Skip to content. Search for books, journals or webpages All Pages Books Journals. View on ScienceDirect. Editors: Donald Beitz. Imprint: Academic Press. Published Date: 28th January Page Count: Flexible - Read on multiple operating systems and devices. Easily read eBooks on smart phones, computers, or any eBook readers, including Kindle. When you read an eBook on VitalSource Bookshelf, enjoy such features as: Access online or offline, on mobile or desktop devices Bookmarks, highlights and notes sync across all your devices Smart study tools such as note sharing and subscription, review mode, and Microsoft OneNote integration Search and navigate content across your entire Bookshelf library Interactive notebook and read-aloud functionality Look up additional information online by highlighting a word or phrase.
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- Influence of physiological status on residues of lipophilic xenobiotics in livestock.;
Institutional Subscription. Free Shipping Free global shipping No minimum order. Introduction II. Chronology III. Impact of Increased Costs V. Research Needs VII. Status of World Aquaculture IV. Status of United States Aquaculture V. Overview of Individual Diets IV. Nutrients Contributed by Food Groups V. Retention of Vitamins and Minerals IV. Changes in Lipid Composition V. Potential Compositional Changes IV. Consequences of Xenobiotic Exposure IV. Xenobiotic Transformation as Detoxification V.
Xenobiotic Biotransformation as Activation VI. Distribution of Body Calcium II. Calcium Homeostasis IV. Review and Discussion III. Obesity and Hypertension III. Salt and Hypertension IV. Lactose Digestion IV. Lactose-Hydrolyzed Milk V. One approach is to conduct a total residue study with sufficiently widely-spaced sacrifice intervals to assess the rate of depletion of total residue over the projected range of probable safe concentrations. A zero-withdrawal sacrifice interval should be included. If a major portion of residue is non-extractable bound and the marker is undetectable at times when total residue is still significant, a residue bioavailability study may be necessary.
To complete the data package, final residue and comparative metabolism studies are conducted. Studies on the metabolism of flunixin in cattle will illustrate this approach. When biosynthetically prepared 14C-semduramicin sodium, a new anticoccidial ionophore, was fed at 25 ppm in feed to broilers for 7 days, the tissue containing the highest total residues at all withdrawal times was liver.
Two metabolites were isolated from chicken bile. Based on a chemical assay procedure utilizing HPLC with post-column derivatization, unchanged residues of semduramicin sodium declined from 0. In the case of furazolidone, a number of known in vivo toxic effects, like the inhibition of pyruvate metabolism and monoamine oxidase activity, could be reproduced and their mechanisms further studied. The biotransformation of furazolidone by these cells resulted in the formation of a number of unknown hydrophilic compounds, in addition to small amounts of the cyano-metabolite and protein-bound metabolites.
Using a new analytical method for the detection of these protein-bound metabolites, it was shown that these metabolites should be considered "drug-like". No proof was obtained for the binding of reactive intermediates of furazolidone to the DNA of the cells. It is concluded that in vitro models like hepatocytes, prepared from tissues or organs of food-producing animals can be a valuable tool not only for studying the biotransformation of compounds in these animals, but also for investigating the toxic effects and their underlying mechanisms.
Dermal absorption of agricultural chemicals and animal drugs in food-producing animals must be considered as a potential route from which tissue residues of drugs and chemicals may occur. This has been supported in studies of topical pesticide exposure in cows and sheep. Despite the many advances made in in vitro and in vivo techniques for assessing percutaneous absorption in laboratory animals and man, very little systematic attention has been focussed on food-producing animals.
The only exception is the pig since it is an accepted model for human studies. The purpose of this manuscript is to overview the literature on dermal xenobiotic absorption in food-producing animals to illustrate the risk that is present, and to outline how in vitro and in vivo methods could be applied to this problem. Factors which might alter dermal absorption and metabolism of xenobiotics will be presented.
This work will hopefully provide a framework for the systematic investigation of comparative dermal absorption across the diverse species of food-producing animals. The worldwide demand for fish and shellfish as a major item of the human diet has led to an increase in the use of aquaculture. Disease is often a problem in culturing aquatic species, and has led to the perceived need for veterinary drugs for disease control.
Xenobiotics and Food-Producing Animals, Metabolism and Residues. - Free Online Library
In order to use these drugs efficiently and safely, it is necessary to understand how they are handled by the fish and shellfish in which they will be used. The design of pharmacokinetic studies in fish and shellfish must take into account the methods for obtaining samples of blood and excreta in the aquatic environment without unduly stressing the animal. Many quantitative and some qualitative differences in drug biotransformation exist between fish, shellfish, and more commonly encountered veterinary and laboratory animals.
These differences must be considered in appropriately designing in vivo and in vitro studies.
