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Co-extraction of multiple types of target substances is the key to achieve high throughput detection. In this work, PDA@MOF-808/PAN NFsM was prepared by co-modified polyacrylonitrile nanofiber membrane (PAN NFsM) with polydopamine (PDA) and metal-organic framework-808 (MOF-808), and its potential as a solid-phase extraction (SPE) adsorbent was investigated by using the most typical nine veterinary drug residues in eggs and chicken as model target substances. The results show that PDA@MOF-808/PAN NFsM could effectively co-extract all the target substances (adsorption efficiency ranged from 81.46 % to 96.78 %), and had good capability of sample matrix purification (matrix effect was lower than -15.26 %), so a new SPE method has been established. Combined with UPLC-MS/MS, the detection limits were 0.3 to 3.1 μg/kg, the recoveries were between 71.02 % and 106.48 %, and the relative standard deviations were lower than 12.03 %, indicating that the method has considerable good sensitivity, accuracy and precision., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Due to the unexpected detection of chloramphenicol isomer residues in honey, we have studied the hypothesis of unauthorized or unintended use of unregistered veterinary drug preparations. First, we have investigated honey samples in which a discrepancy was observed between the results of the immunological screening methods and the confirmatory liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. In all samples, previously identified to be contaminated with the banned antibiotic chloramphenicol according to LC-MS/MS only, the presence of dextramycin (SS-para isomer of chloramphenicol) was detected by chiral LC-MS/MS. The source of dextramycin in honey was investigated by studying the preparations utilized in apiaries from which the above non-compliant honey samples have been received. In all these preparations (beehive strips applied against the mite Varroa destructor) chloramphenicol was detected in the concentrations ranging from 33 to 34,400 μg kg -1 . Chiral LC-MS/MS demonstrated the presence of chloramphenicol and dextramycin in different ratios, and it was concluded that these preparations can be the source of chloramphenicol and dextramycin residues in honey. These preparations were of foreign production and are not officially registered in accordance with current legislation., (Copyright © 2017 John Wiley & Sons, Ltd.)

The distributions of eight drugs (acetaminophen, acetylsalicylic acid/salicylic acid, ciprofloxacin, clarithromycin, flunixin, phenylbutazone, praziquantel, and thiamphenicol) were determined in milk products (skim milk, milk fat, curd, whey, and whey protein) and used to expand a previous model (from 7 drugs to 15 drugs) for predicting drug distribution. Phenylbutazone and praziquantel were found to distribute with the lipid and curd phases (≥50%). Flunixin distribution was lower but similar in direction (12% in milk fat, 39% in curd). Acetaminophen, ciprofloxacin, and praziquantel preferentially associated with casein proteins, whereas thiamphenicol and clarithromycin associated preferentially to whey proteins. Regression analyses for log [milk fat]/[skim milk] and log [curd]/[whey] had r 2 values of 0.63 and 0.67, respectively, with p of <0.001 for 15 drugs (7 previously tested and 8 currently tested). The robustness of the distribution model was enhanced by doubling the number of drugs originally tested.

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., (Copyright © 2016 John Wiley & Sons, Ltd.)

The toxic effect of aflatoxins (AF) and zearalenone (ZEA) and their combination on laying performance, egg quality and toxins residues in eggs, as well as the efficacy of Bacillus subtilis biodegradation product (BDP) for ameliorating these effects in layers were evaluated. Layers were submitted to a two phase experiment. The first phase was an intoxication period (18-23 wk) with birds fed 7 (3 × 2 + 1) diets (3 treatments with mycotoxins: AF (123.0 μg/kg), ZEA (260.2 μg/kg), or AF + ZEA (123.0 + 260.2 μg/kg); 2 treatments with or without BDP (1000 g/t); and a control group contained no toxins nor BDP). The next phase was a recovery period (24-29 wk) in which birds were fed a toxin-free diet. In the intoxication period, AF and AF + ZEA groups exhibited lower egg production, feed intake and shell thickness, and higher AFB1, AFB2 and AFM1 residues as compared with the control group. In addition, AF and ZEA exerted synergistic effects on egg production and feed intake. Moreover, AF alone or combined with ZEA had a continuous toxic effect on laying performance in the recovery phase. Addition of BDP offset these negative effects, showing that BDP has a protective effect on layers fed contaminated diets., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Gentamicin (Gent) is an aminoglycoside antibiotic being used in livestock sector. Gent residues could cause some genetic disorders by nonsense mutations. This study aimed to develop IgY-based ELISA for the detection of Gent in animal products. Gent was conjugated with Bovine serum albumin (BSA) by carbodiimide method for further immunization in the laying chickens. PEG-6000 extraction method was employed to extract IgY from the egg yolk. The titer of anti-Gent-IgY attained the peak of 1:256,000 after the 5(th) booster immunization. Checkerboard titration confirmed that, anti-Gent IgY in 1:2,000 dilution could give an Optical Density (OD) 1.0 at 2 µg mL(-1) of Gent-OVA coating concentration. IgY-based indirect competitive ELISA (Ic-ELISA) showed that, the IC50 value of anti-Gent IgY was 2.69 ng mL(-1) and regression curve equation was y = -16.27x + 56.97 (R(2) = 0.95, n = 3), confirming that, the detection limit (LOD, IC10 value) was 0.01 ng mL(-1). Recoveries from fresh milk, pork and chicken samples were ranged from 69.82% to 94.32%, with relative standard deviation lower than 10.88%. Our results suggested that generated anti-Gent IgY antibodies can be used in routine screening analysis of Gent residues in food samples.

