Chemistry:Ractopamine

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Short description: Animal feed additive
Ractopamine
Ractopamine.svg
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 their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references
Tracking categories (test):

Ractopamine (/rækˈtɒpəmaɪn, -miːn/) is an animal feed additive used to promote leanness and increase food conversion efficiency in farmed animals in several countries, but banned in others. Pharmacologically, it is a phenol-based TAAR1 agonist and β adrenoreceptor agonist that stimulates β1 and β2 adrenergic receptors.[1][2] It is most commonly administered to animals for meat production as ractopamine hydrochloride.[3] It is the active ingredient in products marketed in the US as Paylean for swine, Optaflexx for cattle, and Topmax[4] for turkeys.[5] It was developed by Elanco Animal Health, a division of Eli Lilly and Company.

As of 2014, the use of ractopamine was banned in 160 countries,[6] including the European Union, China and Russia ,[7][8] while 27 other countries, such as Japan , the United States , South Korea , and New Zealand have deemed meat from livestock fed ractopamine safe for human consumption.[9][10][11]

Commercial ractopamine is a mixture of all four possible stereoisomers.[12] It is also a positional isomer of dobutamine, a related drug.

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 to murine (mouse or rat) TAAR1, a receptor protein (not necessarily in humans).[1] It is also an agonist to beta-adrenergic receptors.[2] 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 per animal, and improves feed efficiency by 10%.[13] In cattle on 28 January 2004 Elanco Animal Health made Optaflexx commercially available in the US. Optaflexx is a "medicated feed additive that is labeled only for use in steers or market heifers (not breeding heifers or bulls) during the last 28–42 days on feed."[14]

Regulation around the world

On 6 July 2012, the international reference standard Codex Alimentarius Commission narrowly approved the adoption of a maximum residue limit (MRL) of 10 parts per billion (ppb) for muscle cuts of beef and pork.[15] 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.[15] Consumers International, a world federation of consumer groups that represents 220 consumer organizations in 115 countries, strongly opposed the move.[15]

Ractopamine use in food animals is banned in over 160 countries.[16][17]

European Union

Ractopamine has not been allowed in the European Union, based on the 2009 EU's 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 children or people with cardiovascular disease, and that simply increasing the "uncertainty factor" built into the calculation as a safety factor would rapidly become arbitrary.[18][19]

Canada, United States, Mexico

Ractopamine use as a feed additive is authorized in the United States, Canada, and Mexico.[18] In the US, 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), or five times the standard set by the Codex 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.[20]

In 2015, the USDA approved of a new label, "No ractopamine — a beta-agonist growth promotant" to be used.[21]

The Canadian 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.[22][23][24] 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.[25]

Currently, the label for USDA 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.[26]

For Canadian domestic consumption of non-CRFPCP pork, ractopamine hydrochloride is permitted to be sold over the counter with applications in meal or pellet feed for finishing barrows and gilts (up to 10 mg/kg for last six weeks), confined finishing 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.[27]

Japan, South Korea

Japan , which had permitted its feed additive use at least until 2009,[18]: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.[28]

Taiwan

In October 2006, Taiwan banned ractopamine along with other beta-adrenergic agonists.[29] In a 2012 climb-down, its legislature passed amendments to its Act Governing Food Sanitation, authorising government agencies to set safety standards for ractopamine.[30] The Taiwanese Department of Health ultimately established an MRL of 10 ppb for ractopamine in beef on 31 July 2012.[31] The American 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";[9] 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 the Trans-Pacific Partnership trade pact.[32]

In 2020, restrictions on imports of US pork with ractopamine were relaxed, leading to protests.[33] A referendum took place on December 18, 2021 , deciding whether to ban the import of pork with ractopamine, and the ban was rejected.[34]

China, Russia

In 2013, Russia and China banned ractopamine in pork,[35] and Russia also in beef,[16] deeming it unfit for human consumption. Because the traditional Chinese diet embraces pig offal, 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 of tied trade access as a proxy for conflict has somewhat mitigated their reactions.[22][36][37]

New Zealand, Russia

In 2017, Russia banned imports of beef from New Zealand after finding ractopamine in New Zealand beef.[38] Ractopamine is not registered for use in cattle in New Zealand.

