National Residue Program Research Articles

A Survey of the Levels of Selected Metals in U.S. Meat, Poultry, and Siluriformes Fish Samples Taken at Slaughter and Retail, 2017–2022

The U.S. Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) conducts surveillance of metallic elements in U.S. meat, poultry, and Siluriformes fish samples collected immediately postmortem as part of its National Residue Program (NRP). From 2017 to 2022, 13,966 samples were analyzed under the NRP. The Federal Emergency Response Network (FERN) Cooperative Agreement Program (CAP) tests meat, poultry, and Siluriformes fish products collected at retail in the United States for metals. From 2018 to 2022, 2,902 samples were analyzed by FERN CAP laboratories. Meat and poultry samples collected by FSIS show that most metals were not detected at all or were detected infrequently. Meat is a rich source of iron and zinc, and iron was detected in 22% (1,255/5,623) and zinc was detected in 48% (2,742/5,676) of meat and poultry samples, respectively. The percentage of samples testing positive for manganese, molybdenum, lead, and cadmium were higher in the FERN CAP retail samples than in FSIS samples. Expected human exposure from average levels of lead and cadmium found in meat and poultry was compared to toxicological reference values and was not found to exceed these values. Detections of arsenic and mercury were found more often in Siluriformes fish samples (2017–2022) than in terrestrial animals. Trace amounts of arsenic and mercury were detected in 8% and 4% of Siluriformes samples, respectively, but were not detected at levels that raise concern. On the whole, both the FSIS and FERN CAP datasets provide reassuring evidence of the safety of the FSIS-regulated food supply with regard to the studied elements.

Extract-and-Inject Analysis of Veterinary Drug Residues in Catfish and Ready-to-Eat Meats by Ultrahigh-Performance Liquid Chromatography – Tandem Mass Spectrometry

Validated analytical methods are needed to conduct regulatory monitoring of ready-to-eat meats and fish for food safety, risk assessment, and other purposes. The methods should be cost-effective, high-throughput, and meet acceptable performance standards for a wide scope of drugs and matrixes. The goal of this study was to demonstrate the validity for possible implementation in the US National Residue Program of an efficient method for qualitative and quantitative analysis of 176 targeted drugs at levels as low as 10 ng/g in hot dogs, catfish and swai (Siluriformes), chicken tenders, fried bacon, and sausage using ultrahigh-performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS). Sample preparation simply involved a 5 min extraction by shaking 2 g comminuted samples with 10 mL of 4/1 (v/v) acetonitrile/water followed by centrifugation and UHPLC-MS/MS analysis of 2 μL injections. For cleanup comparison purposes only, sausage extracts were also prepared using a cartridge-based EMR-Lipid method prior to analysis. Acceptable validation of 70-120% recoveries with <25% RSDs was met for 156-176 out of 186 drugs and quality control analytes without cleanup depending on the matrix. The EMR-Lipid method for sausage improved results for some analytes, such as mectin anthelmintics, due to reduction of indirectly interfering fats in the final extracts, but it also led to significantly worse results for several other drugs, resulting in 32 fewer analytes meeting the given validation criteria than without cleanup. The simple, high-throughput method was demonstrated to be valid to meet routine regulatory and other monitoring needs for many diverse targeted drugs in fish and ready-to-eat meat matrixes.

Risk-based approach to develop a national residue program: prioritizing the residue control of veterinary drugs in fishery products

Veterinary drugs are widely used to protect production-related diseases and promote the growth of farmed fish. The use of large amounts of veterinary drugs may have potential risk and cause adverse effects on both humans and the environment. In this study, we developed risk-based ranking based on a scoring system to be applied in the national residue program. In this approach, the following three factors of veterinary drugs that may occur as residues in fishery products were considered: potency (acceptable daily intake), usage (number of dose and withdrawal period), and residue occurrence. The overall ranking score was calculated using the following equation: potency × usage (sum of the number of sales and withdrawal period) × residue occurrence. The veterinary drugs that were assigned high score by applying this approach were enrofloxacin, amoxicillin, oxolinic acid, erythromycin, and trimethoprim. The risk-based approach for monitoring veterinary drugs can provide a reliable inspection priority in fishery products. The developed ranking system can be applied in web-based systems and residue-monitoring programs and to ensure safe management of fishery products in Korea.

