. 42 (1994) 381-387.

To access this journal online: www.edpsciences.org