The Cyanobacteria or
blue green algae are an ancient and ubiquitous family of photosynthetic
organisms (Chorus 1999, Carmichael 1994, Falconer 1989, NHMRC 1994). Many of these organisms are able to fix
nitrogen, and are therefore an important part of the food chain. The cyanobacteria frequently are found
growing in marine, brackish and fresh waters, including freshwater surface
drinking sources, such as lakes and drinking water reservoirs. Similar to the marine algal blooms,
cyanobacteria periodically will grow exuberantly, known as “blooms.” The reasons for these blooms are not
completely understood, but in some cases they may be related to nutrients added
naturally and through man-made sources such as fertilizer runoff or sewage
(Philipp 1991, Carmichael 1993, Rapala1997, Ling 2000). These blooms can cause significant
environmental impact due to the decrease in oxygen in the water, resulting in
the die-off of fish and other organisms.
Furthermore, again similar to marine algal blooms or red tides, these
blue green algal blooms can produce significant quantities of natural toxins,
for reasons as yet unknown. When they
produce these highly active natural biotoxins, these blue green algal blooms
are known as a “harmful algal bloom (HAB).”
To date at least 12 different species of Cyanobacteria have been shown
to produce toxins, often several different toxins per species (Carmichael
1994). The main toxic cyanobacterial
genera include Anabaena, Aphanizomenon, Nodularia, Oscillatoria,
and Microcystis (Carmichael 1993,
NHMRC 1994, Chorus 1999).
These toxins, along
with those produced by the marine organisms such as dinoflagellates and
diatoms, are extremely toxic to many species.
There is a wide spectrum of blue green algal toxins, predominantly
affecting the nervous, hepatic and dermatologic systems (ie. Neurotoxic,
hepatotoxic and dermatotoxic).
The dermatotoxins
include aplysiatoxins and lyngbyatoxin, and are often reported from marine
cyanobacteria blooms. These are potent
tumor promoters and protein kinase C activators. These toxins can cause severe dermatitis with only skin contact,
as well as gastrointestinal inflammation with oral exposure (Chorus 1999).
The neurotoxins
include: anatoxin a and anatoxin a (S) (both unique to the cyanobacteria), as
well as saxitoxin and neosaxitoxin (also elaborated by marine dinoflagellates
and associated with the human disease paralytic shellfish poisoning or
PSP). Anatoxin a acts like the
neurotransmitter acetylcholine except that it cannot be degraded by
acetylcholinesterase; anatoxin a (S) is a natural organophosphate, binding to
the acetylcholinesterase enzymes; the saxitoxins are sodium channel
blockers. Singly or in mixtures, these
cyanobacterial neurotoxins can cause death within minutes secondary to
respiratory paralysis (Codd 1997, Carmichael 1994, Carmichael 1993).
The hepatotoxins are
cyclic peptides, predominantly microcystins, nodularins, and
cylindrospermopsin. Of note, these
toxins are particularly toxic to the liver in part due to selective transport
mechanisms that concentrate these toxins from the gut and blood into the liver
cells; they damage the liver by deranging the cytoskeletal architecture of the
hepatocytes. Microcystin is also believed
to cause damage to cells' DNA by the activation of endonucleases (Jochimsen
1998). Cylindrospermopsin is a protein
synthesis inhibitor, resulting in wide spread necrosis of the tissues of many
organs. The microcystins and the
nodularins are protein phosphatase inhibitors, as well as being potent tumor
promoters in animals (similar to the carcinogen, okadeic acid, elaborated by
marine dinoflagellates and associated with the human disease diarrheic
shellfish poisoning or DSP). The
microcystins cause liver necrosis leading to death within hours to days (Elder
1993, Carmichael 1994, Humpage 1999, Yu 1995, Ohtani 1992, MacKintosh 1990,
Repavich 1990, NHMRC 1994, Chorus 1999).
At lower doses, enteritis and hepatitis are seen shortly after ingestion
of these toxins.
The same
cyanobacteria species can produce both neurotoxins and hepatotoxins, even
during the same bloom; often the presence of the hepatotoxin is masked by the
premature death of the animal due to the neurotoxin. In addition, there exist other toxins (including
lipopolysaccharides, endotoxins and additional neurotoxins), as well as yet
undescribed cyanobacterial toxins including additional tumor promoters
(Falconer 1989, Codd 1997, Falconer 1994, Falconer 1996, Chorus et al.,2000).
