Animal Drugs and Human Health

<p>While it is certain that various veterinary drugs used for the prevention and treatment of livestock animal diseases contribute to the stable production of animal products in recent years, on the other hand, the overuse or misuse of these drugs is of great concern because it can result in their presence in animal-derived foods for human consumption.To assure the safety of animal-derived foods for the consumer, Codex Aliamentarius sets maximum residue limits (MRLs) for veterinary drugs. Because determinations for veterinary drugs in the animal-derived foods are therefore an important specific activity to guarantee food safety, the validated analytical method for the determining target drugs are presently required.</p><p>In answer to the present expansion and diversification in the international animal product trade, the development of international harmonized analytical methods (= universal standard methods) to determine veterinary drug residues in animal products is essential to guarantee equitable international trade in these foods and ensure food safety for consumers. Without regard for industrial nations and developing countries, the optimal harmonized analytical method for residue monitoring in foods must be quick, easy, reliable, inexpensive, and capable of quantifying residues at concentrations less than the target drug’s MRL in animal products and must cause no harm to the environment and analyst.</p><p>Although several methods have been described in the literature for quantifying veterinary drugs in foods, these methods have three crucial drawbacks as follows: 1) the sample preparation operations are complicated and labor intensive, which are time-and cost-consuming, do not permit the determination of large number of samples, and can give low reproducibility; 2) organic solvents are used as extraction solvents, purification eluent, and/or as LC mobile phases without fail -Risk associated with these solvents extend beyond direct implications for the health of humans and wildlife to affect our environment and the ecosystem in which we all reside. Eliminating the use of organic solvents is an important goal in terms of environmental conservation, human health and the economy; 3)the detections/identifications are based on LC-MS or -MS/MS - The facilities that LC-MS/MS system is available are limited to part of industrial nations because these are hugely expensive, and the methodologies use complex and specific. These are unavailable in a lot of laboratories for routine analysis, particularly in developing countries. No optimal method that satisfies the aforementioned requirements has yet been identified.</p>As an optimal technique that can be recommended as an international harmonized analytical method for the routine residue monitoring in animal-derived foods, this paper describes a quick, easy, and small-scale sample preparation followed by an isocratic water mobile phase HPLC method for determining sulfadimidine (SDD) in cow’s milk under no-use organic solvent conditions. The SDD selected here is one of the most frequently used veterinary drugs worldwide, and has only the Codex’s MRL (0.0025 μg/mL for SDD in milk) set for several kinds of sulfonamides.Cow’s milk contains a good balance of protein, fat, and carbohydrate, is an indispensable food because it is inexpensive and readily available.

Modern agriculture depends highly on pesticides and pharmaceutical preparations, so controlling exposure to these substances in the feed and food chain is essential. This article presents the first study on residues of a broad spectrum of pesticides and veterinary drugs in the diets of dairy cattle. One hundred and two representative samples of the complete diets, including basal feed rations and additional fed concentrate, were collected in three Austrian provinces (Styria, Lower and Upper Austria) in 2019 and 2020. The samples were tested for >700 pesticides, veterinary drugs and related metabolites using a validated method based on liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI–MS/MS). In total, 16 residues (13 pesticides and three veterinary drug residues) were detected. > 90% of the diets contained pesticide residues and <10% veterinary drug residues, whereas banned pesticides were not found. The most frequent pesticide residues were fluopyram (62%), piperonyl butoxide (39%) and diethyltoluamide (35%). The following pesticides exceed the default EU maximum residue level (MRL) (10 μg kg−1) for products exclusively used for animal feed production: Benzovindiflupyr (proportion of samples > MRLs: 1%), bixafen (2%), fluopyram (6%), ipconazole (1%) and tebuconazole (3%). Three residues (dinitrocarbanilide, monensin and nicarbazin) of veterinary drugs were identified, all below the MRLs. Over 60% of the evaluated samples contained mixtures of two to six residues/sample. Only one pesticide (diethyltoluamide) presented a significant difference among regions, with higher concentrations in Upper Austria. Brewery's spent grains were the dietary ingredient that showed the strongest correlation to pesticide residues. These findings evidence the realistic scenario of highly occurrent low doses of pesticides cocktails in the feed/food chain, which may affect the animal, human and environmental health. Since the risk assessments are based on single pesticides, the potential synergistic effect of co-occurring chemicals (“cocktail effect”) requires further investigations.

