Distribution among tissues and

Metabolism in the rat is qualitatively similar to that in humans. Four male and four female Wistar rats were exposed individually to 14C-labeled HFC134a at 10,000 ppm for 1 h (Ellis et al. 1993). Atmospheres were monitored with a gas chromatograph. After exposure, urine and feces were collected at 6 h intervals up to 24 h and every 24 h for up to 5 d thereafter. Approximately 1% of the inhaled dose was recovered in urine, feces, and expired air of that 1%, approximately two-thirds was exhaled within 1 h postexposure as unchanged HFC-134a. Exhaled C02 was the primary metabolite and accounted for approximately 0.22% and 0.27% of the inhaled dose in males and females, respectively. Excretion in the urine and feces occurred within 24 h and accounted for 0.09% and 0.04% of the inhaled dose, respectively. The only metabolite identified in urine was trifluoroacetic acid. At sacrifice, 5 d postexposure, radioactivity was uniformly distributed among tissues and accounted for 0.14-0.15% of the inhaled dose. The average total metabolized dose in male and female rats was 0.37% of the inhaled dose. 

T4, both involving the removal of the inner ring 5-iodide. The type III enzyme is widely distributed among tissues and is responsible for the formation of almost all (95%) of the circulating rT3. Its activity is not altered by most of the factors or conditions that inhibit the activity of types I or II deiodinases, and this explains why there is a reciprocal relationship between the plasma levels of T3 and rT3. 

Studies with rats and chickens given oral doses of TOCP and tn-/ ara-cresyl phosphate provide more definitive evidence that, following absorption, organophosphate esters in hydraulic fluids (or their metabolites) may be widely distributed among tissues with a preferential distribution to fatty tissues, the liver, and the kidneys (Abou-Donia et al. 1990a, 1990b Kurebayashi et al. 1985 Somkuti and Abou-Donia 1990 Suwita and Abou-Donia 1990). 

After intravenous administration, about 80-90% of the dose is catabolized in the liver by dihydropyrimidine dehydrogenase (DPD) [38] (Figure 14.3). The formation of the inactive 5-fluoro-5,6-dihydrouracil (5-FUH2) by DPD is the rate-limiting step of 5-FU catabolism [39]. DPD is widely distributed among tissues, with the highest levels found in the liver. Once 5-FU entered tumor cells, its antitumor effect is mainly dependent on the extent of 5-FU anabolism. After two sequential anabolic steps involving thymidine phosphorylase (TP) and thymidine kinase... 

Toth GB, Pavia H (2006) Artificial wounding decreases plant biomass and shoot strength of the brown seaweed Ascophyllum nodosum (Fucales, Phaeophyceae). Mar Biol 148 1193-1199 Tugwell S, Branch GM (1989) Differential polyphenolic distribution among tissues in the kelps Ecklonia maxima, Laminaria pallida and Macrocystis angustifolia in relation to plant-defence theory. J Exp Mar Biol Ecol 129 219-230... 

The anthracyclines, apart from valrubicin, are administered intravenously. Doxorubicin is rapidly distributed to tissues and slowly eliminated in faeces and urine with an elimination half-life of several days. Daunorubicin undergoes extensive metabolism in the liver, among others to the active daunorubi-cinol, and is eliminated as inactive products with an elimination half-live of approximately 30 hours. Epimbicin and idambicin have similar kinetic profiles as daunombicin with respectively epirubici-nol and idarubicinol as their major metabolic products. The kinetic behavior of mitoxantrone resembles more that of doxorubicin with a very slow elimination from the body mainly as parent compound or as inactive metabolites. The anthracyclines do not cross the blood-brain barrier. 

No studies were located regarding the distribution of 1,1,1-trichloroethane among human or animal tissues following dermal exposure however, dermally applied 1,1,1-trichloroethane, once absorbed, is probably widely distributed among tissues, with preferential accumulation in fatty tissues, based on results from oral and inhalation studies with animals. 

The canning process was also shown to reduce toxicity levels in PSP-contaminated Japanese scallops [8,9] and mussels [10]. The high transfer of domoic acid from the scallops to the packing media rather than destruction of DA was also described, which posed a threat to consumers of this processed product [11]. In conclusion, processing methods must be carefully evaluated for each product and specihc toxin to determine their effect on total toxicity and toxin distribution among tissues. 

