Withdrawal Time

Florfenicol (2) has been approved in Japan for the treatment of pseudo-tuberculosis caused by Pasteurellapiscicida and streptococcosis m. yeUowtail fish. The recommended dose is 10 mg/kg for up to one week and the drug withdrawal time is five days after cessation of treatment. Florfenicol is active in bovine respiratory disease caused by Pasteurella species and mastitis caused by Staphylococci and Streptococci. It is also effective in neonatal cohbacillosis caused by E. coli. The drug is being developed worldwide by Schering-Plough Animal Health for the treatment of aquatic and bovine diseases. 

Withdrawal time is the period of time that must pass after the last treatment or exposure to a certain dmg, chemical, or pesticide before an animal can be consumed. None has been estabUshed if there is no notation. 

Anesthetics. Tricaine is the only currendy registered anesthetic and requites a 21-day withdrawal time (9,11). The withdrawal time for MS-222 is of special concern to PDA when the broodfishes of salmon or other species are taken immediately after spawning for pet or human food. Both carbon dioxide and sodium bicarbonate [144-55-8] have also been used as anesthetics however, both chemicals are difficult to use with consistent results and involve long induction and recovery periods (9). 

Product(trade oraltemative name) CAS Regis tryNumber Molecularformula Withdrawal time... 

No official withdrawal time has been established for this product under the proposed investigational use. 

Withdrawal times if animal is to be slaughtered for human consumption or produces eggs or milk... 

As long as hormones are used as directed (as pellets or as prescribed ear implants) and proper treatment and withdrawal times are adhered to, the probability of unwanted residues is relatively low. If hormones are not correctly administered, there is little possibility of predicting either the presence or the concentration of residues in the food product. 

A withdrawal time is the time from the last availability of a medicated feed to an animal until its slaughter. This time is set so that the level of residues drops below the lower level of detectability of the antibiotic and is based on a tissue residue study in which animals are dosed with the highest level of drug in the feed for the longest time permitted. The method of analysis must be sufficiently sensitive to detect fractions of a microgram per gram in tissue. 

There is an additional protection against residues, because antibiotics in meat tend to be destroyed by cooking.. For example, Broquist and Kohler found that chicken breast muscle containing 12 parts per million of chlortetracycline had 0.14 parts per million after roasting at 230 C for 15 minutes and no detectable amounts after half an hour. The original level of 12 ppm was about 60 times as high as would be produced by 400 ppm in the animal feed, without a withdrawal period W. The UK Swann Committee reported that the only possible effect of residues on consumers arose from penicillin in milk from cows treated for udder infections in which the withdrawal time for the antibiotic had not been observed. Cases of skin rashes were reported from the consumption of such milk by sensitive patients. The Committee commented that "there are no known instances in which harmful effects in human beings have resulted from antibiotic residues in food other than milk" ( ) ... 

With respect to veterinary medicines, the US-FDA establishes tolerances to include a safety factor to assure that the drug will have no harmful effects on consumers of the food product. The US-FDA first determines the level at which the dmg does not produce any measurable effect in laboratory animals. From this, the US-FDA determines an acceptable daily intake (ADI), and the drug tolerance and withdrawal times are then determined so that the concentrations of dmg residues in edible tissues are below the ADI. Depending on the dmg, safety factors of between 100-fold to 2000-fold are included in the calculations used to set the tolerances. 

From residue data with pigs, poultry, and cattle after oral administration, and with cattle after intravenous administration, it appears that the distribution profde of doxycycline in these animals is roughly comparable to that of oxytetracycline. Highest residue concentrations are found in kidney, followed by liver, skin, fat, and muscle. Tissue depletion studies in pigs treated intramuscularly with doxycycline at a 10 mg/kg bw dose for 4 days showed that the parent compound was absorbed and efficiently distributed in tissues (252). The concentrations of doxycycline detected in lung, muscle, liver, and kidney tissues at day 6 after treatment were 0.067, 0.047, 0.18, and 0.47 ppb, respectively detectable doxycycline residues were not present in fat at that withdrawal time. 

When pigs were given a single oral dose of radiolabeled dimetridazole, the concentrations of total residues in muscle, liver, kidney, and fat were found to be 8.6, 15.4, 36.1, and 3.6 ppm, respectively, at 0 withdrawal time, declining to... 

When day-old broilers were fed a ration containing 66, 90, or 120 ppm salinomycin sodium for 6 weeks, concentrations of salinomycin at 0 withdrawal time in breast skin/fat, tliigh skin/fat, and abdominal fat increased as the level of the drug in the ration also increased after 6 h of withdrawal, salinomycin concentrations in tissues were decreased, whereas after 24 h of withdrawal, salinomycin could not be detected in any tissue. It appears that salinomycin residues are concentrated in tire more fatty tissues, such as subcutaneous fat, and follow the order liver kidney thigh breast muscles (40). 

The absoqrtion profile of semduramicin is characterized by low levels in plasma, muscle, kidney, fat, and skin, but higher levels in the bile and liver (43). Liver constitutes the edible tissue with the highest total residues at all withdrawal times. Over a 5 day withdrawal period, total residues in each of liver, kidney, muscle, fat, and skin/fat tissues were depleted to 0.057, 0.022, 0.015, 0.011, and... 

Even when Community MRLs have been established, similar products in various member states may differ greatly with respect to the withdrawal times established by national authorities. Most member states employ a simple method by which the withdrawal time is set at the time when residues in all tissues in all the animals have depleted to below the respective MRL values. In addition, some member states then add an additional safety period if, for example, there are large variations in the depletion data set or other shortcomings are found in the studies. On the other hand, some other member states use statistical methods to establish withdrawal times. A greater degree of harmonization would be possible if a standard approach for calculating the withdrawal time was adopted throughout the European Union. Moreover, this would aid both the centralized and the decentralized procedures. 

G Weiss, HJ Laurencot, A MacDonald, PD Duke, K Misra, GM Horton, SE Katz, SM Brady. Determination of sulfadimethoxine withdrawal time from milk. Part I Dosing, sampling, and assay. J AOAC lnt 78 358-371, 1995. 

Barbiturate withdrawal time is related to whether the drug is short or long-lasting. Symptoms accompanying withdrawal include apprehension, weakness, tremors, anorexia, muscle twitches, and possible delirium. However, barbiturate withdrawal is seldom symptom-free and can be more difficult than heroin withdrawal. 

A. Linear rates of change must be obtained at all temperatures used in the study by a consistent mathematical treatment of the data. This can be verified by measurements at multiple withdrawal times from accelerated-aging ovens. 

Values for activation energies and the rate of change at room temperature calculated for these data and the values for retention of folding endurance obtained from the single-temperature (105°C), single-withdrawal time (72 hr) TAPPI method (16) are listed in Table V. 

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