Toxin Crew

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Stoner Sloth

Toxin Crew Thread Index

Introduction to Toxicology

Introduction to Toxicology 1: Rules Zero through Two; Basic Principles

Introduction to Toxicology 2: Rule 3; Toxins, Toxicants, Venoms and Poisons

Introduction to Toxicology 3:Rules 4 & 5; Functional Classes & Chemical Ones

Introduction to Toxicology 4: Solubility and the Cell Membrane

Introduction to Toxicology 5: Methods of Entry

Creature Features!

Cnidaria - part 1: Hydrozoans, Anemones and Parasitic 'Jellyfish'

Cnidaria - part 2: Of Corals and Cubozoans

GODSPEED JOHN GLENN posted:

I didn't read that, but I get the toxins out of my body by cutting a lemon in half and squeezing the halfs into my open eyeballs.

lol'd

City of Glompton posted:

5'd and subscribed

thanks!

the next post should have some pretty pictures that I'm scouring for and some fascinating and deadly little beasties so hopefully should be less dry reading

feel free to make suggestions and stuff about creatures that you're interested in in the meantime!

# ¿ Apr 19, 2019 05:42

Stoner Sloth

GODSPEED JOHN GLENN posted:

Real question, though, how common are antidotes? They're all over fiction, but I'm sure they don't work like that in real life.

It's a complex question - in terms of venoms though we basically rely on anti-venoms produced by injecting the venom into a large animal, usually a cow or horse, and then extracting the antibodies specific for that toxin (and perhaps closely related ones) from the blood of the animal after it's had time to produce them.

I used to work 'milking' deadly venomous snakes to extract the venom necessary for this and it's always in demand since treating a single dose of snake venom can easily take more than 10 vials of antivenom and a fair amount of venom is needed to make each of them. We did this mostly for Aussie snakes - my main experience was with death adders, eastern brown snakes and red belly black snakes but we also extracted venom from a number of imported species like vipers and cobras that were common in south east asia and africa.

These were acquired funnily enough from some mad bastard who had tried to smuggle them into Australia!! Like carrying coals to Newcastle or something - why would you bring more venomous critters here? Anyways customs intercepted the shipment and at a loss for what else to do they gave them to us.

There are other forms of 'antidotes' including things that reverse or inhibit a toxin's effect or even things like activated charcoal or chelation therapy which remove the toxins from the person's system in one way or another. But in the end antidotes are always specific to a toxin or related group of toxins rather than being a universal cure all. This means fairly precisely identifying the venomous creature in question is key to treating the patient.

I'd also note that anti-venoms, being produced by animals and retaining some residues of that process, can cause allergic reactions that result in anaphylaxis and death so despite being our most effective weapon at the moment most certainly have their risks. Perhaps some day we'll be able to invent and produce purely synthetic antidotes or antibodies that can counteract specific venoms without this kind of drawback but for now it's always a risk.

e: Some toxins don't have any effective antidote though... however often that isn't as bad as it sounds, in many cases simply treating the patient by keeping their heart and/or lungs functioning until the venom is out of their system is enough for survival (such as in the case of tetrodotoxin). As a result there simply may not have been a good reason to develop an expensive antidote or antivenom.

# ¿ Apr 19, 2019 06:41

Stoner Sloth

Cnidaria - part 1

The phylum Cnidaria's estimated 11,000+ species represent some of the most diverse sets of marine animals you can imagine - ranging from the Anthozoa (sea anemones, corals and sea pens) living almost entirely immobile existences to free swimming Scyphozoa (jellyfish) and Cubozoa (box jellyfish) through to the bizarre Hydrozoa - diverse group that includes fresh water Cnidaria, stationary Hydra species as well as colonial swimmers (or floaters is perhaps more apt) like the Portugese Man-o-War.

Also within this diverse group are the parasitic Cnidarians - the Myxozoa and the Polypodiozoa, only conclusively reconized as part of the phylum within the last couple of decade, and the Staurozoa - living fossils with only one extent order; Stauromedusae.

So, what do all these vastly different creatures have in common? Well they are all radially symetrical in their body plans but more importantly they are all venomous!

In fact the term Cnidaria is a reference cnidocytes (also called cnidoblasts or nematocytes) which are the distinguishing, characteristic feature of this phylum.

Cnidaria are the oldest known venom using animals still in existence - fossils dating back over 580 million years have been found and genetic analysis (particularly microchondritic analysis) suggests they're probably 200 million years older still - and seem to show the evolution of multi-cellular organisms from simpler colonies of different types of cells. Cnidaria straddles both sides of this loosely defined line.

Nematocytes (as I'll use more commonly than cnidocytes) are basically the stinging cells or cells containing the venom delivery appartus of Cnidaria and they must have been a massive game changer in terms of evolution. Venom, you see, was the oldest predatory weapon to ever develop - long before things such as teeth or claws or cunning, strength or speed or intelligence. It allowed animals to go from passively gathering food to actively hunting other creatures. We don't know exactly when venom first evolved - probably in the ancestors of Cnidaria or related species, but after hundreds of millions of years of refinement their venom delivery system is a model of amazing biological engineering. Each nemtaocyte contains a cellular organelle (think internal organ of a cell) known as a netamocyst that is like a tiny harpoon and delivers venom to the target prey:

Incredibly once it's triggered the stylet (or 'harpoon') is shot out in the fastest known motion in the animal kingdom - accelerating from 0-100 kmph (62 mph) in just 700 nanoseconds! It has roughly the piercing power of a bullet. One it penetrates its prey the filament behind it is turned inside out via a twisting, drilling motion to reach deeper into the tissue of its victim and the toxic contents of the nematocyst are released to cause paralysis and tissue destruction. Nematocysts are the most complex of all animal cell organelles despite being so ancient.

As mentioned earlier the nature of Cnidaria is such that in some species such this Portugese Man-o-War:

are actually colonies of different parts - in this case seven distinct medusa-like and polyp-like parts, one of the polyp-like parts in this case bearing long tentacles carrying many nematocysts which are used to catch squid and fish. Sometimes these tentacles can get detached from the colony and can drift around and potentially sting bypassers human or otherwise.

Some other Cnidarians, however, use the detached venom delivery as an adaptive strategy:

This is the starlet sea anemone, Nematostella vectensis, which looks like a rather non-descript sea anemone but species within the genus Nematostella are unique in producing free-swimming structures called nematosomes (pictured as the small round thing in the bottom left of image) which carry multiple nematocysts capable and venom capable of rendering small crustaceans incapacitated. These are generally contained within the body cavity ('gut') of the Nematostella where they are thought to both help in processing ingested prey and also contribute to the immune system.

In addition to this they are also built into the jelly like matrix of egg clusters - enabling them to protect developing sea anenome embryos from predators!

Although they are able to move under their own power using cilia, nematosomes are technically not indepedent organisms because they lack their own reproductive and regenerative abilities - they're more like mobile drones produced by little factories in the 'gut' called mesenteries and loaded up with active stinging organellles before being budded off to where they are needed.

While these aren't animals themselves there are some Cnidarians that remain extremely simple throughout their lives - Myxozoans are a truly weird bunch:

They have undergone a drastic reduction in body complexity and size to become perfect parasites - so much so that they were for a long time mischaracterized as protozoans (single celled organisms). Their adaptation to a fully parasitic lifestyle has reduced their body to just a few cells and they live as internal parasites of a number of different species. Some species are even able to live as intracellular parasites - in the egg cells or muscle cells of their hosts. Most rely on two hosts to complete their life-cycle, usually a vertebrate such as a fish and an invertebrate such as an annelid worm.

Despite only consisting of a handful of cells, Myxozoans have retained the cnidarian stinging apparatus - known as 'polar capsules' in this case. Originally thought to just be a sort of boarding hook system to attach to a host and initiate infection they have, on closer study, been revealed as being several distinct varieties of cells including some that are able to deliver venom. The exact purpose of that venom is at this time unknown but it does contain several toxin types used by other cnidarians. They also hold the title of smallest and most simplified venomous organisms known - barely measuring 5 micron across!

This is getting dangerously long so I'll break it up - next time the infamous Cubozoans and hopefully some aspects of coral that don't get much airplay!!

Stoner Sloth fucked around with this message at 09:53 on May 7, 2019

# ¿ Apr 19, 2019 08:09

Stoner Sloth

Manifisto posted:

this is very cool stuff! thanks for the effortposts.

your bringing up the topic prompted me to go read the wikipedia page on amanita muscaria, aka fly agaric mushrooms. I'd remembered hearing them described as toxic (much more dangerous and less pleasant than the more common psilocybin "magic mushrooms") but also having "deliriant" qualities at lower doses, and indeed having been used ritually/ceremonially in some cultures. the wiki page is consistent with that and kind of an interesting read.

those are very pretty mushrooms by the way, they are more or less what inspired the shrooms in alnilam's sig

are there other examples of lesser-known stuff that's basically poison but has interesting enough effects at lower doses that certain populations choose to take the risks on a regular basis?

