Sciencemadness Discussion Board

OP Toxicity

DDTea - 5-8-2004 at 10:39

This is a simple question but it is something that I don't understand... It relates to the difference in Organophosphate toxicity. Why is Soman more toxic than Sarin which is more toxic than Tabun?? And more generally, how is it that such a small amount can kill??

Here's my logic.. One molecule of Sarin disables one molecule of Cholinesterase, right?
One molecule of Tabun also disables one molecule of Cholinesterase. So how is it that Sarin is more toxic than Tabun?

One solution that I'm thinking is that since Sarin has a lower molar mass (140 g/mol) than Tabun (162 g/mol), there are more Sarin molecules per gram than Tabun molecules...as such, it can be said that Sarin is "more toxic per gram" then. But then Soman is 182 g/mol and by all accounts is more toxic than Sarin! :( And needless to say, VX is more massive than any of the above.

So what is it that causes the variance in toxicity? I can understand that some maybe enter the nervous system more readily, and so more molecules are put to use... But if that's the case, can it truly be said that on an individual molecular basis that one Organophosphate is "more toxic" than another?

And furthermore, how is it that such small amounts cause such drastic effects? Does a slight loss in cholinesterase cause dramatic effects like that? Is there a only small amount of cholinesterase in the body?

I suppose this fits under Biochemistry :)

Nick F - 6-8-2004 at 04:55

I don't know much about organophosphates at all, but here's what I'm guessing:

Cholinesterase is an efficient enzyme, meaning that it is reused quickly, and so one molecule can perform many reactions very quickly. Therefore, the body only needs very small amounts, and so only very small amounts of organophosphate are required to interfere to a fatal degree.
That might be why they are so toxic. I believe a similar reasoning leads to cyanide's toxicity. It doesn't, as is commonly believed, bind to haemaglobin like carbon monoxide. Rather, it interferes with the action of some enzyme that I think is important for oxygen usage. This enzyme works fast, so there is only a small amount, and so cyanide is toxic in low doses.

As far as relative toxicity is concerned, it might be due to how well the molecules bind to cholinesterase. I assume they're competing for acetylcholine in the cholinesterase's active site, or perhaps they are non-competative inhibitors which just alter the enzyme's shape by binding elsewhere. Either way, if one binds more irreversably than another, it will be more effective at disabling the enzyme, and this will lead to higher toxicity.

But like I said, all that is just guess work! I'm more of a fan of alkaloid toxicity, organophospahes ain't my thing...
Edit: talking of alkaloids, I might make a post with all my entheogenic/toxic plants. It kinda fits in biochemistry, and I'm proud of them so I want to show them off :).

[Edited on 6-8-2004 by Nick F]

IPN - 7-8-2004 at 05:59

Quote:

Edit: talking of alkaloids, I might make a post with all my entheogenic/toxic plants.


Do post them if you can. I am also growing some interesting plants and would be highly interested to see your 'collection' :)

Nick F - 7-8-2004 at 06:59

OK, I'll try and get some photos up. I have

Psychotria viridis
Lophophora williamsii
Trichocereus pachanoi, peruvianus and spachianus
Salvia divinorum
Catha edulis
Ariocarpus fissuratus
Heimia salicifolia
Calea zacatechichi
Delosperma cooperi
Sceletium tortuosum
Atropa belladonna
Hyoscyamus niger
Datura metel
Lactuca virosa
Aconitum ferox
Pereskiopsis spathulata (for grafting)
And I've just planted some Brugmansia arboreum and Argyreia nervosa. I also have anadenanthera colubrina, desmanthus illinoensis and phalaris arundinacea seeds, but no room to grow them! And there are hemp seeds that I've found in some seed that I put out for the birds, which although contains practically no THC, it would make an interesting houseplant.
All are grown from seed, except the calea, psychotria and salvia.
I want to get some more poisons, especially in solanaceae, and branch out into mycology a bit. I'd love to get some muscarias growing under my birch tree, but cultivation of them seems notoriously difficult :(.
In fact recently I've been spending a lot more time growing things than playing in my lab. Growing is fun :).

(sorry for the OTness!)

