3D model (JSmol)
|Molar mass||301.39 g·mol−1|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
Ractopamine is a feed additive, banned in most countries, to promote leanness in animals raised for their meat. Pharmacologically, it is a TAAR1 agonist and β adrenoreceptor agonist that stimulates β1 and β2 adrenergic receptors. It is the active ingredient in products known as Paylean for swine and Optaflexx for cattle, developed by Elanco Animal Health, a division of Eli Lilly and Company, for use in food animals for growth promotion.
Ractopamine use is banned in the European Union, mainland China and Russia while 27 other countries, such as Japan, the United States,and South Korea, have deemed meat from livestock fed ractopamine safe for human consumption.[dead link]
- 1 Mode of action
- 2 Regulation around the world
- 3 Pharmacokinetics in humans
- 4 Safety concerns
- 5 Adverse effects
- 6 Analytical method for residues in meat
- 7 International controls
- 8 In popular culture
- 9 References
- 10 External links
Mode of action
When used as a food additive, ractopamine added to feed can be distributed by the blood to the muscle tissues, where it serves as a full agonist at mouse (not necessarily human) TAAR1. It is also an agonist at beta-adrenergic receptors. A cascade of events will then be initiated to increase protein synthesis, which results in increased muscle fiber size. Ractopamine is known to increase the rate of weight gain, improve feed efficiency, and increase carcass leanness in finishing swine. Its use in finishing swine yields about 3 kg (6.6 lb) of additional lean pork and improves feed efficiency by 10%.
Regulation around the world
As of 2015, ractopamine use as a feed additive is authorized in the United States, Canada, and Mexico. The American Institute in Taiwan, which represents U.S. interests in Taiwan, claims that these "and many other countries have determined that meat from animals fed ractopamine is safe for human consumption"; this is in the context of an ongoing trade dispute between Taiwan and the U.S. on this subject, which threatened to prevent Taiwan's entry to the Trans-Pacific Partnership trade pact. In the U.S., ractopamine is allowed to be used at a feed concentration of 5–20 mg/kg feed for finishing pigs and in dosages of 5–10 mg/kg feed for finishing pigs heavier than 109 kg. The maximum residue limit for ractopamine for meat in the USA is 50 parts per billion (ppb).
The USDA approved of a new label, "no ractopamine — a beta-agonist growth promotant" to be used. Currently, the USDA label for organic means no synthetic compounds can be used other than those on the list of allowed synthetics, therefore, ractopamine would not be allowed in certified organic production.
Japan, which had permitted its feed additive use at least until 2009,:1 and South Korea only allow import of meat with ractopamine residues up to the maximum residue limit (MRL), but do not permit its use in beef production.
On 6 July 2012, the international reference standard Codex Alimentarius Commission narrowly approved the adoption of a MRL of 10 parts per billion (ppb) for muscle cuts of beef and pork. Setting any limit was a controversial move. Countries with major meat export markets had been lobbying for the establishment of such a standard for several years to use it as leverage to erode individual national-level bans in World Trade Organization disputes. Consumers International, a world federation of consumer groups that represents 220 consumer organizations in 115 countries, strongly opposed the move.
As of 2013[update], ractopamine use in food animals has been banned in over 160 countries. It has not been allowed in the 28 member countries of the European Union, based on the 2009 European Food Safety Authority's opinion on its safety evaluation, which concluded that available data were insufficient to derive a maximum residue limit as a 'safe residue level for human consumption'. The uncertainty was particularly great for people who might be thought to be more susceptible than most to an increase in β adrenergic stimulation from consuming the additive, such as people with cardiovascular disease or children, and that simply increasing the "uncertainty factor" built into the calculation as a safety factor would rapidly become arbitrary.
Russia and China banned ractopamine in pork, and Russia also in beef, deeming it unfit for human consumption. Taiwan banned ractopamine along with other beta-adrenergic agonists in October 2006, but in 2012, its legislature passed amendments to the Act Governing Food Sanitation, authorising government agencies to set safety standards for ractopamine. The Department of Health ultimately established an MRL of 10 ppb for ractopamine in beef on 31 July 2012.
