A review on the effect of macrocyclic lactones on dung-dwelling insects: Toxicity of macrocyclic lactones to dung beetles

Abstract

Avermectins and milbemycins are commonly used in agro-ecosystems for the control of parasites in domestic livestock. As integral members of agro-ecosystems with importance in maintaining pasture health through dung burial behaviour, dung beetles are an excellent nontarget bio-indicator taxon for examining potential detrimental effects of pesticide application. The current review focuses on the relative toxicity of four different anthelmintics (ivermectin, eprinomectin, doramectin and moxidectin) in dung residues using dung beetles as a bioindicator species. One of the implications of this review is that there could be an effect that extends to the entire natural assemblage of insects inhabiting and feeding on the dung of cattle treated with avermectin or milbemycin products. Over time, reduced reproductive rate would result in decreased dung beetle populations and ultimately, a decrease in the rate of dung degradation and dung burial.

Full text

hp://www.ojvr.org doi:10.4102/ojvr.v82i1.858
Page 1 of 8 Review Arcle
Introducon
The importance placed on anthelmintics to bring parasite populations under control has resulted
in a challenging arms race to develop a product that exhibits the perfect balance between host and
non-target organism toxicity and pest resistance. The need for more effective products is becoming
increasingly important because pest resistance appears to be keeping pace with the development
of new products. Pest resistance is arguably one of the top challenges as far as protecting livestock
is concerned and probably the main driving force behind parasite control research in the livestock
industries (Sangster 1999; Wolstenholme et al. 2004) as it has been reported in many countries, in
a variety of nematodes and against all currently available anthelmintics (Sutherland & Leathwick
2011).
Anthelmintics, which control helminth pests by removing them, are grouped according to their
common chemistry and mode of action (Sangster & Dobson 2002; Vercruysse & Rew 2002).
Currently, the avermectins (ivermectin, eprinomectin and doramectin) and the milbemycins
(moxidectin), collectively known as macrocyclic lactones, are amongst the most effective
anthelmintics on the market.
The avermectins are naturally produced by strains of a soil-dwelling actinomycete, Streptomyces
(Burg et al. 1979; Shoop & Soll 2002). All the avermectins have a unique pharmacophore that
consists of a 16-membered macrocyclic lactone backbone (Shoop & Soll 2002) with a disaccharide
chain at C-13 (Steel 1993; Vercruysse & Rew 2002). Although the avermectins are a glycosidic
derivative of the pentacyclic 16-membered lactone (Albers-Schoenberg et al. 1981; Chabala
et al. 1980), they do not possess the antifungal and antibacterial properties associated with the
macrolide antibiotics (Albers-Schoenberg et al. 1981; Burg et al. 1979; Chabala et al. 1980). They
act by interfering with invertebrate neurotransmission rather than inhibiting protein synthesis
(Albers-Schoenberg et al. 1981; Chabala et al. 1980).
Ivermectin was the first avermectin to be introduced in 1981 (Steel 1993; Vercruysse & Rew
2002). Ivermectin (22, 23-dihydroavermectin) is a disaccharide derivative of the pentacyclic
16-membered lactone (Burg et al. 1979; Campbell 1985; Chabala et al. 1980; Römbke et al. 2010).
The antiparasitic effect of ivermectin is extremely potent against insects, nematodes and acarines
(Campbell 1985; Putter et al. 1981). Although potent, ivermectin is not equally active against all
species and is often highly stage specific (Campbell 1985), so that a genus known to be susceptible
to ivermectin may not be susceptible at all life stages (Campbell & Benz 1984).
Abamectin, a combination of 80% avermectin B1a and 20% avermectin B1b, is the starting material
for ivermectin. It is effective against nematodes as well as acarines and to date remains the only
Avermectins and milbemycins are commonly used in agro-ecosystems for the control of
parasites in domestic livestock. As integral members of agro-ecosystems with importance in
maintaining pasture health through dung burial behaviour, dung beetles are an excellent non-
target bio-indicator taxon for examining potential detrimental effects of pesticide application.
