Influence of manure application method on veterinary medicine losses to water.

Veterinary medicines are routinely used within modern animal husbandry, which results in frequent detections within animal manures and slurries. The application of manures to land as a form of organic fertiliser presents a pathway by which these bioactive chemicals can enter the environment. However, to date, there is limited understanding regarding the influence of commonly used manure application methods on veterinary medicine fate in soil systems. To bridge this knowledge gap, a semi-field study was conducted to assess the influence of commonly used application methods such as, broadcast, chisel sweep, and incorporation on veterinary medicine losses to waters. A range of veterinary medicines were selected and applied as a mixture; these were enrofloxacin, florfenicol, lincomycin, meloxicam, oxytetracycline, sulfadiazine, trimethoprim and tylosin. All the assessed veterinary medicines were detected within surface runoff and leachates, and the concentrations generally decreased throughout the irrigation period. The surface runoff concentrations ranged from 0.49 to 183.47 µg/L and 2.26-236.83 µg/L for the bare soil and grass assessments respectively. The leachate concentrations ranged from 0.04 to 309.66 µg/L and 0.33-37.79 µg/L for the bare soil and grass assessments respectively. More advanced application methods (chisel sweep) were found to significantly reduce the mass loads of veterinary medicines transported to surface runoff and leachate by 13-56% and 49-88% over that of broadcast. Incorporating pig slurries reduced the losses further with surface runoff and leachate losses being 13-56% and 49-88% lower than broadcast. Our results show that manure application techniques have a significant effect on veterinary medicine fate in the environment and as such these effects should be considered in the decision-making processes for the management of manures as well as from a risk mitigation perspective for aquatic compartments.

The effect of anaerobic pig slurry redox potentials on the degradation of veterinary medicines.

Veterinary medicines are frequently used within intensive livestock husbandry and there has been a growing interest regarding their fate in the environment. However, research has seldom assessed the influence of pig slurry properties on the fate of veterinary medicines even though such an understanding is essential for a more robust environmental risk assessment. Changes within manure degradation rates have the potential to alter the concentration of antibiotics applied to land, and the outcome of the risk assessment. The aim of this work was to investigate whether commonly reported redox potentials affect the degradation rates of acetyl-salicylic acid, ceftiofur, florfenicol, oxytetracycline, sulfamethoxazole, and tylosin. The employed redox potentials were -100 mV (reduced), -250 mV (anaerobic) and -400 mV (very anaerobic). A compound specific relationship was observed where the degradation of ceftiofur, florfenicol, oxytetracycline and sulfamethoxazole was inhibited under reduced conditions over that of very anaerobic; the respective DT50 values were 0.7-1.84 h, 1.35-3.61 h, 22.2-49.8 h, 131-211 h and 35.4-94 h. In contrast, tylosin was found to degrade faster at reduced conditions over very anaerobic (DT50 6.88-19.4 h). The presented research demonstrates the importance of redox potential on degradation rates and suggests we need stringent and harmonized redox control to improve the environmental risk assessment of veterinary medicines. Environmental relevance and significance: Given the significant effect of anaerobic redox potentials on veterinary medicine fate tighter regulation is required in manure degradation trials.

High Concentrations of Pharmaceuticals in a Nigerian River Catchment.

Pharmaceutical contamination of the environment is recognized as a global problem although most research has focused on Europe and North America to date, and there remains a dearth of information for developing countries, including those in Africa. To address this data gap, the occurrence of 37 pharmaceuticals belonging to 19 therapeutic classes was monitored in surface water and effluents in Lagos State, Southwest Nigeria. Samples were collected quarterly between April 2017 and March 2018 from 22 sites, and 26 compounds were detected at least once, many in the µg/L range. Maximum concentrations for those compounds detected ranged from 75 to 129 µg L-1 , and even mean concentrations for 13 compounds were in the order of µg L-1 . These values are among the highest ever measured globally. Sewage effluent was more important than drug manufacturing waste in polluting rivers, although there are likely to be numerous unregulated sources of effluent being discharged to rivers that require further study, including urban waste collection areas and vacuum trucks that collect effluent. Seasonal trends in the data were complex, with some compounds being found at higher concentrations in the dry season and, conversely, others being greater during the wet period; this variation potentially relates to the variety of pollution sources in the catchment. Pharmaceuticals are indispensable to human health, although their usage and discharge into the aquatic environment may lead to ecological problems and antibiotic resistance. The data we present indicate that pharmaceutical pollution of freshwaters is a serious issue in Nigeria, and management efforts are needed to improve this problem. Environ Toxicol Chem 2022;41:551-558. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Assessing the influence of pig slurry pH on the degradation of selected antibiotic compounds.

