Structure and Function of Skin
The structure of the skin consists of three layers: the subcutaneous fat, the dermis, and the epidermis, and includes appendages such as hair follicles, sebaceous glands, sweat glands, and nails. Among these, the dermis is mainly composed of fibroblasts, which produces collagen to provide strength and durability to the dermis, supports the epidermis, and produces elastin to make the skin elastic and flexible. Immune cells such as macrophages and dendritic cells are located here, so inflammatory responses begin in this layer, and hair follicles are also located here. The epidermis is the outermost layer of the skin, and has a few nerve endings that can sense pain, but no blood vessels or lymphatic systems. The epidermis varies in thickness from 50 to 150 µm and is composed of five layers.
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| Structure of the human epidermis |
The human skin is the largest organ of the body, accounting for 15% of the total body weight and covering an area of approximately 2 m2. It provides physical barrier protection, immune surveillance, UV protection, and helps the body maintain homeostasis by preventing excessive water loss from the body and maintaining electrolyte balance.
What is the skin barrier?
The outermost layer, the stratum corneum, is composed of a lipid matrix made of ceramides, free fatty acids, and cholesterol, and 10-15 layers of flattened dead cells (corneocytes) made of keratin, which is called the 'brick and mortar' model (Am Ins Chem Eng. 1975). This thin layer, which is only 10 µm thick, acts as the first line of defense protecting the human body from microorganisms, ultraviolet rays, toxic substances, and mechanical damage, and is therefore called the 'skin barrier'.
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| Structure of the stratum corneum (Cosmetics 2019) |
Path of chemical absorption through the skin
In essence, the skin is a defense organ, not an absorption organ. The stratum corneum (SC), the front line of defense, has difficulty permeating molecules larger than 500 Da or hydrophilic molecules due to its dense structure and composition (Exp. Dermatol. 2000). On the other hand, substances smaller than 500 Da and fat-soluble can be absorbed through the stratum corneum. The stratum corneum varies in thickness depending on the body part, and also varies depending on age and external environment, so the degree of drug absorption varies. However, areas composed of mucous membranes such as the anus and genitals do not have a stratum corneum, so they are absorbed more easily and enter the bloodstream directly. Suppositories are commonly made using this principle.
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| suppository |
Three routes of percutaneous absorption
There are three routes for drug absorption into the skin: ① Appendageal route (absorbed into the dermis through hair follicles and sweat glands), ② Intracellular route (directly passing through the cell membranes of the epidermis), and ③ Intercellular route (absorbed into intercellular lipids). Through these routes, the drug is diffused and divided, penetrates into the skin, diffuses through the epidermis into the dermis, is absorbed into the capillaries, and is then delivered to the entire body to exert its effects. This is called transdermal drug delivery (TDD) or percutaneous absorption. Since corneocytes are made of crystalline keratin, intracellular diffusion is difficult, so the intercellular route is the general skin absorption route. However, recently, the route through hair follicles is also considered an important route for percutaneous absorption.
 The route by which drugs are absorbed into the skin (J pharma. invest. 2018) |
The transdermal absorption route is recognized as an alternative to oral intake because it is not metabolized in the liver or stomach, so the drug effect takes effect immediately, the drug concentration is maintained continuously, and problems such as gastrointestinal disorders can be reduced. However, it is not easy to penetrate the skin barrier of the stratum corneum, so only a few products are commercialized, and most of them are fat-soluble drugs with small molecular weights (Experi. Derma. 2000). The first transdermal delivery drug approved by the FDA was the scopolamine patch for motion sickness in 1979, and the well-known 'Kymite' is the scopolamine patch. |
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| 'Kimite', a motion sickness patch containing scopolamine as the main ingredient |
Does shampoo really cause hair loss?