The current review focuses on the relative toxicity of four different anthelmintics (ivermectin,
eprinomectin, doramectin and moxidectin) in dung residues using dung beetles as a bio-
indicator species. One of the implications of this review is that there could be an effect that
extends to the entire natural assemblage of insects inhabiting and feeding on the dung of cattle
treated with avermectin or milbemycin products. Over time, reduced reproductive rate would
result in decreased dung beetle populations and ultimately, a decrease in the rate of dung
degradation and dung burial.
Authors:
Carmen T. Jacobs1
Clarke H. Scholtz1
Aliaons:
1Department of Zoology and
Entomology, University of
Pretoria, South Africa
Correspondence to:
Carmen Jacobs
Email:
ctjacobs@zoology.up.ac.za
Postal address:
Private Bag X20, Haield
0028, South Africa
Dates:
Received: 07 Aug. 2014
Accepted: 09 Dec. 2014
Published: 16 Apr. 2015
How to cite this arcle:
Jacobs, C.T. & Scholtz, C.H.,
2015, ‘A review on the eect
of macrocyclic lactones
on dung-dwelling insects:
Toxicity of macrocyclic
lactones to dung beetles’,
Onderstepoort Journal of
Veterinary Research 82(1),
Art. #858, 8 pages. hp://
dx.doi.org/10.4102/ojvr.
v82i1.858
Copyright:
© 2015. The Authors.
Licensee: AOSIS
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licensed under the Creave
Commons Aribuon
License.
A review on the eect of macrocyclic lactones on
dung-dwelling insects: Toxicity of macrocyclic
lactones to dung beetles
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Page 2 of 8 Review Arcle
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avermectin or milbemycin to be used in both the animal
health and crop industries (Shoop, Mrozik & Fisher 1995).
Eprinomectin was introduced to the animal health industry
in 1997 as an alternative to ivermectin as it was considered
to be the only topical endectocide safe for use in lactating
dairy animals (Shoop et al. 1996b; Vercruysse & Rew 2002).
Although ivermectin has no side-effects on the host and
has a very broad spectrum of activity, with few exceptions
it cannot be used in lactating dairy animals because of the
levels of residue that remain in the milk (Shoop et al. 1996a,
1996b; Vercruysse & Rew 2002).
Doramectin was commercialised in 1993 (Vercruysse et al.
1993) and is the easiest avermectin to administer. In a study
by Grandin, Maxwell and Lanier (1998), it was found that
doramectin caused significantly less discomfort during
administration than ivermectin.
The milbemycins, although structurally similar and with
a similar range of biological activity to the avermectins,
differ in substituents in a few of the side chains at the C-13
position and can basically be considered to be deglycosylated
avermectins (Sangster & Dobson 2002; Steel 1993; Vercruysse
& Rew 2002). Although they were discovered in 1973, before
the discovery of ivermectin, they were originally developed
for use in crop protection and have been used in veterinary
practice from about 1986 only (McKellar & Benchaoui 1996;
Takiguchi et al. 1980).
Moxidectin, the only milbemycin available on the market as
an endectocide, was introduced in 1989 and commercialised
worldwide by the early 1990s (McKellar & Benchaoui
1996; Steel 1993). The milbemycins are highly lipophilic
(moxidectin is about 100 times more lipophilic than the
avermectins), soluble in organic solvents and insoluble in
water, and after an initial increase in its plasma concentration
post-administration, it is redistributed throughout the body
fat reserves, from which it is slowly released (McKellar &
Benchaoui 1996).
Various studies have shown that a characteristic of the
avermectins, regardless of the animal or method of
administration, is that most of the dose is excreted largely
unaltered in the dung, where it retains its insecticidal activity
(Campbell 1985; Steel 1993; Strong 1993; Wardhaugh &
Rodriguez-Menendez 1988). This is the focus of the present
review.
