After last week’s last blog: Lost Keys Under Street Lamp Part II – Dermal
Exposure, I received an email from
Chris Packham. An excerpt from Chris’
email is reproduced below:
“Mike
In response to your latest blog, perhaps the attached document
may be of interest. I think it explains some of the complexities and why my
approach to skin exposure risk assessment is that, with the exception of
perhaps specific research projects, attempting to measure or model the
significance of skin exposure will be time consuming and not for most of us a
productive use of our time. I know that hygienists tend to feel that unless one
can measure then they are not perhaps achieving a reliable result. However, as
I keep saying, we should keep in mind Einstein’s saying: “Not everything that
can be measured counts, and not everything that counts can be measured”.”
He attached a PDF file to this email:
About
skin measurement.pdf in which he outlines, in some detail, the complications associated with the measurement of dermal
exposure, let alone any modeling of the exposure potential. Chris has granted me permission to send
anyone who requests it the full text of this file (it is about one page in
length). Just email me at mjayjock@gmail.com. I have
cut and pasted an excerpt from it below that I would like to make the basis for
future discussion:
“As this document
suggests, measurements of skin exposure are fraught with complications,
particularly when it comes to interpreting the significance of the measurements
themselves. My view is that assessing the effects of skin exposure, except in very
specific situations, will be by its nature subjective and likely to remain so in the real world
for some considerable time.
As a final word,
consider the view of the European Agency for Safety and Health at Work:
“However, there is
no scientific method of measuring the results of the body’s exposure to
risk through dermal contact. Consequently no dermal exposure standards
have been set.” - from “Occupational skin diseases and dermal exposure in
the European Union (EU-25):policy and practice overview - European
Agency for Safety and Health at Work””
I must say that I was aware that regulatory bodies have been slow to
accept dermal exposure modeling but I thought that some progress had been made
on this front in recent years especially in Europe with REACh.
Clearly, Chris paints a somewhat dismal picture of the current
state-of-the-science around quantitative dermal exposure measurement and
modeling. I have expressed my opinion on
this in recent blogs but I would really prefer to hear from others on this
topic. I am especially interested in
hearing from folks who are much more expert than I in the realm of dermal
exposure measurement and exposure estimation via modeling. This will include those who might
incidentally read this blog and those who I am going to send it to directly.
You can either reply to this blog or send me an email. I will publish the best of them in a subsequent blog or blogs.
On an administrative manner, I have been in the habit of “Sharing” this
blog with LinkedIn Groups of which I am a member. This utility automatically posts the blog to
the identified LinkedIn Group page. When I attempted to do so for last week’s
blog most of my groups (e.g., American
Industrial Hygiene Association) did not show up for sharing access. If
this continues I will post directly to the selected LinkedIn Group with a link
to the blog.
Something I'd said in my previous posts is that doing the experiments to quantify skin absorption will certainly be costly and time-consuming, and folding that into a PBPK model will take even more time, though simpler modeling approaches should also be useful. I would agree that if it constituted 10% or less of total absorption, that it's not important, not worth counting. But for NMP the absorption of *vapor* through the skin was measured as 40% of what's absorbed when inhalation also occurs, not insignificant, and any liquid contact increases that considerably. The fact that it's difficult doesn't mean it's not worth doing.
ReplyDeleteThe EASH statement is a bit odd. We generally don't do dose-response experiments on humans, going high enough to cause toxicity, so we typically don't have *measurements* of risk from dermal contact in humans. But the same is true for inhalation or oral ingestion of many chemicals. We *do* have scientific means of *estimating* risk in humans for all these routes of exposure, though. For systemic effects it doesn't matter how it gets into the circulation, just the concentration (peak, AUC, or perhaps other), and with the appropriate PK data we can estimate that about as well for dermal as for other routes. So the statement is simply incorrect.
Figuring or estimating the surface area of skin exposed, especially to incidental liquid contact, may be a bit subjective. But the alternative, which is to ignore the risk, seems a lot worse than a bit of subjectivity.
-Paul Schlosser