James,

What you wrote doesn't look like official risk assessment document. However, 
your essay is very informative and entertaining. Thank you.

Regards,

Vaheh Oganesyan
www.medimmune.com


-----Original Message-----
From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of James 
Holton
Sent: Wednesday, September 06, 2017 2:45 PM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] Risk assessment for heavy atom soaking - examples?

Something that could perhaps be of use here is what I like to call the 
"Anchovie Pizza Equivalent" (APE), which is about 1 microgram of mercury.  
According to the Food and Drug Administration website here in the USA the 
average mercury content of anchovies is 0.34 ppm, which is about 1 microgram 
per ounce of fish.  Tuna can be higher, but varies a lot from fish to fish.  My 
point here is that most institutions regard the amount of mercury you bring 
onsite for purposes of eating for lunch, be it sushi or pizza, as small enough 
to be negligible.  I tend to agree.  So, one could argue that 1 microgram of Hg 
per day is a "safe amount".  Especially if you don't eat it.

In terms of protein crystals, a 100 micron wide cube has a volume of 1 
nanoliter, and if it were soaked to a final concentration of 50 mM Hg that is 
1e-9 L * 50e-3 mol/L *200 g/mol = 10 ng.  So, 100 protein crystals soaked with 
Hg add up to roughly 1 APE.  Please note that I am in no way encouraging you to 
eat your protein crystals, and especially not the solutions you soak them in.  
You should do your own APE calculations for those.  But I do think it important 
to note just how tiny the amount of metal in our crystals really is.

Now, mercury is purportedly the second-most-toxic metal after Plutonium.  But 
Pu derivatives are uncommon.  In fact, until recently
(4zhd) Pu derivatives were unheard of. The authors I'm sure will tell you 4zhd 
involved no small amount of paperwork.  But as long as you are not working with 
Pu, you can regard every other metal as less toxic than Hg.

Another good example is selenium; by far the most common metal derivative.  
Although toxic, Se is also a dietary requirement.  I suppose this is an 
excellent demonstration of what "moderation" really means.  The Recommended 
Daily Allowance (RDA) of selenium in the USA for adult men and pregnant women 
is 55-60 micrograms per day.  In crystals, one Se atom per 100 amino acids at 
50% solvent comes to an overall concentration of 50 mM.  So, a 100 micron 
crystal contains about 4 ng of Se.  It would take 15,000 such crystals to add 
up to the US RDA.  The synchrotrons I work at don't go thought that many 
crystals every day. But even if they did, I'd stick to my commercially 
available multivitamin to get my dietary selenium.

So, although it is never a good idea to be sloppy with chemicals in the lab, I 
think it is also important to do the math and think about not just the toxicity 
of the things we work with on the bench, but the everyday items all around us.  
It is never a good idea to be antagonistic with regulators about such things.  
They are only trying to do their job, and all they are trained to know about 
are LD50s and how to stay as far below them as possible.  A little 
gently-pointed-out insight into non-lethal applications of heavy metals can be 
helpful all around.  The over-the-counter drug Pepto Bismol (bismuth 
subsalicylate) is almost 50% bismuth by weight, a metal that is right next to 
mercury on the periodic table. Brominated vegetable oil contains no bromine, by 
the way.  And dandruff shampoos such as Selsun Blue make an excellent and 
surprisingly radiation-hard reference for the selenium edge.

-James Holton
MAD Scientist

On 9/4/2017 3:13 AM, Dr Stephen Graham wrote:
> Hi all,
>
> (This email is aimed primarily at my UK colleagues, but feel free to
> read on and gloat that you don't have to write safety forms in your
> lab/country!).
>
> I need to sort out written risk assessments for heavy atom soaking of
> crystals in my lab. I wondered whether anyone would be willing to
> share the risk assessments they have in their institute/company so
> that I can seek inspiration and make sure I'm keeping up with best
> practice.
>
> Many thanks,
>
> Stephen
>
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