Study on Residue Elimination of 14C-Clenbuterol Hydrochloride in Pigs

Study on Residue Elimination of 14C-Clenbuterol Hydrochloride in Pigs

Clenbuterol is a beta-stimulant that can be added to feed to increase the lean percentage of several livestock including pigs. Because it is available on the black market, Clenbuterol is illegally used for livestock in Europe, the United States, and Asia. In some countries, illegal use of residues in clenbuterol's cattle tissue has caused human poisoning. Recently, it was reported that people have consumed pork containing clenbuterol to cause poisoning. Although 14C-residues of clenbuterol hydrochloride residues and clenbuterol residues in bovine and broiler chickens have been reported, there have been no reports of 14C-clenbuterol or nonradioactive clenbuterol. Disposal and elimination rules in pigs. Radioactive markers serve as the basis for the study of residual elimination rules because the dynamics of the prototype drug and its metabolites are easy to estimate and the percentage of the original drug in the total residue can also be estimated. Purpose of the experiment: 1 Determination of 1ppm14C-clenbuterol hydrochloride in pigs treated in feed; 20, 3, and 7 days slaughter after slaughter, 14C-clenbuterol in swine edible tissues Distribution of non-edible tissue; Concentration of clenbuterol in liver, kidney, muscle, fat, and lung after 30, 3, and 7 days of drug holiday. First, after testing, 9 head warts and 9 sows were purchased, immediately weighed, eared, dewormed, and then divided into 3 groups of 3 warthogs and 3 sows. Before the experiment, the animals were fed for two weeks to adapt to the experimental environment. During adaptation, animals are trained in metabolic cages until they can stay in metabolic cages overnight. At the same time, animals were trained to feed and fed two times a day at a dose of 0.5-0.6 kg per head. After 30 minutes of feeding, you can usually eat completely. Two weeks later, in a formal experiment, 1 ppm of 14C-clenbuterol hydrochloride was added to the feed for 7 consecutive days, and 3 feedings were started. Feeding amount was 0.5 kg/head, and then 0.5 kg of feed was observed for each pig. Pigs cannot eat enough. As a result, the subsequent feed increase to 0.6 kg/head. By calculation, in a 7-day dosing period, a total of 81,598 g of feed supplemented with 14C-clenbuterol hydrochloride was consumed per pig. The total dose of 14C-clenbuterol hydrochloride consumed per pig was an average of 76.1 μCi, ie 8.3. Mg clenbuterol. 0, 3, and 7 days after discontinuation, 1 piglet and 1 sow were randomly selected for slaughter from each experimental group, ie, 3 piglets and 3 sows were slaughtered during each drug withdrawal period. After slaughter, various tissue samples were collected, such as liver, kidney, lung, spleen, gastrointestinal tract, skin, brain, eyes, heart, bile, fat, muscle, cryopreservation, and the samples were analyzed and processed. 2. During the drug withdrawal period, the mean starting weight, final body weight, total weight gain, or average daily weight gain of warty pigs and sows were not significantly different (p>0.2). See Table 1 (omitted). The drug withdrawal period has a significant effect on the final body weight and total weight gain (P urine, feces, carcasses, and viscera 14C-clenbuterol hydrochloride recovery rates are shown in Table 2 (abbreviated). Pigs and sows in 14C- The total recoveries of clenbuterol hydrochloride were 95.1% and 99.3%, respectively.14C-clenbuterol hydrochloride had the highest urinary excretion rate (55%-75.4%), followed by manure. During the withdrawal period, 14C in the sow dung - Clenbuterol hydrochloride content was significantly greater than that of pig manure (p0.11). Due to the structure of the metabolic cage, the urine and feces of the sow were not completely separated, but the urine and feces of the piglets were easily separated. The difference in the elimination of 14C-clenbuterol in the urine and feces of sows and pigs may be due to the design of the metabolic cage rather than to the physiology of the pig. After 3 days of withdrawal, 14C-clenbuterol hydrochloride dropped to a total of 14C in the carcasses. At 2% of the dose, the 14C-clenbuterol hydrochloride content in the carcass, the 14C-clenbuterol hydrochloride content in the viscera or the total recoveries of the 14C-clenbuterol hydrochloride radioactivity were not related to gender. The total residual amount (ppb) of 14C-clenbuterol hydrochloride is shown in Table 3. The lung is an edible tissue because it was reported that some people had consumed it. Clenbuterol poisoning occurred in swine lungs, and 14C-clenbuterol residues in edible tissues were not related to sex. During the zero drug withdrawal period, clenbuterol residue in liver and lung was the largest, exceeding that in kidneys. 