The transport of foreign substances through the skin and into the body is known as dermal or percutaneous absorption. This process is a significant route of exposure for toxins, chemicals, and medications. While the skin provides a robust defense against the external environment, it is not entirely impenetrable, allowing some molecules to pass through its layers. Understanding the specific routes and factors that govern this entry is essential for assessing chemical hazards.
The Skin’s Role as a Permeability Barrier
The skin acts as a sophisticated barrier, protecting the internal environment and regulating water loss. The primary obstacle to chemical entry is the outermost layer of the epidermis, called the stratum corneum. This layer is often described using a “brick-and-mortar” analogy. The “bricks” are corneocytes, which are flattened, dead cells filled with keratin filaments.
The “mortar” is a highly organized, complex lipid matrix surrounding these cells, composed mainly of ceramides, cholesterol, and fatty acids. This lipid-rich, hydrophobic layer determines the skin’s low permeability to most substances. Although relatively thin (typically 15 to 20 layers of cells), the stratum corneum limits the rate at which chemicals diffuse into deeper tissues. Any substance must first navigate this dense, lipid-based layer to reach the living cells below.
Detailed Pathways of Dermal Permeation
Once a substance breaches the surface, it can follow one of three primary pathways to penetrate the skin layers. The most common route is the intercellular pathway, which requires the toxin to move through the narrow channels of the lipid matrix surrounding the corneocytes.
The transcellular route is another possibility, where the substance must pass directly through the interior of the corneocytes themselves. This requires repeatedly crossing the lipid cell membranes and the internal cellular components. The chemical’s molecular properties, particularly its size and lipid solubility, determine which transepidermal route it favors. Small, lipid-soluble molecules generally find the lipid-rich intercellular route easier to navigate.
The third, less common but faster route is the transappendageal or shunt pathway, which utilizes the skin’s appendages. These include hair follicles and the ducts of sweat and sebaceous glands. Although these structures account for a small fraction of the total skin surface area, they offer a less restrictive path to bypass the dense stratum corneum. This shunt pathway is relevant for the rapid initial absorption of large or highly polar molecules that struggle to cross the main epidermal barrier.
Chemical and Biological Factors Influencing Absorption
Dermal absorption is governed by a combination of chemical and biological variables. Chemically, molecular weight is a major factor; molecules typically need to be under 500 Daltons to penetrate the stratum corneum effectively. A substance’s partition coefficient, which describes its relative solubility in oil versus water, is also influential. Lipophilic substances generally penetrate the lipid-rich barrier more readily than hydrophilic ones.
The concentration and duration of contact directly impact the total amount absorbed. Additionally, the vehicle, or the formulation in which the substance is delivered, can alter its penetration. Biological factors also modify absorption, such as skin hydration, where increased moisture weakens the barrier function and boosts permeability. Damage to the skin, including cuts, abrasions, or dermatitis, compromises the stratum corneum, allowing substances to bypass the primary defense layer and increasing absorption.
Systemic Entry and Biological Impact
After a toxin navigates the stratum corneum, it reaches the dermis layer. The dermis contains a network of blood vessels and lymphatic capillaries that absorb the penetrating substance. This absorption into the microvasculature marks the point of systemic entry, where the substance is swept away from the contact site. Blood circulation then rapidly distributes the absorbed toxin throughout the body.
Once circulating, the chemical can reach various target organs, causing systemic toxicity remote from the initial exposure. The body’s detoxification mechanisms, including metabolism by enzymes in the skin and liver, attempt to modify the toxin into less harmful, excreted forms. If the absorbed dose is sufficient, however, the toxin can disrupt normal biological functions, leading to effects such as neurotoxicity or organ damage.