This morning I decided to look and see what's been done to demonstrate IMI metabolites (and their fates) in the environment.

First, it is important to realize that metabolic pathways differ according to the organism.  You cannot assume that all life forms metabolize a given compound in the same way.  Think of ammonia....a very toxic byproduct of protein digestion.  We metabolize it into urea, birds metabolize it into uric acid.  Some of the metabolic steps are the same, but that is not a "given" for other compounds.  So looking at just one form of metabolism is not enough.


Another point to make quickly here is that imidacloprid is just ONE neonicotinoid.  We cannot assume that they all have the same inactivation profiles.


Here's what I have found so far:

Roberts, Terence Robert, and David Herd Hutson. Metabolic pathways of agrochemicals: insecticides and fungicides. Vol. 1. Royal Society of Chemistry, 1999.

Description:  “Imidacloprid is a systemic insecticide with contact and stomach action.  It acts on the central nervous system causing irreversible blocking of postsynaptic nicotinergic acetylcholine receptors.” (page 111).  (CW comment:  Notice they write "irreversible blocking".  This is not the organic chemistry definition.  It is the PHYSIOLOGICAL definition....meaning, it interferes irreversibly with synaptic function.)

They do not discuss insect metabolites, but they have a lot to say about metabolism in soil and some crop plants:

Imidacloprid in soil:

Tests on sandy and loamy soils, all moist.
DT50 in range of 188-997 days.
“The amounts of unextractable residues increased with time and were in the range 17-25% of applied radioactivity after 100 days and 23-40% after 366 days.  Seven metabolites were identified in the four soils…
olefinic cyclic nitroguanidine
cyclic guanidine and nitroso and nitro derivatives
6-chloronicotinic acid
4 and 5 keto cyclic ureas

No metabolite accounted for more than 1.8% of the applied radiocarbon after 100 days.
Rate of degradation of IMI was more rapid in soil cropped with grass (DT50 69 days)

5-hydroxy-IMI was detected on the cropped soils.

Photodegradation at 1.4 times natural sunlight levels was rapid, DT50 4.7 days, but after that it was slower.  5-hydroxy-IMI was the main product (6.4% of applied radioactivity).

Metabolism in plants:

Studied in tomatoes, potatoes, and maize, also Swiss chard, beets, and wheat.

In the tomatoes IMI was applied to the fruits. 21 days after application most radioactivity was recovered as the parent IMI (80%) and main metabolites were 4 and 5-hydroxy-IMI.  When injected into tomato plants, additional metabolites recovered included 6-chloronicotinic acid.

Potatoes:  IMI sprayed onto plants.  64 days later analysis by proton NMR, MS, TLC, and HPLC produced IMI as main recovered compound, metabolites similar to tomato plants.

Similar results in potatoes when when IMI was applied as granules to furrows where potatoes were grown.

Maize (corn) IMI applied to seeds.  Sampled 134 days after planting.  Metabolites similar to tomatoes and potatoes, also broadly similar results found when IMI applied to soil around Swiss chard, wheat, or beetroots.

Much of the IMI from treated seed remained in soil where it was fairly persistent.  Maximum IMI at tops of plants 64 days after sowing was 5.3% of that applied.  Presence of the olefin in 64 and 97 days was appreciable, and this compound has been shown to be more active against aphids than the parent IMI. (Suchail says olefin is also very toxic to honeybees)

Metabolism in animals

Rats:  IMI single oral doses.  95% rapidly absorbed and excreted by liver rapidly too (>90% in 12 hours).  In another study, IMI was given over 14 days.  Males had a greater tendency to metabolize IMI than females.  The main metabolites were 6-chloronicotinic acid and its glycine conjugate.

Interestingly, in this reference:

Gilbert, Lawrence I., and Sarjeet S. Gill, eds. Insect control: biological and synthetic agents. Academic Press, 2010.

…the above book by Roberts and Hutson on agrochemicals was cited and selectively quoted as evidence that IMI degrades rapidly and completely...not how I read that chapter, at all.  The only information they present on how IMI is metabolized in any insect is a mention that nontarget tissues are a “sink” in less responsive insects.

On further quest for information about metabolites in insects, I found the following in the book “Insect Resistance Management:  Biology, Economics, and Prediction” edited by Onstad:

“B. tabaci that are IMI susceptible typically do not metabolize C14-IMI into P450-mediated metabolites (Rauch and Nauen, 2003).  The IMI/neonicotinoid resistance of the Q- and B- type B. tabaci strains does not appear to be based on target site insensitivity (Rauch and Nauen, 2003)  The resistance appears to be associated with monooxygenase-mediated activity, with 5-hydroxy-IMI being the only resultant metabolite after topical application of IMI (Rauch and Nauen 2003).”  They go on to say that in these insects (the pests), IMI has a much higher binding affinity to the ACH receptors than the olefin and hydroxy derivatives, quoting Byrne et al 2003, and Nishiwaki et al 2004.

As we have seen, in honeybees those same derivatives seem to be highly toxic.

 I haven't found much else yet on how metabolism of IMI proceeds in insects...specifically honeybees, other than Suchail's studies.

As to Randy's question about synapses.  First, a reminder that interstitial spaces around cells are not a uniform soup...local cellular environments differ greatly.  For instance, cartilage dies if a blood supply is provided to it (!!!)  and it is usually then replaced by bone, or scar tissue.  Think about that!  Cartilage is practically anoxic, compared to other tissues in our bodies.   It is also nearly impossible to repair, as anyone who's had knee or hip surgery is well aware.

Chaos results when tissues are disrupted.  It is well-known that the synaptic space is a highly controlled environment. It is one of the reasons that nervous tissue is so energetically expensive...the environment around neurons must be tightly regulated.  The metabolic machinery of the Malpighian tubules in insects, liver in mammals, P450 cascades in plants and animals, etc are not available in the synapse.  Indeed, some of the metabolic machinery is membrane-bound, thus limiting distribution even more.

The only "degradation" that is supposed to happen in a synapse is rapid and complete inactivation of neurotransmitters...in this case, we are talking about acetylcholine.  That is the job of acetylcholinesterase.  Unfortunately, acetylcholinesterase does not break down IMI or its metabolites.   To add insult to injury, IMI has a very high binding coefficient for the receptor...it won't let go!  There is an equilibrium, meaning once in a while an IMI falls off the receptor (it is not covalently bound, Dick, you are right about that), but since it isn't immediately degraded, and since the synaptic space is confined by membranes, it bounces around in there and is just as likely to re-attach to a receptor as it is to diffuse out of the synapse around the margins.

So how does IMI get into the synapse in the first place, if the synaptic space is tightly controlled?  That is the result of engineered molecules.  We did not evolve to recognize many of them.  Just like the bees when a new pest arrives, the body tends to ignore the unknowns and so they can infiltrate to spaces where they don't belong.

Got to go help a newbee pack her colonies for winter now.  Cold, dark, and rainy here.  Ugh.

Christina


             ***********************************************
The BEE-L mailing list is powered by L-Soft's renowned
LISTSERV(R) list management software.  For more information, go to:
http://www.lsoft.com/LISTSERV-powered.html