2 times, about 15 times that of fat and muscle. After 3 days of withdrawal, the total residual amount of clenbuterol in the liver is the largest, and the residual concentrations in lung, kidney, and adipose tissue are nearly equal, and the total residual muscle mass is still approximately It is 1/15 in the liver. After 7 days of drug withdrawal, the total residual clenbuterol in fat is approximately 25% of the zero drug withdrawal period. The total clenbuterol residues in kidney, lung, and muscle are approximately 0%, 5%, 2%, and 6% of the zero drug withdrawal period.The concentration of clenbuterol in the edible tissue and the percentage of the clenbuterol remaining in the 14C-clenbuterol residual Table 4. In the zero holiday period, the ratio of clenbuterol in 14C-clenbuterol remains greater than 5% in fat, kidney, and muscle, and the ratio of total residual clenbuterol in liver in liver. At 42%, the ratio of clenbuterol in fat, kidney, and muscle decreased significantly after 3 days of withdrawal, but it was not as low as in liver or lung. Obviously, after 7 days of drug withdrawal, the ratio of clenbuterol in liver and lungs dropped to 15% to 30%, and the content of clenbuterol in fat or muscle was less than 0.25 ppb. Clenbuterol is easily detected in the lungs, and during the zero holiday period, the concentration of clenbuterol in the lungs is greatest in all edible tissues, but after 7 days of withdrawal, the clenbuterol in the lungs The concentration of clenbuterol in the edible tissues was not related to the sex during the drug withdrawal period, which was lower than that in the liver.Sex did not affect the total clenbuterol residues in non-edible tissues except for blood after 3 days of drug withdrawal. In any withdrawal period, the total residual clenbuterol in the eye is above 200 ppb, and 14C-clenbuterol residues in the blood are less than in other unusable food tissues. Clenbuterol is present in both, indicating that at least part of clenbuterol or its metabolites is excreted through the bile. 3. Discussion 14C-Clenbuterol hydrochloride excretion data from urine showed that Clenbuterol is rapidly and widely absorbed in pigs. The absorption rate of 14C-clenbuterol hydrochloride in warthogs is at least 73.8% and that in sows is at least 64%. For gilts, 64% is the lowest estimate because its urine and feces cannot be completely separated when collected. The elimination of bile in warts and sows by clenbuterol had no effect on the elimination of 14C-clenbuterol in the feces because no flow rate of bile was measured during the 7-day dosing period. However, the presence of clenbuterol in bile during slaughter suggests that the elimination of bile in clenbuterol has a potential impact on the elimination of 14C-clenbuterol in feces. Clenbuterol is well-absorbed in domestic animals and humans, and its bioavailability compared to other β-stimulants is so high that it poisons pork containing clenbuterol. Zimmer (1976) confirmed that humans take 20 μg of 14C-clenbuterol hydrochloride at the peak concentration. In the plasma, clenbuterol in the plasma accounted for 75% of the total 14C-clenbuterol hydrochloride. The fact that clenbuterol is highly bioavailable for oral administration is important for estimating that consumers have consumed clenbuterol-containing tissues. The animal tissue that causes human poisoning contains a large amount of clenbuterol. Martinez-Navarro (1990) reported that the residual amount of clenbuterol in yak liver was 161-291 ppb. Pulce et al. (1991) reported that clenbuterol residues in calf's liver ranged from 375 to 500 ppb. Salleras (1995) reported that clenbuterol residues in yak livers ranged from 19 to 5395 ppb. In addition, Maistro et al. (1995) reported that clenbuterol residues in yak muscles were 500 ppb. Brambilla et al. (1997) reported that clenbuterol residues in “meat samples” were 450 ppb. Sporan et al. (1998) reported that it is probably the most serious. He reported that the residual amount of clenbuterol in the “meat” of contaminated carcasses was 800-7400 ppb. This meat sample was from a meat stall selling Meat causes poisoning. Given that clenbuterol has a bioavailability of 75% in the human body, consumption of 267 grams of meat containing 100 ppb Cromentiogen can reach a therapeutic dose of 20 μg. In addition, if the meat contains 500 ppb of clenbuterol, a toxic reaction will occur if only 53 grams is consumed. The stability of clenbuterol under conventional cooking conditions and its high bioavailability in the human body make meat products the most suitable medium for delivering clenbuterol treatment or toxic doses. The therapeutic dose of clenbuterol in children is 5 μg, so children can reach a therapeutic dose of 5 μg by eating 67 g of tissue containing 100 ppb of clenbuterol. Due to the high bioavailability of clenbuterol for oral administration, the dosage for adults who take clenbuterol without any reaction is only 2.5 μg, and the mean dose for a non-response is 0.042 μg/kg body weight in terms of an average body weight of 60 kg or 42ng/kg body weight. In the