Chapter 5 - Sampling and Testing

5.2 Chemical Residues

5.2.1 Introduction

5.2.1.1 Definition

A chemical residue is the presence of a chemical in one or more tissues of the body at some time after administration or exposure, particularly at the time of slaughter. The tissues of importance for the purposes of the chemical residues program are skeletal muscle, liver, kidney, and fat. Techniques and instrumentation used today are sufficiently sophisticated to detect a variety of drugs in small amounts.

5.2.1.2 Concerns

Although microbial contamination of food continues to account for the majority of instances of illness, consumers still have a high level of concern about chemical residues in food. Drugs developed for use by the animal industry in Canada must be thoroughly tested and approved by Health Canada's Health Products and Food Branch, Veterinary Drugs Directorate, prior to being offered for sale in Canada. Veterinary biologics are regulated by the CFIA under the Health of Animals Act.

Concerns raised about the possible presence of antibiotics, hormones, or pesticides in meats include the following:

  • Allergic reactions are known to occur in sensitized persons. Penicillin causes the most severe adverse reactions and is implicated more frequently than all other antimicrobials combined. Small amounts of penicillin are metabolized in the body to penicilloic acid, which is a potent allergen. Allergy to the sulfa drugs is also common.
  • The development of antimicrobial resistance by bacteria has received widespread media attention. The concern has been raised that exposure of humans to low levels of antimicrobials through food could contribute to the development of resistant strains of pathogenic bacteria in the human population.
  • Residues could have direct pharmacologic effects if ingested. This is primarily a concern with the ß-adrenergics.
  • Residues could have direct, acute toxic effects. This effect has been seen as a result of consuming fish and shellfish. The banned antibiotic chloramphenicol is known to cause aplastic anemia in some individuals. Most acutely toxic compounds are unlikely to pose a problem in meats, because levels high enough to affect the consumer will cause severe illness or death in the affected animal.
  • It has been postulated that chronic toxicity could occur from exposure to minute amounts of some chemicals over prolonged periods of time. This concern has been directed mainly at carcinogens and at compounds which are known to bio-accumulate.
  • Consumer confidence in our food supply may be reduced, even when there is little or no health risk.
  • Presence or suspicion of drug residues in a product can jeopardize export markets.

5.2.1.3 Causes

Veterinary drugs and agricultural chemicals used according to label directions should not result in residues at slaughter. Possible reasons for such residues include:

  • not following recommended label directions or dosage (extra-label usage);
  • not adhering to recommended withdrawal times;
  • administering too large a volume at a single injection site, resulting in the formation of a depot;
  • use of drug-contaminated equipment, or failure to properly clean equipment used to mix or administer drugs;
  • dosing, measuring, or mixing errors;
  • allowing animals access to spilled chemicals or medicated feeds;
  • animal effects - age, pregnancy, congenital, illness, allergies;
  • chemical interactions between drugs;
  • variations in water temperature for fish species;
  • environmental contamination; and
  • improper use of agricultural chemicals such as pesticides.

5.2.1.4 Legal authorities

5.2.1.4.1 Food and Drugs Act

Section 4(d) of the Food and Drugs Act prohibits the sale of "an article of food that ... is adulterated."

Section 23(1)(d) authorizes an inspector to detain any product which he "believes on reasonable grounds" does not comply.

5.2.1.4.2 Food and Drug Regulations

Maximum Residue Limits (MRLs) are set by Health Canada in the Food and Drug Regulations. MRLs for meat are set in Division 15, Sections B.15.001 to B.15.003, and the accompanying Tables. Table I deals with metals, Table II deals with agricultural chemicals and Table III deals with veterinary drugs.

A current version of the Food and Drug Regulations can be found on the Justice Canada web site at: http://laws-lois.justice.gc.ca/eng/index.html

Section B.15.002 sets a default MRL of 0.1 ppm for any agricultural chemicals not explicitly listed in Table II. Note that there is no equivalent provision for veterinary drugs; the MRL for veterinary drugs is therefore zero unless stated otherwise in Table III.

