Terminal residue and dietary intake risk assessment of prothioconazole-desthio and fluoxastrobin in wheat field ecosystem.

BACKGROUND: Wheat is one of the most important cereal crops worldwide, and use of fungicides is an essential part of wheat production. Both prothioconazole and fluoxastrobin give excellent control of important seed and soilborne pathogens. The combination of these two fungicides shows a complementary mode of action and has a wide usage around the world. But the residue levels of these fungicides in the wheat matrix are still unknown. RESULTS: In the current study, a simple, low-cost and highly sensitive method using modified QuECHERS procedure combined with high-performance liquid chromatography-tandem mass spectrometry was developed to simultaneously quantify E- and Z-fluoxastrobin and the main metabolite prothioconazole-desthio of prothioconazole in the wheat matrix. The recoveries of prothioconazole-desthio, E-fluoxastrobin and Z-fluoxastrobin ranged from 84% to 101%, with relative standard deviation of less than 13.2%. The terminal residues of prothioconazole-desthio and E- and Z-fluoxastrobin were studied in wheat grain and straw under field conditions. The results showed that the terminal residue of the target compounds ranged from <0.01 to 0.029 mg kg-1 and <0.05 to 7.6 mg kg-1 in wheat grain and straw (expressed as dry weight), respectively. The risk quotients of prothioconazole-desthio and fluoxastrobin were 0.2% and 3.2%. CONCLUSIONS: The residue levels of the target analytes in wheat grain were lower than the maximum residue limits recommended by the Chinese Ministry of Agriculture. And the calculated risk quotient values were far below 100%, indicating a low dietary intake health risk to consumers. © 2021 Society of Chemical Industry.

Assessment of veterinary drug residues in food: Considerations when dealing with sub-optimal data.

The use of veterinary drugs in food-producing animals may lead to residues in animal-derived foodstuffs, potentially posing a risk to human safety. While the process of veterinary drug residue risk assessment continues to evolve as new data emerges, a recurring challenge is when sub-optimal or incomplete data are provided with the expectation of supporting a robust risk assessment. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) is comprised of international experts who routinely deal with such data challenges when performing veterinary drug residue evaluations. Recent developments in veterinary drug residue risk assessment are described, including specific consequences of sub-optimal data during the risk assessment process. When feasible, practical solutions to such challenges are also highlighted. Case examples from recent JECFA veterinary drug evaluations are provided to clearly quantify and illustrate the concepts described. The information provided is intended to facilitate the generation of improved quality data, enabling more timely and robust veterinary drug residue risk assessments.

Multiantibiotic residues in commercial fish from Argentina. The presence of mixtures of antibiotics in edible fish, a challenge to health risk assessment.

The occurrence of 46 antibiotics (amphenicols, cephalosporins, dihydrofolate reductase inhibitors, fluroquinolones, macrolides, nitrofurans, penicillins, quinolones, sulfamides and tetracyclines) in Argentinean market fish were investigated by UPLC-MS/MS. Veterinary and human antimicrobials enrofloxacin, clarithromycin, roxithromycin, doxycycline and oxytetracycline were detected in 100% of the samples, being to our knowledge the first report of clarithromycin in edible fish muscle. Maximum Residual Limits were exceeded for at least one antibiotic in 82% of pacú, 57% of shad, 57% of trout and 50% of salmon samples. Chloramphenicol, furazolidone and nitrofurantoin (banned compounds in food items) were detected in 41%, 22% and 4% of the samples, respectively. Based on the estimated daily intake calculation, samples do not pose a serious risk to public health. Further investigation on the chronic impact and risk calculation of the mixture of antibiotics on the aquatic environment and human health is urgently needed.

Validation of Multi-Residue Method for Quantification of Antibiotics and NSAIDs in Avian Scavengers by Using Small Amounts of Plasma in HPLC-MS-TOF.