Herein, a label-free electrochemiluminescence (ECL) aptasensor for highly sensitive determination of kanamycin was developed based on a novel "on-off-on" switch system. The first "switch on" state with remarkably high ECL intensity was obtained by the tri-layer composite films modified glassy carbon electrode towards the S2O8(2-)-O2 system. To be specific, the first layer was the Au nanoparticles decorated C60 nanoparticles (abbreviation as Au@nano-C60) as inner-layer which was prepared by the in situ generating of Au nanoparticles onto the surface of bovine serum albumin decorated nano-C60 nanoparticles. Then poly-L-histidine was first selected as a novel coreactant of S2O8(2-)-O2 system and it was adsorbed on the Au@nano-C60 modified electrode as inter-layer. Finally, a self-assembling layer of colloidal Au nanoparticles (AuNPs) was the outer-layer. The three layers were interaction by the Au-N covalent bond which could achieve a desirable initial amplified ECL signal. Successively, the capture probes (CPs) of the aptamer for the target of kanamycin was anchored on the resultant tri-layer composite films modified electrode. Later, the "switch off" state was made by the quenching effect of hemin/G-quadruplex DNAzymes towards S2O8(2-)-O2 system according to the DNA hybridization reaction of an assistant probes (APs, guanine-rich nucleic acid) with CPs which could generate a large amount of hemin/G-quadruplex DNAzymes in the presence of hemin with a simple and label-free process. As expected, the second "switch on" state was the ECL signal recovery when the target of kanamycin was present, it is attributed to that the formation of the aptamer-kanamycin complex makes the quencher of hemin/G-quadruplex DNAzymes release from the sensing interface. With the association of "on-off-on" switch system, a linear response about 9 orders of magnitude for kanamycin detection was obtained from 0.15 nM to 170 mm as well as a detection limit down to 45 pM., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The Korean National Residue Programme comprises three different approaches for evaluating domestic and imported foods of animal origin: monitoring, surveillance/enforcement and an exploratory test programme. Monitoring and surveillance/enforcement testing programmes are routinely implemented by 17 Provincial Veterinary Services for domestic products and regional offices of the Animal and Plant Quarantine Agency (QIA) for imported products. The exploratory project conducted at QIA headquarters is designed to test substances that are not included in monitoring and enforcement testing programmes. Here, we carried out exploratory testing for determining the presence of 42 veterinary drugs that have no established Korean maximum residue limits and analysed their levels simultaneously, in a total of 3108 samples of domestic and imported animal-origin foods. Of the tested drugs, acetylsalicylic, paracetamol, clopidol, diclazuril, amprolium, toltrazuril and its metabolites (toltrazuril sulphone and toltrazuril sulphoxide) and phenylbutazone and its metabolites (oxyphenylbutazone) were detected.

The aim of this study was to determine the binding capacity of a hydrated sodium calcium aluminosilicate (HSCAS) for aflatoxin B(1) (AFB(1)), and the efficacy of the HSCAS to reduce the concentrations of residual AFB(1) and its metabolites in the liver and kidney of broilers fed AFB(1). One hundred 1-d-old male broilers (Ross 708) were maintained in chick batteries and allowed ad libitum access to feed and water. A completely randomized design was used with 5 replicate pens of 5 chicks assigned to each of 4 dietary treatments from hatch to 21 d. Dietary treatments included the following: A) basal diet (BD), with no HSCAS or AFB(1), B) BD supplemented with 0.5% HSCAS only, C) BD supplemented with 2.5 mg of AFB(1)/kg of feed, and D) BD supplemented with 2.5 mg of AFB(1)/kg of feed and 0.5% HSCAS. On d 21, 5 chicks from each treatment were anesthetized with carbon dioxide, killed by cervical dislocation, and samples of liver and kidney were collected for analysis of AFB(1) residues. The percentage of AFB(1) bound for each concentration of adsorbent (100, 10, 1, 0.5, 0.25, and 0.05 mg/10 mL) was 100, 91.1, 81.8, 75.4, 40.1, and 8.8%, respectively. Concentrations of aflatoxin residues (AFB(1), aflatoxicol, aflatoxins B(2) and G(1)) were lower (P < 0.05) in livers and kidneys of birds fed AFB(1) plus HSCAS (diet D), when compared with birds fed AFB(1) alone (diet C). However, histopathology data from the in vivo study indicated that HSCAS did not prevent lesions associated with aflatoxicosis. The decrease in the bioavailability of AFB(1) caused by the HSCAS reduced aflatoxin residues in liver and kidney, but not enough to completely prevent the toxic effects of AFB(1) in broilers.

