Samenvatting Toxins in Amphibians & Reptiles
H1: Introduction and overview of toxic taxa
Studying animal toxins benefits many areas of biology & applied science (such as physiology, biochemistry, ecology,
evolution, & medicine) while also drawing on knowledge from these same fields to advance toxin research itself.
Example: 3D structure of Erabutoxin b => neurotoxin produced by black-banded sea krait.
1.1: Intro
1.1.1: What is a toxin?
Theophrastus of Hohenheim (1493 – 1541) definition = All things are poison & nothing is without poison. Only dose
makes something not to be poison. (AKA dose that matters!)
Wikipedia definition for
• Poison = Any chemical substance that is harmful or lethal to living organisms
• Toxin = Naturally occurring organic poison produced by metabolic activities of living cells or organisms
These definitions emphasize potential negative effect of substance & differ from currently used definitions in
scientific literature.
Ecological definition = Molecule used by organism to cause biochemical effect in another, in function of predation,
defense or competition. => This definition emphasizes molecules functional value & doesn’t put any restrictions on
• range of taxa that produce toxins or against which toxins are used
• origin of toxin (is it obtained exogenously or produced endogenously)
• type or severity of biochemical effect in “receiving” organism
Example of competition: Cane toad tadpoles produce waterborne chemical cues that suppress viability of
conspecifics during embryonic development. Brief (72 h) exposure to these cues in egg & post-hatching
phases reduced survival rates & growth of larvae. Body sizes at metamorphosis (ca 3 weeks later) were
almost 2x smaller in tadpole-exposed larvae, than in control larvae.
Revised definition:
• Biological toxin or biotoxin = Substance produced by living organism, capable of causing dose-dependent
pathophysiological injury to itself or another living organism.
• Environmental toxin = naturally occurring substance in environment that is not produced by organism, capable
of causing dose-dependent pathophysiological injury to living organism (such as arsenic, mercury, lead).
• Anthropogenic toxin or “toxicant” = Substance produced by humans that otherwise does not occur in
environment, capable of causing dose dependent pathophysiological injury to living organism (such as DDT,
dioxin, PCBs).
Toxins are bioactive molecules (term used in pharmacology field).
Bioactive molecule = molecule with biological effect on living matter (cells, tissues or organisms) => This definition
does not specify if effect is beneficial or adverse. Bioactivity is used in terms of desired effect of potential drug
candidate. Example of bioactive molecules: toxins, drugs, …
Toxicology = Scientific discipline dealing with adverse effects of chemicals on living organisms, communities,
ecosystems. => Study of symptoms, mechanisms, treatments & detection of poisoning.
Toxinology = Scientific discipline dealing all toxic substances produced by or accumulated in living organisms (poison,
venom or toxins of microbial, plant & animal), their properties, & biological significance for involved organisms. =>
Study of biological toxins & their aspects (pathophysiology, treatment, ecology, evolution).
,1.1.2: Venom vs. Poison
Venom = Toxin or mixture thereof, injected into circulatory system (such as blood stream or lymphatic system) of
animal via specialized venom delivery structure (such as fangs, beaks, spines, stinger)
• Venoms may have predatory & defense function
• Derived words = “venomous”, “envenomation”, “venom glands” => “venom” & “venomous” only apply to
animals. Plants are called poisonous & not venomous, even if they use spines to inject toxins.
Poison = Toxin or mixture thereof, passively administered through epithelia (such as skin, gills, lungs, intestines) by
absorption, ingestion or inhaling.
• Poisons in biology mostly have defensive function
• Derived words = “poisonous”, “poisoning”, “poison glands”
Definitions by
• Fry et al.
o Venom = Secretion produced in specialized cells in 1 animal that is delivered to target animal through
infliction of wound & that disrupts normal physiological or biochemical processes in receiving animal to
facilitate feeding, defense or competition by producing animal.
o Poison = Secretion delivered to target animal in passive way (by epithelial absorption), without inflicting
wound & in function of defense.
• Nelsen et al.
o Venom = Toxic substance (comprised of 1 or more toxins) causing dose-dependent physiological injury that
is passively or actively transferred from 1 organism to internal milieu of another via delivery mechanism &
mechanical injury.
o Poison = Toxic substance (comprised of 1 or more toxins) causing dose-dependent physiological injury that
results in self-induced toxicity (such as bacterial endotoxins) or is passively transferred without delivery
mechanism from 1 organism to internal milieu of another organism without mechanical injury, usually
through ingestion, inhalation, or absorption across body surface.
Toxungen = Toxic substance (comprised of 1 or more toxins) causing dose dependent physiological injury. It’s actively
transferred via delivery mechanism from 1 organism to external surface of other organism without mechanical injury.
Example: Sprayed or projected secretions to fend off attacking predator.
