Absorption across the skin

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... 

No quantitative studies were located regarding bromomethane absorption across the skin of humans or animals. 

In developing protein and peptide trans-dermal delivery systems, one must be mindful of the high interindividual variation in drug absorption across the skin. Large variations in bioavailability have been demonstrated with fentanyl patches, initially intended for postoperative pain relief but later abandoned due to unacceptable variability among individuals receiving the same dose [9]. Response in postoperative patients to the application of a fentanyl patch ranged from ineffective pain relief to severe respiratory depression, and effects were correlated with variations in plasma fentanyl levels [9]. 

This is the primary barrier to drag absorption across the skin. Transdermal bioavailability therefore and strategies to improve delivery often involve changing the composition or the organization of the intercellular lipids. Such enhancing technologies are of course feasible, but not without problems (see below). 

Absorption across the skin is probably slight and methods of pesticide use rarely include a hazard of inhalation, but uptake of ingested fluoride by the gut is efficient and potentially lethal. Excretion is chiefly in the urine renal clearance of fluoride from the blood is rapid. However, large loads of absorbed fluoride poison renal tubule cells. Functional tubular disturbances and sometimes acute renal failure result. 

There is limited absorption across the skin and intestinal lining of mammals, after which enzymatic hydrolysis and excretion rapidly eliminates the pesticide from tissnes. Irritant effects are not reported, and systemic toxicity is low. Methemoglobinemia is a theoretical risk from chloroaniline formed hydrolytically, bnt no reports of this form of toxicity have been reported in hnmans or animals from diflnbenznron exposnre. 

In addition to the descriptors already identified for use with the LD50 value, species and time at which decedents are counted, another must be added regarding LCtso (route need not normally be considered LCtso usually refers to inhalation, although in experimental studies absorption across the skin might be being studied). 

Absorption across the skin has long been recognised as an important primary route of entry of toxic agents into the body. However, percutaneous absorption is complex, variable and affected by a variety of factors and still defies simple measurement. The rates of skin penetration are unknown for most liquids, solids and gaseous substances. 

Toxicity values are separately developed for different exposure routes. Typically, values are developed for the oral and inhalation routes of exposure because the majority of toxicity studies are based on these exposure routes. In most cases, the oral values are used for the skin exposure route, adjusted for decreased absorption across the skin relative to the oral route. Two types of toxicity values are currently used in risk assessment those describing cancer potency and those for non-cancer effects. Some chemicals are known to have both cancer and non-cancer effects. In these situations, both cancer and non-cancer values might be developed. Therefore, each chemical might have up to four toxicity values. Toxicity values for cancer and non-cancer effects are separately discussed below. 

Hexachloroethane caused reversible corneal injury in rabbits following ocular contact, but contact with the skin for 24 hours resulted in no dermal effects (Weeks et al. 1979). The physical properties of hexachloroethane suggest that absorption across human skin would be limited (Fiserova-Bergerova et al. 1990). Therefore, unless dermal absorption studies indicate that this prediction is incorrect, there is no need for additional studies of acute dermal toxicity. 

Kirschner, L. B. (1983). Sodium chloride absorption across the body surface frog skins and other epithelia, Am. J. Physiol., 244, R429-R443. 

Term (that takes area into consideration) used to describe the movement of a chemical across a harrier. Most typically used to describe the absorption of a chemical across the skin as... 

Substances that can potentially be taken up across the skin include gases and vapors, liquids and particulates. Liquids and substances in solution are taken up more readily than dry particulates. Dry particulates will have to dissolve into the surface moisture of the skin before uptake can begin. Absorption of volatile liquids across the skin may be limited by the rate at which the liquid evaporates off the skin surface. As a result of binding to skin components, the uptake of chemicals with the following groups can be slowed certain metal ions, acrylates, quaternary ammonium ions, heterocyclic ammonium ions, and sulfonium salts. 

The occurrence of coma, death, and systemic effects in two humans dermally exposed to cresols (Cason 1959 Green 1975) indicates that these compounds can be absorbed through the skin. No studies were located that sought to quantify the rate or extent of absorption in intact humans. An in vitro study of the permeability of human skin to cresols found that these substances had permeability coefficients greater than that for phenol, which is known to be readily absorbed across the skin in humans (Roberts et al. 1977). 

The skin represents the largest organ in the human body, and one of its primary functions can be seen as a physical barrier to absorption of toxicants. The other major routes of toxicant entry into the body are through the respiratory and gastrointestinal tract, which can be seen to offer less resistance to toxicant absorption than the skin. In general, the respiratory tract offers the most rapid route of entry, and the dermal the least rapid. One reason for this major difference is primarily because membrane thickness, which is really the physical distance between the external environment (skin surface, air in the lung, or lumen of the gut) and the blood capillaries, varies across these portals of entry. The overall entry depends on both the amount present and the saturability of the transport processes involved. 

QSARs utilized by the U.S. EPA for the prediction of the dermal uptake (absorption through the skin) of compounds are well described by Walker et al. (2002). Predictions of the ability of chemicals to be absorbed across the skin allowed for the potential of dermal toxicity to be assessed. Typically simple regression-based QSARs, which were based either on hydrophobicity and molecular size, or hydrophobicity alone, were utilised. 

Dermal absorption, the process by which a substance is transported across the skin and taken up into the living tissue of the body (USEPA, 1992), is a complex process. The skin is a multilayered biomembrane with particular absorption characteristics. It is a dynamic, living tissue and as such its absorption parameters are susceptible to constant changes. Upon contact with the skin, a portion of the substance can penetrate into the non-viable stratum comeum and may subsequently reach the viable epidermis, the dermis and, ultimately, the vascular network. During the absorption process, the compound may be subject to biotransformafion (Noonan and Wester, 1989). The stratum comeum provides the skin its greatest barrier function against hydrophilic compounds, whereas the viable epidermis is most resistant to highly lipophilic compounds (Flynn, 1985). 

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