Pharmaceuticals are still considered emerging pollutants affecting both aquatic and terrestrial ecosystems. Scavenging bird species may be exposed to veterinary drugs when they feed on livestock carcasses provided at supplementary feeding stations, as these are often stocked with ailing and/or recently medicated animals. Because those animals may be a source of several different pharmaceutical compounds, analytical methods to evaluate residue levels and exposure potential should enable detection and quantification of as many different compounds as possible, preferably from small sample volumes. Four different extraction methods were tested to conduct HPLC-MS-TOF analysis of some of the most common veterinary drugs used in livestock in Spain. The method deemed most viable was a simple extraction, using methanol and 100 µL of plasma, that allowed quantification of seven antibiotics (tetracycline, oxytetracycline, ciprofloxacin, enrofloxacin, nalidixic acid, trimethoprim, sulfadiazine) and five nonsteroidal anti-inflammatory drugs (NSAIDs) (meloxicam, flunixin, carprofen, tolfenamic acid, phenylbutazone). The method was then applied to analysis of 29 Eurasian griffon vulture (Gyps fulvus) nestling samples, wherein enrofloxacin and tolfenamic acid were most commonly detected (69% and 20%, respectively). To our knowledge, this is the first study including NSAIDs in the exposure assessment of different classes of veterinary pharmaceuticals in live avian scavengers.

Comparison of international legislation and standards on veterinary drug residues in food of animal origin.

Current legislation governing monitoring of drug residues in foodstuff of animal origin is being revised at the European level. This study provides a qualitative comparison of the legislation, public and private standards in the European Union, the United States of America (USA) and the Eurasian Customs Union/Russia. We made a quantitative comparison of Maximum Residue Levels (MRLs) applied in each region for pork kidneys for tetracycline (with a focus on doxycycline), penicillin and chloramphenicol. The Customs Union generally applied lower levels than the other regions, with MRLs for tetracyclines in pig kidneys being 1200 times lower than those applied in the USA. Growing consumer interest and concern about chemicals in their food could be leveraged to support and enhance the implementation of new initiatives to improve veterinary public health. Farmers and veterinarians could help reduce findings of drug residues in meat through the judicious use of preventive actions when using veterinary medicine.

Instrumental and sensory methodologies to characterize the residual film of topical products applied to skin.

BACKGROUND: The work is aimed at the development of a methodology to characterize the tactile properties of topical products during application. Specific attention was paid to the study of the residual properties left at the surface of the skin. This approach was interestingly used to better understand the formulation factors governing the skinfeel of topical preparations. MATERIALS AND METHODS: Cosmetic and pharmaceutical topical products were selected based on their various texture, galenic form (gel or emulsion), and composition (polymer used as texturing agent). Key texture attributes namely Firmness, Stickiness, Spreadability, and Amount of residue were objectively evaluated using sensory analysis. Additionally, texture analysis (compression test), rheology (flow test), and tribology (in vivo friction test) were carried out. RESULTS: Sensory evaluations highlighted a great diversity of tactile properties among products when applied to skin. For example, assessors perceived an important amount of residue left by emulsions whereas gels were not leaving any residue after application to the skin. These results were confirmed by in vivo tactile friction measurements with two distinct evolutions in time of the residual film properties. CONCLUSION: The present investigation shows how the tactile properties of topical gels and emulsions are studied using complementary tests in order to understand and improve the skinfeel of topical preparations.

Importance of antibiotic residues in animal food.

Veterinary medicines, especially antibiotics, are among the most important components related to animal feed production. Generally, the main use of antibiotics in animals is for the treatment and prevention of diseases and growth promotion. Antibiotic usage in animals may result antibiotic residues in foodstuffs such as milk, egg and meat. These residues may cause various side effects such as transfer of antibiotic resistant bacteria to humans, immunopathological effects, allergy, mutagenicity, nephropathy (gentamicin), hepatotoxicity, reproductive disorders, bone marrow toxicity (chloramphenicol) and even carcinogenicity (sulphamethazine, oxytetracycline, furazolidone). The most important adverse effect of antibiotic residues is the transfer or antibiotic resistant bacteria to the humans due to the mobile properties of resistance. Because of these undesirable effects, it is important to regulate the use of antibiotics in food animals. The individuals and the local procedures should be aware of the problem through education by authorities. In this review, antibiotic use in the foodstuffs and their effects on the human health will be discussed.

Veterinary Drug Residue in Food of Animal Origin in Switzerland: A Health Concern?

Many drugs are used in livestock farming, particularly antibiotics, with almost 80% of world antibiotic production used for animals. Therefore, veterinary drugs may be present as residues in food of animal origin even if their use is fully regulated to ensure the proper use of veterinary medicinal products, to protect consumers from undesirable residues, and to ensure the supply of quality, safe and effective veterinary medicinal products to safeguard animal health. Analytical techniques for residue analysis have improved significantly with routine use of liquid chromatography coupled with tandem or high-resolution mass spectrometry. This improvement enabled specific searches for several hundred target compounds within minutes in complex matrices such as milk, eggs, honey or meat and organs after slaughter. For many years, a national residue control programme in food has been effective. The rate of non-compliant samples remains low and shows that consumers do not have to worry too much about the presence of drug residues in food of animal origin produced in Switzerland. Despite the significant reduction in antibiotic consumption observed in recent years, the resistance rate and distribution of multidrug-resistant bacteria is steadily increasing, even in countries where drug consumption has decreased significantly. Reducing antimicrobial resistance will undoubtedly be one of the most difficult food safety challenges in the coming years.

