The purpose of this information is to help you gain understanding of antibiotic safety and how this relates to food products - milk in particular - that are safe for human consumption.
Food safety. If you are involved in the production of milk, you cannot afford not to be concerned about it. Consumer confidence in safe, wholesome milk and the dairy industry's success go hand-in-hand.
The good news is that milk is as safe or safer than it's ever been. A heightened commitment from all players in the dairy industry - including producers, veterinarians, product researchers, co-operatives and government regulators - has resulted in an improved capacity to meet the market demand for unquestioned quality.
The bad news is that few consumers thoroughly understand the use of antibiotics in milk production. They don't hear the whole story. Instead of understanding that antibiotics can be used safely, they tend to view with suspicion all antibiotic use in food-producing animals - and view the potential presence of even the most minute traces of these antibiotics in milk as hazardous.
Advances in antibiotic-testing technology have made it possible to identify traces of compounds as low as a few parts per billion. What is overlooked is that, while sophisticated testing has been able to detect progressively lower levels of antibiotics in milk, the established "safe" levels have not been changed.
Who Determines What "Safe Antibiotic Use" Is?
Every country with a thriving dairy industry has established a regulatory body to protect the health and confidence of its consumers
Pharmaceutical companies like Zoetis are required by such regulatory bodies to conduct extensive safety research on each new product they develop - safety in terms of animals treated with drugs and in terms of humans who consume meat and milk products from treated animals.
Finally, and perhaps most fundamentally, it's up to dairy producers and their veterinarians to use antibiotics and other drugs prudently and legally.
Producers rely on the use of antibiotics and other drugs to stay in business. Without the ability to control animal disease, food quality and availability would plummet, and the cost of food production would soar.
What Does "Safe Concentration" Mean?
A Safe concentration is the concentration of total residue of a drug in edible tissues, milk or eggs of animals that is deemed to be safe when consumed by humans.
To understand residues, it is important to know what they are. When a drug is administered to an animal through the feed, by injection or through udder infusion, it may be metabolised; in other words, the drug may break down after it enters the animal's body. Therefore, you are not only concerned with the residue of the drug itself (the parent drug), but also with the pieces (metabolites) it breaks into if they show any biological activity.
The parent drug plus its metabolites comprise the total residue. The drug given to an animal - plus all the pieces into which it breaks down - must be safe for humans eating the meat, milk or eggs from the animal.
All drugs legally used in food animals have allowable, legal concentrations for muscle, milk and certain edible organs such as the kidney or liver. The amount is related to the relative consumption of these food products and their tendency to concentrate in certain tissues.
Maximum Residue Limits
In Australia, the Australian Pesticides Veterinary Medicines Authority (APVMA) sets maximum residue limits (MRLs) for agricultural and veterinary chemicals in agricultural produce, particularly produce entering the food chain. These MRLs are set at levels that are not likely to be exceeded if the agricultural or veterinary chemicals are used in accordance with approved label instructions. At the time that the MRLs are set, the APVMA undertakes a dietary exposure evaluation to ensure that the levels do not pose an undue hazard to human health.
For more details on Australian MRLs refer to the Australian Pesticides & Veterinary Medicines Authority (APVMA).,
Why Do Some Antibiotics Have Zero Withholding Periods and Some Do Not?
The term withholding period (WHP) refers to the time period during which a producer or veterinarian must discontinue treating an animal with a drug before the meat and/or milk can be marketed for human consumption. Some drugs have lengthy WHP (or in the case of milk, discard time); others have no withhold, or "zero-day withholding period."
Certain drugs are able to have zero-day withdrawal or zero milk withholding period because the total residues of the drug in meat and milk are below the maximum residue levels (MRLs) within a 12-hour period after dosing - a period considered to be a practical zero withdrawal time.
Many drug residues at this time exceed the MRL and it becomes necessary to calculate withholding or milk discard times. Following a drug's last use in an animal, the residue level in the animal's tissues drops over time. The time period from last drug administration to the point where the levels are below the MRL is known as the Withholding period.
The work that goes into establishing withholding periods is extensive, because the company developing the drug must usually provide the regulatory body with a method for when the meat and/or milk from the treated animal can be marketed safely.
Most drugs are metabolised when administered to an animal. It would be virtually impossible to monitor all metabolites hence the company must identify a reliable marker compound (either the parent drug or one or more of its metabolites) and compare its depletion in the animal to that of the total residue.
The concentration of the marker compound has a known relationship to the total residue and is used to set the time that the total residue reaches the MRL. The withholding period is based on the time period when drug levels in edible tissues are above the MRL. Drug levels that exist in higher concentrations than the MRL are violative, whereas drug levels below the MRL are non-violative, but considered suspect in Australia if more than half the MRL.
