Sorption of selected antiparasitics in soils and sediments.

BACKGROUND: Veterinary pharmaceuticals can enter the environment when excreted after application and burden terrestrial and aquatic ecosystems. However, knowledge about the basic process of sorption in soils and sediments is limited, complicating regulatory decisions. Therefore, batch equilibrium studies were conducted for the widely used antiparasitics abamectin, doramectin, ivermectin, and moxidectin to add to the assessment of their environmental fate. RESULTS: We examined 20 soil samples and six sediments from Germany and Morocco. Analysis was based on HPLC-fluorescence detection after derivatization. For soils, this resulted in distribution coefficients K D of 38-642 mL/g for abamectin, doramectin, and ivermectin. Moxidectin displayed K D between 166 and 3123 mL/g. Normalized to soil organic carbon, log K OC coefficients were 3.63, 3.93, 4.12, and 4.74 mL/g, respectively, revealing high affinity to organic matter of soils and sediments. Within sediments, distribution resulted in higher log K OC of 4.03, 4.13, 4.61, and 4.97 mL/g for the four substances. This emphasizes the diverse nature of organic matter in both environmental media. The results also confirm a newly reported log KOW for ivermectin which is higher than longstanding assumptions. Linear sorption models facilitate comparison with other studies and help establish universal distribution coefficients for the environmental risk assessment of veterinary antiparasitics. CONCLUSIONS: Since environmental exposure affects soils and sediments, future sorption studies should aim to include both matrices to review these essential pharmaceuticals and mitigate environmental risks from their use. The addition of soils and sediments from the African continent (Morocco) touches upon possible broader applications of ivermectin for human use. Especially for ivermectin and moxidectin, strong sorption further indicates high hydrophobicity and provides initial concern for potential aquatic or terrestrial ecotoxicological effects such as bioaccumulation. Our derived K OW estimates also urge to re-assess this important regulatory parameter with contemporary techniques for all four substances. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12302-021-00513-y.

Automated thin-film microextraction coupled to a flow-through cell: somewhere in between passive and active sampling.

A prototype for the automated thin-film microextraction of pharmaceuticals from aqueous solutions has been developed and is presented here for the first time. With a software-controlled setup, extraction methods for ivermectin and iohexol have been developed. The widely used antiparasitic agent ivermectin is non-polar and has a high tendency to sorb to surfaces. In contrast to this, the nonionic but polar iodinated X-ray contrast agent iohexol is freely water soluble. With these two substances, a wide range of polarity is covered. Sorption kinetics and thermodynamics of ivermectin and iohexol were studied. With the presented passive sampling approach, it was possible to extract up to 96.2% ivermectin with a C18-phase within 1 h and up to 74.6% of iohexol with a PS-DVB phase within 36 h out of water. Using abamectin as internal standard, it was possible to quantitatively follow dissipation of ivermectin in a simulated surface water experiment. Predominantly, the newly developed prototype can be used for automated and time-resolved extraction of xenobiotics from waterbodies under field conditions, for the extraction of substances under laboratory conditions as an alternative to the elaborate solid-phase extraction, and for the automated control of chemical reaction kinetics.

The Anthelmintic Ingredient Moxidectin Negatively Affects Seed Germination of Three Temperate Grassland Species.

In animal farming, anthelmintics are regularly applied to control gastrointestinal nematodes. There is plenty of evidence that also non-target organisms, such as dung beetles, are negatively affected by residues of anthelmintics in faeces of domestic ungulates. By contrast, knowledge about possible effects on wild plants is scarce. To bridge this gap of knowledge, we tested for effects of the common anthelmintic formulation Cydectin and its active ingredient moxidectin on seed germination. We conducted a feeding experiment with sheep and germination experiments in a climate chamber. Three wide-spread plant species of temperate grasslands (Centaurea jacea, Galium verum, Plantago lanceolata) were studied. We found significant influences of both, Cydectin and moxidectin, on germination of the tested species. Across species, both formulation and active ingredient solely led to a decrease in germination percentage and synchrony of germination and an increase in mean germination time with the formulation showing a more pronounced response pattern. Our study shows for the first time that anthelmintics have the potential to negatively affect plant regeneration. This has practical implications for nature conservation since our results suggest that treatments of livestock with anthelmintics should be carefully timed to not impede endozoochorous seed exchange between plant populations.

Occurrence and transformation of veterinary pharmaceuticals and biocides in manure: a literature review.

The spread of veterinary medicinal products (VMPs) and biocides via manure onto agriculturally used areas represents a very important emission into the environment for these product groups. Within this literature study, publicly available transformation studies with liquid manure are summarized. Transformation studies were evaluated regarding the transformation fate of tested substances, the origin and characteristics of used manure, the experimental setup, and the measured parameters. As main topics within the 42 evaluated transformation studies, the high dependency of transformation on temperature, redox potential, dry matter content, and other parameters is reported. Test duration throughout the studies ranged from 2 to 374 days and study temperature ranged from 5 to 55 °C. Only seven publications gave information on the redox potential of the manure. Further, the characterization of the matrix in many cases was inadequate due to missing parameters such as dry matter content or pH. Only three publications studied transformation of biocides. To allow for a consistent assessment of studies within the registration process, a harmonized internationally accepted and validated test method is needed. Additionally, monitoring data of VMPs in manure were collected from literature and evaluated regarding the origin and characteristics of the manure, the minimum/maximum found concentrations, and the percentage of identified compounds. Within the 27 evaluated publications, 1568 manure samples were analyzed and 39 different active substances for VMPs and 11 metabolites and transformation products of VMPs could be found in manure. Most often, the samples were analyzed for sulfonamides, tetracyclines, and fluoroquinolones. Not one study searched for biocides or worked with a non-target approach. For sulfadiazine and chlortetracycline, concentrations exceeding the predicted environmental concentrations were found.

