Toxicology: the study of Poisons

Note, this page will not contain poisonous plants, as those are already covered in the botany page. This page will cover poisonous animals and fungi.

Toxicology classifies about 4 types of poisons, depending on their origin or intent. When a poison comes from a plant or microbes, those are called toxins. If they are naturally-occurring, like arsenic, then they are referred to as toxicants. Xenobiotics are pharmaceuticals, that contain unintended effects. The last category are pesticides.

Venoms are very complex, containing polypeptides, high- and low-molecular-weight proteins, amines, lipids, steroids, aminopolysaccharides, quinones, glucosides, and free amino acids, as well as serotonin, histamine, and other substances. Some venoms are known to consist of more than a hundred proteins. The venom is a source of peptides and proteins that act on myriad exogenous targets such as ion channels, receptors, and enzymes within cells and on cell membranes.

Spiders
Of the 30,000 or so species, at least 200 have been implicated in significant bites on humans. Spider poisons are peptides, such as Gomesin from Acanthoscurria gomesiana.

All spiders except the Uloboridae family possess a venom apparatus that produces neurotoxins designed to paralyze or kill prey. Spider venoms are complex mixtures of low-molecular-weight components, including inorganic ions and salts, free acids, amino acids, biogenic amines and neurotransmitters, and polypeptide toxins. The acylpolyamines, composed of a hydrophobic aromatic carboxylic acid linked to a lateral chain of 1 to 9 aminopropyl, aminobutyl, or aminopentyl units, are voltage-dependent open-channel blockers (sodium, calcium, and potassium channels) and/or blockers of the ion channel associated with glutamate receptors. They also act on nicotinic acetylcholine receptors. The acylpolyamines possess insecticidal activity and induce fast insect paralysis via a reversible block of the insect neuromuscular junction.

Tarantulas: ~800 species. At least 33 peptide toxins have been described from various tarantula venoms. These have a molecular weight of 3000 to 5700, and targets include voltage-gated potassium, sodium, and calcium channels, tetrodotoxin-sensitive channels, and acid-sensing ion channels, which are sensitive to extracellular pH.

Funnel-web spiders in Australia, secretes venom called delta hexatoxin.

Snakes
Of the approximately 2700 known species of snakes, about 20% are considered to be venomous. That means at least 400 species of snakes are considered dangerous to humans. Venomous snakes primarily belong to the following families: Viperidae (vipers), Elapidae, Atractaspididae, and Colubridae.

The vipers are further divided into subfamilies, an example of which is the Crotalinae, or pit vipers, which possess a pit between the eyes and nostrils that serves as a heat sensor to detect warm-blooded animals.

It is estimated that there are over 2.5 million snakebites annually, and that over 100,000 victims will die.

These venoms are complex mixtures: proteins and peptides, consisting of both enzymatic and nonenzymatic compounds, make up over 90% of the dry weight of the venom.

At least 26 different enzymes have been isolated from snake venoms, which can be a sequence of 150 to 1500 amino acids (as of 2003). No single snake venom contains all 26 enzymes

Phosphomonoesterase (phosphatase) is widely distributed in the venoms of all families of snakes except the colubrids. It has the properties of an orthophosphoric monoester phosphohydrolase. There are 2 nonspecific phosphomonoesterases, and they have optimal pH at 5.0 and 8.5.

Many types of venom contain both acid and alkaline phosphatases, whereas others contain one or the other. Phosphodiesterase has been found in the venoms of all families of poisonous snakes. The enzyme is an orthophosphoric diester phosphohydrolase that releases 5-mononucleotide from the polynucleotide chain, and thus acts as an exonucleotidase, attacking DNA and RNA. More recently, it has been found that it also attacks derivatives of arabinose.

Polypeptides
Snake venom polypeptides are low-molecular weight proteins that do not have enzymatic activity. More than 80 polypeptides with pharmacologic activity have been isolated from snake venoms.

Frogs
A difference between frogs and toads, are the poison from frogs comes from their skin, whereas for toads, poison comes from their glands. Toxicology textbooks don't tend to have anything on frog poison, as humans generally do not get poisoned by poisonous frogs, as bites from frogs do not poison humans. As stated, the poison from frogs are on their skin, so humans only get poisoned by frogs from eating them (or licking them).

But here is some trivia about frogs. The principle poison from poison dart frogs, is batrachotoxin (BTX), a neurotoxic alkaloid. Batrachotoxins binds to, and irreversibly opens the sodium channels of nerve cells, and prevents them from closing, resulting in paralysis and death. No antidote is known. It was 1st discovered by Fritz Marki and Bernhard Witkop at the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, in Bethesda, Maryland. The 2 separated the poison from the Phyllobates bicolor (black-legged poison dart frog), and determined its chemical properties in 1963. But frogs do not produce these poisons on their own, they do so from the insects they eat that contain them, so frogs raised in captivity do not produce them.

The compound epibatidin comes from the skin of the South American frog, Epipedobates tricolor. A substance called magainin 2, which comes from the skin of frogs, is an effective antibiotic to which bacteria do not appear to develop resistance.

Bees
The venom contains biologically active peptides, such as melittin, apamine, mast cell-degranulating peptide, and others, as well as phospholipases A2 and B, hyaluronidase, histamine, dopamine, monosaccharides, and lipids (as of 2002).

