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

[pcrdude]

So, you came to the discussion late, claimed your opinion was somehow more valid because you say you work in a lab, ignore information provided by the Society of Toxicologists, compare the central tenet of Toxicology to alchemy, and dismiss information from said scientific discipline as undergraduate disinformation?

Did I get that right?

You working in a lab under a PI does not make your opinion somehow more valid (even though you think it does). I didn't deny that you worked in a lab, I just don't think that has anything to do with this debate.

At this link:

http://toxlearn.nlm.nih.gov/Toxicology/tx010101/tx010101.pdf (and I can't believe I have to re-post it) it states how toxicologists define their field of study. See page 6.

For clarity, I will repeat (again).

The term poison is imprecise scientifically, and has no meaning without regard to dosage of said compound. That is how toxicologists define their scientific field of study.

In addition, the mechanism of action doesn't matter either. High enough concentrations of compunds that have poor PK/PD can be more toxic than molecules that covalently bind and permanently block receptors.

It depends on the dosage. Which is what I've been trying to tell you all along.

 

[Baldr]

Of course you don't think so. Because it doesn't prove your point.

You can keep pretending it's a dangerous poison that is going to kill a bunch of people. It just makes you look stupid, so I don't mind at all.

 

[X T C]

I thoroughly believe that nicotine is a drug (which it is) not a poison at all. Many drugs have the same effects, ingesting too much will kill you or cause serious health problems.

Everything in moderation

 

[ckn71nm]

So, you came to the discussion late, claimed your opinion was somehow more valid because you say you work in a lab, ignore information provided by the Society of Toxicologists, compare the central tenet of Toxicology to alchemy, and dismiss information from said scientific discipline as undergraduate disinformation?

Did I get that right?

You working in a lab under a PI does not make your opinion somehow more valid (even though you think it does). I didn't deny that you worked in a lab, I just don't think that has anything to do with this debate.

At this link:

http://toxlearn.nlm.nih.gov/Toxicology/tx010101/tx010101.pdf (and I can't believe I have to re-post it) it states how toxicologists define their field of study. See page 6.

For clarity, I will repeat (again).

The term poison is imprecise scientifically, and has no meaning without regard to dosage of said compound. That is how toxicologists define their scientific field of study.

In addition, the mechanism of action doesn't matter either. High enough concentrations of compunds that have poor PK/PD can be more toxic than molecules that covalently bind and permanently block receptors.

It depends on the dosage. Which is what I've been trying to tell you all along.

No, you didn't get it right.

First the link. Ok, I missed it. Did you look at the footnote? "Printed form ToxoLearn" What in all my previous posts leads you to believe that slapping more teaching material in my face will change my opinion about teaching vs. research?

I came to the discussion late. Just like you did. Granted I was later, but if anyone who does not post within a certain time of the thread starting is not permitted to post, it should say so. I read the articles you linked. Not right away but early on. I just didn't think they were all that relevant to what I had to say.

I never say anywhere that my opinion is more valid. You are putting words into my mouth (well, into my posts). My opinion is different from yours. Does that really piss you off that much?

I agree, I should not have used the alchemy strawman, or put down a important principle in the field of toxicology as undergraduate misconception. That's the word I used. Very different form disinformation. Can you please stop putting words into my mouth?

For clarity, I will repeat (again).

I never denied that everything in high enough dose can kill you. You should really stop telling yourself that I disagree with you on that. I don't. However, you say that the mechanism of action is not important, I say it is. I think you look at it from a strictly physiological point of view and that's fine. I separate the effect of any substance into physiology and biochemistry. In that case the mode of action is important.

You are also correct that the term poison is imprecise scientifically. It is often used, even in science. It is much easier to tell somebody who does not have knowledge about toxicology that something is poison or toxic, rather then explaining everything form dose-response curves to first pass effect and resulting blood levels to him/her. I do agree with you though. It is imprecise.

Are we done know? I'm tired of this.

 

[ckn71nm]

You can keep pretending it's a dangerous poison that is going to kill a bunch of people. It just makes you look stupid, so I don't mind at all.

Sorry for the outburst. I didn't mean to offend you.

Edit: It's difficult enough for me to stay as collected as I am on this thread. What I should have said is this:

It may not have a major impact on the basic premise of this thread. However it shows that nicotine can be lethal. Even the nicotine we can get in any gas station in form of cigarettes. It was a response to a specific question not the premise of the thread.