Published studies
Numerous laboratory and field studies have been undertaken
on the effects of avermectins and milbemycin in cattle dung
on non-target organisms and on their effects on different
aspects of dung beetle biology. Countries with large cattle
populations were chosen based on Food and Agriculture
Organization of the United Nations, Statistic Division
(FAOSTAT)’s live animal production database (Food and
Agriculture Organization of the United Nations [FAO] 2013).
Although the methods used were different in each country
and changed somewhat over the years, the results have
remained more or less consistent.
Ivermecn
Ivermectin is the most extensively studied of all the
avermectins. The first study that set the scene for interest in
the field was that of Wall and Strong (1987), who conducted
an experiment in the UK to investigate the environmental
consequences of treating cattle with ivermectin. In contrast to
the control dung pats, the experimental pats contained few to
no Coleoptera or Diptera. The results also indicated that there
was no visible dung degradation in the ivermectin-treated
dung when compared to the controls. This field trial showed
that treatment with a ruminal bolus that delivers 40 µg/kg
ivermectin per day was enough to disrupt the entire dung-
inhabiting insect community. Various subsequent studies
have simulated or repeated this experiment with variable
results.
Lethal and sublethal eect studies
Lumaret et al. (1993) studied the effects of ivermectin residues
on dung beetles by running a field trial on a farm in Spain in
spring. Dung toxicity was assessed by recording the mortality
of the dung beetles feeding on the dung. In addition, the
numbers of larvae and pupae were recorded after 29 days.
No adult mortality was recorded for the duration of the
study but 100% larval and pupal mortality was observed in
dung collected on the day after treatment. No differences in
offspring numbers between treated and untreated dung were
observed from day 6 onwards. A delay in development was
observed for beetles bred in treated dung when compared to
the control offspring. Pitfall traps baited with dung collected
10 and 17 days after treatment were similarly attractive with
treated and untreated dung for the first 3 days, and then
a peak of attraction occurred between days 4 and 6, when
the dung was most attractive and still relatively fresh. From
day 6 onwards, the attraction to the treated dung persisted
for 30 days whilst the untreated dung became unattractive
after day 7. Lumaret et al. (1993) proposed that increased
attractiveness is a result of biochemical modifications in
the dung composition, most likely as a result of protein
degradation released by ivermectin therapy.
Krüger and Scholtz (1997) ran a laboratory trial to determine
the lethal and sublethal effects of ivermectin residues in
dung from animals treated with a single standard injection of
ivermectin at 200 µg/kg. Laboratory colonies of Euoniticellus
intermedius were provided with 250 mL of dung twice a week
for 2 weeks and monitored for adult mortality as well as for
brood ball numbers. Brood balls were counted, removed and
incubated to monitor for emergence. No results regarding
adult survival were reported. There was no significant
difference between treated and control populations in the
number of brood balls formed; however, on average, the
number of adults emerging from treated brood balls was
significantly lower than in the controls (similar findings

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were obtained by Fincher [1992]). Ivermectin caused
100% mortality in offspring 2–7 days after treatment and
significantly fewer emergences from day 14 after treatment
when compared to the controls. Prolonged development
in treated broods (similar to the findings of Lumaret et al.
[1993]) was also recorded, roughly 2.5 times longer for
dung collected 1, 7 and 14 days after treatment and a larval
developmental time of 5 weeks compared to the control of 3.5
weeks for dung collected 28 days after treatment.
Survival and reproducon studies
Ridsdill-Smith (1988) studied the effect of ivermectin on the
survival and reproduction of the dung beetle Onthophagus
binodis in Australia. Ivermectin had no influence on adult
dung beetle survival. Immature survival, however, was zero
for week 1 after treatment but steadily rose to equal that of
the other anthelmintic by week 8 after treatment. There was
no untreated control.
Fincher (1992) compared the effect of 20 µg/kg and 200 µg/kg
ivermectin on some dung-inhabiting insects, including the
introduced African dung beetle E. intermedius in Texas, USA.
