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.

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.

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.

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.

Pollution as a risk factor for the development of melasma and other skin disorders of facial hyperpigmentation ­ is there a case to be made?

Worldwide air pollution is a major health concern. There is accumulating scientific evidence that air pollution plays an important role in extrinsic aging. This article invites the reader to consider pollution as a possible emerging etiologic agent for the development of melasma. Pollution may be a risk factor for melasma and other facial pigmentary dyschromias. Air pollution in the form of airborne particulate matter (PM) and Polycyclic aromatic hydrocarbons (PAHs) enter the skin via nanoparticles and generate quinones, which are redox-cycling chemicals that produce reactive oxygen species (ROS). The PM increases the amount of ROS that triggers the increase of metalloproteinases that leads to extrinsic aging, which includes skin pigmentation. The incidence of disorders of facial hyperpigmentation specifically, melasma, is increased in persons of skin type III-VI living in India and South East Asia. Interestingly, these are also geographic regions with very heavy pollution. India, South East Asia, China, and United States lead the world in air pollution.

The importance of indicators in monitoring water quality according to European directives.

Directive 2000/60/EC and subsequent legislation provide a list of priority substances to be measured and monitored in EU water bodies and require the adoption of analytical methods that ensure comparability of the data collected in all Member States. These regulations and standards have gradually improved water quality in the EU. However, new drugs, whose effects on ecosystems and health are still to be determined, are detected with growing frequency. The Member States are now called upon to characterize and monitor these pollutants in view of their possible inclusion in the priority substance list.

[Pharmaceuticals as pollution]. / Legemidler som forurensning.

The pharmaceuticals we humans use to treat illness and disease typically enter the aquatic environment via the sewer network and wastewater treatment works. Understanding the risks posed to the aquatic environment by these chemicals requires an understanding of the concentrations that exist in the environment and whether they are sufficiently high to have adverse effects on aquatic organisms. The main source of pharmaceuticals to wastewater treatment works is pharmaceuticals used by the general population. Only a small contribution is believed to come from hospitals. The predicted environmental concentrations of pharmaceuticals suggest that certain pharmaceuticals may pose a risk to the environment, but measurement of the actual concentrations present in effluents and recipient waters suggest that sophisticated wastewater treatment is effective for significantly reducing effluent concentrations, and that environmental concentrations of pharmaceuticals, in the Oslo Fjord, for example, are generally low. Humans also excrete the metabolites of the pharmaceuticals that they have used and these too may be released into the environment, sometimes in greater concentrations than the parent drug. The occurrence of most pharmaceuticals and their metabolites in the environment poses little acute environmental risk. However, the effects of long-term chronic exposure to these compounds are still poorly understood and the long-terms risks to the environment are still not clear. What is clear is that certain pharmaceuticals pose a greater environmental risk than others, and that where possible this knowledge should be used to inform users of more environmentally friendly alternatives.

Impact of drugs on the environment: state of play, risks, evaluation, communication.

The aim of this Round Table was to perform an initial assessment of the state of play of the impact of drugs on the environment. Demographic growth throughout the world and drug consumption which is constantly on the increase result in an ever increasing presence of medicinal substances in the various compartments (air, water, soil) with potential repercussions on the environment and on health. For the first time, the Giens pharmacology workshop have scheduled this topic outside the conventional sphere of action of Giens. A very high level of interest in this topic came forward both from the members of the round table and the listeners and it is certain that the round table opens the door to new initiatives for a subject about which there is still little knowledge. The following issues were therefore successively addressed: the fragmentation of the knowledge about the subject and its deficiencies concerning the impact on health, both of the wastes as a whole and that of specific drugs, the performances of the water treatment methods, the sources of pollution, the environmental impact, the lines of regulatory development, the impact on the environment and health and the training programmes to be set up among all protagonists, both professional and in the general public.

Water for haemodialysis and related therapies: recent standards and emerging issues.