WADA proscription

In 2015, an 18-year-old female karateka (martial arts practitioner) from Egypt gave a urine sample in order for her drugs test to be administered. It was found that the urine contained too much ractopamine and the athlete was sanctioned with ineligibility for four years. The sole arbitrator from the Court of Arbitration for Sport said that ractopamine "is not specifically mentioned by name in the World Anti-Doping Code (“WADC”), but is an Other Anabolic Agent prohibited under S1.2 of the 2015 Prohibited List under the WADC... Athlete did not fulfil her burden of proof to establish the origin of the prohibited substance, [and thus] she has committed an anti-doping rule violation".[39]

In October 2017 at a World Anti-Doping Agency conference, it was suggested in relation with ractopamine[40]

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]

International disputes

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).[41][42] 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.[42]

China

In July 2007, officials of the People's Republic of China seized US-produced pork for containing ractopamine residues.[43] Further shipments of Canadian ractopamine-fed pork were seized in September 2007.[44]

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.[45] Canadian Agriculture Minister Marie-Claude Bibeau stated that the CRFPCP certificate was a forgery and called in the RCMP, while Canadian Public Safety Minister Ralph Goodale stressed that the federal government would vigorously defend Canadian meat producers.[45] It was also revealed that the Canadian 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."[45] 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>[46] It was disclosed on 3 July that the Chinese authorities had discovered 188 falsified CRFPCP certificates.[47]

Taiwan

Ractopamine has been banned in Taiwan since 2006.[48] 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.[49] 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.[50] 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 “...are not based upon science...” and highlights their removal as among the main priorities for the US in its trade with Taiwan.[50] However, Taiwan plans to ease the import restrictions on US pork commencing January 1, 2021 [51]

Malaysia

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).[52] 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.[53] 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.[54][55]

Russia

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.[56]

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.[56]

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.[57]

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.[58] 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.[citation needed]

Safety concerns

Target animal safety

In swine, ractopamine is correlated with adverse effects, especially hyperactivity, trembling, and broken limbs, leading to censure by animal rights groups.[59]

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.[60] In the same column, she also opines that meat from ractopamine-treated animals may be tougher.[60]

Ractopamine use is a factor in the incidence of downer pigs, animals that are unable to move or stand.[61][62]

Adverse effects

Acute toxicity

Oral -1">50 levels in mice and rats are 3547–2545 mg/kg body weight (male and female) and 474–365 (male and female), respectively.[63]

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.[64]

Carcinogenicity

Ractopamine is not considered to be a carcinogen and not listed by IARC, NTP, ACGIH, or OSHA.[citation needed]

Cardiovascular effects

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.[citation needed]

Musculoskeletal effects

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.[citation needed]

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.[64]

Analytical method for residues in livestock

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 by high performance liquid chromatography (HPLC) 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 (1 ppb).[65] In cattle, a 2018 Chinese study promoted the use of hair as an indelible test of feed containing ractopamine.[66]

In popular culture

Stuntman and comedian Steve-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."[67]