The results revealed that neither dosage had any significant
effect on adult survival, as described by Ridsdill-Smith (1988)
and Wardhaugh and Rodriguez-Menendez (1988), or brood
ball production when compared to the controls; however,
emergence of adult E. intermedius from brood balls made
with dung from cattle that received 200 µg/kg ivermectin
was reduced for no more than 2 weeks after treatment
(Fincher 1992).
Cruz Rosales et al. (2012) evaluated the effect of ivermectin
on the survival and fecundity of E. intermedius adults as well
as on the survival and development of E. intermedius from
egg to adult in Mexico. They found that at low concentrations
(10 µg/kg) the ivermectin had no effect on the survival or
fertility of the adults or on the survival of the larvae, but
they did record an increase in the larval development time.
At the medium concentration (1 mg/kg) the survival of
adults was reduced to almost half and no larvae emerged.
At the highest concentration (100 mg/kg) 100% mortality
was observed and no oviposition was performed. They
concluded that the prolonged development time may cause
a phase lag in the field activity cycle, which may reduce
the number of E. intermedius individuals and the efficiency
of the environmental services that they provide, and that
more analyses with higher concentrations between 0.01 ppm
and 0.1 ppm of ivermectin are needed to establish lethal
concentrations for larvae and adults of E. intermedius.
Dung decomposion studies
Wardhaugh and Rodriguez-Menendez (1988) studied the
effect of ivermectin on the development and survival of the
dung beetles Copris hispanus, Bubas bubalus and Onitis belial
in southern Spain. The results showed no adult mortality,
reduced egg-laying and reduced juvenile survival as
described by Ridsdill-Smith (1988). A marked reduction in
adult feeding activity was observed in treatments suffering the
highest mortalities, namely day 1–8 dung, and the inference
was made that mortality was a result of the accumulating
toxic effects, which suppressed feeding (Wardhaugh &
Rodriguez-Menendez 1988). Whilst this study was aimed at
the development and survival of the dung beetles, a decrease
in the rate of dung decomposition as a result of reduction in
adult feeding activity was observed.
Madsen et al. (1990) conducted field as well as laboratory
experiments in Denmark to show how treating cattle with a
single therapeutic ivermectin injection affected the fauna and
decomposition of dung pats. The results from the field trial
showed that ivermectin had an effect on beetle larvae 1–10
days after treatment but that the number of larvae was not
affected by ivermectin applied 20–30 days before collection.
The decomposition rate was significantly delayed when
compared to control dung but also depended on variables
such as climate, season, soil type, faunal inhabitants and
microclimate. The results from the laboratory bioassays
showed a 95% – 100% mortality rate in Musca domestica
as well as Musca autumnalis for dung collected one day
after treatment. There was no clear reduction in excreted
ivermectin placed in the field for 7–62 days and the 62-day
assay was obscured by natural mortality. Most of the
variance found in this experiment was attributed to seasonal
conditions.
Sommer et al. (1992) ran a field trial in Denmark to assess the
impact of ivermectin residues on dung fauna and the resulting
effect on dung degradation. According to the arthropods
found in the treated dung, there was no significant difference
between the residues found in the pour-on and injectable
formulations even though the pour-on formulation was
2.5 times the dose of the injectable formulation; however,
dung collected from cattle 1–2 days after treatment with the
injectable formulation showed delayed dung degradation
for up to 45 days but no effect was observed on dung
collected 13–14 days after treatment. Dung collected from
cattle 1–2 days after treatment with the pour-on formulation
led to delayed dung degradation for up to 13–14 days after
treatment, which was a similar result to that of Wardhaugh
and Rodriguez-Menendez (1988) and Madsen et al. (1990).
Iglesias et al. (2011) evaluated the local effects of ivermectin on
dung fauna and degradation under different meteorological
and biological conditions in the same area in Argentina in
2011. The results showed that fewer arthropods were found
in the dung of the calves treated with ivermectin, but the
difference was not statistically significant.