 

[pcrdude]

So when did "teaching material" from the Society of Toxicology become somehow bad or wrong? It isn't. You came on here implying that you know more about toxicology because you work in a lab. That doesn't mean a thing. Your arguments are all you have, otherwise it's the logical fallacy of "appeal to authority". In this case, not much of an authority, unless you post why your credentials trump the Society of Toxicology.

Nice dodge on the PK/PD and covalent receptor inactivation example. Just like the warfarin example. Just keep ignoring the good science from experts in the field if it makes you feel good.

Nothing you posted angers me. Not at all. I suggest you keep up with the debate, since you clearly could use the education.

Just sayin'

 

[pcrdude]

The problem is you are not getting it.



Patronizing me is not going to help you make more sense.

Taking my argument, chopping it up and use part of it to make it look like I'm agreeing with you is actually kind of rude.

I'm not agreeing with you. I know you keep on going back to your Toxicology 101, trying to make the argument that because everything is toxic at some concentration on the physiological level, we can't single certain thing out that are more harmful than others, and call them something different in order for non scientist to be aware of the danger.

I agree. Everything has a lethal dose. Everything has the potential to kill you. I draw a line. That line is rooted in practical application of toxicology in research and real live. That line is the biochemistry of things. You stick with undergrad toxicology, I stick with research. Fine with me.

OK, on a different note. 4 posts in row and I'm getting more and more frustrated with each one. I'm finding the ignorance about the actual process and inner workings of science on this thread disturbing. I'm going to retire from this thread. Don't want to have a heart attack and be in need of some toxins to save my life.

The bolded part.

See what you did there?

 

[pcrdude]

OK, lets be more scientific about it then. Like I said before I worked in a research lab for the last 13 years. My former boss teaches toxicology. Like in every toxicology class, the opening is usually the dreaded "Dose makes the poison" statement along with a history of Paracelsus and all that jazz. A main point of the class is exactly what you are saying about everything being a poison and so on.

Things start to change when you actually do research and get beyond basic education. Toxicology 101 has very little to do with the real world. To treat everything as a potentially toxic substance makes absolutely no practical sense, in a lab or in real life. One thing we do in research is to classify things by their danger to living organisms in the setting the exposure happens. That's why for example a tank with pure oxygen is classified as dangerous (I know, not a scientific term, but just go with it) but the air around us is not. Nicotine in its pure form, as you would encounter it in a laboratory, would be considered extremely toxic; but we can buy liquid with 36 mg/ml at almost every street corner these days. The reason air and e-liquid are considered non toxic is because in the setting in which we encounter them (as O2 and nicotine), they are non toxic. But that does not make the chemicals themselves non-toxic, only the circumstance.

Another very common method of classification is the chemical properties of a substance. I eluded to that earlier. Warfarin for example is a chemical that has one purpose, and one only.

In low doses it has the benefit of preventing blood clots. In high doses it will lead to hemorrhage. Regardless of the dose, every single molecule will still have the same toxic effect. That makes its toxic property dose independent. The toxic effect on the human body as a whole is, of course, dose dependent. In other words the biochemical effect is toxic and independent of dose, the physiological effect is toxic and dose dependent.

Same is true for nicotine:

The difference in Biochemical and Physiological properties are the same as above in the example of Warfarin.

Now, substances like water, molecular nitrogen (N2), calcium, magnesium, most types of monomeric sugars or sugar as polymers (cellulose) work very differently. They do not have a toxic effect on the single molecular (or Biochemical) level. They do not disrupt any pathways or essential function of living organisms. Of course they can be ingested is such a high dose that they become toxic on a physiological level. But by default, ingested in a reasonable, normal physiological manner they are non-toxic, on both the Biochemical and physiological level.

I hope you see now that saying that everything is a poison is a simplified, dangerous, impractical (in real life and science) and truly a 500 year old misconception.

The difference for me is that nicotine (as warfarin) is, first not essential to the body, and second dose independently toxic on the biochemical level. Therefore, in common nonscientific terms, poison. Water is essential and only toxic in insane doses on only the physiological level. Hence not poison.

Dose independently toxic on the biochemical level?????

That doesn't even make sense.

 

[pcrdude]

No, you don't have to go back. I went through them, and still stick to my points.

I feel personally attacked by your last post. The mode of action of sildenafill and the mode of action of any substance is relevant when it comes to evaluating its toxicity. Its not nonsense.

I make the claim of having worked in lab? Are you saying you know that I don't? In fact I'm writing this on my computer in the lab hoping that my PI won't notice that I'm doing this instead of my job. I was using it to bolster my position. Not to lift myself above anyone, but to point out that I in fact have experience in the scientific process and, for the most part, know what I'm talking about. You mentioned in an earlier post that you did lot's of research to be able to prove your point. It shows. And isn't that bolstering your position?