References

  1. ↑ 1.0 1.1 Liu, X; Grandy, DK; Janowsky, A (July 2014). "Ractopamine, a livestock feed additive, is a full agonist at trace amine-associated receptor 1". The Journal of Pharmacology and Experimental Therapeutics 350 (1): 124–9. doi:10.1124/jpet.114.213116. PMID 24799633. 
  2. ↑ 2.0 2.1 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. 
  3. ↑ Aroeira, C. N.; Feddern, V.; Gressler, V.; Molognoni, L.; Daguer, H.; Dalla Costa, O. A.; de Lima GJMM; Contreras-Castillo, C. J. (2019). "Determination of ractopamine residue in tissues and urine from pig fed meat and bone meal". Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment 36 (3): 424–433. doi:10.1080/19440049.2019.1567942. PMID 30785370. 
  4. ↑ Co, Elanco Animal Health. "Topmax - Elanco Animal Health Co: Veterinary Package Insert". https://vetlabel.com/lib/vet/meds/topmax/. [yes|permanent dead link|dead link}}]
  5. ↑ 5.0 5.1 LE BIZEC, Bruno (October 2017). "A GENERAL PERSPECTIVE ON THE USE OF WADA PROHIBITED SUBSTANCES FOR ANIMAL HUSBANDRY". WADA. https://www.wada-ama.org/sites/default/files/bruno_le_bizec_animal_husbandry_symposium_oct2017.pdf. 
  6. ↑ Pacelle, Wayne (July 2014). "Banned in 160 Nations, Why is Ractopamine in U.S. Pork? (Op-Ed)". Expert Voices: Op-Ed & Insights. Live Science. https://www.livescience.com/47032-time-for-us-to-ban-ractopamine.html. 
  7. ↑ Bottemiller, Helena (January 25, 2012). "Dispute over drug in feed limiting US meat exports". Bottom Line. http://bottomline.msnbc.msn.com/_news/2012/01/25/10220221-dispute-over-drug-in-feed-limiting-us-meat-exports. 
  8. ↑ Garina, Anastasia (11 December 2012). "Russia throws poisonous meat back to US". Pravda.ru. http://english.pravda.ru/business/companies/11-12-2012/123129-russia_usa_meat_imports-0/. 
  9. ↑ 9.0 9.1 "The Facts about U.S. Beef and Ractopamine". American Institute in Taiwan. http://www.ait.org.tw/en/officialtext-ot1201.html. 
  10. ↑ AIT- American Institute in Taiwan: 'The Facts about U.S. Beef and Ractopamine' (archived) Accessed January 21, 2018
  11. ↑ Environmental Risk Management Authority (22 August 2006). "Environmental Risk Management Authority Decision - Application HSR05114 "PAYLEAN: to import and release this granular premix for use as a feed additive for pigs "". https://www.epa.govt.nz/assets/FileAPI/hsno-ar/HSR05114/HSR05114.doc. 
  12. ↑ 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). http://www.scielo.br/scielo.php?pid=s1516-89132012000300016&script=sci_arttext. Retrieved 9 December 2014. 
  13. ↑ Apple, JK; Rincker, PJ; McKeith, FK et al. (June 2007). "Meta-analysis of the ractopamine response in finishing swine". The Professional Animal Scientist 23 (3): 179–196. doi:10.15232/S1080-7446(15)30964-5. http://pas.fass.org/content/23/3/179.full.pdf. 
  14. ↑ "The Facts about Optaflexx™: Ractopamine for Cattle". AgriLIFE Extension (Texas A&M System) 12–10. https://aglifesciences.tamu.edu/animalscience/wp-content/uploads/sites/14/2012/04/beef-optaflexx.pdf. Retrieved 2019-06-26. 
  15. ↑ 15.0 15.1 15.2 Bottemiller, Helena (July 6, 2012). "Codex Adopts Ractopamine Limits for Beef and Pork". Food Safety News. http://www.foodsafetynews.com/2012/07/codex-votes-69-67-to-advance-ractopamine-limits-for-beef-and-pork/#.VEZ1xFfGuSo. 
  16. ↑ 16.0 16.1 Quilty, Simon (March 27, 2013). "Russian Ban On Ractopamine Boosts Brazilian Exports". Penton. http://beefmagazine.com/foreign-trade/russian-ban-ractopamine-boosts-brazilian-exports. 