Background/Objectives: This systematic review evaluates unconventional mammalian models from wild, agricultural, and urban/domestic ecosystems for genotoxicity assessment under the One Health framework. Non-human primates (NHPs), cattle, and domestic dogs are analyzed as sentinel species due to their distinct environmental niches, unique human interactions, and species-specific traits. In conjunction with this, evidence is presented about the in vitro use of cells of these mammals for the genotoxicological evaluation of different chemical substances, such as veterinary drugs, environmental pollutants, and pesticides. The synthesis focuses on standardized genetic toxicology assays (e.g., chromosomal aberrations, micronucleus, comet assay) aligned with Organization for Economic Cooperation and Development (OECD) guidelines. Methods: A structured search of international literature identified studies employing OECD-compliant genotoxicity assays in NHPs, cattle, dogs, and others not listed in OECD. Data was categorized by species, assay type, chemical class evaluated, environmental context (wild, agricultural, urban), and merits of the papers. Results: NHPs, despite their phylogenetic proximity to humans, show limited genotoxicity data in contrast to biomedical research, which has been constrained by ethical concerns and fieldwork logistics. Cattle emerge as robust models in agricultural settings due to the abundance of studies on the genotoxic capacity of pesticides, veterinary drug, and environmental biomonitoring, with direct implications for food safety. Domestic dogs are recognized as powerful sentinels for human health due to shared exposomes, physiological similarities (e.g., shorter cancer latency), and reduced lifestyle confounders; however, genotoxicity studies in dogs remain sparse compared to chemical exposure monitoring or cancer research. Conclusions: This review advocates for expanded, integrated use of these models to address genotoxic threats across ecosystems, which would benefit both animal and human health. In the application of biomonitoring studies with sentinel animals, a critical gap persists: the frequent lack of integration between xenobiotic quantification in environmental and biological samples, along with genotoxicity biomarkers evaluation in sentinel populations, which hinders comprehensive environmental risk assessment.

Waste from agricultural livestock operations has been a long-standing concern with respect to contamination of water resources, particularly in terms of nutrient pollution. However, the recent growth of concentrated animal feeding operations (CAFOs) presents a greater risk to water quality because of both the increased volume of waste and to contaminants that may be present (e.g., antibiotics and other veterinary drugs) that may have both environmental and public health importance. Based on available data, generally accepted livestock waste management practices do not adequately or effectively protect water resources from contamination with excessive nutrients, microbial pathogens, and pharmaceuticals present in the waste. Impacts on surface water sources and wildlife have been documented in many agricultural areas in the United States. Potential impacts on human and environmental health from long-term inadvertent exposure to water contaminated with pharmaceuticals and other compounds are a growing public concern. This work-group, which is part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards—Searching for Solutions, identified needs for rigorous ecosystem monitoring in the vicinity of CAFOs and for improved characterization of major toxicants affecting the environment and human health. Last, there is a need to promote and enforce best practices to minimize inputs of nutrients and toxicants from CAFOs into freshwater and marine ecosystems.