United States, clenbuterol is approved only for non-edible horses. Considering food safety, veterinarians are not allowed to use clenbuterol off-label. Because the United States does not approve clenbuterol for food animals, the FDA's Veterinary Drugs Center has not established its residue limits. However, in Europe clenbuterol can be used for early delivery of cattle and treatment of animal bronchial spasm or airway blockage. European regulations require the use of clenbuterol for food animals for a 28-day drug holiday and a maximum residue limit (MRL) of 0.5 ppb in all edible tissues. The European MRL was applied to this experiment. We could easily calculate that 1 ppm of clenbuterol was added to pig feed for 7 consecutive days. The clenbuterol residues in all edible tissues greatly exceeded the European MRL. During the zero holiday period, the residual amount of clenbuterol in fat was the lowest among all edible tissues, but it was more than 30 times that of Europe's MRL. After 7 days of drug withdrawal, clenbuterol residues in fat, muscle, and kidneys fall below the MRL in Europe, but clenbuterol residues in the liver still exceed Europe's MRL by 30 times. Lungs are not considered edible in Europe. More than 60 times the European MRL. Although these data only clarified the residual elimination rule of 1 ppm clenbuterol added to feed administration, it could not reflect the elimination rule of other concentrations of clenbuterol in pigs. The significant difference in the residual data of clenbuterol illegally used in animals (front) indicates that it is impossible to predict the illegal use of clenbuterol. Since it is impossible to predict the illegal use of clenbuterol, it is difficult to predict the illegal elimination of clenbuterol for use in animals. Therefore, illegal use of clenbuterol in animals and its carcasses cannot be consumed by consumers. The choice of 1 ppm of clenbuterol added to feed was based on reports that adding this concentration of clenbuterol was sufficient to increase lean meat. According to the animal body weight conversion dose, the dose of this experiment pig (starting at 50μg/kg body weight, 42μg/kg body weight at the later period of administration) greatly exceeds the recommended therapeutic dose for intravenous or internal administration (0.8μg/kg body weight, 10μg 3 times a day, also greatly exceeds the commonly used 10 times the therapeutic dose (16 μg/kg body weight) of the growth promoting dose. However, the content of clenbuterol in animal products that cause human poisoning indicates that the illegally used growth promoting dose is significantly greater than 10 times the therapeutic dose. In this experiment, the total residue of 14C-clenbuterol in the liver was 300 ppb during the zero drug withdrawal period, and the clenbuterol drug accounted for only 41% (120 ppb). Clenbuterol residues in edible tissues that cause human poisoning are significantly greater than 120 ppb. The residual amount of clenbuterol in the experimental animal's liver ranged from approximately 30 to 300 ppb, depending on the animal species, dose, and duration of administration. In conclusion, the residual amount of clenbuterol in the experimental animals was lower than that in animal tissues that caused human poisoning. This may be due to the fact that the amount of animal used in this experiment was lower than the dose used illegally. The clenbuterol residue in the eyes is the longest and longest. Seven days after the drug was withdrawn, the total residue of 14C-clenbuterol in the eyes remained above 200 ppb, indicating that the eye was the best target for monitoring the illegal use of clenbuterol. Clontro's elimination in the eyes was slow, so the eyes played a big role in monitoring the illegal use of Clenbuterol. Any off-tag use of clenbuterol as a human or animal growth promoter is illegal and potentially harmful to humans. In the last decade, illegal use of clenbuterol as a growth promoter has been reported in Europe, Asia, North America, and Central America. Although Europe has banned the use of anabolic hormones in food animals, Europe has still detected a large number of illegal use of clenbuterol. The ban does not prevent the illegal use of clenbuterol and other beta-stimulants. Animal foods still have dangerous residue problems. The constant case of poisoning seems to confirm Meyer's (1991) conclusion: The ban not only failed to solve the existing problems, but also provoked new security issues. IV. Summary 1 ppm clenbuterol is added to pig feed for growth, and human consumption of pig or pig lung is sufficient to cause poisoning. There is no formal agency in the world to approve clenbuterol as a feed additive for animal growth promotion. Use outside the label as a growth promoter is illegal and can cause meat products that are harmful to humans. According to the label instructions for treatment, no one has confirmed that clenbuterol appears to be insecure residues in food animals.