Amine oxidase is widely distributed among vertebrate and invertebrate tissues, and attacks many aliphatic and aromatic amines, including adrenaline and tyramine. It is distinct from histamine oxidase, which oxidises diamines. 

Reviews of the literature reveal numerous studies on atherosclerosis are concerned with cholesterol, its presence in or absence from the diet, its synthesis and catabolism, and its distribution among plasma and various tissues. Epidemiological studies in man suggest that diet -high in fat or cholesterol along with fat - plays a prominent role in the human atherosclerotic disease. Cholesterol, linked to the disease by its presence in the atherosclerotic plaques and its effect in diets of animals, iS derived both from diet and by biosynthesis in body tissues. Rats and rabbits, so often used in laboratory studies, differ greatly in susceptibility to atherosclerosis and may well be quite different from humans in this respect. Even on semi-synthetic diets, containing no added cholesterol, rabbits develop atherosclerosis, whereas they do not on stock diets. Furthermore, the plasma cholesterol of rabbits is more easily altered than that of rats, whereas the cholesterol synthesis rate (from acetate) varies widely in rats in response to various diets. 

Histamine in the Blood. After its release, histamine diffuses rapidly into the blood stream and surrounding tissues (12). Histamine appears in blood within 2.5 min after its release, peaks at 5 min, and returns to baseline levels by 15 to 30 min. In humans, the diurnal mean of plasma histamine levels is 0.13 ng/g. In urine, elevations of histamine or metaboUtes are more prolonged than plasma elevations. Consequendy, abnormahties are more easily detected by urinary histamine assay. About one-half of the histamine in normal blood is in basophils, one-third in eosinophils, and one-seventh in neutrophils the remainder is distributed among all the other blood components. Increases in blood histamine levels occur in several pathological... 

DHBs after absorption distribute rapidly and widely among tissues but bio accumulation is low (121). They are metabolized to their respective benzoquinone and then detoxified by conjugation and excreted in the urine mainly as conjugates. Some deconjugations may occur in the urine. Resorcinol is also excreted in the urine in a free and conjugated state, essentially glucuronide and sulfate. 

Pharmacokinetic studies are designed to measure quantitatively the rate of uptake and metaboHsm of a material and determine the absorbed dose to determine the distribution of absorbed material and its metaboHtes among body fluids and tissues, and their rate of accumulation and efflux from the tissues and body fluids to determine the routes and relative rates of excretion of test material and metaboHtes and to determine the potential for binding to macromolecular and ceUular stmctures. 

The distribution of endosulfan and endosulfan sulfate was evaluated in the brains of cats given a single intravenous injection of 3 mg/kg endosulfan (Khanna et al. 1979). Peak concentrations of endosulfan in the brain were found at the earliest time point examined (15 minutes after administration) and then decreased. When tissue levels were expressed per gram of tissue, little differential was observed in distribution among the brain areas studied. However, if endosulfan levels were expressed per gram of tissue lipid, higher initial levels were observed in the cerebral cortex and cerebellum than in the spinal cord and brainstem. Loss of endosulfan was most rapid from those areas low in Upid. Endosulfan sulfate levels peaked in the brain at 1 hour postadministration. In contrast, endosulfan sulfate levels in liver peaked within 15 minutes postadministration. The time course of neurotoxic effects observed in the animals in this study corresponded most closely with endosulfan levels in the central nervous system tissues examined. 

Hyaluronic acid consists of an unbranched chain of repeating disaccharide units containing GlcUA and GlcNAc. Hyaluronic acid is present in bacteria and is widely distributed among various animals and tissues, including synovial fluid, the vitreous body of the eye, cartilage, and loose connective tissues. 

Following dermal exposure, trichloroethylene has been detected in blood and expired breath in human studies (Sato and Nakajima 1978). Studies of distribution among other tissues after dermal exposure in humans and animals were not located in the available literature. 

Evans RD, Addison EM, VUleneuve JY, MacDonald KS, Joachim DG. 2000. Distribution of inorganic and ethylmercury among tissues in mink Mustela vison) and otter (Lutra canadensis). Environ Res 84 133-139. 

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