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Cyanobacterial Toxins in Florida’s
Freshwater
Center for Risk Analysis and
Management
USF College of Public Health
Introduction
• Cyanobacteria (blue-green algae) are
found in freshwater sources, such as
ponds, lakes, rivers and streams.
• Discharge of nutrients into the water can
cause eutrophication, and promote
cyanobacterial growth.
• During their growth phases some
species of cyanobacteria can produce
toxins.
Introduction
• The toxic effects and the target organs
vary greatly between the toxins.
• Livestock and wildlife may become ill, as
can recreational water users.
• Agents used to kill cyanobacterial
blooms can result in the release of
toxins into the water, due to cell lysis.
Introduction
• Surface water will be an increasing
source of Florida’s drinking water in the
future.
• Filtering the cyanobacteria from
drinking water does not remove free
toxins, but is necessary to prevent cell
lysis from later treatments.
• Water suppliers can employ UV light,
ozone or chlorine to break down toxins.
Introduction
• Boiling drinking water does not appear
to significantly break down toxins, and
could lyse any cyanobacteria from
unfiltered water.
• Metabolites and breakdown products of
these cyanobacterial toxins have not
been studied extensively.
Cylindrospermopsin
Cylindrospermopsin
• Cylindrospermopsis raciborskii,
Umezakia natans and Aphanizomenon
ovalisporum produce this alkaloid during
growth phases.
• It is a hepatotoxin, with a five day
median lethal dose (LD50) in mice
(intraperitoneal injections) of 200 mg/kg
and a one day LD50 of 2 mg/kg.
Cylindrospermopsin
• Cylindrospermopsin has a tricyclic
guanidine moiety bridged to
hydroxymethyl uracil.
• A deoxy- analog of cylindrospermopsin,
which is also frequently found, is much
less toxic.
• The mechanism of toxicity involves the
inhibition of protein synthesis.
Cylindrospermopsin
• A study in mice suggests that oxidation
by cytochrome P450 is a necessary step
in the bioactivation of
cylindrospermopsin.
• The heightened cytochrome P450
activity in mice relative to humans may
explain the severe hepatotoxicity in
mice.
Cylindrospermopsin
• C. raciborskii is found at depths of six to
eight feet, as are most water intakes.
• It is recommended that alternative water
sources be used for up to a week after
blooms subside, if algaecides are used.
• Treatment of a C. raciborskii bloom in
Australia with copper sulfate lysed cells
and poisoned 149 people.
Cylindrospermopsin
• A number of cases of acute liver failure
occurred in a Brazilian dialysis center,
where the water source contained
cylindrospermopsin and microcystins.
• Pending further review, the World Health
Organization recommended a range of
1-13 mg/L for cylindrospermopsin.
Cylindrospermopsin
• Relatively low chlorine concentrations
(< 1 mg/L) have been found sufficient to
degrade cylindrospermopsin.
• Organic matter tends to consume
chlorine, requiring more chlorine to
effectively degrade cylindrospermopsin.
Cylindrospermopsin
• Titanium dioxide has been found to
catalyze the UV-mediated degradation
of cylindrospermopsin.
Microcystins
Microcystin-LR
Microcystins
• Microcystins are a grouping of over 50
hepatotoxins with highly similar
monocyclic heptapeptide structures.
• There are a number cyanobacterial
genera that produce microcystins,
including Microcystis, Oscillatoria,
Anabaena and Nostoc.
• Microcystis aeruginosa is the best
studied microcystin producing species.
Microcystins
• The most commonly studied and most
prevalent member of this group is
microcystin-LR (leucine and arginine are
the variable amino acids).
• Microcystin-LR has LD50 values in mice
and rats ranging from 36 to 122 mg/kg by
a number of routes, including inhalation
of aerosols.
Microcystins
• Microcystins can inhibit protein
phosphatases, with a reported 50%
inhibition at 3 mg/L for microcystin-LR.
• The only direct associations between
microcystins and human deaths involved
the 43 hepatitis fatalities at a dialysis
clinic in Brazil, and possibly a similar
incident in Portuguese clinic.
Microcystins
• Symptoms of microcystin poisoning
include diarrhea, vomiting, piloerection,
pallor and weakness.
• The liver is the target organ of
microcystins, with cytoskeletal damage,
necrosis and blood pooling.
• In vitro blebbing of hepatocytes was
reported with microcystins.
Microcystins
• Primary degradation of microcystin-LR
at low levels (10mg/L) in water occurs in
less than one week.
• Sunlight was observed to decompose
the toxin in roughly ten days.
• Microcystins –LR and –RR were
degraded in minutes by UV light with
wavelengths of 238-254 nm.
Microcystins
• Chorine or calcium hypochlorite levels of
1 mg/L degrade 95% of microcystins.
• The World Health Organization
established a recommended limit of 1
mg/L for microcystin-LR.
• Higher concentrations of other
microcystins may be acceptable,
depending on toxicities relative to
microcystin-LR.
Other Toxins
• Anatoxin-a is a neurotoxin in some species of
Anabaena, Cylindrospermopsis, Plankthorix,
Aphanizomanon and Microcystis.
• Anatoxin-a is a muscle depolarizer with LD50
values of 1 to 10 mg/kg in different species.
• No human deaths have been associated with
anatoxin-a.
• High doses caused hydrocephaly in rats.
Other Toxins
• Anatoxin-s, found in Anabaena flos-aquae
and Anabaena lemmermanii, is the only
known naturally occurring organophosphate.
• Intraperitoneal dosages at or above 4 mg/kg
of A. flos-aquae were toxic in rats.
• Rats displayed salivation, lacrimation,
incontinence, fasciculation, convulsion,
paralysis and death within 2 to 20 minutes.
• A. flos-aquae is used as a dietary supplement.
Other Toxins
• Saxitoxins are carbamate alkaloids
found in marine dinoflagellates and in
Anabaena circinalis, Cylindrospermopsis
raciborskii and Lyngba wollei.
• Sodium channel blocking can be used in
assays that can detect as low as 2 mg/L.
• The main concern with saxitoxins is that
concentration in marine fish can cause
paralytic shellfish poisoning.
Conclusions
• There are a variety of toxins that can
originate from cyanobacteria.
• The primary toxins of concern, based on
human and animal data are
cylindrospermopsin and microcystins.
• These toxins may potentially cause
adverse health effects depending upon
the amount, frequency and duration of
exposure.