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.

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.

Resíduos de medicamentos veterinários em alimentos de origem animal / Veterinary drug residues in food from animal origin / Residuos de medicamentos veterinarios en alimentos de origen animal

É crescente a preocupação de consumidores quanto à presença de resíduos químicos em alimentos de origem animal, principalmente antimicrobianos, hormônios e agrotóxicos. Com o uso massivo de fertilizantes e medicamentos veterinários, muitas vezes, estimulado pela indústria química, é cada vez mais comum a presença desses compostos em alimentos. Possíveis consequências prejudiciais à saúde humana podem surgir como resultado da exposição aguda e/ou crônica a resíduos de medicamentos veterinários. Esses resíduos normalmente são detectados em níveis abaixo do limite máximo permitido, favorecendo o aparecimento de tumores a longo prazo, embora as reações de hipersensibilidade em consumidores sensibilizados e a resistência a antibióticos possam ocorrer. A atuação de programas de monitoramento e vigilância, bem como das boas práticas agropecuárias, tornam-se fundamentais para a prevenção e controle de resíduos em alimentos. Este estudo atualiza informações referentes à indústria de medicamentos veterinários e revisa as principais causas de seus resíduos em produtos de origem animal, principais tipos de resíduos encontrados, incidências e aspectos regulatórios com ênfase nos riscos à saúde pública...

There is a growing concern by consumers about the presence of chemical residues in food from animal origin, mainly antimicrobial drugs, hormones and pesticides. With the massive use of fertilizers and veterinary drugs, often stimulated by the chemical industry, it is increasingly common to have the presence of these compounds in food. Possible harmful consequences to human health may arise as a result of acute and/or chronic exposure to veterinary drug residues. These residues are usually detected at levels below the maximum permitted levels, favoring the appearance of tumors in the long term, although hypersensitivity reactions in sensitized consumers and antimicrobial resistance may occur. The role of monitoring and surveillance programs, as well as of good agricultural practices, has become crucial for the prevention and control of residues in food. This study updates information relating to veterinary drug industry and reviews the main causes of such residues in products from animal origin, main types of residues found, their effects and the regulatory aspects, with emphasis to public health risks...

: Existe una creciente preocupación de los consumidores sobre la presencia de sustancias químicas en alimentos de origen animal, principalmente antimicrobianos, hormonas y plaguicidas. Con el uso masivo de fertilizantes y medicamentos veterinarios, a menudo, estimulados por la industria química, es cada vez más común la presencia de esos compuestos en alimentos. Las posibles consecuencias nocivas a la salud humana pueden surgir como resultado de la exposición aguda y/o crónica a residuos de medicamentos veterinarios. Esos residuos suelen ser detectados a niveles abajo del máximo permitido, lo que favorece la aparición de tumores a largo plazo, aunque se puede presentar reacciones de hipersensibilidad en los consumidores sensibles y resistencia a los antibióticos. El papel de los programas de control y vigilancia, así como de las buenas prácticas agrícolas, se han convertido fundamentales para la prevención y control de los residuos en alimentos. Este estudio actualiza informaciones relativas a la industria de medicamentos veterinarios y revisa las principales causas de sus residuos en productos de origen animal, principales tipos de residuos encontrados, incidencias y aspectos reglamentarios con énfasis en los riesgos a la salud pública...

Can the unauthorised use of ceftiofur be detected in poultry?

Ceftiofur is a third-generation cephalosporin antibiotic used to treat cattle and swine for bacterial infection of the respiratory tract. It is not authorised for use in poultry within the European Union. Due to the complexity of the chemistry and metabolism of ceftiofur, maximum residue limits (MRLs) are based on desfuroylceftiofur (DFC) equivalents after chemical conversion of all compounds that have an intact ß-lactam ring. In practice the DFC is usually stabilised as the acetamide (desfuroylceftiofur acetamide - DFCA) for analysis. Because of recent evidence of off-label use in the European Union, a policy need emerged to develop a cost-effective method for the detection of ceftiofur residues in poultry tissues. One-day-old chicks were each dosed subcutaneously with ceftiofur and samples taken from day 1 to day 44 post-dosing. Residues of ceftiofur parent compound were detected in whole chicks, wing feathers and faeces. On the basis of this finding it was decided to evaluate ceftiofur parent, as the marker, instead of proceeding with the time-consuming conversion to DFCA. Expected metabolites, DFC and desfuroylceftiofur cysteine disulfide (DCCD), were not detected in whole chicks, muscle or liver, but DFC was found in wing feathers. These results indicate that determination of ceftiofur parent compound in either whole chicks or possibly wing feathers and faeces may allow the detection of the misuse of ceftiofur.