Studies of the fate and residue dynamics of several drugs and model xenobiotics, including oxolinic acid, sulfadimethoxine, ormetoprim, erythromycin, phenol and benzoic acid have shown that of the many factors that influence the metabolism and elimination of drugs, species is perhaps the most important. These findings underline the need for conducting studies in the target species. Pirlimycin hydrochloride I , a lincosaminide antibiotic, is a new therapeutic agent under development for the treatment of mastitis in the dairy cow.
Absorption, distribution, metabolism, excretion and residue decline studies of I have been conducted in the dairy cow following intramammary infusion of an aqueous gel formulation of I into all four quarters of the udder via the teat canals. Nearly half of the dose was thus absorbed for systemic circulation. Drug residue concentrations in blood were best fit to a two- compartment pharmacokinetic model.
Pirlimycin sulfoxide was the major residue found in the liver, the target tissue for residue analysis. GI tract microflora converted part of the fecal drug residue to 3- 5'-ribonucleotide adducts of pirlimycin and pirlimycin sulfoxide. The comparative metabolism of I in the rat following oral administration was nearly identical to that in the cow following intramammary infusion. The tissue residue levels and plasma pharmacokinetics of albendazole in cattle administered via a new sustained release 'Captec' device were studied.
The daily dosage level released by the device of 0. Thus, this type of sustained release formulation of albendazole lowered both the plasma and tissue residue levels of albendazole in cattle. Although not proven in this study, it is also highly likely that the relationship between the marker and total residue Rm is different from that of the single dose case. This difference may present a regulatory dilemma for the drug sponsor since a uniform method and marker threshold must be applied for each individual drug regardless of the type of formulation. Tilmicosin, deoxo 3,5-dimethylpiperidinyl -desmycosin is a new macrolide antibiotic which is being developed for treatment of bovine respiratory disease by single subcutaneous injection into cattle.
Excretion, tissue residue, and metabolism studies were conducted with 14C-tilmicosin-treated cattle and rats.
Xenobiotics and Food-Producing Animals: Metabolism and Residues (ACS Symposium Series)
Radioactivity was excreted primarily in the feces after parenteral dosing of cattle and oral dosing of rats. Among edible tissues from treated cattle, liver and kidney contained the highest concentrations of radioactivity. The most abundant metabolite was N-desmethyl tilmicosin. Comparative metabolism studies with cattle and rats indicated that the pattern of metabolism was the same for both species. Excreta from all three species, daily milk from the goats, and egg samples from the hens were collected.
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In addition, selected tissues were taken following animal sacrifice. All samples were analyzed to determine the total radioactive residues, and metabolites were identified and quantified in excreta and selected tissues. The results showed that, in all three species, the majority of the administered dose was eliminated in excreta.
Residues were observed in milk, eggs, tissues, and organs; liver and kidney showed the highest total radioactive residue levels. Metabolites in the rat were isolated, purified, and identified by thin-layer chromatography, high performance liquid chromatography, and various mass spectroscopic techniques. The results obtained from the rat were compared with those obtained from the ruminants and poultry.
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The cows metabolized 14C-Sulmet by the following mechanisms: 1 acetylation at the N4-position; 2 hydroxylation at the 5-position of the heterocyclic ring followed by sulfate ester or hexuronic acid conjugation; 3 oxidation of a methyl group to a hydroxymethyl group followed by sulfate ester conjugation; 4 conjugation of the N1-position with a hexose or a hexuronic acid; 5 hydroxylation of the 3-position of the benzene ring followed by hexuronic acid conjugation; and 6 cleavage of the N1-C bond to yield sulfanilamide.
For AVM or its major component B1a , however, both metabolic pathways were evident in all species tested. Hydroxylation of the methyl group was the major metabolic pathway in cattle and goats, while 3"-O-desmethylation was identified as a minor pathway. In in vitro studies of [3H]H2B1a and [3H]B1a with microsomes from livers of untreated steers, swine and rats, similar metabolic profiles were obtained.
Thus, the rat is a good laboratory animal toxicity model for both cattle and swine. The results of these studies indicate that IVM and AVM are metabolized qualitatively similarly by cattle, swine and rat and that the metabolic profiles for each compound are qualitatively similar among the species. Luprostiol is a prostaglandin derivative of the type PGF2a which was developed as a potential agent for estrus synchronization in dairy cows. The depletion of 35S-Luprostiol residues in milk, liver, kidney, fat and muscle was investigated 12 hour, 1 day and 3 days after intramuscular administration of the drug.
However, the residues were quickly depleted to 11 ppb within 3 days. The residue levels in milk were less than 2 ppb in the first 12 hour sampling period. Several metabolites were detected. The tissue residue levels at different withdrawal periods, and the metabolic profiles in urine, liver and kidney are presented. Residue and metabolism studies were carried out using 14C ractopamine HCl in swine, dogs, and rats.
High performance liquid chromatography of liver and kidney extracts from 14C ractopamine HCl treated swine, dogs, and rats showed four major metabolites of ractopamine HCl. The metabolites were characterized as three monoglucuronides and a diglucuronide of ractopamine. Pair your accounts. Your Mendeley pairing has expired.