There have been
frequent reports of thirsty domestic animals and wildlife
consuming freshwater contaminated with toxic blue green algal blooms, and dying
within minutes to days from acute neurotoxicity and/or hepatotoxicity
(Jochimsen 1998, Elder 1993, Carmichael 1994, Codd 1997, Mahmood 1988, Carbis
1995, Negri 1995, Repavich 1990). Toxic
blooms of cyanobacteria with associated animal poisonings have been reported in
all continents except Antartica (NHMRC 1994).
Mammals and birds appear to be more susceptible to the blue green algal
toxins than aquatic invertebrates and fish, with some species variability. Prolonged morbidity and mortality have also
been reported in animals exposed to blue green algae in the wild. For example, Carbis et al (1995) followed
sheep exposed to Microcystis aeruginosa
in a lake in Australia for 6 months; there was a 34% mortality over this period
among the exposed sheep without clear etiology even after resolution of the
initial liver toxicity observed during the first 3 weeks.
Experimentally,
acute high dose administration of microcystin can lead to death from
hepatoencepholopathy with in hours, and chronic administration to mice of
sublethal amounts of Microcystis
extracts in drinking water results in increased mortality with chronic active liver
disease, even at fairly low doses and in relatively short time periods (Heinze
1999). Falconer et al (1992) gave intra
peritoneal (ip) injections to mice of the gut and gut contents of boiled edible
mussels from a water bloom of Nodularia in Western Australia. The cell density of the bloom in the water
had been up to 100,000 cells/mL. The ip
injections were lethal secondary to acute (within 24 hours) hepatotoxicity to 1
kg mice at 89 mg dry weight/kg; the Nodularia bloom LD50 was
24.4 mg dry weight/kg. Based on this
research, Falconer et al (1992) concluded that edible mussels should not be
collected for human consumption during a toxic blue green algal bloom.
In laboratory
experimental animals, teratogenic activity has been demostrated with oral
administration of Microcystis extracts;
approximately 10% of otherwise normal neonatal mice had small brains with
extensive hippocampal neuronal damage (Carmichael 1993, Astrachan 1980).
Studies in cultured
cells have also shown tumor promotion, and microcystins are preferentially
taken up by hepatic cells, so that hepatic tumor promotion is likely (Falconer
1996, Carmichael 1994, Carmichael 1993, Sugimura 1986, Humpage 1999, Ito 1997).
As noted above, the microcystins can cause tumor promotion in animals exposed
to chronic low level non-lethal doses.
Nishikawa et al (1992) showed that microcystins are powerful tumor
promoters of hepatic liver tumors in rats mediated through the inhibition of
protein phosphatase type 1 and type 2A activity (Hong-Bing 1996). Lyngbyatoxin A has been shown to be a potent
tumor promoter in a two stage mouse skin carcinogenesis study by Fujiki et al
(1984).
There are relatively
few case reports and even fewer epidemiologic studies of the human health
effects of the blue green algal toxins (Carmichael 1993, Jalaludin 1992,
Falconer 1999, Chorus 1999, Ressom 1994). Humans can be exposed to the
cyanobacteria and their toxins through direct skin contact or by drinking
contaminated waters; other possible routes of exposure include inhalation of
aerosol, consumption of contaminated food, and even through dialysis (Codd
1997, Chorus 1999). Occupational
exposures for fishermen, watermen, and scientists, as well as recreational
exposures for the general public, are both possible (Codd 1997, Baxter 1991,
Philipp 1991).
Seasonal
gastroenteritis has been reported worldwide and may be related to the
consumption of contaminated drinking water (Carmichael 1993, Volterra 1993,
Codd 1984, Falconer 1999). Algal
blooms are known to occur mainly in the late summer and early Fall because
light intensity and temperature are known to play a role in their formation
(Duy 2000).
