 | |
| Names | |
|---|---|
| Preferred IUPAC name 4-(1-Hydroxy-2-{[4-(4-hydroxyphenyl)butan-2-yl]amino}ethyl)phenol | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
|
| MeSH | Ractopamine |
| UNII | |
| |
| |
| Properties | |
| C18H23NO3 | |
| Molar mass | 301.386 g·mol−1 |
| 4100 mg/L | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Ractopamine (/rækˈtɒpəmaɪn,-miːn/) is an animalfeed additive used to promote leanness and increasefood conversion efficiency in farmed animals in few countries, banned in most. Pharmacologically, it is aphenol-basedTAAR1 agonist andβ adrenoreceptor agonist that stimulatesβ1 andβ2 adrenergic receptors.[1][2]It is most commonly administered to animals for meat production asractopamine hydrochloride.[3] It is the active ingredient in products marketed in the US asPaylean for swine,Optaflexx for cattle, andTopmax[4] for turkeys.[5] It was developed byElanco Animal Health, a former division ofEli Lilly and Company.
As of 2025, the use of ractopamine "is banned or its use restricted in 168 nations",[6][7] including theEuropean Union,China andRussia,[8][9] while it is legal in some other countries, with differingmaximum residual limits (MRLs) in meat. Examples include theUnited States[10] (50 ppb in pork, 30 ppb in beef);Japan,[11]Taiwan[12] andSouth Korea[13] (10 ppb, in accordance with theCodex Alimentarius Commission); andNew Zealand[14] (0.1 ppb).
Commercial ractopamine is a mixture of all four possiblestereoisomers.[15] It is also apositional isomer ofdobutamine, a related drug.
When used as afood additive, ractopamine added to feed can be distributed by the blood to themuscle tissues, where it serves as afull agonist tomurine (mouse or rat)TAAR1, a receptor protein (not necessarily in humans).[1] It is also an agonist tobeta-adrenergic receptors[2] and adopamine releasing agent.[16] A cascade of events will then be initiated to increaseprotein synthesis, which results in increasedmuscle fiber size. Ractopamine is known to increase the rate of weight gain, improve feed efficiency, and increase carcassleanness in finishing swine. Its use in finishing swine yields about 3 kg (6.6 lb) of additional lean pork per animal, and improves feed efficiency by 10%.[17] In cattle on 28 January 2004 Elanco Animal Health made Optaflexx commercially available in the US. Optaflexx is a "medicatedfeed additive that is labeled only for use insteers or marketheifers (not breeding heifers or bulls) during the last 28–42 days on feed."[18]
On 6 July 2012, the international reference standardCodex Alimentarius Commission narrowly approved the adoption of amaximum residue limit (MRL) of 10 parts per billion (ppb) for muscle cuts of beef and pork.[19] 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 inWorld Trade Organization disputes.[19]Consumers International, a world federation of consumer groups that represents 220consumer organizations in 115 countries, strongly opposed the move.[19]
A 2020 petition to theFood and Drug Administration to reconsider the approval of ractopamine stated that 168 other nations had banned or restricted its use.[6] In 2025 and in response to an unreasonable delay lawsuit, the FDA responded acknowledging the number had increased from 160 in 2012, and questioned the relevance of the figure.[7]
Ractopamine has not been allowed in theEuropean Union, based on the 2009 EU'sFood 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 children or people withcardiovascular disease, and that simply increasing the "uncertainty factor" built into the calculation as a safety factor would rapidly become arbitrary.[20][21]
Ractopamine use as a feed additive is authorized in the United States, Canada, and Mexico.[20] In the US, ractopamine is allowed to be used at a feed concentration of 5–20 mg/kg feed forfinishing pigs and in dosages of 5–10 mg/kg feed for finishing pigs heavier than 109 kg. Themaximum residue limit for ractopamine for meat in the US is 50parts per billion (ppb), or five times the standard set by theCodex Alimentarius. Ractopamine was approved by the FDA in 1999 for use in swine, in 2003 for use in cattle, and in 2008 for use in turkeys.[22]
In 2015, the USDA approved of a new label, "No ractopamine — a beta-agonist growth promotant" to be used.[23]
TheCanadian Food Inspection Agency (CFIA) maintains the Canadian Ractopamine-Free Pork Certification Program (CRFPCP) so that Canadian exports to Asian countries are not disallowed by their authorities.[24][25][26] Hundreds of commercial feed facilities, including some from overseas, are enrolled in the CRFPCP, a programme that is essentially based on self-certification and backed up by a randomized testing policy.[27]
Currently, the label forUSDA organic means no synthetic compounds can be used other than those on the list ofallowed synthetics; therefore, ractopamine would not be allowed in certified organic production.[28]
For Canadian domestic consumption of non-CRFPCP pork, ractopamine hydrochloride is permitted to be soldover the counter with applications in meal or pellet feed for finishingbarrows andgilts (up to 10 mg/kg for last six weeks), confinedfinishing cattle (up to 30 mg/kg for last 42 days), and finishing heavy turkeys (up to 9 mg/kg for 14 days). The withdrawal period was set to 0 days.[29]
Japan, which had permitted its feed additive use at least until 2009,[20]: 1 andSouth Korea only allow import of meat with ractopamine residues up to themaximum residue limit (MRL), but do not permit its use in beef production.[30]