Residues of veterinary drugs and feed additives used extensively in animal husbandry are sometimes found in edible matrices. In this study, broilers received experimental feed, containing either flubendazole or tylosin, at cross-contamination levels of 2.5%, 5%, and 10% of the therapeutic dose to determine the transfer ratio of these molecules from feed to poultry matrices. Breast and thigh muscle and liver samples were collected during treatment and depletion periods and then analyzed using liquid chromatography-tandem mass spectrometry. The parent molecule flubendazole and its 2 major metabolites were quantified. After 3 to 5 d, a plateau phase was reached, and a few days after withdrawal of the experimental feed, a depletion of residues was noted. Significant difference between both muscle types was noted for flubendazole. Strong metabolization of flubendazole in the liver was seen. For tylosin, no residue concentrations above the limit of quantification could be detected in muscle. None of the residue concentrations for either molecule exceeded the corresponding maximum residue limits.

This study surveyed tetracycline residues in foods marketed in Kuwait using various techniques to determine their prevalence above the threshold level. A total of 1517 locally produced and imported food samples of animal origin were collected for analyses, comprising dairy products, eggs and tissue samples (meat, poultry and fish) to give a representative picture of the current use and/or misuse of the drug in Kuwait. Screening was carried out using the Charm II test for tetracycline residues. Positive and suspect positive samples were confirmed by LC/MS/MS. Negative and positive controls, in triplicate, were applied to each method and showed 80-100% agreement. The results showed that 100% of tested eggs, meat, fish, ice cream and cheese were within the limit, while 5% of poultry and 18% of milk samples were above the permitted limit.

The aim of this study was to evaluate the ability of AflaDetox (Adiveter, Agro-Reus, Reus, Tarragona, Spain) in counteracting the deleterious effects of aflatoxin B(1) (AFB(1)) in broiler chicks. A total of 120 Ross 308 one-day-old male broiler chicks were assigned to 8 treatments for 42 d. The experiment had a 2 x 4 factorial arrangement of treatments involving 0 and 1 mg of AFB(1)/kg feed and 0, 1, 2, and 5 g of AflaDetox/kg feed. Chicks were fed on the ground during the first 7 d and in cages (3 chicks/cage; 5 cages/treatment) from 7 to 42 d. Growth performance was measured from d 7 to 42 and whole-tract digestibility of gross energy and protein on d 40 to 41. Serum biochemical parameters, organ weights, histopathological examination of liver, and AFB(1) residues in liver and breast muscle tissues were determined on d 42. Aflatoxin B(1) significantly decreased the BW gain, feed intake, and impaired feed conversion rate (P < 0.05). The addition of AflaDetox in the contaminated diets significantly diminished the inhibitory effects of dietary AFB(1) (P < 0.05) on the growth performance with no differences compared to the control diet. Feeding AFB(1) alone decreased serum protein concentration, increased the serum activity of alkaline phosphatase, and caused significant increases in the relative weights of livers. Treatment with AflaDetox significantly alleviated the negative effects of AFB(1) on these parameters (P < 0.05) with no effect on uncontaminated diets. Liver tissue of broilers receiving AFB(1) alone had perilobular inflammation and vacuolar degeneration of hepatocytes as compared with the tissue from the control group (P < 0.05). Residues of AFB(1) were detected in the liver tissues of broilers fed on the AFB(1) diet (0.166 microg/kg). Supplementation of AflaDetox reduced the incidence and severity of the hepatic histopathology changes associated with aflatoxicosis and the amount of AFB(1) residue in liver. In conclusion, our results showed that addition of AflaDetox may reduce the adverse effects produced by the presence of AFB(1) in broiler chickens diets.

Residues of veterinary drugs have potential implications for human food safety and international trade in animal-derived food commodities. A particular concern is the slow depletion of residues of some injectable formulations from the site of administration. Licensing authorities have adopted different approaches to the human food safety assessment of injection site residues. European agencies apply the maximum residue limit (MRL) for muscle to muscle at the injection site and specify a withdrawal period sufficient to ensure the ingestion of a 300 g portion of muscle, if comprised entirely of injection site tissue, does not exceed the acceptable daily intake. The agencies in Australia, Canada and the USA also exclude injection site residues from the MRL-setting process. These agencies evaluate the risk to consumers posed by potential acute manifestations resulting from the infrequent ingestion of injection site residues based on acute dietary exposure considerations. While all of these approaches protect the safety of consumers, the adoption of different approaches has potential implications for residue surveillance programs in the international trade in meat. In particular, when an exporting country establishes standards for residues at injection sites based on acute dietary exposure considerations and the importing country assesses these residues against the MRL for muscle, the unnecessary condemnation of meat and disruption to market access may result. The latter may represent a potential economical impost to the exporting country. An internationally harmonized approach to the risk analysis of residues of veterinary drugs at injection sites, which protects the safety of consumers and facilitates the international trade in meat, is needed.