Drug residues and endocrine disruptors in drinking water: risk for humans?

The presence of pharmaceuticals and endocrine disruptors in the environment raises many questions about risk to the environment and human health. Environmental exposure has been largely studied, providing to date a realistic picture of the degree of contamination of the environment by pharmaceuticals and hormones. Conversely, little information is available regarding human exposure. NSAIDS, carbamazepine, iodinated contrast media, ß-blockers, antibiotics have been detected in drinking water, mostly in the range of ng/L. it is questioned if such concentrations may affect human health. Currently, no consensus among the scientific community exists on what risk, if any, pharmaceuticals and endocrine disruptors pose to human health. Future European research will focus, on one hand, on genotoxic and cytotoxic anti-cancer drugs and, on the other hand, on the induction of genetic resistance by antibiotics. This review does not aim to give a comprehensive overview of human health risk of drug residues and endocrine disruptors in drinking water but rather highlight important topics of discussion.

Successful relactation--a case history.

A healthy, term male infant was weaned at 10 days postpartum because of his mother's illness. The baby was breastfed by his mother's sister, but mostly he was fed with his aunt's expressed milk and with formula by bottle. At 9 weeks postpartum relactation began. Techniques used were a supplemental nursing support system device; frequent suckle at the breast, supplemented by formula given by bottle; breast pumping; domperidone; and support from an International Board Certified Lactation Consultant and family. Problems that appeared during relactation were that at 12 postpartum weeks the baby refused the supplemental nursing system device, and at 12 weeks and 3 days he refused the breast; after 3 weeks of relactation, the milk supply was still low, needing supplementation; and in the first week of exclusive breastfeeding, the baby stopped growing, then he gained weight slowly, and his gain fell down to the 15(th) percentile. Solutions and interventions used to solve the problems were usage of an artificial nipple during breast strike for 3 days and cessation of supplementary formula and frequent suckling at the breast. Four days after relactation started, colostrum appeared (for 2 weeks), and within 1 month from the beginning of relactation the baby was fully breastfed. He was exclusively breastfed until 7 months, and he was continually breastfed until 2 years. His growth was good and was around the 50th percentile on the weight/length curve. Thus relactation is possible at 9 weeks postpartum, if the mother's motivation to breastfeed is strong. The best technique to increase milk supply is frequent, short breastfeedings.

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.

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.

Medicamentos de consumo humano en el agua, propiedades físico-químicas / Physic-chemical properties of human consumption drugs in water

En los años más recientes se reconoce que los compuestos farmacéuticos activos en el ambiente acuático, constituyen uno de los eventos emergentes en la química ambiental, originados por la disposición de las aguas residuales municipales, hospitalarias y de producción, tratadas o no. Su presencia crea resistencia antibiótica, afectan los procesos biológicos de tratamiento y sobrepasan las etapas de potabilización, etc. El objetivo del trabajo es abordar los aspectos relacionados con la presencia de residuos de un grupo de medicamentos de consumo humano en el agua, su cuantificación y características físico-químicas, reportados por diversos autores en la última década, problema que aborda la contaminación que provocan estos compuestos y la necesidad de su estudio. Las características físico-químicas del grupo de medicamentos se obtuvieron consultando diferentes bases de datos y del estudio de más de 100 artículos científicos sobre el tema. Se evidenció su detección en el agua, se reporta la concentración en el agua del grupo de medicamentos seleccionados y sus características físico-químicas. Se reconoce que estos compuestos potencialmente se transportan de forma mayoritaria en los sistemas acuíferos. Se requiere profundizar más en el tema.