Simultaneous analysis of aminoglycosides with many other classes of drug residues in bovine tissues by ultrahigh-performance liquid chromatography-tandem mass spectrometry using an ion-pairing reagent added to final extracts.

The way to maximize scope of analysis, sample throughput, and laboratory efficiency in the monitoring of veterinary drug residues in food animals is to determine as many analytes as possible as fast as possible in as few methods as possible. Capital and overhead expenses are also reduced by using fewer instruments in the overall monitoring scheme. Traditionally, the highly polar aminoglycoside antibiotics require different chromatographic conditions from other classes of drugs, but in this work, we demonstrate that an ion-pairing reagent (sodium 1-heptanesulfonate) added to the combined final extracts from two sample preparation methods attains good separation of 174 targeted drugs, including 9 aminoglycosides, in the same 10.5-min ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The full method was validated in bovine kidney, liver, and muscle tissues according to US regulatory protocols, and 137-146 (79-84%) of the drugs gave between 70 and 120% average recoveries with ≤ 25% RSDs in the different types of tissues spiked at 0.5, 1, and 2 times the regulatory levels of interest (10-1000ng/g depending on the drug). This method increases sample throughput and the possible number of drugs monitored in the US National Residue Program, and requires only one UHPLC-MS/MS method and instrument for analysis rather than two by the previous scheme. Graphical abstract Outline of the streamlined approach to monitor 174 veterinary drugs, including aminoglycosides, in bovine tissues by combining two extracts of the same sample with an ion-pairing reagent for analysis by UHPLC-MS/MS.

Monitoring and surveillance testing for residual veterinary drugs and pesticides in domestic meat between 2012 and 2013

The Korean National Residue Program (KNRP) use three plans for the sampling of domestic meats: monitoring, surveillance, and exploratory testing. We analyzed the results of monitoring and surveillance for residual veterinary drugs and pesticides in meat during 2012 and 2013. KNRP targets food-producing animals including cattle, pigs, chickens, ducks, sheep (goats), and horses. Sampling mainly focuses on veterinary drugs and pesticide residues found in tissues such as muscle, kidney, and liver. A total of 548 residue violations occurred between 2012 and 2013, mainly in pigs (427 violations) and cattle (113 violations). The most commonly found compounds were antimicrobials such as penicillins, fluoroquinolones, aminoglycosides, tetracyclines, sulfonamides, and macrolides. Pig residue violations were mainly for the presence of penicillins (34%) and fluoroquinolones (28%), while most residue violations in cattle were due to the presence of penicillins (32%) and aminoglycosides (27%). The overall rates of violations were 0.21% in 2012 and 0.10% in 2013. A major cause of violations was the failure to follow the appropriate withdrawal periods (68.8%). The results of the KNRP were analyzed to provide information on agricultural chemical residues that are of public health concern and to help control and prevent residue violations for ensuring food safety.

