skin contact with acrylamide
pxpst2 at unixs.cis.pitt.edu
Tue Jul 21 14:27:15 EST 1998
In article <35B44F62.3522 at bcc.orst.edu>, fordb at bcc.orst.edu wrote:
> As with many stories in toxicology, the direct toxicity of the a
> compound is one thing but the toxicity of an immediate metabolite may
> well be another. The epoxide of acrylamide, glycidamide, is indeed an
> initiator, and a classical mutagen. An Ames assay that includes the
> appropriate CYP 450s will show direct adduction to guanine for example--
> whereas acrylamide itself is not an Ames mutagen, but is a known
> initiator in whole organisms.
> Ref: Segerback, D. etal (1995) "Formation of
> N-7-(2-cabamoyl-2-hydroxyethyl)guanine in DNA of the mouse and the rat
> following intrperitoneal administration of [14C]acrylamide"
> Carcinogenesis 16:1161-1165.
Wow is that not what I said? You are very wordy. And BTW, all epoxides
will do this not just the epoxide of acrylamide. Activation of chemicals
in vivo is fairly common. The classic example is the p450 activation of
CCl4 in the liver. But now I digress like you Bryon.
> > >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,
So Dr Ford the Molecular biologist is now a chemist and knows more than
the experts who work with the stuff and write the MSDS sheets.
> > > 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.
> OK, a few, I have *real* work to do.
> For the issue of wide tissue distribution see for example: Crofton, KM
> etal (1996) "The impact of dose rate on the neurotoxicity of acrylamide:
> the interaction of administered dose, target tissue concentration tissue
> damage, and functional effects" Toxicol. and Applied Pharmacol.
Most interesting....I used to work in the Lab of Dr Hugh Tilson(currently
at EPA but was at NIH) who is one of the PIs that wrote that paper. Have
you even read it? I doubt it. My guess is that you did a medlib search
of acrylamide and mapped the subject heading to Pharmokinetics. How
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. This
implies that scavengers are preventing the acrylamide from reaching the
> For the danger of dermal exposure from an epidemiologic perspective see
> for example: He FS etal (1989) "Neurological and electroneuromyographic
> assessment of the adverse effects of acrylamide on occupationally
> exposed workers" Scand. J. Work Environ. Health 15:125-129.
Wow, acrylamide is a neurotoxin and exposure to large amounts can cause
problems with sensory neurons. I already said that the sensory neurons
were going to bear the brunt of the damage. The primary neurons were not
affacted to a great extent. What does this paper tell me that I have not
already told you? Once again you are doing a lame search and not reading
the articles or even the abstracts.
>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.
> For a broad reading of the subject, search PubMed using "acrylamide
> neurotoxicity" (in quotes as given) this will give about 96 citations,
> including 12 reviews. And as Peter recommends, pay close attention to
> the MSDS.
I am SURE that your health and safety guys would recommend that the MSDS
should be the FIRST THING YOU READ.
> 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.
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.
I would suggest that you stick to your p53 expression in zebra Fish and
leave the chemistry to chemist. Also, quit being so presumptive with your
Dept of Pathology
University of Pittsburgh
"Don't you eat that yellow snow
watch out where the Huskies go" FZ
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