USDA REGULATION OF RESIDUES IN MEAT AND POULTRY PRODUCTS 1

Transcription

1 USDA REGULATION OF RESIDUES IN MEAT AND POULTRY PRODUCTS 1 M. K. Cordle 2 Food Safety and Inspection Service, USDA Washington, DC ABSTRACT 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. (Key Words: Residues, Meat, Poultry, Regulations, Monitoring.) I ntroduction Prevention of chemical residues in meat and poultry is a top priority of the FSIS. Concern about pesticide, drug and other chemical residues ranks high among consumers, as shown by results from the 1986 Food Marketing Institute Survey (table 1). Residues continue to receive a great deal of attention from the news media and government overseeing committees. The meat and poultry industry experiences economic loss when contaminated products have to be destroyed and when markets drop in response to consumer perceptions that some foods are less safe and wholesome than others. 1Paper presented at a symposium titled "Occurrence and Regulation of Residues and Toxins in Plant and Animal Tissues," held Feb. 3, 1987, at the Southern Section Amer. Soc. of Anim, Sci., Nashville, TN. The symposium was sponsored by ASAS, Eli Lilly and Co., International Minerals and Chemical Corp. and Hoffman-LaRoche, Inc. 2 Deputy Director, Residue Evaluation and Planning Division, Science Program, Food Safety and Inspection Service, USDA. Received April 3, Accepted August 24, As a result, the meat and poultry industry, in general, is much more aware of the need for residue control as part of its management system. Some producers have opted to avoid the use of antibiotics and hormones and declare this on product labels. Others have voluntarily adopted quality control programs, including residue testing of feeds and animals, to prevent illegal residues in the food they produce. Increasingly the industry recognizes residue prevention as good business and a necessary part of production management to provide the product consumers want. These changes within the industry have not occurred by chance. The FSIS has provided stimulus backed by consumer demands. For more than a decade, the FSIS, with its analytical capability, has conducted a strong residue testing program. Although residue testing of carcasses at slaughter must he an integral part of a modern inspection system, it is not the most effective or efficient way to prevent residues. Prevention of residues at all stages of animal production must be an objective and a responsibility taken seriously by all involved industry segments. 413 J. Anim. Sci :

2 414 CORDLE TABLE FOOD MARKETING INSTITUTE SURVEY a Item Response, % Serious Some None Not sure Residues Cholesterol Fat Salt Additives & Preservatives Irradiation Sugar Artificial Colors afood Marketing Institute, Responses are to the questions "How concerned are you about the following items being in food? Would you say that there is a serious health hazard, somewhat of a hazard, or not at all?" Residue Prevention Activities Late in 1982, the FSIS began funding a program conducted by the Cooperative State Extension Service (CSES) to identify the critical points for residue prevention and to educate producers to adopt these controls to assure that market animals do not contain illegal residues. This program involved CSES and many land grant universities throughout the nation, as depicted in figure 1. The FSIS funded over 3 million dollars matched by CSES funding through 1986, when the formal program terminated. However, residue avoidance education is now an integral part of CSES activities and is a recognized need among the industry associations that worked closely with the USDA in the program. One of the major benefits of the Residue Avoidance Program (RAP) is an increased awareness that residues are a vital concern and Figure 1. Area ranking of livestock and poultry receipts and extension projects.

3 CHEMICAL RESIDUES IN MEAT AND POULTRY 415 the recognition of what could be accomplished by working together effectively. These working relationships, and the cadre of expertise developed among those who became actively involved in RAP, now provide a national resource whose value will continue to be realized for many years. Another benefit was th~ willingness of the packer and producer industries to enter into voluntary residue control agreements with FSIS. These agreements, which give the FSIS access to company records, allow the FSIS to verify that a company's quality control procedures and residue testing program ensure that products do not contain illegal residues. Such voluntary agreements were in effect in the poultry industry prior to RAP; the first one was signed with a turkey establishment in However, RAP stimulated renewed interest among the poultry industry and new participation among the meat industry. The FSIS does not have jurisdiction before an animal is presented for slaughter, so the FSIS has been limited in its ability to develop residue control agreements in the red meat industry, which tends to be less vertically integrated than the poultry industry. To expand participation, the FSIS plans to issue a proposed regulation describing conditions under which integrated and nonintegrated companies alike may participate and acknowledge participation on product labeling. What effect such labels will have on consumer buying practices and trends in the industry remains to be seen, but it could be substantial. As of December 1986, residue control agreements were in force for nine companies involving 45 slaughtering establishments. The combined slaughter in these establishments has been estimated at 7 billion pounds per year, representing about 10% of the total annual slaughter of all species. By production class, expressed as a percentage of total annual slaughter, the agreements include about 45% of young turkeys (17 plants), about 30% of young chickens (21 plants) and about 3% of fed cattle (7 plants). The FSIS is in the process of completing agreements with five additional companies and has received requests for participation from many others that could be developed when the verified production control (VPC) rule-making process is completed. A National Research Council report (NRC, 1985) stated that the primary focus of the National Residue Program should be preventive rather than remedial. Although the Council recognized that the Food and Drug Administration (FDA), not the FSIS, has jurisdiction over livestock and poultry before their presentation for slaughter, it is recommended that the FSIS, nevertheless, consider enhanced prevention strategies under its National Residue Program. The FSIS agrees with the NRC recommendation and believes that the continuing residue avoidance cooperative activities with the Extension Service and the regulated industry, and the VPC rule-making initiative, are responsive to this need. The prevention programs, however, do not supplant the need for residue testing as a part of inspection. Enforcement of residue standards is just as important in protecting public health as the control of disease, microbiological contamination and sanitation. Residue Testing Programs The FSIS inspectors, as part of the National Residue Program, collect samples of meat and poultry at slaughtering establishments and from import shipments at the ports of entry. The samples are analyzed for the presence of illegal residues of pesticides, drugs and other potential- ly harmful chemicals. These activities are carried out as part of the FSIS responsibilities under the Federal Meat Inspection Act and the Poultry Products Inspection Act to ensure that USDA-inspected products in commerce are safe, wholesome and free of adulterating residues. Adulterating residues are defined as those above safe tolerance limits established for pesticide chemicals by the Environmental Protection Agency (EPA) and for animal drugs and unavoidable contaminants by the FDA. In the absence of a tolerance, FSIS applies action levels recommended by the EPA or FDA, as appropriate. Residue testing programs are subdivided into three major activities: monitoring, surveillance and exploratory projects. Under these three activities about 400,000 laboratory analyses and 150,000 in-plant tests are performed annually. Monitoring. Monitoring activities are designed to provide profile information on the occurrence of residue violations in specified animal populations on an annual national basis. The focus is on violations; therefore, only compounds with tolerances or action levels are included in the monitoring plan. Monitoring information is obtained through a statistical-

