Dermal penetration

General metabolism (biotransfomiation) Dermal penetration Domestic animal safety... 

Exercise also increases skin circulation and perspiration, which both enhance dermal penetration of compounds into the body. Furthermore, skin lesions, such as wounds and dermatitis, can increase the permeability of the skin to chemicals. Also, exposure of the skin to solvents and removal of skin fat increase dermal penetration of a number of compounds. Compounds penetrate the skin more readily in places where the skin is thin, like the face, hands and scrotum. Increased dermal blood flow due to exercise facilitates the penetration of the skin by chemicals. 

Because skin exhibits many of the properties of a lipid membrane, dermal penetration can often be enhanced by increasing a molecule s lipophilicity. Preparation of an ester of an alcohol is often used for this purpose since this stratagem simultaneously time covers a hydrophilic group and provides a hydrophobic moiety the ready cleavage of this function by the ubiquitous esterase enzymes assures availability of the parent drug molecule. Thus acylation of the primary alcohol in flucinolone (65) with propionyl chloride affords procinonide (66) the same transform... 

Sex differences in uptake and metabolism of trichloroethylene have been seen in both humans and animals (see Section 2.8). Studies with male and female rats given various levels of testosterone have implicated this hormone in determining the degree of dermal penetration of trichloroethylene (McCormick and Abdel-Rahman 1991). The mechanism behind this effect is still unclear. 

Snodgrass HL, Metker LM. 1992. Dermal penetration of C-14-labelled diisopropyl methylphosphonate in swine. J Toxicol Environ Health 36(4) 367-376. 

Trigard 75 WP is a new insecticide with a unique mode of action and a unique triazine structure. It is a solid formulated as a wettable powder and is packaged in water-soluble bags. The active ingredient in Trigard has the common name cyromazine. Cyromazine is a triazine, but, unlike the well-known triazine herbicides, this compound has insecticidal properties and no herbicidal activity. Cyromazine has low mammalian toxicity and low vapor pressure. It is hydrophilic, so dermal penetration is expected to be... 

The presence of titania particles in sunscreens was the main reason for the investigation of its dermal penetration properties, and a study suggested that fine particles (10-50 nm) can penetrate the skin, although the sample size was too small to... 

Grissom, R.E., Jr. C. Brownie, and F.E. Guthrie. 1987. In vivo and in vitro dermal penetration of lipophilic and hydrophilic pesticides in mice. Bull. Environ. Contam. Toxicol. 38 917-924. 

Research studies investigating exposure to JP-8 via oral administration offers an alternative examination of the systemic effects of JP-8 on immune function. Admittedly, this does not ideally mimic occupational exposures, but it does eliminate technical limitations associated with inhalation and dermal penetration of JP-8. It has been suggested that the only route available that can assess the whole mixture (JP-8 in its entirety), without fractionation due to volatilization of components, is the oral route [1] as select components of JP-8 may have increased permeability during dermal exposure, other specific components may be enriched following inhalation exposures[71]. 

Turkall, R., Skowronski, G., Suh, D., and Abdel-Rahman, M., Effect of a chemical mixture on dermal penetration of arsenic and nickel in male pig in vitro, J. Toxicol. Environ. Health, Part A, 66, 647, 2003. 

Hexachloroethane has been found in the plasma of workers wearing protective clothing and respiratory protection suggesting that hexachloroethane can be absorbed following inhalation and/or dermal exposure. Based on the minimal effects seen on target tissues (liver and kidney) in animal studies, absorption from the lungs seems to be limited. Dermal absorption was also estimated to be low based on calculated dermal penetration rates. 

Gute, B. D., Grunwald, G. D., Basak, S. C. Prediction of the dermal penetration of polycyclic aromatic hydrocarbons (PAHs) A hierarchical QSAR approach. SAR QSAR Environ. Res. 1999, 10, 1-15. 

Absorption Across the Skin. An aqueous carrier may be used for a variety of dermal products. In fact, carriers can be designed to limit the transportation of the penetration of the active ingredient (such as an insect repellent), if the desired effect is to keep the activity on the surface of the skin. Once again, however, only those materials that are dissolved will be available for penetration across the skin to gain access to the systemic circulation. For almost all chemicals in or about to enter commerce, dermal penetration is a passive process. The relative thickness of the skin makes absorption (into the systemic circulation) slower than the absorption across the GI or pulmonary barriers. This is compounded by the fact that the stratum comeum ftmction is to be impervious to the environment. One of the skin s major functions is protection from infection. Once a chemical penetrates into the dermis, it may partition into the subcutaneous fat. Essentially, absorption across the skin is a two-step process with the first being penetration and deposition into the skin and the second being release from the skin into the systemic circulation. The pattern of blood levels obtained via dermal penetration is generally one with a delayed... 

