Don't let anyone tell you that nicotine is a poison...

[pcrdude]

Lets get back to dose independent toxin. Think if it in a binary way. If one molecule is present, and has the effect in question, the effective dose is one molecule. If that one molecule isn't there, dosing did not occur.

Therefore it is dose dependent.

 

[ckn71nm]

You made the following claim:

"and second dose independently toxic on the biochemical level"

Dose independently toxic???

The presence of the toxin IS a dose.

I'm not sure in how many different ways I can explain it I have not tired yet.

Something being independent of dose does not mean that there is no dose. It only means that what ever effect the substance has does not depend on the amount of the substance present. The effect will be small and slow with low amounts and large and fast with large amounts. But regardless of dose, concentration or what ever you want to call it, the effect is still there.

A few years back we studied the effect of an inhibitor on the contraction of blood vessels. The mechanism was very interesting. The binding of the inhibitor (a small peptide) to the catalytic site of the enzyme resulted is such a strong conformational change that two parts of the enzyme came together that would never have meet under normal conditions. The two parts formed a di-sulfide bond an that resulted in the irreversible inhibition of the enzyme. After that the inhibitor moved on the the next enzyme. This effect was independent of the concentration of the inhibitor. In small doses it would take longer for the blood vessel to contract, in large doses it was immediate. But the contraction always happened independent of dose.

Does that make it clearer?

 

[ckn71nm]

Lets get back to dose independent toxin. Think if it in a binary way. If one molecule is present, and has the effect in question, the effective dose is one molecule. If that one molecule isn't there, dosing did not occur.

Therefore it is dose dependent.

see post #442

 

[sobi]

Nicotine is a neurotoxin. 60 - 120 mg is fatal dosage if taken in all at once.

I suppose it would be fair to say that neither water nor CO2 are toxins, but if your house was full of either, you couldn't live in it. All things in moderation, but do not be confused--poison it is.

 

[ckn71nm]

Lets get back to dose independent toxin. Think if it in a binary way. If one molecule is present, and has the effect in question, the effective dose is one molecule. If that one molecule isn't there, dosing did not occur.

Therefore it is dose dependent.

I was reading back through the last few posts and it became apparent to me that this discussion is pointless. I will always disagree that the effect of a toxin/drug (I'm not saying the P word) is only dependent on dose. And I guess you will always disagree that mechanism plays an important role in toxicity.

While I am having a discussion to consider important scientific data and reasoning, I'm frustrated and hurt by the feeling that you simply need to be right no matter what. I have agreed with you that dose is important. I have addressed all of your concerns and criticisms, even apologized for mistakes I made. And in the process endured your insults and patronizing, bringing out the worst in me in terms of how I talk to people. I don't need that.

I know that I will rest better not having to think about this anymore.

 

[pcrdude]

I was reading back through the last few posts and it became apparent to me that this discussion is pointless. I will always disagree that the effect of a toxin/drug (I'm not saying the P word) is only dependent on dose. And I guess you will always disagree that mechanism plays an important role in toxicity.

While I am having a discussion to consider important scientific data and reasoning, I'm frustrated and hurt by the feeling that you simply need to be right no matter what. I have agreed with you that dose is important. I have addressed all of your concerns and criticisms, even apologized for mistakes I made. And in the process endured your insults and patronizing, bringing out the worst in me in terms of how I talk to people. I don't need that.

I know that I will rest better not having to think about this anymore.

You came here with full arrogance that you knew more than anyone else because you worked in a lab. You dismissed the Society of Toxicology definition of toxicology as "teaching material", and instead used the dictionary to (attempt) to support your point.

And the mechanism still doesn't matter. It is interesting to elucidate why a toxin is a toxin, but doesn't matter that it IS a toxin. Your example of the enzyme inhibitor is interesting, but doesn't have anything to do with toxicity to an organism. In fact, toxicity doesn't even play role in your example now does it? It is an enzyme inhibitor, and there are LOTS of them that cause an irreversible effect on the enzyme, and are not altered in the process. Again, interesting, but it doesn't really have anything to do with toxicity. Now, the DOSE of that inhibitor in an organism, very well could be related to toxicity.

Does that clear things up for you?

 

[pcrdude]

I'm not sure in how many different ways I can explain it I have not tired yet.

Something being independent of dose does not mean that there is no dose. It only means that what ever effect the substance has does not depend on the amount of the substance present. The effect will be small and slow with low amounts and large and fast with large amounts. But regardless of dose, concentration or what ever you want to call it, the effect is still there.

A few years back we studied the effect of an inhibitor on the contraction of blood vessels. The mechanism was very interesting. The binding of the inhibitor (a small peptide) to the catalytic site of the enzyme resulted is such a strong conformational change that two parts of the enzyme came together that would never have meet under normal conditions. The two parts formed a di-sulfide bond an that resulted in the irreversible inhibition of the enzyme. After that the inhibitor moved on the the next enzyme. This effect was independent of the concentration of the inhibitor. In small doses it would take longer for the blood vessel to contract, in large doses it was immediate. But the contraction always happened independent of dose.

Does that make it clearer?

You have shown inhibition of an enzyme, but where is the toxicity data? It seems you have gone off track a little. Now, show the effects of that molecule in an organism (where toxicity data is relevant), and you will have protein binding, bioavailablity, enzyme clearance, etc. that will all add up to.....

You guessed it.

Dose effect.