ISSN:0098-4108    

DOI:10.1080/15287397709529483

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

In this paper are discussed (1) the three general mechanisms by which radioisotopes may be retained in animal tissues long after labeled drugs are administered, (2) ways of differentiating these mechanisms, and (3) possible relationships between the toxic effects of drugs and their metabolism. It is emphasized, however, that studies on the disposition of drugs should be coordinated with toxicity studies in order to make the results of bioavailability and pharmacokinetic studies more meaningful in setting limits for food residues.

ISSN:0098-4108    

DOI:10.1080/15287397709529484

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

In vivo and in vitro covafent binding of foreign chemicals to tissue macromolecules via metabolic activation is described, using the analgesic acetaminophen as an example. Acetaminophen is metabolized through a variety of pathways. The arylating metabolite is formed by a cytochrome P‐450 dependent N‐hydroxylation process. The resulting hydroxamic acid is then conjugated with glutathione, and the resulting conjugate is subsequently excreted as the mercapturic acid in the urine. It is not until the glutathione concentration is reduced to about 20% of the initial concentration that covalent binding of acetaminophen to amino acids of proteins occurs and subsequent liver necrosis is seen. The extent of in vitro binding correlates with treatments that alter hepatic necrosis and in vivo binding, indicating that in vitro binding is a valid index of acetaminophen hepatotoxicity. A simple bacterial test system for detecting chemical carcinogens as mutagens is described.

ISSN:0098-4108    

DOI:10.1080/15287397709529485

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

Serious problems of interpretation may arise when metabolic studies are carried out with radioactively labeled drugs and other foreign chemicals. Detection of free or bound radioactivity in tissues or body fluids may indicate the presence of the unchanged chemical or of various products of its decomposition. Some radioactivity may, however, represent incorporation of certain metabolites of foreign chemicals into body constituents by normal biosynthetic pathways. The interpretation of the results of such metabolic experiments from the standpoint of safety evaluation will be profoundly different if the radioactivity represents covalent binding to a cellular macromolecule than if it results from normal endogenous incorporation.

ISSN:0098-4108    

DOI:10.1080/15287397709529486

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

The anthelmintic cambendazole is rapidly metabolized to at least 13 urinary metabolites. Radioactivity was found in liver for weeks after a single dose in cattle, but even at 3 days’ withdrawal, cambendazole and metabolites previously identified in urine accounted for only a small fraction of liver radioactivity. The radioactivity was ubiquitously distributed in protein and nucleic acid fractions, and /14C/ glutamic acid was identified, indicating incorporation of14C into the endogenous pool. Part of the residual liver radioactivity at 7 days was convertible chemically to 5‐nttrobenzimidazole, indicating a drug‐related macromolecular residue. However, data from rats fed radio‐labeled steer liver indicate that the residue is minimally bioavailable and therefore of substantially less toxicological concern than cambendazole itself.

ISSN:0098-4108    

DOI:10.1080/15287397709529487

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287397709529488

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287397709529489

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287397709529490

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

Twenty‐two female big brown bats (Eptesicus fuscus) were collected in a house attic in Montgomery County, Maryland. Seventeen were fed mealworms (Tenebrio molitor larvae) that contained 166 ppm DDE; the other five were fed uncontaminated mealworms. After 54 days of feeding, six dosed bats were frozen and the remaining 16 were starved to death. In a second experiment, 21 female big brown bats were collected in a house attic in Prince Georges County, Maryland. Sixteen were fed mealworms that contained 9.4 ppm Aroclor 1254 (PCB). After 37 days, two bats had died, four dosed bats were frozen, and the remaining 15 were starved to death. Starvation caused mobilization of stored residues.

ISSN:0098-4108    

DOI:10.1080/15287397709529491

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

Forty 100 g male rats were fed, in groups of eight, either 0, 5, or 25 ppm cadmium in a purified diet for 14 wk. Three groups were fed each of the levels of cadmium on an ad libitum basis. Two other groups were fed either 0 or 5 ppm cadmium in amounts that were equalized to that consumed by the 25 ppm group fed ad libitum. Cadmium ingestion decreased daily diet consumption, weight gain, and terminal body weight. These parameters were not significantly different in rats whose diet consumption was equalized. Packed cell volume and serum iron as well as serum zinc were decreased in the rats fed 25 ppm cadmium. These effects were not related to diet intake. No major differences were observed in serum ceruloplasmin, glucose, protein, leucine aminopeptidase activity, or copper in any of the groups. Blood urea nitrogen and renal leucine aminopeptidase activity were decreased by cadmium ingestion in the rats fed ad libitum only. In contrast, serum alkaline phosphatase activity was elevated by cadmium in the equalized‐intake groups only. Cadmium and zinc concentrations were elevated and the iron concentration was decreased in the kidney, liver, and intestinal mucosa of the cadmium‐fed rats irrespective of level of diet consumption. The increased uptake of cadmium in these tissues was coincident with the increased content of the cadmium‐binding protein, metallothioneln, in the cytosol fraction. The results indicate that some parameters of chronic cadmium toxicity are associated with diet consumption whereas others are not.

ISSN:0098-4108    

DOI:10.1080/15287397709529492

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor