First assessment of the comparative toxicity of ivermectin and moxidectin in adult dung beetles: Sub-lethal symptoms and pre-lethal consequences

Abstract

Among macrocyclic lactones (ML), ivermectin (IVM) and moxidectin (MOX) potentially affect all Ecdysozoan species, with dung beetles being particularly sensitive. The comparative effects of IVM and MOX on adult dung beetles were assessed for the first time to determine both the physiological sub-lethal symptoms and pre-lethal consequences. Inhibition of antennal response and ataxia were tested as two intuitive and ecologically relevant parameters by obtaining the lowest observed effect concentration (LOEC) values and interpolating other relevant toxicity thresholds derived from concentration-response curves (IC50, as the concentration of each ML where the antennal response is inhibited by half; and pLC50, as the quantity of ingested ML where partial paralysis was observed by half of treated individuals) from concentration-response curves. Both sub-lethal and pre-lethal symptoms obtained in this study coincided in that IVM was six times more toxic than MOX for adult dung beetles. Values of LOEC, IC50 and pLC50 obtained for IVM and MOX evaluated in an environmental context indicate that MOX, despite needing more time for tis elimination in the faeces, would be twice as harmful to dung beetles as IVM. This approach will be valuable to clarify the real impact of MLs on dung beetle health and to avoid the subsequent environmental consequences.

Perspectives on the utility of moxidectin for the control of parasitic nematodes in the face of developing anthelmintic resistance

“…Noteworthy advances in this regard were derived from studies on the sensitivity of multiple species of dung flies to MLs (Blanckenhorn et al, 2013), which found that the toxicity of MLs varies considerably across the phylogenetic range of dung flies, and that sensitivity to MOX, though lower in potency, was correlated with sensitivity to IVM, suggesting that variations in either internal accumulation or target affinity are conserved among these arthropod species. A detailed study of the toxicity of MOX and IVM in juvenile and adult dung beetles ( Scarabaeus cicatricosus ) using multiple physiological and developmental assays found that MOX is 5–6 times less potent than IVM against these organisms (Verdú et al, 2018), a finding consistent with previous work. Based on threshold concentrations required for observable effects, this study also reported that fecal concentrations of MOX declined to sub-toxic levels more quickly than for IVM (2 vs. 4 weeks).…”

Moxidectin: an oral treatment for human onchocerciasis

“…It is derived by chemical optimization of F-alpha or nemadectin (LL F-2924α), a fermentation product of the bacterium Streptomyces cyanogriseus ssp. noncyanogenus, through the addition of a methoxime moiety at carbon 23 [18]. Moxidectin differs from ivermectin (also a macrocyclic lactone but of the avermectin family) in the absence of a disaccharide attached to carbon 13, the presence of an olefinic side chain at carbon 25, and a methoxime moiety at carbon 23.…”

“…Moxidectin differs from ivermectin (also a macrocyclic lactone but of the avermectin family) in the absence of a disaccharide attached to carbon 13, the presence of an olefinic side chain at carbon 25, and a methoxime moiety at carbon 23. The chemical structures of ivermectin and moxidectin are compared in [18].…”

Comment on: “The treatment of sarcoptic mange in wildlife: a systematic review”

“…In soil, ivermectin shows a half-life degradation between 7 and 217 days, depending on the solar radiation [3]. Once on the environment, this drug has pre-lethal consequences for dung beetles [30] and for other dung-dwelling invertebrates [3]. If the drug is delivered orally in feeding stuff, as per common practice in game ungulate populations in Spain, soil contamination and thus the potential effects of ivermectin on other terrestrial fauna, and possibly food chain effects, could be expected not only through fecal contamination but through the drug preparation itself.…”