User:570lil/sandbox

=Ractopamine=

Ractopamine is pharmacologically a beta-adrenoceptor agonist (see Beta-adrenergic agonist,beta agonist). It is neither a hormone, antibiotic nor genetically modified organism. 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 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 kilograms of additional lean pork and improves feed efficiency by 10%. In steers and heifers, ractopamine use increases hot carcass weight by about 5.5 kilograms and 5 kilograms, respectively.

Mode of action
When used as a food additive, ractopamine added to feed can be distributed via the blood to the muscle tissues, where it will bind to specific beta receptors in the muscle cell membranes. Cascade of event will then be initiated to increase protein synthesis, which results in increase in muscle fiber size.

Metabolism
Ractopamine has been shown to be absorbed, distributed and eliminated rapidly in pigs, cattle, laboratory animals and primates. It is excreted mainly via urine and feces in the original form or its metabolites. The metabolites, which were formed by conjugation of the hydroxyl group, are identified to be monoglucuronides of ractopamine. Significant biliary excretion occurs, which is indicative of first pass metabolism. The metabolic fate of ractopamine is similar among various species.

Regulations of ractopamine around the world
Ractopamine is currently allowed to be used as growth promoters to increase lean muscle mass in pigs and cattle in around 25 countries worldwide, including USA, Canada, Korea, Mexico and Indonesia. In the USA, 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. In Canada, ractopamine is allowed in meal or pellet feed for finishing barrows, gilts, finishing beef cattle and finishing heavy turkeys (toms and hens) only. The maximum residues limit of ractopamine is 50 ppb and 10 ppb in the USA and Japan, respectively.

On the contrary, over 150 countries, including EU, China and Taiwan, have prohibited the use of ractopamine as leanness-enhancing agent. In Taiwan, shipments of beef from the USA are reported to be rejected by the health authority, due to positive result for ractopamine tested with the beef. There is still no global consensus on the safety of the feed additive

Human use and route of exposure
Ractopamine is not for use in humans for any medical purposes. The more probable route of exposure to ractopamine in humans is through the consumption of food animals which have been fed ractopamine and its residue remains.

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 the volunteers. Ractopamine was rapidly absorbed. The mean half-life was around 4 h. Ractopamine was not detected in plasma 24 hrs after dosing. It was shown that <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.

Safety concerns
570ajd (talk) 17:48, 21 November 2011 (UTC)Has a risk assessment been done on ractopamine?

Target animal safety
Ractopamine is safe for finishing pigs heavier than 240 pounds when administered in the diet at concentrations up to 10 ppm and fed for up to 35 days. However, there was an increase in the number of ractopamine hydrochloride-treated animals exhibiting signs of injury during the final drive to slaughter. (FDA)

Human safety
As codified under 21 CFR 556.570, the safe concentrations for total residues of ractopamine hydrochloride are: 0.25 ppm in muscle, 0.75 ppm in liver, and 1.5 ppm in kidney and fat. The acceptable daily intake for total residues of ractopamine is 1.25 micrograms ractopamine hydrochloride per kilogram of body weight per day. The human safety of meat products derived from food animals fed ractopamine has been confirmed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2004, 2006, and 2010 and by 27 regulatory authorities from around the world.

Acute toxicity
Oral LD50 in mouse and rat are found to be 3547-2545 mg/kg bw (male and female) and 474-365 (male and female), respectively.

Genotoxicity and mutagenicity
Mutation studies in prokaryotes and eukaryotes show that ractopamine is non-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.

Carcinogenicity
Ractopamine is considered not to be a direct carcinogen. It is not listed by IARC, NTP, ACGIH, or OSHA. The induction of benign leiomyomas (tumors of smooth muscle) in mice and rats can possibly be due to a general feature of beta-adrenergic activity of ractopamine.

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.

Musculo-skeletal 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 low-twitch muscle groups of the extremities, and its severity varies greatly between individuals. No such effects were recorded at the NOEL determined in the toxicological studies conducted in laboratory animals given ractopamine or in the study in humans on cardiovascular effects of ractopamine.

Behavioural changes
Feelings of restlessness, apprehension, and anxiety were reported side-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. It is unclear whether long-term treatment with these drugs results in the development of tolerance to these adverse effects.

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 (HPLC) with fluorescence detection. The confirmatory method include reversed-phase HPLC/ electrospray ionization triple tandem quadrupole mass spectrometry (LC/ESI-MS-MS). The limit of quantification (LOQ) of the drug using LC/MS was shown to be 1 ng/g.

Comparision of Ractopamine and Clenbuterol
Similar to Ractopamine, Clenbuterol is a growth promoting compound belonging to the beta-agonist family. It is known to have the effect of enhancing weight gain and proportion of muscle to fat. However, clenbuterol is known to have a much longer half-life in blood than ractopamine and thus has a greater potential for bioaccumulation.

Clenbuterol is reported to induce unintended side effects on humans, such as increased heart rate, muscular tremors, headache, nausea, fever, and chills. The US FDA has concluded these side effects to be unacceptable. Its use has been prohibited in almost all countries, including the USA, Canada, Taiwan, Hong Kong. On the contrary, ractopamine is allowed to be used at the recommended concentrations in food animals for growth promotion in some countries such as the United States, Canada, Australia. 570ajd (talk) 17:52, 21 November 2011 (UTC)http://www.fsis.usda.gov/oa/background/clenbute.htm This is an older article, but maybe some useul information. 570ajd (talk) 17:52, 21 November 2011 (UTC)Do you have numbers of how many people affected?