This review concerns a statistical method for calculating withdrawal period for injection site residues. A recently adopted Committee for Medicinal Products for Veterinary Use/European Agency for the Evaluation of Medicinal Product (CVMP/EMEA) guideline recommends to apply the same method for the calculation of withdrawal period for injection site residues as for other edible tissues. For reasons in this study developed below, this approach is deemed to be inappropriate for the injection site residues. The injection site residues often violate regression assumptions with regard to homoscedasticity (same variance in residue concentrations for different slaughter times) and linearity (of the mean depletion curve in log(e)-scale). The currently recommended method cannot adequately handle these aspects. An alternative pragmatic method taking into account the last slaughter time with all data below the reference threshold, combined with a safety span, is proposed for injection site residues. A nonparametric approach for calculating the withdrawal period is also presumed to be a sound alternative. The references commonly used are the Maximum Residue Limit (MRL) and the Acceptable Daily Intake (ADI). Unfortunately these references are not relevant to the acute risk exposure associated with injection site consumption. The use of alternative references, such as the Acceptable Single Dose Intake (ASDI) or the Acute Reference Dose (ARD) are thought to be more appropriate.

The recent adoption of the guideline on injection site residues in food producing animals by the Committee for Medicinal Products for Veterinary Use (CVMP) raised the question on the risk specifically related to injection site consumption. As noted in this guideline, residues at injection sites commonly deplete erratically. For the calculation of withdrawal time, treating residues at the injection site like those that occur in other tissues is questionable. An assessment of the risk related to the consumption of a whole or part of an injection site during a year was performed using a probabilistic approach. The risk assessment was modelled on the regimen of a 7-day antibiotic treatment, and was calculated on the scale of the European Union (EU) as a whole or of each European country. Our analysis indicated a maximal risk of 4 days of injection site consumption during a year in the EU. It also indicated that 37% of consumers would never eat an injection site in the same period. These results suggest that the risk of injection site consumption belongs more appropriately to an acute exposure risk than to a chronic one which is usually posed by the residues present in other edible tissues.

Shellfish culture is a major sector of aquaculture production worldwide, and zoonoses and drug residues associated with shellfish farm practice are of concern to public health. This paper focuses on three of the most important shellfish species: molluscs, crabs and shrimp. Although many diseases can affect shellfish, they do not appear to be transmittable to humans. Rather, the main hazards are associated with the methods used to farm the different species. The risk to human health from shellfish most commonly relates to contamination by biotoxins produced by marine algae. Another well-recognised problem associated with shellfish culture is the contamination of shellfish with domestic sewage that contains human pathogenic bacteria and viruses, which causes diseases such as typhoid fever and hepatitis. In shrimp farming, the main potential food safety hazards are zoonoses, chemical contamination and veterinary drug residues. Untreated effluent from shrimp farms is a major concern to the environmental sector as it is known to promote plankton blooms if directly discharged into natural water sources.

In the European Community and in Germany drug residues are scarcely found in food of animal origin. Therefore, a high degree of safety is ensured for consumers. Problems may result from imported foods, because limitations of drug use in livestock of the European Community do not exist everywhere. Because antibacterial drugs are administered frequently, the problem of transferred multiple-drug resistance of bacteria has to be especially considered.

Chemical food contaminants are substances which are neither present naturally in the usual raw material used for food production nor are added during the regular production process. Examples are environmental pollutants or contaminants derived from agricultural production of crops or livestock or from inadequate manufacturing of the food product itself. More difficult is the classification of those compounds formed during regular manufacturing such as products of thermal processes including flavoring substances. In these cases, it is common practice to call those compounds contaminants which are known for their adverse effects such as acrylamide, whereas constituents which add to the food-specific flavor such as Maillard products formed during roasting, baking etc. are not termed contaminants. From a toxicological viewpoint this distinction is not always clear-cut. Important groups of chemical contaminants are metals such as mercury or lead, persistent organic pollutants such as polychlorinated biphenyls and related pollutants, which are regularly found in certain types of food originating from background levels of these compounds in our environment. Furthermore, natural toxins form microorganisms or plants, and compounds formed during thermal treatment of food are of major interest. In general, a scientific risk assessment has to be carried out for any known contaminant. This comprises an exposure analysis and a toxicological and epidemiological assessment. On these grounds, regulatory and/or technological measures can often improve the situation. Major conditions for a scientific risk assessment and a successful implementation of regulations are highly developed food quality control, food toxicology and nutritional epidemiology.

This article reviews clinical pharmacology in food animal production in Canada and Mexico. The authors discuss topics such as drug availability, the drug-approval process, availability (prescription or over-the-counter) of drugs to producers, withdrawal times, and extralabel drug use. Drugs that are prohibited and proactive measures for drug use in Canadian food animals also are reviewed.

The author's interpretation of some of the regulations involved in drug selection and usage by bovine veterinarians has been presented here. If necessary, the practitioner should address further questions to the appropriate regulatory agencies. The role of the veterinarian in protecting the US food supply has never been more critical, and familiarity with the applicable regulations regarding drugs used in food animals is an important component of the food animal veterinarian's knowledge base.

