Setting Standards for Maximum Residue Limits (MRLs) of Veterinary Drugs Used in Food-Producing Animals

For Your Information:

Health Canada's mandate is to help Canadians maintain and improve their health. Health Canada's Veterinary Drugs Directorate (VDD) is responsible for ensuring the safety of foods produced in Canada from food-producing animals that have been treated with veterinary drugs. To accomplish this, VDD conducts comprehensive scientific reviews of veterinary drugs before they are approved for sale in this country and also sets standards, e.g., maximum residue limits (MRLs), in the tissues and food products derived from such food producing animals.

Data to demonstrate the safety, effectiveness and quality of a new product

As per the Food and Drug Regulations, the sponsor of a veterinary drug has the responsibility to generate data to demonstrate the quality, effectiveness and safety of the product. It may take years for a manufacturer to do the work required to develop sufficient information to demonstrate the safety, effectiveness and quality of a new product. Products are evaluated thoroughly before they can be sold or used in Canada. Manufacturers must submit very detailed scientific data to show that their product can be used safely, and that it meets all of the criteria for acceptability prescribed by the regulations.

Following the approval of products, the Canadian Food Inspection Agency (CFIA) undertakes monitoring and compliance activities to make sure that MRLs are adhered to. In addition, targeted research is conducted by Health Canada or CFIA to ensure the continued safety of our food supply. For example, veterinary drugs are part of national residue monitoring studies which provide data on the exposure of Canadians to a variety of substances. Regulatory scientists work closely with researchers in the planning of these studies, and in other areas of research and monitoring related to chemical and microbiological substances and food safety.

Maximum residue limits for veterinary drugs

A Maximum Residue Limit is an amount of residue(s) that could remain in the tissue or food product derived from a food-producing animal that has been treated with a veterinary drug. This level of residue is considered to pose no adverse health effects if ingested daily by humans over a lifetime. MRLs are established only after VDD has conducted extensive review of data submitted by manufacturers and has determined that foods containing these veterinary drug residues up to the recommended levels, are safe for human consumption.

The List of Maximum Residue Limits (MRLs) for Veterinary Drugs in Foods includes the following information: Column I (Veterinary Drug); Column II (Name of the Substance for Drug Analysis Purposes); Column III (Foods); and Column IV (Maximum Residue Limits p.p.m.). Note that the MRLs listed in Column IV are applicable to food derived from all production classes of species indicated in Column III, unless otherwise specified. For example, MRLs listed for edible tissues of “cattle” apply to tissues of adult cattle, as well as calves. MRLs for veterinary drugs listed for edible tissues of “cattle, other than calves to be processed for veal” are not applicable to tissues of veal calves. For that reason, calves that have been administered these drugs should not be processed for veal.

Health Canada's multi-step health risk assessment process to establish MRLs

Health risk assessments of veterinary drugs used for food-producing animals are carried out using the best available data and highest possible standards.

This process involves six key steps:

• Studies on metabolism of veterinary drugs conducted in the food-producing animals (e.g., swine, chickens, cows, etc.) are reviewed to determine the amounts and length of time it takes for a drug and its transformation products (metabolites) to be excreted. These studies also identify the types and nature of drug metabolites produced by the animals.
• Comparative metabolism studies conducted in laboratory test animals are also reviewed to ensure that similar patterns of metabolism exist in these animals.
• Toxicity of the substance is determined by toxicity/carcinogenicity (cancer) testing. This information allows VDD scientists to determine the safe quantity of substances that humans can consume each day for a lifetime, without any threat to their health. This quantity is called the Acceptable Daily Intake (ADI).
• In the next step, the safe concentration for Total Residue Levels (TRLs) are established by ensuring that consumption of edible tissues, for example, muscle, liver, kidney and fat or food products such as milk, eggs and honey do not exceed the ADI. A substance that could be used for the purpose of drug analysis, called marker residue, is identified, and a relationship between the marker residue and the TRLs in tissues or food products is established. An MRL is then set for the concentration of the marker residue that will ensure that humans are not exposed to residues above the safe concentrations for the total residues.
• The analytical methodology developed for the marker residue in food is evaluated.
• A withdrawal period is then established based on the residue depletion data for the marker residue in the target tissue, e.g., the tissue in which the residues are found in highest concentrations and/or persist the longest, or withholding time for other food products such as milk. This information is included on the drug product labels under warning statements.

Warning statements on the labels of veterinary drugs

The labels for the respective veterinary drug product must include WARNING statements that highlights the human safety related issues on its use. These include withdrawal periods for tissues or withholding times for milk, when applicable, restrictions of use, and safety precautions for the handler of the drug. When a drug is used in a food producing animal, the specified withdrawal period or the withholding time must be observed before the animal is slaughtered or the milk is harvested for use as food to allow the residues to deplete below the MRL.

A number of veterinary drugs in Canada are marketed with no requirement for withdrawal (e.g., a zero day withdrawal period) of the medication prior to slaughter. During the establishment of the withdrawal period of a drug it is considered internationally that there will be a practical lag period between the last treatment and slaughter of an animal due to feeding practices, transportation and other pre-slaughter requirements. The practical zero day is considered to be 8-12 hours for cattle, sheep, goats, swine and horses, and 4-6 hours for poultry including chickens and turkeys. For this reason, it is important that this practical zero (which is on the drug label) should not be interpreted literally as "zero" and that the animals should be withheld for a minimal amount of time, as highlighted above, prior to slaughter. Producers are expected to observe these requirements in order to comply with the MRLs, and avoid compliance and enforcement actions. It should be noted that the concept of practical zero applies to slaughter situation only and is not applicable to the production of animal-derived products (e.g. milk, eggs).

Producers should be aware that additional quality requirements for animal-derived food products may be required by provincial, territorial, or local authorities, or by the processing plant to which the animal or animal-derived food product is shipped. In such cases, the permitted levels of residues in animal-derived food products may be lower than Health Canada's established MRLs and a longer withdrawal period/milk withholding time may be required.

Potential risk to Canadians of dietary exposure to veterinary drug residues

Dietary exposure to veterinary drugs occurs when residues remain in food products derived from animals treated with a veterinary drug. Health Canada's multi-step, health risk assessment process that is internationally recognized ensures that when residues are at or below the MRLs, the dietary exposure to veterinary drug residues even to the heavy consumers of animal meat or products does not exceed the ADI.

When a potential health risk is identified in foods in the marketplace, e.g., residues detected above the MRLs or residues detected in tissues in which MRL is not established, Health Canada, through VDD is called upon to assess the risk to Canadians. The CFIA is authorized under the Food and Drugs Act to take corrective action if warranted.

Public consultation on MRLs for veterinary drugs

Once the evaluation of a drug is complete, the proposed MRL must go through a consultative review with our stakeholders. Any scientific or safety issues raised by the stakeholders will be addressed by Health Canada before finalizing the MRLs. The List of MRLs for Veterinary Drugs in Foods which is published through incorporation by reference to the Food and Drug Regulations is publicly available through Health Canada's website.

Applicable Act: Food and Drugs Act