Arsenic Levels in Chicken: Nachman et al. Respond

In our paper (Nachman et al. 2013) we focused on dietary arsenic exposure from the use of arsenic-based drugs in food animal production, specifically chicken. We thank Lasky for broadening the discussion on arsenic regulations for food to include federal agencies beyond the Food and Drug Administration (FDA). The results of our study (Nachman et al. 2013) indicate that the use of arsenic-based drugs increases the levels of inorganic arsenic in chicken meat. Based on these findings, we recommend banning the use of arsenic-based drugs in food animal production, which are under the jurisdiction of the FDA. It is important, however, to recognize the potential role that could be played by the U.S. Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) under its National Residue Program (NRP). Under its mandate, the NRP facilitates the monitoring of arsenic levels in poultry products and supports enforcement actions for animal products in violation of arsenic standards (USDA FSIS 2012). Unfortunately, the NRP faces constraints (in addition to those noted by Lasky) that limit its effectiveness (Silbergeld and Nachman 2008). The most important of these constraints is the current arsenic standard for meat, which was set before 1963 (FDA 1963) and does not account for recent epidemiologic research. In addition, the standard applies to total arsenic concentrations rather than to inorganic arsenic, the species of greatest health relevance. Because arsenic can be present in food in various forms that have widely varying toxicity, standards might need to be species specific. The U.S. Environmental Protection Agency (EPA) is currently revising its toxicological assessment for inorganic arsenic (U.S. EPA 2010) as part of its Integrated Risk Information System (IRIS) program. The purpose of this revision is to produce health-based guidance that can be useful in setting arsenic standards in different media (including foods) that reflect our current understanding of dose–response relationships between arsenic exposures and adverse health outcomes. To achieve this goal, coordination between the FDA, U.S. EPA, and NRP is essential. By applying appropriate standards and methods with adequate sensitivity for the arsenic species of interest, the NRP could play a central role in minimizing dietary exposure to arsenic through animal products. Although sale of roxarsone remains suspended in the United States, nitarsone, a chemically similar arsenical drug, continues to be sold (Zoetis 2013). Industry statements in the media have confirmed nitarsone use in the turkey industry (Aubrey 2013), and the USDA estimates of per capita turkey consumption are increasing (USDA 2013). Research is needed to characterize potential contributions of nitarsone to inorganic arsenic concentrations in turkey meat. For these reasons, monitoring efforts remain relevant. In the absence of regulations that limit inorganic arsenic in our foods, the banning of arsenic-based drugs would minimize dietary arsenic exposures in poultry consumers.

Arsenic Levels in Chicken

I commend Nachman et al. (2013) on their careful study of arsenic content in market samples of chicken and am dismayed to learn that arsenic levels in chicken remain high despite our report of arsenic levels in Environmental Health Perspectives in 2004 (Lasky et al. 2004). One possible explanation is the very complicated lines of authority around the regulation of drugs fed to food animals, along with the enforcement of those regulations. Nachman et al. (2013) focused their discussion on the role of the Food and Drug Administration (FDA), but many other agencies participate in the regulation and enforcement of residue safety in food animals. As noted by the Food Safety and Inspection Service (FSIS) in the introduction to their 2012 Residue Sampling Plans (FSIS 2012), The U.S. National Residue Program (NRP) for Meat, Poultry, and Egg Products, administered by the USDA [U.S. Department of Agriculture] FSIS, is an interagency program designed to identify, rank and test for chemical contaminants in meat, poultry, and egg products. They continue, The NRP requires the cooperation and collaboration of several agencies for its successful design and implementation. The USDA FSIS, the EPA [U.S. Environmental Protection Agency], and the Department of Health and Human Services (DHHS) FDA are the primary federal agencies managing this program. The FDA, under the Federal Food, Drug, and Cosmetic Act, establishes tolerances for veterinary drugs, and action levels for food additives and environmental contaminants. The EPA, under the Federal Insecticide, Fungicide, and Rodenticide Act (as modified by the Food Quality Protection Act), establishes tolerance levels for registered pesticides…. Representatives from FSIS, FDA, EPA, the USDA Agricultural Research Service (ARS), the USDA Agricultural Marketing Service (AMS), and the DHHS Centers for Disease Control and Prevention (CDC) collaborate to develop the scheduled sampling program. Setting and enforcing safety levels involves several steps, one of which is the collection of meat and poultry samples, followed by statistical analysis, interpretation, and action. The NRP sampling plan is designed to identify samples with residues above the allowed levels. The data are then analyzed as categorical values (violation, no violation). Current methods of data analysis do not include estimation of mean values that can then be extrapolated to the national food supply. It was by analyzing the data as a continuous variable that my coauthors and I were able to describe the high levels of arsenic in chicken in 2004 (Lasky et al. 2004). Concerns about arsenic levels in chicken are of increasing importance because of the increased per capita consumption of chicken over the past decade (USDA Economic Research Service 2013).

