Sunday, November 17, 2013

Learning from our Mistakes in Modeling

After the discussion of the octanol/water partition coefficient in the last blog, I thought this would be a good point to go over what was perhaps my biggest professional surprise and how we learn a lot from our mistakes.   What I am recounting below is my recollection of the facts.   To “blind” the identity of the product some of the numbers are changed but the scientific facts remain unchanged.

I was responsible for a risk assessment for a water treatment chemical that was used to treat large circulating systems within a plant.  The active ingredient in the product was highly lippophillic (had a high octanol water partitioning coefficient) and limited water solubility (about 500 ppm) (see previous blog on this subject).   It was used in the water at about 5 ppm by weight.   The vapor pressure of the active ingredient is relatively low such that the saturation or head space concentration of the pure material (see previous blog on this subject) was only about 1 mg/m3.    The exposure limit was relatively low at 0.4 mg/m3 based on its ability to cause local tissue upper respiratory irritation response seen in rat inhalation studies at relatively low concentrations in air.  

So I ran the models (UNIFAC and modified Raout’s Law):  Even with a large thermodynamic activity coefficient (see previous blog on UNIFAC) the worst case saturation concentration of this active ingredient at 5 ppm in water was a VERY small portion of the exposure limit.   I told my internal clients that I could not see any problem with inhalation exposure and risk from this active in this application. 

Imagine my surprise when we started getting reports of upper respiratory irritation in systems where older actives were being substituted with our new product.   I requested that some air monitoring be done in selected area within a specific plant.   To my complete and utter amazement, some of the values came back around 0.5 mg/m3.   This is 50% of the value for PURE active!   How could this be?   How could a 5 ppm solution in water generate this much airborne active ingredient?   I had to know so I booked a trip ASAP  to visit the site, to see things for myself and repeat the monitoring.

The highest sampled airborne concentration occurred over an open sump that contained about 5000 gals of the treated water.   As soon as I saw the sump, the whole thing started to made sense.   On top of the liquid surface was a 1-2 inch layer of FOAM.   Apparently some part of the plant process resulted in a foaming agent going into the water and the agitation within the process produced the foam.  

Because foam is typically much more "oily" than water, our active was partitioning into the foaming agent and thus into the foam.   Subsequent analysis of the foam showed that it had very high concentrations of our active ingredient.   As the form bubbles “popped” they released aerosol particles to the air that were rich in our active which further concentrated as the water and any other more volatile components evaporated from the aerosol particles because of their high surface area to volume ratio.   The entire mix of aerosol and active vapor produced the high breathing and irritating breathing zone concentrations above the sump.

If there was no foam there was no concentrating of the active ingredient into the foam and no high levels of airborne exposure.   The reality from a product stewardship perspective became clear to me; namely, that when foam was present in some systems that these scenarios where clearly capable of producing unacceptably high airborne concentrations.  

For me, the moral of this story is twofold.  First, one should always have some level of “ground truthing” for the predictions of a model.   That is, do some monitoring.   Those who model should always be open to monitoring.   They are not two separate camps.   The modeling informs the monitoring and the monitoring “ground truths” the models.   Second, we should always be ready to have Mother Nature throw us a curve ball.  We can predict a lot with models but we should always be open to potential game changers from unanticipated factors. 


  1. This is a note from Chris Packham from the UK and someone with a lot of experience in dermal exposure assessment. I thought I would add it as a comment to the above. MikeJ


    This is something that in my field I am very aware of. Indeed when conducting a risk assessment for skin exposure frequently the most difficult aspect is identifying the real hazard. This is seldom the original chemical. We purchase chemicals to use them. When using the chemical it is usual that we change its characteristics and thus the hazards. I can show you many examples of this. For example an epoxy impregnated carbon fibre mat being used in an aerospace plant which contained a potent skin sensitiser. For one task this remained non-bioavailable, in another the combination with another chemical rendered it strongly bioavailable. Same product, different hazards. The key is observation of what is really happening in the workplace when the product is used. This is one reason why I seldom do modelling. I concentrate firstly on identifying exactly what is happening in that workplace for that particular task.
    Take a very simple example, in the form of a degreasing tank, containing, say, toluene. It is only toluene when the tank is first filled. Once we start to degrease components the toluene becomes mixed with the substances that we are removing from components. So the hazard is no longer pure toluene. Suppose that we are cleaning items that have been returned from other workplaces for refurbishment or repair. We might not know what is in the soil that we are removing. This may contain potent skin sensitisers or other nasty chemicals. If we were to model the exposure risks based on toluene, how valid would these be?
    Best regards

    P.S. Please feel free to add this to your blog if you so wish.

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

  2. I agree with you Mike. Risk assessment should be made compulsory in every field, I guess. It is because of no or very little risk assessment that there are health hazards, workplace accidents, and road accidents taking place.