Cyanobacterial Toxins
Microcystins are a group of more than 80 cyclic heptapeptide toxins that are produced by cyanobacteria (blue-green algae, such as Microcystis aeruginosa) that bloom in freshwater lakes and ponds. Consumption of contaminated water from these blooms in several countries has resulted in injury to liver and other organs in fish, domestic animals, and humans.

Mushroom Toxins
Most non-edible mushrooms may cause mild discomfort and are not life threatening; however, repeated ingestion of the false morel, Gyromitra esculenta, has been found to cause hepatitis. The toxin gyromitrin is inactivated generally by boiling. Most fatal poisonings related to wild mushrooms are from ingestion of different species within Amanita, Galerina, and Lepiota. The dangerousness of Amanita phalloides and Amanita ocreata is why they are named death cap and death angel. 2 types of toxins, phalloidin and amatoxins, can be found within A. phalloides. Phalloidin is capable of binding actin in muscle cells; however, it is not readily absorbed during digestion, which limits its harmful effects.

There are several toxic, cyclic peptides that occur in various species of wild mushrooms. These mushrooms have been mistaken for edible species, and consumption of them has been responsible for numerous poisonings and deaths over the years, especially in Europe and North America. Of these mushroom species, Amanita phalloides (death cap) has been of greatest concern due to its ability to cause life-threatening toxicity. This mushroom produces several bicyclic heptapeptides known as phallotoxins and octapeptides known as amatoxins. Of these, phalloidin and α-amanitin, respectively, have received the most attention as hepatotoxins.

Hydrazinobenzoic acid is a nitrogen-nitrogen bonded chemical that is present in the cultivated mushroom Agaricus bisporus. This hydrazine derivative causes smooth muscle cell tumors in the aorta and large arteries of mice when administered over the life span of the animals. These tumors have the characteristic appearance and immunocytochemical features of vascular leiomyomas and leiomyosarcomas. Smooth muscle cell lysis with vascular perforation apparently precedes malignant transformation.

Kidney tubular degeneration
Consumption of the mushroom species Cortinarius has been found to cause acute renal failure but different species vary widely in toxicity and, therefore, edibility. In an investigation of a series of 135 poisonings related to Cortinarius ingestion, where death occurred in almost 15% of the cases, renal biopsy showed acute degenerative tubular lesions with inflammatory interstitial fibrosis. Cortinarius orellanus and C. rubellus contain the deadly toxin orellanin, which triggers renal failure.

Parasympathetic Stimulation
Certain mushrooms of the genera Inocybe, Clitocybe, and Omphalatus contain significant amounts of muscarine, which mimics the action of acetylcholine, the principal neurotransmitter in the parasympathetic nervous system. Consumption of any of these species results in extreme parasympathetic activation resulting in miosis, diarrhea, sweating, salivation, lacrimation, urination, bradycardia, and bronchoconstriction.

Tetrodotoxins (TTX)
This was 1st discovered in pufferfish, but it wasn't known until the mid-1980s that pufferfish only get it from bacteria. No animal can make it. TTX is also found in rough-skin newts (Taricha granulosa 14,000 μg, Taricha torusa 3,000 μg California newt). As of 2024, TTX is not known to kill any bacteria. TTX blocks voltage-gated Na channels, which are widespread among mammals. Only some marine invertebrates use only Ca channels instead of Na.

Related: deaths from alligators in Florida.

How many people are killed by alligators in Florida? These data are recorded by the Florida Fish and Wildlife Conservation Commission. They document alligator fatalities since 1948. Majority years are 0, and there has never been more than 3 killed per year. The only years 3 were killed by alligators in Florida are 2006 and 2001. Some recent cases are of extreme age, such as that for an 85 year-old in 2023, or to that of a 2-year in 2016, in Disney World. From 1948, to 2022, totals 26 killed by alligators. The length of the alligators are recorded, they all tend to be over 6 foot in length, with most over 10 foot. An estimated 1.3 million alligators are in Florida and can be found in all 67 counties. Now, while only 26 have died in that period, there are over 100 minor bites and over 300 major bites.

Organic aromatic solvents.

Toxicity and fate of these 4 aromatic solvents.

Benzene undergoes metabolic oxidation by cytochrome P450 enzymes in the liver to form an electrophilic epoxide which can alkylate proteins and DNA. The cytochrome P450 enzyme responsible for hydroxylating benzene is CYP2E1. Benzene is therefore a carcinogen.

Toluene (methylbenzene) is now used as a solvent in place of benzene. Toluene is also oxidized by cytochrome P450 enzymes, but the metabolite produced is less toxic and is rapidly excreted. Toluene is well metabolized, but a portion is still exhaled unchanged. Cytochrome P450s catalyze metabolism of toluene primarily to benzyl alcohol and lesser amounts of cresols. Benzyl alcohol is converted by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) to benzoic acid, which is primarily conjugated with glycine and eliminated in the urine as hippuric acid.

Phenol (hydroxybenzene). Cytochrome P450 converts some benzene to phenol (after an epoxide), which in turn is oxidized to hydroquinone, which can be converted to DNA-reactive metabolites by myeloperoxidase in bone marrow leukocytes and by PHS (Prostaglandin H synthase), also in bone marrow. Myeloperoxidase has also been shown to convert phenol to diols.