Dermal penetration and systemic level

Dermal penetration studies are conducted to determine how much of a chemical penetrates the skin, and thereby whether it has the potential to be absorbed into the systemic circulation. Dermal penetration is considered to occur by passive diffusion; however, biotransformation of the test substance within the deeper viable regions of the skin metabolism prior to systemic absorption can occur OECD, a. It may provide an indication that the substance penetrates the skin if it produces systemic toxicity, but the amount of chemical absorbed is not quantified by dermal toxicity testing. One of the primary roles of the skin is to act as a barrier to protect humans from substances contacted in the environment. Permeation of a substance through the skin depends upon a number of factors, including: the formulation or vehicle in which it is presented to the skin; physicochemical properties of the test substance such as lipophilicity fat solubility , molecular weight, charge, and concentration of the test substance; and area and duration of exposure.

Increased awareness of skin cancer and mosquito-transmitted diseases has increased use of insect repellents and sunscreens. The challenge in setting recommendations for use and reapplication, especially when used concomitantly, lies in finding the balance between applying a durable product effective in withstanding natural and physical factors such as water, sweat, temperature and abrasion, while limiting percutaneous absorption and decreasing risk of potential dermal and systemic toxicity. Inorganic sunscreens show no or little percutaneous absorption or toxic effects in comparison to organic sunscreens, which show varying levels of dermal penetration and cutaneous adverse effects. An alternative to N,N-diethyl-m-toluamide DEET , the traditional gold standard compound in insect repellents, picaridin appears as efficacious, has lower risk of toxicity, and when used simultaneously with sunscreen may decrease percutaneous absorption of both compounds. Conversely, combined use of DEET and sunscreen results in significantly higher absorption of both compounds. It is important to increase consumer awareness of "washing in" of various compounds leading to increased risk of toxicity, as well as differences in reapplication need due to "washing off" caused by water, sweat and abrasion.

Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointment that delivers the drug into the circulation for systemic effect. Although the skin is a large and logical target for drug delivery, its basic functions limit its utility for this purpose.

This project will develop decision-making procedures and risk communication documents for prevention of occupational skin exposures. The methods for hazard recognition and exposure assessment and the recommendations for workplace interventions including using chemical protective clothing will be documented and published as NIOSH products and disseminated to workers and workplace management. This project also participates in planning and convening NORA DERP-supported international conferences aiming to promote awareness of occupational skin exposures and research.