Examples: Venomous or Poisonous?
• Venomous
o Irukandji jellyfish (nematocysts to inject
venom through skin)
o Blue-ringed octopus (delivers venom via
bite)
o Bulldog ant (has stinger)
o Flower urchin (pedicellariae inject venom
when touched)
• Poisonous
o Sea apple
o Pyrenean brook salamander, Spanish rib
salamander or Fire salamander (skin
secretions)
,1.2: Poison/venom in Animal Kingdom
Poison & venom systems are widespread in Animalia & occur in modern representatives of
major animal lineages.
Schematic tree of venomous life in animal kingdom shows frequency with which venom
systems are found in animal kingdom. Colored branches highlight animal lineages that
include members with venom systems & their role
• Red branches = predatory
• blue branches = defensive
• green branches = intraspecific competition
1.2.1: Porifera (sponges)
Species are laced with abrasive needle-like strands of spicules that contain irritating toxins.
1.2.2. Cnidaria
Anthozoa (corals & sea anemones) & Medusozoa (jellyfish) have
cnidocytes. It works as follow:
1. contact between tentacle & prey.
2. cnidocyte (= cells housing nematocysts & coiled thread) is triggered by this contact
3. Rapid discharge of thread, that is connected to nematocyst (= structure with venom
organelles).
4. Thread penetrates prey & delivers venom.
1.2.3: Worms
Platyhelminthes (flatworms) => In Planicera multitentaculata, has neurotoxin Tetrodotoxin (TTX) in various tissues,
including eggs. TTX used to immobilize gastropod prey, by enveloping victim & secreting TTX (= poison for predation).
Annelida (Ring worms) => Polychaeta (Bristle worms) are predatory bloodworms, that possess everting proboscis
with mineralised jaws connected to venom glands.
Chaetognatha (Arrow worms) => Several species are known to use TTX to paralyze prey.
Nemertea (Ribbon worms) = Carnivorous nemerteans use proboscis to entangle or stab prey. In some species (such
as Paranemertes peregrina) this structure secretes paralyzing toxins, including TTX.
1.2.4: Mollusca
Gastropoda:
Most cone snails (genus Conus) use venomous harpoon to capture & paralyze
prey. Some Conus species engulf their fish prey & release “nirvana cabal” (=
mixture of toxins). Several of these are insulin analogs, causing rapid depletion of
sugar levels in prey’s blood.
Cephalopoda:
Cuttlefish produces similar proteins in its posterior glands, indicating that many cephalopods may be
venomous. Example: Blue ringed-octopus have posterior “salivary” glands that guide toxins to beak.
, 1.2.5: Arthropoda
Arachnida (spiders & scorpions):
From left to right:
• Sidney funnelweb spider (Atrax robustus) => mygalomorph spider
• Redback (Latrodectus hasselti) => araneomorph spider
• Deathstalker (Leiurus quinquestriatus)
Myriapoda:
Centipedes have powerful fangs connected to venom glands. Example: Amazonian giant centipede
Insects:
Hymenoptera => especially fire ants, bees, wasps have stings or bite
Lepidoptera (butterflies & moths) => Some genera are known to be poisonous & some
do mimicry. Example: Caterpillars of Saturniid moth genus Lonomia are covered by urticating
venomous bristles, causing “lonomiasis” (= hemorrhagia, renal failure, hemolysis) & may be lethal.
Neuroptera (net-winged insects) => Antlion (doodlebug) larvae stabs with their large fangs, trapped insects
& inject paralyzing/digestive venom.
Hemiptera (“true bugs”) => Predatory bugs that stab their prey with proboscis & inject venom.
Example: Assassin bug (Zelus sp.) killing small bee
Crustacea:
Speleonectes tulumensis => 1st known venomous crustacean, which has sophisticated
venom system that produces cocktail of toxins (Shown in purple is cephalon, ductus,
gland, tentorium, reservoir, maxillule & pharynx).
Echinodermata:
From left to right:
• Sea apple (Paracucumaria tricolor) => sea cucumber species that
releases toxin upon stress.
• Crown-of-thorns starfish (Acanthaster planci) => Venomous spines.
• Flower urchin (Toxopneustes pileolus) => venomous pedicellariae (= flower-
like structures with venom glands injecting venom when touched).
1.2.6: Vertebrates
Chondrichthyes (cartilagenous fishes) => Examples (from L to R):
• Chimaera monstrosa (Holocephali) => has serrated spine
anterior to 1st dorsal fin.
• Heterodontus portusjacksoni (Elasmobranchi) => Has spine
anterior to each dorsal fin.
• Stingrays (Elasmobranchi) => Has serrated caudal barb & when barb is withdrawn from wound,
laceration results & venom is injected. Can cause sharp pain, swelling, fever, nausea, tremors.