In recent past years it is recognized that the active pharmaceutical compounds in aquatic environment are one the emerging events in environmental chemistry, originated by disposition of the municipal, sewage, from hospitals and for production waters treated or not. Its presence originates an antibiotic resistance, affecting the treatment biological processes and exceeding the fitness for drinking, etc. The aim of present paper is to approach the features related to presence of wastes from human-consumption drugs present in water, its quantification and the physic-chemical characteristic, reported by many authors in past decade, it is a problem approaching the contamination provoking these compounds and the need of its study. Physic-chemical characteristic of drugs group were obtained consulting different databases and from study of more than 100 scientific articles on this matter. Its detection in water was demonstrated, concentration in water of the drugs selected and its physic-chemical characteristic was reported. It is recognized that these compounds potentially are carried in a majority was in aquiferous systems. We must to make a study in depth on this matter.

A survey of antimicrobial use during bovine abdominal surgery by western Canadian veterinarians.

Members of the Western Canadian Association of Bovine Practitioners were surveyed regarding their use of antimicrobials in bovine abdominal surgery. Perioperative antimicrobials were used in 100% of abdominal surgeries by 96 of 98 respondents. Although postoperative administration was the most common perioperative period for antimicrobial use, intraoperative intraperitoneal use was reported by more than half of the veterinarians surveyed. Procaine penicillin G and oxytetracycline were the most commonly administered perioperative antimicrobials.

[Impact on human health of hormonal additives used in animal production]. / Impacto en el humano de aditivos hormonales empleados en bovinos productores de carne.

The establishment of the impact of environmental compounds or additives with hormone-like activity on human health still requires further investigation, as well as a reexamination of biologic models and experimental methodology employed so far. In 1988, the FAO/WHO Expert Committee on Food Additives Joint with the Federal Drug Administration (FDA) considered that sexual hormone residues usually present in meat do not represent a risk for human consumption. Nevertheless, this resolution seems to be uncertain since the scientific elements employed for this statement may not be adequate. In this review the principal objections to the evidence used to establish the innocuousness of growth promoter hormones are considered.

Evaluation of certain veterinary drug residues in food.

The first part of the report presents the views of the Committee on assessment of carcinogenic risk, quality of data, marker residues, and the Joint FAO/WHO Project to update the principles and methods for the risk assessment of chemicals in food. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two antimicrobial agents (neomycin and flumequine), an antiprotozoal agent (imidocarb), three insecticides (deltamethrin, dicyclanil, and trichlorfon) and one production aid (carbadox). Annexed to the report is a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and Maximum Residue Limits. Corrigenda to WHO Technical Report Series 911: Evaluation of certain veterinary drug residues in food, 2002, are also included.

Helminthic control on grazing ruminants and environmental risks in South America.

The control of ruminant gastrointestinal nematodes and ectoparasites, one of the major production health problems, are heavily reliant on the systematic and sometimes abusive use of anthelmintic drugs. Endectocides are the most frequently used drugs, having high potency against arthropods and nematodes. Their dung pat residues enhance the risk of adverse effects on non-target invertebrates and on the general grazing cattle ecosystem. In this scenario, our objective is to review current knowledge of the agro-environmental and biodiversity impact and risks of endectocides in South America. The effects of faecal drug residues of ivermectin and doramectin on dung colonising invertebrates and dung degradation have been reported in studies carried out in the temperate centre of Argentina and in the subtropical region of Brazil. The results from Argentina showed a depression in invertebrate colonisation and degradation of dung recovered from endectocide treated cattle during the autumn. Comparisons have shown that ivermectin and doramectin have similar adverse effects. A decrease of Coleoptera larvae, Diptera larvae, Staphylinidae, Collembola, Acari and dung specific nematodes was noted in pats from both endectocides. The results from Brazil showed that dipterous larvae, Polyphaga coleopteran larvae and adults and mites were significantly reduced in the ivermectin treated group. The disturbances that macrocyclic lactones can produce on non-targeted invertebrates and on their associated participation in dung degradation and soil element recycling, are unpredictable and can negatively influence biodiversity and the agricultural ecosystem sustainability.