4 416 CORDLE TABLE 2. LIVESTOCK GROUPS USED AS THE SAMPLING FRAME IN THE NATIONAL RESIDUE MONITORING PROGRAM Sample units normally Livestock groups Apportionment analyzed per year Horses 100 Bulls/cow s 10%/90% 300 Heifers/steers 40%/60% 300 Calves 300 Sheep/lambs (seasonal) 10%/90% 200 Goats 100 Hogs, market 300 Sows/boars 75%/25% 300 ly based selection of random samples from animals under inspections that appear healthy. Although most monitoring activities are national in scope, area monitoring (e.g., statewide) may be conducted where a potential problem appears localized. The monitoring plan is based on a "residue-species pair" design concept, in which the animal groups that make up the sampling frame are determined by commonalities in rearing, because these factors affect an animal's exposure and the likelihood of residues occurring at time of slaughter. Tables 2 and 3 show how livestock and poultry usually are subdivided in the statistical design apportionment of samples between production classes and the minimal number of samples normally planned for each compound data set. It is important to understand this design when interpreting FSIS monitoring data, because production classes at higher risk of containing residues are frequently sampled at higher levels in proportion to slaughter volume for the species as a whole. Normally, the sampling for each animal group is sufficient to provide a probability of 95% that a residue problem will be detected (i.e., at least one violation will be found in 300 samples analyzed), if the problem occurs in 1% or more of a major species or production class group. Although the monitoring program is not designed to provide statistical estimates of the percentage of violations in large populations, such estimates are available as auxiliary information, but without a high degree of precision. Readers should bear this in mind as testing resuits are discussed later in this paper. Other auxiliary uses of the data are to indicate frequency and levels of residue occurrence, to evaluate residue trends and to identify problems within particular industry segments where educational and other corrective efforts may be needed. In addition to profile information, the monitoring program provides a basis for further action. Data on all violative samples are sent to the FDA and the appropriate stage agency for follow-up investigation and enforcement sanctions, when warranted. When the producer of a violative carcass can be identified, he or she is notified of the violation. Subsequent animals brought to slaughter from that source are retained by the FSIS for surveillance testing (described below) until compliance with residue limits is demonstrated. Surveillance. Surveillance is designed to investigate and control the movement of potentiauy adulterated products. The sampling is biased and directed at particular carcasses or products in response to information about a potential problem or from observations during ante-mortem or post-mortem inspection. Rapid, inexpensive tests performed in the plant by an FSIS veterinarian are a very impor- TABLE 3. POULTRY GROUPS USED AS THE SAMPLING FRAME 1N THE NATIONAL RESIDUE MONITORING PROGRAM Poultry groups Chickens, young Chickens, mature Turkeys, young (seasonal) Turkeys, mature (seasonal) Ducks Geese (seasonal) Sample units normally analyzed per year

5 CHEMICAL RESIDUES IN MEAT AND POULTRY 417 rant part of the surveillance program. For example, a microbiological screening test for antibiotic residues, called STOP for Swab Test on Premises (Johnson et al., 1981), is used to test suspected animals (e.g., those with injection site lesions or disease symptoms). The test can determine within 16 to 18 h whether a carcass contains antibiotic residues. A negative STOP test can be used to pass a "suspect" carcass, but when the test is positive, samples must be sent to the laboratory for identification and quantification of the residue present. When the FSIS has information about a potential contamination situation that may be widespread, the surveillance activities are managed through the Contamination Response System. This may include placing a team on-site to coordinate activities with other involved agencies. Such a procedure was used in Arkansas and surrounding states during 1986, when heptachlor-treated (seed) grain was used in an ethanol-enriched production system and the byproduct mash was sold for animal feed-resulting in residues of heptachlor epoxide and octachlor epoxide in livestock and milk. The rapid and coordinated response of the regulatory agencies to this situation allowed the identification and testing of all herds involved, minimizing the entry of contaminated products into consumer channels. Exploratory Activities. In addition to monitoring and surveillance, the FSIS conducts exploratory projects. An exploratory project may investigate the occurrence of residues for which tolerances or action levels have not been established but may be needed. Also, exploratory projects may investigate new methods of approaches to monitoring, may develop regulatory programs or may develop additional information for determining the need to include a compound in monitoring. Setting Priorities for Monitoring. The NRC report (1985) stated that risk assessment should play a greater role in the National Residue Program. Risk assessment principles are essential in developing the annual residue testing plans. It is not feasible to monitor all the hundreds of chemicals used in raising food animals and producing feed crops, or that may be contaminants in the environment. Therefore, the FSIS must determine which of these compounds should receive greatest attention. A risk profile is constructed for each compound to assess the potential for residues occurring in food animals at slaughter and what effect a residue may have on human health. Factors considered in constructing the risk profile include a) the amount of actual or probable use of the compound; b) conditions of use as they relate to the potential for residues at slaughter; c) potential for misuse; d) metabolic patterns of the chemical in animals, plants and the environment, including bioavailability and persistence of the residues; and e) acute and chronic toxicity; i.e., potential hazard based on the intrinsic toxicity of the compound. These compound profiles are then used to assign a two-tiered, hierarchical ranking based on hazard and exposure classifications, as depicted in figure 2. A compound ranked A.1. would have the highest order of intrinsic toxicity, reflected by the letter A, and the highest exposure potential, reflected by the number 1. Conversely, a compound ranked D.4. would indicate a negligible concern. A document that describes the evaluation and ranking criteria soon will be available to the public, and comments will be solicited through a notice in the Federal Register. The rankings developed from the compound profiles are used to develop the annual testing plans, but sometimes a suitable method of analysis is not available for an important compound. It is then included in our methods research plan, and development work is initiated as resources permit. Ranking is a dynamic process that requires frequent updating as new information develops and agricultural practices change. An interagency group of USDA, EPA and FDA scientistics helps the FSIS to remain current in compound evaluation and advises the FSIS on monitoring and research priorities on methods. "" Exposure Haza rd" ~" "-... A B C D A1 A2 A3 A4 B1 B2 B3 B4 C1 C2 C3 C4 D1 D2 D3 D4 Z is used to designate an element that lacks sufficient information for classification Figure 2. Two-tiered compound evaluation system.

