> I had been under the impression that most
> of the time we were talking about PPM or PPb,
> it was molecules......

Just to further complicate matters, we can only count the molecules that can
be detected, and it is not at all certain that we have a complete list of
metabolite molecules to count, nor is out ability to count them as good as
we'd like right now.

As Richard said recently: "Five ppb of most pesticides in one gram of nectar
is something like 10 to the 12th power of molecules or ten trillion
molecules."

Given that as the starting point, we are discussing fairly simple concepts
here that should not raise any ire, like why do the bees' (and also, the
plants'!) metabolization of a single molecule of a neonic pesticide like
imidacloprid seem to produce multiple metabolite molecules that each bind
with same receptors as the pesticide did, and perhaps do so more "tightly"
than the original pesticide molecule?  Anyone who saw Mickey Mouse in
"Sorcerer's Apprentice" can understand that a reproduction ratio of 1:2 or
1:3 is not a good thing when one starts with large numbers of either
pesticide molecules or mops.

So, after the initial steps in metabolization, one can take that ten
trillion molecules, and double, maybe triple it to get the number of
molecules that will block a receptor.  And this very basic point was not
made clear by anyone who was selling this stuff, and there are some who seem
to be still denying that this multiplication happens.

Randy said:

> I'm getting pretty  sick of hearing the "denial" claim, or the
> labeling of posters as taking black or white positions.
> Or as being "pro neonic."

When did "pro-neonic" become an epithet?
I  >>AM<< "pro neonic", and proud to say so!
I will be so bold as to go further and say that any beekeeper with half a
brain and a decade in the field would be "pro neonic", as the systemics are
clear and compelling improvements over the pesticides they replaced.

But the actual question at hand is - "Are they all that they are cracked up
to be, or do we see unintended consequences?"
I keep seeing more and more evidence of well-documented unintended
consequences, and as I hummed before, "the more I see, the less I know".

And more to the point, have we be fed assurances that have been misleading
about these chemicals?
If everyone was misled, then there seems to be work to do.
But if only we were misled, we need to get much smarter about neurology and
neurochemistry.

Here's a handy list of those metabolites:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827204/
http://tinyurl.com/nckk4z8

I think "Table 3" in the above is about the most complete list we have of
the known breakdown products of several of the neonics (and their molecular
weights in AMUs), but don't waste any time trying to figure "ppb" from them.
Instead, get the gist of this next paper with the very long title:

"Refined Methodology for the Determination of Neonicotinoid Pesticides and
Their Metabolites in Honey Bees and Bee Products by Liquid Chromatography
-Tandem Mass Spectrometry (LC-MS/MS)"
http://tinyurl.com/qfahtfp
This was written by an EPA employee in the Office of Pesticide Programs who
works at the chem lab at Ft. Meade

He found that, as usual, one can detect much smaller numbers of molecules
than one can quantify (count), but what they could detect and count in 2010
led them to conclude:

"It was suggested that the high toxicity of imidacloprid and its
metabolites, at very low doses, to honey bees could reflect the existence of
binding sites with different affinities..."

"The study also showed that mortality rose with low doses, fell with
intermediate doses, and rose again with high doses. The authors
suggest that at high doses imidacloprid and the metabolites that resemble it
(olefin, 5-hydroxy, and urea) fit into specific receptors
binding to the guianidine ring differently from the high-affinity receptors
binding to the 2-chloropyridinyl moiety, which all compounds may act on at
very low doses."

"Mortality rose with low doses and fell with intermediate doses..." sounded
like experimental error at the time, as the "binding differently" escaped
notice or evaded understanding.

This different binding activity at low doses vs medium vs high doses seems
to throws the whole concept of a "dose-response curve" out the window, as a
dose-response curve assumes that one gets more of the SAME activity as one
increases the dose, and these results seem to indicate that the type of
activity CHANGES with the dose.  Curiouser and curiouser, but all this
seemed merely academic at the time, as the recent set of bumblebee results
had not appeared at that time.

The same author gave a talk down at EPA in 2009 or 2010 that I was invited
to attend, and he explained that the Limits of Detection got much lower with
new gear:

Analyte...........................Quattro Premier......Xevo
.......................................LOD(ng/g)............LOD(ng/g)
=-=-=-=-=-=-=-=-=-=-=-=-=-=...=-=-=............=-=-=-=
imidacloprid................................1..................0.2
imidacloprid olefin....................10..................0.8
5-hydroxy imidacloprid.............10..................1
imidacloprid urea........................0.5...............0.2
imidacloprid desnitro olefin........0.75.............0.2
imidacloprid desnitro HCl............0.75.............0.2
6-chloronicotinic acid...............25...................8

So, the ability to detect has gotten MUCH better, and the ability to count
has also gotten better, but not as dramatically.

Back in 2004, Suchail, et al wrote a paper:
"In vivo distribution and metabolisation of 14C‐imidacloprid in different
compartments of Apis mellifera L."
Pest management science (2004): 1056-1062.
http://tinyurl.com/qha7vvf
in that study, they used radioactive markers, and found that the metabolites
remain longest in the head, thorax, and abdomen, which is where most of the
acetylcholine synapses are located.

We need to do something similar, but with the newer gear, and with some real
(physical structural) identification of metabolites.

There are, of course, the same familiar rebuttals offered as those
traditionally offered in defense of smoking, continued excessive CO2
emissions, and other "debatable" points.  But the gross-level harms that are
stridently demanded as prerequisite "proof" to satisfy the self-appointed
arbiters of "objective" and "grounded in evidence" has appeared in several
recent bumblebee-related studies, where colony numbers are smaller, and
thereby, easier to track at a bee-by-bee level, and see the negative impact
on the colony as a whole.

So, while many people say that things have to be "seen to be believed", this
seems to be a case of something that has to be "believed to be seen", in
that one must have the will to go and look at the actual chemistry, rather
than to accept the flat assurances of those who clearly do not understand
the chemistry themselves at a level sufficient to, for example, grock the
whole "Sorcerer's Apprentice" aspect of the actual metabolization of these
pesticides in a living bee in a colony, as opposed to a bee in a cage, which
never lives for long, even under the best of conditions.  (I think it was
the Smashing Pumpkins that sang "Despite all my rage, they are still testing
bees in a cage..." or something like that.)

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