skin contact with acrylamide

Peter pxpst2 at unixs.cis.pitt.edu
Mon Jul 20 22:31:23 EST 1998


In article <35B3CE58.43CE at bcc.orst.edu>, fordb at bcc.orst.edu wrote:

  
> Ford wrote:
> 
> > > This is erroneous advice. Acrylamide monomer is a small, amphipathic,
> > > molecule with considerable ability to dissolve in polar and non-polar
> > > substances (that is in plasma and to pass cell membranes. Acrylamide
> > > monomer has high mobility through normal latex lab gloves as well.
> > > Immediate and extended washing with water should be strongly advised.
> > > Immediate further treatment might have been beneficial but any delays
> > > increase the likelihood of permanent and progressive damage.

when two phases are present the material will partition according to its
solubility coefficients into the two phases.  As for having "high mobility
through normal latex gloves" is complete garbage.  If you looked on the
MSDS you would see and I quote " wear water impermeable gloves".  So it is
safe to asssume that BUTYL RUBBER, NITRILE, PVC, OR EQUIVALENT should
suffice in protecting you. If you disagree with this then please offer a
URL/ refernce that says this gloves commonly used in labs are not
sufficient protection. I would be very interested in reading them.

> 
>  
> Peter wrote:
> 
> > Acrylamde can only travel through the skin if you have it dissolved in a
> > carrier capable of passing through the skin.  I have always seen the
> > monomer disolved in aqueous solutions therefore it will not travel through
> > the skin. 

I was incorrect in saying that this can not pass through the skin, it can.
But due to the fact that it is more far more soluble in water than oil, it
is safe to assume that most will indeed partition in the aqueous phase. 
And as long as you promptly wash it off assorption through the skin 
should be quite minimal.
> 
> Ford replies:
> 
> Such an argument, presumably rooted in thinking about partition
> coefficients, is not correct even if acrylamide were a large and
> non-amphipathic molecule. Acrylamide itself can partition into the skin
> and widely distribute in tissues and into cellular compartments. The
> aqueous solution is perhaps less dangerous than other conceivable
> solutions with higher dermal transport rates, but even this is not
> proven.

There is no presumption here.  It will prefer to remain in the aqueous
phase.  If you disagree then please post the partition coefficents of
acrylamide in Water and in Oil to support your supposition.  
> 

> Peter wrote:
> 
> > In solution on
> > your skin, it is not capable of causing great harm.  It is reactive enough
> > that it will not travel far in the plasma. 
> 
> Ford replies:
> 
> We are discussing the free monomer, are we not? (Once polymerization is
> underway in solution the danger from aqueous dermal absorption begins to
> drop progressively with time since the concentration of monomer
> declines, at a variable but often rapid rate.) Absorbed free monomer,
> the component of a typical gel mix that is most likely to be absorbed,
> is not particularly reactive in plasma. The distribution rate constants
> exceed those for reaction/metabolism considerably. 

Yes we are talking about the free monomer and IF you read the MSDS, you
would note that acylamide  SPONTANIOUSLY reacts with hydroxyl-, amino-,
and sulfhydryl-containing compounds.  How many of those groups do you
think acyrlamide will see on the way to your plasma?  And how many will
acrylamide see in the plasma?
One more question for you is how does the "free monomer,the component of a
typical gel mix"  not going to be any more reactive than the free monomer
discribed in the MSDS?  As for the Distribution rates....care to provide a
source? 
> 
> Peter wrote:
> 
> > The primary target of aqueous
> > contact with acrilamide is the cross-linking of sensory neurons.  They
> > will regenerate over time.
> 
> Ford replies:
> 
> There is not "cross-linking of sensory neurons". I presume you mean
> cross-linking within sensory neurons. The damaging effects of such
> crosslinking result in defective axoplasmic transport within such
> neurons. As a note to other readers: these lesions have nothing to do
> with the catalytic agents that are in the typical gel prep-- the monomer
> alone provokes the neuropathology, the crosslinking reagents (if they
> were to be absorbed) have entirely distinct, and also potentially
> dangerous toxicology. The degeneration of sensory neurons is generally
> not reversible although some recovery from the milder effects of shorter
> term exposure has been reported.

(First, the secondary neurons do have the ability to regenerate over
time.  Please do not confuse secondary neurons with primary neurons which
have no ability to regenerate.)

Actually to be more accurate, ACRYLAMIDE MONOMER WILL CROSS LINK THE
RECEPTORS ON THE CELL SURFACE TOGETHER. Remember that arcylamide will
spontaneously react with free hydroxyl and amino groups.
If I understand your explination correctly then you are impling that the
proteins involved in "axoplasmic transport" ( the correct term should be
axonal transport btw) are more suseptable to cross linking than the
surface receptors.  I would again ask you for a reference for this.  I
would also like you to give me a reason why the Monomer will not
spontaniously react with any free Hyroxyl/sulhydryl groups on the cell
surface proteins.  

As for the Bis which is the crosslinking reagent, that was not part of the
discusion and is its own story, but it is in all arylamide solutions that
I have used.




<BIG SNIP>


I and others in labs make it a point to not be regularly exposed to
acrylamide monomer  in solution or powder.  And the first person described
a large single exposure.

 
> Ford replies:
> 
> I agree completely with this particular assertion.  The solid powder is
> extremely dangerous. The pulmonary absorption rate is far higher than
> the already dangerous dermal rate, hence even greater danger.

duh....


> Also the
> specific concentrations that pulmonary tissues near a dissolving
> fragment of the solid monomer may experience have their own specific
> toxicological hazards, including possible carcinogenicity or
> co-carcinogenicity. 

Possible?  If the acrylamide does not kill the cell and the cell is a
progenitor cell(lots of those in the lung) then you can say it(acyrlamide)
could without a doubt act as an "initiator" of cancer.  I say that because
it will act to alter segments of the DNA and if those segments just happen
to have some proto oncogenes then all that is needed is a promoting
agent.  BTW, acrylamide powder inhaled by rats was shown to cause cancer
in rats.  Animal tests are required for chemicals in California and that
is in the MSDS.  

>However, once a given amount enters the plasma the
> distribution is similar regardless of entry portal. Contrary to the
> assertion made by Peter, the unpolymerized monomer does not rapidly
> react in plasma,

Contrary to Peter... what crap.  You should say contrary to the MSDS.  Do
you think that the plasma is void of scavenger molecules?  Do you think
that the plasma is void of proteins that lack Hydroxlyl groups or
sulfhydryl groups?  The most likly scavenger would be Albumin which
exsists in the plasma in High concentrations.


> but instead rapidly distributes across many
> physiological compartments. The vulnerability of long neurons of sensory
> tracts has to do with their extremely long axoplasmic flow requirements,
> and possibly their relatively low cytoplasmic turnover rates. The
> latency to observable sensory decrements is well-documented and the poor
> reversibility is also well documented.

Okay, Why don't you posts some of references.


> I recommend that lab workers
> avoid the use of powdered acrylamide as much as possible. Instead, I'd
> suggest using the available acrylamide/bisacrylamide e.g. 19:1 40%
> premixes, since there is much lower likelihood of inhalating these. But
> again one needs to be aware of, and limit dermal exposures.
> 

I will remember not to pour it on my skin

Peter

-- 
"Don't you eat that yellow snow
            watch out where the Huskies go"    FZ

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