H1: Introduction and overview of toxic taxa
Studying animal toxins benefits many areas of biology & applied science (such as physiology, biochemistry, ecology,
evolution, & medicine) while also drawing on knowledge from these same fields to advance toxin research itself.
Example: 3D structure of Erabutoxin b => neurotoxin produced by black-banded sea krait.
1.1: Intro
1.1.1: What is a toxin?
Theophrastus of Hohenheim (1493 – 1541) definition = All things are poison & nothing is without poison. Only dose
makes something not to be poison. (AKA dose that matters!)
Wikipedia definition for
• Poison = Any chemical substance that is harmful or lethal to living organisms
• Toxin = Naturally occurring organic poison produced by metabolic activities of living cells or organisms
These definitions emphasize potential negative effect of substance & differ from currently used definitions in
scientific literature.
Ecological definition = Molecule used by organism to cause biochemical effect in another, in function of predation,
defense or competition. => This definition emphasizes molecules functional value & doesn’t put any restrictions on
• range of taxa that produce toxins or against which toxins are used
• origin of toxin (is it obtained exogenously or produced endogenously)
• type or severity of biochemical effect in “receiving” organism
Example of competition: Cane toad tadpoles produce waterborne chemical cues that suppress viability of
conspecifics during embryonic development. Brief (72 h) exposure to these cues in egg & post-hatching
phases reduced survival rates & growth of larvae. Body sizes at metamorphosis (ca 3 weeks later) were
almost 2x smaller in tadpole-exposed larvae, than in control larvae.
Revised definition:
• Biological toxin or biotoxin = Substance produced by living organism, capable of causing dose-dependent
pathophysiological injury to itself or another living organism.
• Environmental toxin = naturally occurring substance in environment that is not produced by organism, capable
of causing dose-dependent pathophysiological injury to living organism (such as arsenic, mercury, lead).
• Anthropogenic toxin or “toxicant” = Substance produced by humans that otherwise does not occur in
environment, capable of causing dose dependent pathophysiological injury to living organism (such as DDT,
dioxin, PCBs).
Toxins are bioactive molecules (term used in pharmacology field).
Bioactive molecule = molecule with biological effect on living matter (cells, tissues or organisms) => This definition
does not specify if effect is beneficial or adverse. Bioactivity is used in terms of desired effect of potential drug
candidate. Example of bioactive molecules: toxins, drugs, …
Toxicology = Scientific discipline dealing with adverse effects of chemicals on living organisms, communities,
ecosystems. => Study of symptoms, mechanisms, treatments & detection of poisoning.
Toxinology = Scientific discipline dealing all toxic substances produced by or accumulated in living organisms (poison,
venom or toxins of microbial, plant & animal), their properties, & biological significance for involved organisms. =>
Study of biological toxins & their aspects (pathophysiology, treatment, ecology, evolution).
,1.1.2: Venom vs. Poison
Venom = Toxin or mixture thereof, injected into circulatory system (such as blood stream or lymphatic system) of
animal via specialized venom delivery structure (such as fangs, beaks, spines, stinger)
• Venoms may have predatory & defense function
• Derived words = “venomous”, “envenomation”, “venom glands” => “venom” & “venomous” only apply to
animals. Plants are called poisonous & not venomous, even if they use spines to inject toxins.
Poison = Toxin or mixture thereof, passively administered through epithelia (such as skin, gills, lungs, intestines) by
absorption, ingestion or inhaling.
• Poisons in biology mostly have defensive function
• Derived words = “poisonous”, “poisoning”, “poison glands”
Definitions by
• Fry et al.
o Venom = Secretion produced in specialized cells in 1 animal that is delivered to target animal through
infliction of wound & that disrupts normal physiological or biochemical processes in receiving animal to
facilitate feeding, defense or competition by producing animal.
o Poison = Secretion delivered to target animal in passive way (by epithelial absorption), without inflicting
wound & in function of defense.
• Nelsen et al.
o Venom = Toxic substance (comprised of 1 or more toxins) causing dose-dependent physiological injury that
is passively or actively transferred from 1 organism to internal milieu of another via delivery mechanism &
mechanical injury.
o Poison = Toxic substance (comprised of 1 or more toxins) causing dose-dependent physiological injury that
results in self-induced toxicity (such as bacterial endotoxins) or is passively transferred without delivery
mechanism from 1 organism to internal milieu of another organism without mechanical injury, usually
through ingestion, inhalation, or absorption across body surface.
Toxungen = Toxic substance (comprised of 1 or more toxins) causing dose dependent physiological injury. It’s actively
transferred via delivery mechanism from 1 organism to external surface of other organism without mechanical injury.
Example: Sprayed or projected secretions to fend off attacking predator.
