Introduction to Toxicology
EV 460/660 & BI 460/660
Fall 2014
Some Selected Examples of Toxins
Bacterial Toxins
1.
include some of the most toxic substances known:
botulinum toxin, diptheria toxin, tetanus toxin
2.
some beneficial -- ex. insecticidal uses of Bacillus thuringiensis, BT-engineered crops
-- ex antiparasitic action of avermectins from Streptomyces avermitilis
3.
structures are often proteins or mucoproteins
Protozoa (protista and algae) Toxins
1.
saxitoxin – produced by dinoflagellates (Gonyaulax spp.), mollusks ingest the dinoflagellates via filter
feeding and concentrate the toxin; problem during “red tides”, results in paralytic shellfish poisoning,
neurotoxic and cardiotoxic
2.
ciguatoxin – produced by dinoflagellate (Gambierdiscus toxicus), another food chain poison, reported in
over 400 species of fish, results in ciguatera, neurotoxic and cardiotoxic
Mycotoxins (molds, fungi, mushrooms)
1.
highly diverse chemical structures
2.
mushrooms – ex. Amanita phalloides – the death cap, Amanita ocreata – the death angel, hepatoxic
3.
ergot alkaloids – ergotamine, produced by Claviceps spp., mold on stored grains, historical human
outbreaks – St. Anthony’s fire, neurotoxin, vascular toxin, abortifacient, structurally related to lysergic
acid
4.
aflatoxins – common mold of stored grains & peanuts, produced by Aspergillus spp., demonstrated
carcinogenicity, difficult problem for human and animal food supply
5.
trichothecenes – family of compounds, moldy grains, produced by Fusarium and Myrothecium spp.,
hematopoietic and vascular toxicity
Vascular Plant Toxins
1.
Common plant toxins of use and abuse:
cocaine
nicotine
caffeine
morphine
2.
Some plants commonly reported to Poison Control Centers:
Philodendron
Aloe
Jade plant
String-of-pearls
Wandering Jew
Pothos
Swedish ivy
Poinsettia
Spider plant
Schefflera
Dieffenbachia
Holly
Asparagus fern
Rhododendron
3.
Some major categories of poisonous compounds found in plants:
Alcohols
Amines
Alkaloids
Glycosides
Polypeptides
Oxalates
cannabinoids
Honeysuckle
Coleus
Ficus
Oleander
Hibiscus
Phenols
Resins
Metals
4.
Some specific examples of plant toxins:
plant
castor bean (Ricinus communis)
poison ivy (Toxicodendron radicans)
stinging nettle (Urtica urens)
foxglove (Digitalis purpurea)
oleander (Nereum oleander)
mistletoe (Phoradendron tumentosum)
several (Strychnos spp.)
larkspur (Delphinium barbeyi)
locoweed (Astragalus lentiginosus)
hellebore (Veratrum californicum)
toxic compound
toxic effect
ricin
GI toxicity
urushiol
contact dermatitis
histamine, ACh, 5-HT contact dermatitis
digitalis
cardiotoxin
oleandrum
cardiotoxin
phoratoxin
cardiotoxin
curare
neurotoxin
methyllycaconitine
neurotoxin
swainsonine
neurotoxin
cyclopamine
teratogen
Animal Toxins
1.
representatives found in nearly all animal phyla; used both defensively (protection from predators and
aggressors) and offensively (food-getting and facilitation of digestion), may result from food-chain
accumulation (ex. Ciguatera fish)
2.
“venomous” usually applied to species producing toxin in specialized exocrine secretory gland or cells
and capable of delivering the toxin by biting or stinging often via specialized body parts.
“poisonous” usually applied to animals whose tissues are, in part or whole, toxic and lack specialized
structures for delivery of the poison.
3.
diverse chemical structures and often mixtures: proteins (both high and low molecular weight), amines,
lipids, steroids, aminopolysaccharides, quinines, 5-HT, glycosides, and others
Arthropoda
1.
approximately 1 million arthropod species, but only a few thousand are sufficiently venomous to be
dangerous to humans, arthropods are responsible for more human poisonings than all other phyla
combined
2.
highly diverse chemical structures of the toxins
3.
Spiders – over 200 species responsible for significant toxic bites of humans, familiar examples include:
widow spiders – 5 species, including the black widow spider – venom is a mixture of proteins and is a
neurotoxin; violin spiders – 100 species, including the brown recluse – venom is a complex mixture of
proteins and other constituents and is a hemotoxin, vascular toxin, and causes tissue necrosis
4.
Scorpions – 75 of the 800 species are sufficiently toxic to be of human concern, high incidence of stings
and fatalities in areas such as the southwestern United States and Mexico.
5.
Hymenoptera (bees, wasps, hornets) – responsible for more deaths in the United States than all the
bites and stings of all other venomous creatures; particularly dangerous to sensitive individuals that
may show acute anaphylactic reactions, venoms are complex mixtures of proteins (both enzymatic and
non-enzymatic) and amines.