Veterinary medicines are routinely used in animal husbandry and the environment may consequently be exposed to them via manure applications. This presents potential environmental and societal risks such as toxicological effects to aquatic/terrestrial organisms and the spread of antimicrobial resistance. Regulatory studies that assess the degradability of veterinary antibiotics during manure storage currently permit the use of just one manure per animal type although we speculate that heterogenic properties such as pH could be driving significant variability within degradation rates. To bridge this knowledge gap and assess degradation variability with pH, laboratory degradation studies were performed on a broad range of antibiotics (ceftiofur, florfenicol, oxytetracycline, sulfamethoxazole and tylosin) at three different environmentally relevant pH levels (5.5, 7, and 8.5). The effect of pig slurry pH on degradation rates was found to be significant and compound specific. Usually, acidic slurries were found to inhibit degradation when compared to neutral pH, for florfenicol, tylosin, and ceftiofur; the associated changes in DT50 (half-life) values were 2-209 h, 35.28-234 h, and 0.98-2.13 h, respectively. In some circumstances alkaline slurries were observed to enhance the degradation rate when compared to those for neutral pH, for tylosin, the respective changes in DT50 values were from 3.52 to 35.28 h. Comparatively, the degradation of sulfamethoxazole was enhanced by acidic conditions compared to neutral (DT50 20.6-31.6 h). Tentative identification of unknown transformation products (TPs) was achieved for sulfamethoxazole and florfenicol for the first time in pig slurries. These results reveal the importance of considering slurry pH when assessing the degradation of antibiotic compounds, which has implications for the acidification of manures and the environmental risk assessment for veterinary medicines. Environmental relevance and significance: Given the significant effect of pig slurry pH on degradation rates, manure degradation studies need to be harmonised and standardized, taking into account the influence of pH.

Isolation and characterization of metaldehyde-degrading bacteria from domestic soils.

Metaldehyde is a common molluscicide, used to control slugs in agriculture and horticulture. It is resistant to breakdown by current water treatment processes, and its accumulation in drinking water sources leads to regular regulatory failures in drinking water quality. To address this problem, we isolated metaldehyde-degrading microbes from domestic soils. Two distinct bacterial isolates were cultured, that were able to grow prototrophically using metaldehyde as sole carbon and energy source. One isolate belonged to the genus Acinetobacter (strain designation E1) and the other isolate belonged to the genus Variovorax (strain designation E3). Acinetobacter E1 was able to degrade metaldehyde to a residual concentration < 1 nM, whereas closely related Acinetobacter strains were completely unable to degrade metaldehyde. Variovorax E3 grew and degraded metaldehyde more slowly than Acinetobacter E1, and residual metaldehyde remained at the end of growth of the Variovorax E3 strain. Biological degradation of metaldehyde using these bacterial strains or approaches that allow in situ amplification of metaldehyde-degrading bacteria may represent a way forward for dealing with metaldehyde contamination in soils and water.

Toxicological and ecotoxicological risk-based prioritization of pharmaceuticals in the natural environment.

Approximately 1500 active pharmaceutical ingredients are currently in use; however, the environmental occurrence and impacts of only a small proportion of these have been investigated. Recognizing that it would be impractical to monitor and assess all pharmaceuticals that are in use, several previous studies have proposed the use of prioritization approaches to identify substances of most concern so that resources can be focused on these. All of these previous approaches suffer from limitations. In the present study, the authors draw on experience from previous prioritization exercises and present a holistic approach for prioritizing pharmaceuticals in the environment in terms of risks to aquatic and soil organisms, avian and mammalian wildlife, and humans. The approach considers both apical ecotoxicological endpoints as well as potential nonapical effects related to the therapeutic mode of action. Application of the approach is illustrated for 146 active pharmaceuticals that are used either in the community or in hospital settings in the United Kingdom. Using the approach, 16 compounds were identified as a potential priority. These substances include compounds belonging to the antibiotic, antidepressant, anti-inflammatory, antidiabetic, antiobesity, and estrogen classes as well as associated metabolites. In the future, the prioritization approach should be applied more broadly around the different regions of the world. Environ Toxicol Chem 2016;35:1550-1559. © 2016 SETAC.