A dose response study was carried out with piglets to examine the effects of increasing amounts of Fusarium toxins in the diet on performance, clinical serum characteristics, organ weights and residues of zearalenone (ZON) and deoxynivalenol (DON) and their metabolites in body fluids and tissues. For this purpose, Fusarium toxin contaminated maize (1.2 mg ZON and 8.6 mg DON per kg maize) was incorporated into a maize based diet for piglets at 0, 6, 12.5, 25 and 50% at the expense of control maize. The experimental diets were tested on 100 female piglets allotted to 20 boxes (five animals per box) covering a body weight range of 12.4 +/- 2.2 kg to 32.5 +/- 5.6 kg. Voluntary feed intake and, consequently, body weight gain of the animals receiving the highest proportion of Fusarium toxin contaminated maize were significantly decreased while the feed conversion ratio was not affected by the treatment. The mean weight of the uterus related to the body weight of the animals of the same group was increased by almost 100% as compared to the control. For this group, significantly decreased values of total serum protein were determined, while the serum activity of the liver enzyme glutamate dehydrogenase and the serum concentration of the follicle stimulating hormone were decreased for all treatment groups receiving 6% contaminated maize or more in the diet. Serum concentrations of immuneglobulins were not consistently altered by the treatment. Corresponding to the dietary exposure, increasing concentrations of ZON and alpha-zearalenol were detected in the bile fluid, liver and in pooled urine samples. The metabolite beta-zearalenol was detected only in bile fluid. The total concentration of ZON plus its metabolites in bile fluid correlated well with the diet contamination (r = 0.844). DON was found in serum, bile fluid and pooled urine samples while de-epoxy-DON was detected only in urine. The serum concentration of DON correlated well with the respective toxin intake 3-4 h prior to slaughtering (r = 0.957). For all mentioned analyses of residues it has to be noted that toxin residues were detectable even if negligible concentrations were present in the diet.

Immuno-sensing with optical biosensors is a new technique that is currently being exploited for detection of residues in foods. The present study explores the possibilities of obtaining fast screening assays for a number of illegal veterinary drug residues at low concentrations. Analyte specific sensor surfaces were prepared and used to construct inhibition assays with various antibody reagents. Assay sensitivities for calibration curves in buffer solutions around 0.5 ng ml(-1) in terms of IC50 (concentration of the inhibitor) values were achieved for the beta-agonist clenbuterol and the hormone analogues ethinylestradiol and trenbolone. Assay performance was optimised by evaluating factors such as sensor surface ligand density, active antibody concentration, biosensor flow rate, etc.

Improvements in food safety in the United States of America are currently limited by the lack of an open, reliable and uniform animal identification system. Public health would benefit from the development of such a system because this would permit accountability for an prevention of food safety hazards, including residues and harmful pathogens. In addition, the public would benefit because data collection and long-term research studies are currently hampered by the lack of animal identification. Understanding of the ecology of food-borne pathogens in the production and handling period before slaughter needs to be improved. Animal identification will permit packers and consumers to reward producers for using food safety-related production practices. Food animal producers do not regularly receive an economic advantage for voluntarily undertaking food safety-related production practices. As a result, the original source of many food animals that enter official establishments is unknown. However, the hazard analysis and critical control point system allows some producers to offer identified animals under verified production control programmes or to enter into agreements with packers with regard to the food safety status of animals.

Foods of animal origin have an important role in a balanced diet and must be safe for human consumption. Equally important is the need for the food to be perceived as safe by the consumer. Safe food of animal origin must be free from animal pathogens that infect man and from contamination by residues. While intensive farming practices have been linked with the rise in foodborne illness in humans, it is interesting to note that the rise has continued even when there has been a shift to less intensive farm production systems. While the production of meat, milk and eggs, regardless of new technology or changes in production methods, cannot be expected to achieve zero bacterial risk, there is the need to reduce the risk and, where possible, eliminate it at the 'on the farm stage'. The current use of the terms 'farm-to-table', 'stable-to-table' and 'plough-to-plate' clearly identifies the farm as one part of the production chain which must be considered in terms of food safety.

The National Residue Program is a dynamic risk-based program involving many Federal agencies, with the objective of preventing illegal drug residues and chemicals in the food supply. Surveillance is the systematic collection, analysis, and interpretation of residue data for public health action. This consists of assessing the cause(s) of the problem, recommending educational incentives, and intervention of prevention and control measures. The role of residue databases in formulating policy decisions and identifying risk factors for drug residues is discussed. A descriptive analysis, of 5 years (1992-1996) field investigative reports of drug residue occurrence in food animals is presented. The results showed that violative residues occurred predominately in culled dairy cows and bob veal calves.

Steroidal sex hormones and synthetic derivatives are used in the US to enhance growth in food-producing animals. The European Economic Community has banned use of these same substances, reportedly on the grounds of food safety. The US maintains that this ban was and is a disguised restriction on trade. The technical grounds for bringing this case and the impact of the findings of the World Trade Organization on the regulation of animal drugs in the US is discussed.

