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Our First Line of Defense
Protecting the Skin Against Chemical Agents
BY ROBERT N. PHALEN
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The skin is often considered our body’s first line of defense. One of our largest organs, the skin helps protect us against foreign invaders and infections, helps regulate our body temperature, prevents water loss, synthesizes vitamin D, and performs many other important endocrine, immunological, and metabolic functions. It also provides a protective barrier against water and many chemical agents.
Despite the resilience of our skin, industrial hygienists should not overlook it as a route of exposure for occupational disease. NIOSH estimates that skin diseases, which are a leading cause of illness-related lost workdays in the U.S., account for 15 to 20 percent of all reported occupational diseases.
These data also do not adequately account for systemic illnesses associated with skin absorption as an additional route of entry into the body. Both ACGIH and NIOSH provide skin notations that industrial hygienists rely on to recognize potential skin absorption hazards. But only a small number of chemicals have skin notations; for many chemicals without published occupational exposure limits, we must evaluate the potential for skin absorption and take precautionary actions as needed.
The key message is that if we are not considering the skin as a route of exposure or disease, we may not be adequately recognizing, evaluating, and controlling these potential risks. Moreover, many people are sensitive about their skin and may not report their work-related condition until it affects their work. Thus, skin exposure should be integral to our hazard assessment and management system for workplace chemicals.
COMMON SKIN DISEASES Dermatitis is a general term used to describe irritation or inflammation of the skin. The cardinal signs of inflammation include redness, swelling (sometimes as blisters), heat, pain, and a loss of function (usually due to swelling and pain). Additional itching, scaling, cracking, or drying of the skin may be present. The characteristics of the inflammation can vary depending on the type of dermatitis, but in general, the signs of redness and swelling are displayed on the skin (see Figures 1 and 2). In some cases, we may see small red and swollen patches (as with oil folliculitis) and widespread inflammation and blistering in other cases (as with poison ivy or ethylene oxide).
Two types of occupational skin disorders are common: direct skin effects, such as irritant contact dermatitis (ICD), and delayed immune-mediated skin effects, such as allergic contact dermatitis (ACD).
ICD is the result of the direct action of an agent on the skin, which generates a more immediate response at the site of contact. ICD is typically caused by irritants such as detergents, oils, and solvents; corrosives such as acids and alkalis; or oxidizers. People who handle chemicals at work are more susceptible to ICD; susceptible workers include agricultural workers, cosmetologists (such as hairdressers and manicurists), electroplaters, food service workers, healthcare workers, jewelers, machinists, mechanics, and printers. Most cases of dermatitis in the workplace are associated with ICD.
ACD is an immune-mediated hypersensitivity reaction in which the inflammation is often delayed at least 12–24 hours, can occur beyond the area of contact, and can increase with subsequent exposures. Thousands of chemicals are known to cause ACD. The following have a high prevalence of reactivity: acrylates, dichromate, epoxy resins, isocyanates, natural latex proteins, nickel, and p-phenylenediamine used in hair dyes and the manufacturing of rubber and plastic. Once again, people who handle chemicals at work are more susceptible to ACD. One major concern is that if workers become sensitized to one of these agents, they may not be able to return to their job. In these cases, even very small skin exposure to the agent can result in a severe and debilitating reaction. To learn more about dermal sensitizers, see the November 2019 Synergist article “Dermal Sensitizers.”
Figure 1. Acute irritant contact dermatitis.
Figure 2. Irritant contact dermatitis resulting from oil folliculitis.
Skin cancer is also a concern for those working outdoors with direct sun exposure. A higher prevalence of basal cell and squamous cell carcinoma occurs among workers in occupations that require exposure to sunlight and ultraviolet radiation. In addition, certain chemicals are associated with skin cancer, such as inorganic arsenic, coal tar, and polyaromatic hydrocarbons (PAHs). With skin cancer, the signs of inflammation are not always present. Instead, a skin growth with an asymmetric shape, irregular border, variable color, and increasing diameter over time may indicate a cancerous lesion.
THE SKIN AS A PROTECTIVE BARRIER A basic model for the skin (see Figure 3) includes the outer nonvascular epidermis, in which the outermost layer or stratum corneum (SC) consists of nonliving skin cells, and the vascular dermis. The SC is composed mostly of flattened corneocytes, which contain a nonpolar protein called keratin (also present in our nails and hair). A lipid matrix of ceramides, fatty acids, and cholesterol surrounds the layers of corneocytes to form a barrier to water and polar compounds. The dermis contains connective tissues, nerve receptors, glands, hair follicles, and vascular tissues (that is, capillary arteries and veins). Because the dermis contains blood vessels, chemical compounds that penetrate the epidermis and reach the dermis are available for uptake into the blood and transport within the body.
