Investigation of doxycycline residues in bones after oral administration to broiler chickens.

Introduction: Chicken bones, a by-product of the poultry industry, can directly or indirectly enter the food chain. Bone meal and bone products could be sources of many contaminants. Considering the wide range of uses made of bones in the culinary and food industries, this material needs to be safe and antibiotic residue-free. To determine if such is the case, the concentration of doxycycline in chicken bones was investigated, this antimicrobial being one of the most commonly used in poultry production. Material and Methods: Ross 308 broilers were grouped into three experimental and one control group. Doxycycline was administered in drinking water at therapeutic and sub-therapeutic doses, as well as via spray treatment. The concentration of doxycycline in bones was determined post slaughter by ultra-high performance liquid chromatography-tandem mass spectrometry. Results: Doxycycline was quantified at 135 µg/kg 22 days after the last day of antibiotic administration at therapeutic doses; 2,285 µg/kg after sub-therapeutic treatment for 27 days and 9.62 µg/kg 22 days after the end of spray application. Conclusion: High concentrations and long persistence of doxycycline in bones were found in this study. Doxycycline can contaminate all bone-derived products in the food and fertiliser industries.

Simultaneous determination of 68 antimicrobial compounds in pigs oral fluid by ultra-high performance liquid chromatography-tandem mass spectrometry.

Improper use of antimicrobials in veterinary medicine can lead to residues in food of animal origin. Post-mortem monitoring of antibiotics in animal products is carried out as part of official EU programmes on food safety and consumer health. Oral fluid testing is a promising surveillance method to monitor appropriate treatment in pigs and to avoid residues in edible tissues. Oral fluid analysis can be implemented in an antibiotic residue control programme, thus preventing economic losses due to meat disposal as a result of drug detection in tissues after the withdrawal period. An analytical method was developed for the analysis of 68 compounds from 12 groups (penicillins, cephalosporins, sulfonamides, macrolides, fluoroquinolones, tetracyclines, aminoglycosides, pleuromutilins, diaminopyrimidines, lincosamides, polypeptides and sulfones) in pig oral fluid. Extraction of antibacterials was performed with 0.5 % formic acid. Analyses were carried out by ultra-high performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-MS/MS) detection. The chromatographic separation was achieved on a Zorbax analytical column (2.1 × 50 mm) with a mobile phase consisting of acetonitrile and heptafluorobutyric acid (HFBA). The total run time was 7 min. The method was validated as a confirmatory method according to the Commission Implementing Regulation (EU) 2021/808. The reliability of the method was verified by testing real samples from pig farms.

Investigation of 29 Antimicrobial Compounds in Soil Using Newly Developed UHPLC-MS/MS Method.

While the prudent and reasonable use of veterinary antimicrobial agents in food-producing animals is necessary, researchers over the decades have shown that these antimicrobial agents can spread into the environment through livestock manure and wastewater. The analysis of the occurrence of antimicrobial compounds in soil samples is of a great importance to determine potential impacts on human and animal health and the environment. In this study, an affordable, rugged and simple analytical method has been developed for the determination of twenty-nine antimicrobial compounds from five different classes (tetracyclines, fluoro(quinolones), macrolides, sulfonamides and diaminopirimidines). Liquid-liquid extraction (LLE) with extract filtration combined with ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was the best strategy for the simultaneous determination of all analytes. The developed method was validated according to the Commission Implementing Regulation (EU) 2021/808. The limit of detections (LODs) ranged from 0.5 to 2.0 µg/kg, while the limit of quantitation (LOQ) was established at 1.0 to 20.0 µg/kg. The developed method was successfully applied for the determination of antimicrobial residues in one hundred and eighteen soil samples obtained from four European countries (Austria, Czech Republic, Estonia and Portugal). Doxycycline in the concentration levels of 9.07 µg/kg-20.6 µg/kg was detected in eight of the analysed samples. Samples were collected from areas where natural fertilizers (swine or cow manure) were applied. Our method can be efficiently used to monitor anti-microbial compounds in soil samples.

Analysis of Aminoglycoside Antibiotics: A Challenge in Food Control.