In October 2006, Taiwan banned ractopamine along with otherbeta-adrenergic agonists.[31] In a 2012 climb-down, its legislature passed amendments to itsAct Governing Food Sanitation, authorising government agencies to set safety standards for ractopamine.[32] The Taiwanese Department of Health ultimately established an MRL of 10ppb for ractopamine in beef on 31 July 2012.[33]TheAmerican Institute in Taiwan, which represents US interests in Taiwan, states that these "and many other countries have determined that meat from animals fed ractopamine is safe for human consumption";[34] this is in the context of an ongoing trade dispute between Taiwan and the US on this subject, which threatened to prevent Taiwan's entry to theTrans-Pacific Partnership trade pact.[35]
In 2020, restrictions on imports of US pork with ractopamine were relaxed, leading to protests.[36] A referendum took place on December 18, 2021, deciding whether to ban the import of pork with ractopamine, and the ban was rejected.[37]
In 2013, Russia and China banned ractopamine in pork,[38] and Russia also in beef,[39] deeming it unfit for human consumption. Because the traditional Chinese diet embraces pigoffal, and because ractopamine is concentrated by the gastro-intestinal system of animals, Chinese officials have banned ractopamine. Other countries in Asia, whose traditional diet is similar to that of the Chinese, have had similar concerns, but the American use oftied trade access as a proxy for conflict has somewhat mitigated their reactions.[24][40][41]
In 2017, Russia banned imports of beef from New Zealand after finding ractopamine in New Zealand beef.[42] Ractopamine is not registered for use in cattle in New Zealand.
In 2015, Radwa Arafa Abd Elsalam, an athlete fromEgypt, underwent adoping control where ractopamine was identified in the sample. Elsalam was sanctioned by the Egyptian Anti-Doping Organisation (EGY-NADO) with a two year ineligibility period for non-intentional presence of a prohibited substance, in violation of Article 2.1 of the EGY-NADO rules. While not mentioned by name in the2015 Prohibited List, ractopamine was determined to — much likeclenbuterol, anotherβ2-adrenergic agonist — constitute anOther Anabolic Agent prohibited under S1.2. Elsalam appealed the decision, claiming that ractopamine is used in the meat industry overseas, so she must have inadvertently consumed food contaminated with ractopamine. EGY-NADO accepted her appeal, reduced the sanction to six months, and provided theWorld Anti-Doping Agency (WADA) with records pertaining to the case.
WADA filed an appeal with theCourt of Arbitration for Sport (CAS) against EGY-NADO and Elsalam with respect to the appealed decision. WADA asserted ractopamine was "undisputed[ly]" an Other Anabolic Agent, that "[i]t is not sufficient for an athlete merely to make protestations of innocence and suggest that the prohibited substance must have entered her body in inadvertently", and that "her explanations are nothing more than mere speculation". Elsalam asserted she was not aware ractopamine was a prohibited substance, that ractopamine was commonly used overseas to increase meat yields, that she was "a normal Arabic girl", that her family consumed a large quantity of meat duringRamadan (providing a receipt "for the purchase of 20 kilos of Brazilian meat, hot dog and green sausage"), that she was not warned meat could contain prohibited substances, and that further sanctions were "unfair" and "will affect her whole life causing her depression".
CAS determined there were two key issues in dispute: Firstly, whether the presence of ractopamine in the athlete's sample constituted a violation of EGY-NADO rules; and secondly, if a violation was committed, the extent to which sanctions should be applied. On the first issue, CAS found "there can be no doubt that Ractopamine is indeed a non-specified substance falling under the category of Other Anabolic Agents" and that no evidence was submitted to suggest otherwise. On the second issue, CAS stated they could not "permit an athlete to establish how a substance came to be present in his body by little more a denial that he took it", that there was "nothing more than speculation, unsupported by any evidence of any kind", that Elsalam did not substantiate her hypothesis with any evidence aside from the receipt presented, that little attempt was made "to establish the causal link" and that it was "noteworthy" that Elsalam had not "produced a single piece of evidence demonstrating or even substantiating that other consumers (including athletes) having purchased and eating [sic] meat in Egypt within the relevant time have been subjected to food contamination with [ractopamine]"
CAS upheld WADA's appeal, ruling a violation was committed, and that Elsalam had not met her burden of proof, so the violation "must be deemed to have been intentional". It was explicitly stated that they had "not pronounced the Athlete as a 'cheater'". Elsalam's ineligibility period was extended to four years.[43]
In October 2017 at a WADA conference, it was suggested in relation with ractopamine:[44]
One conclusion reached in October 2017 was that there was a "clear risk for athletes to be tested positive" when consuming meat with residues at the MRL concentration.[5]
In the late 1990s, theWorld Trade Organization authorized theUnited States andCanada to impose retaliatorytariffs of US$116.8 million per year on theEuropean Union after it found the EU beef hormone ban to be in violation of the WTOAgreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement).[45][46] In September 2009, the trade representatives from the US and EU signed a memorandum of understanding, which established a new duty-free import quota in the European Union for grain-fed, high-quality beef as part of a compromise solution.[46]
In July 2007, officials of thePeople's Republic of China seized US-produced pork for containing ractopamine residues.[47] Further shipments of Canadian ractopamine-fed pork were seized in September 2007.[48]