6 418 CORDLE Typically, an annual monitoring plan will include analyses for residues of about 100 agricultural chemicals or environmental contaminants. When monitoring results confirm that a particular residue is not a current problem, it may be dropped from the plan for a few years and reintroduced later. This cycling allows the FSIS to expand the number of compounds monitored over time (within budgetary limits). Publications. Each year the FSIS publishes two documents about its testing program. The first, "Compound Evaluation and Analytical Capability: Annual Residue Plan" (FSIS, 1987a) provides a listing of the compounds considered and their ranking, the established residue limits for each compound in the edible tissues, the analytical methods FSIS uses and their sensitivity, an historical listing of compounds included in the monitoring and exploratory programs over the past 10 yr and details about the testing planned for the current year. The second publication, "Domestic Residue Data Book"(FSIS, 1986b,c), presents results of testing in the previous calendar year. The publications are available on request from the Science Program of FSIS. a Domestic Residue Monitoring Results This section of the paper discusses results from domestic monitoring over the years, organized by major compound classes or types of drugs. It shows trends in the occurrence of residues, discusses data on compounds that do no appear to be a problem, explains what the FSIS is doing to reduce violations when problems have been identified and provides a broad overview on what is known about the presence of residues in domestically produced meat and poultry. The monitoring program is not designed to estimate the total incidence of violative residues in the meat and poultry supply, but simply to indicate whether a particular residue is a problem in a given subset of the animal population. Thus, the data could be used, for example, to identify sulfonamide residues as a problem in swine. However, they cannot be used to estimate the percentage of swine slaughtered that contain one or more violative residues of all compounds tested in the monitoring plan for a For address, see footnote 2. swine. Usually, different sample sets are collected for each compound, or for each group of compounds when a multiresidue method is used. Many of the data sets yield negative results. The accumulation of such data on more and more compounds each year adds to the assurance that most agricultural chemicals are being used safely and need not cause concern among consumers about residues in meat and pouhry. Overall, the number of monitoring samples found with violative residues is very low, representing about 1% of the total samples analyzed. This reflects the large number of residues monitored that are not a problem. The geographical distribution of total monitoring sample violations in 1985 indicates no apparent major differences between the five FSIS inspection regions (figure 3). However, there are apparent geographical differences for some drugs that are a problem in particular types of animals, as will be seen in the discussion of particular data sets. Pesticide Residues Pesticides are, of course, an important part of the FSIS monitoring program. Major changes have occurred through the years as use of environmentally persistent compounds such as DDT has diminished andless persistent products have taken their place. The monitoring data reflect these changes, showing that the chlorinated pesticides are no longer as great a problem as they once were (Duggan et al., 1983). However, accidents involving chlorinated pesticides still occur occasionally. These can require considerable expenditures by the regulatory agencies to identify and test affected herds or flocks and to prevent contaminated carcasses from entering the food supply. Yet these costs are minor when contrasted with the economic losses by producers, consumers and taxpayers. For example, the 1986 heptachlor contamination in Arkansas and surrounding states has already resulted in indemnity payments to producers of more than 7 million dollars. These costs are borne by American taxpayers. No acute, short-term harmful effects were found in studies of affected farm families. The FSIS has not found any other class of pesticides to be a problem in food animals, although the agency's monitoring capability for pesticide residues is limited. Information is lack-

7 CHEMICAL RESIDUES IN MEAT AND POULTRY 419 Figure 3. Geographical distribution of total violative monitoring samples collected in ing, in many cases, on the nature of residues that may occur when food animals are exposed, thus' hindering methods development. Chlorinated Hydrocarbon Pesticides. The FSIS routinely uses a gas chromatographic (GC) screening procedure that can detect the presence of 17 chlorinated hydrocarbon pesticide residues and polychlorinated biphenyls (FS1S, 1986a). The pesticides include those most commonly found in food animals because of environmental contamination arising from prior approved uses (i.e., aldrin, dieldrin, BHC, chlordane, DDT, TDE, DDE, endrin, HCB, heptachlor, heptachlor epoxide, lindane, methoxychlor, mirex, nonachlor, terpene polychlorinares and toxaphene). Other halogenated compounds also may elicit a chromatographic response with this method. Although it may not be possible to identify such residues, use of this method provides an early alert that a previously unsuspected residue is appearing in meat or poultry products. The method varies in its sensitivity to the different compounds; some (e.g., DDT residues) are detectable at concentrations several orders of magnitude below the tolerance or action level. When the FSIS began residue testing in the late 1960s, most of the animals slaughtered for food contained measurable levels of chlorinated hydrocarbon residues, and violative concentrations were found frequently. However, the monitoring data in more recent years indicate an improved situation in both the frequency of occurrence and the concentrations found. Figure 4 shows the percentage of fat samples collected in the monitoring program over the years from bovine, ovine, porcine and poultry species that contained violative concentrations of one or more chlorinated hydrocarbon residues. Among the most frequently found residues of this class of compounds are DDT and its metabolites, DDE and TDE, even though most uses had been discontinued by Figure 5 shows the decline in the percentage of fat samples from livestock that contained detectable DDT residues. Most of the DDT residues in 1985 occurred at concentrations well below the action level of 5 ppm, as illustrated by the data in table 4 on the frequency distribution of DDT concentrations in bovine fat. With the exceptions of dieldrin, BHC, HCB, and heptachlor epoxide, chlorinated pesticides are now found much less frequently in meat and poultry than they were before Organopbospbate Pesticides. For more than 10 yr, the FSIS has used a GC multiresidue procedure for monitoring organophosphate resi-

8 420 CORDLE ~ Porcine O'C ~'-- Bovine 0 ~ Poultry --O--e 0 -- Ovine --p~-p ~1.5 ci ;7 b~ I, I l.., 'xr.o t...~ ~ t B2 83 Year Figure 4. Percentage of fat samples containing violative concentrations of chlorinated hydrocarbon residues. FSIS National Residue Monitoring Program. dues, including chlorpyrifos, crufomate, diazinon, dichlorvos, dioxathion, disulfoton, fenitrothion, fenthion, stirofos, malathion, methyl parathion, parathion, ronnel, trichlorfon, coumaphos and its oxygen analog and ethion and its oxygen analog (FSIS, 1986a). Although these residues have a much shorter halfqife than chlorinated hydrocarbon residues, many organophosphate residues are very toxic. These inhibit cholinesterase andcausenervous system dysfunction, but only at levels well above those expected in human food when the pesticides are used properly (Taylor, 1985). Yet this compound class is important because of extensive use of feed crops and its use directly on food animals. Although residues are occasionally detected in surveillance samples, current national monitoring data show that the organophosphate resi- ioo Porcine Poultry BO '@ i 6~ B~Vi~e Ovine YeaP Figure 5. Percentage of fat samples containing detectable DDT residues in the FSIS National Residue Monitoring Program.