Human milk antibiotic residue levels and their relationship with delivery mode, maternal antibiotic use and maternal dietary habits.

OBJECTIVE: It is important to identify undesirable toxins and metabolites present in human milk that may be passed on to nursing infants. Such residues may derive from the antibiotics that are widely used to treat infectious diseases in both humans and food-producing animals. To the best of our knowledge, there are no reports in the literature on human milk antibiotic residue levels. PATIENT AND METHODS: As a part of the Human Milk Artificial Pollutants (HUMAP) study, we aimed to evaluate human milk antibiotic residues among mothers with 7 to 90-day-old babies. Pregnant women who had received antibiotic treatment during pregnancy were excluded. The use of antibiotic prophylaxis with cefazoline sodium during labor was noted among the study subjects. Human milk antibiotic residues were evaluated with the InfiniPlex for Milk Array (Randox Laboratories, London, United Kingdom), a semi-automated system with a multi-array biochip designed to detect antibiotic residues and toxins. RESULTS: The HUMAP study included 83 mothers, ranging in age from 17 to 41 years (mean 29.7 ± 6.2 years). Of these, 59% received cefazoline sodium shortly after birth, while 41% did not receive any antibiotics during the pregnancy, delivery or lactational periods. Testing revealed that 71/83 (85.5%) human milk samples were positive for beta-lactams and 12 (14.5%) samples were positive for quinolones. There was no difference in maternal age, gestational week, delivery type, sampling time, maternal dietary habits between the mothers with quinolones or beta-lactam residues in their milk and those without (p > 0.05 for both). Beta-lactam and quinolone residues were detected in 85.7% and 23.5%, respectively, of the human milk samples of mothers who did not receive antibiotics at birth and/or during the first seven days after birth. CONCLUSIONS: We found that the majority of human milk samples included beta-lactams or quinolones, even though the mothers did not receive these antibiotics during pregnancy and lactation. Antibiotic residues in human milk may affect early maintenance of the intestinal microbiota. Previous studies have shown that antimicrobials in food might increase the risks of allergies and could lead to the development of antibiotic-resistant bacterial strains. Effective policies on food safety and appropriate antibiotic use during pregnancy and lactation are needed.

Does the dry cow treatment with monensin controlled release capsule affect Parmigiano Reggiano cheese production?

We investigated the effects of monensin controlled-release capsule (CRC; Kexxtone, Eli Lilly and Company Ltd., Indianapolis, IN) preventative ketosis treatment on the traditional cheesemaking process as well as the final characteristics of Parmigiano Reggiano (PR) cheese. The use of this prevention product to reduce the incidence of ketosis in transition dairy cows was approved by the European Medicines Agency in 2013. No previous studies are available concerning the effects of this treatment on prolonged-ripening cheese production such as PR. In PR cheese production, feed, feed additives, and cow treatments are strictly regulated to avoid any possible interference with traditional manufacturing processes. For these reasons, on 1 farm where all milk was used for PR cheese production, monensin CRC was administered to 33 cows, 21 d before calving in the monensin-treated group (TRT), whereas untreated cows with similar breed and parity characteristics constituted the control group (CTR). For 20 wk, milk obtained from each group and whey starter were separately managed and transported in the cheese factory, where 2 cheese wheels per group were produced daily, making 552 PR cheese wheels in total. Morning bulk tank milk composition, cheesemaking properties, and whey starter fermentation activities were analyzed twice a week. Every aspect of the cheesemaking process was recorded and the resulting cheese was evaluated after 36 h and 6, 12, and 18 mo from production for yield, texture defects, composition, and fatty acids profile. Milk from the 2 groups differed for somatic cell content (TRT = 3.04 vs. CTR = 4.06, somatic cell score), total bacterial count (TRT = 4.08 vs. CTR = 6.08 × 1,000 cfu/mL), titratable acidity (TRT = 3.66 vs. CTR = 3.72 Soxhlet-Henkel degrees/50 mL), and casein content percentage (TRT = 2.4 vs. CTR = 2.5%). Whey starter parameters were comparable between the 2 groups. Final cheese composition and organoleptic profile were not influenced by the treatment, except for C18:1 content being enhanced (TRT = 22.8 vs. CTR = 20.8% of fatty acids). Percentage of defected ripened cheese was significantly lower in the treated group, both at x-ray evaluation performed at 6 mo (TRT = 6.2 vs. CTR = 12.3%) and at the consortium inspection, performed at 12 mo of ripening (TRT = 1.5 vs. CTR = 6.5%). On the other hand, average cheese yield at 18 mo of ripening was partially reduced (TRT = 7.5 vs. CTR = 7.7%). Overall, the use of monensin CRC had no negative effect on the cheesemaking process, prolonged ripening cheese characteristics, milk composition, or whey starter quality.

