# he first gene-encoded neurotoxin found in amphibians



## earthfrog (May 18, 2008)

http://www.jbc.org/content/284/33/22079


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## edwardsatc (Feb 17, 2004)

Good article. Good read.

To a toxicologist, there is one thing that just sticks out ..... I found it a bit odd that they used intraperitoneal injection for the acute toxicity tests when the normal mode of exposure would be dermal contact or ingestion. People do some crazy things ...


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## billschwinn (Dec 17, 2008)

So in plain english what does all this mean?


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## johnc (Oct 9, 2009)

It means it is the first time a neurotoxin that is made by the amphibian itself has been found/defined/isolated.

Donn - I imagine they did the tests that way because the substance doesn't readily traverse skin. Remember they are talking about a "huge" toxin molecule, not something small and nasty.


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## ClintonJ (May 11, 2009)

After google-defining intraperitoneal  I believe that they did the tests that way because they wanted to test toxicity as if the animal were just eaten, not handled. Introduction of the toxin directly into the stomach probably allows more accurate dose measurement as well. My very un-professional theory.


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## johnc (Oct 9, 2009)

Clinton - intraperitoneal is an injection into the blood stream, not into the stomach. It simply indicates that it is injected into the main part of the body, rather than a limb, etc.


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## edwardsatc (Feb 17, 2004)

johnc said:


> It means it is the first time a neurotoxin that is made by the amphibian itself has been found/defined/isolated.
> 
> Donn - I imagine they did the tests that way because the substance doesn't readily traverse skin. Remember they are talking about a "huge" toxin molecule, not something small and nasty.


True, but the first thing one must consider when considering the toxicity of a substance is the route of exposure. If there is no exposure, then there is no toxicity. If an organism can't absorb the toxicant in some manner then toxicity is not an issue. In addition, an intraperitoneal injection versus the normal route of exposure may have much different affects on how much toxicant is absorbed and reaches the site of action, metabolic activity, and distribution. 

As a toxicologist, I would say this was a major flaw in experimental design and renders the acute toxicity data invalid.

Of course, acute toxicity is not primary focus of the research so it's a relatively small issue. I'm sure someone in the tox world will will take the ball and run with it .... wish I had the time.


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## johnc (Oct 9, 2009)

Donn, I wasn't disagreeing with you. My initial thoughts on following the link were "Oh, it's in JBC...". Not exactly the cream of the crop, journal-wise.


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## edwardsatc (Feb 17, 2004)

johnc said:


> Donn, I wasn't disagreeing with you. My initial thoughts on following the link were "Oh, it's in JBC...". Not exactly the cream of the crop, journal-wise.



No problem, I didn't think you were. I was just trying to clarify for others who may be reading. I had the same thought about JBC.


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## johnc (Oct 9, 2009)

edwardsatc said:


> I had the same thought about JBC.


I would have thought something this seminal would have appeared in a much more significant title.


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## edwardsatc (Feb 17, 2004)

johnc said:


> I would have thought something this seminal would have appeared in a much more significant title.


Yeah, makes me think there are probably other issues with the paper. Most of my research is in aquatic ecotox and whole organism toxicity, and I'm not very up to speed when it comes to molecular methodology. So it's not very likely that I'd be able to spot what those issues may be


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## earthfrog (May 18, 2008)

edwardsatc said:


> True, but the first thing one must consider when considering the toxicity of a substance is the route of exposure. If there is no exposure, then there is no toxicity. If an organism can't absorb the toxicant in some manner then toxicity is not an issue. In addition, an intraperitoneal injection versus the normal route of exposure may have much different affects on how much toxicant is absorbed and reaches the site of action, metabolic activity, and distribution.
> 
> As a toxicologist, I would say this was a major flaw in experimental design and renders the acute toxicity data invalid.
> 
> Of course, acute toxicity is not primary focus of the research so it's a relatively small issue. I'm sure someone in the tox world will will take the ball and run with it .... wish I had the time.


I think they were doing it via injection not to determine toxicity, but to determine the effectiveness of the antibody response against the toxin itself in the New Zealand rabbits' bodies. The other animals probably served as the controls.


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## edwardsatc (Feb 17, 2004)

earthfrog said:


> I think they were doing it via injection not to determine toxicity, but to determine the effectiveness of the antibody response against the toxin itself in the New Zealand rabbits' bodies. The other animals probably served as the controls.


"Similar to other neurotoxins, anntoxin showed lethal toxicities against potential aggressors or predators including insect, snake, bird, and mouse at a low dose. Most of the tested animals showed obvious intoxication symptoms a short time after administration of anntoxin."

This statement makes it clear that they were looking to determine toxicity. They also published the LD50's - a clear claim of toxicity. A claim which IMO is not supported due to a flawed method. 

The toxicological methods used here would definitely raise a red flag for reviewers in tox related journals such as ET&C.

The rest of the research appears to be sound, but as I said, it is not an area in which I have enough knowledge to make any critical commentary.


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## earthfrog (May 18, 2008)

edwardsatc said:


> "Similar to other neurotoxins, anntoxin showed lethal toxicities against potential aggressors or predators including insect, snake, bird, and mouse at a low dose. Most of the tested animals showed obvious intoxication symptoms a short time after administration of anntoxin."
> 
> This statement makes it clear that they were looking to determine toxicity. They also published the LD50's - a clear claim of toxicity. A claim which IMO is not supported due to a flawed method.
> 
> ...


I guess so. I can't really take a firm stance on all that, either. The title just intrigued me.


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