Most food containing drug residues is consumed after cooking or processing, yet surveillance for these residues is almost always conducted on raw tissue. This investigation was to establish the effect of cooking on residues of the nitroimidazole drugs dimetridazole and ronidazole in chicken muscle and egg, to enable dietary intake calculations based on surveillance results. In model aqueous and lipid solutions, dimetridazole and its 2-hydroxy metabolite, which is usually found when residues are present, were relatively stable for times and temperatures normally encountered during standard cooking methods. Ronidazole in hot aqueous solutions, except at acidic pH, was converted into the 2-hydroxy metabolite. Chicken meat and eggs from birds treated with dimetridazole or ronidazole were used to investigate the effects of cooking on food containing these residues. It was apparent that these residues were not destroyed by cooking chicken meat although some of the residue leached from the sample with juices which exuded as it cooked. Residue concentration in egg reduced during cooking by between 14% and 32% of the original concentration.

During the last one-and-one-half decades, FARAD has established an unparalleled compilation of residue and pharmacokinetic information for veterinary species. In order to fulfill its mission, FARAD has become as much a research project as an educational one. Pressing problems, such as disease-altered kinetics, minor-species drug use, and industrial contaminants in livestock, require the new methods of analysis FARAD is developing. The data upon which this work is based can be greatly augmented by participation by other nations. In the United States, it was the cooperation of both academic and regulatory organizations that made the success of FARAD possible. Similar international cooperation can facilitate use of the FARAD model in other countries for the economic benefit of all participants, enhancement of food safety, and promotion of animal welfare.

There are a number of factors that must be considered in any attempt to control animal drug residues in milk and milk products. Dairy herds vary greatly in number of cows. Milk from individual cows and farms is pooled, diluting drug residues that may be present in the milk from a single treated cow. Management techniques, including the handling, administration, and record keeping of animal drugs, vary greatly from one dairy to another. It is important that both veterinarians and nonveterinarians adhere to adequate milk discard times for animal drugs used to treat dairy animals. Observance of appropriate safeguards at the farm level, such as record keeping and clearly identifying treated animals, is critical for controlling and preventing the presence of illegal animal drug residues. Within the framework of the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act, the FDA is working with state and other regulatory agencies and industry to better ensure the absence of illegal animal drug residues in milk and milk products. Preventive measures concentrate on minimizing the need to administer animal drugs to lactating cows, and diverting milk containing drug residues from the human food supply. Monitoring programs concentrate on screening milk and tracing violations to the individual producer. Minimizing illegal drug residues in milk and milk products requires close cooperation between farmers, veterinarians, the dairy industry, the pharmaceutical industry, and regulators.

Monensin, salinomycin and narasin were detectable in six, two and one, respectively, out of 161 eggs surveyed in Northern Ireland in 1994. In all cases, the concentrations detected were less than 2.5 ng/g. Lasalocid was detectable in 107 eggs at concentrations ranging from 0.3 to 129 ng/g. Cross-contamination of unmedicated feeds with monensin during feed manufacture (up to eight batches of unmedicated feed contaminated with monensin) was similar to that previously observed for lasalocid (up to nine batches contaminated). Therefore differences in the incidence in eggs could not be explained by differential carry-over during feed manufacture. In a feeding trial it was shown that the relative ability of monensin, salinomycin and lasalocid to accumulate in eggs was in the ratio 0.12:3.3:63 ng/g egg per mg/kg feed, respectively. This indicated that the potential for monensin and salinomycin to cause residues in eggs was very low, by comparison with lasalocid. In 1995, a granular formulation of the lasalocid premix was introduced into the United Kingdom that decreased the carry-over of this drug from medicated to unmedicated feed. Six months after the introduction of this formulation, the incidence of lasalocid residues in eggs (21%) was lower than that found (66.5%) in an earlier survey (1994) carried out, and published, by this laboratory.

Experimental design was applied to an agar-diffusion inhibition test for the screening of residues of veterinary antimicrobial drugs in slaughter animals. The effects and interactions of four independent parameters were studied: the dextrose content of the culture medium, the trimethoprim concentration in the culture medium, the thickness of the agar-layer and the preincubation time. The effects on the inhibition zones of sulphadimidine, oxytetracycline, streptomycin and tylosin, substances of four different antibiotic groups were measured. An optimized multi-residue test was established with the parameter values that yielded the best sensitivity for the four substances.

A rapid and reliable method using microwave energy is described for the extraction of spiked and incurred (freeze-dried and fresh) sulphamethazine residues from swine tissues/organs (muscle, liver and kidney). Incurred tissues were obtained from an abattoir and freeze-dried pig tissue reference materials were produced as part of a reference material study for the Community Bureau of References, European Communities. The extraction was achieved by irradiating the sample in methanol for 25 s in a household microwave oven, commonly referred to as microwave-assisted extraction (MAE). The extracts were analysed without clean-up by high performance liquid chromatography (HPLC) using a C18 column and detected at 450 nm after derivatization with 4-dimethylaminobenzaldehyde (DMABA) in a heated rector at 40 degrees C. The limit of quantitation was 2.5 micrograms kg-1 of wet tissues. A comparison of MAE with an homogenization technique indicated that MAE worked extremely well for freeze-dried samples, while it showed significant variation for wet tissues. No sulphamethazine was detected in retail pork meat and liver samples when analysed by the MAE technique.