LOL - in general mushrooms aren't something I know a lot about, but this one I actually have (fortunately) second hand experience with. My brother and a couple of his dumber mates decided to try and get high off fly agaric once when we were all teenagers (gently caress that's a while ago).

For a short while after consuming them they did get a sort of strange high - presumably while the dosage absorbed was still pretty low... but trying to be 'heroes' did them in and they spent about 8-10 hours vomiting. Not something I'd recommend given that magic mushrooms are considerably safer!

Fly agaric are very pretty though, a friend of mine got a tattoo of one on his arm (he was into magic mushies but liked the look of them). He got into working on 3d stuff for video games (did some of that for Arkham Knight for example) mostly in Europe. He told me, not that there is any way of verifying it, that he got stoned with Andy Serkis while they were working on one of these games and he kept doing the Gollum voice asking for bongs.

Now I'm not sure that's true but I'd like to believe that it is.

As for lesser known-stuff that's basically poison or venom that has interesting effects at lower doses - yes, absolutely - I could probably do a whole post on this and probably will at some point but much of our medicine is either synthetic compounds inspired by natural toxins or is synthetically produced natural toxins - things ranging from diabetes drugs (gila monster venom) to the next generation of viagra (based on brazillian wandering spider venom).

Further many cultures have used venomous animals for spiritual, religious or intoxicating purposes - this includes venoms ranging from powerful ant venoms used to induce 'spiritual journeys' to allowing scorpions or snakes to envenomate you to get a high. Some people also smoke scorpions. I will go into more details about this at some point if you're interested - not sure if I'll do a whole segment on it or split it up into the appropriate animal topics but either way there's plenty to talk about with it!!

# ¿ Apr 20, 2019 01:53

Stoner Sloth

Manifisto posted:

wow, cool! yeah, when/if you are so inclined that sort of thing is very interesting to me, sort of in the same way free climbing is--while I'm never gonna do it personally it's kind of fun to hear the experiences of the nutters who do it

Will definitely post stuff about it since ya interested! hmmm... actually could post a little bit about the ant stuff now since GAG already mentioned the type of ant in his awesome thread and I probably won't be addressing ants much since he knows way more than me about them... but I do have a bit of stuff about their use in indigenous Californian cultures that I could write a bit about

# ¿ Apr 20, 2019 02:56

Stoner Sloth

Anthropologists have documented widespread use of red ants as a ritual intoxicant among many ethnic groups of indigenous Californian Indians before the 20th century.

The red ants being used were California harvester ants, Pogonomyrmex californicus, with very painful, long lasting stings - like other kinds of harvester ants these are among the most toxic to vertebrates of any insect venom. In this case the LD50 is 0.6mg/kg - this puts them gram for gram on the same level as many dangerous snakes including mambas, cobras, kraits and vipers!

https://imgur.com/DFwAogG

So how did they make use of these ants?

The indigenous tribes of southern California considered venom to be a conduit to the spirit world. They believed that animals such as rattlesnakes, harvester ants and black widow spiders could transfer shamanic powers through bites or stings and give access to dream helpers in the spiritual realm. Everyone who hoped to live a long and healthy life required one of these dream helpers and the way to find them was through vision quests.

To induce these hallucinogenic vision the indigenous Californians could choose one of a sacred trinity of powerful ritual medicines: tobacco, toloache or harvester ants. Tobacco smoked or ingested in sufficient quantities can produce a trance like state. Toloache is a plant, [i]Datura wrightii[i], in the nightshade family that is known to produce auditory, tactile and visual hallucinations when ingested. Now smoking tobacco or ingesting toloache might sound to you a good deal more attractive than getting high on ant stings. If you assumed that then you would be correct.

The harvester ant ritual was considered so unpleasant that only men and boys who had gone through puberty were allowed to attempt it. The basics of the procedure went something like this:
For three days prior to undertaking the ritual the would be spiritual traveller prepared by fasting and nightly vomiting to purge and purify their body, mind and spirit. Then, guided by a tribal elder, the traveller would lie down on his back before being semi force-fed large numbers of living harvester ants that were rolled in balls of moistened eagle down to make them easier to swallow.

One had to be careful not to chew the ant balls (lol). Then after eating as many as they could - up to 90(!) each containing about 5 ants - the traveller was ready to embark on their spiritual journey. The attending ant doctor would then startle, poke and otherwise agitate the traveller in an attempt to rouse the ants to action. The ingested insects would bite and sting at the traveller's innards until he would lose consciousness. This was the result they were aiming for. Having been rendered unconscious by the venom a successful traveller would experience powerful hallucinations in which the traveller would meet his dream helper, usually in the form of an animal spirit, a force of nature personified or a dead relative.

This loss of consciousness was interepreted as a kind of quasi death, one in which the traveller was 'killed' by the supernatural entities he sought to contact in order to gain access to the spirit world. it's been calculated that 90 ant balls with 4-5 ants each would correspond to about 35 percent of the LD50 dose for a human of about 45 kilograms (100 pounds) if all the ants were to sting. Such a dose would be enough to undoutably cause horrific, mind-numbing pain and a loss of consciousness.

After waking from the vision quest the spiritual traveller would drink hot water to induce vomiting so as to purge the ants from their system. He would then seek guidance from his tribal elder about the meaning and interpretation of the visions he'd experienced and receive further instructions about how to continue to build up the relationship with their dream helper - often through prayer and ritual offerings of seed, shell beads, tobacco and eagle down.

These ant rituals were widespread and quite similar between different ethnic groups with widely divergent cultures and languages. Members of some tribes would repeat this agonizing procedure many times over several days and those who sought to acquire shamanic powers themselves would undergo this ordeal many, many times over a period of months or years.

Ritual ant ingestion was also used for medicinal purposes witht he number of ants adjusted to the severity of the illness and with the regurgitated ants playing a role in establishing the prognosis for a patient. They were also used as a sort of preventative medicine or spiritual protection - as a sort of spirtual prophylactic to neutralize bad omens. They were also used by parents to contact a dream helper in order to try to help cure a sick child.

Given the method of administration combined with the dramatic physiological effects of envenomation this probably qualifies these spiritual rituals of the native Californian people as the most extreme use of venomous animals on the planet.

*much of this is sourced from the work of Kevin Groark, an anthropologist studying these rituals over many years. If there's anything incorrect, ignorant or otherwise disrespectful to indigenous Californian people then my apologies and feel free to PM or correct me ITT - I'd love to learn more if you know it!

Stoner Sloth fucked around with this message at 04:51 on Dec 1, 2019

# ¿ Apr 20, 2019 03:44

Stoner Sloth

Goons Are Great posted:

As officially elected spokesman of the ant crew, I can announce that we as Ant Crew Tncorporated Registered Trademark can offer a collaboration project to cover similar grounds if desired.

Actually I did want to look that up again for more details, gonna throw a few books on my head real quick!!

Should have waited for ya post before I started writing it up - but would love to collaborate on this and happy to correct things or let you add to it if there's anything more that you can tell us my friend!

# ¿ Apr 20, 2019 03:45

Stoner Sloth

Goons Are Great posted:

One question that came to my mind while reading and might be of certain byobian interest are psychoactive substances in regards to them being a kinda-venom.

For example, the for byob entirely unknown hemp plant produces THC, magical mushrooms produce Psilocybin, claviceps purpurea produces lysergic acid and papaver somniferum produces opium - stuff that we humans for some reason looked at and thought, neat, let's inject it and have fun with drugs!!

Do those organisms produce this stuff that we use as drugs as a form of toxin to defend themselves against something else, or does this not directly count as toxin? If it does count as toxin, isn't it generally the case that toxins are always sort of dependent on relation? Stuff that is toxic for predators that want to eat the organisms are shooed away by its effect, while we humans use it as drugs specifically to induce the (somewhat?) toxic effect.

If so, would that mean that a toxin is generally only defined as such towards a certain target organism? Not only the dose makes the toxin, but also the target, then.

I was not intoxicated while asking this, don't judge me.

Oh drat - I missed this post earlier, sorry mate!

But certainly a toxin is also defined by the target in a sense - we just usually think about that in human terms - many things are toxic to arthropods but not toxic at anything like an imaginable dose to mammals. LD50's in fact usually specify not just a dose but what animal it was tested in and using which method of delivery: ingestion, inhalation, subcutaneous injection, intravenous and so on.

But the toxins we have drugs usually are still toxic to us - though sometimes it's possible to isolate a similar chemical compound that has the desired effect without the side effects - it's just there is a dosage at which the benefits outweigh the costs and/or they're not very toxic at low doses.