Section B.01.048 of the Food and Drug Regulations prohibits the sale, for food, of animals which have been treated with certain drugs, specifically

  1. chloramphenicol and its salts and derivatives;
  2. 5-nitrofurans;
  3. clenbuterol and its salts and derivatives;
  4. 5-nitroimidazole compounds; and
  5. diethylstilbestrol and other stilbenes.

Health Canada has set "administrative" MRLs (aMRLs) for some compounds. These and the MRLs may be found on the Health Canada Web site at:

http://www.hc-sc.gc.ca/dhp-mps/vet/mrl-lmr/index-eng.php

Product which contains a residue at a level less than or equal to an MRL in the Food and Drug Regulations, or an administrative MRL posted on Health Canada's website, is not considered adulterated, and may be released.

5.2.1.4.3 Meat Inspection Act

Section 13.(1)(b) authorizes an inspector to inspect and take samples of any meat product or other thing that the inspector believes on reasonable grounds does not comply with this Act or the regulations.

Section 15.(1) authorizes an inspector to seize and detain any meat product or other thing if he believes on reasonable grounds that the product is out of compliance.

5.2.1.4.4 Meat Inspection Regulations, 1990

Section 2(1) of the Regulations provides a definition of "adulterated".

Section 20(1) of the Regulations authorizes an inspector to detain an adulterated product until it can be brought into compliance, or condemn it if it cannot be brought into compliance.

Section 68(1) requires an operator to comply with an instruction from an official veterinarian to hold and segregate an animal.

Section 131(1) of the Regulations requires an operator or importer to provide any samples requested, free of charge.

5.2.1.4.5 Health of Animals Act

The Health of Animals Act empowers inspectors to deal with named "toxic substances." However, no toxic substances have been named under the Act. Therefore, powers of inspectors under this Act cannot be invoked. Regulations relating to this section of the Act and a list of substances are under development.

5.2.2 Individual exposure

5.2.2.1 Introduction

Some medications are normally administered to individual animals to treat specific disease conditions, by injection, bolus, or infusion.

In addition, individual animals may be exposed to agricultural chemicals or environmental contaminants through accidental ingestion or environmental exposure, and then culled because of signs of illness or impaired production.

Treatment or exposure may result in residues in edible portions of the animal.

5.2.2.2 Sample selection

Every animal which an inspector believes on reasonable grounds may have been treated with a medication or exposed to a chemical is a residue suspect, and must be detained until its status can be determined.

"Reasonable grounds" may include (but are not limited to):

  • the presence on ante mortem examination of signs of a disease condition for which a medical therapy is available;
  • the presence on post mortem examination of pathological changes typical of a disease condition for which a medical therapy is available;
  • behavioural changes or clinical signs associated with exposure to or treatment with a particular substance or class of substances (such as dystonia with botulina toxin or pupillary constriction with organophosphates);
  • the presence on ante mortem or post mortem examination of anatomical changes associated with exposure to or treatment with a particular substance or class of substances (such as heavy muscling with ß-agonists, or development of sexual structures with estrogens or androgens); and
  • a history of recent medical treatment, such that the animal may not have reached the withdrawal period, or such that slightly delayed clearance may result in residues still being present.

Additional guidance may be found in the following sections on specific compounds. The Area Program Specialist, Chemical Residues, may also be able to provide advice.

5.2.2.3 Testing

Appropriate testing is dependent on the particular compound. See the following sections on specific compounds for guidance. The Area Program Specialist, Chemical Residues, may also be able to provide advice.

5.2.2.4 Follow-up

Hold the carcass and all its parts until laboratory results are received. Alternatively, the company may elect, with the inspector's permission, to treat the held product as condemned material in accordance with Section 88 of the Meat Inspection Regulations, 1990, rather than incur the cost or inconvenience of storing it pending results. However, portions must be disposed of under inspectional control. It is also prudent to keep samples for repeat tests or additional testing. Additional guidance may be found in the following sections on specific compounds.