SKIN ABSORPTION Skin absorption of chemicals typically occurs by diffusion from an area of higher concentration to an area of lower concentration. In humans, the two primary routes of skin absorption through the protective SC include the intercellular route and the transcellular route. With the intercellular route, chemicals repelled by the SC and surrounding lipid matrix must pass around the overlapping layers of corneocytes. It is a tortuous route that can slow the diffusion and limit the amount of a chemical that can pass through the SC. This is why the SC is an excellent barrier to many polar compounds, including water. In contrast, if the chemical, like many organic solvents, is more nonpolar, it may diffuse directly through the corneocytes and surrounding lipid matrix. This transcellular route has a rate of absorption that can be much higher compared to the intercellular route (see Figure 4). Skin absorption through the hair follicles and glands can also occur, but these appendages often make up a smaller portion of the skin in humans and do not play as big a role in the transport of chemicals through the skin.
In addition to polarity, the key factors or parameters associated with skin absorption include: • the octanol-water partition coefficient (log Kow or P), which is a measure of whether the substance is more likely to be lipophilic (lipid-soluble) or hydrophilic (water-soluble) • the molecular weight (MW) or size of the molecule: smaller molecules can more readily permeate the skin or skin cells • the concentration (C): increasing concentration often results in increased permeation across the skin • the vapor pressure (VP): evaporation from the skin can reduce the rate of diffusion across the skin
Figure 3. Illustration showing the epidermis and dermis of the skin.

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Combinations of these parameters are used in various models to predict the rate of skin permeation. This rate is commonly represented as the flux (an amount of flow through an area) in units of mass per square centimeter of skin per time (mg/cm2 h). In some cases, in vitro human skin permeation data may be available in the scientific literature, but typically, models must be used. NIOSH uses log Kow, MW, and C in its freely available Skin Permeation Calculator, which is used to predict the flux of a chemical through the skin. This in turn can be used to calculate the estimated skin absorption and systemic dose (in mg/kg body weight) using the surface area of skin contact and the duration of exposure:
As an example, the calculator can be used to estimate the systemic dose of a worker exposed to 1,840 cm2 (surface of the exposed skin) of methanol with hand and forearm contact for up to 2 hours per day. Methanol has an ACGIH Threshold Limit Value (TLV) of 200 ppm, a skin notation, an MW of 32 g/mole, and a log Kow of -0.77. The NIOSH calculator returns a range of fluxes from 0.13 to 1.6 mg/cm2 h based on three different skin permeation models. Using a conservative approach, the upper bound estimate of the systemic dose can be calculated as follows for an individual weighing 70 kg (approximately 154 pounds):
To compare this dose to a corresponding dose via inhalation, we can use a standard ventilation rate, exposure time, and body weight:
An equivalent inhalation exposure at the TLV of 200 ppm (152.6 mg/m3) and with an inhalation rate of 1.2 m3/h (20 L/min) representing light physical exertion would result in an estimated systemic dose of 5.2 mg/kg:
Even if the inhalation exposure was two or three times higher than the TLV, the upper bound dermally absorbed systemic dose will be higher than that associated with inhalation. This is likely a reason why ACGIH includes a skin notation with the TLV for methanol.
One drawback of the NIOSH Skin Permeation Calculator is that it does not include vapor pressure in its model, which can be an important factor with volatile compounds such as methanol. NIOSH has a Finite Dose Skin Permeation Calculator that considers evaporation and many other factors, but it is limited to single exposures of a known amount. The AIHA Exposure Assessment Strategies Committee’s IH SkinPerm tool accounts for additional factors such as evaporation from the skin and provides greater flexibility for different exposure scenarios (for example, instantaneous, continuous, and vapor-to-skin depositions). For the same methanol scenario, IH SkinPerm returns a total absorbed systemic dose of 68.2 mg with most of the methanol evaporating from the skin. The dermal dose equivalent is 0.97 mg/kg (68.2 mg/70 kg body weight), which is much lower than the 5.2 mg/kg obtained using the NIOSH Skin Permeation Calculator. However, if the methanol was trapped under the worker’s gloves or another garment and not allowed to evaporate, then the NIOSH model may be more appropriate. These results still indicate that skin absorption can contribute to the systemic (internal) dose of methanol in addition to the inhalation route.
These skin permeation tools can help industrial hygienists recognize and evaluate the potential contribution of skin absorption associated with a vast number of chemicals. Recognition of the potential for skin absorption is a critical step in the industrial hygiene process. We cannot evaluate, control, and manage risks that we do not first recognize.
It is highly recommended that any practicing industrial hygienist who wants to use these skin permeation tools attend one of the AIHA Exposure Assessment Strategies Committee’s professional development or elearning courses on dermal exposure assessment. Resources for learning more about these methodologies are provided at the end of this article.