Analysis and dissipation of the antiparasitic agent ivermectin in cattle dung under different field conditions.

Cattle treated with the veterinary parasiticide ivermectin fecally excrete residues. The authors report the exposition and dissipation characteristics of these residues in dung of ivermectin-treated cattle and in soil beneath this dung on pastures in Canada, France, Switzerland, and The Netherlands. Residues were quantified for dung collected from cattle after 3 d, 7 d, 14 d, and 28 d posttreatment and subsequently exposed in the field for up to 13 mo. The authors optimized a high-performance liquid chromatography-fluorescence detection method to detect ivermectin residues in dung and soil matrices. They showed that a solid phase extraction and purification step generally can be eliminated to reduce the time and cost of these analyses. They also found that the addition of water to relatively dry samples improves the extraction efficiency of residues. They then analyzed the field samples to document differences in ivermectin dissipation in cattle dung among sites, with 50% dissipation times of up to 32 d and 90% dissipation times >396 d. They further showed that the dissipation characteristics of residues are comparable between dung of ivermectin-treated cattle and dung to which ivermectin has been added directly. Lastly, they report the first use of a desorption electrospray ionization-high-resolution-mass spectrometric method to detect residues of metabolites in a dung matrix. Environ Toxicol Chem 2016;35:1924-1933. © 2016 SETAC.

Nontarget effects of ivermectin residues on earthworms and springtails dwelling beneath dung of treated cattle in four countries.

The authorization of veterinary medicinal products requires that they be assessed for nontarget effects in the environment. Numerous field studies have assessed these effects on dung organisms. However, few studies have examined effects on soil-dwelling organisms, which might be exposed to veterinary medicinal product residues released during dung degradation. The authors compared the abundance of earthworms and springtails in soil beneath dung from untreated cattle and from cattle treated 0 d, 3 d, 7 d, 14 d, and 28 d previously with ivermectin. Study sites were located in different ecoregions in Switzerland (Continental), The Netherlands (Atlantic), France (Mediterranean), and Canada (Northern Mixed Grassland). Samples were collected using standard methods from 1 mo to 12 mo after pat deposition. Ivermectin concentrations in soil beneath dung pats ranged from 0.02 mg/kg dry weight (3 mo) to typically <0.006 mg/kg dry weight (5-7 mo). Earthworms were abundant and species-rich at the Swiss and Dutch sites, less common with fewer species at the French site, and essentially absent at the Canadian site. Diverse but highly variable communities of springtails were present at all sites. Overall, results showed little effect of residues on either earthworms or springtails. The authors recommend that inclusion of soil organisms in field studies to assess the nontarget effects of veterinary medicinal products be required only if earthworms or springtails exhibit sensitivity to the product in laboratory tests. Environ Toxicol Chem 2016;35:1959-1969. © 2015 SETAC.

A four-country ring test of nontarget effects of ivermectin residues on the function of coprophilous communities of arthropods in breaking down livestock dung.

By degrading the dung of livestock that graze on pastures, coprophilous arthropods accelerate the cycling of nutrients to maintain pasture quality. Many veterinary medicinal products, such as ivermectin, are excreted unchanged in the dung of treated livestock. These residues can be insecticidal and may reduce the function (i.e., dung-degradation) of the coprophilous community. In the present study, we used a standard method to monitor the degradation of dung from cattle treated with ivermectin. The present study was performed during a 1-yr period on pastures in Canada, France, The Netherlands, and Switzerland. Large effects of residue were detected on the coprophilous community, but degradation of dung was not significantly hampered. The results emphasize that failure to detect an effect of veterinary medicinal product residues on dung-degradation does not mean that the residues do not affect the coprophilous community. Rather, insect activity is only one of many factors that affect degradation, and these other factors may mask the nontarget effect of residues. Environ Toxicol Chem 2016;35:1953-1958. © 2015 SETAC.

Validation of a standard field test method in four countries to assess the toxicity of residues in dung of cattle treated with veterinary medical products.

Registration of veterinary medical products includes the provision that field tests may be required to assess potential nontarget effects associated with the excretion of product residues in dung of treated livestock (phase II, tier B testing). However, regulatory agencies provide no guidance on the format of these tests. In the present study, the authors report on the development of a standardized field test method designed to serve as a tier B test. Dung was collected from cattle before and up to 2 mo after treatment with a topical application of a test compound (ivermectin). Pats formed of dung from the different treatments were placed concurrently in the field to be colonized by insects. The abundance, richness, and diversity of insects developing from egg to adult in these pats were compared across treatments using analysis of variance tests. Regression analyses were used to regress abundance, richness, and diversity against residue concentrations in each treatment. Results of the regression were used to estimate mean lethal concentration (LC50) values. The robustness of the method and the repeatability of its findings were assessed concurrently in 4 countries (Canada, France, Switzerland, and The Netherlands) in climatically diverse ecoregions. Results were generally consistent across countries, and support the method's formal adoption by the European Union to assess the effects of veterinary medical product residues on the composition and diversity of insects in dung of treated livestock. Environ Toxicol Chem 2016;35:1934-1946. © 2015 Crown in the right of Canada. Published by Wiley Periodicals Inc., on behalf of SETAC.