For most compounds, where only a single animal is involved, disposal of the carcass or portions via inedible rendering is permissible, due to the considerable dilution. This may not apply in the case of known or suspected carcinogens.

5.2.3 Exposure of a lot

5.2.3.1 Introduction

Section 5.2.2 deals with medications normally administered to individual animals.

Other medications are customarily administered to groups of animals, usually through medicated feed or water, for the purpose of:

  • growth promotion or other production enhancement;
  • disease prevention; and
  • treatment of a disease outbreak.

If an animal is found to have residues of medications normally administered to groups of animals, it is likely that other animals from the same production group (farm, herd, flock, barn, pen, etc.) or herdmates have similar residues.

Detection of a residue of a herd or flock medication in one animal of a lot is sufficient grounds to suspect presence of a residue in the other animals in the same lot presented for slaughter at the same time.

Occasionally, an owner may seek advice on a herd or flock known to have received treatment prior to slaughter, when doubt exists whether the observed withdrawal time was sufficient to clear the medication from tissues. All requests of this type which are submitted to the Veterinarian in Charge must be discussed with the Program Specialist, Chemical Residues. In general, the producer is responsible to ensure that animals he sends for slaughter are free of chemical residues, and the abattoir is required to have controls in place to assure this. If the situation warrants it, and the shipping of pre-test animals is indicated, the producer should send only the number of animals specified by the Program Specialist, usually six. The carcasses and all their parts must be held until the appropriate tissues have been analysed. Other samples may be collected at the time of slaughter of the production lot which the pre-test animals represent.

If a medication was administered extra label by a veterinary practitioner, that veterinarian can contact the Canadian Global Food Animal Residue Avoidance Database (CgFARAD) to obtain a recommended withdrawal time.

For some antibiotics, rapid urine test kits are available.

The Veterinarian in Charge will consult the residue specialist to determine what measures are required in each case. The consultation process shall happen before the animals are brought to the plant, to permit preparation for the arrival of animals and avoid a premature or accidental kill of the lot before a decision is made. The CFIA will provide the operator with conditions to be met to allow the animals to be slaughtered. These shall be accepted by the plant operator before the kill actually occurs.

Operators are responsible to accept only animals which are free of harmful chemical residues for the preparation of meat. This should have been addressed by the plant's HACCP plan. If an operator wishes to bring animals of uncertain status into his plant, he should provide all available information to the veterinarian in charge in advance, so that an assessment can be made and to avoid the need to hold large amounts of animals or product.

In cases in which the shipping of pre-test animals is not practical, such as poultry flocks, the producer may euthanize, or have euthanized, a number of animals and send them for residue testing in advance of the anticipated slaughter date. All testing of live animals or animals euthanized for the purpose of demonstrating freedom from residues will be done at the producer's expense. Samples should be selected by a competent, objective, independent third party, such as a private veterinary practitioner, and submitted to an accredited private laboratory. A list of available Standards Council of Canada (SCC)/CFIA accredited labs providing testing for such samples is available at:

http://palcan.scc.ca/SpecsSearch/SpecsSearchAction.do

The producer or veterinary practitioner should contact the accredited lab to schedule the testing and to confirm sampling, packaging and shipping requirements.

If the Veterinarian in Charge is not satisfied that the animals have been demonstrated to be residue-free, he still has the discretion to hold the carcasses and all their parts and submit samples for testing, in consultation with the Area Program Specialist, Chemical Residues.

