skin contact with acrylamide

Peter pxpst2 at SPAM.SUXS.unixs.cis.pitt.edu
Wed Jul 22 10:54:50 EST 1998


In article <35B4F026.553 at bcc.orst.edu>, fordb at bcc.orst.edu wrote:

> Peter wrote:
> 
 


> > Some of the salient features of this paper say that:
> > 1) damage by acryamide depended on the dose.  Note that the experiments
> > were accute and short term chronic exposure at really high concentrations
> > relative to what a lab worker would see by incidental contact.
> > 2)Neuro toxicity was not as bad as predicted by dose vs time curves. 
> 
> Yes, that is one inference.

And science is filled with one inference leading to a new inference till
you retire and stop doing research....
> 
> > This
> > implies that scavengers are preventing the acrylamide from reaching the
> > neurons.
> 
> Perhaps, I won't deny that this is one possible inference. Perhaps you
> are neglecting to consider that these results fit very well with the
> known damage to axoplasmic transport (or axonal if you prefer). Under
> such a model the accumulation of moderate damage can be at least
> partially repaired in the absence of the toxin, but longer term doses
> cause accumulation of damage to levels that are substantially
> irreversible. 

Yes and look at the concentraqtion of acrylamide used.  Not exactly
pysiological.  One would have to either breath the powder or eat the
powder to get those concerntrations in vivo.  I have no doubt that If the
acrylamide does enter into the neuron then these effects would be seen. 
Other agents that can react/crosslink with proteins can show similar
effects.
Remember that this thread was started by a person that had incidental
contact with an acrylamide stock solution.  You have obviously forgatten
this and have gone to the extreme.
> 
> Before you jump to the conclusion that this proves your point about the
> regeneration, you should note that acrylamide damage is progressively
> less repairable in longer neurons. Humans have some sensory neurons
> approaching a meter in length. These are very dependent on axoplasmic
> transport. It is these very neurons that are most susceptible to
> acrylamide toxicity in humans. 

I have jumped to no conclusions, I am simply stating what was already
stated in the article by Crofton, KM etal (1996).  I do not claim to be an
expert in Acrylamide poisening and after doing a literature search on your
work, YOU ARE NOT AN EXPERT EITHER.

> You were one
> who earlier appeared to minimize the danger of dermal exposure routes.

The dermal route that I was refering to was the route first described by
the origional poster.  As best that I can surmise from the description is
that the person had a few mls of acrylamide stock(at best) on her lab coat
and she was afraid of the damage it could do. I would think that those
levels would show the minimal damge at best. and the study you pointed out
impies that.
> 
> > >For the specific neuronal lesions involved in at least a major part of
> > >acrylamide neurotoxicity see for example: Sickles, DW etal (1996)
> > >"Direct effect of the neurotoxicant acrylamide on kinesin-based
> > >microtubule motility" J. Neurosci. Res. 46:7-17.
> > 
> > This study was not at all representitive of in vivo because the MT were
> > lifted from a bed of Kinesins and then exposed to acrylamide(0.1mM-1mM).
> > I would say that is significantly higher than a lab worker will see while
> > incidently exposed to Acrylamide in the lab.
> 
> Now, I wonder about your motives Peter. This is but one of a large
> number of articles relating to the specific cellular lesions that may
> best explain the observed facts of acrylamide toxicity. This article and
> its companions are constructive efforts. Where is the article on your
> "receptor crosslinking" idea, or supporting literature for the high
> levels of sulphydryls in the plasma?

I said sulhydryls and Hydroxyls and yes they are in the serum.  For more
reading, please look at the article:

       Blatt etal. The association of acrylamide with proteins. The
interpretation of fluorescence quenching experiments. 

What you fail to realize is that Acyrliamide is spontaneously reactive to
these groups whether you want to believe it or not.  And there are a lot
of these groups in the plasma.
> 
> > >
> > > However, I would not recommend using MSDS assertions to promote
> > > dismissive claims about the harmlessness of contact with aqueous
> > > solutions of potential toxins regardless of their modest solubility in
> > > "oil". Lipophilic materials as a rule do not have the highest dermal
> > > transport parameters, nor do strictly polar materials-- amphipathic
> > > materials generally absorb better than either. The size of the
> > > acrylamide molecule and perhaps its olefinic structure as well as its
> > > amphipathic qualities make it remarkably mobile across skin, and then
> > > well dispersed as a potential systemic toxin.