Aminoglycosides are a widely used group of antibiotics in veterinary medicine. However, misuse and abuse of these drugs can lead to residues in the edible tissues of animals. Due to the toxicity of aminoglycosides and the exposure of consumers to the emergence of drug resistance, new methods are being sought to determine aminoglycosides in food. The method presented in this manuscript describes the determination of twelve aminoglycosides (streptomycin, dihydrostreptomycin, spectinomycin, neomycin, gentamicin, hygromycin, paromomycin, kanamycin, tobramycin, amikacin, apramycin, and sisomycin) in thirteen matrices (muscle, kidney, liver, fat, sausages, shrimps, fish honey, milk, eggs, whey powder, sour cream, and curd). Aminoglycosides were isolated from samples with extraction buffer (10 mM NH4OOCH3, 0.4 mM Na2EDTA, 1% NaCl, 2% TCA). For the clean-up purpose, HLB cartridges were used. Analysis was performed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) with a Poroshell analytical column and a mobile phase of acetonitrile and heptafluorobutyric acid. The method was validated according to Commission Regulation (EU) 2021/808 requirements. Good performance characteristics were obtained for recovery, linearity, precision, specificity, and decision limits (CCα). This simple and high-sensitivity method can determine multi-aminoglycosides in various food samples for confirmatory analysis.

Analysis of Antimicrobials in Muscle and Drinking Water in Terms of Reducing the Need of Antimicrobial Use by Increasing the Health and Welfare of Pig and Broiler.

Antimicrobial residues may pose harmful effects on the health of consumers. At the same time, an adequate quality of drinking water for animals is one of the important element to ensure animal welfare and food without antibacterials. The presented study is aimed at estimating the residue levels of antibacterial compounds, such as penicillins, cephalosporin, macrolides, tetracyclines, quinolones, sulphonamides, aminoglycosides, diaminopirymidines, pleuromutilines and lincosamides in meat and on-farm drinking water samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS), as a part of a surveillance system on pig and broiler farms within the project Healthy Livestock. A total of 870 samples of muscle from pig and broiler, as well as 229 water samples were analysed for antibiotic residues. Samples were collected from farms in EU countries in two steps, before and after implementation of a tailor-made health plan. In muscle samples, the detected concentrations of doxycycline in the post-intervention step (15.9-70.8 µg/kg) were lower than concentrations in the pre-intervention step (20.6-100 µg/kg). In water samples, doxycycline in an average concentration of 119 µg/L in the pre- and 23.1 µg/L in the post-intervention step, as well as enrofloxacin at concentrations of 170 µg/L in the pre- and 1.72 µg/L in the post-intervention step were quantified. Amoxicillin was only present before intervention. The obtained results confirm the effectiveness of the intervention actions. The concentrations of antibiotics in muscles and water were lower after implementation of a health plan on the farms.

A Preliminary Study on the Concentration of Oxytetracycline and 4-Epi-Oxytetracycline in Sow Milk.

Even though modern analytical chemistry has developed a methodology enabling evaluation of the presence of OTC in milk, data regarding its concentration in the material collected from lactating sows are missing. Therefore, this paper was intended to provide new data on the transmission of OTC and its epimer, 4-epi-oxytetracycline (4-epi-OTC), in the milk of lactating sows after a singular intramuscular administration of a long-acting form of the antibiotic. The determination of OTC and 4-epi-OTC was carried out using ultrahigh-performance liquid chromatography with mass spectrometry (UHPLC-MS/MS). The highest average concentration of antibiotic (1132.2 µgL-1) was observed in samples collected 1 day after the administration of the drug. The average OTC level at day 3 was 358 µgL-1. The average concentration of the antibiotic found on the 21st day was 12.3 µgL-1. The highest average concentration of 4-epi-OTC-i.e., 54 µgL-1-was noted 1 day after the administration. Amongst samples collected at day 3, the average level of the substance in question was 26.4 µgL-1. The average value observed at day 21 was 1.5 µgL-1. Our results indicated considerable OTC and 4-epi-OTC transmission into the milk of lactating sows.

Acetaminophen pharmacokinetics in geese.