There are individual
case reports of persons exposed through swimming to blue green algal blooms
with skin irritation and allergic reactions (both dermatologic and respiratory)
with continued positive reaction on skin testing (Falconer 1989, Carmichael
1993, Falconer 1999, Hashimoto 1974, NHMRC 1994, Chorus 1999). In particular, urticaria (hives), blistering
and even deep desquamation of skin in sensitive areas like the lips and under
swimsuits has been reported, especially with Lyngbya majuscula in tropical areas. Consumption of or swimming in cyanobacterial toxin-contaminated
waters has also yielded increased case reports of gastointestinal symptoms,
especially diarrhea (Billings 1981, Probert 1995). Turner et al (1990) reported
2 cases of pneumonia in healthy army recruits following probable inhalation
from a canoe on waters with a blue green algal bloom of Microcystis aeruginosa; 16 other exposed recruits reported of a
variety of gastrointestinal (hepatoenteritis), dermatologic and respiratory
complaints (Turner 1990).
In addition to
gastrointestinal and dermatologic symptoms, eye irritation, asthma, and “hay
fever symptoms” have been reported repeatedly with contaminated recreational
water exposure in the US, Canada, UK, and Australia. Actual Type I hypersensitivity to cyanobacteria (as detected via
skin patch testing and bronchial provocation testing) has also been
reported. Airborne cyanobacteria and
cyanobacteria present in house dust have been investigated as causes of
naso-bronchial allergies (NHMRC 1994).
In general, the few
epidemiologic studies available have been performed after a significant
community exposure event.
Some of the first
reports of adverse health effects from exposure to the blue green algae were by
Veldee (1931) when an estimated 9000 persons out of a population of 60,000 in
Charleston (West Virginia) reported acute gastroenteritis after a period of low
rain fall and reportedly contaminated drinking water; other outbreaks were seen
along the Ohio River in the same year (Tisdale 1931). Lipp and Erb (1976) reported that 62% of the population of 8000
of Sewickley (Pennsylvannia) suffered from acute gastroenteritis; the reservoir
was found to be contaminated by Schizothrix
calcicola. In 1988, severe
gastroenteritis was reported in Brazil after the flooding of a newly
constructed dam and reservoir with 2000 cases and 88 deaths (particularly
children) over a 42 day period; cases were restricted to the areas supplied by
drinking water from the reservoir and those ill had only consumed boiled water
with negative bacterial and viral cultures. Anabaena
and Microcystis blooms were present
in the reservoir at the time of the flood (Chorus 1999, Teixera 1993).
With a long history
of episodes of possible adverse health effects in animals and humans in
Australia, Pilotto et al (1997) studied the effects in South Australia of
exposure to blue green algae as a result of recreational water activities. They used a serial symptom questionnaire on
a large sample (777 “exposed” and 75 “unexposed”), as well as water sampling
for cyanobacteria and toxin. Although
there was no difference in the type and quantity of symptoms reported acutely,
the Investigators found a significant trend to increasing symptom occurrence
with duration of exposure, and a symptom dose response that correlated with
exposure to 5000 cells per ml for more than one hour; however, symptoms did not
correlate with the presence of hepatotoxins in the water. The Investigators suggested that the current
safety threshold for exposure of 20,000 cells per mL may be too high. El Saadi et al (1995) performed a case
control study in 11 South Australian towns along the Murray River, a
cyanobacterial historic epicenter, using gastrointestinal and dermatologic cases
and controls with similar town distributions.
Persons who drank the river water, even after chlorination, were
significantly more likely to have gastrointestinal symptoms, while those using
river water for domestic purposes were significantly more likely to have both
gastrointestinal and dermatologic symptoms, compared with persons using
rainwater. Furthermore, there was a
correlation with report of symptoms and mean log cyanobacterial cell counts.
Liver enzymes,
especially GGT, have also been found to be increased after consumption of drinking
water contaminated with Microcytis toxins in Australia. Other Australian episodes have included a
severe outbreak of hepatoenteritis after drinking water with a novel
cyanobacterial toxin contamination on Palm Island in Queensland (Australia)
(Falconer 1983, Carmichael 1993, Bourke 1983, Probert 1995, El Saadi 1995,
Chorus 1999). In this particular
episode, the drinking water reservoir had been dosed with copper sulphate to
remove a persistent cyanobacteria bloom of Cylindrospermopsis
raciborskii, leading to lysis of the algal cells and substantial release of
toxins into the drinking water.
Reportedly some of the children were critically ill with severe
hepatoenteritis and kidney failure, and 150 persons (140 children) were
ultimately hospitalized. Subsequent research identified the cytotoxic
cylindrospermopsin as well as other toxins as the probable cause of the
outbreak. In another study by Falconer (1994) in different area of Australia
with a similar situation of cyanobacterial toxin contamination of a drinking
water supply after the use of copper sulfate, clinical liver function data were
examined. There was a statistically
significant increase in the liver enzyme GGT in persons drinking from the
contaminated reservoir only during the period of bloom and cell lysis compared
to all others in the same area with different water supplies. GGT has also been used as an effective
marker for liver injury in experimental animal studies with microcystin
exposure (Falconer 1994a, Chorus 1999).
