Sunday, November 30, 2014

In Defense of Dermal Exposure Modeling

A couple of weeks ago this blog had an Argument Against Dermal Exposure Modeling from Chris Packham which I thought made some good points.   However, being an advocate of modeling myself, I thought I would open the discussion to others for their input and publish some of the counter arguments. 

Before I get to this, one of my colleagues asked for specific clarification.  She was not sure from the discussion exactly what the purpose of estimating dermal exposure might be in our discourse.  My sense is that we are looking for quantitative estimates of systemic and local tissue exposure and dose estimation to use in comparison with dose-response information to determine or estimate the potential risk to human health from dermal exposure.  This determination of risk would be used like any other risk assessment to make decisions about potential risk management.

I had a few folks write to me defending the “no need to quantitatively model dermal exposure” approach but I also found two good examples of a cogent defense of dermal exposure modeling.    The first comes from Paul Schlosser (an Environmental Health Scientist  at the US EPA).   Paul has been working on a chemical where a significant amount of vapor uptake is via the skin. An abstract is available online :

As such, he had some very recent experience with these models.  The second set of comments comes from friend and colleague Wil tenBerge from the Netherlands who has been a thought leader in this area for many years.   Their comments are presented below:

“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.

The EASH [European Agency for Safety and Health] 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 “

“Dear Mike, Your blogs are always very interesting. I would like to give my opinion on the statement that modelling dermal exposure and dermal absorption is not very productive. Modelling dermal exposure and absorption is certainly not straight forward. One of the problems is to define the type of exposure. There is a need to define type and conditions of dermal exposure to: - gas, vapour - spilling liquid or solids - aerosol of liquid via air - aerosol of solid via air and further: - exposure to bare skin - exposure to skin protected by clothes and further: - exposure to pure substance - exposure to a mixture - exposure to aqueous solution and finally the fraction absorbed - which amount in mg/cm2 is deposited on the skin? - which part adheres to the skin and for what time? - which part evaporates? - which part is permeating the skin (minutes to weeks)? - which parts resides in the stratum corneum? - which part is removed by desquamation (weeks) from the stratum corneum? The IH-SkinPerm is able to quantify: - dermal absorption by whole body exposure to vapour. - dermal absorption by spill of liquid or of solid on the bare skin during a limited period of time. - dermal absorption of aerosol of liquid or of solid, deposited on the bare skin during a limited period of the working day. The deposited amount per day on the skin in relation to the type of work can be read off from so-called guidance documents for risk assessment, based on experimental observations. The real absorption of the dermal deposited dose is assessed by IH-SkinPerm. The accuracy of dermal absorption estimates by IH-SkinPerm for the few dermal exposure scenarios has been assessed by experimental exposures in volunteers. The simulated and experimentally measured absorption fractions were in fair agreement. IH-SkinPerm covers only a few but not all possible types of dermal exposure. The developed theoretical background for IH-SkinPerm is still able to simulate exposure for other exposure conditions and also for mixtures. I would highly appreciate receiving the note of Chris Packham. Best regards, Wil 

-Wil tenBerge

This subject remains open to anyone who wants to respond to this blog or send me an email at; however, I remain strong in my opinion of the positive value of Dermal Exposure Modeling for risk assessment in the context I outlined above.

Monday, November 24, 2014

We do NOT spend enough on Risk Assessment

I think I mentioned in previous blogs that my friend and colleague, Gurumurthy Ramachandran or “Ram” is a brilliant teacher and researcher.   A few years ago he and J.Y. Choi conducted a survey of technical experts on the occupational oversight framework in this country.  They used nanotechnology as the example.

The mathematical techniques they used were quite sophisticated in their analysis of the survey.   That is not my primary area of expertise but it appears to be very well done.  Indeed, as he always does, it is a very careful piece of research and its conclusions are properly couched in terms of the uncertainty and limitations of the study. Notwithstanding these caveats, I was struck by the following excerpts from the paper:

Despite the large investments in nanotechnology, corresponding investments in studying the health and safety aspects of this technology and its products have been minimal.

The most striking finding is that experts in our sample tend to believe that the current oversight system for chemicals in the workplace is not adequate and effective. About 17 (or 70 percent) of the 25 criteria were scored below 50 out of 100. The mean score of the 25 criteria across all experts is 42.4 and median is 41.3 out of 100.

This reference is:

Choi, J.Y, Ramachandran, G. Review of the OSHA Framework for Oversight of Occupational Environments. Journal of Law, Environment, and Ethics, 37(4):633-650, 2009.