Community structure studies
Krüger and Scholtz (1998a, 1998b) conducted a large-
scale field study to determine the ecotoxicological effect of
ivermectin on the dung beetle community structure under
drought and high rainfall conditions. The results showed
a large effect on the dung beetle community in the form of
significantly lower species richness and evenness as well
as increased species dominance in treated dung during

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drought conditions (Krüger & Scholtz 1998a). During high
rainfall conditions, however, fewer beetle and fly larvae were
found in the pats after 7 days, but no effect of ivermectin was
detected after a year (Krüger & Scholtz 1998b). This suggests
that these ecotoxicological effects are likely to be more severe
in times of drought than under more favourable conditions.
Kryger, Deschodt and Scholtz (2005) carried out a long-term,
large-scale field study in South Africa to assess the effect
of ivermectin on the structure of dung beetle communities.
No observable effects of ivermectin on the dung beetle
communities were found, as the disparities between treated
and untreated dung were insignificant and most probably
a result of differences in microclimate. Species richness and
diversity were also unaffected and ecologically similar to the
control communities. This study showed that treatment with
ivermectin under extensive farming conditions in the South
African Highveld can be considered safe with regard to the
dung beetle communities under high rainfall conditions.
Strong et al. (1996) carried out a comparative field trial to
examine the effects of ivermectin and fenbendazole boluses on
dung-colonising Diptera and Coleoptera in the UK. Although
there were no significant differences in adult beetle numbers
between the treated and untreated dung, not only was there
a significant difference in larval and pupal numbers between
the ivermectin and fenbendazole treated and untreated
dung, but the larvae found in the ivermectin-treated dung
were inhibited in their development. Pitfall trapping showed
no significant difference in adult beetle numbers between
treated and untreated dung, although a trend towards higher
numbers of beetles attracted to the treated dung was noted.
Römbke et al. (2010) carried out a field study in Spain to
determine the effects of ivermectin on the structure and
function of dung and soil invertebrate communities. They
observed a significantly lower abundance of adult dung
beetles on the dung from cattle treated with ivermectin
compared to the control group. They also noted that although
adult dung beetles were attracted to the ivermectin-spiked
dung, the rate of degradation was slower than for the
control dung.
Dung aracveness studies
Errouissi and Lumaret (2010) studied the effects on the
attractiveness to dung beetles of dung treated with ivermectin.
They found that the ivermectin-contaminated dung showed
a significant attractive effect, which highlighted the danger of
wide-spread ivermectin use as this potentially puts the dung
beetles’ offspring and, indirectly, future beetle generations’
survival at risk.
Eprinomecn and doramecn
Only comparative studies involving the effect of these
products on dung beetles were available and are discussed
in the next section, but two studies involving effects on other
taxa are briefly described.
Lumaret et al. (2005) examined the larvicidal activity of
eprinomectin residues on the dung-inhabiting fly Neomyia
cornicina in France and found that eprinomectin residues in
dung had a significant effect on N. cornicina as no emergences
were observed on the dung from days 1–11 but after day 12
the first flies emerged.
Floate et al. (2008) addressed concerns raised about the
use of endectocides affecting birds that feed on dung-
breeding insects by testing the toxicity of faecal residues
after doramectin treatment. A significant reduction in insect
emergence was noted for dung from cattle treated ≤ 4 weeks
prior, which was attributed to higher concentrations of the
residues.
Moxidecn
Fincher and Wang (1992) tested the effects of moxidectin
on two introduced African species of dung beetle, namely
E. intermedius and Onthophagus gazella. They found no
significant differences between the mean number of brood
balls produced by either species or on the emergence of
progeny between treated and untreated dung. There also
seemed to be no effect on the sex ratio for either species.
They concluded that moxidectin seemed to be compatible
with beneficial dung-burying beetles when used at the
recommended dose.