A recent and
infamous outbreak occurred in Brazil when over 100 patients on kidney dialysis
developed visual disturbances, nausea and vomiting, followed by 50 deaths from
acute liver failure. Apparently the
dialysis water had been contaminated with blue green algal toxins from the
reservoir supplying the clinic; microcystins produced by cyanobacteria were
subsequently identified in the water and in the human tissues. Inadequate water
treatment procedures and the failure of the clinic staff to change filters
usually used in preparation of the local water for the dialysis procedure were
two factors leading to the contamination and the subsequent deaths (Jochimsen
1998). There is some disagreement
between studies over whether the water the clinic received had been chlorinated
prior to its being trucked to the clinic (Pouria 1998, Jochimsen 1998); as far
as can be determined, it seems that the water had not been chlorinated, only
flocculated. A second dialysis clinic
supplied by the same reservoir received water which went through the entire
process of treatment including chlorination; no illness was reported at the
second clinic.
The following is a
table showing dates and studies of a list of known human exposures to
cyanobacterial toxins.
Table 1. Reported Human Outbreaks associated with Cyanobacteria.
|
Study Year |
Location |
Population Affected |
Exposure Route |
References |
|
1930-31 |
West Virginia |
9000/60,000 |
Unknown |
Veldee 1931 Tisdale 1931 |
|
1959 |
Saskatchewan |
12 people |
Swimming |
Dillenberg 1960 |
|
1960-65 |
Harare, Zimbabwe |
Children |
Drinking water |
Zilberg 1966 |
|
1975 |
Sewickey, PA |
62%0f 8000 |
Drinking water |
Lippy 1976 |
|
1979 |
Palm Island, Aust. |
139 children |
Drinking water |
Byth 1980 |
|
1980-81 |
Pennsylvania/Nevada |
>100 people |
Swimming, water
skiing |
Carmichael 1985 |
|
1989 |
Staffordshire,UK |
18 recruits ill |
Swimming, canoeing |
Turner 1990 |
|
1992 |
Outback Aust. |
Unknown |
Drinking |
Hayman 1992 |
|
1992 |
River Murray,
Aust. |
26 people |
Drinking |
El Saadi 1993 |
|
1994 |
China |
High rates liver
cancer |
Drinking |
Yu 1994 |
|
1996 |
Caruaru, Brazil |
63 deaths |
Dialysis |
Jochimsen 1998 |
(adapted from Duy 2000)
Perinatal Effects
Pilotto et al (1999)
attempted to look at perinatal outcome and the possible relationship with
cyanobacterial contamination of drinking water in an ecological study. The investigators examined the perinatal
outcome (prematurity, low birth weight and very low birth weight, and
congenital defects detected at birth) for 32,700 singleton live newborns of
non-Aboriginal mothers from 1992-94 in South Eastern Australia; exposure data
was based on weekly cell counts from 29 drinking water storage sites for the
156 towns in the same area (percentage of time occurrence and average cell
counts), and the mother’s address at the time of the newborn’s birth. This work was based on the concern raised by
laboratory animal studies showing impaired fetal development (especially
neurologic) and low birth weight after exposure to untreated reservoir water
sampled during a bloom, as well as fetal mortality, small fetuses, and
congenital malformation with injection of microcystins into pregnant rats. Although there were statistically
significant associations with particular exposure levels and particular birth
outcomes (especially the very low birth weight category and exposure during the
first trimester with percentage of time occurrence, and congenital
malformations with average cell counts), there was an overall lack of dose
response; similar results were seen for the whole gestation and the last 12
weeks of gestation. The authors
concluded that their ecological study did not provide clear evidence for an
association. However, as they pointed
out, there were no individual drinking water exposure data and in areas with
frequent known cyanobacterial contamination, systematic avoidance of drinking
water can be common.