9 CHEMICAL RESIDUES IN MEAT AND POULTRY 421 TABLE 4. DISTRIBUTION OF DDT a RESIDUES IN BOVINE FAT TISSUES COLLECTED IN THE 1985 NATIONAL RESIDUE MONITORING PROGRAM Concentration interval (ppm) Percentage of samples Cows Steers Heifers Calves None detected > Number of samples adiehlorodiphenyltrichloroethane. dues detected by the muhiresidue method are not a problem in meat and poultry. All species have been monitored, and no violations have been found since Out of 478 liver samples from cattle tested in 1985, the species in which residues are most likely to be found because of direct treatment, no residues were detected. Although these monitoring results are encouraging, limitations in analytical capability preclude a comprehensive assessment of the potential risk of organophosphate residues in meat and poultry for several reasons. These compounds are rapidly metabolized. Thus metabolites, rather than parent drug, are more likely to occur in animal tissue, but the method used for monitoring detects only a few metabolites. Also, additional compounds with significant use have not been monitored, but they are included in the FSIS methods research plan. The FSIS would like to have a general screening method for cholinesterase-inhibiting residues that might be used in an exploratory program to determine whether such residues do occur, to ascertain the urgency for obtaining more complete metabolic information and to develop additional methods of analysis for specific compounds. Herbicides. Herbicides, although widely used, have not been a high priority concern as residues in food animals, because most of the compounds are rapidly degraded. In 1982, the FSIS completed development of a capillary column CG multiresidue method for four triazine herbicides: atrazine, propazine, simazine and terbtutylazine (FSIS, 1986a). The triazines were thought to be among the more persistent of the various classes of herbicides used. During 1983 and 1984, a total of 690 monitoring samples were collected from cattle, calves and chickens and analyzed for the triazine residues, but no residues were detected. Fumigants. This pesticide group is important because of postharvest use on feed ingredients, but most of the compounds are very volatile and not persistent. Therefore, the FSIS did not consider monitoring a high priority until 1983, when the FSIS received a report that unconfirmed residues of ethylene dibromide (EDB) had been detected in two steaks purchased at a supermarket in the Washington, DC area. The FSIS was concerned about the report, even though it was unconfirmed, because EDB is carcinogenic in experimental animals (IARC, 1982). The FSIS initiated a national random survey in 1983, designed to measure EDB levels in at least 100 fat samples, each of domestically slaughtered cattle, swine and poultry, and 30 samples from imported boneless beef. A GC screening method was used, sensitive to 1 ppb of EDB (FSIS, 1986a). Confirmation by mass spectrometry was attempted when the GC response suggested the presence of a residue at or above 1 ppb. Samples were reported positive only when confirmed by mass spectrometry. In accordance with these guidelines, only 1 of 345 samples tested was positive, a sample of boar fat that contained 3 ppb of EDB. Ten additional boar samples from the same slaughtering establishment and auction market were tested, but no EDB was found. Although it was concluded from this study that EDB in meat and poultry did not pose a significant health hazard, EDB testing was continued during 1984, with the primary focus on random samples collected from mature animals. Of 818

10 422 CORDLE samples of fat tested during 1984, EDB was found in only two (one with 5 ppb from a cow, and another with 4 ppb from a mature chicken). Subsequently, EPA revoked those uses of EDB likely to cause residues in food animals and concluded that action levels for EDB in meat and poultry are not necessary to protect the public health. Although there is some concern among the regulatory agencies about residues that may result in crops from the use of alternative fumigants, available information suggests that a low priority should be given to concern about residues in meat and poultry resulting from grain fumigation. The FSIS is reexamining monitoring needs associated with the permitted use of fumigants, such as methyl bromide in meat and poultry establishments, and for treatment of processed products. Cyromazine. The FSIS has also monitored for cyromazine, which is marketed in the United States under the trade name Larvadex, and is added to the feed of laying hens to control flies in their waste. The high-pressure liquid chromatography (HPLC) method used by the FSIS detects cyromazine and its metabolite, melamine, at their respective tolerance levels of 50 ppb (FSIS, 1986a). During 1984 and 1985, the FSIS analyzed 547 monitoring samples of muscle tissue collected from mature chickens. No residues of cyromazine or melamine were detected. Because cyromazine is used in some foreign countries as a feed-through pesticide for cattle, and because the FSIS was concerned about possible misuse in cattle in the United States, 392 muscle samples from steers and heifers were tested during 1984 and No cyroma- zine residues were detected, nor have any residues of cyromazine been found in imported products. Carbamates. Until recently, the FSIS did not have suitable methods for monitoring carbamate residues in meat and poultry. However, in 1987, an FSIS-developed multiresidues method for three carbamates (aldicarb, carbaryl and caxbofuran) will be used in the monitoring program. The FSIS hopes to extend the technology to include additional carbamates in the future. Like organophosphate pesticides and drugs, carbamates in general are rapidly metabolized and degraded, so a significant problem with residues in food animals is not expected. However, carbamates are widely used in crop production, and monitoring data in meat and poultry will provide important information for evaluating human dietary exposure. Pentacblorpbenol. Pentachlorphenol (PCP) is a pesticide that has no approved uses for food production, but it is a ubiquitous contaminant found in livestock and poultry. Exposure may occur when animals are in contact with wood preserved with PCP, or through contaminated feed. Pentachlorphenol is used in hide-tanning operations, and, when contaminated by-products of tanning are rendered and sold as feed ingredients, PCP residues can occur in meat, poultry and eggs. Industrial uses and waste are other sources of contamination in the environment. The FSIS, in exploratory projects, has been determining PCP residues in livestock and poultry for several years. Data through 1986 will be compiled for evaluation by the EPA and the FDA to determine whether residue limits need to be established. The data collected TABLE 5. LIVER SAMPLES CONTAINING RESIDUES OF PENTACHLOROPHENOL (PCP) a Animal group Mean Number of Percentage concentrations samples with PCP ppm SE Sows Barrows/gilts Boars/stags Bulls Cows Steers Chickens, mature Chickens, young O1 afood Safety and Inspection Service Exploratory Program, 1985.

11 CHEMICAL RESIDUES IN MEAT AND POULTRY , Oetected (77.3)~ NO tolerance est~b~ishe~ T~tal samplss ~ ~g~:o~oo ~.'~ N\\\N ,9 ~ 3,5 Although the pesticide monitoring data, in general, lend confidence that residues detected by current methods in meat and poultry are not likely to endanger human health, residues may remain that are not being monitored. Those ranked high in priority for methods development include synthetic pyrethrins and pyrethroids, amitraz, alachlor, metolachlor, captan, benomyl, acephate, phorate, several of the ethylene-bis-dithiocarbamates linuron and 2, 4-D. Each of these raises toxicological concern, but there is no evidence that they occur as significant residues in food animals. 0 k\\\x).ool-,1% , ,610-,710-.8t0-,9t , , ,700.BOO, >t.00 Concentration Inteeval (OPm) Figure 6. Pentachlorophenol residues in liver tissue from market hogs collected in an exploratory program in during 1985 are typical of findings in other years and show that residues occur in over 75% of hogs slaughtered, but much less frequendy in cattle and poultry. Table 5 shows the percentage of liver samples from the major production classes tested in 1985 that contained PCP, the mean concentration in parts per million and the standard deviation. Figure 6 shows the distribution of PCP concentrations found in liver samples of market hogs. Although they occur frequently, PCP residues are usually present at very low concentrations. One of the concerns about PCP residues is whether they indicate possible exposure to dioxins and dibenzofurans. Currently, the FSIS does not have the capability to test for these contaminants. Drug Residues Drugs are used extensively in food animal production for the treatment and prevention of disease, to improve feed efficiency and promote growth and to manage reproduction. The importance of drug residues in the National Monitoring Program is reflected in the proportion of resources devoted to this area, typically 70% to 80% of the annual plan. Antibiotics. Antibiotics have been included routinely in the monitoring program since the early 1970s because of extensive use in all animal species and concern about toxicological effects of exposure to violative residues. Also, there is concern about whether antibiotic use in food animal production increases human risk from antibiotic-resistant bacteria. That is a subject beyond the scope of this paper. This important and controversial public health issue is under evaluation by the FDA. The FSIS is particularly concerned about therapeutic treatment of animals under conditions contrary to approved label directions. Extra-label use can result in extremely high residue levels (over 100-fold above tolerance limits), negating the TABLE 6. ESTIMATED PERCENTAGE OF LIVESTOCK SLAUGHTERED IN 1985 CONTAINING VIOLATIVE CONCENTRATIONS OF ANTIBIOTICS IN KIDNEY TISSUE -,,,;,._ -, Number of Percentage of Upper 95% Animal samples violations C.L. Cows 1, Steers Calves 1, Barrows/gilts Sheep/lambs Goats Horses