Iwasa, Suzuki and Maruyama (2008) examined the effects
of moxidectin on non-target coprophilous insects, more
specifically the dung beetle Caccobius jessoensis, in cattle
dung in field as well as laboratory trials in Japan. The results
showed that concentrations were at maximum levels 3 days
after treatment, showed a marked decline by day 7 and
were not detectable by day 21. No significant differences
were found between the control and the treated cattle dung
with regard to numbers and weight of brood balls as well
as emergence rates. Results of the field study, again, showed
no significant differences between the control and the treated
cattle dung. They concluded that moxidectin has no, or at
most, the least effect compared to other avermectins on non-
target coprophagous insects.
Comparave studies: Comparison of
two products
Comparative studies have been undertaken between
ivermectin and doramectin (Dadour 2000; Suárez et al. 2003;
Webb et al. 2010); ivermectin and moxidectin (Doherty
et al. 1994; Strong & Wall 1994); moxidectin and doramectin
(Suárez et al. 2009) and moxidectin and eprinomectin
(Wardhaugh, Longstaff & Morton 2001).
Dadour (2000) examined the impact that abamectin and
doramectin have on the survival and reproduction of
the dung beetle O. binodis. This study was carried out in
Australia and abamectin, rather than ivermectin, was
chosen because it was the first avermectin sold commercially
for the treatment of endoparasites in Australia. Significant

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adult mortality was observed in abamectin-treated dung
3–6 days after treatment and in doramectin-treated dung
9 days after treatment. Whereas abamectin residues had
no effect on adult mortality in sexually mature beetles,
sexually immature (newly emerged) beetles, which
went through a period of intense feeding during which
they were exposed to maximum abamectin residues,
were found to be much more affected by the residues. In
contrast to other studies (Fincher 1992; Krüger & Scholtz
1997), brood ball production was also significantly lower
in beetles fed on dung from cattle treated with abamectin
for up to 42 days after treatment. Brood ball production
was also significantly lower in beetles fed on dung from
cattle treated with doramectin, but only for 3–6 days after
treatment. The enhanced brood mass in beetles fed on
dung from doramectin-treated cattle at 24–34 days after
treatment could not be explained. According to the high-
performance liquid chromatography (HPLC) results,
doramectin reached maximum concentration on day 3 after
treatment, following a linear decline, with an elimination
half-life of 15 days (Dadour 2000).
Suárez et al. (2003) compared the effects of ivermectin and
doramectin on the invertebrate colonisation of cattle dung
in Argentina. No significant differences were found in the
numbers of adult beetles, regardless of the treatment. Faecal
residue concentrations for both ivermectin and doramectin
were highest in the first few days and remained relatively
high throughout the experimental period. Doramectin
concentrations were higher than ivermectin concentrations,
as the results showed that after 180 days of exposure to
environmental conditions, dung collected 27 days after
ivermectin treatment still contained 56% residue compared to
dung collected from doramectin treatment, which contained
75% residue.
Webb et al. (2010) assessed the abundance and dispersal
of dung beetles in response to ivermectin and doramectin
treatment on pastured cattle in Scotland by running a 2-year
field trial. In the field-scale study, significantly more beetles
were trapped in fields grazed by cattle treated with an
avermectin than in fields where cattle remained untreated.
The colonising trials, however, indicated that Aphodius
beetles preferred colonising dung from untreated cattle
rather than dung from cattle treated with doramectin and
could discriminate between dung from untreated cattle and
dung from cattle treated with doramectin at a spatial scale of
at least 70 m.
Doherty et al. (1994) compared the larvicidal activities of
different concentrations of moxidectin and abamectin on
O. gazella to assess the level of threat they pose to dung fauna,
and consequently dung degradation, in Australia. Although
oviposition was not affected by either treatment, larval
survival was affected by all concentrations of abamectin and
by all concentrations of moxidectin over 128 µg/kg. In fact,
moxidectin at 256 µg/kg and 512 µg/kg produced survival
comparable to 4 µg/kg and 8 µg/kg abamectin.