What Are Violative Residues and How Can They Be Avoided?
When the level of total residue in meat or milk is at or below maximum residue level, that level is a safe residue. In other words, as long as the residue being monitored (the marker residue) is below the MRL, the residues are not violative.
On the other hand, if the residue level in meat or milk being marketed is above the MRL, it is called a violative residue. Violative residues are illegal.
There are many ways to create a violative residue; all involve drug misuse. One way is not to follow the designated withholding period for a drug to elapse before produce is allowed to enter the food chain. Another is to give the animal a higher-than-labeled dose. Still another way is to administer the drug via an unlabeled route (for instance, administering a drug by the intramammary route when the product is labeled for intramuscular injection).
How Is the Milk Supply Monitored for Safety?
Any drug used in lactating dairy cows is going to come under close scrutiny. The farmer can wait out the drug withholding period (WHP) for an animal going to slaughter, but you market milk every day. If there is a WHP for a drug used in a lactating cow, the milk from that cow has to be discarded for the period of the milk withhold.
The AVPMA determines what are acceptable residues in milk, based on the drug's maximum residue level. If a drug has a required milk discard time, there will be an officially approved test or method for determining whether a violative residue is present in the milk.
Each drug has a different regulatory method or testing procedure for determining whether milk has violative residues. Usually this testing procedure has two parts: a determinative portion and a confirmatory portion. The determinative procedure is used to quantify or measure the amount of compound present in the milk. Since the determinative procedure is not always specific for the compound being tested, the confirmatory procedure is used to verify the identity of the compound that was measured by the determinative test.
Another type of test is the screening test used by milk processors. A positive result on the screening test, however, does not indicate whether a drug has been misused as the level of drug picked up in these tests is usually well below the MRL.
The regulatory testing procedures are run on the same sample of milk as the screening test. They determine 1) what the drug is and 2) how much of the drug is there, indicating whether a violative residue exists.
It may be some time before the average consumer understands that there is such a thing as a safe residue or maximum residue level. Nevertheless, the process of better understanding begins at the level of the veterinarian and the farmer. Understanding how violative residues are avoided helps assure the consumer that the milk he or she consumes is safe.
Used properly and according to label instructions, antibiotics are an integral part of dairy management. Moreover, used properly, they do not present a safety risk.
Antibiotic Screening at the Tanker Level vs. Testing Individual Animals
In many countries, all fluid-milk tanker trucks must be screened for beta-lactam antibiotics before the milk is processed. Usually, suspect milk samples are then tested by certified laboratories and confirmation is required before action is taken against the dairy farmer.
This is a typical screening sequence when fluid milk is shipped:
- The milk tanker driver keeps a sample from each bulk tank.
- The processing plant uses one of the accepted assays to test the sample for beta-lactam antibiotics.
- If the test indicates "positive," a confirmation test procedure is required.
- If an assay tests positive, two sets of the same test, or an equivalent assay, are used to test the sample. If one of those tests shows positive, and the lab in which it was run is certified, the milk is considered adulterated. A positive test in an uncertified lab is considered "presumptive positive," but is not officially considered adulterated until a certified lab has tested the sample, again using two sets of the same or an equivalent test.
- Milk confirmed positive is discarded.
- All farm bulk tank samples that contributed to the tanker are tested to determine the cause of the violation.
- The farmer in violation is usually restricted from marketing milk for a period of time. Often, the marketing agency also bills the producer for the contaminated load. Some countries impose civil fines. Repeat violators may have restrictions placed on their ability to ship milk.
If drugs are used according to label directions, the probability of contaminating a tanker is extremely remote. However, it is possible that, when using an approved drug according to label directions on an entire herd (Blitz therapy on lactating cattle), and that herd is the only one represented on a given tanker, a positive could result. These conditions are likely to happen in a very small percentage of the tested tankers.
Screening Tests are Inappropriate for Individual Animals
To prevent violative drug residues in milk, the obvious solution would seem to be testing the milk from individual cows to ensure a completely unadulterated product. Unfortunately, it is not that simple.
Cow-side testing has been tried in many countries. Yet when researchers undertook several studies examining the efficacy of testing individual cows, the results were disturbing. Rather than helping farmers, the practice was unnecessarily costing them money, while providing little scientific value.
The problem with testing individual cows is that most of the accepted assays for screening milk for beta-lactam drugs were not developed for use on individual cows. While none of these tests appears to produce a negative result on an antibiotic-spiked milk sample containing a violative residue, many produce "false positive" and "false violative" results when used to test milk samples from individual cows.
