Toxins

My recently acquired Taricha giants seemed cramped when I put them in a tank with the two smaller ones I had already. So pending my move to a new house in December, they've been sharing a giant tank with my C. e. popei. They're very active in the tank (spending about half the time on land) and get along fine with the popei. But a recent visitor warned me that if they released their toxin, I could lose all my popei in one fell swoop. Is this really possible? I know they're very toxic, but isn't it basically the same toxin as that of the popei? The volume of water in this tank, by the way, is pretty huge. And how about when the newts crawl on top of each other on land? Is the toxin normally present on the skin or is it only released when the newts feel provoked. Mind you, these two Taricha are the calmest, most mild-mannered newts you'll ever encounter I gave myself the better-safe-than-sorry lecture before putting them together but it seemed like an acceptable risk at the time. I don't normally mix different species that hail from different parts of the globe, but wanted to make a temporary exception in this case...

tim-yeah separate them, not the same toxin

I'm going to defer to Uwe and other Taricha/Cynops experts on this one. You know the Caudata.org mantra of "don't mix species, especially from different continents." The idea of having a Taricha poison a Cynops in the water is intriguing though.

Tarichas do not start secreting massive amounts of toxins unless they are stressed.

Well, but I see both species do have "tetrodotoxin".

See:

Newt Toxins
By Wes von Papineau
http://www.caudata.org/cc/articles/newt_toxins.shtml

The Toxicity of Newts
By Heather Björnebo
http://www.caudata.org/cc/articles/toxin.shtml

Are there different TTX types among the different species? I found something that says 6-Epitetrodotoxin (6-epiTTX) and 11-deoxytetrodotoxin (11-deoxyTTX) have been isolated from Cynops ensicauda.

See:

Actions of 6-epitetrodotoxin and 11-deoxytetrodotoxin on the frog skeletal muscle fiber
By Yang L, Kao CY, Yasumoto T.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1325687&dopt=Abstract

Anyway, I have separated them, if for no other reason than to set a good example

Paris, what makes you say the toxins are different? The following report seems to suggest they could be the same:

Distribution of tetrodotoxin, 6-epitetrodotoxin, and 11-deoxytetrodotoxin in newts.
By Yotsu M, Iorizzi M, Yasumoto T.

"Tetrodotoxin was detected in all nine species of newts tested, 6-epitetrodotoxin in six species, and 11-deoxytetrodotoxin in five species. Only one species lacked the analogues, thus suggesting that the analogues were common metabolites among newts. Toxin levels were high in Taricha granulosa and Notophthalmus viridescens followed by Cynops spp."

source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1325687&dopt=Abstract

Ah, I see, it does go on to say, "Distinct differences in toxin contents and profiles existed among species and tissues."

In a perfect world...

If you were new here you'd be getting the reaming of your life, Tim

Even if the toxins are identical (and I doubt they're exactly the same) they're present in different amounts. I wouldn't risk it.

Yeah, I know. It reminds me when I was 5 and was told by my mother not to put my finger under the sewing machine needle. What happened next was...not pleasant

About the possible difference in toxin levels, well, using that argument, assuming the toxins are the same, I guess one could then make a case for keeping separate origin-unknown Taricha. According to Wes von Papineau's article mentioned above, skin extracts from T. granulosa from somewhere in Oregon were found to be at least 1,000 times more toxic than those obtained from T. granulosa on Vancouver Island. This may be an extreme example, but the skin of male Taricha torosa was found to be more than three times as toxic as that of females. Notable regional variation in toxin levels is also found with Cynops.

I'm not trying to justify the mixing of species (the Cynops and Taricha have already been separated), just discussing "toxin compatibility"

By the way, here's an interesting abstract pertaining to C. pyrrhogaster toxin:

Toxicity and toxin profiles of the newt, Cynops pyrrhogaster from western Japan

By K. Tsuruda, O. Arakawa, T. Noguchi

"A total of 382 specimens of a Japanese newt, Cynops pyrrhogaster, were collected from western Japan during 1996 to 1999, and assayed for their individual, geographical, sexual, seasonal variations, and anatomical distribution of toxicity by mouse. Most of the specimens tested showed toxicity scores ranging from 5 to 370 MU/g, where no seasonal, but large individual, sexual, and regional variations of toxicity were clearly recognized. Among the parts, skin and muscle showed higher toxicity scores (56 MU/g) than liver, stomach, intestine and gonad, whose toxicity ranged from less than 2 to 33 MU/g. The C. pyrrhogaster toxin was purified by several steps of column chromatography and was shown to consist of tetrodotoxin (TTX) and 6-epiTTX as main components, and 4-epiTTX, 4,9-anhydro-6-epiTTX, and 4,9-anhydroTTX as minor ones by means of HPLC and 1H-NMR analyses."

