Date: 02/21/2012
AIT Official Text #: OT-1201E
What Is Ractopamine?
Ractopamine hydrochloride is a feed ingredient that helps increase the animals’ ability to efficiently turn what they eat into lean muscle rather than fat. This leads to reduced feed demand, less waste and higher quality and more affordable meat for consumers. The United States has approved the use of ractopamine in cattle since 2003. Major beef producing or importing countries, including Japan, South Korea, Mexico, Canada and many others, have also determined that meat from animals fed ractopamine is safe for human consumption. Ractopamine is sold under the brand name Optaflexx for use with cattle and Paylean for use with pigs.
Beta-agonists are commonly prescribed medications used to treat asthma in humans. They work by relaxing the muscles of the bronchial tubes to improve breathing and are available as quick-acting or long-acting inhalers and tablets. As with any medication, there may be side effects, including increased heart rate or tremors. Serious side-effects, however, are extremely rare.
Some beta-agonists, such as clenbuterol and salbutamol, are sometimes used illegally and without safe usage guidelines to promote meat production in cattle and pigs. There have been reports from China and other countries of poisonings in people who had consumed pork from pigs that have been fed clenbuterol, salbutamol or other beta-agonists. These beta-agonists, which are in fact the subject of many erroneous media reports, have not been approved by the food safety authorities in any country as a feed ingredient to promote meat production.
Ractopamine is part of the beta-agonist compound family. Ractopamine, however, was developed through years of research to be used safely and specifically to improve meat production in livestock. Regulatory authorities in 27 countries, including Japan, South Korea, Mexico, Canada, the United States and many others, have determined that meat from animals fed ractopamine is safe for human consumption.
Extensive Studies Confirm That Ractopamine and U.S. Beef Are Safe
There have been extensive scientific studies that reviewed the use of ractopamine as a feed ingredient and considered its impact on human health in terms of toxicity, reproductive abnormalities, carcinogenicity and other factors. Based on these studies and government-directed risk assessments, 27 countries, including Japan, South Korea, Australia, New Zealand, Canada and the United States, have determined that meat from animals fed ractopamine is safe for human consumption.
The Joint Expert Committee on Food Additives (JECFA), which operates under the United Nations’ Food and Agriculture Organization and World Health Organization and is comprised of scientists from around the world, also reviewed ractopamine and has recommended maximum residue levels (MRLs) for beef and pork. Countries that adopt the JECFA-recommended standards can be assured that meat from animals fed ractopamine is safe and will have no negative effects on human health.
Some have questioned the fact that a single human study with only six test subjects was used to support the JECFA MRL recommendations for ractopamine. In fact, JECFA conducted multiple reviews of the use of ractopamine in animals and based its recommendations on more than 20 animal studies, including long-term studies with primates, in addition to the human study. It would be highly unusual to take the extra step of testing humans with drugs that are intended for use in animals, and therefore the sample size for the human study was limited for ethical reasons. The human study was intended only to verify that humans react to ractopamine in a way similar to primates, so that the levels determined to be safe for primates could help determine safe levels for humans. Drawing from the results of these extensive studies, additional safety factors were used to account for variability in testing and to ensure the safety of more susceptible populations. As a result, the JECFA-recommended MRLs were set at levels well below the maximum safe levels.
It is very important to note that Taiwan also conducted its own risk assessment for ractopamine and in 2007 notified the WTO of Taiwan’s intention to establish MRLs for ractopamine in beef and pork. This historical fact is often overlooked in media reports.
U.S. Authorities Test to Confirm Safe Ractopamine Residue Levels
The U.S. Department of Agriculture’s Food Safety Inspection Service (FSIS) takes samples of beef, veal and pork to test for beta-agonists, including ractopamine. This testing is conducted mainly at the FSIS Western Laboratory in Alameda, California. It involves screening and confirmation for beta-agonists by High-Pressure Liquid Chromatograpy with Mass Spectrometry (HPLC-MS-MS.)
In 2012, samples specifically designated for beta-agonist testing will be divided among fresh beef, fresh pork, and fresh veal. For more information, please refer to the National Residue Program Sampling Plan or “Blue Book.” The “Blue Book” contains a description of the FSIS National Residue Program, as well as links to the Program Plans for the past several years. A link to the “Blue Book” follows:
http://www.fsis.usda.gov/Science/2011_Blue_Book/index.asp
It is important to note that Taiwan’s own testing of imported meat products confirmed that ractopamine residues in U.S. beef fell well within the MRLs recommended by the Joint FAO/WHO Expert Committee on Food Additives, which are the same draft MRLs that Taiwan notified to the WTO in 2007.
