Monday, September 1, 2014

Risk Assessment as a Cause and Effect Continuum

When you think about it, the risk to human health from chemical exposure can be described by a source-to-dose line of successive cause–and-effect events.   I do not remember all who were involved in the construction of the graphic below or even what the context might have been but I remember I had a part in it.

I also know that I have found the concepts in this particular graphic helpful over the years to gain a big picture perspective of what is happening within the risk assessment process. 

Clearly, Exposure Assessment is definitely to the left of the verticle human interface line.   Indeed, the elements of source, transport and contact are essentially pure exposure assessment.  It is the “power alley” of the exposure assessor and the Industrial Hygienist.   In last week’s blog  I wrote how I have been begging for information on these predecessors of exposure in order to do a better job of modeling exposure especially inhalation exposure to workers.    When we monitor, we go right to the end of this exposure assessment line and roll all of those causes of exposure into one ball as we gauge the actual level of exposure at the human interface.   It is a system that has worked for a long time but the purpose of last week’s blog was to assert that we could do better and develop the science with more data.

The line of demarcation for exposure/toxicology for dermal exposure assessment seems less clear to me than that for inhalation.   Even after “contact” we have issues of retention at the human interface (skin) and rate and bioavailability of the agent of interest from a matrix and through the interface.   There will be a blog here about dermal bioavailability in the next few weeks.   I just wanted to make some of you aware of what I believe is a difference between inhalation and dermal exposure.

The realm to the right of the human interface line belongs to the toxicologists.    Sometimes when they test animals they tend to roll up most of the elements into determining the doses that cause effects (i.e., dose-response).   

This combined approach has been called “dose ‘em, kill ‘em and count ‘em”. In such instances our toxicological colleagues typically do not look at the details of all the elements in between which could help inform a more complete picture of the toxicology especially as it might relate to humans.   There are, of course, toxicological scientist who are looking at the various elements to the right of the line in detail as they relate to the ultimate effect in animals and people.   Some great strides have been made in physiologically based pharmacokinetic (PBPK) modeling but these studies (like exposure model development) are invariably more expensive than the more summary approaches.   More recently, molecular biologist have been looking at the genetic elements of toxicology and these provide even more promise in our understanding a chemical’s toxicology.

However, what I really wanted to talk about in this week’s blog is the situation where you have an adverse health effect in the work place but no understanding or even a signal of any of the elements that preceded it in the above line of cause and effect.    This, of course, is the subject of some dose-reconstruction efforts in the service of epidemiological studies in which an apparent adverse effect appears to have happened and the source is sought. 

Beyond the realm of retrospective epidemiology, this situation can sometimes happen in the contemporary workplace.   That is, workers can be showing acute effects of chemical exposure for which the cause has been here-to-fore either unknown or even anticipated.    As Industrial Hygienist we owe it to ourselves to do a number of tasks:

  1.      Confirm that the effects are real
  2.      If real, form hypotheses to help you hunt down the possible causes within the workplace
  3.     Test the  suspected causes first with modeling and then with monitoring
  4.     Depending on your degree of ownership of Risk Management resources, recommend and invoke controls to eliminate the exposure and risk.

If you have not seen or even anticipated an exposure, doing any or all of these steps could be quite challenging because it means the problem is furtive at best else you would have caught before now. My sense is that step 1 is critical. Indeed, working with effected workers and medical staff is critical in determining if the effects are real and a result of the worker’s employment.  Listen to the workers and listen for patterns in their reports.   Most workers are honest witnesses to events and should be taken seriously.

After establishing that you have a problem, albeit a sneaky one, you should start building a hypothesis or two as to what might be happening using everything you know about their symptoms and the workplace.   

For example, it may be that the exposure is happening as bolus doses of very short duration (see previous blog on bolus dosing) and that time-integrated sampling could be missing it.   You may not be monitoring for a potential cause at all because you dismissed it.    It may be occurring via un-monitored and here-to-fore un-noticed dermal exposure.    The point is that you have a problem that has to be addressed.  Once you determine that it is more likely than not that the workers’ adverse effect happened because of exposure at work you are now on the hook to hunt the source of  that exposure.

In the above situation, you are starting at the end of the source-to-dose continuum and working backwards.

Discussion Questions for LinkedIn Groups:

Has this every happened to you?   If so, what turned out to be the cause and the fix?


  1. Pertti (Bert) HakkinenSeptember 2, 2014 at 3:47 AM

    Hi Mike. Good blog post. Some readers and you might be interested in a "continuum" publication from 2003:
    "Aligning chemical assessment tools across the hazard-risk continuum."

    (Disclaimer: Opinions are my own and don't necessarily reflect those of NIH or other parts of the Federal government."

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  2. Chris Packham has a keen interest in dermal exposure and really expanded on my comment above that "dermal is different" relative to the continuum. His note to me is below:
    When you start to consider skin exposure the whole issue becomes much more complex.
    Just for openers, look at this statement from the EU 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

    When it comes to skin measurement there is no generally applicable method. Questions one will need to address are:

    What are we measuring?
    What lands on the skin – what adheres to the skin – what is absorbed by the skin – what penetrates through the skin – combinations of the above

    Where on the skin will you measure?
    Skin on different areas of the body will respond differently to the chemical. If you have exposure on more than one part of the body how will you correlate the results?
    What is the actual skin condition at the time of contact?

    Damaged skin, even at a sub-clinical stage, can significantly influence the impact of chemicals in contact with that skin. Furthermore, there can be a combination of different effects, as illustrated in our document “Why measure…”

    What ambient conditions prevailed at the time?
    These can have a significant influence on skin uptake

    What was the true cause – or more realistically, what were the true causes – of the damage to health that has occurred in a particular case. Take a look at the diagram that illustrates the different factors that we have to take into account.
    In my experience in almost all cases I investigate there will be more than one of these to account for. I have even had cases of dermatitis with accompanying anaphylaxis purely due to a psychosomatic condition. The lady in question had been diagnosed as sensitised to natural rubber latex, but could handle this with no problem, provided she was unaware that what she was handling was natural rubber latex. However, she would react to plastic if she was told it contained latex!

    I had a case of a worker who had suffered a facial rash. He was diagnosed as allergic to formaldehyde and as this was used in the factory the dermatologist had stated that this was an occupational skin problem. My investigation showed no exposure to formaldehyde in the workplace but a reaction to formaldehyde that resulted from his drinking sugar free soft drinks. These contained a sweetener called aspartame and in his case digestion of this was metabolising the sweetener with one of the metabolites being formaldehyde.

    There is much more to this than many assume. In one recent case I had to find a laboratory that could do DNA analysis on dog dander, just to prove that one employee’s dog was not causing another’s asthma!

    You will find more on this in our Guide to Occupational Skin Management.

    Best regards

    Chris Packham
    EnviroDerm Services
    Unit 10, Building 11, The Mews, Mitcheldean, GL17 0SN
    Tel: 01386 832 311
    Mobile: 07818 035 898

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