In accordance with the maximum residue limit of 100 micrograms kg-1 established by EU legislation, a simple and sensitive high-performance liquid chromatographic (HPLC) method was developed for the measurement of tylosin residues in pig tissues (fat, kidney, liver and muscle). Tylosin, a macrolide antibiotic, is extracted with water-methanol and cleaned-up by solid-phase extraction (SPE) on cation-exchange cartridges using methanol elution. Tylosin was determined by reversed-phase HPLC with UV detection at 280 nm and the mean recovery from pig tissues fortified in the range 50-200 micrograms kg-1 was 70-85%, with intra- and inter-day RSDs in the ranges 3.4-9.1 and 3.9-10.1% respectively.

An efficient extraction and sensitive gas chromatographic method is described for the determination of the anthelminthic drug levamisole in milk. Levamisole was extracted from alkaline milk with ethyl acetate. Clean-up of the extract was by a series of liquid-liquid extraction steps. Levamisole residues in the extract were determined by gas chromatography with a nitrogen-phosphorus detector. This method was satisfactory for determining levamisole residues in milk as low as 0.5 ng/g. Mean recoveries of 0.5-10.0 ng/g fortified milk samples ranged from 84.5 to 95.2%. Five replicate analyses performed on a milk containing incurred levamisole residues yielded a mean of 3.34 ng/g levamisole with a CV of 3.0%.

PET packaging materials have been tested for volatile content after exposure to high temperatures. Samples included laminates, bottles, and roasting bags, and were heated at 120 degrees C, 150 degrees C and 230 degrees C for 50 min, according to sample type. Volatiles released from the material were trapped on Tenax, identified by GC-MS and assessed against a 10 micrograms/kg migration threshold limit. Few volatiles were found for samples composed only of PET. Volatiles from laminates varied according to the sample structure, but the main substances identified were not related to PET, but probably came from printing inks and adhesives. It is concluded that the migration potential of PET in high temperature applications is very low and that the formation of volatiles during use is unlikely to cause any special problems in polymer recovery in recycling schemes, provided that other packaging residues are removed effectively.

Procaine penicillin G was administered by intramuscular (i.m.) injection to groups of healthy 100 kg market pigs at the approved label dose (15,000 IU/kg body weight), once daily for three consecutive days; or an extra-label dose (66,000 IU/kg body weight), once daily for five consecutive days. Penicillin G residue depletion was followed in plasma, tissue and injection sites using a liquid chromatographic method. Groups of pigs were killed 1, 2, 3, 4, 5 and 8 days after the last injection with the label dose. Penicillin G was not detected in liver after 1 day of withdrawal, in muscle and fat after 2 days of withdrawal, in plasma after 4 days of withdrawal, in skin after 5 days of withdrawal, or in kidney and the injection sites after 8 days of withdrawal. Other groups of pigs were killed 1, 2, 3, 5 and 7 days after injection with the extra-label dose. In these pigs penicillin G was not found in liver after 2 days of withdrawal, in fat after 3 days of withdrawal, or in the muscle, skin, plasma and injection sites after 7 days of withdrawal. Penicillin G was found at all times in the kidneys of the groups of pigs that received the high dose. The technique used for neck injections was critical to obtain intramuscular rather than intermuscular injections. The Bureau of Veterinary Drugs, Health Protection Branch, Health Canada calculated that the appropriate withdrawal period for pigs was 8 days for a dose of 15,000 IU procaine penicillin G/kg body weight and 15 days for a dose of 66,000 IU/kg.

This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluated 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 the assessment of the effects of antimicrobial drug residues in food on the human intestinal microflora as well as well as of analytical methods used to obtain residue-depletion data. A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two adrenoceptor agonists (clenbuterol and xylazine), two anthelminthic agents (abamectin and moxidectin), seven antimicrobial agents (chlortetracycline, oxytetracycline, tetracycline, neomycin, spiramycin, thiamphenicol and tilmicosin), and two insecticides (cypermethrin and alpha-cypermethrin). Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and Maximum Residue Limits, further toxicological studies and other information required, and a discussion of procedures for assessing the effects of antimicrobial drug residues in food on the human intestinal microflora.

A method is described for the determination of the antibacterial drug trimethoprim in tissues. Minced tissue is homogenised with chloroform-acetone (1 + 1 v/v), filtered, and the filtrate evaporated to an oily residue using a rotary evaporator. The residue is redissolved in methanol-water-acetic acid (50 + 48.7 + 1.3 v/v) and any fats present are partitioned into hexane. The aqueous phase is analysed by liquid chromatography-thermospray mass spectrometry in positive mode with the protonated molecular ion at m/z 291 being monitored. Recoveries ranged between 60% in liver and 79% in muscle. The limit of determination was 25 micrograms kg-1 and the limit of detection was approximately 4 micrograms kg-1. The method is suitable for monitoring tissues taken under national surveillance schemes for veterinary drug residues.