The toxins we use as drugs are basically refined chemicals from an often complex mixture (venoms can contain hundreds or thousands of different components in complex cases but even simple ones often contain more than a dozen components) so we often are able to reduce the nastier effects of the crude venom that way too.

But a toxin is essentially any toxic compound produced by or derived from a living organism so defensive stuff is certainly a toxin - regardless of the species targeted any biologically created or derived toxic substance is still a toxin after all. And we make use of things that doesn't directly effect humans in things other than drugs - naturally derived pesticides for example!

Hope that answer your question, if not happy to add to it

# ¿ Apr 20, 2019 10:20

Stoner Sloth

Goons Are Great posted:

Heh, those guys were quite certain really insane doing this stuff.
I read once that the ant balls were already less poisonous than the actual sting of those ants would have been though, which means that the venom was already less potent the moment he swallows the things, as the ants start stinging everywhere as soon as they are forced into the ball. As ants have very limited carrying capacity of their venom in their abdomen, the venom was already weakened a fair bit until it was actually swallowed - imagine if he would actually directly have all of this venom injected, that would be either one hell of a trip, or even a serious problem for his body!
Now, it may be that the venom can stick inside the ball and does not spread and evaporate already, SS may correct me here, as I don't know how quickly sprayed venom fades away.

A similar situation is given when those south american guys stick their hands into gloves filled with bullet ants biting and stinging the poo poo out of the hands. As the ants already spread most of their stored venom into the gloves, the actual pain caused is much, much, much weaker than having one or several ants stinging you directly with a full buttload (get it??) of venom, which is the reason challenges like this are even biologically possible.

Well if they were crazy they aren't alone - the oldest known temple in existence shows that people respected/feared/worshipped venomous animals at least 12,000 years ago - humans have probably understood their power and danger and had a fascination with them going much further back and also probably understood their potential for powerful effects on the body. To use such a thing medically or spiritually is so very human, I think.

You may well be right there but on the other hand the fact that they were able to routinely induce unconsciousness suggests a fair whack of venom was reaching the blood stream - it's possible they were diluting it further in this manner though, even likely. Sprayed venom is going to depend on the components, temperature, acidity/alkalinity and other environmental conditions... and funnily enough lots of microbial life will eat venom compounds - in fact most venomous animals actually have anti-microbial compounds contained in their venom to stop it going bad! (we're currently researching these compounds from a variety of species as they might prove superior to our anti-biotics and at the least will allow something new to treat drug resistant bacteria)

But in these conditions I'd suggest a short venom life span for venom not directly injected - in most cases venoms will not survive or be able to have an effect through the stomach lining - in general it's safe to drink most venoms (other than ones that are chemically like poisons) unless there is a cut in the mouth or in this case digestive system. The acidity of the stomach would also likely destroy the venoms rapidly - most venoms are proteins that have evolved to function in conditions far less acidic and this is likely to denature the proteins and peptides involved, reshaping them to the point that they'd not be able to act on their regular target. (remember the specificity of many venoms - particularly in the case of neurotoxins like this one)

I'd agree about the bullet ants though - and it's interesting that they also use a layer of charcoal on the hands - that might absorb and bind with some of the toxin possibly?

Goons Are Great posted:

It does! I find it funny to think that stuff that we love and happily digest is incredibly toxic to other animals, while stuff they do is fine for them and potentially deadly for us. After all, toxins seem to never be omnipotent and deadly for all living things, but only for a few.
Do you know how this corresponds to the venom injecting animal is vulnerable to its own venom? We had this already in the ant crew for a short bit, but is it generally speaking safe to assume that poisonous animals are immune to their own stuff - or immune to other animal's stuff as long as they are the same or a similar species, or is this a one way ticket to hell, no matter if you're in a snake fight or hunting for rodents?

It certainly is interesting but it makes sense when you think about how specific some of these venoms are in their actions - where something isn't evolutionarily conserved as a pathway for some vital biological process then there is room for things being able to affect one group of creatures but not another. Also sometimes the reasons are physiological - Sydeny funnelweb venom contains a neurotoxin that effects humans because of the physical structure of our nervous system but doesn't effect most other mammals. Save for rabbits less than 48 hours old.

The venom immunity stuff though... interestingly many, many venomous animals are not immune to their own venom. It varies by species and I can do a whole post about venom immunity both in venomous creatures and also in their prey (usually there is something of an arms race between the two in this regard). This sort of arms race also occurs in animals with venoms used for intraspecific competition like platypus. Some scorpions on the other hand use stinging each other as part of a mating dance - these clearly have evolved resistance. But also many species prey on and eat younger members of their own species and clearly need venom to work for that! So no - it's a complex thing, as per usual in toxinology and the study of toxin using creatures!

We'll definitely talk more about this point though at some stage because it's interesting to look at the different ways immunity or resistance to a venom can work too

# ¿ Apr 20, 2019 14:27

Stoner Sloth

take the moon posted:

i did it, i think it looks neat next to my av. u always think of being a shaman as a lol cool job where u just do a lot of drugs but turns out you have to eat ants then puke them up.

sure but it still beats paying off student loans!

:hfive:

and welcome to Toxin Crew my fren!

# ¿ Apr 21, 2019 00:57

Stoner Sloth

Goons Are Great posted:

The ant crew is getting outnumbered

but Ant Crew inspired this thread, so we'll always have ants in our heart!

plus it's a boss looking gang tag

# ¿ Apr 21, 2019 02:01

Stoner Sloth

prepuce repurposed posted:

toxic aunt: you wore one of the two sweaters I made you for christmas!

me: yep I love it (lying, lol)

T. A. : where's the other one

me: I can only comfortably wear one sweater at a time it's April for christ's sake

T. A. : you hate it don't you

# ¿ Apr 21, 2019 02:26

Stoner Sloth

prepuce repurposed posted:

someone told me alcohol is a neurotoxin is this true

also how can i get my mitts on both the toxin crew and ant crew gang tags

Sorry I missed this one!

Yeah - alcohol is a neurotoxin, it's a toxin because it's produced from a natural source and it has neurotoxic effects.

That said 'neurotoxic' or 'neurotoxin' are basically just functional categorizations of toxins - a toxin or even a single component of that toxin can be a neurotoxin and also a myotoxin (we'll encounter this particular circumstance later on at some point).

Alcohol could also just as readily be called a 'hepatotoxin' cause it damages the liver or a 'cytotoxin' because it damages cells.

I'll deal with this a little more at the end of the next effort post for reasons that will become clear

Stoner Sloth fucked around with this message at 09:57 on Apr 21, 2019

# ¿ Apr 21, 2019 09:46

Stoner Sloth

Goons Are Great posted:

Meanwhile, some scary toxin stories of a wasp injecting venom into a cockroach brain (not really a brain, because you know, insects don't have those, but an important thing in the head called supraesophageal ganglion) to turn it into her servant.

https://www.youtube.com/watch?v=-ySwuQhruBo

Nice find - such pretty but mildly terriffying creatures

these were the ones that made me think about those vampire ants maybe being able to judge the health of their larvae through tasting of haemolymph!

They're still trying to figure out exact the molecular mechanisms by which jewel wasp venom managed to 'zombifie' the host cockroach but from what I'd read there's certain somewhat eerie similarities between these the state of these 'zombie' roaches and human patients with some forms of neurological disorder.

Basically after the grooming bit they sort of simplify things by saying it's 'stupefied' but the reality is that the instead manage to reduce the ability and/or drive of the roach to self-initiate locomotion - it's not paralyzed obviously can't start movements on it's own.

It's correlated with an insensitivity to dopamine suggesting that the wasp's venom disrupts the normal dopamine-dependent signalling in the roach's nervous system.

This can be seen as not unlike severe Parkinson's disease and particularly patients who survived the early 20th century sleeping-sickness epidemic - they weren't paralyzed technically but were essentially frozen in place until an appropriate external stimulus happened. For example, these locked in patients could perfectly catch and return a ball thrown to them.

Thanks for this GaG and feel free to post more about our venomous hymenopteran frens anytime!

Stoner Sloth fucked around with this message at 09:59 on May 7, 2019

# ¿ Apr 22, 2019 15:12

Stoner Sloth

cool video - I read a few things about this despite not having much of a background in fungi. It's a pretty complex process that we're still in the infancy of understanding.

An interesting (read horrifying) thing about these fungi is that for the most part they don't invade or damage the brain of the ant other than in really specific areas - instead they grow through the muscle fibers of the ant, connect up and then start releasing chemicals that damage the motor centers of the brain but otherwise leave it untouched. Then they use chemicals to control the muscles of the ant... basically the ant is a prisoner in it's own body until the fungi finally kills it.

https://www.theatlantic.com/science/archive/2017/11/how-the-zombie-fungus-takes-over-ants-bodies-to-control-their-minds/545864/

seems like a good, brief, not overly technical summary.