Impacts of feeding preweaned calves milk containing drug residues on the functional profile of the fecal microbiota.

Feeding drug residue-containing milk to calves is common worldwide and no information is currently available on the impact on the functional profile of the fecal microbiota. Our objective was to characterize the functional profile of the fecal microbiota of preweaned dairy calves fed raw milk with residual concentrations of antimicrobials commonly found in waste milk from birth to weaning. Calves were assigned to a controlled feeding trial being fed milk with no drug residues or milk with antibiotic residues. Fecal samples collected from each calf once a week starting at birth, prior to the first feeding in the trial, until 6 weeks of age. Antibiotic residues resulted in a significant difference in relative abundance of microbial cell functions, especially with genes linked with stress response, regulation and cell signaling, and nitrogen metabolism. These changes could directly impacts selection and dissemination of virulence and antimicrobial. Our data also identified a strong association between age in weeks and abundance of Resistance to Antibiotics and Toxic Compounds. Findings from this study support the hypothesis that drug residues, even at very low concentrations, impact the gut microbiota of calves and result in changes in the functional profile of microbial populations.

Effects of five sulphonamides on duckweed (Lemna minor) after prolonged exposure time and their dependency on photoradiation.

Sulphonamides (SAs) are one of the most commonly used veterinary drugs and therefore their residues are regularly found in the environment. So far scientific attention has mostly been paid to the evaluation of their acute ecotoxicological effects with data on long-term effects for non-target organisms still largely missing. Therefore, the main aim of this study was to evaluate the potential toxicities of five sulphonamides to duckweed (Lemna minor) after prolonged exposure time (14days). To elucidate whether their phytotoxic effects result from potential photodegradation products, the toxicity of standard solutions of selected sulphonamides was also investigated in a standard 7-day test but after irradiation (by keeping them under the test conditions) for the selected time (after 7 and 14days). The ecotoxicological tests were accompanied by chemical analyses to be able to link the observed effects to the concentrations and nature of the exposed compounds. The results showed a shift in the toxicity of SAs: a strong decrease in toxicity for the two most toxic sulphonamides (sulphamethoxazole and sulphadimethoxine) and a slight increase in toxicity for three other SAs (sulphadimidine, sulphathiazole, sulphamerazine) in the prolonged test. However, a decrease in the toxicity and concentration of all the SAs was observed when stock solutions were irradiated prior to the toxicity experiment, which suggests that the observed effects towards L. minor of five SAs in the prolonged test cannot be directly associated with the degradation of these compounds under the test conditions but with their different mode of toxic action towards these organisms.

Effect of enrofloxacin on the proteome of earthworms.

The environmental and human health risks of veterinary drugs are becoming public health issues. Enrofloxacin (EF) is an extensively used animal-specific antibacterial agent that leaves drug residues in the environment. This study investigated the proteomic response of the earthworm Eisenia fetida to EF exposure. Earthworms were exposed to EF in soil at 1-500mg·kg-1, and samples were collected at intervals during a 28 day period. The extracted proteins were separated by two dimensional electrophoresis to detect differentially expressed proteins (DEPs) in EF-exposed earthworms. In total, 35 unique DEPs were found. These proteins were subjected to MALDI-TOF/TOF-MS analysis and identified through comparison of their mass spectra with those in protein databases. The DEPs were grouped on the basis of their function, into metabolism, stress-related, transport, transcription, and predicted/hypothetical protein categories. Knowledge of proteins that are induced or repressed by EF in earthworms could provide insight into mechanisms of sub-clinical physiological effects of xenobiotic residues in the environment, and may also help understand synergy between pollutants. As several DEPs in E. fetida showed similarity to human protein sequences, E. fetida has potential as an indicator species to assess the environmental and biological risks of drug residues.