12 424 CORDLE margin of safety applied in setting tolerances. Thus, antibiotic-sensitive individuals might risk serious, life-threatening effects from exposure when certain drugs are used contrary to approved labels. Table 6 shows the estimated percentage of different types of livestock slaughtered in 1985 with violative residues of antibiotics in the kidneys. The microbiological methods used can detect residues of penicitlins, tetracyclines, streptomyeins, bacitracin, erythromycin, neomycin, neomycin, gentamycin and tylosin, when residues occur at or above the respective tolerance levels (FSIS, 1974). The methods will also detect other antibiotics, but some of these cannot be detected at the tolerance level, and the identity of some cannot be confirmed. The tests are conducted on kidney tissue. Residues in the muscle of treated animals are much lower than in kidney or liver, particularly for the aminoglycosides that deposit in kidney tissue. When residues are found in the kidney, the muscle sample taken from the same animal is also analyzed, but the vast majority of these muscle samples have not contained violative residues. Many of the illegal antibiotic residues occur in mature or culled animals that are sold through intermediate markets. Because it is difficult to trace these animals to the producer, the FSIS has been limited in its ability to force corrective action. The FSIS is examining ways to provide more directed sampling programs and increased use of the STOP test (Johnson et al., 1981) on aged and diseased animals. The FSIS field compliance officers are more actively involved in the investigation of residue violations, working in coordination with FDA investigators and compliance officers. The FSIS remains concerned about illegal antibiotic residues, but the situation has improved considerably. In the early 1970s, the FSIS found that culled cows had a high incidence of antibiotic residues, which prompted development of the STOP test. The STOP program, combined with an extensive education program, resulted in a decrease in the incidence of antibiotic violations in cows (figure 7). A particularly acute residue problem arises on dairy farms when a newborn calf that is not kept for herd replacement is medicated and then slaughtered before time has elapsed for the drugs to clear the animal's system. Microbiologists at the FSIS developed a calf antibiotic and sulfonamide test (CAST) that is used at slaughtering plants to determine whether calves up to 3 wk of age contain violative residues. Under the CAST regulatory program, initiated in 1984 (FSIS, 1984), producers and dealers could certify that their calves did not contain violative residues, in which case the certified calves that appeared healthy could be processed without delay. In contrast, each lot of uncertifled calves had to be held overnight until a statistically-based number of calves were tested and passed. All calves showing signs of disease or treatment, and calves from previously identified violative sources, had to be tested. The CAST program has been very effective in reducing violations from more than 5% of calves tested during June and July, 1984, to about 2% during December, 1986 (figure 8). however, the rate of individual establishments varies from less that.5% to as high as 9%, with no clear geographical differences. Changes have occurred in treatment and marketing of calves. Initially, sulfonamides accounted for a large percentage of the CAST violations. Now, a greater number and diversity of antibiotics are found, some of which cannot be identified with current methods. However, neomycin remains the most frequently encountered antibiotic residue. Neomycin is poorly absorbed when ingested orally (Sande and Mandel, 1985a) and is not of as much concern as some of the other antibiotics found (e.g., penicillin). As a result of marketing changes, some establishments can no longer purchase certified 3,7 0~ 7'9 8~--,'~ 8'~ ~'3 ~ 9',,'~ Figure 7. Estimated percentage of cows slaughtered in 1978 through 1985 in the U.S. containing violative levels of antibiotics. Year

13 CHEMICAL RESIDUES IN MEAT AND POULTRY TESTED POSITIVE FY FY PY ,6 FY ,3 2, ,0 J0o t,s, s~'0 0~'0 J0.'1s85 s~'0 0-'0 ~00'1s86 s~'0 D~'c Figure 8. Percentage of bob veal calves tested and found violative under the CAST program. calves. This places a burden for testing on the FSIS unrelated to an establishment's compliance history. On January 20, 1987, the FSIS announced changes in the CAST program to improve its effectiveness (FSIS, 1987b). Under the new CAST interim regulation the number of calves tested that appear healthy will be based on a percentage of the estimated day's slaughter. Initially, the rate in all establishments will be 5% for certified calves and 10% for uncertified calves, but the rate may increase or decrease at each establishment based on its compliance history. Among other changes in the interim rule, plant personnel will be allowed to assist in the testing under the supervision of the FSIS inspection personnel, and explicit authority is given to reduce line speeds to accommodate testing in those plants that require a high level of testing because of lack of compliance. Cblorampbenicol. The FDA does not permit the use of chloramphenicol for treatment of food animals, and the FSIS has been concerned about residues that may occur from its use in food animals. Exposure of highly sensitive individuals to chloramphenicol can cause fatal aplastic anemia (Sande and Mandel, 1985b). The multiresidue antibiotic methods used in monitoring are not sensitive enough to detect chloramphenicol at levels of concern, so the FSIS had to develop new methods. Currently, three methods are used to determine the presence of chloramphenicol: a chemical method (FSIS, 1986a), a competitive enzyme-linked immunoassay method and an immunoassay card test. 1,3 These tests can detect chloramphenicol at or below 5 ppb. Confirmation by GC-mass spectrometry is required using a method sensitive to 10 ppb. Chloramphenicol is rapidly metabolized by animals and humans, but the metabolites that occur in edible tissues of treated food animals have not been identified, and toxicological effects and safe human exposure levels have not been determined. Consequently, methods are not available to monitor metabolites that may be of human health concern. The FSIS began monitoring for chlorampenicol in 1981, and found residues in 4 of 585 muscle samples from calves that were tested. Over 1,000 samples from calves were tested each year from 1982 through 1984, and almost 300 samples were tested in Chlorarnphenicol was found in four of the samples tested in 1982, five of the samples tested in 1983 and in one of the samples tested in Although we have monitored for chloramphenicoi in all livestock and poultry groups and in imported products, no chloramphenicol residues have been found, except in calves slaughtered in the United States. Although these monitoring results are encouraging, and they indicate that illegal use of chloramphenicol (if still occurring) is not as prevalent as it once was, the FSIS thinks that the seriousness of potential residues is such that every effort must be made to prevent the slaughter of treated animals for food. Accordingly, studies are being conducted to develop a urine screening test for calves that FSIS veterinarians could use to test animals suspected of chloramphenicol treatment and to improve the sensitivity of the confirmatory methods. Sulfonamides. Sulfonamides are used in virtually all food animal species, not only to treat and prevent disease but also (at subtherapeutic levels) for weight gain. However, their use requires extreme care and good husbandry to prevent illegal residues. The swine industry, which uses sulfamethazine-medicated feed extensively, must guard against the contamination of withdrawal feed. As little as 2 ppm of sulfamethazine in the withdrawal feed of previously medicated hogs can cause illegal tissue residues at slaughter (Ashworth et al., 1986). Failure to clean pens can cause recycling of the drug through fecal contamination, and the use of drinking water medication, common in the poultry industry, requires thorough flushing of the line after treatment. Only granulated formulations of sulfamethazine should be used in feed medications,

