Methylmercury in Your Child’s Brain

Politics

Under other circumstances, I might try to provide a discussion of the nuances of modeling the dose-response relationship between a mother’s exposure to methylmercury and neurobehavioral development of the child.  But, the fact of the matter is I probably wouldn’t do much better than I and others have done in the past (e.g. FDA, 2014), so I won’t bother.  Besides, a discussion of the vying political interests associated with having a dose-response model at all just might be far more interesting anyway.

With methylmercury, the political story revolves around an arbitrary number called the Reference Dose (RfD).  The meaninglessness of the RfD is entirely intentional – it was specifically designed to be devoid of any and all information value.  While the RfD and similar values do have some legitimate regulatory uses, the RfD is also often used as a form of political rhetoric.  The fact that it doesn’t mean a damn thing makes it perfect for that. 

The Environmental Working Group (EWG) discussion of the toxic effects of methylmercury provides a nice concise example of the use of the RfD as political propaganda.  Specifically, they make the following statement concerning the RfD:

In 2001 the EPA concluded that a pregnant woman could consume 0.1 micrograms of mercury per kilogram of bodyweight daily without ill effects to her fetus and that this amount of mercury would also be safe for children and adults (EPA 2001).

Actually, that’s wrong.  The EPA description of the Reference Dose is “likely to be without an appreciable risk of deleterious effects”, not “without ill effects”.  Maybe that sounds picky, but the difference is that the second sentence implies that scientists actually have some way of identifying a dose that has absolutely no “ill effects”.  No, we really don’t.   They then go on to say;

government and independent scientists have not reached a consensus on a safe level of mercury exposure

Yeah, well maybe that’s because there is no such thing.  Scientists have never agreed on how many angels can dance on the head of a pin either.  But that doesn’t stop EWG from taking one “safe” level and morphing it into another:

EWG recommends that pregnant women and children consume no more than 75 percent of EPA’s safety level.  By doing so, they are likely to build an extra margin of safety from lifelong damage mercury can inflict on the developing brain.

They’re just making stuff up – can you tell? I’m sure EWG thinks their political adversaries are dastardly money-grubbing fishmongers.  Maybe some of them are.  But, I’m all about defending the environment from ignorant political pablum.  That means I’m in favor of both science and democracy.  If that sounds trite, well trust me it isn’t. I want to give decision makers the best information possible – even if they happen to be Democrats, Republicans, or citizens of some other ilk.  Furthermore, I want scientists to be able to say what they know about methylmercury without passing moral judgment at the same time.  Is all that too much to ask?  No, it is not:  A nice scientifically-defensible dose-response function will send all those 'safe’ levels back to the netherworld from whence they came.

Science

Rant over; the FDA risk-benefit analysis used three different dose-response analyses, all of which have been published.  They are all derived from populations with either very high level fish consumption (New Zealand, Seychelles, and the Faroe Islands) or from an epidemic where there was accidental exposure to methylmercury.  There are also many studies at lower exposure levels, but they aren’t very useful for establishing a dose-response relationship.  The reason for that is straightforward:  Since many many factors can influence the behavioral development of a child, any statistical association observed in a low dose study can only be reasonably interpreted to be causal if it is consistent with what has been observed at higher doses (i.e. if there is a toxic effect a at a low dose, a bigger effect is to be expected at higher doses).  So, we may just as well stick with the higher dose studies:

• Delayed Walking and Talking.  This is an analysis I did while I was at the FDA (Carrington and Bolger, 2000).  It is based on a pooled data set from both Iraq and the Seychelles where the age at which each child began to walk or talk was recorded.  The exposure of mothers to methylmercury during pregnancy was measured by taking hair samples.  The main advantage this data set has over the others is that you don’t really have to worry about the whether or not the associations are really causal – the effects that occurred in Iraq were big and obvious (for example, there were two children who could not walk or talk at age 5).  In addition, it is also possible to tell something about how variable the effects are – not all the children exposed to very high levels of methylmercury responded in exactly the same way.
• Intelligence Quotient (IQ). This analysis (Axelrad et al, 2007) was developed by the EPA for doing cost-benefit analyses.  It was used by the Office of Air to support the Mercury Rule enacted in 2011.  Because the agency already had developed a methodology for calculating a dollar value for impacts on IQ, it was especially important to quantify the impact of methlymercury on this standardized measure of intelligence.  Sinc the Faroe island study only completed four of the 10 tests that are part of measuring IQ, (both the New Zealand and the Seychelles studies did the full set), this isn’t exactly IQ – but it’s as close as anyone is going to get.  [The Office of Water tried to block the use of this analysis because they correctly surmised that it would make the Reference Dose irrelevant].
• Domains.  The New Zealand, Faroes Island, and Seychelles studies all conducted a wide variety of different tests on each child in the study.  A group of scientists at Harvard (Cohen et al, 2005) went through the results from all three studies and sorted them into different functional “domains”: Motor, attention, visuospatial/visuomotor, language, memory, and intelligence.  By doing so, they hoped to determine whether or not methylmercury impacted specific areas of the brain.  But, as it turned out, there were no clear cut differences between the different categories of performance, which suggests that methylmercury has effects throughout the brain.  Nonetheless, this analysis does a good job of showing how big the effects of methylmercury may be across a wide variety of behavioral tests.

Software

Besides providing an opportunity to peruse the different dose-response models in isolation, the VBA macros provided here can be used as part of a larger model:

MeHg DR_Functions.xls

MeHg_DR_Function_Reference

References

Axelrad D.A., Bellinger, D.C., Ryan L.M., and Woodruff T.J. (2007), Dose-Response Relationship of Prenatal Mercury Exposure and IQ:  An Integrative Analysis of Epidemiological Data.  Environmental Health Perspectives 115:609-615.

Carrington, CD and Bolger, PM (2000).  A Pooled Analysis of the Iraqi and Seychelles Methylmercury Studies.  Human Ecological Risk Assessment 6:323-340.   Also, in Appendix E here.

Cohen, J.T., Bellinger, D.C., and Shaywitz, B.A. (2005). A Quantitative Analysis of Prenatal Methyl Mercury Exposure and Cognitive Development.  American Journal of Preventive Medicine 29:353-365.

Official Post Soundtrack

Rush (2007).  Workin’ Them Angels.  In: Snakes & Arrows, Track 3.

Post Notes

Thesis Post #57.  Part of the Individual Risk/Methylmercury series.