FAO/WHO Expert Committee Recommends MRLs for Ractopamine
In 2004, the 62nd meeting of JECFA determined an acceptable daily intake (ADI) level and recommended maximum residue levels (MRLs) for ractopamine in cattle and pig tissues (muscle, liver, kidney and fat.) JECFA established the ADI based on extensive animal studies and one human study, also noting that JECFA had factored in a wide margin of safety. In 2006, the 66th JECFA meeting again considered ractopamine and reconfirmed the ADI and MRLs of its previous meeting.
In 2010, at the request of the Codex Alimentarius Commission, JECFA undertook a review of new data on residues of ractopamine in pig tissues including lung, heart, large and small intestines and considered whether these data would have any implications for the recommended MRLs. Based on the data provided, including information on dietary consumption, JECFA concluded that its previously recommended MRLs are compliant with the ADI for consumption of muscle, liver, kidney and fat.
The published JECFA risk assessments/reviews are available from the WHO Technical Report Series:
http://www.who.int/foodsafety/chem/jecfa/publications/reports/en/index.html
The risk assessments are also available as FAO Residue Monographs on:
http://www.fao.org/food/food-safety-quality/en/
In determining safe maximum residue levels or standards for any pesticide, veterinary drug or other compound, researchers must first determine a “no observable effect level” (NOEL) — in other words, the level at which there is no effect of any kind. JECFA commissioned Professor Fritz R. Ungemach, Institute of Pharmacology, Pharmacy and Toxicology Veterinary Faculty, University of Leipzig, Germany, and the other JECFA experts to conduct a thorough review of the extensive clinical research to establish a NOEL for ractopamine. This maximum level was further reduced by a safety factor of 10 to account for individual variability and by an additional safety factor of 5 to protect sensitive individuals, thus resulting in a combined safety factor of 50, which was then applied to calculate an acceptable daily intake (ADI) level. This approach provided a margin of safety that is at least 20,000 times the NOEL as determined in extensive tests on mice and rats.
A link to JECFA study follows:
http://whqlibdoc.who.int/publications/2004/9241660538_ractopamine.pdf
JECFA used the assumption that a person on a high-meat diet will eat 300 grams of muscle, 100 grams of liver, 50 grams of fat and 50 grams of kidney every day for a lifetime. Even with that high level of consumption, using mean values, the exposure to ractopamine residues was only 15 percent of the calculated ADI. Importantly, the dosage of ractopamine fed to animals for determination of tissue residues and used in establishing the human safety included one- and- one- half times the highest approved dose level in pigs and one- and- one- third times the highest approved dose in cattle. Further, the MRLs also incorporate what are considered good veterinary practices. In fact, to reach the “no observable effect level” or NOEL, a person would need to eat more than 270 kilograms of beef or more than nine kilograms of beef liver every day. It is clear that this would be impossible even for someone who consumes large amounts of beef.
Japan food safety authorities thoroughly reviewed ractopamine, determined that it was safe and established acceptable daily intake (ADI) levels and maximum residue levels (MRLs) for both beef and pork. Japan has not yet approved ractopamine for domestic use with cattle and pigs although the application for approval is still under review. Hence, Japan’s ADI and MRLs currently apply only to imported meat products. This is sometimes referred to as the “Japan model.”
It is important to note that, aside from identifying the country of origin for all meat products, there are no marketing restrictions or additional labeling requirements for U.S. beef sold in Japan, contrary to recent claims made in the Taiwan media. In fact, U.S. beef is available for sale in Japan in 35,000 retail outlets, including convenience stores. Japan imported nearly US$900 million of U.S. beef in 2011, an increase of almost 40 percent compared to 2010.
FAO/WHO Expert Committee Rejects EU Study That Claims Ractopamine Is Unsafe
Local media reports have referenced EU studies that were supposedly used as the basis for the EU’s decision to ban ractopamine. In fact, however, the EU had established a general ban on beta-agonists in 1996, long before ractopamine was even introduced to the market. The EU did not conduct any studies on ractopamine prior to adding it to the list of already-banned beta-agonists. The European Food Safety Authority (EFSA) subsequently conducted a review of existing research on ractopamine in 2009, long after the EU ban was implemented.