In June 2019, customs inspectors in China detected ractopamine in a shipment of Canadian pork products destined for Chinese consumption. The Chinese government thereupon suspended not only pork, but also beef imports from Canada.[49] Canadian Agriculture MinisterMarie-Claude Bibeau stated that the CRFPCP certificate was a forgery and called in theRCMP, while Canadian Public Safety MinisterRalph Goodale stressed that the federal government would vigorously defend Canadian meat producers.[49] It was also revealed that theCanadian Cattlemen's Association said in a statement that "We are fully confident in our meat production systems in Canada and the safeguards we have in place."[49] Meanwhile, holes were found in the CRFPCP programme because the meat packer at the centre of the controversy was a chilled butcher shop only.<what>[50] It was disclosed on 3 July that the Chinese authorities had discovered 188 falsified CRFPCP certificates.[51]
Ractopamine has been banned inTaiwan since 2006.[52] 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.[53] 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 amaximum residue level of 10 parts per billion of the additive.[54] The remaining restrictions have been an obstacle to the two nations signing a free-trade agreement, and theOffice of the United States Trade Representative (USTR)'s 2018 Trade Policy Agenda and 2017 Annual Report assert that these remaining restrictions "...are not based upon science..." and highlights their removal as among the main priorities for the US in its trade with Taiwan.[54] However, Taiwan plans to ease the import restrictions on US pork commencing January 1, 2021[55]
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).[56] 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.[57] On 30 December 2008, the Malaysian Veterinary Services Department quarantined 10 of the 656 pig farms inMalaysia, as the livestock were found to contain the banned chemical.[58][59]
The use of ractopamine inRussia is prohibited. On 6 June 2011, the RussianMinistry of Agriculture notified key meat import/exporters in Russia of a future prohibition of ractopamine in meat imported to Russia.[60]
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.[60]
A study was conducted to define the pharmacological response of humans to ractopamine. A single oral dose of 40 mg ofractopamine hydrochloride was given to human volunteers. The drug was rapidly absorbed; the meanblood 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 monosulfateconjugates, withractopamine monosulfate being the major metabolite present.[61]
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 astachycardia and other heart rate increases, tremor,headache,muscle spasm, orhigh arterial blood pressure.[62]
In swine, ractopamine is correlated with adverse effects, especiallyhyperactivity, trembling, and broken limbs, leading to censure by animal rights groups.[63]
In a conversation with Boulder Weekly newspaper,Colorado State University Professor of Animal ScienceTemple 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.[64] In the same column, she also opines that meat from ractopamine-treated animals may be tougher.[64]
Ractopamine use is a factor in the incidence ofdowner pigs, animals that are unable to move or stand.[65][66]
OralLD50 levels in mice and rats are 3547–2545 mg/kg body weight (male and female) and 474–365 (male and female), respectively.[67]
Mutation studies inprokaryotes andeukaryotes show that ractopamine is notmutagenic. However, the results of severalin 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.[68]
Ractopamine is not considered to be acarcinogen and not listed byIARC,NTP,ACGIH, orOSHA.[citation needed]
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.[69]
Skeletalmuscle 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.[citation needed]
Restlessness, apprehension, and anxiety were reported effects after the use of various beta-agonists, particularly after oral orparenteral 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.[68]
In cattle and swine tissue, it was found in 2007 that a procedure for the analysis of ractopamine residues in liver or muscle can be performed byhigh performance liquid chromatography (HPLC) with fluorescence detection. The confirmatory method include reversed-phase HPLC/electrospray ionization triple tandem quadrupole mass spectrometry. Thelimit of quantification of the drug using this LC/MS instrument was shown to be 1 ng/g (1 ppb).[70] In cattle, a 2018 Chinese study promoted the use of hair as an indelible test of feed containing ractopamine.[71]
Stuntman and comedianSteve-O 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 says "Based on how dangerous the study was, the more money you get."[72]
In the livestock production world, that's really the major goal of most livestock producers: to produce a product that's efficient," Bohrer said. "They have low input costs or lower input costs, so they're consuming less feed, and with less feed, they're producing meat that's both larger and leaner.
The Canadian Food Inspection Agency (CFIA) is responsible for certifying that pork products exported from Canada originate from pigs that have never been fed and/or exposed to ractopamine hydrochloride (to be referred to as ractopamine in this document). This document describes the general requirements for the production and certification of ractopamine-free pork products for export.
The facilities listed below have determined that they have met the requirements for enrollment in the Program by submitting Annex 7 of the Canadian Ractopamine-Free Pork Certification Program. Changes to this list will be made in as timely a manner as possible, but interested parties should always communicate directly with the facility to verify their status. List as of: May 22, 2019
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