Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA

 Sharpe, MA, Livingston AD, and Baskin DS,  Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA  J Toxicol. 2012; 2012: 373678. doi:  10.1155/2012/373678

This paper has been touted recently by anti-vaccination folk as "evidence" that thimerosal is causal in autism, most recently by David Kirby at the Huffington Post

I haven't found formal analysis of this paper yet, but it was the subject of an online discussion.

Martine O'Callahan

First off, the whole study hinges on a presumption not referenced or so far tested "We postulate that this compound is preferentially taken up into the mitochondria of NHA causing damage to the respiratory chain and subsequent ROS production" There are no studies that I can find in support of this and I'm not entirely sure what they're basing it on other than they want it to be true... 

Linda Tock

We have to realize that this is an in vitro experiment. It's done in a cell line in a lab in little plastic containers like these:

http://www.nuncbrand.com/en/page.aspx?ID=229

So the first thing we have to realize; this study only looks at one specific focus; those particular cells and their reaction to thimerosal. It does not take into account the rest of the organism; the circulatory system, the liver, etc - so there is no adsorption, distribution, metabolism or excretion (often called just ADME) here - all things which occur in our bodies.

So we have to first understand that the results here may not accurately reflect what happens in a 'whole' organism. 

If we look at Figure 1 (which is actually mislabeled a/b wise in the 'window' of the study - but that's neither here nor there), we see two graphs. The top (a) graph shows the changes in mitotracker and ROS induced DCF levels as the concentration of thimerosal increases.

(ROS = Reactive Oxygen Species)

DCF = 2,7-dichlorofluorescein (I'm assuming - since they don't actually say specifically ANYWHERE in the paper what DCF is an abbreviation for).

So how much ethyl mercury was there?

At a concentration of about 2.5 uM (micro molar) we see a definitive (ie: significant) upswing in the fractional change, which is sustained through about 7.5 uM before it begins to tail off.

How much mercury is in 2.5 uM of ethyl mercury?

uM = umol/L

(2.5 umol Et-Hg/L) * (1 umol Hg/1 umol Et-Hg) * (202.59 ug Hg/1 umol Hg) = 506.48 ug Hg/L

There's 1 mole of Hg for every 1 mole of Et Hg, so there must be 1 micromole of Hg for every micromole of Et-Hg, and there's 202.59 grams of Hg per mole of Hg, therefore there must be 202.59 micrograms of Hg per micromole of Hg.

So, we have 506.48 ug of Hg in each L. 

So now what?

Well - we don't know how relative that number is. How does it compare to other studies of mercury? 

Let's compare that figure with the levels of Hg found in this study:

http://www.ncbi.nlm.nih.gov/pubmed/19560158

This study is in *preemies* - ie: low birth weight babies.

Why am I comparing the two studies? Well - the preemie study looked at the excretion of mercury from the infants - as well as the blood concentrations. 

This is relevant, because you cannot get mercury into or past the BBB without it being in the bloodstream.

So let's look at Figure 1. The highest amount of blood mercury recorded during this study was roughly 7.6 ng/mL.

How does that compare to our 506.48 ug/L from the previous study?

Well, that's rather simple. 1 ng/mL = 1 ug/L. So, the highest amount of blood mercury in the preemies in that study was 7.6 ug/L. (It's also interesting to note that the stools contained 10X the amount of mercury - on average - than the blood).

(506.48/7.6) = 66.6

emphasis added by editor The lowest amount of mercury which caused ROS generation in those astrocyte cells was over 60X the amount of mercury found in the bloodstream of infants within 48 hours of vaccination.

The *average* amount of mercury found in those infants was 3.6 (+/- 2.1) ng/mL or 3.6 ug/L. That means that emphasis added by editor the cell lines were exposed to 140 times (on average) the amount of mercury than what is found in the bloodstream of premature, low birthweight babies 48 hours after vaccination.

So, while direct application of thimerosal might induce ROS generations in a cell culture line, the amounts of thimerosal used for the study are not representative of the typical exposure window, nor do they account for the other biological factors (ADME) which can influence the toxicity to the cell line.

 

Update: Martine and Linda have published another version of our online discussion, Overdosing Brain Cells With Stuff Is Bad

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