Dialysis is a well-established and widely used procedure. For a number of years, the focus has been on ensuring that water used in the preparation of dialysis fluid meets the required chemical and microbiological quality and complies with national or international standards which have recently been updated. Continued vigilance is required, in particular when new chemicals such as silver-stabilized hydrogen peroxide and chlorine dioxide are used to prevent growth of Legionella bacteria in hospital water systems, since residues are harmful to patients receiving dialysis. To achieve the required quality, large volumes of water are processed, and a substantial portion is sent to waste via the municipal sewer systems with little attempt to reuse such water on site. In view of concern about global warming and climate change, there is a need to adopt a more environmentally conscious attitude requiring dialysis providers to focus on this aspect of water usage.

Drug residues in serum of dogs receiving anticancer chemotherapy.

BACKGROUND: The presence of drug residues in blood samples can represent an occupational hazard. However, studies on cytotoxic drug residues in serum of dogs are lacking in veterinary oncology. OBJECTIVE: To evaluate possible occupational hazards associated with handling of blood samples from dogs receiving oncolytic drugs 7 days after treatment. ANIMALS: Twenty-seven client-owned dogs treated for lymphoma or mast cell tumors with vincristine, vinblastine, cyclophosphamide, or doxorubicin. METHODS: Prospective, observational study. Serum samples were either taken 7 days after administration of vincristine, cyclophosphamide, doxorubicin (lymphoma), and vinblastine (mast cell tumor), or 1-2 days after the last concurrent oral administration of cyclophosphamide (mast cell tumor). Additionally, serum was collected within 5 minutes of treatment. Measurement of drug residues in serum was performed by liquid chromatography tandem mass spectrometry (LC/MS/MS). RESULTS: In 33 samples collected within 5 minute of treatment, the median serum concentrations were vincristine: 37 microg/L (range: 11-87 microg/L), vinblastine: 13 microg/L (range: 13-35 microg/L), cyclophosphamide: 2,484 microg/L (range: 1,209-2,778 microg/L), doxorubicin: 404 microg/L (range: 234-528 microg/L). In 81 serum samples collected 7 days after treatment vinblastine (7 microg/L) was detected in 1 sample, and cyclophosphamide (7 and 9 microg/L) in 2 samples collected 1-2 days after oral administration of cyclophosphamide. Medications were not detected in any of the other samples. CONCLUSIONS AND CLINICAL IMPORTANCE: Handling of blood samples from dogs receiving oncolytic chemotherapy 7 days after treatment with vincristine, vinblastine, cyclophosphamide, and doxorubicin should not present a health hazard.

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.

Cellular and humoral immunodepression in vultures feeding upon medicated livestock carrion.

Veterinary pharmaceuticals contained in dead livestock may be ingested by avian scavengers and negatively affect their health and consequently their population dynamics and conservation. We evaluated the potential role of antibiotics as immunodepressors using multiple parameters measuring the condition of the cellular and humoral immune system in griffon (Gyps fulvus), cinereous (Aegypius monachus) and Egyptian vultures (Neophron percnopterus). We confirmed the presence of circulating antimicrobial residues, especially quinolones, in nestlings of the three vulture species breeding in central Spain. Individuals ingesting antibiotics showed clearly depressed cellular and humoral immune systems compared with nestlings from the control areas, which did not ingest antibiotics. Within central Spain, we found that individuals with circulating antibiotics showed depressed cellular (especially CD4(+)and CD8(+)T-lymphocyte subsets) and humoral (especially acellular APV complement and IL8-like) immune systems compared with nestlings without circulating antibiotics. This suggests that ingestion of antibiotics together with food may depress the immune system of developing nestlings, temporarily reducing their resistance to opportunistic pathogens, which require experimental confirmation. Medicated livestock carrion should be considered inadequate food for vultures due to their detrimental consequences on health derived from the ingestion and potential effects of the veterinary drugs contained in them and for this reason rejected as a management tool in conservation programmes.

Microbial pollution in wildlife: Linking agricultural manuring and bacterial antibiotic resistance in red-billed choughs.