Source: J Nat Toxins. 2001 May;10(2):79-89.

The toxins of animals are mostly so called cocktails, because this is the best way of having effect on other organism. This is the same in Newts and also dendrobates and for example firesalamanders.
To my opinion it is most unlikely that newts are releasing toxin into their sorrounding without cause. So an intoxication from newt to newt is very unlikely.
BTW the origin of the toxin is still not clear.
I think one reason not to mix is the aggression of one species that might attack and injure other newts. But if there is enough space as Tim has shown this seems not the case.
The other reason of not mixing would be different temperature/climate needs.

Uwe

They also mention disease possibilities-but diseases and germs are almost considered "supernatural". Chances are your Cynops have inadvertently shared buckets etc. with your taricha unless you have taken those precautions.

in the report i did it only mentioned the toxicity of taricha newts, and blow fish - i never got any real data on the other guys-but they must not be strong enough to get the mention in the reports i read. saying that though -arent cynops sold dried as natural medicine there in markets? the ttx levels in the tarichas are very very high -if i restrain mine i can smell the toxin released-so if during a feeding frenzy a taricha leg is grabbed by a cynops there is a risk of poisoning. i often wonder if there are cases of MAD (mutual assured destruction) within newt species-i had a pair of paddletails that both died years ago-one attacked the one to death and the other i suspected died from all the white sticky poison he had in his mouth.

Hi Paris. I wonder to what extent the pungency of the skin secretion is an indication of toxicity. I'm very familiar with this smell, especially with C. ensicauda directly caught from the wild (not so much with handling of ones that have already been captive for some time). The most potent I've ever smelled was that of some suspect Paramesotriton deloustali. Very strong! I've never detected this smell with my Taricha though.

By the way, TTX is supposed to be good for menstrual cramps and migraines As far as dried Cynops in the markets here, no, I only know of one small traditional medicine shop that has a few baked ones for use as love potions. Some places in the deep countryside have dried Onychodactylus japonicus (Japanese Clawed Salamander) available for medicinal use though. But I'm not aware that any hynobiids have TTX.

Joseph, I had thought to mention pathogens but the points you just made stopped me from doing so. That falls into the category of "acceptable risk". I only have one tank (of Yambaru C. e. popei) in which I take special precautions

Cynops and Taricha both have tetrodotoxin (as does Notophthalmus), and have different isomers of it, as Tim cited above. There is huge variation in how toxic any individual is, primarily depending on where it was collected. Taricha granulosa is the most toxic species overall, but there are populations with essentially zero TTX and populations with ungodly amounts of TTX. I think the same is true of all the other species, but has not been as well studied. Taricha are supposedly resistant to TTX, although I can't find the citation, but it would make sense that they would not be able to poison themselves. I would think it would be the same in other species with TTX also.

To make it more complicated, it is unclear if the different forms (6-epiTTX; 11-deoxyTTX; 4,9-anhydroTTX) are more or less toxic than the standard TTX.

The only way to find out how toxic your newts are is to test skin samples, which is not that easy (and only a few people know how to do it).

I don't think the Taricha are going to poison the Cynops, but you never know. And if you happen to have non-toxic Taricha, the Cynops could potentially posion them! I doubt they would release the toxins out of their skin glands, it usually takes a LOT of provocation to get any, but you never know what animals are thinking...

Thanks for that input, Liz.

About newts poisoning themselves, I have had a bad experience a couple of years ago with some large Paramesotrito (deloustali?) , one of which released its toxins while temporarily placed in a small cube container for examination. One minute it was fine and the other minute it was dead as a doornail. The smell of the toxin was very strong. I suspect the secreted volume was especially high as it was visible. I even experienced an uncomfortable tingling sensation on my fingers after handling the newt.

At the time, Ed commented that some amphibians may have a bad reaction to their own toxins if the animals are unable to escape the toxin (no carbon filtration, water changes etc.) , though it could have been just a sign of severe stress in the animal.

Jen then provided a link to this abstract:

TTX resistivity of Na+ channel in newt retinal neuron
By Y. Kaneko, G. Matsumoto, Y. Hanyu
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9398620&dopt=Abstract

Here's what else Ed had to say:

"Jen, I checked the abstract that you listed (and wished I had a subscription to read the entire article to make sure I had my conclusions correct but here goes). They used a LC50 concentration of tetrodotoxin to test the resistance of the cells to the toxin. LC50 is defined as the concentration of a substance dissolved in air or water that will kill 50% of the test animals in four hours. So while the newts are resistant to the toxin, I still think that given that it was in a static amount of water and could not escape it could easily have poisioned itself. I have seen this happen with Bufo species (granted they do not have tetrodotoxins but their own mix of alkaloids).
Puffers are also resistant to tetrodotoxins but have been known to wipe their tank out and take themselves out at the same time. with a secretion of tetrodotoxin. Mother Nature does not always make the animal totally resistant to its own toxin (I've also seen rattlesnakes under anesthesia bite themselves as they recover and die from envenomation (Crotalus. d. durissus).