14 426 CORDLE because the electrostatic properties of powdered sulfamethazine, which is not approved for feed use, increase the risk of violative residues. Sulfonamide residues rank highest among all compounds in the incidence of residues found and are a particular problem in both swine and turkeys. A multiresidue, thin-layer chromatographic fluorescence method is used to monitor for the following sulfonamides: sulfabromornethazine, sulfadimethoxine, sulfamethazine, sulfaquinoxaline, sulfathiazole, sulfamethoxypyridazine, sulfaethozypridazine, sulfapyridine and sulfachloropyridazine (FSIS, 1986a). The test is conducted on liver tissues of swine and kidney tissues of turkeys. Liver typically will contain residues two to five times greater than the concentration in muscle tissue, and the ratio is highly variable among individual animals and the withdrawal period (Randecker et al., 1987). The method is specific for the parent drug compounds, and it does not measure metabolites that may have similar biological activity. The tolerance of.1 ppm in all edible tissues is based on the parent drug. The FSIS monitoring data prior to 1978 indicated that up to 13% of slaughtered hogs had violative residues of sulfonamides in liver tissue. Most of the violations were for sulfamethazine. Through cooperative efforts, the USDA and industry conducted a national campaign to inform producers and their feed suppliers about the problem and prevention measures they could take to correct it. As a result, the violation rate decreased substantially, as shown in figure 9. However, in spite of continuing education efforts, the incidence of violations remains unacceptably high. Figure 10 depicts the geographic distribution of market hogs slaughtered in 1985, the number of hogs tested for sulfonamide residues and the incidence of liver violations for the five FSIS inspection regions. Nearly all violations were related to sulfamethazine. These data show geographical differences (P<.001) that may reflect the comparative intensity and success of education efforts in different parts of the country. Figure 11 shows the distribution of the sulfamethazine concentrations in liver tissues of market hogs. Sulfamethazine violations in liver were found in 5.3% of market hogs tested; in 46% of these hogs the muscle tissues also were violative. Almost 2% of the market hogs tested contained residues in liver above.45 ppm, indicating that producers of those hogs made little effort to observe a withdrawal period after treatment. A similar pattern was observed for sows. At least 17% of the violative liver samples from sows and 13% of the violative liver samples from market hogs contained concentrations above 5 ppm (> 50 times tolerance). Not all residues above.5 ppm were quantified, so the actual percentage may have been higher. In March, 1985, the FSIS and FDA sent a joint letter to 110,000 producers stressing the seriousness of the problem and the government's intention to enhance enforcement. The letters were followed by the FSIS's May, 1985, advance notice of proposed rule making, announcing plans for a regulatory program that may include in-plant testing of hogs (FSIS, 1985). Chemists at the FSIS have developed a test 4, called SOS for Sulfa On-Site, that is performed on urine with results available in a few hours. The urine test is designed to predict whether the organ tissues and(or) carcasses contain violative sulfa residues. Field trials using the new test are nearing completion; the results appear promising for use of the SOS test in a regulatory screening program. The test is easy to perform and inexpensive, so producers also could use it on the farm to test hogs before marketing. A commercially available immunoassay card I01 ~.7 Tolerance -.I r 6, Environmental Diagnostics, Inc., undated. Performing the sulfa on site test (SOS): A self instructional guide. Environmental Diagnostics, Inc. EDI 187, Burlington, NC BI Year Figure 9. Percentage of swine liver samples containing violative levels of sulfamethazine.

15 CHEMICAL RESIDUES IN MEAT AND POULTRY 427 Figure 10. Geographical distribution of market hogs slaughtered and sulfonamide violations in liver tissue collected in the 1985 National Residue Monitoring Program. test kit for sulfamethazine also is under evaluation by the FSIS. The FSIS staff are developing a proposed rule for implementing an in-plant testing program that the FSIS hopes to publish in the Federal Register during Sulfa residues are also a problem in turkeys. Figure 12 shows the percentage of sulfonamide violations found in kidney tissue of young and mature turkeys from 1981 through All the violations in 1985 were either sulfaquinozaline or sulfadimethoxine residues. However, unlike the situation in hogs, the concentrations in the violative samples are not so high. None of the residues found in 1985 was above.5 ppm. Hormonal Drugs. Letters to the FSIS indicate that consumers are very concerned about residues of hormonal drugs in meat. However, monitoring data and information from research studies do not substantiate cause for concern. Most cattle are given drug implants when they enter the feedlot. The implants may contain estradiol, alone or in combination with progesterone or testosterone, or they may contain zeranol, which is a synthetic drug with estrogenic activity. Residue research studies have been conducted by sponsors of implants containing the naturally occurring hormones. Through the use of radiolabeled drugs and highly sensitive radioimmunoassays, these studies have shown that any increase above the normal level of these hormones in implanted animals is so small that it is insignificant. Toxicologists at the FDA have concluded that an increase is toxicological- Violative limit: O.i ~pm 2.5' TOtal samdles - I~35 /f---? Noo~iolative ~ 2.o. (7.3Z) L ~ ~ ' 7 Violative None (5.3X) 1.5- (87.4I]... \xxxx\ ~ \\\\\\ o ~\\~.05, >.45 Concentration Endpoint {ppm] Figure 11. Sulfamethazine residues in liver tissue from market hogs collected in the 1985 National Residue Monitoring Program.