The root part of the hair follicle (infundibulum) is the starting point of epidermal differentiation, so the size of the epidermal cells is small and the structure is not dense, so the function as a barrier is incomplete (Pinkus et al, 1981). In addition, because of the cylindrical structure of the hair follicle, it acts as a kind of storage (reservoir) for storing chemicals and is a route that can directly reach the dermis, so the hair follicle is evaluated as having the highest efficiency of percutaneous absorption (Exp Dermatol, 2000). It was known that the area of the hair follicle is only 0.1% of the total skin area, so the effect on percutaneous absorption is minimal, but it was recently revealed that the density and size of the hair follicle greatly differ depending on the body part, and the surface area can be up to 10% larger in the skin around the mouth and scalp, and the degree of drug absorption also varies accordingly (J. Dermatol. Sci. 2010). In particular, the scalp has numerous hair follicles, approximately 80,000 to 100,000, so even large chemicals can be easily absorbed. Hair follicles contain one or more sebaceous glands, so it is recognized as the body part with the highest sebum production, making it easy to absorb hydrophobic compounds.
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| Structure of the hair follicle (ParmSciTech, 2009) |
Shampoo composition
The composition of shampoo is anionic surfactants, cationic surfactants, and nonionic surfactants. Among them, anionic surfactants are used as the main ingredient of shampoo because they produce foam (foaming power) and have excellent cleansing effects, while cationic and nonionic surfactants play auxiliary roles. As a representative anionic surfactant, sodium lauryl sulfate (SLS) is used in various skin irritation reaction studies, and when stimuli that damage the skin barrier are classified as corrosive and stripping, it is a representative corrosive irritant that chemically damages the skin barrier, causes inflammation, and increases skin moisture loss. SLS is used up to 50% in wash-off products, and is especially used in shampoos and is the most widely used because it is cheap.
Toxicity of Shampoo
According to the 2018 Food and Drug Administration's risk assessment report, SLS was evaluated as having a low risk of causing harm to the human body when exposed to the whole body. Since SLS is not managed as a raw material with a ban or usage limit in Europe, Japan, and the United States, Korea has not set a usage limit accordingly (Korea seems to mostly follow foreign countries when setting standards). However, the toxicity standard value used to calculate the safety margin in this report is the result of an experiment conducted by oral administration, so it is limited in judging the hazard when exposed to the skin for a long period of time through the percutaneous absorption route. It is regrettable that the safety of cosmetic raw materials applied to the skin was evaluated based on toxicity in a systemic aspect while including references to skin irritation in the report.
The occurrence of irritant contact dermatitis caused by surfactants is more often caused by repeated long-term exposure at low concentrations than by short-term contact at high concentrations in real life. The effect can be accelerated by differences in individual hair washing habits (washing hair tightly twice at a time, not rinsing properly, washing hair several times a day, or using a large amount of shampoo (absorption rate increases in proportion to concentration)). Even a small amount of 0.1% of SLS remaining on the skin can cause skin irritation, and repeated exposure can destroy the immune system of the scalp and skin, so it is thought that shampoo can sufficiently cause hair loss by lowering scalp function. There are various causes of hair loss, so it is difficult to determine which one is the culprit, but the fact that what used to be a male-type disease is now occurring in women as well may be due to surfactants. Women's skin is thinner than men's skin, so it can be affected more easily, and they use cosmetics much more than men.
Among the anionic surfactants of the sulfate series widely used in shampoos, sodium (ammonium) laureth sulfate (SLES) and ammonium lauryl sulfate (ALS), like SLS, are not banned or restricted raw materials in Europe, the United States, Japan, and Korea, but can be used without restrictions. However, as anionic surfactants, they have high skin penetration and can cause irritation, and they also act as catalysts that increase the skin penetration of other substances. This is why they are mixed with surfactants to make a foam formulation to increase the absorption of minoxidil, a hair loss treatment.
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| Minoxidil foam product |
Surfactants are typical environmental hormones that not only irritate the skin, but also disrupt the endocrine system when absorbed into the body. Unlike traditional toxic substances, environmental hormones are affected by complex interactions with hormones in the body, so it is not easy to evaluate their safety and set limits for use because their toxicity does not increase in a concentration-dependent manner. At least, it seems clear that the exposure standards for chemicals set in the traditional toxicity concept are not accurate in terms of environmental hormones. Since we cannot avoid being exposed to numerous environmental hormones and chemicals while living in modern society, it is impossible to completely avoid them even if standards are set, but at least if we are aware of them, we can minimize the effects on our bodies.