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A Closer Look At Dermal Penetration and How It is Measured

October 12, 2012

Following on from my article earlier this week I have done a little more research into dermal penetration.  The result?  It is as complex and confusing as I thought it would be.

Enjoy – and if you don’t enjoy the article why not enjoy looking at this yummy cheese and wine that I’ve been supping with the team at New Directions!

The skin is made up of many layers with the stratum corneum located at the top of the epidermis being the part that we apply our cosmetics to.  Below the Stratum Corneum or horny layer lies the viable epidermis which can metabolize chemicals that pass through.  In addition to that are hair follicles, sebaceous and sweat glands which can offer an alternative route to topically applied chemicals.

The important questions on the lips of many a cosmetic chemist are these:

Just how much of my active-packed product gets through the skin

and

When it does, are all of the chemicals metabolized in the same way?

Those questions are tricky enough to answer when the chemical in question is applied at a known concentration in an inert base but become almost impossible to answer when you consider how many variables there are in a typical cosmetic!  Also we must not forget that the skins ability to resist or succumb to a chemical is also related to its thickness (where it is located on the body), its age, and the sex of the person that it is attached to, its general health and its individual genetics.   That’s a lot to measure and try to control!

That said methods have existed for many years to characterize the passage of a chemical through the skin.  One such method utilizes a Franz Static Diffusion cell to measure the rate of passage through the skin. This method has been used with some success since the 1970’s to track chemicals and is still being used today.

Diffusion is a form of passive transport where ions in a solution are driven to move from areas of high concentration to lower concentration until the concentrations balance (if possible).  Think of it like sharing, diffusion tries to ensure that ‘everyone’ gets the same!

Basically the cell can be fitted with either real human skin (usually collected from plastic surgery) or a skin-like substance (there are various different ‘man-made’ skins available that mimic the skins properties).   The test chemical is added into the top of the cell at a known dilution and applied to a small area of the skin sample.  At varying time intervals the test fluid is sampled to measure the concentration of the known chemical remaining in the bulk liquid.  The different layers of skin can also be analyzed to track how much substance passed into the skin and how far it got.

Another way of testing has been to use animals (pigs skin is the closest to humans in case you were wondering) but due to ethical reasons, advances in alternatives and issues in structural and metabolic differences between animals and humans that method is now less common.  A third method which is becoming increasingly popular is to use a mathematical model based on inputting data on the chemical structure, functional groups, usage dose and product format to calculate a penetration rate.   All of the above methods have their faults and are generally much better at evaluating physical movement rather than complex metabolism although that remains of value.

So, back to the skin metabolism and it is time to consider whether what goes through our skin gets changed or not.  The skin is metabolically active and is able not only to process chemicals that originate in the skin (hormones, inflammatory agents, steroids etc) but also chemicals that come from the outside – from cosmetics, household cleaners and other environmental sources.   We call these Xenobiotics which are a word to describe chemicals that originate from outside of the organism.  This ability is very important for as our skin is the largest organ AND it is so exposed (through lack of hair and varying thickness) it is vulnerable to environmental toxins.   However, our skin can’t do everything and sometimes instead of detoxifying a chemical and rendering it harmless and excretable (via our urine or sweat usually) it turns it into something more toxic – out bodies are amazing but not perfect!

The skin is particularly efficient at metabolizing chemicals (via hydrolysis, oxidation or reduction)  that are acid, alcohol, amine or ester based which is great in skin care as this accounts for a wide range of actives (vitamin A, C, AHA’s, BHA’s, Hyaluronic Acid etc.  However, more complex reactions only seem to take place at specific places on the skin including around hair follicles and sebaceous glands and some chemicals can’t be broken down at all!  Interestingly the most robust studies of parabens and skin absorption demonstrate the ability of full thickness human skin to metabolize these chemicals rather than let them pass through un-encumbered.  This begs the question, how do intact parabens end up in our bodies………

The ability of the skin to metabolize a chemical and turn it into something either useful or excretable is good only to a point as If the concentration of active exceeds the body’s ability to process it you may get an overload that can be irritating and a waste of money at best or at worst toxic.

As you can see from the above, it is very difficult if not impossible to be able to answer our questions with any certainty.   Our previous article highlighted some of the many variables that play a part in deciding how much of a topically applied product gets into the skin while here we have tried to work out what (if anything) might happen to the chemicals that do make it through.  The answer is that it is complicated.   We have found out that methods exist for measuring the speed and degree at which chemicals pass through the skin and in doing that have discovered that it is definitely not a case of ‘one size fits all’.   We have also discovered that our skin plays an active role in managing any skin-introduced imposters by employing any one of a number of metabolic processes to disable them.  However, we have also seen that this process isn’t perfect either and can be outsmarted at times and overwhelmed at others.   Finally we must look at how we go about measuring all of this in the first place and on analyzing that we notice that our methods are not set, our variables not tight and our results not always comparable.   All that and all we have managed to do with any accuracy is get an idea of how a single active works in a single (or at least un-complex) base.   That is not the reality of many cosmetic formulations!

So the safest way to answer my questions at the moment is to say that I don’t know exactly but what I do know is that there are many hundreds of scientists out there trying to get me some answers.

References:

1)       WHO  Look at dermal penetration: http://www.inchem.org/documents/ehc/ehc/ehc235.pdf

2)      Parabens and the EU legislation: http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_041.pdf

3)      Franz Cell and skin penetration of essential oil and fragrance components: http://www.rifm.org/doc/SBhatia%20SOT%20Poster%20032006.pdf

4)      Skin Metabolism Focus Group Meeting: http://www.skin-forum.eu/posters/skin_metabolism_meeting_2011/skin_forum_skin_metabolism_meeting_PROGRAMME.pdf

5)      Entry and fate of chemicals in humans: http://extoxnet.orst.edu/tibs/entryfat.htm

6)      Elimination of toxins: http://www.ndhealthfacts.org/wiki/Elimination_of_Toxins

One Comment leave one →
  1. Peter L. Mattei permalink
    October 16, 2012 9:08 am

    Indeed: The higher the accuracy and responsiveness of test measurement equipment/methods, the more we see the complexity of interactions within the skin. Of note, age and neglect are two great influencers. Of age, we can do very little. Smoking and overexposure to UV radiation; yes, that’s manageable.

    One area of increased scrutiny – even within the military – is the cellular respiration decline beginning in one’s early twenties (!). Getting mitochondrial support on-board is critical for numerous reasons. Science has, for years now, elucidated paths toward improved mitochondrial health.

    Accordingly, there are a few recognized methods of supporting the mevalonate channel and ATP production; however, the personal care industry has not employed the rigorous science to meet this potential market.

    One elegant solution is routine personal use of Xenobiotics with reduced levels of synthetic additives. Yes, it can be done.

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