Given the overwhelming influence of the physical properties of skin in determining bioavailabilities via the dermal route, assessment of dermal penetration is one area in metabolism and toxicology where in vitro methods can be effectively used to predict in vivo results and to screen chemicals. Apparatus and equipment exist that one can use to maintain sections of skin (obtained from euthanized animals or from human cadavers or surgical discard) for such experiments (Holland et al., 1984). These apparatus are set up to maintain the metabolic integrity of the skin sample between two reservoirs the one on the stratum comeum side, called the application reservoir and the one on the subcutaneous side, called the receptor reservoir. One simply places radiolabeled test material in the application reservoir and collects samples from the receptor fluid at various time points. 

R. H. Larsen, F. Nielsen, J. A. Sorensen, and J. B. Nielsen. Dermal penetration of fentanyl Inter- and intraindividual variations. Pharmacol. Toxicol. 93 244-248 (2003). 

Skowronski GA, Kadry AM, Turkall RM, et al. 1994. Soil decreases the dermal penetration of phenol in male pig in vitro. J Toxicol Environ Health 41 467-479. 

Preliminary predictions of absorption of a substance can be made from its physico-chemical properties if no other information is available. Also elaborate computer programs are available that make predictions about, e.g., dermal penetration or metabolic pathways. However, these systems have often not been extensively validated against appropriate experimental data and it is not always certain if the results obtained in such models reflect the situation in vivo. On this basis, modeled data should only be used for risk assessment purposes where it is supported by other kinds of evidence. 

Dermal penetration of butane is not expected to any large extent, as skin contact would be transient because of volatility. n-Butane did not cause respiratory or eye irritation in rabbits, but it was mildly to moderately irritating to the skin. Liquefied butane may cause frostbite when applied directly to the skin. ... 

Dermal penetration of/V-nitroso[ C]diethanolamine (4 xg/cm ) in vivo was investigated by applying skin lotion and acetone to 3-15 cm of the skin of monkeys (the abdomen) and pigs (the back) for a 24-h contact time. The skin penetration capacity was greater in monkeys (23% in skin lotion, 34% in acetone) than in pigs (4% in skin lotion, 11.5% in acetone) and the permeability was greater from acetone than skin lotion (Marzulli et al., 1981). 

A different but very important area of chemical engineering in the life sciences involves the design and manufacture of health care systems for diagnostic or therapeutic purposes. Consider the example of controlled release drugs or dermal penetration drugs. Here the emphasis is on the system rather than on the compound. The design of these systems requires an understanding of reactions, kinetics, fluid mechanics, and membrane systems. 

Shah PV, Monroe RJ, Guthrie FE, et al. Comparative rates of dermal penetration of insecticides in mice. Toxicol AppI Pharmacol 1981 59 414 23. 

In connection with studies on structure-property relationships with dermal penetration enhancers, substituted azepinone derivatives (e.g., 74, R = Me and 75, R = Me) were made by Kim et al. from the 3-aminoazepanone 71 via 72 and 73 using standard functional group manipulations (Scheme 8) <2001MI183>. 

Although for a variety of reasons extrapolation from experimental animals to humans presents problems, including differences in metabolic pathways, dermal penetration, mode of action, and others, experimental animals present numerous advantages in testing procedures. These advantages include the possibility of clearly defined genetic constitution and their amenity to controlled exposure, controlled duration of exposure, and the possibility of detailed examination of all tissues following necropsy. 

Carbamates are most frequently absorbed by inhalation, ingestion, or dermal penetration, and actively metabolized via the liver. Their degradation products are excreted by both the kidneys and liver. 

Infrared microscopic imaging provides the significant advantages of direct spatially resolved concentration and molecular structure information for sample constituents. Raman microscopy (not further discussed in this chapter) possesses the additional benefit of confocal acquisition of this information and a 10-fold increase in spatial resolution at the expense of reduced signal-to-noise ratios compared with IR. The interested reader is urged to check the seminal studies of the Puppels group in Rotterdam,38 0 as well as our own initial efforts in this direction.41 The current section describes the initial applications of IR microspectroscopic imaging to monitor the permeation and tissue distribution of the dermal penetration enhancer, DMSO, in porcine skin as well as to track the extent of permeation of phospholipid vesicles. 

Michniak, B.B., et al. 1993. In-vitro evaluation of a series of azone analogs as dermal penetration enhancers. Int.]. Pharmaceutics 91 85-93. 

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