  17. ↑ Pacelle, Wayne; Ceo 2014-07-26t07:47:28z (26 July 2014). "Banned in 160 Nations, Why is Ractopamine in U.S. Pork? (Op-Ed)" (in en). https://www.livescience.com/47032-time-for-us-to-ban-ractopamine.html. 
  18. ↑ 18.0 18.1 18.2 "EU opposes ractopamine limit". 8 July 2012. https://www.foodnavigator.com/Article/2012/07/09/EU-opposes-ractopamine-limit. 
  19. ↑ "Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) on a request from the European Commission on the safety evaluation of ractopamine". The EFSA Journal 1041: 1–52. 2009. http://www.efsa.europa.eu/en/efsajournal/pub/1041. 
  20. ↑ Smith, M. (2014). "Veterinary Drugs Residues: Anabolics". Encyclopedia of Food Safety. pp. 55–62. doi:10.1016/b978-0-12-378612-8.00244-4. ISBN 9780123786135. 
  21. ↑ "A Muscle Drug For Pigs Comes Out Of The Shadows". NPR. https://www.npr.org/sections/thesalt/2015/08/14/432102733/a-muscle-drug-for-pigs-comes-out-of-the-shadows. 
  22. ↑ 22.0 22.1 "Why China has a beef with Canadian meat exports". CBC. 27 June 2019. https://www.cbc.ca/news/business/china-pork-beef-ban-1.5190574. 
  23. ↑ "What is ractopamine, the drug banned in China but permitted in Canadian pork?". Global News, Corus Entertainment Inc. Corus News. 26 June 2019. https://globalnews.ca/news/5434060/ractopamine-canada-pork-china-safety/. "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." 
  24. ↑ "Annex T: Canadian Ractopamine-Free Pork Certification Program (CRFPCP)". Canadian Food Inspection Agency. 2019-06-03. http://www.inspection.gc.ca/food/exporting-food/specific-requirements/meat/crfpcp/eng/1434119937443/1434120400252. "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." 
  25. ↑ "Commercial Feed Facilities Enrolled in the Canadian Ractopamine-Free Pork Certification Program". Canadian Food Inspection Agency. 22 May 2019. http://www.inspection.gc.ca/animals/feeds/inspection-program/canadian-ractopamine-free-pork-certification-progr/eng/1437148393953/1437148949738. "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" 
  26. ↑ "7 CFR 205.603 - Synthetic substances allowed for use in organic livestock production". US Code of Federal Regulations › Title 7 › Subtitle B › Chapter I › Subchapter M › Part 205 › Subpart G. https://www.law.cornell.edu/cfr/text/7/205.603. 
  27. ↑ "Ractopamine hydrochloride (RAC) – Medicating Ingredient Brochure". Canadian Food Inspection Agency. August 2018. http://www.inspection.gc.ca/animals/feeds/medicating-ingredients/mib/mib-82/eng/1331129686310/1331129741124. 
  28. ↑ "Description of the Ractopamine Standards in Livestock Products of Different Countries". Food and Drug Administration; Ministry of Health and Welfare. 23 March 2012. http://www.fda.gov.tw/EN/newsContent.aspx?id=8524&chk=ceb0dd88-ff44-43a9-96c9-b4b614ceb0dd&param=pn%3D9%26cid%3D118%26cchk%3D5bad4865-9037-437c-a198-9e673d42dd81. 
  29. ↑ "行政院農業委員會公告 Executive Yuan notice" (in zh). Taiwan Council of Agriculture. 11 October 2006. http://gazette.nat.gov.tw/EG_FileManager/eguploadpub/eg012193/ch07/type1/gov62/num16/Eg.htm. 
  30. ↑ "Legislature votes to allow ractopamine". Taipei Times. 26 July 2012. http://www.taipeitimes.com/News/front/archives/2012/07/26/2003538652. 
  31. ↑ "DOH experts choose ractopamine residue cap for beef imports". Taipei Times. CNA. 2 August 2012. http://www.taipeitimes.com/News/taiwan/archives/2012/08/02/2003539254. 