Current research, regulation, risk, analytical methods and monitoring results for nicarbazin in chicken meat: A perspective review.

This review presents up-to-date information about current research on nicarbazin, one of the most used anticoccidials in poultry production. The focus is to elucidate regulation concerning nicarbazin, limits for its residues in food, how maximum residue limits in different countries are calculated regarding edible chicken tissues and the possible implications in human health. Analytical methods to extract and quantify this residue, expressed as dinitrocarbanilide (DNC) are presented and discussed, including qualitative screening and quantitative/confirmatory analytical methods. Monitoring results and occurrence of DNC residues in chicken meat are discussed. Additionally, the causes of eventual chicken meat contamination and possible solutions to reduce or eliminate DNC residue in tissues are also presented. The paper concludes with perspectives, the current state of DNC residue analysis and suggestions for future research, especially considering the gap in the study of residue recycling effect due to continuous chicken litter use.

An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome.

The human gastrointestinal tract ecosystem consists of complex and diverse microbial communities that have now been collectively termed the intestinal microbiome. Recent scientific breakthroughs and research endeavours have increased our understanding of the important role the intestinal microbiome plays in human health and disease. The use of antimicrobial new animal drugs in food-producing animals may result in the presence of low levels of drug residues in edible foodstuffs. There is concern that antimicrobial new animal drugs in or on animal-derived food products at residue-level concentrations could disrupt the colonization barrier and/or modify the antimicrobial resistance profile of human intestinal bacteria. Therapeutic doses of antimicrobial drugs have been shown to promote shifts in the intestinal microbiome, and these disruptions promote the emergence of antimicrobial-resistant bacteria. To assess the effects of antimicrobial new animal drug residues in food on human intestinal bacteria, many national regulatory agencies and international committees follow a harmonized process, VICH GL36(R), which was issued by a trilateral organization of the European Union, the USA, and Japan called the International Cooperation on Harmonization of Technical Requirements for Veterinary Medicinal Products (VICH). The guidance describes a general approach currently used by national regulatory agencies and international committees to assess the effects of antimicrobial new animal drug residues in animal-derived food on human intestinal bacteria. The purpose of this review is to provide an overview of this current approach as part of the antimicrobial new animal drug approval process in participating countries, give insights on the microbiological endpoints used in this safety evaluation, and discuss the availability of new information. Copyright © 2016 John Wiley & Sons, Ltd.

Agricultural Applications for Antimicrobials. A Danger to Human Health: An Official Position Statement of the Society of Infectious Diseases Pharmacists.

The use of antibiotics in agriculture, particularly in food-producing animals, is pervasive and represents the overwhelming majority of antibiotic use worldwide. The link between antibiotic use in animals and antibiotic resistance in humans is unequivocal. Transmission can occur by ingesting undercooked meats harboring resistant bacteria, by direct contact of animals by animal handlers, and by various other means. Antibiotics used in aquaculture and antifungals used in horticulture are also an evolving threat to human health. Regulations aimed at decreasing the amount of antibiotics used in food production to limit the development of antibiotic resistance have recently been implemented. However, further action is needed to minimize antibiotic use in agriculture. This article describes the extent of this current problem and serves as the official position of the Society of Infectious Diseases Pharmacists on this urgent threat to human health.

Health concerns and management of select veterinary drug residues.

The aim of this manuscript is to review the potential adverse health effects in humans if exposed to residues of selected veterinary drugs used in food-producing animals. Our other objectives are to briefly inform the reader of why many of these drugs are or were approved for use in livestock production and how drug residues can be mitigated for these drugs. The selected drugs include several antimicrobials, beta agonists, and phenylbutazone. The antimicrobials continue to be of regulatory concern not only because of their acute adverse effects but also because their use as growth promoters have been linked to antimicrobial resistance. Furthermore, nitroimidazoles and arsenicals are no longer approved for use in food animals in most jurisdictions. In recent years, the risk assessment and risk management of beta agonists, have been the focus of national and international agencies and this manuscript attempts to review the pharmacology of these drugs and regulatory challenges. Several of the drugs selected for this review can cause noncancer effects (e.g., penicillins) and others are potential carcinogens (e.g., nitroimidazoles). This review also focuses on how regulatory and independent organizations manage the risk of these veterinary drugs based on data from human health risk assessments.