Although a Taiwan toxicologist has praised EFSA for its “complete and in-depth scientific evaluation reports on Paylean in 2009,” the EFSA review actually offered no new research, largely focusing on the six-person study and minimizing the importance of the extensive animal study data that typically forms the basis of every MRL application review and approval. As previously noted, a small human study is sometime used during reviews of veterinary compounds to confirm or validate the animal proxy studies, but the bulk of the clinical research is always conducted on lab animals.
In the final analysis, EFSA was able only to raise questions about whether the reviews conducted by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) were sufficient to demonstrate the safety of ractopamine. EFSA could not, however, substantiate its claim that ractopamine was unsafe. The JECFA Secretariat reviewed the EFSA report and disagreed with the conclusions, noting that the report offered no new data. The most recent JECFA assessment in 2010, which requested all data be submitted, reaffirmed its recommendation for MRLs to the Codex Alimentarius Commission (CAC). Unfortunately, due to opposition from some CAC members, primarily the EU and China, the CAC could not reach a consensus and decided to reconsider the issue in the next CAC session. In effect, some countries simply refused to allow the issue to be considered. Taiwan itself in the past has often faced a similar situation when agenda items it has proposed are blocked from consideration in various international fora.
A link to JECFA study follows:
http://whqlibdoc.who.int/publications/2004/9241660538_ractopamine.pdf
FAO/WHO Expert Committee Finds China Studies Support Prior Determination That Ractopamine Is Safe
Recent media reports have cited questions raised by mainland China, which has alleged that the maximum residue levels for ractopamine recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) do not take into account the greater consumption of internal organs, especially lung, by consumers in China. In response, in 2010, JECFA reviewed the additional data on the consumption of lung tissue provided by China and concluded: “The Committee recognizes consumption of lung tissue to be a specific issue that has not been addressed in other residue evaluations. There is no international consensus value to estimate an appropriate consumption of lung tissue. …” On that basis, JECFA deferred recommending an MRL for lung tissue and suggested that further study regarding the consumption of lung tissue might be warranted.
Nonetheless, JECFA noted that this decision did not affect JECFA’s previous research and conclusion that ractopamine is safe. JECFA reaffirmed its original recommendation on MRLs for ractopamine in muscle meat, fat, liver and kidney. Also, the 2010 assessment substituted other organ data in the model diet, and except for lung, the resulting dietary intakes were below the upper bound of the acceptable daily intake (ADI) and thus safe for human consumption. The JECFA reviews were submitted to the full body of the Codex Alimentarius Commission (CAC). Unfortunately, due to opposition from some CAC members, primarily the EU and China, the CAC could not reach a consensus and decided to reconsider the issue in the next CAC session in July 2012. Taiwan media reports often fail to recognize that both the EU and mainland China may have their own non-scientific reasons for refusing to import meat from ractopamine-fed livestock.
The JECFA report can be found at:
http://www.fao.org/docrep/012/i1618e/i1618e00.pdf
The U.S. Food and Drug Administration (USFDA) has disputed a story carried by the Food Safety News and MSNBC that claimed ractopamine was responsible for illness and death in U.S. pigs and has asked that “… a correction be made to both stories and that the statements be removed or modified to reflect accurate information.” According to the FDA’s Center for Veterinary Medicine (CVM), the statement that “ractopamine sickened or killed pigs” cannot be substantiated using CVM data. FDA further noted that CVM data “…rarely establishes a causal association because of multiple confounding factors such as: underlying disease, concomitant medications, and poor quality of reports.”
Ractopamine and Research on Dogs
Local media have cited a U.S. study that reported significant damage to the heart and other muscles of greyhound dogs fed ractopamine. This report, however, titled “Toxicity to myocardial tissues of grey hounds fed with ractopamine,” was not designed to determine the possible effects of ractopamine on humans. Rather, the study was conducted for “the purpose of validating assays to detect illicit drugs in canine urine.” Dogs have been determined to be overly sensitive to the effects of beta-agonists and, for that reason, are not a good predictor of the effects in humans. In addition, the study failed to follow traditional study protocols, further making the results inappropriate for predicting possible effects on humans. It is also important to note that the experiment used ractopamine levels at very high doses that were equivalent to the daily intake for a 20 kilogram dog of 2,000 kilograms of meat from cattle or pigs fed ractopamine.