And here's the newt in question:

Actually, the Kaneko et al. paper you mention is not about LC50, it is about IC50. That is the concentration at which half of the sodium channels exposed to TTX are inactivated by TTX binding to them, and are thus no longer able to initiate action potentials. It is a measure of resistance to TTX of specific sodium channels. And it is specifically in regards to retinal nerves in Cynops pyrrhogaster. Its unclear how this would translate to overall sensitivity of newts to TTX--sodium channels in muscle or brain might be more or less sensitive. For example, rat brains have sensitive channels, but rat hearts have resistant channels.

So, how sensitive a newt is to TTX may be a factor of how they are exposed to it. Absorbing it through tissue in contact with water may be particularly bad for some reason, maybe because they can't escape it. But I know that for Taricha granulosa, they are perfectly capable of eating their own toxic eggs with no ill effects, so the oral route seems OK.

Hi Liz,

good points. LD50 is far of to IC50 as it looks at the whole body of an animal.

Just one question, is there any literature that shows that the eggs of Taricha are containing the poison?

Uwe

Uwe,
Here are some citations for eggs containing TTX (tetrodotoxin). They also show that TTX is present in many species of newts, and in various parts of their bodies.

Hanifin, C. T., E. D. Brodie, III, and E. D. Brodie, Jr. 2003. Tetrodotoxin levels in eggs of the rough-skin newt, Taricha granulosa, are correlated with female toxicity. Journal of Chemical Ecology 29:1729-1739.

Brodie, E. D., Jr., J. L. Hensel, Jr., and J. A. Johnson. 1974. Toxicity of the urodele amphibians Taricha, Notophthalmus, Cynops and Paramesotriton (Salamandridae). Copeia 1974:506-511.

Mosher, H. S., F. A. Fuhrman, H. D. Buchwald, and H. G. Fischer. 1964. Tarichatoxin-Tetrodotoxin: A potent neurotoxin. Science 144:1100-1110.

Twitty, V. C. 1937. Experiments on the phenomenon of paralysis produced by a toxin occurring in Triturus embryos. Journal of Experimental Zoology 76:67-104.

Wakely, J. F., G. J. Fuhrman, F. A. Fuhrman, H. G. Fischer, and H. S. Mosher. 1966. The occurrence of tetrodotoxin (tarichatoxin) in amphibians and the distribution of the toxin in the organs of newts (Taricha). Toxicon 3:195-203.

Liz

Hi Liz,

thanki you for the references. As it is not known where the toxin is coming from it is interesting, that the eggs have toxin-content.

Uwe

tim-check this out

Tetrodotoxin levels of the rough-skin newt, Taricha granulosa, increase in long-term captivity

Charles T. Hanifin, , a, Edmund D. Brodie, III b and Edmund D. Brodie, Jr. a
if im allowed to post the abstract -here it is
Abstract
We investigated the persistence of the neurotoxin tetrodotoxin (TTX) in individual captive newts (Taricha granulosa) from the Willamette Valley of Oregon using a non-lethal sampling technique. We found that the TTX levels of newts held in the laboratory for 1 yr increased. TTX stereoisomer-analog profiles were not affected by captive husbandry. Levels of TTX were high in newts from our study population and we observed substantial within population variation in quantitative levels of TTX. Females possessed more TTX than males, but the response of TTX levels to captivity did not differ between females and males. The stability of TTX toxicity in newts is consistent with other amphibian species where TTX is present and may indicate that exogenous factors play a less important role in TTX toxicity of newts than previously thought


its not suprising that they didnt loose toxicity -but the fact that the TTX levels rose is whats interesting. i have copies of this in my student account.

interesting new article:

Secretion and regeneration of tetrodotoxin in the rough-skin newt (Taricha granulosa).

Brian L. Cardall, Edmund D. Brodie, Jr., Edmund D. Brodie III and Charles T. Hanifin

Toxicon
Volume 44, Issue 8 , 15 December 2004, Pages 933-938

Abstract
Rough-skin newts (Taricha granulosa) released tetrodotoxin (TTX) in their skin secretions in response to mild electric stimulation. This release resulted in a large (21% to almost 90% of the pre-stimulation levels) reduction in the amount of TTX present in the dorsal skin of individual newts. Over the next 9 months newts significantly regenerated the levels of TTX in their skin. These data, in combination with previously published results, are consistent with the hypothesis that these newts produce their own TTX.