  32. ↑ Lin, Enru (December 30, 2015). "Taiwan's pig farmers threaten large-scale protest over US pork". Asia News Network. http://www.asianews.network/content/taiwans-pig-farmers-threaten-large-scale-protest-over-us-pork-6518. 
  33. ↑ "Inflatable pig flies over Taiwan pork protest". BBC.com. https://www.bbc.com/news/av/world-asia-55037852. 
  34. ↑ "「反萊豬」公投是什麼？正反方怎麼說？公投第18案懶人包一次看" (in zh). Yahoo News. 2021-11-22. https://tw.news.yahoo.com/%E5%85%AC%E6%8A%95-2021-%E5%8F%8D%E8%90%8A%E8%B1%AC-%E5%85%AC%E6%8A%95%E7%AC%AC-18-%E6%A1%88-%E5%9C%8B%E6%B0%91%E9%BB%A8-%E6%9E%97%E7%82%BA%E6%B4%B2-051234369.html. Retrieved 2021-12-09. 
  35. ↑ Felberbaum, Michael (June 14, 2013). "Smithfield Foods' profit falls 63%". USA Today. Associated Press. https://www.usatoday.com/story/money/business/2013/06/14/smithfield-foods-4q-profit-falls-63/2423401/.  s.a. Smithfield Foods
  36. ↑ "Glenn Kennedy - Trade". 2012-07-31. https://www.panaftosa.org/copaia6/dmdocuments/COPAIA%206_Glenn%20Kennedy1.pdf. 
  37. ↑ Devitt, Polina; Mano, Ana (31 October 2018). "Russia to resume some beef and pork imports from Brazil". Reuters.com. https://www.reuters.com/places/brazil/article/us-russia-brazil-meat/russia-to-resume-some-beef-and-pork-imports-from-brazil-idUSKCN1N52Q9. 
  38. ↑ "Russia to ban New Zealand beef" (in en-NZ). The New Zealand Herald. 2017-02-03. ISSN 1170-0777. https://www.nzherald.co.nz/business/news/article.cfm?c_id=3&objectid=11794354. 
  39. ↑ "Arbitration CAS 2016/A/4563 World Anti-Doping Agency (WADA) v. Egyptian Anti-Doping Organisation (EGY-NADO) & Radwa Arafa Abd Elsalam, award of 16 January 2017". Court of Arbitration for Sport. 16 January 2017. https://jurisprudence.tas-cas.org/Shared%20Documents/4563.pdf. 
  40. ↑ "OUTCOMES OF THE CHINADA-WADA INTERNATIONAL SYMPOSIUM ON FOODSTUFF RESIDUES AND IMPACT ON ANTI-DOPING ANALYSIS IN SPORT". WADA. October 2017. https://www.wada-ama.org/sites/default/files/outcomes_chinada-wada_symposium_oct2017.pdf. 
  41. ↑ "DS26: European Communities — Measures Concerning Meat and Meat Products (Hormones)". World Trade Organization. https://www.wto.org/english/tratop_e/dispu_e/cases_e/ds26_e.htm. 
  42. ↑ 42.0 42.1 Office of the United States Trade Representative (March 2017), 2017 National Trade Estimate Report on Foreign Trade Barriers, pp. 148–149, https://ustr.gov/sites/default/files/files/reports/2017/NTE/2017%20NTE.pdf#page=156 
  43. ↑ "China fights back, goes after U.S. meat", USA Today, July 14, 2007.
  44. ↑ "China stops imports from Canadian pork plant over banned additive", Canada Press (2007-09-19) [|permanent dead link|dead link}}]
  45. ↑ 45.0 45.1 45.2 "Canada launches probe into false documents as China halts imports of meat". CBC. 26 June 2019. https://www.cbc.ca/news/politics/carr-trade-china-1.5190373. 
  46. ↑ "Frigo Royal, Quebec company named in pig-drug scandal, may be victim of fraud". Toronto Star Newspapers Ltd.. 28 June 2019. https://www.thestar.com/business/2019/06/28/frigo-royal-quebec-company-named-in-pig-drug-scandal-may-be-victim-of-fraud.html. 
  47. ↑ "Ottawa croit que la Chine reprendra bientôt les importations de viande canadienne". Société Radio‑Canada. 3 July 2019. https://ici.radio-canada.ca/nouvelle/1208833/economie-viande-agriculture-chine-canada-exportation. 
  48. ↑ Lin, Hermia (August 22, 2007). "Swine farmers get rowdy over ractopamine issue". Taiwan News. http://www.taiwannews.com.tw/etn/news_content.php?id=506889&lang=eng_news&cate_img=49.jpg&cate_rss=news_Society_TAIWAN. 
