Friday, May 24, 2013

We do not estimate Quantitative Risk for Most Chemicals

In last week’s blog I discussed the difference between calculated actuarial risk and the risk we estimate using the risk  assessment of chemicals.   I mentioned that instead of actuarial risk which is born of historical response (e.g., deaths from auto accidents) that the estimated health risk from our exposure to chemicals is not calculated in this manner and is not nearly as accurate.  Indeed, most of the time it is not calculated at all.   At that point I did not explain any further but promised to get back to you.    Well here is the further explanation.
We have tested relatively few chemicals for their ability to cause cancer (carcinogenicity).   The reason for this is that it is very expensive (millions $)  to test rats or mice for a majority of their life span by housing and exposing them to the chemical every day or most days and then killing and studying their body tissues at the end of the study.   I had a professor who told me that about half the chemicals we test for carcinogenicity come out positive.   I have not checked this as a fact but it makes sense to me.   The manner of testing is that you exposed the animals to very high doses on the high end group of the study.   This is the so call Maximum Tolerated Dose (MTD).   A dose that is so high that the animals can just barely tolerate it without dying.   Such doses especially over a lifetime can cause all kinds of reactions in the body.   Even simple irritants can cause the cells of the body to react by reproducing prematurely and in doing so they can make mistakes in the DNA synthesis and produce a cancer.  
Even though it may be quite common when we look for it, we historically treat the identified cancer causing chemicals very differently.    The assumption is that there is no dose without risk (no threshold) and therefore the smallest amount (one molecule) presents some cancer risk and two molecules presents twice this level of risk.   This is the so call linear dose response estimate.   So we have used a linear model to estimate the dose or exposure that gives an “acceptably” low level of risk (a virtually safe dose).   This risk is often the exposure that results in 1 in 1,000,000 estimated additional cancer risk for members of the general public but about 1 in 1000 for workers.   I hope to get into the reasons for this difference in “allowable risk” in the next blog but for now it’s enough to see that we estimate a quantitative level of risk for any exposure to an identified or declared carcinogen.  
Most chemicals are not considered to be carcinogens but they are known to cause some bad health effect (e.g., liver , kidney or nervous system toxicity) given high enough dose.   Historically we do not treat non-carcinogens in the same manner.   Indeed, the conventional wisdom is that there is some threshold of exposure below which NOTHING bad happens.   Here we set “acceptable” exposure as the level that did not cause a bad effect in an animal study divided by an uncertainty or a safety factor.    The critical piece here is the assumption that a threshold exists.   The way risk is estimated is that the estimated exposure (EXP)  to the chemical is compared to the allowable exposure limit  (EL) as a ratio:   EXP/EL  =  Hazard Index (HI).    If the HI is less than 1 then everyone is happy.   If it is greater than 1 then something has to be done to control the risk.   Please note that in this scheme there is NO quantitative estimate of the risk at the exposure limit or any fraction of the limit.

For many years I would argue with my colleagues in toxicology that most thresholds cannot be proven because of limitations in our methodology.   My argument was that we should estimate the quantitative level of risk for all chemicals including non-carcinogens at and below their exposure limit or the level of “acceptable” exposure.    I wrote a paper about this in 2001 with two colleagues that was largely ignored.     More recently (2009) the 'National Academy of Sciences (NAS) published the so called “Silver Book” which basically agrees with me that the distinction between carcinogens and non-carcinogens is not valid and that the quantitative level of risk should be estimated for all.   The NAS now offers all its books as free PDFs for 'download.   If you are interested in getting this book go to:
Chapter 5 is where the action is on this topic.

I will be happy to send anyone a PDF our 2001 paper if you send me an email request:

So far the occupational health community has continued to successfully ignore this issue and continues to not estimate quantitative levels of risk for non-carcinogens.
Next time I will discuss the difference between exposure limits for workers and the general public.


1 comment:

  1. Mike, I had no idea you had a blog. By the way, have you come across anything related to prescription drugs in the waterways, particularly municipality systems? After seeing it in the news multiple times I looked into it to find surprisingly little data. The most reliable study I found actually quieted my fears rather than heightening them.