Tissue residue studies

Bush, P.B., M. Tanner, and J. Kiker. 1978. Tissue residue studies on toxaphene in broiler chickens. Jour. Agric. Food Chem. 26 26-30. 

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. 

JM Delmas, AM Chapel, V Gaudin, P Sanders. Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration bioavailability and tissue residue studies. J Vet Pharmacol Ther 20 249-257, 1997. 

DONOIIO ET AL. Tilmicosin in Cattle Metabolism and Tissue Residues 161 Tissue Residue Studies... 

Three tissue residue studies were conducted to characterize the pattern of residues in cattle treated with tilmicosin. In the first study, four steers and one bull calf weighing 157 to 202 kg were injected subcutaneously with 20 mg/kg Pip- " C-tilmicosin. One calf was euthanized 3 days after dosing, two were euthanized at 21 days, and two at 56 days after dosing. Total RA was measured in muscle, liver, kidney, fat, injection site, lung, and bile. In addition, blood was collected from one calf at 4, 8, 24,48,... 

In the third tissue residue study, twelve cattle, eight steers, and four heifers, weighing approximately 200 kg, were dosed with 10 mgAg unlabeled tilmicosin. Groups of 2 steers and one heifer were euthanized at 14, 28, 35, and 42 days after treatment. Muscle, liver, kidney, fat, and injection site samples were collected and assayed for parent tilmicosin. The mean residue concentrations are shown in Table III. 

Comparison of total RA and HPLC muscle and injection site data indicated that approximately half was parent tilmicosin (44% for the 3-day muscle, and 50 to 60% for injection sites). No further fractionation of muscle RA was done. The unlabeled tissue residue study demonstrated that tilmicosin in muscle was <0.05 ppm at 14 days withdrawal. 

Data are scarce on the toxicity of PCP to mammalian wildlife, but studies with livestock and small laboratory animals show that the chemical is rapidly excreted. However, there is great variability between species in their ability to depurate PCP, as well as in their overall sensitivity. Acute oral LD50 values in laboratory animals were 27 to 300 mg/kg BW. Tissue residues were elevated at dietary levels as low as 0.05 mg/kg feed and at air levels >0.1 mg/m3. Histopathology, reproductive impairment, and retarded growth were evident at doses of 0.2 to 1.25 mg/kg BW, and when the diets fed contained >30 mg PCP/kg. 

Blood-tissue uptake rates (l< ) can often be approximated from data at early (t < 10 minutes) time points in IV studies, provided the blood has been washed from the organ (e.g., liver) or the contribution from blood to the tissue residue is subtracted (fat). High accuracy is not usually required since these parameters can be optimized to fit the data when they are used in more complex models. Tissue-blood recycling rates (A y) and residence times can be computed from partition coefficients if estimates of uptake rates are available. 

The EPA is conducting a major study in the Los Angeles basin on the effects of photochemical oxidants on health. It is a survey of schoolchildren in seven communities representing a gradient of oxidant exposure. In addition to comprehensive environmental monitoring data, specific health characteristics will be followed, including chronic respiratory disease in adults, lower respiratory disease in children, acute respiratory disease in both children and adults, pulmonary function in children, aggravation of asthma, irritation of mucous membranes, and tissue residues of trace metals. Complete data from this study will not be available for another 3 yr, but data from the first 2 yr may become available sooner. 

Food Chain Bioaccumulation. Diazinon has an estimated low bioconcentration potential (BCF=77) (Kenaga 1980) in aquatic organisms, which is generally confirmed by measured BCF values obtained from laboratory studies with fish and other aquatic invertebrates (El Arab et al. 1990 Keizer et al. 1991 Sancho et al. 1993 Tsuda et al. 1989, 1995). Further information on measured BCF values for additional edible fish and shellfish would be helpful, as would information on tissue residues of diazinon and its major degradation products in edible species. No information was found on studies associated with plant uptake, but diazinon is rarely detected above EPA tolerance limits (Hundley et al. 1988). Bioaccumulation in aquatic food chains does not appear to be important, and no further information on biomagnification is required. 

The pharmacokinetic characteristics of florfenicol have been described in goats (40), calves (41), and chickens (42). The efficacy of florfenicol in aquaculture has been also demonstrated against bacteria involved in some major fish pathologies, especially in salmon and trout (43, 44). Pharmacokinetic studies in Atlantic salmon indicated that the compound was well absorbed and distributed following oral administration (45). Tissue residue depletion studies after an oral daily administration of 10 mg/kg bw florfenicol in rainbow ftout at 10 C for 10 days showed that muscle/skin tissue contained 150 ppb drug at 15 days after the last dose (46). 

Pharmacokinetic studies in pigs following a single oral administration of 20 mg kitasamycin/kg bw showed that the drug was rapidly absorbed and distributed in the body. A maximum plasma concentration of 4.5 ppm was attained within 0.5 h, the half-life in plasma being 0.7 h. Highest tissue residue concentrations (21 ppm) were detected in kidney within 1-2 h. The ratio of the maximum concentrations determined in kidney to that in liver was around 3 2. 

This nonextractable radioactivity was probably the result of covalent binding of the furazolidone intermediates to endogenous macromolecules. The bioavailability of these bound tissue residues from the above pig residue depletion study was determined by feeding rats lyophilized samples of liver and muscle tissues from animals sacrificed at 0 and 45 days after the last treatment (132). Results showed that the fraction of the bound residues bioavailable to rats was in the range 16-41%. The toxicological impact of these bioavailable bound residues has not been yet determined. 

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. 

Residue studies (253) performed on calves after oral administration at a dosage of 10 mg/kg bw/day for 5 days showed that residues of the drug could remain in kidney and liver tissues for more than 14 days after cessation of the medication. Following a single oral or intravenous administration of doxycycline to chickens at dosage rates of 100 mg/kg or 20 mg/kg bw, respectively, residue... 

At 168 h postadminisfration, the parent drug represented 48% of the total radioacUvity in muscle, 87% in fat, 61% in liver, and 78% in kidney. In a pertinent radiometric depletion study (64) carried out in horse, moxidectin residues in fat were found to be 221, 165, 130, and 131 ppb at 28, 35, 42, and 49 days, respectively. In all other edible tissues, residue concentrations were below 10 ppb even at the first sampling. 

Intramammary use of bacitracin resulted in residues in milk, but not in plasma, udder, or any other tissue. Residue depletion studies in cows given intramammary bacitracin treatment showed that muscle, liver, kidney, fat, udder, and milk from untreated quarters did not contain detectable residues ( 0.003-0.005 lU/ml) after the end of treatment. In milk from treated quarters, however, residues of bacitracin could be detected during treatment, declining to around 0.04 lU/ml at the sixth milking after treatment. 

Chemical analytical methods used in veterinary drug residue depletion studies in target animals constitute a potential source of suitable methods for determining compliance of tissue residues with established MRLs. In some situations. 

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