Now the literature you posted.

A book on Amazon, even though based on research, is study material.
The Cornell bit (Assesing Toxic Risk: Student Edition), even though based on research, is study material

My point from the earlier post was that teaching toxicology is different than doing the research. Lines get a little blurry and shifted. Something you can't do teaching. My assessment of what toxicity means is based in research not teaching. I have the feeling that the only position you can take because of the reading you did on the subject, makes it impossible for you to argue with me on the level of research. Is that why you feel the need to personally attack me and doubt that I work in lab? If I have, in any previous post, attacked you personally I apologize and I hope we can refrain from doing so in the future.

How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century - Springer
Intravenous Nicotine and Caffeine: Subjective and Physiological Effects in ....... Abusers

Good articles. They don't however dispute in any way the biochemical mode of action. Which is my starting point.

http://www.nytimes.com/2011/01/25/science/25qna.html?_r=1&

A NYT Q&A essentially saying that you probably wont die form a caffeine overdose drinking coffee but might if you drink to much energy drinks. OK, agreed.

Appeal to (false) authority, and ad hominem logical fallacies.

I could do this to your posts all day.

The Society of Toxicology is an expert source for information on what toxicology is. If you feel they are wrong, and your "biochemical toxicity" mumbo jumbo somehow refutes what they are teaching, I welcome you to contact them, then post up their reply right here in this very thread.

Otherwise, take THEIR word for it.

 

[ckn71nm]

The bolded part.

See what you did there?

I missed that, you are right. I sounds very different from how I meant it.

Again, I'm not saying that teaching material is bad or wrong. It just doesn't tell the entire story. Unfortunately in modern science education there is way to little emphasis on how different fields overlap. Toxicology teaches toxicology. And only that. In many cases it leaves out the biochemical aspect of things entirely. I understand your line of argument as "Toxicology and it's principles are the only thing that counts". I very strongly disagree with that position. Look at the following two articles:

The role of mode of action studies in extrapola... [Toxicol Lett. 2003] - PubMed - NCBI
Mode of action and toxicity of trace elements | Arun Shanker - Academia.edu

Both examples highlight the importance of combining toxicological and biochemical principles. I just don't understand how you can say that the mode of action is not important when (for me) clearly the biochemical function of a substance is what makes it toxic in the first place. It is not only a valuable tool in assessing the risk associated with the substance and probably the most important tool to counteract its toxicity, but also a tool to classify substances for all sorts of things like storage (radioactive materials), control of purchase (mind altering substances) and so on. The only way you can explain the toxicity dose response is by first pass effect and mode of action.

You are saying I need some education? Well, I make you a deal. You tell me what I need to learn and you go take a Biochemistry class. You seem to desperately need it.

Just sayin'

 

[ckn71nm]

Dose independently toxic on the biochemical level?????

That doesn't even make sense.

To you. That's why it's so difficult to explain it to you.

 

[ckn71nm]

Appeal to (false) authority, and ad hominem logical fallacies.

I could do this to your posts all day.

The Society of Toxicology is an expert source for information on what toxicology is. If you feel they are wrong, and your "biochemical toxicity" mumbo jumbo somehow refutes what they are teaching, I welcome you to contact them, then post up their reply right here in this very thread.

Otherwise, take THEIR word for it.

You seem to be very much into debating and know a lot about the patterns that emerge in arguments. Maybe you should reflect a little about what it means when one side of the argument gets personal and words like "mumbo jumbo" and "nonsense" get thrown around.

 

[ckn71nm]

So, you came to the discussion late, claimed your opinion was somehow more valid because you say you work in a lab, ignore information provided by the Society of Toxicologists, compare the central tenet of Toxicology to alchemy, and dismiss information from said scientific discipline as undergraduate disinformation?

Did I get that right?

You working in a lab under a PI does not make your opinion somehow more valid (even though you think it does). I didn't deny that you worked in a lab, I just don't think that has anything to do with this debate.

At this link:

http://toxlearn.nlm.nih.gov/Toxicology/tx010101/tx010101.pdf (and I can't believe I have to re-post it) it states how toxicologists define their field of study. See page 6.

For clarity, I will repeat (again).

The term poison is imprecise scientifically, and has no meaning without regard to dosage of said compound. That is how toxicologists define their scientific field of study.

In addition, the mechanism of action doesn't matter either. High enough concentrations of compunds that have poor PK/PD can be more toxic than molecules that covalently bind and permanently block receptors.