Porifera (Sponges)
1.
compounds appear to be defensive secretions against predators, human poisoning occurs primarily
due to skin abrasions and produces contact dermatitis and pain, rarely systemic
Cnidaria (Coelenterates) – hydroids, jellyfish, sea anemones, corals
1.
stinging unit of cnidarians is the nematocyst- used both defensively and in food-getting, over 9000
species with nematocyts, approximately 100 species have been involved in human injuries, the
Portuguese man-of-war jellyfish is a familiar example
Echinodermata – starfish, sea urchins, sea cucumbers
1.
venom apparatus is the pedicellaria, primary human poisoning is through puncture wounds; some
human injuries, but rarely fatal
Mollusca – see also paralytic shellfish poisoning
1.
two (Gastropoda and Cephalopoda) of the five classes contain the majority of venomous species
2.
Gastropoda (snails and slugs) – most dangerous gastropods are in the genus Conus (approximately
400 species) largely restricted to tropical and subtropical marine habitats, cone shells primarily use
venom as an offensive, food-getting weapon, the venoms have not been well characterized, but appear
to be a relatively low molecular weight proteins with paralytic, neurotoxic effects, some impacts on
humans, but usually not fatal
3.
Cephalopoda (cuttlefishes, squids, nautiluses, and octopods) – venom is an offensive, food getting
weapon and is an integral part of the digestive process (e.g., venom also acts as a digestive enzyme),
venoms are highly complex mixtures of proteins, carbohydrates, and amines, some impacts on
humans, but usually not fatal
Fishes – see also ciguatera
1.
includes both poisonous (> 700 species) and venomous (>200 species) species
2.
Tetrodotoxin (TTX) as an example toxin
-- present in puffers, ocean sunfishes, and porcupinefishes (also in some salamanders and one
octopus), commonly known as puffer or fugu poisoning, highest concentration of the toxin is found in
liver and gonads, fugu chefs are licensed in Japan - despite this there are numerous deaths annually, a
potent neurotoxin that has become a research tool of neurobiologists
3.
venomous fishes – include stingrays, scorpionfishes, stonefishes, toadfishes, some sharks and
catfishes, and other species, diverse chemical structures to the toxins, venomous species are often
non-migratory, slow swimmers found in protected habitats (rocks, reefs, kelp beds), venoms are
primarily used as defensive weapons, human injury is common, but fatalities are rare.
Amphibians
1.
approximately 2600 species divided into Anura (frogs and toads) and Urodela (salamanders and
newts), many species are known to be poisonous, but very few are of danger to humans
2.
toxins are produced in cutaneous secretory glands for defensive protection against predators, some
evidence for anti-bacterial actions also; diverse chemical structures
3.
some example toad toxins are: bufotenin, bufotenidin and bufoviridin, these are vascular, cardiac, and
neurotoxins
4.
among frogs, species of Phyllobatis and Dendrobates are the most poisonous
5.
Batrachotoxin (BTX) – an example frog poison, very highly toxic alkaloid, a potent neurotoxin that has
become a research tool of neurobiologists
Reptiles
1.
perhaps the most studied group, maybe due to deep-rooted human emotional responses to venomous
snakes.
2.
approximately 3,500 snake species, 400 snake species are sufficiently venomous to be dangerous to
humans
3.
a selective, partial list of venomous snake groups:
Elapidae – cobras, kraits, mambas, coral snakes
Hydrophiidae – sea snakes
Viperidae – old world vipers and adders
Crotalidae – rattlesnakes, water moccasins, copperheads, fer-de-lances, bushmasters
Colubridae -- boomslang
4.
snake venoms are complex mixtures, chiefly proteins, a number of which have enzymatic activity, some
venoms are rich in proteases and responsible for marked tissue destruction, generally the actions are
as hemotoxins, vascular toxins, and neurotoxins
5.
lizards – two venomous species – the Gila monster (Heloderma suspectum) and the beaded lizard
(Heloderma horridum), less dangerous than believed – slow moving and nocturnal, relatively few
human injuries
Birds
1.
toxic quail ???, myths regarding raptors
Mammals
1.
relatively few species are poisonous or venomous
2.
Australian duckbill platypus (Ornithorphynchos anatinus) males have venom glands associated with
spurs on hind legs, venom is typically used in intraspecific competition, a few human injuries have been
described.
3.
Spiny anteaters (Tachyglossus spp. and Zaglossus spp.) have venom apparatus similar to the platypus
4.
the short-tailed shrew has toxic and anti-coagulant secretions present in saliva, the venom has not
been well characterized, but is thought to resemble the neurotoxin of elapid snakes
5.
polar bears, walrus, and some seal species have livers that are very high in vitamin A, toxic
hypervitaminosis A from ingestion of liver has been reported, other body tissues are safe