Toxicokinetics subcutaneous

Toxicity data in animals indicated that similar effects occur after exposure to CDDs by oral, dermal, or parenteral routes. Toxicokinetic data in mice showed that 2,3,7,8-TCDD hepatic levels were similar following oral, intraperitoneal, and subcutaneous exposure (Nau and Bass 1981). However, recent data in rats showed that intratracheal administration of a 2,3,7,8-TCDD dose resulted in a relatively higher accumulation of 2,3,7,8-TCDD in the liver than after oral administration of the same dose (Diliberto et al. 1996). Intraperitoneal administration of 2,3,7,8-TCDD was less toxic than oral dosing in acute-exposure experiments with hamsters (Olson et al. 1980a). 

Due, A.H., Trap, H.C., Langenberg, J. P, and Benschop, H.P, Toxicokinetics of soman stereoisomers after subcutaneous administration to atropinized guinea pigs. Arch. Toxicol, 68, 60, 1994. 

Studies in laboratory animals have also shown the influence of metals on the toxicokinetics of plutonium. Pretreatment of rats with a subcutaneous injection of cadmium or copper followed by an intravenous injection of plutonium-239 or plutonium-238 resulted in changes in the distribution patterns of plutonium, but not in total retention of either isotope. Plutonium retention of both isotopes, following pretreatment with either metal, was increased in the spleen and the kidneys, as compared to animals treated with plutonium only (Volf 1980). Copper pretreatment appeared to increase the retention of plutonium in the liver, while cadmium pretreatment appeared to decrease plutonium retention in the liver. These differences in retention of plutonium in the liver may reflect different properties of the respective metal- binding proteins or different mechanisms of action (Volf -1980). 

There are very limited quantitative toxicokinetic data on L. Although there are no published estimates of the diffusion rates of L through the skin, observations from acute toxicity studies indicate that it penetrates rapidly. Studies of the kinetics of elimination of arsenic after subcutaneous injection of L in rabbits show that it is eliminated with a half life of 55-75 hours. The primary metabolite of L is 2-chlorovinyl-arsenous acid, which is formed by hydrolysis. This metabolite, like the parent compound, is able to bind to sulphydryl containing proteins. It is this property that is believed to be responsible for the toxicological effects of L, although no primary biochemical lesion has been identified. In rabbits the apparent volume of distribution... 

A. H. Due, H. C. Trap, J. P. Langenberg and H. P. Benschop, Toxicokinetics of Soman Stereoisomers After Subcutaneous Administration to Atropinized Guinea-Pigs, Arc/ . Toxicol, 1994,68, 60-63. 

Zhang and Wu (1987) chose the small pig (male and female, black, 4.2-13.0 kg) because of the aforementioned resemblance of its skin to that of humans. They chose this model to study the percutaneous toxicokinetics of occluded liquid sulfur mustard, and studied the iv route in this species as the reference route, as well as the toxicokinetics after subcutaneous (sc) exposure. 

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