OBJECTIVE: To evaluate the pharmacokinetics of acetaminophen (APAP) after single-dose IV and PO in the goose; to quantify APAP and its main metabolites in goose muscle, heart, lung, liver, and kidney; and to perform a histopathologic evaluation of goose stomach, duodenum, liver, and kidney tissues for potential signs of toxicity. ANIMALS: 24 geese. PROCEDURES: Geese were randomly divided into 3 groups (n = 8). Group I received APAP (10 mg/kg) IV, and groups II and III received the same dose PO. Groups I and II were used for the pharmacokinetic assessment, and group III was used for the residue analysis and histopathologic evaluation. APAP and its metabolites were quantified in plasma and tissues by ultra-high-performance liquid chromatography-tandem mass spectrometry, and the pharmacokinetic analysis was performed using a noncompartmental approach. RESULTS: APAP plasma concentrations were lower than those of the metabolites in similar selected time points after both treatments. After IV treatment, the APAP area under the curve value was statistically higher than that after PO administration, resulting in an oral bioavailability of 46%. In contrast, the area under the curve of the metabolites following PO administration was statistically higher than those found after IV administration. Tissue residues of APAP were highest in the liver, with an accumulation index > 1. Fatty degeneration of hepatocytes was observed 24 hours after administration of APAP. CLINICAL RELEVANCE: In geese, treatment by PO administration of APAP shows incomplete absorption and a slight accumulation in lung and liver. Tissue alterations occurred in the liver at 24 hours, while no signs of toxicity were found in the other tested organs.

UHPLC-MS/MS Analysis of Antibiotics Transfer and Concentrations in Porcine Oral Fluid after Intramuscular Application.

The monitoring of antibiotic use in animals is a crucial element to ensure food safety. The main goal of this study was to analyse the distribution of selected antibiotics to porcine oral fluid, as well as to demonstrate that an oral fluid is an alternative to other biological matrices used in the control of antibacterials. Therefore, an animal study with pigs treated using seven different antibiotics was performed. Sulfadoxine (SDX) with trimethoprim (TRMP), lincomycin (LIN), tiamulin (TIAM), tylosin (TYL), amoxicillin (AMX) and penicillin G (PEN G) were injected intramuscularly to pigs, and concentrations of these analytes in the oral fluid were assessed. Ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) was used to quantify the analytes. On the first day of medication, the highest concentrations for SDX and TRMP at the level of 22,300 µg/kg and 14,100 µg/kg were found, respectively. The concentrations of LIN (10,500 µg/kg) and TIAM (7600 µg/kg) were also relatively high. The peak of TYL was recorded on the second day of drug administration. Most of the analytes were present in oral fluid for 30 days, apart from TYL, which was detected for 27 days. It was found that AMX and PEN G were quantified only for 5 and 8 days, respectively, at very low concentrations. It was found that oral fluid can be used for the verification of antibiotics on pig farms.

Risk to Public Health Regarding Doxycycline Residues in Chicken Claws.

Doxycycline residues in claws may pose a potential risk to humans. A study with broiler chickens was performed to find the concentrations of doxycycline in claws after treatment. For the quantification of the antibiotic of interest in claws, an ultrahigh-performance liquid chromatography-tandem mass spectrometry method was developed. Doxycycline was detectable at 3043 µg/kg at sub-therapeutic treatment, 223 µg/kg after therapeutic doses, and 14 µg/kg after spray application on the last day of the experiment (day 22). Almost 70 days is required for the concentration of doxycycline to reach zero. The obtained results show that monitoring of doxycycline in claws should be implemented.

Propacetamol in dogs: First description of its pharmacokinetics after intravenous and oral administration.