16 428 CORDLE ly insignificant if it does not exceed 1% of the daily production rate of these natural hormones in prepubertal children with the lowest rate (Farber and Arcos, 1983). Residues are not distinguishable from the endogenous hormones, and the FDA has not required a regulatory method for residues in support of the approval of these implants (Farber et al., 1983). Zeranol is approved for use in cattle, suckling calves and sheep, with the stipulation that animals not be slaughtered for food within 65 d after implantation. No residues are permitted in food. The official method of analysis (21 Code of Federal Regulations ) is sensitive to 20 ppb and defines "no residue" for purposes of enforcement. In support of the approval of zeranol implants, the manufacturer, International Minerals and Chemical Corp. s, funded residue research studies that show residues are well within the regulatory limit. In one study, calves were implanted with tritium-labeled, 36-mg zeranol implants, and total radioactive residues were determined in liver, kidney, muscle and fat tissue at 2, 5, 15, 30, 45 and 65 d after implantation. Residues were highest in liver tissue, 8.2 ppb, 5 d after implantation. At 65 d liver residues were 1.5 ppb. Muscle residues also were highest (.13 ppb) at 5 d after implantation, and they decreased to.05 ppb after 30 d. Each of the values represent the average of three calves (International Minerals and Chemical Corp., unpublished data). The FSIS found the zeranol method published in the Code of Federal Regulations unsuitable for monitoring, and it recently acquired a solid-state extraction method followed by polymethylsilation for GC/mass spectrometry confirmation, which can detect residues as low as 250 ppt in liver tissue 6. The new method was introduced in the monitoring program in 1986; no residues were reported in data compiled through June of If there is any food safety risk involved with the use of approved implants, it most likely would occur from improper placement (i.e., other than in the ear, which is removed and discarded at slaughter). As a precaution, FSIS inspectors carefully examine edible tissue taken from the cheek and neck area for any sign of a misplaced implant. One other anabolic drug, melengestrol acetate (MGA), is used in the feed of heifers to suppress estrus and improve feed efficiency. The synthetic drug is chemically similar to, but biologically more active than progesterone. The FSIS monitored for MGA in 1,624 fat samples collected from heifers from 1978 to 1983, and it is again monitoring in The gas chromatographic method used (AOAC, 1985) detects MGA at levels well below 25 ppb, which is the sensitivity of the official method of analysis (21 CFR ) defining "no residue" for purposes of enforcement. No MGA above 25 ppb has ever been found in the monitoring program. Over 90% of the residues in fat, which were detected in about 40% of the heifers tested during 1983, occurred at levels below 10 ppb. The use of stilbenes (e.g., diethylstilbestrol, DES) is not permitted in the United States for treating animals, and the FSIS cooperates with the FDA in follow-up investigations of any alleged illegal use. The FSIS currently monitors for DES residues, using the same method for quantification and confirmation as previously described for zeranol. The limit of detection for DES is 100 ppt. No DES residues have been found in steers or heifers since the new test was introduced in the monitoring program in In 1983, following discovery of DES residues in four lots of fancy veal calves slaughtered Young Turkeys K\\\\\H Tolerance = 0,1 ppm Matupe Turkeys s International Minerals and Chemical Corp., Terre Haute, IN Chemistry Division, Science Program, FSIS, Washington, DC " Year' Figure 12. Estimated percentage of turkeys slaughtered containing violative levels of sulfonamide drugs in kidney tissue.

17 CHEMICAL RESIDUES IN MEAT AND POULTRY 429 in the state of New York, FSIS initiated an extensive survey in all calf slaughtering plants to see whether illegal use was more widespread. A nonspecific histopathological screening test of the prostate gland, developed in the Netherlands (Kroes et al., 1971), was used for the survey. This test determines whether a calf has been treated with an estrogenic substance, but it cannot determine which drug was used. When the test on prostate gland was positive, edible tissues from the same animal were analyzed for DES. No DES residues were found in almost 1,200 samples tested in the survey. The prostate screening program for calves has continued, and iambs have been added to the program in The new, more sensitive methods for DES and zeranol are now used to analyze edible tissues from animals when the prostate gland is positive. No residues of DES or zeranol in edible tissue were reported in the samples analyzed through June Antbelmintic Drugs. Anthelmintic drugs are widely used for the treatment of internal parasites, particularly gastrointestinal and lung worms and liver flukes. Two of the drugs, levamisole and thiabendazole, have been used for many years, ranking them among the top 10 animal drugs in dollar volume sales in the 1970s. In the 1980s a number of new anthelmintics were approved. Although methods of analysis were provided by the sponsors of the newer drugs and the FSIS was able to monitor for those drugs as they came on the market, suitable methods for the older drugs were not available until recently. In 1985, FSIS scientists completed development of an HPLC multiresidue method for benzimidazoles (FSIS, 1986a) that detects residues of thiabendazole (and its 5-hydroxy metabolite), fenbendazole, oxfendazole and mebendazole (a drug only approved for use in non-food animals). Monitoring in cattle and sheep was begun in No residues were detected in 365 samples analyzed during 1985 or during the first 6 mo of testing in Prior to completing the benzimidazole method, monitoring was conducted for fenbendazole, using the method provided by American Hoechst Corp 7. Out of 479 liver samples tested 7 American Hoechst Corp., Somerville, NJ s Pfizer, Inc., Elizabeth, NJ Merck and Co., Rahway, NJ in 1984 from horses, fed cattle, sheep and hogs, fenbendazole was found in only one sample (a liver sample from a horse, which contained a nonviolative residue). During 1983 and 1984, a GC multiresidue method provided by Pfizer 8 was used to monitor liver tissues of cattle, sheep and hogs for residues of morantel and pyrantel tartrate. Out of 898 samples tested in 1983 and 1,165 samples tested in 1984, no violative residues were found. Levamisole, detected by a GC method (FSIS, 1986a), was included in the monitoring program in 1984 for sheep and hogs, and it was monitored in 1985 for these species and also for cattie. No detectable residues were found in 383 liver samples tested in Out of 1,035 liver samples tested in 1985, nonviolative residues were found in two hog liver samples; one liver sample from a cow contained a violative residue. Test results reported through June of 1986 show no additional levamisole violations. Ivermectin is one of the newer broad-spectrum anthelmintics. Monitoring with an HPLC method (FSIS, 1986a) was initiated in Out of 231 swine samples tested in 1984, only one violation was found, in a liver sample from a boar. Monitoring was extended in 1985 to include samples from steers, heifers and sheep also. Out of 748 samples tested in 1985, only one liver sample from a market hog contained a violative residue. However, monitoring results reported through June of 1986 show three additional violations: two liver samples from sows and one liver sample from a boar. Albendazole, which is an investigational drug formerly authorized by the FDA for emergency use in 18 states and Guam for the control of liver flukes (with a stipulation that treated animals were not to be slaughtered for 180 d following treatment) also has been monitored using an HPLC method (FSIS, 1986a). Out of 386 liver samples from cattle and sheep tested for albendazole during 1984 and 1985, no residues were found. In January 1986, the FDA withdrew authorization for its use. An alternative drug for treatment of liver flukes in cattle, clorsulon, was approved in 1986 and was included in the monitoring plan for detection by an HPLC method provided by Merck and Co. 9 Through June, 1986, no violations were reported. Thus, although FSIS experience in monitoring for anthelmintics is relatively recent, resuits are encouraging,. With the exception of