Pharmacokinetics in humans
A study was conducted to define the pharmacological response of humans to ractopamine. A single oral dose of 40 mg of ractopamine hydrochloride was given to human volunteers. The drug was rapidly absorbed; the mean blood plasma half-life was around 4 hrs and it was not detected in plasma 24 hrs after dosing. Less than 5% of total ractopamine excreted represented the parent drug, while the urinary metabolites were monoglucuronide and monosulfate conjugates, with ractopamine monosulfate being the major metabolite present.
The metabolic fate of ractopamine hydrochloride is similar in the target species (pigs and cattle), laboratory animals, and humans. Besides the pharmacology effect, ractopamine may cause intoxication effect; therefore, any consumption by humans of a meat and/or byproducts of animals that consumed ractopamine with feed for growth stimulation, may result in such clinical effects as tachycardia and other heart rate increases, tremor, headache, muscle spasm, or high arterial blood pressure. The effect of ractopamine on humans is not entirely known, but consumption of products that contain ractopamine residues is not advisable for persons with cardiovascular diseases.
Target animal safety
In swine ractopamine is correlated with adverse effects, especially hyperactivity, trembling, and broken limbs, leading to censure by animal rights groups.(FDA)
In a conversation with Boulder Weekly newspaper Colorado State University Professor of Animal Science Temple Grandin, an expert on animal welfare, described harmful effects of ractopamine on feedlot animals, such as cattle with stiff, sore, and lame limbs, and increased heat stress. In the same column she also opines that meat from ractopamine-treated animals may be tougher.
When a winning show lamb tested positive for ractopamine in 2014, the owner claimed it was due to negligent feed contamination by the manufacturer, rather than intentional and illegal doping.
Genotoxicity and mutagenicity
Mutation studies in prokaryotes and eukaryotes show that ractopamine is not mutagenic. However, the results of several in vitro studies, including chromosome aberration tests in human lymphocytes, are positive. The positive genotoxic results are explained with limited evidence to be due to a secondary auto-oxidative mechanism from ractopamine-catechol-producing reactive intermediates.[which?]
Dose-dependent changes of heart rate and cardiac output are observed within the first hour after administration of ractopamine and gradually return to baseline values. The systolic blood pressure will also increase in a dose-dependent manner, while the diastolic pressure remains unchanged.
Skeletal muscle tremor is the most common adverse effect of beta-agonists, and is more likely to be seen after oral administration than after inhalation. Tremor results from an imbalance between fast- and slow-twitch muscle groups of the extremities, and its severity varies greatly between individuals.
Behavioral changes in humans
Restlessness, apprehension, and anxiety were reported effects after the use of various beta-agonists, particularly after oral or parenteral treatment. In pilot clinical trials with ractopamine, four patients showed little evidence for central nervous system stimulation. Whether long-term treatment with these drugs results in the development of tolerance to these adverse effects is unclear.
Analytical method for residues in meat
The determinative procedure for the analysis of ractopamine residues in tissue can be performed, using liver or muscle as the target tissues, by high performance liquid chromatography with fluorescence detection. The confirmatory method include reversed-phase HPLC/electrospray ionization triple tandem quadrupole mass spectrometry. The limit of quantification of the drug using this LC/MS instrument was shown to be 1 ng/g.
US-EU WTO dispute
In the late 1990s, the World Trade Organization authorized the United States and Canada to impose retaliatory tariffs of US$116.8 million per year on the European Union after it found the EU beef hormone ban to be in violation of the WTO Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement). In September 2009, the United States and the European Commission signed a memorandum of understanding, which established a new EU duty-free import quota for grain-fed, high-quality beef as part of a compromise solution.
In July 2007, officials of the People's Republic of China seized US-produced pork for containing ractopamine residues. Further shipments of ractopamine-fed pork were seized in September, though this time they were Canadian in origin.