Propacetamol is a prodrug form of paracetamol (APAP) licensed for human use as a pain reliever in postoperative care. It is prescribed if APAP cannot be administered orally or rectally to a patient and for patients in whom nonsteroidal anti-inflammatory drugs are contraindicated. In this study, we aimed to quantify the pharmacokinetics of APAP and its metabolites, paracetamol sulfate (PS), paracetamol glucuronide (PG), and N-acetyl-p-benzoquinone imine (NAPQI), after a single oral and intravenous (IV) administration of 30 mg/kg of propacetamol to six healthy adult Labrador dogs according to a 2 × 2 crossover study. The analyses were performed using a validated HPLC-MS/MS method. PS and PG exposures were higher than that of APAP, while NAPQI concentrations were constantly below the detection limit of the analytical method. IV propacetamol administration produced 30% more APAP than oral administration. However, propacetamol released a significantly lower amount of active moiety in dogs than in humans. The propacetamol dose administered in this study did not produce plasma APAP concentrations above the threshold sufficient to provide analgesia in adult humans (4 µg/mL). In conclusion, direct IV injection of APAP instead of propacetamol might be a better clinical option for pain relief in dogs.

Transfer of enrofloxacin, ciprofloxacin, and lincomycin into eggshells and residue depletion in egg components after multiple oral administration to laying hens.

Regardless of whether antimicrobial drugs are administered to laying hens legally or illegally, residues of these drugs may be present in the eggs. Even if the eggs are not intended for human consumption, byproducts/biowaste, such as eggshells, may contain residues of the drugs used, which may pose a risk to human health and the environment. In the presented research, 2 different groups of laying hens received enrofloxacin (10 mg/kg body weight) and lincomycin (20 mg/kg body weight) once daily for 5 d. Eggs were collected daily and the concentration of enrofloxacin, its metabolite ciprofloxacin, and lincomycin residue in the eggshells, whole eggs, egg yolks, and egg whites were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. This study demonstrates the transfer of enrofloxacin, ciprofloxacin, and lincomycin into the eggshells and provides evidence for the distribution into the eggshells after administration of these drugs to laying hens. The enrofloxacin residues were detected in the eggshell for 10 d after cessation of treatment, ciprofloxacin and lincomycin were rapidly eliminated and 2 d after finish drugs administration they were no longer detected in the eggshell.

Multi-Class Procedure for Analysis of 50 Antibacterial Compounds in Eggshells Using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

In this work, for the first time, Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed for qualitative and quantitative analysis of veterinary antibiotics (cephalosporins, diaminopyrimidines, fluoro(quinolones), lincosamides, macrolides, penicillins, pleuromutilins, sulfonamides, tetracyclines, and sulfones) in hen eggshells. The sample preparation method is based on a liquid-liquid extraction with a mixture of metaphosphoric acid, ascorbic acid, EDTA disodium salt dihydrate, and acetonitrile. The chromatographic separation was performed on Luna® Omega Polar C18 10 column in gradient elution mode and quantitated in an 8 min run. Validation such as linearity, selectivity, precision, recovery, matrix effect, limit of quantification (LOQ), and limit of detection (LOD) was found to be within the acceptance criteria of the validation guidelines of the Commission Decision 2002/657/EC and EUR 28099 EN. Average recoveries ranged from 81-120%. The calculated LOQ values ranged from 1 to 10 µg/kg, the LOD values ranged from 0.3 to 4.0 µg/kg, depending on analyte. The developed method has been successfully applied to the determination of antibacterial compounds in hen eggshell samples obtained from different sources. The results revealed that enrofloxacin, lincomycin, doxycycline, and oxytetracycline were detected in hen eggshell samples.

Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues.

Paracetamol/acetaminophen (APAP) is one of the most popular pharmacologically active substances used as an analgesic and antipyretic agent. The metabolism of this drug occurs in the liver and leads to the formation of two main metabolites-glucuronic acid and sulfate derivate. Despite the wide use of paracetamol in veterinary medicine, a handful of analytical methods were published for the determination of paracetamol residues in animal tissues. In this paper, a multimatrix method has been developed for the determination of paracetamol and two metabolites-paracetamol sulfate (PS) and p-Acetamidophenyl ß-D-glucuronide (PG). A validation procedure was conducted to verify method reliability and fit purpose as a tool for analyzing acetaminophen and metabolites in muscle, liver, lung, and kidney samples from different species of animals. Established validation parameters were in agreement with acceptable criteria laid by the European legislation. The initial significant matrix effect was successfully reduced by implementing an internal standard-4-Acetamidophenyl ß-D-glucuronide-d3 (PG-d3, IS). The usefulness of the developed method was verified by analyzing samples from an experiment in which paracetamol was administrated to geese.

