Tissue concentrations

An evaluation of the Health Professionals Follow-Up Study (Giovannucci et al., 1995) has detected a lower prostate cancer risk associated with the greater consumption of tomatoes and related food products. Tomatoes are the primary dietary source of lycopene and lycopene concentrations are highest in testis and adrenal tissue (Clinton, 1998). In paired benign and malignant prostate tissue from 25 American men, 53-74 yrs, undergoing 

Adrenal Testes Liver Pancreas Ovary Spleen 

Adrenal Testes Liver Fat Pancreas Kidney Fleart Thyroid Ovary Spleen 

The relationship between serum and tissue concentrations of lutein and zeaxanthin was recently studied by Johnson et al, (2000). Dietary intake of xanthophyll-rich vegetables (for example, spinach and com) resulted in significant increases in lutein concentration in serum, adipose tissue and buccal cells, and this correlated with changes in MP density. However, P-carotene and lycopene are normally the major carotenoids detected in buccal cells (Peng et al, 1994). 

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Lead enters the body through inhalation and ingestion, is absorbed into the circulatory system from the lungs and digestive tract, and excreted via the urine and feces. Normally, intake of lead approximately equals output. However, excessive exposure and intake can cause tissue concentrations to increase to the point where illness can result. 

The adrenal glands and pituitary glands have the highest tissue concentration of ascorbic acid. The brain, Hver, and spleen, however, represent the largest contribution to the body pool. Plasma and leukocyte ascorbic acid levels decrease with increasing age (152). Elderly people require higher ascorbic acid intakes than children to reach the same plasma and tissue concentration (153). 

Measurement of contaminants in fish has concentrated on muscle tissue since the aim has generally been to protect the health of the consumer rather than that of the fish. Endocrine tissue such as the gonads has been much more rarely examined, while data for adrenal, thyroid and pituitary levels are virtually non-existent. More data are available for the liver, as a lipid rich tissue and the major site of xenobiotic catabolism, but the concentrations have rarely been related to its capacity to produce vitellogenin or metabolise endogenous hormones. Tissue concentrations of a wide range of chemicals, are at a level which suggests that, either alone or in combination, they will cause significant endocrine disruption in fish in many polluted habitats. 

The application of biosolids also increases the nutritional value of blue grama. Tissue levels of nitrogen, phosphorus, potassium, and crude protein increased to recommended tissue concentrations with biosolids treatments. Trace metals in blue grama grass did not increase during the study, thereby eliminating concerns that toxic amounts of these elements could be transferred to grazing animals. 

The toxic effect depends both on lipid and blood solubility. I his will be illustrated with an example of anesthetic gases. The solubility of dinitrous oxide (N2O) in blood is very small therefore, it very quickly saturates in the blood, and its effect on the central nervous system is quick, but because N,0 is not highly lipid soluble, it does not cause deep anesthesia. Halothane and diethyl ether, in contrast, are very lipid soluble, and their solubility in the blood is also high. Thus, their saturation in the blood takes place slowly. For the same reason, the increase of tissue concentration is a slow process. On the other hand, the depression of the central nervous system may become deep, and may even cause death. During the elimination phase, the same processes occur in reverse order. N2O is rapidly eliminated whereas the elimination of halothane and diethyl ether is slow. In addition, only a small part of halothane and diethyl ether are eliminated via the lungs. They require first biotransformation and then elimination of the metabolites through the kidneys into the... 

Platelet activating factor (PAF) was first identified by its ability (at low levels) to cause platelet aggregation and dilation of blood vessels, but it is now known to be a potent mediator in inflammation, allergic responses, and shock. PAF effects are observed at tissue concentrations as low as 10 M. PAF causes a dramatic inflammation of air passages and induces asthma-like symptoms in laboratory animals. Toxic-shock syndrome occurs when fragments of destroyed bacteria act as toxins and induce the synthesis of PAF. This results in a drop in blood pressure and a reduced... 

The rate of synthesis is similar for trace amines and monoamine neurotransmitters, however, trace amines undergo a more rapid turnover due to their higher affinity to MAO and the lack of comparable cellular storage. Thus, the tissue concentration of trace amines in the vertebrate central nervous system is estimated to be in the range of 1-100 nM, depending on the trace amine and brain area, in contrast to micromolar concentrations of classic monoamine neurotransmitters. 

Within the plant. Excessive concentrations of some ions occur in the tissue overall, in the cytoplasm, or in the apoplast. Effects include metabolic inhibition, interference with protein synthesis, cellular dehydration, stomatal closure and early senescence of leaves. Since both cytoplasm and apoplast are small compartments, imbalance between compartments may amplify the effects of excess salt, resulting in toxicity despite apparently moderate overall tissue concentrations. 

Even a moderate quantity of salt reaching the leaves has a drastic effect on photosynthesis and leaf ultrastructure, much more than could be accounted for by the average tissue concentration (Flowers etal., 1985). Salt may accumulate in the apoplast (because it is not taken up fast enough by the cells of the leaf), and this would result in severe localised water deficit (Oertli, 1968). Differences in apoplast/protoplast balance are thought to be responsible for varietal differences in tissue salt load which can be accommodated (tissue tolerance Yeo Flowers, 1986). The xylem concentration of Na" is very much lower to young leaves than to older leaves (Yeo et al., 1985). This is advantageous in salt resistance because it means that at least some leaves are protected from salt, which otherwise causes premature leaf death (Yeo Flowers, 1984 Fig. 2). 