A March 2023 publication in the Journal of Occupational and Environmental Hygiene found that many practicing industrial hygienists do not have adequate education and training in conducting dermal exposure assessments. The accuracy of their assessments improved with training on the use of dermal models, such as IH SkinPerm.
Figure 4. The intercellular and transcellular routes of diffusion through the stratum corneum. Graphic created by Robert N. Phalen.
IDENTIFYING SKIN HAZARDS We are fortunate to have a more robust hazard communication system than in years past. The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) health hazard codes provide useful information for recognizing skin hazards. Examples of GHS health hazard codes associated with skin irritation, corrosion, allergy, or systemic toxicity appear in Table 1.
ACGIH has a long history of establishing skin notations for chemicals. These can be found in the ACGIH Threshold Limit Values and Biological Exposure Indices (BEIs) book and its supporting documentation. The skin notation indicates a potentially significant contribution to an overall systemic dose via skin absorption, including the mucous membranes and eyes. These notations are typically supported by evidence of adverse systemic effects following dermal exposure. This notation does not indicate any potential for skin irritation; however, the DSEN notation indicates the potential for dermal sensitization. Currently, there are over 230 TLVs with a skin notation and about 60 with the DSEN notation.
NIOSH established a strategy for assigning skin notations in 2009. To date, the agency has published skin notation profiles for 66 substances. The skin notations indicate one or more of the following designations: • DIR: potential for direct effects to the skin • DIR (COR): potential for a chemical to be corrosive to the skin • DIR (IRR): potential for a chemical to be a skin irritant • ID(SK): chemical was evaluated but the data are insufficient for an accurate assessment • SEN: potential for immune-mediated skin reactions • SK: data did not identify an associated health hazard and did not support a skin notation • SYS: potential for systemic toxicity following skin exposure • SYS (FATAL): potential for fatal systemic toxicity following skin exposure
Overall, these skin notations should be included as an integral part of our hazard assessment and management system for workplace chemicals.
Table 1. GHS Health Hazard Codes for Skin Effects

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PROTECTING THE SKIN When faced with a skin hazard that poses a significant risk, one of the first steps is to turn to the hierarchy of controls. At the top of the hierarchy are elimination or substitution of the hazard. Next, engineering controls that can limit skin contact with the substance must be considered. If these are not feasible and administrative controls do not provide adequate protection, chemical protective clothing (CPC) should be considered. For many of the at-risk occupations previously listed, CPC is often necessary.
The general principles for protecting the skin rely on selecting chemical barriers that limit the penetration, degradation, and permeation of a substance through the CPC. Many manufacturers and suppliers provide chemical resistance charts to aid in the selection of CPC. The Quick Selection Guide to Chemical Protective Clothing, seventh edition, provides a comprehensive list of recommendations based on published and unpublished scientific test data for chemical degradation and permeation.
The AIHA Protective Clothing and Equipment Committee has published a number of Synergist articles intended to help practicing industrial hygienists protect the skin against chemical agents. These include “Chemical Protective Clothing 101” (April 2020) and “Not All Gloves are Created Equal: Guidelines and Tools for Selecting and Using Chemical-Resistant Products” (December 2018). The committee also published Chemical Protective Clothing, second edition, which covers the basic principles needed for establishing an effective protective clothing and equipment program.
ROBERT N. PHALEN, PhD, CIH, FAIHA, is a professor and program chair of Occupational Safety and Health at the University of Houston-Clear Lake, Houston, Texas. Phalen is an industrial hygienist with expertise in chemical protective clothing.
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RESOURCES
AIHA: Chemical Protective Clothing, 2nd ed. (2003).
AIHA: IHSkinPerm.
AIHA: Mathematical Models for Estimating Occupational Exposure to Chemicals, 2nd ed. (January 2009).
ACGIH: 2023 TLVs and BEIs (2023).
Journal of Occupational and Environmental Hygiene: “Accuracy of Professional Judgments for Dermal Exposure Assessment Using Deterministic Models” (March 2023).
NIOSH: “Current Intelligence Bulletin 61: A Strategy for Assigning New NIOSH Skin Notations” (August 2017).
NIOSH: “Skin Exposures and Effects.”
NIOSH: “Skin Notation Profiles.”
NIOSH: “Skin Permeation Calculator.”
The Synergist: “Chemical Protective Clothing 101: A Primer on Permeation, Penetration, and Degradation” (April 2020).
The Synergist: “Dermal Sensitizers: What Does Our Immune System Already Know?” (November 2019).
The Synergist:Not All Gloves Are Created Equal: Guidelines and Tools for Selecting and Using Chemical-Resistant Products” (December 2018).
United Nations Economic Commission for Europe: “Globally Harmonized System of Classification and Labelling of Chemicals.”
Wiley: Quick Selection Guide to Chemical Protective Clothing, 7th ed. (March 2020).