Liver target organ

PLAA, G.L. and HEWITT, W.R. (editors) (1982) Toxicology of the Liver, Target Organ Toxicology Series, edited by R.L.Dixon (New York Raven Press). 

Acetoacetate and /3-hydroxybutyrate are transported through the blood from liver to target organs and tissues, where they are converted to acetyl-CoA (Figure 24.29). Ketone bodies are easily transportable forms of fatty acids that move through the circulatory system without the need for eomplexation with serum albumin and other fatty acid—binding proteins. 

These studies on NPYR are typical of the state of the art in cyclic nitrosamine metabolism ai d activation. The major metabolic pathways have been rather well characterized, but data on the relationship of these pathways to carcinogenesis are limited. This is especially true of the organospecific effects of NPYR and the other cyclic nitrosamines. For example, the main target organs for NPYR in the Syrian golden hamster are the trachea and nasal cavity rather than the liver. This is in spite... 

A protease-specific model has also been reported in which a replication-defective adenovirus encoding an NS3 protease-SEAP fusion protein is injected into mouse tail veins, resulting in expression of the fusion protein in the liver [82, 83]. Protease activity can be detected both by measuring activity of liberated SEAP or by protease-induced liver damage. Protease activity was found to be reduced by administration of protease inhibitors. This model can be used to show that candidate inhibitors have adequate pharmacokinetic properties in mice to function in the intended target organ, but it is not a true disease model. 

The absorption efficiency term allows estimation of the effective dose or the amount of pollutant which crosses the membrane of the exposed tissue (e.g., the lung) and reaches a target organ (e.g., the liver). For many pollutants this type of metabolic data is not available and consequently 100% absorption is a common preliminary assumption in exposure assessments. For well-studied substances such as radionuclides, a methodology for calculation of target organ doses has been developed for bone marrow, lungs, endosteal cells, stomach wall, lower intestine wall, thyroid, liver, kidney, testes and ovaries as well as for the total body. 

Hepatic Effects. Acrylonitrile is metabolized in the liver to potentially toxic metabolites (see Section 2.3). There are limited indications that the liver is a target organ for acrylonitrile toxicity. 

The liver appeared to be a target organ for hexachloroethane following oral administration. When one dose of 500 mg/kg was administered in an olive oil aqueous emulsion to male sheep, the levels of glutamate dehydrogenase, sorbitol dehydrogenase, ornithine carbamyl transferase, and aspartate aminotransferase in serum increased in the 2-day period after compound administration and then normalized (Fowler 1969b). Hexachloroethane had no effect on bromsulphthalein uptake from the blood by liver cells, but the transfer of this dye to bile was reduced in sheep exposed to doses of 500-1,000 mg/kg/day. 

The kidney and liver are the primary target organs for hexachloroethane based on the results of toxicity testing and supported by toxicokinetic information from tissue distribution and binding studies (Lattanzi et al. 1988). Male rats were more susceptible to kidney damage than female rats (NTP 1989), and the kidneys of male rats contained 4-45% more hexachloroethane radiolabel than the kidneys of female rats (Gorzinski et al. 1985). However, there were some effects on kidneys of both sexes. 

There are more data available concerning the effects of hexachloroethane in animals, particularly for exposure by the inhalation and oral routes. These studies identify the liver and kidney as target organs for... 

Chronic-Duration Exposure and Cancer. No studies were located in humans following chrome-duration exposure to hexachloroethane for any exposure route. No chronic animal studies were conducted using the inhalation route of exposure. In oral studies with rats, the kidney was identified as a primary target organ in males and females (NTP 1989). The kidney damage in male rats was the result of hyaline droplet nephropathy and, accordingly, was not suitable as the basis for an oral MRL. In contrast to acute- and intermediate-duration oral exposure, liver toxicity was not evident in rats following chronic oral exposure. There were no studies of chronic dermal exposure to hexachloroethane. 

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