I said, ">> You can never make two metabolites
>> from one IMI that both retain the binding
>> site and block two nerves. "
This does mean two molecules of IMI can undergo different metabolic pathways. IMI number one could go down one pathway that happens to lead to a metabolite that can bind to a synapse. And IMI number two can go down another pathway that leads to a different metabolite that can bind to a synapse. Perhaps in one metabolite you chopped off a methyl group and in the other you added a hydroxy group. You can start with two molecules of IMI each of which potentially can bind to one synapse. If both degrade to different metabolites which can also bind to a synapse you are still only binding a total of two synapses.
Toxicity is a function of a great many factors. Things like:
1. How is the molecule distributed between water and lipids and does it have enough solubility in both to allow effective transport.
2. Overall size and molecular weights which govern diffusion behavior.
3. Is the molecule bound loosely to something that can help transport it to some site where it can exert its toxicity.
4. The molecules binding coefficient to the site where it exerts its toxicity.
5. The rate the critter detoxes the molecule or detoxes toxic metabolites.
6. The rate the active material or active metabolites are excreted.
ETC
You can even have cases where the parent compound is for practical purposes non toxic yet it metabolizes to highly toxic compounds. This is more frequent for drugs than it is for pesticides.
" Any discovery made by the human mind can be explained in its essentials to the curious learner." Professor Benjamin Schumacher talking about teaching quantum mechanics to non scientists. "For every complex problem there is a solution which is simple, neat and wrong." H. L. Mencken
--------------------------------------------
On Thu, 10/29/15, James Fischer <[log in to unmask]> wrote:
Subject: Re: [BEE-L] Neurological effects
To: [log in to unmask]
Date: Thursday, October 29, 2015, 12:27 AM
> Jim seems to be suggesting that
it is building up to a toxic dose.
> Randy is denying it. Are different things meant here?
If by "toxic", you mean "fatal", I do not think anyone means
"fatal".
The "toxicity" here would only be some low level of
"intoxication".
"No Observed Effect" vs a "Measureable Effect" is the
terminology people
use.
(Yes, a navigational or behavioral issue from a claimed low
"chronic"
exposure could mean that the bee does not return from a
flight, so the bee
is just as dead either way, but no one expects the bee to
keel over from
acute pesticide poisoning from a low chronic dose.)
And I don't think that Randy is "denying" anything, as I
don't think that
there is a conversation.
Christina said:
> ALL of the molecules persist for days, especially the
top
> two metabolites, and ALL of them can bind to
synapses.
> So one IMI molecule binds to one synapse. But its
two
> metabolites can bind to TWO synapses, that was Jim's
point.
Yes that was my point, but hold on there... maybe you can
tell us if I
neglected to consider what Richard brings up - he's claiming
that there is
only one unique binding point for an imidacloprid molecule,
and that the
breakdown thereof yields two or more molecules, but only one
that can bind
to a receptor, and one (or more) that cannot.
Apparently, there's no way to
tell which one ends up with the bit that does the binding,
which runs
counter to what I thought I knew about how enzymes do their
jobs.
>> You can never make two metabolites
>> from one IMI that both retain the binding
>> site and block two nerves.
If the above is true, then I don't understand how anyone
could ever get away
with saying things like "the metabolites are more toxic than
the
imidacloprid", which has been said multiple ways by multiple
people. The
toxicity should, in this scenario, be no different before or
after the
initial breaking up of the imidacloprid, and no metabolite
could ever be
"more toxic" to the bee.
What gave me the impression that each of the two major
metabolites could
bind to a receptor was the lack of any qualification to the
statements I've
read about their abilities to bind. If only one of the
two can bind, I'd
have expected someone to mention it. I also remembered
this older paper:
http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2000.751294.x/pdf
"First-generation (CP) and second-generation (CT)
neonicotinoids bind at the
same site in the same way
Structure-activity relationships developed for the action of
neonicotinoids
at the nAChRs of two Dipterans and two Homopterans provide a
unique data set
to evaluate the first- and second-generation insecticides.
Adding the CP or
CT substituent to nithiazine-type Molecules greatly
increases the
insecticidal activity.
Thus, the CT substituent generally confers higher potency in
the
clothianidin and desmethylthiamethoxam series, and the CP
moiety is
preferred in the IMI, thiacloprid, acetamiprid, and
nitenpyram series."
In the above, the specific use of the term "moiety" may have
a different
meaning than I interpreted.
Re-reading it now, I have to concede that these paragraphs
are no basis for
any conclusion on this.
It gaves me the impression that there are two "working
parts" to the
"CP"-type pestcides, each of them able to "work" (block
receptors).
But I cannot point to anything authoritative. As I
have said before,
structural work seems appropriate, as knowing the actual
structures of each
metabolite would help to resolve many unresolved issues of
contention. I
don't think anyone has looked at the actual structures,
although there seem
to be many who are acting as if what they have been told had
some firm basis
in fact, when it seems to be pure assumptions, based upon
what was intended
by the chemists who developed the pesticide.
> As Jim pointed out in an earlier post...
If I am pointing anything out, I hope it is that many of the
flat statements
made here on Bee-L about the nuts and bolts of pesticide
metabolization and
toxicity seem to have nothing to support them that can be
considered
"authoritative evidence". If someone has done some
LC-MS work, and has a
list of weights of each metabolite, I've yet to see
it. If someone has some
actual structural data from looking at real molecules as
metabolized by real
bees, subjected to "field-realistic" doses, I've yet to hear
of it. Without
either one, I don't understand how anyone has any idea
of what's going on
in the early stages of metabolization, which is a very big
missing
prerequisite, given the stentorian tones with which these
points have been
proclaimed.
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