Endosulfan does not bioaccumulate to high concentrations in terrestrial or aquatic ecosystems. In aquatic ecosystems, residue levels in fish generally peak within 7 days to 2 weeks of continuous exposure to endosulfan. Maximum bioconcentration factors (BCFs) are usually less than 3,000, and residues are eliminated within 2 weeks of transfer to clean water (NRCC 1975). A maximum BCE of 600 was reported for a-endosulfan in mussel tissue (Ernst 1977). In a similar study, endosulfan, isomers not specified, had a measured BCE of 22.5 in mussel tissue (Roberts 1972). Tissue concentrations of a-endosulfan fell rapidly upon transfer of the organisms to fresh seawater for example, a depuration half-life of 34 hours (Ernst 1977). Higher BCFs were reported for whole-body and edible tissues of striped mullet (maximum BCF=2,755) after 28 days of exposure to endosulfan in seawater (Schimmel et al. 1977). However, tissue concentrations decreased to undetectable levels 48 hours after the organisms were transferred to uncontaminated seawater. Similarly, a BCE of 2,650 was obtained for zebra fish exposed to 0.3 pg/L of endosulfan for 21 days in a flow-through aquarium (Toledo and Jonsson 1992). It was noted that endosulfan depuration by fish was rapid, with approximately 81% total endosulfan eliminated within 120 hours when the fish were placed in a tank of water containing no endosulfan. 

In freshwater studies, mosquito fish, catfish, and freshwater eels were exposed to endosulfan in static tests. Maximum tissue concentrations in mosquito fish (933 pg/kg a-isomer) were found in fish exposed to 16 pg technical-grade endosulfan/L for 24 hours. The maximum tissue concentrations in fish exposed to 2 pg technical-grade endosulfan/L for 7 days was 143 pg a-isomer/kg. Mean endosulfan residues in... 

Boereboom FT, van Dijk A, van Zoonen P, et al. 1998. Nonaccidental endosulfan intoxication A case report with toxicokinetic calculations and tissue concentrations. Clin Toxicol 36(4) 345-352. 

More rapid elimination was needed than could be provided by passive diffusion in order to prevent tissue concentrations reaching toxic levels. 

FIGURE 9.4 Relationship between scope for growth and whole tissue concentration of 2-and 3-ring aromatic hydrocarbons in Mytilus edulis (mean 95% confidence limits). A, Data from Solbergstrand mesocosm experiment, Oslo Fjord, Norway. , Data from Sullom Voe. Shetland Islands (Moore et al. 1987). 

In general, it is easier to use models such as these to predict the distribution of chemicals (i.e., relationship between exposure and tissue concentration) than it is to predict their toxic action. The relationship between tissue concentration and toxicity is not straightforward for a diverse group of compounds, and depends on their mode of action. Even with distribution models, however, the picture can be complicated by species differences in metabolism, as in the case of models for bioconcentration and bioaccumulation (see Chapter 4). Rapid metabolism can lead to lower tissue concentrations than would be predicted from a simple model based on values. Thus, such models need to be used with caution when dealing with different species. 

The high affinity of the decarboxylase enzyme for its substrate (10 pM in the brain) makes it unlikely that this stage could ever become rate-limiting for the pathway as a whole. Nevertheless, the for this enzyme is considerably higher than tissue concentrations of 5-hydroxytryptophan and so, again, supply of this substrate is likely to be a crucial factor. 

The comparatively straightforward link between 5-HT and its primary metabolite, 5-HIAA, encouraged many researchers to use changes in the ratio of tissue concentrations of 5-HIAA and 5-HT as an index of the rate of release of 5-HT ex vivo. However, it has been clear for some time that the majority of 5-HT is metabolised in the cytoplasm by MAO before it is released from 5-HT nerve terminals. Consequently, the reliability of the 5-HIAA 5-HT ratio as an index of transmitter release is rather dubious, although it could be used as an acceptable measure of MAO activity. In any case, the development of in vivo microdialysis means that changes in the concentration of extracellular 5-HT can now be monitored directly which, under drug-free conditions, provides a far more reliable indication of any changes in the rate of release of 5-HT. 

JOHNSON E J, HAMMOND B R, YEUM K, J, QIN J, WANG X D, CASTANEDA C, SNODDERLY D M and RUSSELL R M (2000) Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density. Am J Clin Nutr. 71(6) 1555-62. 

Measurement of exposure can be made by determining levels of toxic chemicals in human serum or tissue if the chemicals of concern persist in tissue or if the exposure is recent. For most situations, neither of these conditions is met. As a result, most assessments of exposure depend primarily on chemical measurements in environmental media coupled with semi-quantitative assessments of environmental pathways. However, when measurements in human tissue are possible, valuable exposure information can be obtained, subject to the same limitations cited above for environmental measurement methodology. Interpretation of tissue concentration data is dependent on knowledge of the absorption, excretion, metabolism, and tissue specificity characteristics for the chemical under study. The toxic hazard posed by a particular chemical will depend critically upon the concentration achieved at particular target organ sites. This, in turn, depends upon rates of absorption, transport, and metabolic alteration. Metabolic alterations can involve either partial inactivation of toxic material or conversion to chemicals with increased or differing toxic properties. 

Wiener JG, Spry DJ. 1996. Toxicological significance of mercury in freshwater fish. In Beyer WN, Heinz GH, Redmon-Norwood AW, editors. Environmental contaminants in wildlife interpreting tissue concentrations. Boca Raton (FL) Lewis Publishers, p. 297-339. 

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