Cebranopadol, a novel first-in-class drug candidate: Method validation and first exploratory pharmacokinetic study in rabbits.

Cebranopadol is a novel, centrally acting, potent, first-in-class analgesic drug candidate with a unique mode of action that combines nociceptin/orphanin FQ peptide receptor and opioid peptide receptor agonism. The present study aimed to develop and validate a novel UHPLC-MS/MS method to quantify cebranopadol in rabbit plasma and to assess its pharmacokinetics in rabbits after subcutaneous (s.c.) administration. Twelve adult females were administered with 200 µg/kg s.c. injection. Blood samples were withdrawn at 15, 30 and 45 min and 1, 1.5, 2, 4, 6, 8, 10 and 24 hr after administration. The plasma samples were extracted with a liquid/liquid extraction. The new analytical method complied with the EMA requirements for the bioanalytical method validation. The method was selective, repeatable, accurate, precise and robust with a lower limit of quantification of 0.1 ng/ml. In all the rabbits, cebranopadol was quantifiable from 0.25 to 10 hr. Mean Cmax and Tmax were 871 ng/ml and 0.25 hr, respectively. Further studies including the i.v. administration are necessary to fully evaluate the pharmacokinetic features of this novel active compound.

Doxycycline transfer from substrate to white button mushroom (Agaricus bisporus) and assessment of the potential consumer exposure.

The presence of antibiotic residues in the food chain may pose a serious risk to human health. Locating and evaluating new sources of consumer exposure to antibiotic residues in food is a very important element of health protection. The possibility of doxycycline uptake from the substrate for mushroom cultivation by the white button mushroom (Agaricus bisporus) fruit body was investigated. Mushrooms were experimentally cultivated on substrate contaminated with 8 different doxycycline concentrations in substrate and analyte concentrations in mushroom samples were measured using ultra-high performance liquid chromatography - triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) The obtained results clearly indicated that doxycycline transfers from contaminated substrate to mushrooms at concentrations ranging from 0.87 to 72.3 µg/kg, depending on substrate contamination concentration level and order of harvesting.

Effect of feeding on the pharmacokinetics of vilazodone in dogs.

Vilazodone (VLZ) is a drug approved for the treatment of major depressive disorder in humans but no data are available for dogs. The present study aimed to evaluate the pharmacokinetics of a single oral 40 mg dose of VLZ in healthy Labrador dogs (n = 6) in fasted and fed conditions. Dogs were randomly divided in two (n = 3) groups in a cross-over study design (2 × 2). Group I was administered with VLZ at 40 mg/dog after fasting over-night. Group II was fed prior to and after administration of the same dose. A two-week wash-out period was observed. Plasma samples collected underwent LC-MS/MS analysis. VLZ concentrations were quantified in dogs' plasma in two different windows of time: 30 min to 10 h for the fasted group and 4 h to 35 h for the fed group. The values for t1/2λz were statistically different between the groups (fed, 4.6 ±â€¯1.1 h vs fasted, 1.7 ±â€¯0.2 h). Tmax drastically changed between the groups (fed, 10 h vs fasted, 1.5 h), while Cmax did not significantly vary (fed, 39.4 ±â€¯5.6 ng/mL vs fasted, 38.7 ±â€¯4.8 ng/mL). The AUC value was always statistically higher in the fed group. As a result, the average relative oral fasted bioavailability of VLZ was low, 28.8 ±â€¯6.1%. In conclusion, feeding can affect the pharmacokinetics of VLZ in the dog.

Development of a UHPLC-MS/MS Method for the Determination of Quercetin in Milk and its Application to a Pharmacokinetic Study.