It depends on the dosage. Which is what I've been trying to tell you all along.

Text in bold: I'm really not saying that my opinion is more valid. But factual knowledge is. The notion you seem to have that having a scientific degree or working in science has nothing to do with a debate about scientific topics is just plain funny.

Text in Italic: Of course that's possible. It actually confirms my argument. Pharmacokinetics an pharmacodyamics are important parameters for adjusting the dosage of a drug to a point were it has the beneficial effect it should have, but minimal unwanted side effects. That has everything to do with mode of action. You are absolutely right that a high concentration of something can be more toxic than something else. You do realize that you are comparing different modes of action with your statement right?

 

[pcrdude]

To the organism exposed to a lethal amount of a substance, it matters not the mechanism by which said compound exerts its effects. The lethality is all that matters.

Now, please explain how a single molecule can exert toxic effects without regard to dose. In fact, the presence of that molecule in any system IS a dose.

That's why what you wrote makes no sense.

 

[pcrdude]

Text in bold: I'm really not saying that my opinion is more valid. But factual knowledge is. The notion you seem to have that having a scientific degree or working in science has nothing to do with a debate about scientific topics is just plain funny.

Text in Italic: Of course that's possible. It actually confirms my argument. Pharmacokinetics an pharmacodyamics are important parameters for adjusting the dosage of a drug to a point were it has the beneficial effect it should have, but minimal unwanted side effects. That has everything to do with mode of action.

Sorry, you'll have to show why. It's also very interesting that you assume I don't have prior experience with science, and attempt to use it as a point if argument. It matters not if I do or do not. Another appeal to false authority in afraid.

By the way, there are drugs that have pk/pd properties that are quite well understood, yet mode of action is unknown. Just thought you might like to know that.

 

[ckn71nm]

To the organism exposed to a lethal amount of a substance, it matters not the mechanism by which said compound exerts its effects. The lethality is all that matters.

Now, please explain how a single molecule can exert toxic effects without regard to dose. In fact, the presence of that molecule in any system IS a dose.

That's why what you wrote makes no sense.

To complete the circle: But the reason why the substance is toxic in the first place is because of it's mechanism. You are right. one molecule or lethal amount are all doses. Since the mechanism (shutting down the nervous system for example) that in the end will kill the organism does not change with dose (assuming a 1:1 ratio one molecule shuts down one cell, millions will shut down millions) it is dose independent. Obviously the lethal outcome is dose dependent. The mechanism by which it happens not.

 

[ckn71nm]

Sorry, you'll have to show why.

Why what? Which part of that do want me to show? The purpose of PK/PD? Or that the dosage you give depends on the mechanism by which the drug works?

It's also very interesting that you assume I don't have prior experience with science, and attempt to use it as a point if argument. It matters not if I do or do not. Another appeal to false authority in afraid.

I was actually assuming that you have science experience. That's why I brought it up in the first place. Since you never told me that you have as well I wasn't so sure anymore. Glad to know that you do.

By the way, there are drugs that have pk/pd properties that are quite well understood, yet mode of action is unknown. Just thought you might like to know that.

I knew that. So? Just because we don't know the mechanism doesn't mean its not important.

 

[pcrdude]

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.

 

[pcrdude]

Btw, you're doing quite well at avoiding the "P" word.

Looks like you're starting to understand.

Good job!

 

[ckn71nm]

Btw, you're doing quite well at avoiding the "P" word.

Looks like you're starting to understand.

Good job!

Here we go with the patronizing again.

Speaking of avoiding the P word:

From Merriam-Webster:

Full Definition of TOXIN
a poisonous substance that is a specific product of the metabolic activities of a living organism and is usually very unstable, notably toxic when introduced into the tissues, and typically capable of inducing antibody formation

Full Definition of TOXIC
containing or being poisonous material especially when capable of causing death or serious debilitation

Synonyms
envenomed, poison, poisoned, poisonous, venomous

Full Definition of POISON
a substance that through its chemical action usually kills, injures, or impairs an organism

So every time we said toxin or toxic we could have replaced it with poison or poisonous. They are synonyms or according to some sources toxin is a subclass of poison.

Wikipedia (I know, don't care) "Some poisons are also toxins, usually referring to naturally produced substances, such as the bacterial proteins that cause tetanus and botulism"

So when we talk about drugs it would be much more accurate to refer to them as poison instead of toxin.

Just thought you might want to know

I'm working on the "show me" stuff. Don't worry. In the meantime I'm looking forward to hear all the reasons why what I said in this post is false.