Investigation into the occurrence in food of veterinary medicines, pharmaceuticals, and chemicals used in personal care products.

Human exposure to emerging contaminants by indirect routes is of increasing interest. This study assessed the contamination of food by chemicals used in human pharmaceuticals (HPs), veterinary medicines (VMs), and personal care products (PCPs). A prioritization study was undertaken to identify the chemicals and food-producing scenarios most likely to result in contamination of food. Around 400 samples of mushrooms, vegetables, aquaculture products, and animal tissues were collected from sites in the United Kingdom, along with aquaculture products imported from Southeast Asia. A number of multianalyte methods were developed and validated for the analysis of the prioritized compounds in these samples. The analysis of all sample-method combinations required approximately 18000 determinations. Around 325 individual residues, including parabens, musk compounds, and antibiotics, were detected in 118 individual samples, but mostly at low nanograms per gram concentrations. Results suggest that the limited contamination of target chemicals occurred in the realistic food-producing scenarios investigated.

Do natural rubber latex condoms pose a risk to aquatic systems?

The presence and potential adverse effects of plastic-polymers in the environment are receiving increasing attention in the popular and scientific press. However, quantifying emissions, exposure and effects of these materials remains a challenge. This paper describes the application of a questionnaire survey to quantify emissions of condom material from the domestic household to the sewage waste stream. Condoms are an important mainstay for birth control and the reduction of sexually transmitted infections. Survey participants were estimated to flush condoms down the toilet 2.96% of the time, and emissions were calculated as 0.99 mg of condom material per person per day. Using information on screening efficiencies at sewage treatment plants, the questionnaire data was combined with a GIS-based water quality model (LF2000-WQX) to predicted environmental concentrations (PEC) in a UK river basin catchment. Annual average PECs of condom material were 0.08-0.2 µg L(-1), under the model scenario used. To put these PECs into context, rubber latex condom material was degraded in outdoor microcosms. This resulted in the formation of a complex mixture of substances including chemical degradation products and particles in the nano range. The direct effects of the degradation mixture were investigated using two freshwater organisms with different life cycle traits, the water column crustacean Daphnia magna and the sediment-dwelling larval of Chironomus riparius. Ecotoxicity tests investigated both acute and chronic endpoints and were shown to exhibit no toxic effects. This precluded the derivation of a genuine no-effect concentration. Hence, the results suggest that limited risk to invertebrates is associated with latex condom degradation products to the organisms tested. Future studies should extend this risk framework to assess risks of condoms to other taxonomic groups as well as the risks of other polymer materials.

Environmental fate of processed natural rubber latex.

In this study, processed natural rubber latex was degraded in outdoor aquatic microcosms, under a number of treatment scenarios for 200 days. The analytical strategy adopted aimed to characterise a range of volatile, semi-volatile and non-volatile substances. Zinc, was shown to migrate from the latex into solution and increase in concentration over time. Dissolved compounds for which predicted formulas were generated largely consisted of oxygen containing compounds, and are potential oxidised polyisoprene oligomers of various chain lengths. A classification of samples based on principal component analysis showed a clear separation of the degraded latex samples from the representative controls. This technique identified an increase in the complexity of the substances produced and showed that these substances undergo further degradation and transformation processes. A number of volatile substances were also identified indicating the atmosphere to be a potential receiving environmental compartment for polymer degradates. Overall, the results show that complex mixtures of substances are produced when polymer-based materials degrade under environmental conditions.

Effects of environmental conditions on latex degradation in aquatic systems.