Modest solubilities... Now the solubility is modest.  Can you say
"Partition coeffiecent? If the greater protion is partitioned into the
Aqueous phase then it will react in the aqueous phase.  If you are able to
swamp the aqueous system them some of the acrylamide(possibly a
significant amt) will be able to pass through the lipid bilayer and react
with the intracellular proteins  but like you mentioned earlier, you have
to over come the intracelular scavenger glutathione which will be present
in the cell at concentration ranging from 0.1-10 mM depending on cell
type.  But now I digress.
> 
> > First, I do not promote dismissing anything.  I am simply offened by the
> > "know it all " tone that YOU had with Dima.  Dima was wrong in dismissing
> > the FACTS.  And you are wrong in assuming that you know much chemistry.
> 
> Well, I won't claim to have any more or less than two years of
> inorganic, two years of organic, a term of quant, and several years of
> hands on chemistry lab experience. I do know this though, so far, you
> have demonstrated nothing greater than a sophomoric understanding of
> chemistry here. Toxicology risk assessment is hard enough to do
> constructively. It is quite impossible to deduce toxicologic risk from a
> few general chemistry principles, although this is certainly a necessary
> part of such an effort. 

Let see, I too have 2 years of Organic, two years of inorganic, 2 years of
Quantitative analysis, and several years of chemistry lab experience but
by no means do I claim to have the expertise necessary to claim to be an
expert.  Maybe I need to inflate my ego.  My expertise are in the
seperation sciences.  I would say that you have dmonstrated about the same
level of expertise as I.  I am currently working in liver
regeneration/cancer.  I do not profess to be an expert in neurotoxins but
have published in that feild.

 Rogers BC. Mundy WR. Pediaditakis P. Tilson HA. The neurobehavioral
consequences of N-methyl-D-aspartate (N-MDA)
administration in rats. [Journal Article] Neurotoxicology. 10(4):671-84,
1989 Winter.

Tilson HA. Harry GJ. McLamb RL. Peterson NJ. Rodgers BC. Pediaditakis P.
Ali SF. Role of dentate gyrus cells in retention of a
radial arm maze task and sensitivity of rats to cholinergic drugs.
[Journal Article] Behavioral Neuroscience. 102(6):835-42, 1988 Dec.

Tilson HA. McLamb RL. Shaw S. Rogers BC. Pediaditakis P. Cook L.
Radial-arm maze deficits produced by colchicine
administered into the area of the nucleus basalis are ameliorated by
cholinergic agents. [Journal Article] Brain Research. 438(1-2):83-94,
1988 Jan 12.

 and I do not have a "holier than thou" attitude. I believe that when I
wake up everyday, I thrive to learn something new.  From you, I have
learned that some peaple see themsleves as experts when they are not.  


> I will take my toxicology judgements from toxicologists, and my
> chemistry judgements from chemists who appear to have a grasp of
> cellular and organismal physiology.

Good.  I will do the same. 
> 
> 
> Bryan L. Ford
> (all but dissertation PhD. candidate in Toxicology),
> Dept. of Environmental and Molecular Toxicology
> (formerly the Toxicology Program)
> Oregon state University
> Corvallis, OR 97331
> 
> Some areas of interest/expertise:
> 
> Molecular biology
> Molecular oncology
> Molecular evolution
> Subnanosecond fluorescence phenomena
> Nutritional biochemistry
> 
Expertise impies that you have published in these feilds.  Just out of
curiousity have you?

Molecular oncology....now that is an interesting term. 

Peter Pediaditakis
Phd candidate in Medical Sciences
Dept. of Pathology, School of Medicine
University of Pittsburgh

Also, If you wish to waste bandwidth, I would be happy to continue this
discussion/pass of insults via email. I feel that WE are beginning to
waste space on this Newsgroup.

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

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