5.2.3.2 Sample selection

Where a herd or flock is known to have received treatment prior to slaughter and doubt exists whether the observed withdrawal time was sufficient to clear the medication from tissues, several animals from that lot should be tested for the substance suspected. Animals selected for sampling should be the poorest of the lot, as these are the ones most likely to have a residue. Codex Alimentarius document CAC/GL 16, titled "Codex Guidelines for the Establishment of a Regulatory Programme for Control of Veterinary Drug Residues in Foods", section 6.4.1, Sampling suspect lots, states:

"A minimum of 6 to a maximum of 30 primary samples should be collected from a suspect lot. When the suspected adulteration is expected to occur throughout the lot or is readily identifiable within the lot, the smaller number of samples is sufficient."

Consult with your Area Program Specialist, Chemical Residues, to determine the appropriate sample size.

Medications are sometimes used "extra label", in other words not in accordance with the label instructions. This may include exceeding the label dose, or using the product in a species other than that for which the label provides directions. Withdrawal times can vary dramatically between species, even closely related ones.

Guidance on withdrawal times for extra label use can be obtained from the Canadian offices of the Global Food Animal Residue Avoidance Database (CgFARAD). They can be contacted at:

Telephone: 1-866-C-GFARAD (1-866-243-2723)

Dr. Trisha Dowling, DVM, MS, DACVIM & DACVCP
Professor, Veterinary Clinical Pharmacology
Veterinary Biomedical Sciences
Western College of Veterinary Medicine
52 Campus Drive
Saskatoon, SK S7N 5B4
Tel: 306-966-7359
Fax: 306-966-7376
Email: trisha.dowling@usask.ca

Michèle Y. Doucet DVM, DVSc, Dipl. ACVIM, Dipl. ACVCP
Professeur adjointe
Pharmacologie clinique
Département de biomédecine vétérinaire
Faculté de médecine vétérinaire
CP 5000, Saint-Hyacinthe, Québec J2S 7C6
Tel: 450-773-8521 extension 8380
Fax: 450-778-8135
Email: michele.doucet@umontreal.ca
Web: http://www.cgfarad.usask.ca/CgFARADEngStart.html

If gFARAD provides a written opinion regarding an appropriate withdrawal time for an extra label use, and the affected animals have met that withdrawal time, then they are deemed not to be residue suspects, and should not be detained. However, it may be appropriate, in consultation with the program specialist, to collect a check sample to validate our confidence in the advice.

5.2.3.3 Testing

For red meat species, if the residue suspected is an antibiotic, it may be possible to use the STOP test to screen six carcasses from the suspect lot. If the STOP is negative, then the suspect herd can be released. This is only applicable if the STOP is known to be sensitive for the antibiotic suspected. Discuss this option with the Area program specialist, chemical residues, before proceeding. The STOP test is not valid for use in poultry. See section 5.2.7, Antibiotics.

Unscheduled samples must not be submitted without prior arrangement. Contact your Area Program Specialist to make the arrangements, and to determine what samples are required. As a general rule, unscheduled samples should go to a CFIA laboratory, and the cost of the analysis shall be charged to the operator. It will sometimes be necessary to use a private laboratory if the test is of a type not available "in house".

When analysing multiple tissues from a suspect herd, the CFIA will stop the analysis once a violation is demonstrated. Any further testing is the responsibility of the operator.

5.2.3.4 Follow-up

5.2.3.4.1 Herdmates alive

As a rule, no animal suspected of harbouring harmful residues should be brought to a registered establishment, so this should be a rare occurrence.

If the remaining herdmates are alive, they should be withheld from slaughter until they have had time to clear the residue from their system. Another six "pre-test" animals from the group should then be slaughtered and tested.

The suspect group may be held in the company's live receiving area. If so, precautions must be taken to ensure that the animals are not inadvertently slaughtered and their identity lost. Care must also be taken that the animals do not become a source of contamination for other animals in adjacent pens.

Alternatively, the suspect lot may be licensed out of the registered premises back to their farm of origin, or to any other suitable place, to await clearance of the residue. In this case, the animals must be properly identified or otherwise controlled to ensure that they are not slaughtered elsewhere in the interim.

If the animals must be slaughtered, for humane or operational reasons, then they should be segregated during slaughter and handled in accordance with section 5.2.3.4.2, "Herdmates slaughtered."

