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. *********************************************** 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 *********************************************** 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