IPN - 10-8-2004 at 07:00

Nice amount plants you have :o

I am currently growing:

digitalis purpurea
papaver orientale and somniferum
salvia officinalis
convallaria majalis
hyssopus officinalis
aquilegia vulgaris
aconitum napellus
mandragora officinarum
atropa belladonna

I have also seeds of ephedra viridis, cannabis sativa and ipomoea tricolor but the same problem as you, no room to grow them :(

Aah.. mycology, very interesting indeed :)
I have a small shady, cleared space in the nearby forest where I have cultivated some amanita virosa. It's growing quite well, though the mycelium hasn't spread much.. yet :)
You could try using these instructions if you can get some spore samples of muscaria. I could have sent you some, but for an unknown reason I can't find any. Even though it's very common around here :S

Geomancer - 10-8-2004 at 12:35

Amanita spp. are mycorhizal--the instructions you've supplied won't work. You claim to be cultivating A. virosa. How?

chemoleo - 10-8-2004 at 13:12

Gents, let's keep the thread on topic.
If you want to discuss plant growth, then create a new thread - provided it's more than just a few pics and 'put the soil in here, place seeds, and grow under a plant-lamp until it is ready for consumption'. ;)

fritz - 23-11-2004 at 03:54

Hm, very interesting subject! If not already existing (I did not found) I would suggest creating a new thread about growing of plants/fungi and all other stuff like active substances and obtaining them.
If someone is interested I may publish some informations about obtaining plant-drugs (no, NOT the drugs for getting a weird brain, but dried plant-material) or the active substances

Hope that help...

kazaa81 - 27-11-2004 at 15:38

Hallo to all,
I think that the differences between the previously sayed G agents is due to the volatility of each one....and the persistence in the ambient....
I will have a look at War Gases by Mario Sartori, a very good read which helps very much! I would suggest a read of it to everyone!

Thanks at all for help ;)

Blind Angel - 27-11-2004 at 21:35

I'm forwarding that on a very arbitral basis with no background, but maybe metabolism? Like valium who has active metabolist maybe some G-Agent have active metabolist too?

sergius - 28-11-2004 at 04:04

I support kazaa81's vie, given the fact that all the abovesaid OP agents are liquids at standard temperature and pressure. The toxicity of all the OP agents is probably proportional to their volatility and the lipophilicity. The higher the lipophilicity higher the toxicity, because lipophilic agents get transported across the cell membrane more rapidly. The rate of metabolism (biotransformations/detoxification) also should be a determining factor.

Sergius

Dorylaeon - 14-5-2006 at 14:10

Do search for the "Altuntas I." in the Pubmed for the OPI effects, mechanisms and on, i.e. discussions. Seems not so simple in only few ways to be toxic.

unionised - 16-5-2006 at 11:35

A possible difference is that the more toxic OPs are less readily deactivated in the body. For example, in principle they all hydrolyse in water; if one of them hydrolysed so quickly that only half of it got to the nerve cells then it would only be half as toxic. This still holds if the hydrolysis is enzyme mediated. There is also the possibility that the less toxic ones are less site- specific. These compounds migt react with other enzymes or cell constituents. If, for example, one reacted with haemoglobin, which is common, there would be less left to attack the nerves.

The_Simpsons - 16-6-2006 at 13:13

Quote:
Originally posted by Nick F
OK, I'll try and get some photos up. I have

Psychotria viridis
Lophophora williamsii
Trichocereus pachanoi, peruvianus and spachianus
Salvia divinorum
Catha edulis
Ariocarpus fissuratus
Heimia salicifolia
Calea zacatechichi
Delosperma cooperi
Sceletium tortuosum
Atropa belladonna
Hyoscyamus niger
Datura metel
Lactuca virosa
Aconitum ferox
Pereskiopsis spathulata (for grafting)
And I've just planted some Brugmansia arboreum and Argyreia nervosa. I also have anadenanthera colubrina, desmanthus illinoensis and phalaris arundinacea seeds, but no room to grow them! And there are hemp seeds that I've found in some seed that I put out for the birds, which although contains practically no THC, it would make an interesting houseplant.
All are grown from seed, except the calea, psychotria and salvia.
I want to get some more poisons, especially in solanaceae, and branch out into mycology a bit. I'd love to get some muscarias growing under my birch tree, but cultivation of them seems notoriously difficult :(.
In fact recently I've been spending a lot more time growing things than playing in my lab. Growing is fun :).

(sorry for the OTness!)


Waow, how i envy you. I love the plants from the solanaceae family. Currently im only growing 3 Datura metel's. I have though several henbanes growing wild in my garden.