The spread of pathogens in the environment due to human activities (pathogen pollution) may be involved in the emergence of many diseases in humans, livestock and wildlife. When manure from medicated livestock and urban effluents is spread onto agricultural land, both residues of antibiotics and bacteria carrying antibiotic resistance may be introduced into the environment. The transmission of bacterial resistance from livestock and humans to wildlife remains poorly understood even while wild animals may act as reservoirs of resistance that may be amplified and spread in the environment. We determined bacterial resistance to antibiotics in wildlife using the red-billed chough Pyrrhocorax pyrrhocorax as a potential bioindicator of soil health, and evaluated the role of agricultural manuring with waste of different origins in the acquisition and characteristics of such resistance. Agricultural manure was found to harbor high levels of bacterial resistance to multiple antibiotics. Choughs from areas where manure landspreading is a common agricultural practice harbor a high bacterial resistance to multiple antibiotics, resembling the resistance profile found in the waste (pig slurry and sewage sludge) used in each area. The transfer of bacterial resistance to wildlife should be considered as an important risk for environmental health when agricultural manuring involves fecal material containing multiresistant enteric bacteria including pathogens from livestock operations and urban areas. The assessment of bacterial resistance in wild animals may be valuable for the monitoring of environmental health and for the management of emergent infectious diseases influenced by the impact of different human activities in the environment.

Improved management of drugs, hormones and pesticides in Africa.

Drugs, hormones and pesticides are chemical compounds used for alleviation of various diseases in animals. There are many classes of drugs which have been used and in the case of natural steroid hormones these have been used to increase mass gain by stimulating protein anabolism. Pesticides have been used for many years in the control of ectoparasites which transmit important human and livestock diseases. The purpose of the present article is to review procedures for management of veterinary products to facilitate national and international trade. These compounds and/or their metabolites have the potential to cause undesirable health effects to either target animals or consumers. Most African countries do not have competent authorities to conduct risk analysis for veterinary drug and pesticide residues in edible tissues. Because of the possible undesirable health effects from residues of veterinary compounds, the FAO/WHO established expert groups to establish acceptable daily intake and maximum residue levels (MRLs) for each drug or pesticide. In the case of natural steroids like oestradiol, progesterone and testosterone implants, no withdrawal period is required since there is no risk to the consumer. Bulls can have levels of testosterone ranging from 535-10,950 pg/g, heifers 92-250 and treated steers 100 pg/g, respectively. Data to enable approval of drugs and pesticides is to a large extent similar and include toxicity studies, reproductive studies, stability studies, safety, efficacy, tissue residue depletion studies and environmental impact. Good practice in the use of acaricides as indicated on the label is inevitable so that residue levels of these compounds remain below the specified MRL. Enactment and enforcement of legislations by various countries for the control of registration, sale, distribution and usage of ethical products should be enforced including use of prescriptions by veterinarians. Good practice in the use of veterinary drugs is the recommended or authorized usage of drugs. It should be enforced to ensure safe animal products for human consumption and to facilitate regional or international trade. In conclusion, for efficient production of animal protein from food producing animals all veterinary products should be approved prior to use, residue monitoring programs should be implemented; veterinarians and producers must use these compounds prudently using recommended good practices.

Evaluation of certain veterinary drug residues in food.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including a hypothesis-driven decision tree approach for the safety evaluation of residues of veterinary drugs; comments on the Committee for Veterinary Products for Medicinal Use reflection paper on the new approach developed by JECFA for exposure and maximum residue limit (MRL) assessment of residues; residues of veterinary drugs in honey and possible approaches to derive MRLs for this commodity; comments on a paper entitled "Risk-assessment policies: Differences among jurisdictions"; and the use of no-observed-effect level (NOEL) and no-observed-adverse-effect level (NOAEL) in JECFA assessments. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: three antimicrobial agents (avilamycin, tilmicosin, tylosin), one anthelminthic (triclabendazole), one production aid (melengestrol acetate), two antimicrobial agents and production aids (monensin and narasin), a glucocarticosteroid (dexamethasone) and an antimicrobial agent and contaminant (malachite green). Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs) and proposed MRLs.

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.

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.