Absorption (skin)

Skin absorption is a route by which substances can enter the body through the skin. Along with inhalation, ingestion and injection, dermal absorption is a route of exposure for toxic substances and route of administration for medication. Absorption of substances through the skin depends on a number of factors, the most important of which are concentration, duration of contact, solubility of medication, and physical condition of the skin and part of the body exposed. Skin absorption is a route by which substances can enter the body through the skin. Along with inhalation, ingestion and injection, dermal absorption is a route of exposure for toxic substances and route of administration for medication. Absorption of substances through the skin depends on a number of factors, the most important of which are concentration, duration of contact, solubility of medication, and physical condition of the skin and part of the body exposed. Skin (percutaneous, dermal) absorption is the transport of chemicals from the outer surface of the skin both into the skin and into circulation. Skin absorption relates to the degree of exposure to and possible effect of a substance which may enter the body through the skin. Human skin comes into contact with many agents intentionally and unintentionally. Skin absorption can occur from occupational, environmental, or consumer skin exposure to chemicals, cosmetics, or pharmaceutical products. Some chemicals can be absorbed in enough quantity to cause detrimental systemic effects. Skin disease (dermatitis) is considered one of the most common occupational diseases. In order to assess if a chemical can be a risk of either causing dermatitis or other more systemic effects and how that risk may be reduced one must know the extent to which it is absorbed, thus dermal exposure is a key aspect of human health risk assessment. Along with inhalation, ingestion and injection, dermal absorption is a route of exposure for bioactive substances including medications. Absorption of substances through the skin depends on a number of factors: In general the rate of absorption of chemicals through skin follows the following scheme from fastest to slowest: Scrotal > Forehead > Armpit ≥ Scalp > Back = Abdomen > Palm = under surface of the foot. To be absorbed through the skin, a chemical must pass through the epidermis, glands, or hair follicles. Sweat glands and hair follicles make up about 0.1 to 1.0 percent of the total skin surface. Though small amounts of chemicals may enter the body rapidly through the glands or hair follicles, they are primarily absorbed through the epidermis. Chemicals must pass through the seven cell layers of epidermis before entering the dermis where they can enter the blood stream or lymph and circulate to other areas of the body. Toxins and toxicants can move through the layers by passive diffusion. The stratum corneum is the outermost layer of the epidermis and the rate-limiting barrier in absorption of an agent. Thus, how quickly something passes through this thicker outer layer determines the overall absorption. The stratum corneum is primarily composed of lipophilic cholesterol, cholesterol esters and ceramides. Thus lipid-soluble chemicals make it through the layer and into the circulation faster, however nearly all molecules penetrate it to some minimal degree. Absorption of chemicals in municipal water and dental products such as VOC (Volatile Organic Compounds), TTHM (Total Trihalomethanes), fluoride and disinfectants is a major exposure to environmental health hazards. Agents that injure the stratum corneum, such as strong acids, are absorbed faster than chemicals that do not. Skin damage due to burns, abrasions, wounds and skin diseases also increase absorption. Thus populations with skin damage may be more susceptible to adverse effects of agents that are absorbed through the skin. Certain solvents like dimethyl sulfoxide (DMSO) act as carriers and are frequently used to transport medication through the skin. DMSO increases the permeability of the stratum corneum. Surfactants like sodium lauryl-sulfate increase the skin penetration of water-soluble substances, possibly by increasing the skin permeability of water. Dermal application of a medication or chemical allows treatment to be localized, unlike ingestion or injection. Some medications seem to be more effective (or are more efficient) using the dermal route of administration. Some ingested drugs are heavily metabolized by the liver and may be inactivated, but using a dermal application bypasses this metabolic step allowing more parent compounds to enter the peripheral circulation. If a drug is absorbed well through the skin it may be used as a means of systemic medication. Dermal dosage forms include: liniments, braces, lotions, ointments, creams, dusting powders, aerosols, and transdermal patches. Specially designed patches are currently used to deliver fentanyl, nicotine and other compounds. Slower skin absorption versus oral or injectable may allow patches to provide medication for 1 to 7 days. For instance nitroglycerin given transdermally may provide hours of protection against angina whereas the duration of effect sublingually may only be minutes. The amount of chemical that is absorbed through the skin can be measured directly or indirectly. Studies have shown there are species with differences in the absorption of different chemicals. Measurements in rats, rabbits or pigs may or may not reflect human absorption. Finding the rate at which agents penetrate the skin is important for assessing the risk from exposures. A chemical may be directly applied to the skin followed by blood and urine measurements, at set time points after the application, to assess the amount of chemical that entered the body. The concentration in the blood or urine at particular time points can be graphed to show an area under the curve and the extent and duration of absorption and distribution to provide a measure of systemic absorption. This can be done in animals or humans with a dry chemical powder or a chemical in solution. Rats are commonly used for these experiments. An area of skin is shaved before the chemical is applied. Often the area of chemical application is covered to prevent ingestion or rubbing off of the test material. Samples of blood and urine are taken at specific time intervals following application (0.5, 1, 2, 4, 10, and 24 hours) and in some protocols at the chosen end time the animal maybe necropsied. Tissue samples may also be evaluated for the presence of the test chemical. In some test protocols many animals may be tested and necropsies may occur at set intervals after exposure. Biomonitoring, such as taking urine samples at intervals, from workers exposed to chemicals may provide some information but it is difficult to distinguish dermal from inhalation exposure using this method.