The stability of benzylpenicillin to heat and cooking was studied. Stability of this compound in water (at 100 degrees C and 65 degrees C), 5% ethanol, 5% sodium bicarbonate, pH 5.5 buffer at 100 degrees C and in hot cooking oil at 140 degrees C and 180 degrees C was established. Benzylpenicillin was stable at 65 degrees C but not stable at higher temperatures with half-life times varying between 15 and 60 min in the solutions investigated. This drug was not stable to cooking, losses being proportional to the harshness of the cooking regime. Where fluids were released during the cooking process, sometimes over half of the residue passed from the solid tissue into the cooking medium.

A method is presented for the determination of the nitroimidazole drug dimetridazole (DMZ) in poultry tissues and eggs by liquid chromatography (LC)-thermospray mass spectrometry (MS). Deuteriated DMZ was employed as an internal standard. Samples were extracted with dichloromethane (muscle) or toluene (liver, egg) and applied to silica gel cartridges. Dimetridazole was eluted with acetone and the eluate evaporated to dryness at 40 degrees C under nitrogen. The residue was redissolved in methanol-water (1 + 1, v/v) and washed with hexane before LC-MS analysis. Quantification was by the ratios of the positive [M + H]+ ions at m/z 142 and 145 for DMZ and the internal standard, respectively. Internal standard corrected recoveries were between 93 and 102% with RSDs between 1.2 and 7.7% for liver spiked at 5, 10 and 20 ng g-1 and muscle and eggs spiked at 5 ng g-1. Absolute recoveries were approximately 80%. The method is suitable for statutory residue testing and was used to measure DMZ residues in eggs from chickens fed a diet containing DMZ at 10 mg kg-1.

The authors provide an overview of non-biological contaminants in foods from animals. These contaminants comprise chemical and physical hazards which may be introduced during animal production, slaughter and processing or packaging. Emphasis in this paper is placed on those residues which are of most interest to Veterinary Services and for which Veterinary Services have responsibility, namely: residues of veterinary drugs, industrial chemicals, heavy metals and pesticides which may be introduced during animal production. The most contentious residues which occur in meat, milk and eggs are antibacterial drugs, hormonal growth promoters and certain pesticides, heavy metals and industrial chemicals. While rare incidents of human disease have been attributed to hazardous levels of these contaminants in milk and meat, residues of chemical contaminants in foods of animal origin are, in general, rarely detected at more than trace levels and consequently are not of major public health concern. Nevertheless, non-biological contaminants continue to be very important with respect to international trade and consumer confidence, and efforts to reduce the incidence of occurrence in foods is warranted. Furthermore, continued monitoring and periodic reassessment of risks posed by these contaminants is needed to detect or anticipate new problems so that appropriate action can be taken in the interests of public safety.

The Free Trade Agreement between the United States and Canada (FTA) went into effect January 1, 1989. To implement certain provisions of the agreement on technical regulations and standards, the United States Food and Drug Administration's Center for Veterinary Medicine, Health and Welfare Canada's Bureau of Veterinary Drugs, and Agriculture Canada established the Working Group on Veterinary Drug Tolerances. The progress of the working group and its continuing efforts to harmonize tolerances for approximately 15 veterinary drugs are discussed. This paper proposes use of the toxicologically determined acceptable daily intake (ADI) for the drug as the safety standard for reaching conclusions on the acceptability of residues in meat for human consumption. Specifically, the "equivalence" of different MRLs for the same veterinary drug would be determined by considering whether they are likely to result in dietary residues that exceed the other country's ADI for the drug. Estimates are made for the veterinary drugs lasalocid, fenbendazole, morantel tartrate, halofuginone, and tilmicosin. Based on these estimates, the U.S. and Canadian MRLs for each drug would be considered equivalent for trade purposes.

We have been surveying toxic substances in food and foodstuffs and carrying out a total diet study on the intakes of various substances since 1979 in cooperation with local public institutes in Japan. In this paper, we report the daily intakes of mercury, PCB and arsenic from foods, and the relation between the concentrations of these substance in fish and the fish body weight. The intakes of mercury and arsenic were 6.9-11.0 micrograms/ man/day and 120-230 micrograms/man/day, respectively. The intakes of these substances remained on a stable level from 1979 to 1994. On the other hand, the intake of PCB decreased from 3.1 micrograms/man/day in 1979 to 0.9 microgram/man/day in 1994. Most of the intakes of mercury, PCB and arsenic were derived from the diet group "fish and shellfish". The level of mercury in fish increased with increasing fish body weight. For PCB and arsenic, there was no correlation between these concentrations in fish and the fish body weight, except that mackerel and croaker show a higher concentration of PCB when they are small. Arsenic shows almost a constant level in each fish regardless of their body weight.