5.2.3.4.2 Herdmates slaughtered

If a herd problem is suspected during slaughter, then all carcasses and offal from that herd should be held pending test results. This is much easier than attempting to locate the carcasses of herdmates following a violative result.

If a group of animals is not determined to be suspect until after they have been slaughtered, then every effort should be made to locate and detain the affected carcasses and offal. Samples of appropriate tissues from six animals should be selected at random and submitted for analysis to determine whether there are likely to be violative residues in the lot.

Where a flock or herd is deemed suspect, and has been sampled, the lot shall be deemed unacceptable if one animal or carcass exceeds the tolerance limit.

If the product has become mixed with other production and cannot be identified, then all product which might include the affected portions must be held.

If some or all of the carcasses or offal of herdmates have left the plant, a determination must be made whether a product recall is warranted. This decision will be made by the Area Program Specialist in consultation with the National Manager, Chemical Hazards. The decision will be based on the tissues affected, the level of residue suspected, and the degree of hazard associated with exposure to the compound.

5.2.4 In-plant exposure

5.2.4.1 Introduction

Product in registered establishments is sometimes exposed to chemical contamination as a result of an accident in the plant, such as a fire, ammonia leak, or burst hydraulic line. In most cases, such exposure only affects the surface of exposed product. However, potentially contaminated product should be detained until its status can be determined.

Request the plant management to provide a detailed written description of the incident that led to the contamination, signed by the operator, to avoid any dispute at a later time as to what actually happened. The veterinarian or inspector in charge should add a statement that, to the best of his knowledge, the operator's statement is correct.

If the operator wishes to attempt to salvage any of the exposed product, he should also make a written request for risk assessment, including what use the operator wishes to make of the product for the purpose of this assessment.

Contact your Area Program Specialist, Chemical Residues, for guidance.

5.2.4.2 Sample selection

If the contaminant is a volatile agent, such as ammonia or chlorine, the operator should ventilate the area and allow time for the agent to dissipate.

In addition to the hazards of ingestion of residues, the possibility of product adulteration (off flavours or odours) must be considered. For some substances, organoleptic testing (smell and taste) is more sensitive than any laboratory assay.

Depending on the nature of the exposure, product may not have been uniformly exposed. If product is to be submitted for laboratory evaluation, collect a minimum of six samples, from various locations throughout the affected product.

5.2.4.3 Testing

Organoleptic testing should be conducted in the following order:

  • odour test of exposed product at room temperature;
  • odour test of exposed product after heating in a sealed plastic bag; and
  • taste test of cooked product.

Laboratory assays may not be available for the compounds of interest. Consult with your Area Program Specialist, Chemical Residues, for guidance. Where exposure involves a mixture of compounds (such as smoke exposure from a fire), it may be possible to test for an indicator substance, or a compound of particular concern (for example benzo-a-pyrene).

5.2.4.4 Follow-up

Any product which has been visibly affected (such as by smoke discolouration) must be trimmed or condemned.

Any product which has been detectably adulterated, as determined by the presence of off flavours or odours on organoleptic testing, must be condemned.

Any product which contains a chemical in excess of the maximum residue limit, as determined by laboratory analysis, must be condemned.

See Chapter 6 for guidance on disposal of condemned material containing chemical residues.

If the contaminant is volatile and could plausibly dissipate from the product surface, the company may, at its discretion, hold the product for a period of time and then submit further samples at its own expense. However, the product may not be restacked or mixed, in such a way that surfaces which were exposed to contamination become buried in the interior. The product may not be held in such a manner that it poses a contamination hazard to unaffected product.

5.2.5 National Chemical Residue Monitoring Program - Domestic

5.2.5.1 Introduction

The National Chemical Residue Monitoring Program is the CFIA's main program for monitoring various species to determine the prevalence of residues of various compounds of concern. The program consists of a statistical random sampling designed to detect a 1% incidence of violations at a confidence level of 95%. Sampling plans are prepared at headquarters, and distributed in the form of a sampling plan booklet, with one sample per page. One sample may consist of several tissues.

