Percutaneous route

Aniline is lipophilic (pKa of 4.6) and is expected to be rapidly and completely absorbed in the small intestine (Kao et al. 1978). No information on relative bioavailability following inhalation exposure was located, but as indicated by methemoglobin formation during inhalation experiments, systemic absorption by both the inhalation and the percutaneous routes is extensive. Percutaneous absorption of aniline in hairless mice was 4.7% of the nominal applied doses (Susten et al. 1990). 

Discussion An effort to see if the skin was permeable to BZ. We used benzyl alcohol as the vehicle in 31 cases and Cresol/N-ethylmorpholine in 12 cases. We limited the freguency of examination since most subjects showed no significant changes except at the highest dosage. Noticeable effects appeared mostly after a delay of 24 hours, suggesting that the percutaneous route is relatively ineffective. Estimated Intensity of response was only 5-10% of that observed by the intravenous route, but duration of effects was similar (after the 24-hour delay). 

In animal studies, TMAN had a low acute toxicity when administered by the oral or the percutaneous route. Rats given 10,000 ppm in the diet for 90 days showed an increase in the number of white blood cells. Inhalation of... 

The permeability of the skin to a toxic substance is a function of both the substance and the skin. The permeability of the skin varies with both the location and the species that penetrates it. In order to penetrate the skin significantly, a substance must be a liquid or gas or significantly soluble in water or organic solvents. In general, nonpolar, lipid-soluble substances traverse skin more readily than do ionic species. Substances that penetrate skin easily include lipid-soluble endogenous substances (hormones, vitamins D and K) and a number of xenobiotic compounds. Common examples of these are phenol, nicotine, and strychnine. Some military poisons, such as the nerve gas sarin (see Section 18.8), permeate the skin very readily, which greatly adds to then-hazards. In addition to the rate of transport through the skin, an additional factor that influences toxicity via the percutaneous route is the blood flow at the site of exposure. 

Kulkami, A.S., Vijayaraghavan, R. et al. (2006). Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality and toxicity of sulfur mustard administered through percutaneous route. J. Appl. Toxicol. 26 115-25. 

Kumar, O., Sugendran, K., Vijayaraghavan, R. (2001). Protective effect of various antioxidants on the toxicity of sulphur mustard administered to mice by inhalation or percutaneous routes. Chem. Biol. Interact. 134 1-12. 

The G-nerve agents include GA (tabun, ethyl A,A-dimethyl-phosphoramidocyanidate), GB (sarin, isopropyl-methylphosphonofluoridate), GD (soman, 1,2,2-tri-methylpropyl methylphosphonofluoridate), and VX (o-ethyl 5-[2-(diisopropylamino)ethyl] methylphosphonothiolate). The V-type nerve agents are several orders of magnitude less volatile than the G-type agents and act primarily as a liquid via the percutaneous route for example, VX is several orders of magnitude more lethal percutaneously than sarin (Reutter, 1999). 

Blood cholinesterase measurements were made on the 4 subjects that received CD by the percutaneous route. None of these subjects showed any significant decrease In their ChE levels over a 2-week period. No complaints or severe effects reportedly were observed in any of the subjects tested by this route at the doses used. Two of the subjects who received GD by the Intravenous route, although treated with oxime and/or atropine showed significant decrease in the ChE levels, and exhibited the "usual physiological responses from this agent. Weakness and muscle contractions were also... 

Reservoir hosts include especially rats, mice, hedgehogs, hamsters and various domesticated animals. Leptospirosis is therefore a globally distributed zoonosis. Transmission to humans occurs via the oral or percutaneous route with small skin or mucosal lesions serving as portals of entry for the pathogens, which are excreted in the urine of infected animals. 

A comprehensive account of the pharmaceutics and biopharmaceutics of topical preparations is not possible here. This section has therefore been deliberately restricted in scope to deal with the physicochemical principles involved in the process of treating the skin or in systemic medication by the transdermal or percutaneous route. Formulation of topical vehicles for the potent dmgs applied to the skin is now an exact art. It is readily demonstrated that the... 

Nerve agent VX is a persistent agent which presents both a vapor and a percutaneous threat. VX is not very volatile, so it presents much less vapor hazard than GA and GB however, it is 100 times more toxic by the percutaneous route. Therefore, if VX is aerosolized due to an explosive release, it presents a percutaneous downwind hazard. Thermal decomposition rates of VX are 1.5 hours at 200°C (392°F), 4 minutes at 250°C (482°F), and 36 seconds at 295°C (563°F). In practical terms, a toxic dose of VX is more likely to result from skin rather than respiratory exposure however, all nerve agents are sufficiently volatile to pose an inhalation hazard. At agent concentrations of 30 mg/m3 or greater, median lethal inhalation doses can be attained in a few minutes. 

The toxicokinetics of OP/nerve agents including stereoisomers at the inhalation and percutaneous routes of administration should be expanded. 

After exposure to lower concentrations, or exposure to lethal amounts via the oral or percutaneous routes, the effects are slower to develop. For example, after ingestion of a lethal dose of a cyanide salt, the casualty might have 15 to 30 minutes of survival time during which an antidote could be administered. 

As both procedures are safe to perform, the number of contraindications is relatively low. However, in children with a severe non-correctable coagulopathy, severe respiratory or cardiac problems a surgical approach would be more advisable. In some children their inherent anatomy, i.e. the absence of a good percutaneous route, or previous gastric surgery, will preclude a percutaneous approach. Dewald etal. (1999) reported this to occur in 4.4% of... 

Henry Howell (1860-1945) and is extracted nowadays from the mucous membranes in the small intestine of pigs, or from the lungs of cattle. The drug inhibits the transformation of fibrinogen into fibrin, and is now used for the treatment of thromboses, embolisms and for the prophylaxis of cardiac infarction and thrombosis. A disadvantage is, that heparin is not resorbed from the gastrointestinal tract, and has to be administered via an intravenous, subcutaneous or percutaneous route. 

Giard MJ, Uden DL, Whitlock DJ, Watson DM (1983) Seizures induced by oral viscous lidocaine. Clin Pharm 2 110 Gimenez ER, Vallejo NE, Izurieta EM, et al. (1968) Acute alcoholic intoxication by the percutaneous route. Clinical and experimental study. Arch Argent Pediatr 66 121-135 Ginsburg CM, Lowry W, Reisch JS (1977) Absorption of lindane (Y benzene hexachloride) in infants and children. J Pediatr 91 998-1000... 

From a chemical viewpoint, significant absorption of actinides via the percutaneous route would probably require the presence of a stable and lipophilic actinide complex. 

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