While the controversy over compounding for animals is contemporary, the practice of compounding for animals is not. Pharmaceutical compounding is an ancient art and science. Compounding has been an integral part of the practice of veterinary medicine since the first cures were blended together to help an animal patient. Skilled healers have utilized compounds for both human and animal patients for thousands of years. With hundreds of species requiring treatment and dozens of new diseases emerging, the half-life of truth in veterinary medicine is particularly short. As a result of a complex and lengthy approval process, the veterinary pharmaceutical industry can never be expected to adequately supply labeled products to treat every disease encountered in every species. Consequently, in order to provide state-of-the-art veterinary therapy, the veterinarian must frequently alter commercially available dosage forms to meet needs for individual patients. This activity is defined as compounding by the major veterinary drug regulatory agencies in North America, the Canadian Bureau for Veterinary Drugs (BVD) and the United States (US) Food and Drug Administration Center for Veterinary Medicine (FDACVM). In some cases, as with potassium bromide and cisapride, there are no commercially available products for any species, and these life-saving therapies must be compounded from raw chemicals. Often, the safety of the caregiver also depends on the ability to get medications into the animal in the least invasive, most palatable manner possible. Compliance is paramount in achieving successful therapeutic outcomes, but many owners will not administer unpalatable or invasive therapies if they perceive that their pet will “hate” them as a result. Compounding based on individual patient need is an ageless solution for all of these problems.

The excessive use or abuse of pesticides and veterinary drugs leads to residues in food, which can threaten human health. Therefore, there is an extremely urgent need for multi-analyte analysis techniques for the detection of pesticide and veterinary drug residues, which can be applied as screening techniques for food safety monitoring and detection. Recent developments related to rapid multi-residue detection methods for pesticide and veterinary drug residues are reviewed herein. Methods based on different recognition elements or the inherent characteristics of pesticides and veterinary drugs are described in detail. The preparation and application of three broadly specific recognition elements—antibodies, aptamers, and molecular imprinted polymers—are summarized. Furthermore, enzymatic inhibition-based sensors, near-infrared spectroscopy, and SERS spectroscopy based on the inherent characteristics are also discussed. The aim of this review is to provide a useful reference for the further development of rapid multi-analyte analysis of pesticide and veterinary drug residues.

ABSTRACTDairy farm waste, commonly used as agricultural fertilizer, often contains veterinary drugs and their metabolites, posing a potential risk to human and animal health, particularly by promoting antimicrobial resistance. This study investigated the occurrence of 11 veterinary pharmaceuticals in effluents, solid manure, and slurry from 53 dairy farms in a key dairy region of Central Argentina. Samples of cow manure and wastewater effluent were collected and analyzed using LC‐MS/MS after liquid‐liquid extraction. The analyzed drugs were detected in 68% of effluent samples and 38% of manure samples. Oxytetracycline was the most frequent compound in both matrices (effluents and manure) (26.4% and 47.2%), with concentrations of 12 µg/L and 86 µg/kg, respectively. Flunixin, a nonsteroidal anti‐inflammatory, was present in 84.9% of liquid effluent samples (0.01–11 µg/L) and 18.9% of manure samples (1.3–124 µg/kg). Associations were found between pharmaceutical residues in waste and farm characteristics. Higher concentrations and detection rates of oxytetracycline and flunixin in manure were observed in confined production systems, farms with high milk productivity (&gt;25 L/cow/day), and larger herd sizes (≥182 animals). The relative risk of detecting tylosin in effluents was higher in these same farm categories (RR = 7.8, confined systems; 7.3, high milk productivity; and 6.2, larger herd). Similar trends were noted for enrofloxacin, tetracycline, and flunixin in manure. Despite generally low concentrations (in the order of ng/L or kg), this work demonstrates the widespread occurrence of veterinary drugs in dairy farm waste, often overlooked in fertilizer application. This highlights the need for incorporating veterinary drug monitoring for a fair assessment of environmental impacts as dairy production intensifies.