Following use polymer materials may be released to the natural environment distributed to various environmental compartments and may undergo a variety of mechanical and chemical weathering processes. This study characterised the degradation of a latex polymer of different thicknesses under a range of environmental conditions in outdoor microcosms. Samples were immersed in either demineralised water, artificial freshwater and marine water media and exposed for a period of 200-250 days with exposure starting at different times of the year. Effects of pH, agitation and the exclusion of light on degradation were also studied. At the end of the exposure period, recovery of polymer material ≥ 1.6 µm ranged from a low of 22.04% (± 16.35, for the freshwater treatment at pH5.5) to a high of 97.73% (± 0.38, for the exclusion of light treatment). The disappearance of the bulk material corresponded to an increase in nanoparticles and dissolved organic material in the test media. Modelled degradation kinetics were characterised by multi-phasic degradation patterns and the results indicated degradation rate is affected by light intensity and polymer thickness. Mass balance analysis indicates that losses of volatile materials to the air compartment may also be occurring.

Investigation of the fate of trifluralin in shrimp.

Juvenile Pacific white shrimp (Litopenaeus vannamei) were exposed to trifluralin at 0.1 and 0.01 mg L(-1) for 72 h under controlled conditions. Samples of shrimp and tank water were collected at intervals up to 48 days after exposure. Analysis of the shrimp tissues by gas chromatography-mass spectrometry (GC-MS) and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-qToF-MS) in combination with profiling and metabolite identification software (Agilent MET-ID and Mass Profiler Professional) detected the presence of parent trifluralin together with two main transformation products (TPs), 2-ethyl-7-nitro-5-(trifluoromethyl)benzimidazole (TP1) and 2-amino-6-nitro-4-(trifluoromethyl)phenyl)propylamine (TP2). The highest concentration of trifluralin, determined by GC-MS, was 120 µg kg(-1) at 0 day withdrawal. Residues of trifluralin (CCα = 0.25 µg kg(-1), CCß = 0.42 µg kg(-1)) were detectable for up to 7 days after exposure. Similarly, the highest concentrations of TP1 and TP 2, determined by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), were 14 and 18 µg kg(-1), respectively. Residues of TP1 (CCα = 0.05 µg kg(-1), CCß = 0.09 µg kg(-1)) and TP2 (CCα = 0.1 µg kg(-1), CCß = 0.17 µg kg(-1)) were detectable for up to 4 and 24 withdrawal days, respectively.

Effects of repeated pulsed herbicide exposures on the growth of aquatic macrophytes.

Many contaminants are released into aquatic systems intermittently in a series of pulses. Pulse timing and magnitude can vary according to usage, compound-specific physicochemical properties, and use area characteristics. Standard laboratory ecotoxicity tests typically employ continuous exposure concentrations over defined durations and thus may not accurately and realistically reflect the effects of certain compounds on aquatic organisms, resulting in potential over- or underestimation. Consequently, the relative effects of pulsed (2 and 4 d) and continuous exposures of the duckweed Lemna minor to isoproturon, metsulfuron-methyl, and pentachlorophenol over a period of 42 d were explored in the present study. At the highest test concentrations, exposure of L. minor to pulses of metsulfuron-methyl resulted in effects on growth similar to those of an equivalent continuous exposure. For isoproturon, pulsed exposures had a lower impact than a corresponding continuous exposure, whereas the effect of pentachlorophenol delivered in pulses was greater. These differences may be explained by compound-specific uptake and degradation or dissipation rates in plants and the recovery potential that occurs following pulses for different pesticides. Given these results, use of a simple time-weighted average approach to estimate effects of intermittent exposures from short-term standard toxicity studies may not provide an accurate prediction that reflects realistic exposure scenarios. Development of mechanistic modeling approaches may facilitate better estimates of effects from intermittent exposures.

Comparative pharmacokinetics of liquid and lyophilized formulations of IV RhIG immune globulin.

