Saturday, September 20, 2014

Dermal Bioavailability Driving Exposure

I am reproducing the cause to effect continuum graphic from a few weeks ago because it is going to help us understand a point about this week’s blog; namely, after contact a material has to be absorbed within the systemic circulation of the body in order to exert a toxic effect.
I have mostly worked in the realm of bioavailability of chemicals via dermal exposure.   This was a natural result of my employment by a company that made a Type IV contact allergen that was used as an effective biocide but needed to control the exposure so that the risk of contact allergy to users was likely to be deemed to be “not unacceptable”. 

You may find the double negative term “not unacceptable” to be strange; however, I use it for a reason.   My sense is that acceptability of risk is very much a political determination.    As such it is a somewhat subjective judgment made by the body politic.   Indeed, I see it as part of the democratic process that is more of less open to those making and being subject to the decisions of that process.   I see that piece as more management and less science.   I see our job as risk assessors to do the best we can to estimate the risk and, when forced to do so, provide levels of exposure that we believe may not be unacceptable to the body politic.   Indeed,  I see it as analogous to the null hypothesis in statistics.  One does not accept it, one simply fails to reject it at some level of confidence.   

OK, so much for philosophy, the purpose of this blog is to discuss bioavailability via dermal exposure.  During my analysis of bioavailability for product safety I studied two mechanisms that effect or control the amount of a topically applied dose of contact allergen that might make it to the systemic circulation of the body.  Indeed, it is commonly accepted that the contact allergen has to pass through the stratum cornium (SC) or top layer of our skin in order to elicit a contact dermatitis allergic response.

The first mechanism that I thought about, but never got the opportunity to test in the laboratory was the limited bioavailability contact allergens caused by the continuous shedding of our skin.   

The SC layer of our skin is composed of about a dozen or so layers of essentially flat dead cells.   These are shedding from the top as they are replaced from the bottom in a process known as desquamation.   That rate of shedding is about one layer of cells per day.   The “ring” around the bath tub at the end of a bath is composed of some of these dead cells.   Indeed, a lot of house dust is also composed of these skin cells constantly being shed from our body.  

Contact allergens are reactive and theoretically bind with protein to form an immunologically active species that goes on to cause an allergic response.   As it turns out even dead cells in the SC layer have protein bonds that can theoretically react and bind with the allergen.   It is my opinion and hypothesis that this binding essentially detoxifies the allergen because it is not mobile (being locked into the desiccated dead SC cell) and the cell is making its way to the surface to be shed.   When the rate of allergen application overwhelms this process, the allergen makes it past the SC and into the viable dermis to do its thing; however, if the rate of application of contact allergen is low enough it cannot “swim” again the up-welling current of SC cells fast enough to reach the viable dermis.   In this hypothesis we have a natural and demonstrable threshold of toxic effect for dermally applied contact allergens.  

I know that the concept of any threshold for allergic response will spawn some comment from those who do not believe they exist for allergens but I think the above logic is pretty solid and certainly testable as a hypothesis.   It simply has not been tested as far as I can determine.

The other mechanism of bioavailability for allergens in products comes from the partitioning of allergens in products with polymeric aqueous emulsions.    Depending on how lipophilic the allergen is, it will partition more or less into the polymeric emulsion particles, leaving significantly less of the antigen to  go into and through the SC. 

We did get to study this second mechanism in the laboratory and wrote a paper about it.   I would be happy to send a copy of this paper to whomever requests it from me at

1 comment:

  1. Hello Mike,
    I really like your approach based on scientific thinking AND on common sense the latter being absent in so many other blogs and discussions. All the talk about "toxic chemicals" in cosmetics (vs. the benefits of "natural" ingredients) makes particularly no sense when seen in the light of your chart! But why bother with science and logic when "cancerogenic parabens" sell so much better...
    What you say about the allergens is of course true for any ingredient put on the skin.