INTRODUCTION: Quercetin is a polyphenolic flavonoid which has been used in traditional Chinese medicine as a natural therapeutic agent with a broad spectrum of activities (antioxidant, anticancer, neuroprotective, anti-inflammatory, antiviral and antibacterial). The aim of this study was to develop and validate a rapid and simple ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method for the determination of quercetin in milk. MATERIAL AND METHODS: Sample preparation was based on a liquid-liquid extraction with 0.5% formic acid in acetonitrile. The chromatographic separation was performed on a ZORBAX SB-C18 column with methanol and 0.5% formic acid as a mobile phase. RESULTS: The procedure was successfully validated. The mean recovery of the analyte was 98%, with the corresponding intra- and inter-day variation less than 10% and 15%, respectively, and the repeatability and reproducibility were in the range of 3%-7.2% and 6.1%-12%, respectively. The lowest level of quantification was 1.0 µg/kg. CONCLUSION: The proposed method was successfully applied in evaluating the pharmacokinetics of quercetin in milk obtained from dairy cows with clinical mastitis after intramammary administration.

Multi-residues UHPLC-MS/MS analysis of 53 antibacterial compounds in poultry feathers as an analytical tool in food safety assurance.

Under the EU official monitoring programs, the antibiotics are controlled in tissues of food producing animals. However, regarding the overuse of medicines in veterinary practice, there is a strong need to find an alternative to post-mortem analysis of antibiotics. The use of feathers, as an unconventional matrix, enable to control of birds treatment during breeding. Thus, a novel ultra-high performance liquid chromatography-tandem mass spectrometry method for the analysis of 53 compounds from 11 groups of antibacterials, including penicillins, cephalosporins, macrolides, tetracyclines, quinolones, sulfonamides, aminoglycosides, pleuromutilins, diaminopirymidynes, diaminopirymidynes derivatives and lincosamides in chicken feathers has been developed. The isolation of analytes by solvent extraction method with oxalic acid, Na2EDTA and acetonitrile was performed. The extracts were cleaned by filtration with OASIS HLB cartridges. Chromatographic separation was achieved on a Zorbax SB-C18 analytical column using mobile phase consisting of 0.025% heptafluorobutyric acid and acetonitrile. All compounds were successfully validated, with good sensitivity, accuracy and precision. The developed method gives an opportunity to effective monitoring, whether chickens have been given antibiotics, as well as let to identify the medicines that were used.

Simultaneous determination of 45 antibacterial compounds in mushrooms - Agaricus bisporus by ultra-high performance liquid chromatography-tandem mass spectrometry.

A multi-residue method was developed for the determination of 45 antibacterial compounds in mushrooms - Agaricus bisporus. The method is based on liquid-liquid extraction with acetonitrile with addition of trichloroacetic acid and filtration through sodium sulphate, followed by the identification and quantification of the analyte residues by ultra-high performance liquid chromatography triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Satisfactory linearity was obtained for all compounds with regression coefficients greater than 0.99. The mean recoveries of antibacterial agents were in the range of 73% - 118%. Repeatability and intra-lab reproducibility were lower than 10% and 15%, respectively. The limit of detection ranged from 0.3-3.0 µg kg-1 and the limit of quantification was in the range of 1.0 - 10. 0 µg kg-1 depending on analyte. The proposed method can be successfully applied for the determination of antibiotics in commercially available mushrooms.

Imidacloprid slows the development of preference for rewarding food sources in bumblebees (Bombus impatiens).

Bee pollination is economically and ecologically vital and recent declines in bee populations are therefore a concern. One possible cause of bee declines is pesticide use. Bumblebees exposed to imidacloprid, a neonicotinoid pesticide, have been shown to be less efficient foragers and collect less pollen on foraging trips than unexposed bees. We investigated whether bumblebees (Bombus impatiens) chronically exposed to imidacloprid at field-realistic levels of 2.6 and 10 ppb showed learning deficits that could affect foraging. Bumblebees were tested for their ability to associate flower colour with reward value in a simulated foraging environment. Bumblebees completed 10 foraging trips in which they collected sucrose solution from artificial flowers that varied in sucrose concentration. The reward quality of each artificial flower was predicted by corolla colour. Unexposed bumblebees acquired a preference for feeding on the most rewarding flower colour on the second foraging trip, while bumblebees exposed at 2.6 and 10 ppb did not until their third and fifth trip, respectively. The delay in preference acquisition in exposed bumblebees may be due to reduced flower sampling and shorter foraging trips. These results show that bumblebees exposed to imidacloprid are slow to learn the reward value of flowers and this may explain previously observed foraging inefficiencies associated with pesticide exposure.