18 430 CORDLE ivermectin residues in swine, which bear close attention, it would appear that anthelmintics are being used in accordance with approved directions and are not causing a residue problem in food animals. Arsenic. Organoarsenical drugs are widely used, often in combination with other drugs, especially in swine and poultry. A 5-d withdrawal period is required to prevent residues above the tolerance levels, which are based on measurement of elemental arsenic (As). Because As occurs naturally in the environment, it is not surprising that FSIS monitoring (since 1972) has detected low concentrations of As in meat and pouttry. But when residues occur above or near the tolerance levels, they most likely are the result of animal drug use. However, As-containing pesticides, such as those used as wood preservatives, may be a contributing factor. Monitoring data on liver tissue show that young chickens have the highest incidence of detectable As residues, ranging from about 70% to over 90% of the birds sampled from 1972 to 1985 (figure 13). Nearly all the residues were below the tolerance level of 2 ppm in liver. In contrast, the occurrence of detectable residues in liver samples from market hogs is much lower, ranging from about 15% to 40%, with nearly all the residues below the tolerance level of 2 ppm (figure 14). No As violations were found in almost 1,400 poultry monitoring samples tested by an atomic absorption method (FSIS, 1986a) during 1984 and In swine, no violations were found out of 664 samples tested in 1984, but three violations were found in liver samples from market hogs out of 317 samples tested in The sporadic finding of violations over the years indicates a need to reinforce education, particularly in the swine and broiler industries, on proper drug use and on avoidance of contact with wood structures and litter that may have been treated with arsenicals. Coccidiostats. In addition to arsenicals, the FSIS has monitored for decoquinate, clopidol, and halofuginone. In 1983 and 1984, nearly 700 liver samples from chickens and over 1,200 liver samples from cattle were tested for deco- 0 For address, see footnote 7. 1~ Eli Lilly and Co., Indianapolis, IN Hoffman-LaRoche, Inc., Nutley, NJ quinate using a GC method (FSIS, 1986a), but no violative residues were found. For several years during the 1970s, clopidol was included in the monitoring program with detection by a GC method (AOAC, 1985). Out of approximately 700 chicken liver samples tested, no violative residues were found. Halofuginone, which is a more recently approved drug, was included in the monitoring program for chickens in 1986 and 1987, with detection by an HPLC method provided by American Hoechst Corp. l~ No violations in chicken liver tissues have been reported through June of Ionopbores. Monensin and lasalocid, used for control of coccidiosis in birds and for feed efficiency and growth promotion in cattle are two of the most widely used drugs in the cattle and poultry industry. The FSIS has extensively monitored for monensin in over 1,500 samples from young chickens and over 1,800 samples from steers and heifers since 1976, but it has found no detectable residues. A microbiological assay provided by Eli Lilly and CoJ 1, which is sensitive to 50 ppb, was used for monensin detection. No violative residues of lasalocid have been found in over 1,000 samples from steers and heifers or in over 500 samples of young chickens, tested from 1983 through 1985, using methods provided by Hoffman- LaRoche, Inc. 12 Nitroimiclazoles and Nitrofurans. The nitroimidazoles (ipronidazole and dimetridazole) and the nitrofurans (furazolidone and nitrofurazone) are drugs of potential carcinogenic concern (FDA, 1976a,b; 1984a,b). The nitroimidazoles are approved for use only in turkeys. The nitrofurans are used primarily in treating swine and poultry. Research studies using radiolabeled drugs show that metabolite residues, largely uncharacterized, persist in tissue much longer than the parent drug (FDA, 1976a; 1984a,b). The drug uses were approved before the FDA began requiring more extensive data on the occurrence and toxicity of metabolite residues in edible tissues, and before requiring that regulatory methods of analysis be adequate to assure safety of the total residue before approval. Consequently, the FSIS has been handicapped in its ability to develop adequate methods of analysis and to monitor for residues. No suitable methods are available for the nitrofurans or for dimetridazole. The FDA is engaged in the lengthy administrative process of withdrawing approvals for

19 CHEMICAL RESIDUES IN MEAT AND POULTRY 4:31 120" Not-Detectable ppm ppm ppm m ppm mllllllrrm >2.00ppm 100' ~///~ = -z 80 4J (-. u [_ g_ z N\\\\N 40",xxx~\,,\\xx\~ ~\\\\N 20" m N\\\\N t t 1982 Year m 1983 Figure 13. Percentage concentrations of arsenic in broilers (liver) in the United States _1985 use of furazolidone and nitrofurazone in food animals. An opinion from the Administrative Law Judge, following a hearing, was provided to the Commissioner of the FDA. It supported the proposed withdrawal of approvals. On December 17, 1986, the FDA published a Notice of Opportunity for a Hearing (FDA, 1986) proposing to withdraw approval for the use of dimetridazole in turkeys on the basis that use has not been shown to be safe, and that conditions of approved use are not followed in practice. Specifically, the FDA referred to extra-label use of dimetridazole in swine. The FDA subsequently withdrew approval for use of dimetridazole in turkeys effective July 31, 1987 (FDA, 1987). For a number of years, chemists at the FDA and USDA have tried to develop a method of analysis for residues of dimetridazole in turkeys and swine, but they have not been successful. Ipronidazole is approved for use in turkeys to control blackhead. Because it is a suspect carcinogen, no residues are permitted in edible tissue. The sensitivity of the official method of analysis, 2 ppb, defines" no residue ~ for enforce- ment purposes (21 CFR ). The FSIS found this method inadequate for monitoring and enforcement. In 1984, FSIS chemists completed development of a GC method with mass spectrometry confirmation for ipronidazole and its 4-hydroxy metabolite that can detect residues as low as 400 ppt in turkey and swine muscle (FSIS, 1986a). Monitoring was initiated. Out of 352 swine samples and 564 turkey samples analyzed during 1984 and 1985, no violative residues (>2 ppb) were found. Carbadox. Carbadox is approved for use in swine weighing up to 34 kg (75 lb) to treat and prevent enteritis and for improved weight gain and feed efficiency. No residues are permitted because of carcinogenic concern. The official method of analysis (21 CFR ) measures combined residues of carbadox and its major metabolite at concentrations as low as 30 ppb. When use is restricted to young animals and the required lo-wk withdrawal period is followed, residues are well below 30 ppb; however, use in older swine causes illegal residues, which the FSIS occasionally found through monitoring in

20 432 CORDLE 120 Not-Detectable ppm ppm r ~ ppm ppm FFTTII~ >2.00ppm too 80 Y_ 0J f._ ]_ Year Figurel4. Percent~econcen~atmnsofa~enicin m~kethogs(liver) inthe Uni~dgt~es the 1970s. The incidence of residues, however, was low; residues were found in fewer than 1% of samples tested each year from 1974 through No residues were found in subsequent years of monitoring since 1979; nevertheless, about 600 swine liver samples will be analyzed in 1987 to determine again whether carbadox use restrictions are being followed. Conclusions The combined USDA, FDA, and EPA programs to control residues in meat and poultry have been effective in reducing the incidence of violative residues in meat and poultry products and in reducing potential risk, although problems with antibiotic and sulfonamide residues still persist. There continue to be sporadic cases involving chlorinated hydrocarbons that demand extensive use of agency resources to prevent adulteration of food. Monitoring data of the FSIS show that most agricultural chemicals, which benefit consumers by increasing productivity, are not causing contamination of meat and poultry. As the technology for residue detection and control continues to improve, the FSIS should become even more effective in preventing potentially harmful residues in meat and poultry. The key to eliminating unacceptable residues lies in their prevention during all stages of animal production. Therefore, the USDA will continue to encourage industry's participation in sound quality control programs for residue avoidance. Also, the FSIS will continue to strengthen its residue testing and regulatory programs. The FSIS is continuing to build a stronger link between detection and enforcement, and it is improving its liaison activities with other regulatory agencies. A relatively small segment of the food animal industry continues to market adultered animals, but their actions erode consumer confidence in safety of the food supply. The FSIS cannot be complacent. Those producers who show low regard for food safety must be persuaded through education, appropriate regulatory programs and enforcement actions to change their production and marketing practices.

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