Strong and Wall (1994) compared the relative effects of
ivermectin and moxidectin on the colonisation of dung by
dung-inhabiting insects in England. There was no significant
difference between the three treatments in adult Scarabaeidae
numbers showing that neither ivermectin nor moxidectin
residues repel colonising adult beetles. However, dung
collected from ivermectin-treated cattle up to 7 days after
treatment showed high larval mortality, unlike moxidectin-
treated dung and the control.
Suárez et al. (2009) demonstrated the effects of moxidectin
and doramectin faecal residues on the activity of dung-
colonising insects by depositing dung from cattle treated with
moxidectin, dung from cattle treated with doramectin and
control dung from untreated cattle on a field. Comparisons of
dung degradation were inconclusive; however, total numbers
of insects recovered from control pats were significantly
higher than in treated pats. Furthermore, a lower adverse
effect was observed for moxidectin compared to doramectin
with no significant degradation of moxidectin or doramectin
observed.
Wardhaugh et al. (2001) compared eprinomectin to
moxidectin by examining the survival and development of
Onthophagus taurus when fed on dung from treated cattle in
Australia. The results showed that moxidectin had no effect
on the survival or development of the beetles but the opposite
was found to be true for eprinomectin. High juvenile mortality
and suppressed brood ball production amongst those that
survived were recorded. They concluded by designing a
model that simulated the effects of eprinomectin residues
and suggested that a single treatment of eprinomectin is
capable of reducing the next generation by 25% – 35%.
Comparave studies: Comparison of
all four products
Two laboratory studies provided comparative results amongst
ivermectin, moxidectin, doramectin and eprinomectin but
they were performed under different laboratory conditions
(Floate 2007; Floate, Colwell & Fox 2002). Floate (2006) also
wrote a review about the global environmental effects of
faecal residues left by treatment of cattle with ivermectin,
doramectin, moxidectin and eprinomectin on non-target
dung-inhabiting species.
Pour-on formulations of ivermectin, doramectin,
eprinomectin and moxidectin were applied to four groups
of heifers in Canada at the recommended dose of 500 µg/kg
and dung was collected 1, 2, 4 and 6 weeks after treatment.
Artificial dung pats were then randomly deposited in a block
design in a pasture adjacent to grazing cattle and collected
again after 8 days to analyse insect populations. To monitor
dung beetle activity, dung-baited pitfall traps were placed
in the centre and at either end of the study site. Based on
the number of species affected and duration of suppression,
the results showed that treatment of cattle with doramectin,
ivermectin, eprinomectin or moxidectin, in descending
order of adverse effect and reduced levels of insect activity

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in the dung but moxidectin was the least likely to affect
the natural insect assemblage associated with cattle dung
(Floate et al. 2002).
Floate (2006) raised concerns that the use of endectocides in
cattle may reduce the insect diversity in Canada and lead to
the accumulation of undegraded dung on pastures as a result
of reduced insect activity required for dung pat degradation.
Floate (2007) also compared the field effects of ivermectin,
doramectin, eprinomectin and moxidectin residues on the
attractiveness of dung to dung-colonising insects over 3 years
in Canada. Pitfall traps were set in spring and autumn and
re-baited weekly for a month in each season. Insect captures
were compared between pitfall traps baited with dung from
untreated cattle and dung from cattle treated with doramectin,
eprinomectin, moxidectin or ivermectin at the recommended
dose of 500 µg/kg. Twofold and up to sixfold differences in
captures between control and treated dung were observed.
More specifically, 11 out of 29 cases of attraction and 11
out of 29 cases of repellence were recorded for doramectin,
eprinomectin tended to repel insects, with 19 out of 29 cases
of repellence, whilst ivermectin (17 out of 25 cases) and
moxidectin (17 out of 18 cases) showed a strong attractive
effect. Floate (2007) concluded that emergence of offspring
from field-colonised dung should not be used as a measure
of residue toxicity; standardised laboratory tests should still
be the preferred method, but rather as a measure of ‘insect
activity’, which is a composite measure of residual toxicity,
the number and species composition and the mortality factors
such as predation, competition and parasitism.