# ¿ Apr 22, 2019 23:39

Stoner Sloth

Manifisto posted:

(some) fungi are friends indeed, try to imagine life without yeast

thanks fungi!

Lichen is another vital fungi - and pretty amazing, apart from being a symbiotic composite organism of fungi (sometimes two types) and algae or cyanobacteria (can be multiple types per lichen) but they can also form other symbiotic relationships with microorganisms as if they're an entire microscopic ecosystem themselves.

They're also responsible for much of the world's fertile soil, since they're able to break down rocks into minerals that they and other things can use, and probably created the first soils suitable for life to grow in on land since they're in the fossil record for an amazing 2.2 billion years. Individual lichen are also exceptionally long lived - an arctic species has examples of it that appear to be 8,600 years old and may be the oldest living organism on the planet.

Oh and also at least two species of lichen can not only survive in space for at least 15 days but can do so without resorting to the sort of tricks that waterbears do and can then be planted back on earth and can still grow, photosynthesize and function normally. Another experiment suggest that they could keep functioning and photosynthesizing on mars for at least 34 days.

Only a few species are toxic (mostly yellow ones), containing high amounts of vulpinic or usinic acid - both of which show great potential as antibiotics and are formed seemingly exclusively in lichenized fungi, but they're still very cool!

Without them life on land may never have been successful.

# ¿ Apr 23, 2019 05:13

Stoner Sloth

Cnidaria 2 :drugnerd:

Time to talk about corals - beautiful, "sea flowers" that are surely harmless right? Well as I stated in part 1, ALL Cnidarians are toxic and corals are no exception - far from it as we will see.

Zoanthidea (taxonomists also refer to this as Zoantherea) are our first stop - a soft coral that has species ranging from deep sea enviroments to tropical coral reefs to the shells of marine invertebrates. these are often vibrantly colourful and charismatic corals are also often sold to amateur aquarium owners and hobbyists because they're relatively easy to keep, being durable and used to many different marine environments, and because of their beauty:

Like most corals they are symbiotic with a type of dinoflagellates known colloquially as Zooaxanthellae (genus Symbiodinium) - single celled, photosynethic organisms that also are often at least thought to be responsible for the production of a variety of marine toxins (bacteria infecting may be at least partially responsible in many cases). In the case of Zonathidean corals this results in some of them concentrating a toxin called Palytoxin (or PTX).

PTX is an extremely powerful vasoconstrictor and one of the most toxic non-protein substances known to science. Because of it's exact mechanism of targeting the sodium-postassium pump present in and vital for the continuing operation of every cell in a verterbate organism it is toxic through almost any source of exposure - be that contact, an open wound, ingestion or even inhalation of fine particles or vapor. It has a "relatively" high ingested LD 50 in mice of around 510-767 micrograms per kilogram but its intracheal or respiratory value is only 0.36 micrograms per kilogram. Worse still an intravenous LD50 in mice is only 0.045 micrograms per kilogram. If it were the same level of toxicity in humans then this would suggest that only a couple of micrograms (millionths of a gram) would be necessary to kill even a large human being. In reality we're probably slightly more resistant than mice but not nearly enough to make this anything other than an extremely lethal toxin.

Given the sheer number of routes of exsposure here it's not surprising that human envenomations and even fatalities have occured through numerous routes - eating parrotfish that have gnawed on and eaten these corals, cuts on hands while handling corals, cutting up or otherwise disturbing these corals in an aquarium or even just inhalation of vaporized toxin and water have all cause fatalities.

Symptoms vary as does time taken by route of envenomation ranging from flu like symptoms to skin symptoms like rash or dermatitis to gastrointestinal or even ocular symptoms if exposure is through the eyes.

However in severe cases neurological, cadiac or muscular symptoms tend to be present as well and can lead to muscle breakdown, kidney failure, coma and death from cardiac or respiratory failure.

The molecular chemistry of palytoxin is outstandingly complex - I won't go too deeply into it unless anyone's remotely interested but there are approximately 10 to the power of 21 different "variant" arrangements of this molecule (stereoisomers). It, like other dinoflagellate (or possibly bacteria infectingthem) toxins such as tetrodotoxin (TTX), saxitoxin (STX and responsible for Paralytic Shellfish Poisoning), is highly toxic. However even compared to most of these its in a class of its own - exceeded only by maitotoxin (MTX) in terms of toxins from dinoflagellate origins.

TTX, which we met earlier when talking about the distinction between toxins and venoms, you'll remember is the lethal toxin used by both blue ringed octopus and many species of pufferfish in different ways. It is probably the least lethal of these at an intravenous LD50 of 8 micrograms per kilogram in mice (remember 0.045 for PTX) - this compares to an intravenous LD50 of 2.6 MILLIgrams per kilogram for deadly potassium cyanide! In other words TTX is more than 300 times as lethal by this measure and PTX is more than 57,500 times as lethal as potassium cyanide!

There is no antidote.

If all this weren't enough evidence suggests that in sublethal doses palytoxins may promote tumors.

You may at this point have second thoughts about handling coral while not wearing thick gloves or eating reef fish, you have my blessing to do so.

----------

Nightmare fuel aside corals are of course venomous in other ways - they use a variety of venoms injected by their stinging cells to catch fish and other small creatures - some rely solely on this although most practice symbiosis with photosyntheic dinoflagellates as mentioned earlier.

There is however another aspect of corals that is less obvious - many are silently and constantly waging chemical warfare against other corals on a massive scale. This is especially prevalent in species that mostly reproduce asexually - corals will use a variety of toxins dispersed in the water currents to attempt to kill or stall the growth of other, unrelated coral so that its offspring may replace them. While most toxins are for predation or defense this and other forms of intraspecific venom use as competition for resources is probably the most common minor use of toxins (though of course there are many, many other niche uses) by venomous organisms.

Moving on from corals we'll take a look at the most complex of cnidarians - the Cubozoans or box jellyfish. Now everyone reading has probably heard of the most well known of these, the 'sea wasp' or often just 'box jellyfish' - Chironex fleckeri but we shall leave this aside for just a moment. The class of Cubozoans are defined by their cube shaped medusae (duh) and there are over 50 different known species the majority of which, while obviously venomous, are not a threat to human beings. These advanced Cnidaria are all capable of independant movement and have a large number of eyes - interestingly some of which are simple light detectors but others of which are more advanced 'true eyes' featuring retina, cornea and lenses. In addition to this the possess gravity sensing cells allowing them to detect their orientation in the water as well as the ability to propel themselves through contraction of their bodies. They all display complex behaviours and can avoid obstacles and predators as well as actively hunting prey courtesy of a far more complex neural structure than other Cnidarians exhibit.

We'll start here with the little guys of the Cubozoan world - Irukandji:

Irukandji, as they were termed by an Australian group of indigenous people, are actually a number of different species of Cubozoan or box jellyfish. They represent the smallest known species of this class. Ranging in size from a bell of about 5 millimetres to 25 millimeteres and with four tentacles ranging in size from a few centimetres up to 1 metre in length.
While the 'body' of these creatures can be less than the size of a thumbnail, they can inflict fatal envenomation on human beings despite targeting nothing more than small fish and crustaceans. Often the effects of envenomation can take 2-12 hours to fully appear and where fatal result from cardiotoxic effects such as hypertension, pulmonary edema or tachycardia.

And finally we take a look at our old friend the 'sea wasp' or 'box jellyfish', Chironex Fleckeri:

Quite a large Cubozoan, the 'sea wasp' can have up to 16 tentacles each with a maxmimum length of over 3 metres. All up this adds up to quite possibly the most venomous organism on the planet - capable of inflicting severe evenomation that targets a broad range of molecular targets and can cause severe inflammation, pain, neurotoxic, haemotoxic, cytotoxic, cardiotoxic, myotoxic and dermnonecrotic (kills skin cells through lysing <bursting> them) effects. It's a sledgehammer in terms of venom and should be compared to the venoms of most sea snakes or cone shells which can be described accurately as almost purely neurotoxic.

To add insult to injury the 'sea wasp' or 'common box jellyfish' can kill a human being faster than almost any other venomous organism - 2-5 minutes on average from a serious envenomation before cardiac arrest sets in. Even in less serious cases permanent scarring is a certainty.

We'll leave it here for now, hope you've enjoyed this episode of Toxin Crew.