The National Chemical Residue Monitoring Program uses the Multiple Analysis Submission System (MASS), which permits the performance of several analytical operations on a single sample, in an attempt to keep sampling time and associated shipping costs to a minimum. Each sample is uniquely identified on the basis of a sample number, by affixing the sample number to the bag using a CFIA/ACIA 1461, in such a fashion that it will not become detached in transit, and will remain legible. This number tells the laboratory which analyses to perform. The need for the inspector to list the desired tests is thus eliminated.

If a new establishment opens, or an existing establishment closes, or changes the main species it slaughters, it may be necessary to reallocate samples before the end of the fiscal year, in order to ensure that the samples continue to be representative of the entire slaughter population. In the event of an operational change, the Area Program Specialist, Chemical Residues, may assign additional samples to your establishment part way through the year.

5.2.5.2 Sample selection

Only normal (not suspect), domestic animals are to be sampled.

To ensure random sampling, the sampling plan specifies not only the day but also the hour of sampling to avoid bias or duplicate sampling from the same owner if more than one sample is required on the same day.

If an establishment is not slaughtering the applicable species on the day specified in the sampling plan, or for some reason a sample cannot be taken, the sample may be taken at random from one of the next day's production, or the next day on which the applicable species is available. However, do not carry scheduled samples over from one fiscal year to the next, in other words past March 31.

If your plant no longer slaughters the indicated species, notify your Area Program Specialist, Chemical Residues, and return copies of the applicable pages from your sample plan booklet, so that the samples can be reallocated. The original pages should be retained in the sampling plan booklet, and annotated to indicate that this has been done.

The owner's name and address and (where applicable) the national livestock identification number must be recorded in the space at the bottom of each page in the sampling plan. Also include any other identifying information, such as sale or auction backtags, Heath of Animals eartags, brands or tattoos, and the breed and sex of the animal. If residues are found on analysis, you will need to be able to provide this information to permit follow-up. At the end of each fiscal year, the booklet should be filed in the inspection office as a permanent record. Booklets must be retained for three years from the end of each fiscal year.

It is important to collect a sufficient weight of the correct tissues, as indicated in the sample plan booklet.

Where a sampling plan calls for samples of muscle, the requirement is for skeletal muscle. To the extent possible, the sample should be taken from low-value portions of the carcass, such as diaphragm or neck. Avoid sampling injection sites, or tissue which may have been subjected to post mortem contamination.

5.2.5.3 Testing

Only the laboratory which is scheduled to receive the sample will have all the necessary information to complete the testing. It is therefore absolutely essential to submit the sample to the correct laboratory. The name and address of the correct lab is provided on every sheet in the sampling plan booklet. The sampling plans for one establishment may make use of several different labs, so check each sheet carefully and ensure that the sample goes to the correct lab.

Since product is not held for monitoring programs, these samples will be processed as a low priority by the lab. Samples may be accumulated by the lab for several weeks or months, then processed as a batch, to make the most efficient use of lab resources.

To reduce shipping costs, several samples may be shipped together as a single package. However, do not hold samples at the plant for longer than one week. Samples held too long in storage may deteriorate, or be lost or forgotten.

After shipping the sample, record the date and waybill number on the page in the sampling plan booklet, as proof that the sample was submitted, and to permit tracing in the event that the sample is not received at the lab.

See section 5.7.3 for direction on sample submission.

5.2.5.4 Follow-up

Since product is not held for monitoring tests, product disposition will not normally be affected by any violative result. Otherwise, samples which are found to be violative under the National Chemical Residue Monitoring Program will be followed up in the same manner as any other violative test. The presence of a violative residue will trigger a farm visit, similar to that for antibiotics (see section 5.2.7.5). Based on the results of that inspection, the producer may be subjected to compliance testing.

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