The Belgian PCB and dioxin incident of January-June 1999: exposure data and potential impact on health.

In January 1999, 500 tons of feed contaminated with approximately 50 kg of polychlorinated biphenyls (PCBs) and 1 g of dioxins were distributed to animal farms in Belgium, and to a lesser extent in the Netherlands, France, and Germany. This study was based on 20,491 samples collected in the database of the Belgian federal ministries from animal feed, cattle, pork, poultry, eggs, milk, and various fat-containing food items analyzed for their PCB and/or dioxin content. Dioxin measurements showed a clear predominance of polychlorinated dibenzofuran over polychlorinated dibenzodioxin congeners, a dioxin/PCB ratio of approximately 1:50,000 and a PCB fingerprint resembling that of an Aroclor mixture, thus confirming contamination by transformer oil rather than by other environmental sources. In this case the PCBs contribute significantly more to toxic equivalents (TEQ) than dioxins. The respective means +/- SDs and the maximum concentrations of dioxin (expressed in TEQ) and PCB observed per gram of fat in contaminated food were 170.3 +/- 487.7 pg, 2613.4 pg, 240.7 +/- 2036.9 ng, and 51059.0 ng in chicken; 1.9 +/- 0.8 pg, 4.3 pg, 34.2 +/- 30.5 ng, and 314.0 ng in milk; and 32.0 +/- 104.4 pg, 713.3 pg, 392.7 +/- 2883.5 ng, and 46000.0 ng in eggs. Assuming that as a consequence of this incident between 10 and 15 kg PCBs and from 200 to 300 mg dioxins were ingested by 10 million Belgians, the mean intake per kilogram of body weight is calculated to maximally 25,000 ng PCBs and 500 pg international TEQ dioxins. Estimates of the total number of cancers resulting from this incident range between 40 and 8,000. Neurotoxic and behavioral effects in neonates are also to be expected but cannot be quantified. Because food items differed widely (more than 50-fold) in the ratio of PCBs to dioxins, other significant sources of contamination and a high background contamination are likely to contribute substantially to the exposure of the Belgian population.

Lifestyle and environmental contribution to male infertility.

This chapter is an overview of recent developments in our understanding and thinking about the importance and nature of environmental effects on sperm counts and fertility in the human male. This area is plagued by imperfect studies, not necessarily because of imperfect design but because of other 'uncontrollable' constraints. The available data, therefore, need to be placed in context and account taken of the limitations of our understanding or, more correctly, our ignorance. As we enter the new millennium, one of the saddest scientific aspects of human reproduction and infertility is our persisting ignorance about the causes and treatment of male infertility. With one notable exception (Y chromosome microdeletions) there has been little advance in our understanding of the causes of male infertility and its direct treatment over the past 20 years. Although most infertile men can now be offered the chance of fertility via ICSI, it is largely ignored that this does not represent treatment of the patient's infertility (which will persist unchanged), but is a means of circumventing the problem and leaving it for the next generation to tackle. There are many reasons for our ignorance about the causes of infertility, and some of these are outlined below in order to emphasise how this limits our ability to establish whether or not specific lifestyle and environmental factors do, or do not, affect human male reproductive function.

Evaluation of certain veterinary drug residues in food.

This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs and to recommend maximum levels for such residues. The first part of the report considers an approach to assessing the safety of antimicrobial drug residues and their effects on the human intestinal microflora and general issues relating to the recommendation of Maximum Residue Levels (MRLs) for veterinary drug residues in food. A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: one beta-adrenoceptor-blocking agent (carazolol), one anthelminthic agent (doramectin), four antimicrobial agents (dihydrostreptomycin, streptomycin, neomycin and thiamphenicol), two insecticides (deltamethrin and phoxim), four production aids (estradiol-17 beta, progesterone, testosterone and porcine somatotropins) and one tranquillizing agent (azaperone). Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and MRLs, and other information required.