Eect of routes of administraon
on faecal concentraon
There are a variety of ways to administer avermectins
to cattle, namely subcutaneously by injection, topically
in the form of a pour-on and orally in various forms.
Lumaret et al. (2005) determined the faecal concentrations
of pour-on eprinomectin in cattle following treatment at
the recommended dose of 500 µg/kg by using HPLC. The
maximum faecal concentrations were recorded 3 days after
treatment. Eprinomectin remained detectable in the faeces
until 29 days after treatment. Lumaret et al. (1993) measured
ivermectin concentrations in dung from cattle treated with
a single dose of injectable ivermectin at the recommended
dose rate of 200 µg/kg by using HPLC. Chemical analysis
of the ivermectin concentration in fresh dung indicated that
it increased daily on days 1–4 after treatment, reaching a
peak of elimination on day 5 followed by a rapid decrease
until day 12, after which the concentration was under the
detection limit.
One would expect that the injectable formulations would be
more effective than the pour-on formulation but this is not
always the case. In the Denmark field trial by Sommer et al.
(1992), the concentration of subcutaneously administered
ivermectin was compared to the pour-on formulation of
ivermectin using HPLC. Although there was no significant
difference between the residue concentrations of the pour-
on and injectable formulations, even though the pour-
on formulation was 2.5 times the dose of the injectable
formulation, the injectable formulation led to a longer
period of delayed dung degradation than the pour-on
formulation.
Herd, Sams and Ashcraft (1996) examined the persistence
of ivermectin in faeces by comparing the faecal residues
following different modes of administration, namely sustained-
release (SR) bolus, pour-on and injectable formulations, in Ohio,
USA. They emphasised the importance of formulation and
route of administration in drug concentration determination,
persistence and ecotoxic potential. All faecal concentrations
recorded, regardless of mode of administration, were well
above concentrations that are lethal or sublethal to beneficial
dung-breeding invertebrates. They concluded by stating
that the SR bolus and pour-on formulations are likely to be
more ecotoxic to non-target organisms than the injectable
formulation judging from their higher faecal concentrations,
and that the SR bolus formulation is of particular concern
because of the persistent excretion of toxic concentrations for
prolonged periods of time.
The way forward
Most recently, Wall and Beynon (2012) wrote a review on the
impact of macrocyclic lactone parasiticides. They reported
that macrocyclic lactone residues from parasiticide treatments
may play an important role in the loss of coprophilous
insects, which may in turn delay pat decomposition. They
added that field studies have provided contradicting results
that reflect confounding factors such as weather conditions,
pat moisture content, pat location, time of year, dung insect
species phenologies, timing and method of application.
These factors are important in determining whether the
results obtained from experimental and laboratory studies
reflect the real impact on the economically important process
of dung decomposition. The timely removal of dung from
pastures by insects and weathering is both functionally and
economically important; if appropriate decomposition does
not occur, cattle farmers may suffer considerable economic
losses as a result of pasture fouling, increases in dung-
breeding pest fly populations and a higher transmission of
livestock endoparasites. The benefits of rapid dung removal
are therefore rather substantial; not only does it reduce such
losses, but it helps to return nutrients to the soil, particularly
nitrogen, a large proportion of which would otherwise be
lost as ammonia.
Conclusion
Although it is difficult to recommend a control programme
that will suit all forms and styles of livestock farming, a
standardised procedure for the testing of antiparasitic
remedies needs to be developed in order to accurately compare
the toxicity of various products. The best scenario would be to
farm holistically, minimising the need for pesticides.

Page 7 of 8 Review Arcle
hp://www.ojvr.org doi:10.4102/ojvr.v82i1.858
Acknowledgements
Compeng interests
The authors declare that they have no financial or personal
relationships which may have inappropriately influenced
them in writing this article.
Authors’ contribuons
C.T.J. (University of Pretoria) was responsible for the
literature review and writing of the article whilst C.H.S.
(University of Pretoria) gave invaluable input and direction.
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