If Ram gives me the OK I will send this to anyone who asks me for it:

Indeed, this has been my general experience during a long career doing product safety risk assessment for the chemical industry.   About 12 years ago I did a calculation of the amount of money being spent by the chemical industry on health and safety research of chemicals by the chemical industry.   This included the 15-20 million USD being spent every year at that time by the Industry sponsored Chemical Industry Institute of Toxicology (CIIT). Compared to the industry’s profits it came out to be in the parts per million range.   This is not to say that other money was not being spent on health and safety research by individual companies but, like the CIIT efforts, they were primarily reactive in nature in that they were responding to obvious problems that were either easily anticipated or brought to them.  

Chemcials that were clearly toxic, like pesticides or proven carcinogens or endocrine disruptors (all most often initially discovered in academia) received the focus of attention.

For many years almost all of the risk assessments I did for my company were focused on these types of products (e.g., recognized sensitizers, carcinogens, etc).   During my tenure, the vast majority of products produced by most companies never really received any proactive attention relative to the risk of their use in commerce. I believe it is the same today.

It would seem that the Europeans have been trying to reverse that trend with the REACh regulations.  There are also noises being made in this country to reauthorize TSCA to be more REACh-like and do proactive assessment of chemical risk as well.

My read of all this here or in Europe is that unless or until proper resources are allocated to do this research, we will continue to flounder in a sea of uncertainty in which we really do not understand the risk of the chemicals we use.   This is not to say that all or even many of the chemicals we are exposed to are harmful at the exposure we encounter them.   I am quite sure, however, that there are unacceptable risks from the chemicals we use out their today that we have not discovered and we will not find them without these resources.  

That is my read but I would very much like to hear other opinions.   After all, this is a discussion group.   The discussion will appear at the bottom of this blog or in the LinkedIn Group in which it is posted.  However, if you write a good and compelled argument or treatise relevant to this issue, I will publish it, along with my comments, here in a future blog.

Relative to last week’s blog (Argument AGAINST Dermal Exposure Modeling), I got very few folks defending the use of dermal modeling.  I was somewhat surprised in that I made sure that the people I know that are or were doing dermal modeling got the blog.  Perhaps it is because everyone is so busy with the holidays and work.   I will leave the question open for a few more weeks in case folks wanted to comment but just did not have the time. 

Monday, November 17, 2014

An Argument AGAINST Modeling Dermal Exposure

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:


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  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.

Sunday, November 9, 2014

Lost Keys Under Street Lamp Part II – Dermal Exposure

Chris Packham is a colleague from the UK who I met many years ago over there.  For as long as I have known him, and I am sure before that,  he has worked tirelessly trying to raise awareness of dermal exposure as an important source of risk to workers.  He is presenting a talk on the subject at a regional British Occupational Health Society (BOHS) meeting on November 18th and he has graciously allowed me to publish that talk in this blog afterwards.   

Before then he sent me an email which I am reproducing below on the general subject in which, I believe, he makes some very good points.

I continue to be frustrated at the apparent insistence by hygienists on concentrating on inhalation exposure and ignoring skin exposure, particularly when statistics show otherwise.
“Both the number of cases and the rate of skin diseases in the U.S. exceed recordable respiratory illnesses.

In 2006, 41,400 recordable skin diseases were reported by the Bureau of Labor Statistics at a rate of 4.5 injuries per 10,000 employees, compared to 17,700 respiratory illnesses with a rate of 1.9 illnesses per 10,000 employees.” - OSHA Technical Manual, Section II, Chapter 2
“Occupational skin diseases are among the three most frequent groups of occupational diseases. ... However, occupational skin diseases have attracted relatively little attention in the global and national agendas for prevention of occupational and work-related diseases. – World Health Organisation Global Workshop, Geneva, February, 2011
At a skin conference in Amsterdam in 2013 German statistics were presented showing that occupational skin disease represented 35% of all recognised cases of occupational ill health!

And that is just skin disease, ignoring the contribution that skin uptake  makes to systemic toxic effects.

Is it because hygienists believe that they can measure inhalation exposure and confirm compliance with the exposure limits?  As this is not possible with skin they do not feel comfortable with skin exposure assessments? Perhaps they should consider what Einstein once said: “Not everything that can be measured counts, and not everything that counts can be measured”!
My take on this is that while it is certainly more difficult to measure or estimate dermal exposure (compared to inhalation), I believe that some attempt at quantification of dermal exposure is possible.  Dermal penetration modeling, which has been around for some time, is one way of getting a handle on dermal skin exposure potential.    Wil tenBerge has been a pioneer in putting together and sharing useful tools for the assessment of dermal exposure from skin contact with liquids and from skin contact with airborne vapors.   The latest has been his collaboration with Danial Drolet and Rosalie Tibaldi to fashion IH SkinPerm  (see   

Dr. ten Berges previous work on this subject has been freely available for many years on his web site:

Theses tools allow for the estimation (albeit currently unrefined) of how much of a dermally available substance might be absorbed into the body.   A previous blog here highlights the work of Dr. Deborah Lander in evaluating the uncertainty around these models.   Check it out at as the July 7 2014 blog:   Dr. Langer reports  “ that 27% of the model predictions were within a factor of 2,  73% where within a factor of 10 and all of them were within a factor of 30 fold. “  Clearly, 30 is a relatively large factor but my sense is that it can be significantly, if not dramatically, brought down by future experimental data  sets in which the consistency of the quality of the experimental data are carefully monitored and assured.  

