Target organs, for toxicity

The liver is a target organ for toxic effects of 1,2-dibromoethane in experimental animals following exposure by a variety of routes. 

Hepatic Effects. Hepatic effects have been reported in humans exposed orally or by the dermal and inhalation routes to toxic doses of 1,2-dibromoethane (Letz et al. 1984 Olmstead 1960 Saraswat et al. 1986). These effects consist of hepatocellular and Kupffer cell necrosis. Results in humans are supported by animal studies in which the liver is also a target organ for toxic effects of 1,2-dibromoethane following exposure by a variety of routes (Botti et al. 1986 Brandt et al. 1987 Broda 1976 NTP 1982 Rowe et al. 1952). 1,2-Dibromoethane, as well as inducing necrosis, can also act as a hepatocellular mitogen in rats (Ledda-Columbano et al. 1987a). 

The liver, kidney, and testis are the major visceral target organs for toxic effects of... 

Timbrell JA. The liver as a target organ for toxicity. In Cohen GM, ed. Target Organ Toxicity. Boca Raton, FL CRC Press, 1989. 

The primary goals of preclinical safety evaluation articulated in ICH S6 are namely (1) to identify an initial safe dose and subsequent dose escalation schemes in humans, (2) to identify potential target organs for toxicity and for the study of whether such toxicity is reversible, and (3) to identify safety parameters for clinical monitoring. These goals are generally accepted across all product classes. 

The safety and pharmacological profiles of hypromellose acetate succinate are similar to those of other ether and ester derivatives of cellulose.All nonclinical studies reported in the literature identify no target organs for toxicity by hypromellose acetate succinate. It has also been reported that hypromellose acetate succinate does not alter fertility in rats, does not produce any developmental anomalies in rats and rabbits, and does not alter perinatal and postnatal development in rats when assessed up to 2500mg/kg. ... 

The only occupational health observation in humans was of contact dermatitis in factory workers handling butter yellow. The target organs for toxicity are skin, liver, and bladder. Potential symptoms of overexposure are enlarged liver, hepatic and renal dysfunction, contact dermatitis, coughing, wheezing, difficulty in breathing, bloody sputum, bronchial secretions, frequent urination, hematuria, and dysuria. 

BHA is harmful if swallowed, inhaled, or absorbed through skin. It is irritating to the eyes, skin, mucous membranes, and upper respiratory tract. Prolonged or repeated exposure may cause allergic reactions in certain sensitive individuals. The target organs for toxicity are liver, lungs, and forestomach. 

Drug or xenobiotic metabolism is the most significant determinant of toxicokinetics that is, the fate of a compound in vivo is heavily dependent on metabolism. Metabolic steps that take place within the cell are also the main determinants of how much of the parent compound or a specific metabolite reaches a target organelle in a cellular test system. As metabolism in the target organ for toxicity may lead both to detoxification and/or metabolic activation it is essential to investigate the metabolic competence and characteristics of any cell line used for toxicity studies. 

FIGURE 6.3 Schematic representation of the arrangement and relationship of vessels and sinusoids in the liver. The central vein drains into the hepatic vein. From Timbrell, J.A., The liver as a target organ for toxicity, in Target Organ Toxicity, edited G.M.Cohen (Boca Raton, FI CRCPress), 1989, with permission. 

For aflatoxins the liver is the primary target organ for toxicity in all species studied. The precise manifestations of toxicity depend upon a number of factors, including dose and duration of exposure. However it is the potent ability of aflatoxins to induce liver cancer, and the significant economic and public health consequences that follow, that has stimulated much of the work on these compounds over the last 30 years. 

Metal Form Entering Body Route of Absorption Target Organs for Toxicity Treatment ... 

B. Once absorbed systemically, EDB Is converted to active metabolites that become irreversibly bound to macromolecules. Including DMA, and inhibit enzymes. Metabolism of EDB involves an oxidative pathway (cytochrome P-450) and a conjugation pathway (glutathione). The liver Is a principal target organ for toxicity. 

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