A false positive occurs when the test "makes a mistake." The test shows positive, but no drugs are actually present. Many properties of milk from individual cows, including somatic cell count, fat content and viscosity, can cause a false positive. These components do not affect the tests in the same way when diluted at the bulk tank or tanker truck level.
A false violative means that a test shows positive because it has detected drug residues in the milk, but the residues are below the established safe level for the drug. Improved technology has enabled development of extremely sensitive milk screening tests that has increased the likelihood of false violation occurring. Either way, the result is that the producer testing individual cow samples is forced to throw away milk that is perfectly saleable.
Researchers stress that all antibiotics approved for use in lactating dairy cattle are extremely safe when used according to label instructions. Approved antibiotics, when used according to label, have the backing of both the manufacturers and regulatory bodies. In fact, there is more science behind the label directions and withholding periods of approved dairy antibiotics than there is in the current validation of antibiotic residue assays.
Extra-label drug use requires more careful evaluation of withholding periods. There is often no data to support extra-label drug administration, such as higher doses or longer treatments, and such use increases the risk of returning antibiotic contaminated milk to the vat. Screening individual cows may result in unnecessary discard of milk. Farmers should never perform extra-label drug use on their own, and veterinarians are required to advise farmers of appropriate withholding periods for drugs administered to food producing animals.
Test the Tank ... Every Tank
Clearly, dairy farmers have a tremendous incentive to keep violative drug residues out of the milk they ship. However, their concerns can backfire when they allow fear of residues to interfere with sound treatment decisions. Because they do not want to create violative residues, some producers have ceased treating mastitis and other bacterial diseases that should be addressed with antibiotics
The MRL for a drug is established for the bulk tank sample. Producers should consider the result of a bulk tank sample rather than that of an individual cow.
Catching Culprit Cows
One of the problems with testing individual cows for violative residues is that the cows most likely to cause a violative residue usually are not the ones being tested. Most drug contamination risk comes from three types of cows in a herd:
- The recently treated dry cow;
- The dry-treated cow that calves early; and
- The treated lactating cow during her milk discard time.
A cow recently treated with a dry-cow product might have 10,000 to 100,000 parts per billion (ppb) of drug or more in her milk. A cow with a short dry period would be in the 100 to 1,000 ppb range, depending on the length of the dry period. A dry cow with the proper-length dry period at the label discard time would have zero to 100 ppb.
For lactating cows, milk from cows during treatment would have 10,000 to 100,000 ppb, which could easily contaminate a tanker load of milk. In contrast, a cow at the end of her treatment time would be back in the zero to 100 ppb range. Also remember that different antibiotics have different violative levels.
Troubleshooting Drug Violations
Nearly all violative drug residues detected in the milk supply are caused by on-farm mistakes.
Usually, tanker-truck adulteration can be traced to cows milked by mistake, such as:
- cows recently dry-treated that are milked accidentally
- cows treated with an antibiotic that have not reached the end of their discard time
- cows that calve early, with their short dry period going unnoticed
To help avoid adulteration, we recommend these checkpoints whenever a violation occurs:
- Inventory on all drugs used on the dairy, including dry cow treatments, lactating mastitis tubes, injectable antibiotics and all other therapeutic substances.
- Review records of all treated lactating cows, and the dry periods of recently calved cows.
- Interview all individuals who milked the cows during the time of the violation
- Determine if a dry cow could have accidentally re-entered the milking herd (jumped the fence, a broken fence, etc.).
- Inspect all milking equipment to ensure that milk from treated cows is not inadvertently entering the bulk tank. Even a small amount of milk from a treated cow during her discard time could cause a violation.
10 Steps to Prevent Violative Drug Residues
The most important lesson learned from an on-farm violation is awareness of how mistakes can be prevented.
One way to prevent future violative drug residues is to implement the following 10-Point Plan:
The 10 Critical Control Points to Prevent Violative Drug Residues
- Practice healthy herd management.
- Establish a valid veterinarian/client/patient relationship.
- Use only approved drugs with a veterinarian's guidance.
- Make sure all drugs used have labels that comply with regulatory requirements.
- Store all drugs correctly.
- Administer all drugs properly and identify all treated animals.
- Maintain and use proper treatment records on all treated animals.
- Use drug residue screening tests only on cows treated with extra-label drugs, if appropriate test is available.
- Implement employee/family awareness of proper drug use to avoid marketing adulterated products.
- Complete the Quality Assurance Checklist annually.