  49. ↑ "Taiwanese farmers urge continuation of US pork import ban". Associated Press. August 21, 2007. http://english.sina.com/taiwan_hk/1/2007/0821/122485.html. 
  50. ↑ 50.0 50.1 "US report identifies pork ban as 'barrier' to trade". The Taipei Times. Central News Agency. 2 March 2018. http://www.taipeitimes.com/News/front/archives/2018/03/02/2003688519. 
  51. ↑ "Pig Guts Fly as Taiwan Lawmakers Brawl Over US Pork Imports". BBC. 2020-11-27. https://www.bbc.co.uk/news/world-asia-55097091. 
  52. ↑ Fifteenth A Schedule, Table 1, Maximum Permitted Proportion of Drug Residues in Food.
  53. ↑ "Beta-agonists hog the limelight". The Star. November 5, 2006. http://thestar.com.my/health/story.asp?file=/2006/11/5/health/20061105091851&sec=health. 
  54. ↑ "Vet Dept seals 10 pig farms". The Star. December 31, 2008. http://www.thestar.com.my/news/story.asp?file=/2008/12/31/nation/2917634&sec=nation. 
  55. ↑ "10 pig farms under quarantine". The Star. December 30, 2008. http://thestar.com.my/news/story.asp?file=/2008/12/30/nation/20081230193900&sec=nation. 
  56. ↑ 56.0 56.1 Seattle, Food Safety News 1012 First Avenue Fifth Floor; Washington 98104-1008 (2013-02-01). "Russia to Ban U.S. Meat Over Ractopamine Residues This Month" (in en-US). https://www.foodsafetynews.com/2013/02/russia-to-ban-u-s-meat-over-ractopamine-residues-this-month/. 
  57. ↑ RACTOPAMINE (addendum). WHO FOOD ADDITIVES SERIES: 53
  58. ↑ "Safety evaluation of ractopamine EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP)". EFSA Journal 7 (4): 1041. 7 April 2009. doi:10.2903/j.efsa.2009.1041. http://www.efsa.europa.eu/en/efsajournal/pub/1041. Retrieved 2013-03-21. 
  59. ↑ "Dispute Over Drug in Feed Limiting US Meat Exports". The Fern. January 25, 2012. http://thefern.org/2012/01/dispute-over-drug-in-feed-limiting-u-s-meat-exports/. 
  60. ↑ 60.0 60.1 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. http://www.boulderweekly.com/article-13657-oops-we-forgot-to-study-that.html. 
  61. ↑ Paula Crossfield (January 25, 2012). "Controversial Animal Drug at the Heart of International Trade Dispute". Huffington Post. https://www.huffingtonpost.com/paula-crossfield/controversial-animal-drug_b_1230713.html. 
  62. ↑ American Veterinary Medical Association (AVMA) (May 9, 2014). "Use of β-Adrenoreceptor Agonists". AVMA. https://www.avma.org/.../Welfare%20Implications%20of%20the%20Use%20of%20B-.... 
  63. ↑ "Safety evaluation of ractopamine". EFSA Journal 7 (4): 10. 2009. doi:10.2903/j.efsa.2009.1041. 
  64. ↑ 64.0 64.1 "Ractopamine (addendum) (JECFA 53, 2004)". http://www.inchem.org/documents/jecfa/jecmono/v53je08.htm. 
  65. ↑ Sakai T et al. (2007). "Determination method for ractopamine in swine and cattle tissues using LC/MS". Shokuhin Eiseigaku Zasshi 48 (5): 144–147. doi:10.3358/shokueishi.48.144. PMID 18027547. 
  66. ↑ Liu, Jia; Tang, Chaohua; Long, Ruijun; Zhang, Kai; Han, Yunsheng; Zhao, Qingyu; Wang, Hongliang; Zhao, Fuzhong et al. (2019). "The use of hair as a long-term indicator of low-dose β 2 agonist treatments in cattle: Implications for growth-promoting purposes monitoring". Drug Testing and Analysis 11 (6): 745–751. doi:10.1002/dta.2551. PMID 30474322. 
  67. ↑ YouTube title: Joe Rogan Experience #717 - Steve-O. November 3, 2015. Retrieved November 16, 2017.

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