PS peeing on jellyfish stings is unlikely to help - it seems that while it deactivates untrigged nematocysts, it also makes those already injected increase the dose of venom to a victim. It's mostly recommended because it allows scraping off the tentacles more easily but you can safely do that with a glove or even thick piece of cloth. Vinegar and other weak acids face the same problem. Please don't take this as professional medical advice but if someone is stung by this jellyfish the best thing to do is seek urgent medical attention and worry more about keeping their heart and lungs working than pissing on them. Again, not a doctor. Stay safe out there!

Stoner Sloth fucked around with this message at 17:20 on Apr 24, 2019

# ¿ Apr 23, 2019 18:21

Stoner Sloth

take the moon posted:

v good post ty.

ty - figured I'd go for the human interest angle :beerpal:

# ¿ Apr 23, 2019 18:54

Stoner Sloth

this is what 'sea wasps'/'box jellyfish' stings that are relatively minor look like:

this sort of scarring is likely to last a lifetime.

e: it's also possible that peak Big Disney movies have led us to optimistically believe that peeing on thigns will help, usually it does in fact not

Stoner Sloth fucked around with this message at 19:23 on Apr 23, 2019

# ¿ Apr 23, 2019 19:08

Stoner Sloth

Manifisto posted:

another very interesting post, thank you!

I remember hearing that the pain from some jellyfish stings can last for over a year or more, that sounds decidedly unfun

thanks for reading friend!

glad you're enjoying!!

yeah, some pain inducing venoms can last for a considerable length of time - the worst culprit there (imho and ruling out testing on myself) is funnily enough a mammal but we'll get to that one soon enough

# ¿ Apr 24, 2019 02:19

Stoner Sloth

Gonna let anyone interested have a say in what we look at next:

a) continue on with toxic marine animals, looking at molluscs next

b) something completely different, look at toxic mammals next

c) delve a bit deeper into how toxins work

I'll tally up the results and go from there

# ¿ Apr 24, 2019 10:09

Stoner Sloth

Goons Are Great posted:

Those are some drat sexy corals. That's SpongeBob porn

yeah - they're definitely beautiful. Looking for pictures of coral reminded me of diving on the Great Barrier reef when it was still in quite a healthy condition - they still don't do it full justice but gave me a pleasant trip down memory lane at least

Goons Are Great posted:

Personally I'd be very down with c

and one vote for c noted! and don't worry, I'm intending to cover all of these topics and plenty more eventually so feel free to vote whatever you'd like to see first ppl and don't worry too much about missing out on the others!

# ¿ Apr 24, 2019 15:21

Stoner Sloth

Manifisto posted:

I'm down for anything, I am sort of fascinated/horrified by cone snails but the toxin aspect is only a piece of that picture

I've got some good stuff on them that I think you'll definitely find fun/horrifying/fascinating then! But c will easily segue into a or vice versa and I can work with doing the same with b so any choice is a good one

# ¿ Apr 24, 2019 15:28

Stoner Sloth

Barking Gecko posted:

I vote for c, but any of the three is fine, and will undoubtedly be interesting.
Also, this thread

thank you mate! and that's 2 votes for C so far

possibly one for A too but wasn't sure if I am counting Manifisto though wasn't entirely sure if he was voting. We'll count it just to be safe though I think.

# ¿ Apr 24, 2019 16:10

Stoner Sloth

take the moon posted:

in order I am b, c, a *

stands for it doesn't matter I am down to learn about w/e

excellent! well that's 2 for c, one for b, one provisionally for a - the mammals stuff will be fun too, there's quite a few of them that most people don't realize are venomous

I'm gonna give it a about 6 more hours to let anyone else have a chance to cast a vote and then I'll do a final tally in the mornin' and get to writing up the winning topic

# ¿ Apr 24, 2019 17:22

Stoner Sloth

gonna extend voting hours a little cause i gotta go visit a sick friend and brink him some smonkables - so if anyone who's interested still wants a say then they're more than welcome, otherwise it's looking like we're delving deeper into the nature of toxins!

# ¿ Apr 25, 2019 02:00

Stoner Sloth

Stoner Sloth posted:

gonna extend voting hours a little cause i gotta go visit a sick friend and brink him some smonkables - so if anyone who's interested still wants a say then they're more than welcome, otherwise it's looking like we're delving deeper into the nature of toxins!

oookay well that took longer than I thought but was fun - think the votes have been decided, more toxicology 420 and then we can take another vote after on mammals and molluscs!!

not sure if I'll write up the next post tonight or tomozz - either way it should be soon.

# ¿ Apr 25, 2019 12:44

Stoner Sloth

Stoner Sloth posted:

oookay well that took longer than I thought but was fun - think the votes have been decided, more toxicology 420 and then we can take another vote after on mammals and molluscs!!

not sure if I'll write up the next post tonight or tomozz - either way it should be soon.

Sorry for being a bad OP - I swear that I'll post more soon, life's just been being a bit crazy and the next bit is a bit more complex than earlier sections so having to put in a bit more effort to make it worth reading. But fear not, i have not forgotten you toxin crew!

# ¿ Apr 30, 2019 03:49

Stoner Sloth

Manifisto posted:

great to hear! but don't stress too much about keeping the effortposts on a schedule, as a wise sage once said, this is byob and you can hang with me, you can chill out relax and smoke a bong with me

thank you friend, those are words of wisdom to live by :350:

# ¿ Apr 30, 2019 05:22

Stoner Sloth

Okay let's get this back thing back on track!

Rule 4 - more classification stuff, as I mentioned earlier the nature of a toxin's attacks on the body can be catergorized functionally in terms of the nature or form of the attack. This as previously mentioned not a mutually exclusive thing as some toxins or components of toxins can attack in more than one way as we shall see. However these terms are handy to have in one place so as you can instantly check the meaning of them.

Neurotoxic - a neurotoxin attacks the nervous system either destructively or by interfering with the function of the nerves. Typically this is done by interfering with the neurons control over ion concentrations across the cell membrane or with communication between neurons across a synapse. Neurotoxicity is one of the more important types of toxicity due to it's capacity to be rapidly lethal.

Myotoxic - often related to neurotoxins structurally, these peptide and proteinaceous toxins bind to the muscle fibres and cause progressive destruction of muscle cells leading to release of breakdown products from the cells. This process often takes hours to become apparent... by which time tissue is irreparably damaged. The release of the cell contents can also lead to toxic levels of myoglobin and/or potassium in the blood, leading to kidney and/or heart failure.

Cardiotoxic - affects the hearts function, damaging it or causing arrhythymia. These can be through direct action on the heart function or more commonly through indirect effect - for example myotoxins damage muscle tissue which can release sufficient potassium into the blood stream as to interfere with the function of the heart potentially leading to arrythymia or cardiac arrest.

Hepatotoxic -targets the liver through a wide variety of mechanisms, this of course also damages the body's ability to defend against toxic substances. A good example of this kind of toxin is that of the Amanita phalloides or death cap mushroom... it works by selectively inhibiting RNA Polymerase enzymes and thereby causing problems with protein synthesis of various sorts. By the time effects from the destructive hepatotoxic effects become symptomatic, the liver (and often kidneys) are often damaged irreparably and this has made this species the most deadly of mushrooms.

Cytotoxic - targets cells. This is a very broad category naturally and includes our own immune systems cells toxins! They can cause necrosis, thereby losing integrity of the cell membranes and rapidly resulting in death through lysing (bursting) of the cell. Cytotoxic components can alternatively or also cause cessation of cell growth and division or activate a genetic program of cell death (apoptosis). In the case of apoptosis the cell will eventually become necrotic and burst though this follows more slowly than in purely necrotic toxins.

Haemotoxic - also referred to as hemotoxic or hematotoxic, these substances destroy red blood cells, disrupt clotting and/or cause organ degeneration and generalize tissue damage. They tend to be very painful as well as generally destructive and as a result can often be found in venoms - in some cases these can kill with similar frightening speed to neurotoxins!!

Nephrotoxic - damages the kidneys through a wide variety of mechanisms both direct and indirect. As mentioned above this can be simply the result of destruction of other cells causing a buildup of cellular breakdown products in the bloodstream in levels too high for the kidneys to cope with.

There are other forms of toxicity including such things as ototoxicity (toxic to the ear/hearing systems) and infamously mutagens which cause genetic damage. These however are probably beyond the immediate scope of our look into the world of toxins, at least for now.

Rule 5 - there are two more forms of classification/groupings that we'll discuss but these WILL have immediate relevance. You can divide toxins, like any other chemical, into organic and inorganic substances. An organic substance is one containing Carbon - Hydrogen bonds, an inorganic substance is one that does not. While this may seem abstract it's relevant because C-H bonds allow immense complexity, far beyond that displayed in the inorganic world. This is because C-H bonds can form long chains of carbon that can have other functional groups attached. Living chemistry is, as we far as we know, dependent on this complexity that can only come from carbon chemistry. It should be no suprise toxins are organic chemicals - inorganic chemicals may well be toxicants but living things tend to rely on organic chemicals for poisons and venoms.