The point of all this is that some quantification of dermal exposure is possible today given the details of the exposed skin area and duration of exposure.   If we are dealing with systemic toxic effect then we can estimate systemic dose.   Inhalation OELs can be converted to dermal OELs to make the comparison. If we are dealing with irritation or Type IV contact allergy as the primary response of concern then we are focused on determining the worst case amount per cm2 of exposure.  In my previous work we establish working mg/cm2/day exposure limits for contact allergens.  Thus, both primary types of dermal exposure are subject to quantitative estimates.  We should not fail to look for our “lost keys” in this area that is not “under the street lamp” of inhalation exposure assessment.

Sunday, November 2, 2014

Looking for lost keys under a street-light

This statement sums up what a lot of us fall prey to; namely, seeking solutions where the looking is easy rather than striking off into the darkness for the true answers.

A real-world example in the world of Industrial Hygiene might be the situation where there is a continual occurrence of workers with symptoms of chemical overexposure.   The “street-light” approach here would be to determine what chemicals are present within the workplace and then monitor the breathing zone of the workers for the chemical.   In many, perhaps most, cases an overexposure is detected and then controlled and the problem solved.   The “easy” and obvious approached worked.

To stretch the analogy further, street-lights are positioned with a purpose.   They are designed to illuminate spaces that we need to see.  Thus, looking under street-lights for solutions is a good place to start.

In some cases, however, the solution does not reveal itself so readily.   You monitor and monitor, compare the results to all your OELs and nothing presents itself as (to steal another phrase) a “smoking gun.”   In this situation, the easy “street-light” approach has failed you and you need to strike out into the dark.   What to do?

It is now time to bring out the scientific method
  1.        State the problem
  2.        Form a hypothesis as to cause
  3.        Experiment and Observe
  4.        Interpret the Data
  5.        Draw Conclusions and Make Predictions

IF 5 does not work out, THEN you need to go back to step 2.

You can do this on a number of levels.   Perhaps the simplest level you can do it is as a thought experiment.   That is, form a hypothesis and run it through the Hill Criteria of Causation that was the subject of a previous blog.  Just go to:  and expand the “September” link to the right and then click on “The Hill Criteria of Causation” to see a detailed discussion of this important tool.   When you do this consider all of the available data and circumstance to see how good the fit is of your hypothesis to reality.   If it does not fit very well go to step 2 and form another hypothesis.    Just “rinse and repeat” until a coherent picture starts to emerge.

Giving the above problem a number of hypotheses are possible.  Here are a few that I thought of but there are almost certainly others:

   1.   You are measuring the wrong agent:
Perhaps a chemical you did not consider or perhaps it is a biological agent that is causing the problem.  It could be an agent, not directly associated with the operations, occurring in the ambient environment of the workers.

2    You are measuring air and dermal is the primary route of exposure:

    High MW, high Kow compounds will not be in the air as much as they might enter the body unmeasured through the skin.

3.  You are measuring to an 8 hour time-weighted average exposure and very short acute exposures are causing the problem which are not showing up as an over-exposure to an 8 hour OEL.

4.  The workers are lying or "faking it" to get out of work

5.  The effected workers are extremely sensitive; that is, “hypersusceptible” and will react to very low concentrations of chemicals in their workplace environment

On the face of it and without data, any of these could be true, it is up to you to figure out which one is the best fit to the facts at hand and then get as much data as you can or do some experiments to prove it.   Indeed, it is incumbent upon you as the IH to sort through the various hypotheses in a concerted effort to really nail down the cause of the adverse health effects of workers in your charge. 

What you do not want to do is “fall in love” with any particular paradigm designed to evaluate the risk of chemical exposures in the workplace.   You do not want to insist that you have done everything you can to find the answer and that there really is no problem because you cannot find it.  You owe it to your workers and yourself to really look into what they say is happening to them relative to adverse health effects at work.  I have found most workers to be honest witnesses to what is happening to them and their coworkers.   You need to listen carefully to what they are telling you and, unless you are sure that #4 is occurring in this situation, you need to give credence to their accounts.

 If you fail to do the above, if you continue to turn the handle on a paradigm that is not showing you what is happening, you may be guilty of futilely “looking for your lost keys under a street-light”.