China
Africa
Explore chapters and articles related to this topic
Hazard Characterization and Dose–Response Assessment
Published in Ted W. Simon, Environmental Risk Assessment, 2019
PBPK models help greatly to ascertain the dose metric in the target tissue most appropriate for the toxicity being considered. For example, if a particular chemical produces liver toxicity, then oral exposure will likely produce effects at lower administered doses than either dermal or inhalation exposure. The reason is that chemicals absorbed from the gastrointestinal tract enter the hepatic portal system and move first to the liver. Consideration of fat solubility is important as well: highly lipid-soluble chemicals may tend to bioaccumulate in adipose tissue and possibly produce effects on an ongoing basis. The AUC for adipose tissue concentration might be the most appropriate dose metric for such bioaccumulative chemicals. Another chemical might be absorbed by the intestine and thus produce cellular damage in the enterocytes before entering the bloodstream: the example here is hexavalent chromium, and in this case, flux of the chemical from the intestinal lumen into the tissue would be an appropriate dose metric.179,180
Liver
Published in Alan G. Heath, Water Pollution and Fish Physiology, 2018
The well-defined (histologically) lobular structure of the mammalian liver is apparently not characteristic of fish. Instead, the hepatocytes are arranged as tubules of cells. A tubule viewed in cross section is usually surrounded by five to seven hepatocytes with their apices directed toward the central bile canaliculus and/or bile preductule. These tubules are surrounded by the sinusoids which take the place of capillaries in the liver. Blood enters the sinusoids from the hepatic portal system and hepatic artery and the hepatocytes remove nutrients and xenobiotics from that blood. The bile is secreted into the central bile canaliculus from which it ultimately flows into the gallbladder.
Impact of administration route on nanocarrier biodistribution in a murine colitis model
Published in Journal of Experimental Nanoscience, 2022
Catherine C. Applegate, Hongping Deng, Brittany L. Kleszynski, Tzu-Wen L. Cross, Christian J. Konopka, L. Wawrzyniec Dobrucki, Erik R. Nelson, Matthew A. Wallig, Andrew M. Smith, Kelly S. Swanson
The global impact of liver-based normalization on inter-subject variability is shown in Figure 4A, comparing the relative standard deviation (RSD) of each intestinal tissue with and without normalization. For oral gavage, RSD reduced with liver-based normalization in most tissues, presumably because the quantity of probe entering the intestines distributes proportionally to the hepatic portal system and to further regions of the intestines. In contrast, liver-based normalization after enema administration resulted in mixed outcomes in terms of variability of intestine uptake: RSD for small intestinal tissues and the cecum were strongly reduced; however, RSD for large intestine tissues increased. In addition, a trend of increasing RSD was observed with posterior intestinal position, suggesting that liver normalization is most impactful for the most anterior small intestinal tissues where hepatic uptake occurs. For IP delivery, absolute RSD was smaller overall and uptake normalization by liver had less impact on RSD, although normalization was necessary to observe differences between Con and DSS animals.