The second, and more important, classification is one I'd like to talk a fair bit more about.

Chemicals can be soluble in polar (basically meaning that eletrical charge on the molecule is unbalanced resulting in negative and positively charged ends) or non-polar (balanced charge means no poles of charge present) solvents. Like disolves like is one way of putting it since polar molecules dissolve in polar solvents (water being the most important one) while non-polar substances tend to dissolve in non-polar solvents (such as ethanol or more importantly lipids such as fats and oils). This has profound consequences for toxicity of a substance.

It's easy to envision this distinction - imagine you're making a salad dressing with olive oil and water base. This will form an emulsification, a mixture of two substances that can't be blended together permanently. When left to settle they'll form a layer of the less dense oil on top of the water because they cannot be blended.

Now if you add things to this salad dressing like salt or sugar, these will dissolve almost entirely into the water alone. Alternatively if you add things like vanilla or mint extract they'll dissolve into the oil without almost any trace of them in the water component.

If we take our salad dressing and shake it after adding whatever components to it then these differently soluble components will be mixed almost entirely into the oil or the water - or they won't dissolve at all and be found sitting at the bottom of the container.

So based on these two distinctions we can divide up every chemical into one of five categories - water soluble organic, water soluble inorganic, lipid soluble ogranic, lipid soluble inorganic and insoluble (organic or inorganic). An insoluble compound is basically toxicologically inert - if it can't dissolve into water or lipids then it cannot be absorbed into the body and cannot reach target sites to cause a toxic effect.

This leaves 4 relevant categories of which another can be crossed out - lipid soluble inorganics are basically in practice not toxicologically interesting. So we're down to three possible categories of toxic substance of which we'll primarily be exploring the two organic types. To look at why the dichotomy between lipid and water solubility is so important we need to first take a close look at where the chemicals literally bump up against biology: the cell membrane.

Stoner Sloth fucked around with this message at 13:47 on Apr 30, 2019

# ¿ Apr 30, 2019 13:44

Stoner Sloth

Solubility and the Cell Membrane

Before we look at the absorbtion of toxic compounds from the environment via a variety of means, let's take a moment to consider the nature of individual cells. Ask someone to draw a picture of a cell in only a couple of seconds and without fail they'll draw a closed circle - in essence they are drawing the cell membrane. While the nucleus, mitochondria, golgi aparatus and other cell organelles might be vitally important to the life of a cell, it is the cell membrane that separates the inside from the external world - essentially defining what is the cell and what isn't.

The cell membrane is composed of a double layer of phospholipids (lipids that contain a phosphate group shockingly enough!) that are arranged in such a manner that, in the outer layer, the phospholipids polar heads all point outwards from the cell and their large, non-polar tails all point back in towareds the cytoplasm (interior of the cell). The innner layer is the reverse of this - polar heads pointing into the cytoplasm and non-polar tails pointing outwards to form a double layer of non-polar tails in the middle of and separating two polar layers.

The polar heads are critical here - within each of them lies a negative and a positively charged region. Since like charges repel and opposite charges attract this in effect forms an impenetrable barrier to diffusion for any charged inorganic or organic ion.

This relative impenatrability creates a problem however; the inner cyctoplasm cannot wall itself off from vital water soluble compounds entirely. Many essential inorganic ions such as calcium, sodium or chloride as well as organic polar substances such as glucose cannot readily migrate through the cell membrane. So how do they get in?

Well with the help of proteins, a wide variety of which stud the lipid bilayer. These proteins act as pores or carriers that can ferry polar molecules across the cell membrane. The more active a cell or organelle inclosed behind a biological membrane, the more proteins are found studding the membrane.

For a toxic response to occur, the chemical in question needs to reach it's target - this is sometimes a receptor, other times a protein or nuclear DNA, but in general the target is either within the cell, embdedded within the cell membrane, or is the cell membrane (lipid bilayer) itself. As such, for many toxic chemicals the route to biological activity has to cross the cell membrane and this is where solubility of the chemical reenters the picture.

Water soluble compounds obviously can't readily cross the lipid bilayer unless they have help in the form of a protein gate, pore or carrier. As such, water soluble compounds are controllable and many - such as the inorganic ions sodium, chloride, potassium and calcium - are maintained in strict concentrations within the cell. Interestingly however while this system has evolved so that these ions can be closley regulated, the system is not so fine tuned as to guarantee that mistakes do not occur. Ion channels or gates might allow for the precise regulation of inorganic and organic ions but also often allow for the inappropriate uptake of toxic ions from the blood into the cell. Transporters for the micronuterients copper and zinc, for example, cannot differentiate between these essential metal ions and other, more insidious metals such as cadmium, silver and mercury all of which are toxic.

While water soluble toxic chemicals engage in a game of mistaken idenity, being allowed into the cell via channels whose function is to allow the transport of necessary chemicals, toxic lipid-soluble compounds are engaged in a very different process. These chemicals simply do not see the lipid barrier as a boundary at all and as such can move around within an organism without constraint or regulation. They basically are able to entirely avoid the carefully evolved cellular regulation and organization inherent within living cells as one of their defining features.

Now since solubility is clearly such an important thing in understanding the absorbtion and ultimate fate of molecules within the body, we need a way to quantify it. If we go back to our earlier salad dressing metaphor then all we'd need to do to measure the solubility of an unknown added component is to shake the oil and water mixture and then measure the concentration of our mystery compound in the water vs the oil. Expermentally the oil we use isn't delicious olive oil of course but rather octanol and the resulting numeric determination is referred to as the octanol:water partition coefficient or K_ow.

If we think about different molecules ranging from highly water soluble, such as table salt, and highly lipid soluble, such as cholesterol, how different are there K_ow values? It turns out that they are very, very different indeed. It's not unusual for a water soluble compound to be a million times more soluble in water than in octanol, nor is the reverse uncommon either. In fact the numbers are so large that logarithmic expression becomes necessary - the K_ow of a lipid soluble substance may be 1,000,000 (10⁶) or expressed as log K_ow = 6. The difference between solubility of a lipid and water soluble compounds may exceed 10¹², such that the lipid soluble compound is more than a trillion times more soluble into the lipid bilayer than the water soluble compound is relative to that same bilayer.

So, to summarize, a chemical that is water-soluble is, by definition, not lipid-soluble and as such will not be able to dissolve into the membrane. As such its rate of diffusion across the barrier will be minimal. Without the aid of carrier proteins, the uptake of chemical will be minimal - as will it's ultimate toxicity. In contrast to this, a compound that is soluble in oil or fat will easily be absorbed across the lipid bilayer and as such will have a greater potential for eliciting toxic action. With a high log K_ow a substance will readily solubilize into the lipiid bilayer and it's rate of diffusion into cells will be much higher.

This is perhaps the fundamental dichotomy within toxicology - the behaviour of virtually every toxic compound is dictated by the fundamental split betwen water and lipid solubility. It influences absorbtion from the environment, delivery in the blood, diffusion into target tissues, excretion from the target tissue, metabolism, sequestration and whole-body elimination. All of these properties are influenced more by solubility rather than size or shape of the molecule.

e: Just for simplicity sake - we'll call this Rule 6 - the nature of a chemical's effect on an organism is heavily dependent on it's polar vs non-polar solubility.

Stoner Sloth fucked around with this message at 15:02 on Apr 30, 2019

# ¿ Apr 30, 2019 14:48

Stoner Sloth

So uh yeah, hope that all made sense and wasn't too dry. The toxicology stuff is a little abstract sometimes and hard to find illustrations for. Got another decent sized bit to come and then I'll put things up to another vote to see where we head from there - thank you for reading and hope you're finding it interesting friends

e: and as always happy to answer questions too!! :drugnerd:

Stoner Sloth fucked around with this message at 17:15 on Apr 30, 2019

# ¿ Apr 30, 2019 17:12

Stoner Sloth

Manifisto posted:

it's pretty interesting to me, you're bringing back things from long-ago classes. there is this old trope about building up immunity to poisons by taking small doeses and gradually increasing them, e.g. "iocane" in princess bride. I imagine this works okay for some toxins and doesn't work at all for others (e.g. people subtly poisoning others with heavy metals by giving trace amounts over time). do the distinctions you're drawing play into whether tolerances can be increased for various substances?

This is an excellent question - short answer is yes, they do. Longer answer will have to wait for another post but I promise you will get as complete an answer as I can adequately give on this but we've got a ways to go before we get there. "Iocane" is obviously fictional but it does, as presented, bare a decent similarity to tetrodotoxin (TTX) which I'm guessing inspired it and can certainly be found in Australia (and many other places - some newts in north america I believe make use of it).