To compare the pharmacokinetics, safety, and tolerability of the liquid and lyophilized formulations of Rh(0)(D) immune globulin intravenous (human) (IV RhIG) administered intramuscularly (IM) and intravenously (IV). In 2 randomized, parallel arm, blinded, phase I studies, 142 healthy adult volunteers received a single dose of either the liquid or lyophilized formulation administered IM (300 microg in Study 1; 15 microg/kg in Study 2) or IV (50 microg/kg in Study 1). Pharmacokinetics (area under the curve [AUC}, C(max), t(1/2), T(max)) and safety data were assessed over 84 days. The 2 formulations had comparable pharmacokinetics following both IM and IV administration. The ratios (90% confidence intervals) for AUC and C(max) treatment means were, for most assessments, within the predefined FDA acceptance range of 80%-125%, demonstrating the bioequivalence of the liquid and lyophilized formulations. Both formulations were equally well tolerated. Study results demonstrate comparable safety and pharmacokinetic profiles of the liquid and lyophilized formulations of IV RhIG. These findings suggest that the liquid formulation will be therapeutically equivalent to the lyophilized formulation but in a more convenient ready-to-use dosage form that may also reduce preparation errors.

Prioritization of pesticide environmental transformation products in drinking water supplies.

Receiving waters within catchments may be exposed to many different transformation products following the application of pesticides. As environmental waters are abstracted for drinking water treatment these compounds may pose a risk to human health. This paper describes a prioritization approach for identifying the most important transformation products in drinking water sources. The approach can be applied to different geographical areas that have suitable pesticide usage data. The risk based approach incorporates data on pesticide usage and toxicity as well as transformation product formation, mobility, and persistence. The application of the approach is illustrated for two geographical areas that have good quality pesticide usage data: Great Britain and California. The transformation products with the highest risk index and a complete experimentally derived data set for Great Britain were 3,5,6-trichloro-2-pyridinol, thifensulfuron acid, and kresoxim-methyl acid and for California were carbendazim, aldicarb sulfoxide, and RP30228.

Uptake of veterinary medicines from soils into plants.

Medicines play an important role in the treatment and prevention of disease. Whereas the side effects on human and animal health resulting directly from treatment have been widely documented, only recently have the occurrence and fate of medicines in the environment and the potential consequences for human health been recognized as an issue warranting consideration. Medicines have been shown to be released to soils and to persist in the environment. This study was performed to investigate the potential for a range of veterinary medicines to be taken up from soil by plants used for human consumption and to assess the potential significance of this exposure route in terms of human health. Soil analyses indicated that, for selected substances, measurable residues of these are likely to occur in soils for at least 5 months following application of manure containing these compounds. Experimental studies on the uptake of veterinary medicines into carrot roots (tubers) and lettuce leaves showed that only florfenicol, levamisole, and trimethoprim were taken up by lettuces, whereas diazinon, enrofloxacin, florfenicol, and trimethoprim were detected in carrot roots. Measured concentrations in plant material were used to model potential adult human exposure to these compounds. Although exposure concentrations were appreciable in a few instances, accounting for approximately 10% of the acceptable daily intake values (ADI), all were lower than the ADI values, indicating that, at least for compounds with properties similar to those considered here, there is little evidence of an appreciable risk. This exposure route may, however, be important when veterinary medicines have a very low ADI, at which they elicit subtle effects over prolonged periods, or when exposure is occurring via a number of routes at once. Although degradation products (produced in the soil or the plant) were not measured, it is possible for some substances that these could increase the risks to consumers.

Assessing the ecotoxicity of pesticide transformation products.

Once released to the environment, pesticides may be degraded by abiotic and biotic processes. While parent compounds are assessed in detail in many regulatory schemes, the requirements for the assessment of transformation products are less well developed. This study was therefore performed to explore the relationships between the toxicity of transformation products and their parent compounds and to develop a pragmatic approach for use in the risk assessment of transformation products. Data were obtained on the properties and ecotoxicity of transformation products arising from a wide range of pesticides. Generally, transformation products were less toxic to fish, daphnids, and algae than their parent compound. In instances where a product was more toxic, the increase in toxicity could be explained by either (1) the presence of a pesticide toxicophore; (2) the fact that the product is the active part of a propesticide; (3) the product is accumulated to a greater extent than the parent compound; or (4) the product has a more potent mode of action than the parent. On the basis of the findings, an approach has been proposed to estimate the ecotoxicity of transformation products based on chemical structure and data on the toxicity of the parent compound. The assessments can be performed at an early stage in the risk assessment process to identify those substances that require further testing.