Chemical Residues and Contaminants in Foods of Animal Origin in Korea during the Past Decade

Residues of veterinary drugs, pesticides, and environmental contaminants in domestic and imported foods of animal origin were monitored by the National Residue Program and inspection service in Korea in the past decade. In all, 134 substances were analyzed in the monitoring plan; 35 substances were examined in the surveillance and enforcement testing program, and 27 substances were investigated in exploratory projects. The overall trend of violation rates gradually decreased over the past decade. Pesticides were not found in any domestic samples of animal origin. The violation rates of chlortetracycline and oxytetracycline decreased, but quinolone and penicillin detections increased in Korea. Several kinds of residue violations of veterinary drugs, endosulfan, or dioxins were found in the imported products each year. In an example event in 2008, the Korea monitoring plan contributed globally to investigate the dioxin contamination from Chilean pork. Continuous monitoring based on internationally harmonized standards and methods provides the essential scientific basis to manage and ensure food safety.

Development and validation of a streamlined method designed to detect residues of 62 veterinary drugs in bovine kidney using ultra‐high performance liquid chromatography – tandem mass spectrometry

In the USA, the US Department of Agriculture's Food Safety and Inspection Service (FSIS) conducts the National Residue Program designed to monitor veterinary drug and other chemical residues in beef and other slaughtered food animals. Currently, FSIS uses a 7-plate bioassay in the laboratory to screen for antimicrobial drugs in bovine kidneys from those animals tested positive by inspectors in the slaughter establishments. The microbial inhibition bioassay has several limitations in terms of monitoring scope, sensitivity, selectivity, and analysis time. Ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS) has many advantages over the bioassay for this application, and this study was designed to develop, evaluate, and validate a fast UHPLC-MS/MS method for antibiotics and other high-priority veterinary drugs in bovine kidney. Five existing multi-class, multi-residue methods from the literature were tested and compared, and each performed similarly. Experiments with incurred samples demonstrated that a 5-min shake of 2 g homogenized kidney with 10 ml of 4/1 (v/v) acetonitrile/water followed by simultaneous clean-up of the initial extract with 0.5 g C18 and 10 ml hexane gave a fast, simple, and effective sample preparation method for the <10 min UHPLC-MS/MS analysis. An extensive 5-day validation process demonstrated that the final method could be used to acceptably screen for 54 of the 62 drugs tested, and 50 of those met qualitative MS identification criteria. Quantification was not needed in the application, but the method gave ≥ 70% recoveries and ≤ 25% reproducibilities for 30 of the drugs.

Examining the occurrence of residues of flunixin meglumine in cull dairy cows by use of the flunixin cull cow survey

To determine whether cull dairy cows with signs of certain clinical conditions, termed suspect, are more likely than healthy-appearing cull dairy cows to have violative concentrations of flunixin meglumine in their tissues at slaughter. Cross-sectional study. 961 cull dairy cows. Suspect cull dairy cows were selected from 21 beef slaughter establishments with a high production volume of dairy cows, and kidney and liver tissues were collected for screening. Kidney tissues were screened for antibiotics and sulfonamides with the fast antimicrobial screening test (FAST). Liver tissues were screened for flunixin meglumine with an ELISA, and quantitative analysis of ELISA-positive samples was performed with high-performance liquid chromatography. During the same time period, liver tissues from 251 healthy-appearing cull dairy cows were collected for the Food Safety and Inspection Service National Residue Program Scheduled Sampling Plan, but were screened only for flunixin meglumine. Of 710 suspect cull dairy cows, 50 (7.04%) had liver tissue flunixin concentrations higher than the flunixin tolerance concentration (0.125 ppm). Thirty-one of 168 (18.45%) FAST-positive and 19 of 542 (3.51%) FAST-negative suspect cull dairy cows had violative tissue flunixin concentrations. Two of the 251 (0.80%) healthy-appearing cull dairy cows had violative tissue flunixin concentrations. Suspect cull dairy cows, especially those that were also FAST positive, had a significantly higher incidence of violative tissue flunixin concentrations than healthy-appearing cull dairy cows at slaughter. Targeted sampling plans for flunixin meglumine in suspect dairy cows can help to support more efficient use of resources and further safeguard the nation's food supply.

Mean total arsenic concentrations in chicken 1989-2000 and estimated exposures for consumers of chicken.