Examples: Venomous or Poisonous?
• Venomous
o Irukandji jellyfish (nematocysts to inject
venom through skin)
o Blue-ringed octopus (delivers venom via
bite)
o Bulldog ant (has stinger)
o Flower urchin (pedicellariae inject venom
when touched)
• Poisonous
o Sea apple
o Pyrenean brook salamander, Spanish rib
salamander or Fire salamander (skin
secretions)
,1.2: Poison/venom in Animal Kingdom
Poison & venom systems are widespread in Animalia & occur in modern representatives of
major animal lineages.
Schematic tree of venomous life in animal kingdom shows frequency with which venom
systems are found in animal kingdom. Colored branches highlight animal lineages that
include members with venom systems & their role
• Red branches = predatory
• blue branches = defensive
• green branches = intraspecific competition
1.2.1: Porifera (sponges)
Species are laced with abrasive needle-like strands of spicules that contain irritating toxins.
1.2.2. Cnidaria
Anthozoa (corals & sea anemones) & Medusozoa (jellyfish) have
cnidocytes. It works as follow:
1. contact between tentacle & prey.
2. cnidocyte (= cells housing nematocysts & coiled thread) is triggered by this contact
3. Rapid discharge of thread, that is connected to nematocyst (= structure with venom
organelles).
4. Thread penetrates prey & delivers venom.
1.2.3: Worms
Platyhelminthes (flatworms) => In Planicera multitentaculata, has neurotoxin Tetrodotoxin (TTX) in various tissues,
including eggs. TTX used to immobilize gastropod prey, by enveloping victim & secreting TTX (= poison for predation).
Annelida (Ring worms) => Polychaeta (Bristle worms) are predatory bloodworms, that possess everting proboscis
with mineralised jaws connected to venom glands.
Chaetognatha (Arrow worms) => Several species are known to use TTX to paralyze prey.
Nemertea (Ribbon worms) = Carnivorous nemerteans use proboscis to entangle or stab prey. In some species (such
as Paranemertes peregrina) this structure secretes paralyzing toxins, including TTX.
1.2.4: Mollusca
Gastropoda:
Most cone snails (genus Conus) use venomous harpoon to capture & paralyze
prey. Some Conus species engulf their fish prey & release “nirvana cabal” (=
mixture of toxins). Several of these are insulin analogs, causing rapid depletion of
sugar levels in prey’s blood.
Cephalopoda:
Cuttlefish produces similar proteins in its posterior glands, indicating that many cephalopods may be
venomous. Example: Blue ringed-octopus have posterior “salivary” glands that guide toxins to beak.
, 1.2.5: Arthropoda
Arachnida (spiders & scorpions):
From left to right:
• Sidney funnelweb spider (Atrax robustus) => mygalomorph spider
• Redback (Latrodectus hasselti) => araneomorph spider
• Deathstalker (Leiurus quinquestriatus)
Myriapoda:
Centipedes have powerful fangs connected to venom glands. Example: Amazonian giant centipede
Insects:
Hymenoptera => especially fire ants, bees, wasps have stings or bite
Lepidoptera (butterflies & moths) => Some genera are known to be poisonous & some
do mimicry. Example: Caterpillars of Saturniid moth genus Lonomia are covered by urticating
venomous bristles, causing “lonomiasis” (= hemorrhagia, renal failure, hemolysis) & may be lethal.
Neuroptera (net-winged insects) => Antlion (doodlebug) larvae stabs with their large fangs, trapped insects
& inject paralyzing/digestive venom.
Hemiptera (“true bugs”) => Predatory bugs that stab their prey with proboscis & inject venom.
Example: Assassin bug (Zelus sp.) killing small bee
Crustacea:
Speleonectes tulumensis => 1st known venomous crustacean, which has sophisticated
venom system that produces cocktail of toxins (Shown in purple is cephalon, ductus,
gland, tentorium, reservoir, maxillule & pharynx).
Echinodermata:
From left to right:
• Sea apple (Paracucumaria tricolor) => sea cucumber species that
releases toxin upon stress.
• Crown-of-thorns starfish (Acanthaster planci) => Venomous spines.
• Flower urchin (Toxopneustes pileolus) => venomous pedicellariae (= flower-
like structures with venom glands injecting venom when touched).
1.2.6: Vertebrates
Chondrichthyes (cartilagenous fishes) => Examples (from L to R):
• Chimaera monstrosa (Holocephali) => has serrated spine
anterior to 1st dorsal fin.
• Heterodontus portusjacksoni (Elasmobranchi) => Has spine
anterior to each dorsal fin.
• Stingrays (Elasmobranchi) => Has serrated caudal barb & when barb is withdrawn from wound,
laceration results & venom is injected. Can cause sharp pain, swelling, fever, nausea, tremors.