But yeah - in very basic terms it effects things like how the body tries to excrete stuff and also what gets stored in the body over longer periods - heavy metal poisoning or pesticide poisoning being excellent examples of substances excreted only slowly. The body has quite a few tricks up its sleeve but in the case of lipid soluble stuff which get stored long term (water soluble stuff obviously being pretty easy to excrete through urine) what is happening is that the body is trying to chemically alter the substance in question into a water soluble form. This can backfire too as we'll eventually see - sometimes this can increase the toxicity of a substance. The body can also produce specific anti-bodies which can breakdown or disable a chemical, try to reduce the number of target receptors in some cases or try to reduce the effectiveness of carrier proteins for water soluble toxins.

It gets even weirder - there is are people out there who have formed a subculture of trying to immunize themselves from snake venoms - for reasons varying from the pseudo-scientific to the mystical to simply believing it will keep them safe from snake bites to protect them from their hobby/profession of handling snakes. This is extremely dangerous and I would not recommend it to anyone for a number of reasons, starting with the fact that many of these venoms are so toxic that the slightest miscalculation could kill you - also the treatment for such miscalculations could kill you to.

In principle though building resistance is possible in many cases, particularly with venoms, hell it's the basic principle of why we use large animals to produce anti-venoms. In practice any resistance built up may be useless in the face of the overwhelming toxicity of the venom in question - what use is it in resisting 1/100th the bite of a coastal taipan?

Stoner Sloth fucked around with this message at 18:04 on Apr 30, 2019

# ¿ Apr 30, 2019 17:42

Stoner Sloth

Goons Are Great posted:

Took me a while to catch up here, but I really like thisw details! Since I have some academical history with biology this stuff naturally attracts me and reading how this stuff works in detail is so fascinating.

brb injecting myself tons of snake venom to prepare for my next australia visit

Excellent - the next post should be enjoyable too then friend

lol this reminds me of the dumbest thing I've read about venoms recently - there's a product on the market that allegedly uses snake venom to cure baldness. It is literally called Snake Oil^tm :eng99:

# ¿ May 2, 2019 01:02

Stoner Sloth

gonna try to get another post up this weekend - we'll be taking a closer look at how venoms and poisons move into and through the body (as opposed to just individual cells) AND if I get the time we'll look at how exactly neurotoxins work!!

Stay tuned fellow yobbers and hope y'all are having a good weekend!

# ¿ May 4, 2019 04:47

Stoner Sloth

Different methods of toxins making an entrance to the body

Okay so last time we looked at the huge effect that solubility of a toxin has on how it interacts at the cellular level, now let's take a step back so we can see how this plays out in terms of a whole organism.

Now as was mentioned earlier for a toxic chemical to be harmful it must first travel through the body to specific (or even not that specific) target sites. Regardless of how the chemical reaches an animal, whether it's ingested, inhaled or enters through the skin all chemical-biological interactions begin with moving across an epithelial layer. The skin is the most obvious example of a layer of epithelial cells since it's clearly visible and it's here that we'll start.

Skin

Skin, at least in mammals, acts as a barrier between the external environment and our personal, internal one. The outermost layer of skin is made up of dead cells while the underlying dermal layer is constantly dividing and producing new cells that die, dehydrate and then keratinize. The process of keratinization involves the buildup of keratin in the epithelial cell layer. Keratin is a fibrous protein found not only in skin but in nails, hooves, hair and even rhino horn. Bundles of keratin are quite tough clearly and, equally importantly for our purposes, they are insoluble in water. Consequently you can, for the most part, consider the keratinized outer layer of your skin to be a watertight boundary between you and the outside world.

Dead cells also have no active transport proteins associated with them; therefore water soluble compounds cannot make it through since they rely on this method of transit. Fat(lipid) soluble compounds are another story entirely. Dead cells still contain lipids that were in the cell when it was living and as a result fat soluble compounds do absorb into the dead cell layer.

The capacity of the skin to absorb lipid soluble chemicals can be both a blessing and a curse depending on the context - for example transdermal medicated adhesive patches take advantage of this capability of the skin to absorb lipophilic compounds in order to administer chemicals such as scopolamine, an anti-sea sickness drug, or nicotine for those attempting to quit smoking.

Unfortunately it also means that substances like urushiol, the active ingredient in poison ivy, oak and sumac, can also take advantage of the skins capacity to absorb small, lipophilic chemicals to cause considerable pain and irritation. Worse still some creatures have even evolved to deliver poison directly through this path which can have much more severe results - poison dart frogs of the family Dendrobatidae are the most notorious example of this. Although these usually brightly coloured creatures are amazing to look at;

they also have more sinister side. They have developed the ability to absorb a range of small, lipophilic chemicals from the environment such as batrachotoxin, epibatidine, histrionicotoxin , allopumiliotoxin 267A and pumiliotoxin 251D and then exude them from their skin as a chemical defense system. All up there are 28 distinct structural classes of alkaloid toxins known to be absorbed in species of these frogs. Many of these are exceedingly toxic - batrachotoxin in particular is made use of by the golden poison dart frog, Phyllobates terribilis, the most toxic of poison frogs.

Batrachotoxin is one of the most deadly of alkaloid poisons - the LD50 for subcutaneous injection in mice is a mere 2 micrograms (millionths of a gram) per kilogram! It is also an extremely fast acting neurotoxin. It's no wonder that the toxic secretions of these frogs were cleverly used by indigenous Amerindians to poison the tips of blowdarts used for hunting and warfare given that a single dart can almost instantly cause paralysis in large monkeys or birds. Of course great care had to be taken when harvesting this poison - careless would-be hunters could easily find themselves succumbing to the very venom they seek to use!

As a final note the skin is obviously a vulnerable barrier to venomous animals in particular - by using mechanical methods to puncture the skin such toxins receive a much more efficient way of crossing the epithelial barrier than through sheer chemistry. This is particularly important to venomous animals since as noted earlier most venoms are peptides and proteins and are water soluble.

The Lung

Lungs are fundamentally different from the outer skin in the sense that its cells are all very much alive but the two do share an important characteristic - there is no protein mediated transport of compounds from the air sac or alveoli into the lung. Beyond that though the similiarties between these two epithelial layers pretty much comes to an end.

The lung represents a volume of space across which oxygen and carbon dioxide diffuse - in an amphibian such as a frog, the lung is configured like a small bunch of grapes with a few quite large air sacs, a relatively small total surface area (combined surface area of all the 'grapes' in the bunch) and a relatively large diffusion distance from the centre of the air sac to the animals blood.

In contrast to this a mammalian lung of similar volume (say a small rat in comparison to a large bullfrog or toad), the alveoli are much smaller and more numerous. The rat also has a much higher metabolic rate which of course necessitates faster diffusion of oxygen into the blood. This partially accomplished by decreasing the diffusion distance (smaller alveoli means less diffusion distance) and by increasing surface area. Consequently oxygen is delivered from the air to the blood and carbon dioxide is removed from the blood to the alveoli much more quickly and efficiently in the rat relative to the frog.

It's not just simple gases, such as oxygen and carbon dioxide, though that diffuse across the lung epitheleum - vapours can also be absorbed (as most yobbers can probably attest to). A vapour is the gas phase of a substance as it evaporates or volatizes from a liquid (think about the vapours rising from a small drop of perfume for example), and all chemicals do not generate vapours to the same degree. Water soluble compounds do not volatilize (create vapours) and remain stubbornly dissolved in water. Even if the water completely evaporates these compounds are unlikely to enter the atmosphere but will instead be left behind as a solid residue, often in the form of salts.

Consequently, carrier proteins for the transport of water-soluble compounds are not found within the lung as those compounds rarely present themselves to the lung in any appreciable concentration.

What about the more volatile organic compounds? Even for these compounds there aer differences in degree to which they are absorbable and the determing factor is the compound's blood:gas partition coefficient. To understand how this blood:gas partition coeffficient governs absorption consider a vapour enclosed in a cocktail shaker with a bit of water. After this 'cocktail' is shaken the vapour can partition either into the water or can primarily remain in the atmosphere within the shaker. In this case, chemicals that remain in the shaker's atmosphere have low blood:gas partition coefficient, whereas chemicals found predominantly in the liquid have high values for the coefficient.

These tendencies dramatically influence the capacity for absorption because low values of the blood:gas coefficient are indicative of low rates of absorption, whereas higher coefficient values predict much higher rates of absorption across the lung epithelium.