The purpose of this study was to estimate mean concentrations of total arsenic in chicken liver tissue and then estimate total and inorganic arsenic ingested by humans through chicken consumption. We used national monitoring data from the Food Safety and Inspection Service National Residue Program to estimate mean arsenic concentrations for 1994-2000. Incorporating assumptions about the concentrations of arsenic in liver and muscle tissues as well as the proportions of inorganic and organic arsenic, we then applied the estimates to national chicken consumption data to calculate inorganic, organic, and total arsenic ingested by eating chicken. The mean concentration of total arsenic in young chickens was 0.39 ppm, 3- to 4-fold higher than in other poultry and meat. At mean levels of chicken consumption (60 g/person/day), people may ingest 1.38-5.24 microg/day of inorganic arsenic from chicken alone. At the 99th percentile of chicken consumption (350 g chicken/day), people may ingest 21.13-30.59 microg inorganic arsenic/day and 32.50-47.07 microg total arsenic/day from chicken. These concentrations are higher than previously recognized in chicken, which may necessitate adjustments to estimates of arsenic ingested through diet and may need to be considered when estimating overall exposure to arsenic.

Analysis of Microbiological Screen Test Data for Antimicrobial Residues in Food Animals

This study analyzes the National Residue Program (NRP) of the Food Safety and Inspection Service (FSIS), United States Department of Agriculture (USDA), data for the for the years 1983–1998 to determine the effectiveness of all three microbiological screen tests that were developed and used by the FSIS to control antimicrobial residues in food animals. The Swab Test On Premises (STOP) Sulfonamide Test (CAST) and the Fast Antimicrobial Screen Test (FAST). The data for STOP indicates that during 1983–1998, the rate of food animal carcasses with violative levels of was the first screen test introduced in slaughterhouses, followed by the Calf Antibiotic and surveillance plan, the rate reduced from 55.1% to 0.56%. Similarly, the data for CAST indicates that the rate of calf carcasses with violative levels of antimicrobial residue also declined significantly during those years. Because of its higher sensitivity and shorter analytical time, the use of FAST started in 1995. By 1999, it had replaced the use of STOP and CAST in bovine species. The use of only one test such as FAST instead of different tests has removed confusion for testing different species of food animals and thereby has enhanced the efficiency of the NRP.

Federal Surveillance Of Veterinary Drugs And Chemical Residues (With Recent Data)

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.

Changing Pesticide Technology in Meat and Poultry Products

In response to consumer concerns about pesticide residues in meat and poultry, a National Residue Program was introduced in the 1960s. Rapidly developing analytical methods and instrument capability resulted in a laboratory-based program of sufficient size and technical capability to quantitatively determine an increasing number of pesticides. In 1985, at the request of the Food Safety and Inspection Service, the National Academy of Sciences evaluated the program and recommended that more emphasis be placed on preventing residues and providing a higher degree of safety to consumers. In response, FSIS made a commitment to increase and improve capability to test for more residues, including pesticides, and to develop or purchase rapid test systems to facilitate the planned expansion of the National Residue Program. Such systems are now being evaluated and integrated into the program. Factors important for acceptability of rapid tests are reviewed in detail.

USDA regulation of residues in meat and poultry products.

The National Residue Program conducted by the Food Safety and Inspection Service (FSIS) of the USDA includes a comprehensive testing program for residues of pesticides, drugs and other chemical contaminants in meat and poultry. Prevention strategies encourage producers to adopt quality control measures in their production management to prevent illegal residues in food. These activities have been effective in reducing the occurrence of violative residues and the potential for adverse health effects. Overall, the number of domestic monitoring samples containing violative residues is low-about 1% of samples tested. Violative residues are found less frequently in poultry than in livestock. More occur in swine than in other species; the least number occur in fed cattle and broilers. Testing results over the last 10 yr show that most drugs and pesticides used to enhance agricultural productivity are not causing a residue problem in meat and poultry. However, the FSIS cannot be complacent about its program achievements. Unacceptably high incidences of violative residues of certain drugs, namely, sulfonamides and antibiotics, still occur in particular production classes. For example, the incidence of violative sulfonamide residues in liver samples from swine slaughtered in 1985 was about 6%, with significant differences between geographical areas. An estimated 2.5% of market hogs had violative sulfamethazine residues in the muscle tissue. The FSIS is taking steps to correct this and other residue problems by strengthening the link between residue detection and enforcement and by expanding its analytical capability to monitor for residues.