Ractopamine has been banned in Taiwan since 2006. In the summer of 2007, two US shipments including ractopamine-laced pork were rejected by Taiwan's health authorities, while the Taiwan government had been considering lifting the ban on such imports. This resulted in mass protests in the capital city, Taipei, by swine farmers insisting that the ban remain in place. Health Minister Hou Sheng-mou (侯勝茂) declared no lifting of the ban would occur unless related laws were amended. Although the use of ractopamine in livestock is still banned and enforced on the domestic industry, and the government has maintained a “zero tolerance” policy on pork imports that contain it, Taiwan's legislature amended the food safety act in August 2012 to allow the import of beef products containing up to a maximum residue level of 10 parts per billion of the additive. The remaining restrictions have been an obstacle to the two nations signing a free-trade agreement, and the Office of the United States Trade Representative (USTR)’s 2018 Trade Policy Agenda and 2017 Annual Report assert that these remaining restrictions as “are not based upon science” and highlights their removal as among the main priorities for the US in its trade with Taiwan.
According to the Malaysian Food Act 1983 and Regulations (as of 5 January 2010), ractopamine is allowed in pig muscle and fat (MRL of 10 ppb), pig liver (MRL of 40 ppb), and pig kidney (MRL of 90 ppb). Ractopamine is allowed as its half-life is lower, leading to reduced residues in the food, and the dose required to affect humans is much higher than other beta agonists. On 30 December 2008, the Malaysian Veterinary Services Department quarantined 10 of the 656 pig farms in Malaysia, as the livestock were found to contain the banned chemical.
The use of ractopamine in Russia is prohibited. On 6 June 2011, the Russian Ministry of Agriculture notified key meat import/exporters in Russia of a future prohibition of ractopamine in meat imported to Russia.
On 7 December 2012, the prohibition went into force, and pork and beef export to Russia required submission of compliance certificates confirming absence of ractopamine in exported meat.
In popular culture
Stuntman and comedian Steven Glover has publicly spoken of his involvement as a test subject in an early ractopamine study whose aim was to determine the stress limits of ractopamine saturation in humans. Glover claims, "Based on how dangerous the study was, the more money you get."
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- Colbert, WE; Williams, PD; Williams, GD (December 1991). "Beta-adrenoceptor Profile of Ractopamine HCl in Isolated Smooth and Cardiac Muscle Tissues of Rat and Guinea-pig". The Journal of Pharmacy and Pharmacology. 43 (12): 844–7. doi:10.1111/j.2042-7158.1991.tb03192.x. PMID 1687583.
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- Vivian Vezzoni de AlmeidaI; Amoracyr José Costa NuñezII; Valdomiro Shigueru Miyada (May 2012). "Ractopamine as a metabolic modifier feed additive for finishing pigs: a review" (PDF). Brazilian Archives of Biology and Technology. 25 (3). Retrieved 9 December 2014.
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- Canadian Food Inspection Agency (September 2014). "Ractopamine Hydrochloride - MIB #82". Retrieved 29 November 2014.
- "Description of the Ractopamine Standards in Livestock Products of Different Countries". US Food and Drug Administration, Ministry of Health and Welfare. 23 March 2012. Retrieved 27 November 2014.
- Bottemiller, Helena (July 6, 2012). "Codex Adopts Ractopamine Limits for Beef and Pork". Food Safety News. Retrieved 29 November 2014.
- Russian Ban On Ractopamine Boosts Brazilian Exports Simon Quilty, Beefmagazine (Penton), March 27, 2013
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- Smithfield Foods' profit falls 63% Michael Felberbaum, USA Today (AP) June 14, 2013, s.a. Smithfield Foods
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- Rockett, Caitlin (November 20, 2014). "Oops, we forgot to study that: U.S. nonprofits file suit against Food and Drug Administration over ractopamine in our meat". Boulder Weekly. Retrieved 29 November 2014.
- BERGIN, NICHOLAS (March 15, 2014). "Family sues feed company over lamb's failed drug test". Lincoln Journal Star.
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