How dermal tests help determine the safety profiles of these topical products
Forty years ago this month, Steven Spielberg’s blockbuster thriller, “Jaws” turned the seashore into a terrifying place.
Shark attacks do happen, of course, but the biggest risk that beaches pose aren’t underwater but up in the sky. Excessive sun exposure causes many of the 3 million cases of skin cancer diagnosed annually in the US, from deadly melanomas to highly curable and much more common basal cell and squamous cell skin cancers.
Audio: Skin Cancer podcast
Though limiting the amount of time we spend in the sun is arguably the most potent weapon one can aim against skin cancer, using sunscreens and sunblocks also have their place in the sun. The US Food and Drug Administration (FDA) specifies that sunscreen products must shield against harmful ultraviolet B rays (UVB), the main cause of sunburn. European and Canadian regulations are even tougher. Sunscreens and sunblocks must also protect against ultraviolet A (UVA), which is associated with aging and skin damage. UVA rays are less intense than UVB rays, but they are also 30-50 times more prevalent.
Dermatologists generally recommend using chemical sunscreens (which act as filters and reduce ultraviolet radiation penetration to the skin) or sunblocks (which physically block ultraviolet radiation) bearing a sun protection factor (SPF) of between 15 and 50 that protects against both UVA and UVB rays. (So if you use a sunscreen with an SPF of 15, you can be in the sun 15 times longer than you can without sunscreen before burning).
Pharmacy shelves are filled with dozens of sunscreens and sunblocks and the products are continually being redeveloped and reformulated to meet the needs of consumers. Some sunscreens are more waterproof, others more suited to sensitive or dry skin.
Europe has 27 different sunscreen molecules on its approved list, but the US has only 10. The FDA has also held off providing access to eight others because they consider them too risky, according to Chemical and Engineering News.
The synthetic materials that put the “S” in sunscreens—those that protect against UVA rays—are avobenzone, benzophenone and oxybenzone, Padimate-O, octyl methoxycinnamate and menthyl anthranilate. Physical blockers include titanium dioxide or zinc oxide.
Efficacy is obviously important in determining which products make it to market, but manufacturers also need to be sure the sunscreens and sunblocks are safe and free of serious adverse reactions. One of the ways to determine this is by looking at how the skin absorbs sunscreen materials and what the systemic absorption is based on blood and urine testing. To learn more about how skin studies are carried out, we turned to Frank Toner, manager of Dermal Services at Charles River Laboratories’ Edinburgh site, who has been working in this area for over 13 years.
How do you conduct skin absorption tests?
The way we often do it is by incorporating a radio-labeled sunscreen into the formulation . Then we apply the formulation around 2-5 milligrams per centimeter to human skin from elective plastic surgery. We do this over a 24-hour period and try and mimic the in-use scenario of the sunscreen product.
How do you determine if the product is too toxic?
Underneath the surface of the skin is receptor fluid. We have to demonstrate the solubility of the sunscreen in that receptor fluid. How much of the product is being absorbed helps us assess how safe the product is. These skin absorption studies can be quite challenging, though.
Well, in any skin absorption study you need to make sure the formulation is a realistic surrogate of the actual product. Sunscreens are generally very lipophilic molecules, meaning they tend to have an affinity to fats. Some sunscreens are among the most lipophilic compounds you can work on. The formulation is required to be synthesized using small-scale laboratory apparatus, as opposed to specially designed industrial equipment. We need to ensure core formulation characteristics can be replicated effectively. These characteristics include: formulation stability, chemical composition and emulsion properties scaling. Also, the sunscreen must be suitably soluble in receptor fluid, and we can’t use a solvent because it would damage the barrier of the skin.
So what receptor fluid do labs use to measure dermal absorption?
Certain labs use an ethanol/water solution (1:1, v/v) because you can get better solubility, but in that case you are essentially putting your skin in vodka and running the risk of damaging the barrier integrity of the skin. Our preference is to use an aqueous physiologically-based receptor fluid containing a lipophilic accepter in order to maintain barrier integrity. We only consider using ethanol/water in very extreme cases.
How long have skin absorption studies been used for this purpose?
Sponsors have been using them since 1989 to evaluate new products or changes in formulations of existing products. There have been finalized OECD [Organization for Economic Co-operation and Development] regulatory guidelines in place for the past 11 years.
What else is done to assess the safety of sunscreen products?
Manufacturers also collect toxicology information on the sunscreen chemical itself and the formulation excipients. This data is combined with the in vitro skin absorption test data.
What do you think about the use of robots for sunscreen efficacy testing?
One study has shown that a robot reproducibly applies the same amount of formulation evenly, which was harder to do when humans did this process previously. This will allow more accurate SPF categorization.
How to cite:
McEnery, Regina. The Skinny on Sunscreen Tests. Eureka blog. Jun 16, 2015. Available: http://eureka.criver.com/the-skinny-on-sunscreen-tests/