Advancing drug discovery and treatment evaluation for schistosomiasis : improved screening, drug repurposing and rescuing, and the metabonomics of praziquantel treatment

First insight into the occurrence, spatial distribution, sources, and risks assessment of antibiotics in groundwater from major urban-rural settings of Pakistan

Imprudent administration of antimicrobial drugs in food-producing animals can facilitate the development and spread of antimicrobial-resistant organisms and also enhance the occurrence of antimicrobial residue in animal products. This study was undertaken to assess antimicrobial drug administration to food animals in livestock farms in Enugu State and determine livestock farmers' awareness on the consequences of imprudent antimicrobial administration to food animals and finally the prevalence of antimicrobial drug residues in edible tissues of cattle and pigs in the state. Structured questionnaire was used to extract information on antimicrobial drug administration and consequences of irresponsible use of antimicrobials in food animals from 109 livestock farms/farmers randomly selected using multi-stage sampling technique. Premi® test technology (R-Biopharm, Germany) was used to screen for antimicrobial residues in edible tissues from 300 carcasses consisting of 165 cattle and 135 pigs slaughtered for human consumption in two major slaughterhouses in Enugu State. Tetracyclines (90.8%), penicillins and beta-lactams (89.9%), and aminoglycoside (57.8%) were the classes of antimicrobials most frequently administered to food animals in the farms surveyed. Withdrawal period was not observed in 65% of the farms. About 30% of cattle and 23% of pig carcasses screened contained detectable amounts of antimicrobial residues. There is widespread indiscriminate administration of antimicrobial drugs in food animals in Enugu State. This underscores the need for public enlightenment on prudent use of antimicrobial drugs in food-producing animals in order to preserve the therapeutic efficacy for sustainable livestock production and to safeguard human health.

Overview and prospects of food biosafety

Fast and sensitive detection of nitroxynil using a chalcone-based supramolecular fluorescent sensor

Edible insects are expected to become an important nutrient source for animals and humans in the Western world in the near future. However, before insects can be put on the market, the safety of their use for feed and food is warranted. This literature study was prepared to provide an overview of the actual knowledge of possible food safety hazards, including chemical, microbiological, and allergenic agents and prions, to human and animal health upon the use of insects for food and feed, and to highlight data gaps and suggest the way forward. From the data available, heavy metals of concern are cadmium in black soldier fly and arsenic in yellow mealworm larvae. Investigated mycotoxins do not seem to accumulate. Residues of pesticides, veterinary drugs, and hormones, as well as dioxins and PCBs, are sometimes found in insects. Contamination of insects with pathogens to human health is a consequence of a combination of the substrates used and the farming and processing steps applied. Insects harbor a wide variety of microorganisms, and some human pathogenic bacteria may be present. In addition, insects may harbor and transmit parasites. There is no evidence so far insects may harbor pathogenic viruses or prions, but they may act as vectors. Insects and insect-derived products may have allergenic potential. In this review, evidence on some safety aspects is displayed, and data gaps are identified. Recommendations are given for future research to fill the most relevant data gaps.