Gills are an interesting further twist on respiratory organs. Unlike the lung, the fish gill interacts with the water allowing for the uptake of dissolved oxygen from the water and release of carbon dioxide from the blood directly into the water. In addition to this the direct association between the gill and the water allows for transport of water-soluble compounds. As such the fish gill, unlike the mammalian lung, is enriched with proteins that allow for the transport of water-soluble compounds, specifically inorganic ions such as sodium, calcium and potassium. The fish gill is not just a respiratory organ (an organ used to exchange oxygen and carbon dioxide with the environment), but is also an ionoregulatory structure like the mammalian kidney - working to maintain appropriate concentrations of key elemental ions within the blood.

The Digestive Tract

While chemical traffic across the skin is for the most part minor, and the traffic across the lung is restricted to a few highly specific chemical classes, chemical traffic accross the epithelial layer of the digestive tract is rapid and continuous. The primary purpose of the gastrointestinal epithelium is to absorb food on a molecular level. Therefore, the intestinal epitehlial membrane is completely festooned wtih proteins that function to move water-soluble compounds out of the intestinal tract and into the blood where such chemicals can be transported to the liver.

The transport of lipids across the intestinal epithelium, which might be expected to be simple given the way things have gone so far, is actually quite complicated. When consumed lipids - fats and oils - tend to mix together in the stomach and intestine to form large globules rather than remaining isolated as individual chemicals. These larger globules of fat have to be broken down into smaller droplets in a process of emulisifcation. Emulsification occurs in the digestive tract through the action of bile salts and acids that reduce the surface tension of the lipid globule, causing it to thereby break into smaller globules known as micelles. These small aggregates of fat and oil can then migrate across the digestive epithelium membrane to ultimately reach the blood.

The chemical thoroughfare across the digestive system, vital to bring food molecules into the body, is unfortunately also well suited to the absorption of toxic compounds. Proteins designed to trasnport water-soluble food molecules can also mistakenly transport water-soluble toxic compounds. Lipid-soluble compounds generally become incpororated into the large fat droplets within the intestine and are also proportioned out into the micelles as they form. Along with the beneficial fats and oils within the micelle so necessary to our survival, lipophilic contaminants can ride the micelles across the epithelial membrane and into the blood.

It's also worth noting here that many proteins and peptides will not survive a trip through the stomach - for this reason many venoms are technically safe to consume (though you shouldn't since a small cut in the mouth or esophagus could mean they have an alternate route of entry). This is because the acidity of the gut is designed to break most proteins down into amino acids for easier absortion and the fact that a protein designed to operate under such acidic conditions probably wouldn't function well in the more pH neutral environs of the vascular system.

In the Blood

Regardless of how it gets there, whether through direct injection, skin contact, inhalation or ingestion, once a chemical has gotten inside the body it cruises through the blood vessels towards its ultimate sit of action - it's target tissue. How chemicals travel through the vascular system depends upon a number of factors, including of course the chemical's solubility. Water-soluble compounds dissolve intot he blood plasma and ride the flow, for the most part, in a free and unbound form. Lipid-soluble compounds, however, bind to proteins and an equlibrium develops betwen a small pool of free compound in the blood and a much larger pool of bound compound.

This is important, as the free form is the biologically active one, being able to diffuse from the blood to the target receptor. However as the free form of the compound diffuses from the blood into the extracellular fluid and the waiting target cell, the equilibrium shifts and more of the bound form is freed. The bound form of the compound acts like a kind of time-release capsule, slowly releasing free and biologically active compounds into the blood where they can diffuse across the nearby capillary epithelium.

While a toxic compound may intially enter the body through a variety of different means, it's target is often in distant tissues and to get there thecompound will travel within the bloodstream. It's movement into the blood from the epithelial cells where absorption took place will be consistent with the process by which it made its way into the epithelial layers. For fat-soluble compounds, entry into the blood will not be an issue - they will not be barred by the cells making up the blood vessels. Water-soluble compounds, on the other hand, may have to use carrier proteins to shuttle them across cell membranes.

A compounds ability to move from tissues into the blood is not solely determined by its own chemical attributes, for the blood vessels themselves will either help or hinder this exchange. Blood capillaries within the brain adhere tightly together so that no transport can occur without the compound being directed through the cells of the capillary network. Consequently, water-soluble molecules can only enter the brain through the cells that make up the blood-brain barrier.

In contrast to this the capillary network of the liver is less densely organized with holes so that bulk fluid can flow from the blood into the liver tissue and back again easily. The system allows for water-soluble food molecules (such as sugars) to enter the blood readily but it also allows for water-soluble toxic molecules to follow the same route.

Once a compound enters the blood, its residence within the bloodstream depends upon its solubility. In water-soluble compounds, the chemicals remain dissolved in the aqeous blood and are trapped until they are allowed to exit via channels or gates or through large holes or fenestrations such as those that occur in the liver of kidney. Water-soluble compounds are ushered around the bloodstream, then, in a very controlled fashion in general. On the other hand lipid-soluble compounds enter, and often exit, the bloodstream in an uncontrolled fashion.

On a cellular level, our bodies wage an energetic, ongoing battle between control and chaos and uncontrolled lipophilic compounds present a direct confrontation to our commmand over our internal environment. Fortunately, fat-soluble compounds are not maintained in their freestylin, go-anywhere-they-drat-well-please form while in the blood but are instead harnessed to large and charged proteins. This binding creates a charged supermolecule or protein-toxic compound conjugate that is essentially polar and therefore locked into place within the blood. For many toxic compounds (and nonpolar, nontoxics alike such as sex steriods), a large pool of these conjugates are in equlibrium with the much smaller pool of free nonpolar compounds. As the free compound dissociates from the plasma protein it resumes its more nomadic form and can easily diffuse across the cell membranes of the capillary beds, leaving the bloodstream. Therefore the conjugated compound in the blood slowly liberates free compounds that can diffuse and become available at the waiting target receptors where toxic compound can cause adverse impacts.

Sequestration

From the blood, the chemical compound can migrate to cell membranes and bind to the target molecules on the cell surface or it can enter the cell and bind to the target molecules within them. When a compound enteres a target cell, it can follow a number of different routes, with various consequences beyond the obvious one of damaging the cell. Some compounds can become sequestered - that is embedded in the body in a stored form, remaining relatively begning. For example, water-soluble metal ions can become incorporated into the bone (this is not entirely a good thing - think about radioactive strontium 90 which the body treats as calcium) whereas lipophilic compounds can become incorporated, understandably enough, into the fat deposits.

Compounds that are sequestered can remain in tissue depostions for life, or they can be removed from the body in an inert form (think arsenic or organic mercury compounds being excreted into hair or DDT leaving the body through breast milk), or they can be liberated back into the bloodstream (as several cases of pesticide poisoning have shown this can happen in toxic amounts when a person loses weight due to say an illness and the sequestered pesticide is released from adipose tissue as a result). Regardless of the specific pathway along which chemicals travel or their level of toxicity, chemicals obey the rules of diffusion and are carried toward their designated target tissues accordingly.

Okay that's a good place to stop this post, for my next one there's been a slight change of plans but it will work out better I feel - next I'm going to discuss some of the body's defense mechanisms against toxic substances. After that I'll move on to how exactly neurotoxins function, promise! Hope you enjoyed and I'll be back to post more very soon!

e: and as always don't be shy to ask questions if you have them!

Stoner Sloth fucked around with this message at 13:29 on May 20, 2019

# ¿ May 6, 2019 08:37

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# ¿ Apr 28, 2024 04:11

Stoner Sloth

Manifisto posted:

wow, more great information. I feel like I'm getting a master's course in poisoning, which is bad news for my enemies.

drat enemies, I hate those guys! :oldmanyellsatclouds:

Don't get too cocky is my advice though - most of this so far is only obliquely usable for nefarious porpoises and frankly the problem with most toxins (and toxicants for that matter) is that they're highly traceable in these new fangled and modern times. That and dosage makes all the difference - especially in the case of poisons - too much can induce emesis (vomiting) and actually be less effective than a subtler dose.

Still you can probably see why those with sophisticated knowledge (or even relatively primitive knowledge going further back) were rightfully feared throughout history when the general understanding was low and the methods of detection inadequate - especially as the results of exposure to toxic substances can be horrifying particularly with chronic poisonings like arsenic, organic mercury compounds or thallium. Let alone use of venomous animals which have evolved in an arms race of toxicity vs resistance over millions of years.

Oh and also poisoning animals/people is ethically dubious or so I'm told? :shrug:

e: also forgot to lead with the fact that I'm glad you're enjoying my weird posts!! I'm happy to keep this up for as long as folks are interested cause it's such a vast topic and touches on that really interesting area of where biology meets chemistry and/or physics - ties in to how life stems from nonlife in many ways

e2: didn't like the way that this post could be read in a way that seemed to encourage bad things, edited to avoid my fierce levels of stupid causing problems.

Stoner Sloth fucked around with this message at 01:47 on May 7, 2019

# ¿ May 6, 2019 17:46

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