Pesticides in the Modern World -Risks and Benefits 90 system of plants (Knutson et al., 1990).In contrast to the above, there are few cases of pesticides proved dangerous to public health.A typical example is the chlorinated hydrocarbon DDT, which was previously used against mosquitoes.The active substance DDT contributed greatly to reduce the spread of diseases like malaria, but was withdrawn in 1970 as it was considered dangerous for human and environment safety.Active substances are classified into five groups according to their toxicity.The first group (Ia) includes the extremely toxic agricultural plant protection agents, while the four other groups of substances are listed in order of decreasing toxicity (Ib, II, III).The fifth group (U) includes substances that are unlikely to become toxic to humans (International Programme on Chemical Safety, 2004).The adverse effects of these compounds may be observed in a short period (acute toxicity) or after a long time (chronic toxicity).In any case, it should be noted that, although the annual reported number of deaths by poisoning is 355.000,only a part of these poisonings, which is not specified in the World Health Report, are due to pesticides (WHO The World Health Report, 2003).Moreover, all cases of poisoning are due to accidents, like accidental ingestion or inhalation of chemicals, and not by food intake.However, the possibility of indication of various effects in consumer health through chronic toxicity cannot be ignored.Toxicity of a plant protection product depends on various factors, including chemical structure, temperature and humidity conditions, dose, duration of exposure, mode of action and the kind of exposure, like ingestion, inhalation, dermal etc. Different groups of pesticides and veterinary drugs are likely to be responsible for causing malaise, sore eyes, abnormalities to skin and respiratory system.Moreover, some pesticides and veterinary drugs are suspected of causing certain types of cancer, teratogenicity, chromosomal abnormalities and the weakening of the immune system of humans (Banerjee, 1999).The toxicity of various active substances, which can be detected in bee products, varies according to their chemical synthesis.In any case, poisoning or deaths due to the presence of toxic substances exclusively to bee products have not been reported.An exception is the death of infants, which was caused by Clostridium botulinum (Arnon, 1980).Even in these cases, however, the responsibility of honey has not been proven clearly, as this clostridium appears in the environment widely (Midura, 1996).In addition, 65% of infants that became ill had not eaten honey at all (Arnon et al., 1979).In any case, appropriate infant feeding prohibits the consumption of honey until the age of one year to eliminate possible poisoning from toxins of this micro-organism.Another way of classification of active substances, relates to the subject of this investigation, and is based on bee toxicity.In general, active substances are classified as very toxic, moderately toxic and non-toxic to bees.The most significant impact on bee colonies has been observed after treatments with plant protection products during the blooming.Most deaths occurred during the stage of forager worker bee that collects nectar and pollen.Moreover, larvae and domestic bees die because of pesticide residues detected in pollen.Although in many cases the concentration of pesticide found in pollen is not lethal, it is however likely to cause paralysis of bees, irritability, killing and replacing of the queen bee and generally abnormal behavior.This behavior can also be caused by substances that do not kill bees directly (e.g.carbaryl as active ingredient of Sevin®) but are transferred into the hive by foragers and affect the entire population (Sanford, 1993).The long-term persistence of many pesticides in stored pollen has also serious impact of bees' survival.Arsenic from paris green and calcium arsenate was present in pollen stored in comb analyzed six months after application.Methomyl residues persisted in honeybee combs for eight months.Methyl parathion from Penncap M, persisted in combs samples of stored pollen for 7 to 14 months after use and carbaryl similarly persisted over winter for 7-9 months (Erickson et al., 1983) www.intechopen.comPesticide Residues in Bee Products 91 Neonicotinoids like imidacloprid were also detected in stored pollen (Gregorc & Bozic, 2004;Chauzat et al., 2006).Also, the type of formulation and application of the pesticide in relation to toxicity caused to the bees proved particularly important.For example, the standardization of the active ingredient methyl parathion in microcapsules kills 13 times more bees than the formulation of the same substance as an emulsified solution.Furthermore, wettable powder or dust proved less dangerous than microcapsules, but also caused more deaths than aqueous or emulsified solutions (Sanford, 1993).Under the development of framework concerning consumer safety, the European Union created a warning system called RASFF (Rapid Alert System for Food and Feed), which reports hazardous foods and feeds, identified in the markets of the Member States.Bee products like honey and royal jelly have been reported occasionally.The main reason why they have been reported is the detection of residues of antibiotics that have been used by beekeepers to fight various diseases of bees.www.intechopen.com

The marked increase in the demand for animal protein of high quality necessitates protecting animals from infectious diseases. This requires increasing the use of veterinary therapeutics. The overuse and misuse of veterinary products can cause a risk to human health either as short-term or long-term health problems. However, the biggest problem is the emergence of resistant strains of bacteria or parasites. This is in addition to economic losses due to the discarding of polluted milk or condemnation of affected carcasses. This paper discusses three key points: possible sources of drug and chemical residues, human health problems, and the possible method of control and prevention of veterinary drug residues in animal products.