Cyanobacteria-like Bodies and Traveler's
Diarrhea
There have been a
host of articles concerning cyanobacteria as a source of chronic relapsing
diarrhea, especially in travelers (both immunocompromised and not) to
developing nations; the illness seems to be associated with the organisms
rather than the toxins, and furthermore may actually be a separate group of
organisms that are cyanobacterium-like
(Soave 1986, Anon 1991,Hale 1994, Long 1990, Shlim 1991). These may, in fact, be a separate class of
organisms referred to as Cyclospora
(Bendall 1993). Some researchers have
even postulated a role for the blue green algae as a carrier or reservoir of
the bacteria Vibrio cholera, the
latter responsible for the human bacterial disease cholera (Islam 1994, Chorus
1999).
Yu et al and others
(1989a, 1989b, 1995, Junshi 1990, Chorus 1999) have studied the possible
relationship between the consumption of surface drinking water (pond, ditch,
river vs well water or deep well) and an increased risk for primary hepatic
cancer (as well as chronic gastrointestinal diseases) in China. China has an extremely high rate of primary
liver cancer, previously associated with hepatitis B and aflatoxin exposures
(Yu 1995). However, reportedly large
epidemiologic studies in 1973 and in 1983 were performed in Haimen, Quidong and
Nanhui Counties (Guangxi province, China) to evaluate drinking water source,
exposure and risk of primary hepatic cancer.
These studies found not only a significantly increased risk of primary
liver cancer in areas of high surface drinking water consumption (SIR=2.6)
compared with areas of non-surface drinking water consumption (SIR=0.34), but
also a strong dose response relationship.
Reportedly, changing from pond/ditch to deep well (at least 200 m) water
in Quidong lead to a stabilization with subsequent decrease of the mortality
rate from primary hepatic cancer, while in Haimen where there was no change,
the liver cancer mortality rates continued to increase during the same time
period; in an area where there was a mixture of well and river water, there was
no significant change in the mortality rate during this time period. Monitoring studies using a sensitive ELISA
test from microcystins revealed high levels of microcystins, as well as the
presence of blue green algae, in the surface as opposed to other drinking water
sources (Ueno 1996). On average the
surface water sources contained 130 pg/ml of microcystins compared to the well
samples (the vast majority less than 49 pg/ml) (Falconer 1996).
Ito et al (1997) was
able to induce neoplastic nodular formation in mouse liver by repeated ip
injections of sublethal dose (20 ug/kg) microcystin LR without the use of an
initiator; however, repeated oral administration of a sublethal dose (80 ug/kg)
did not result in nodular formation.
Ueno et al (1996) postulated that the combined effects of a potent
hepatocarcinogen such as aflatoxin from the diet with intermittent microcystin
intake through drinking water could explain the high rates of primary liver
cancer associated with surface drinking water source in this area. Yu
(1995) reported on the results of experiments with male F-344 rat
exposed to different mixtures of alflatoxin, deep well water, and pond/ditch
water after partial hepatectomy. The
results showed significant increase in the gamma-glutamyl transferase (GGT)
liver enzyme in rats exposed to alfatoxins and pond/ditch water compared to the
other groups including control. Yu (1995) postulated that mycrocystins are
promoters with a synergistic effect between microcystins and alflatoxins for
primary hepatocellular carcinoma. As a
result of this work, the Chinese government has reportedly urged their people
to use deep water wells or minimally granular activated carbon filtration for
their drinking water, as well as other interventions (ie. hepatitis B vaccine
and shifting to rice instead of corn to avoid aflatoxins), to prevent primary
liver cancer in China.
Fleming et al.(2000)
performed an ecological study of Florida using Geographic Information Systems
to examine the risk of primary liver cancer as related to proximity to a
surface water treatment plant.
Residence within the service area of a surface water treatment plant was
found to be a significant risk factor for primary liver cancer as compared with
those living adjacent to surface treatment plant areas, i.e. areas served with
water from deep wells. This study had
no way of assessing individual exposure to cyanobacteria and the increased risk
was not beyond the normal range of liver cancer rates for the state as a whole.
In addition to liver
cancer, there is recent research suggesting a possible role for the blue green
algal toxins and colon cancer. Humpage
(2000) examined the formation of aberrant crypt foci (ACF) in mice as modified
by exposure to microcystins. He found
while the number of crypts did not increase the depth (or total area) of each
crypt was increased and two overt colonic tumors were observed in the treated
mice. Because ACF's are a known
precursor to colon cancer in humans this study indicates that microcystins
could potentially "stimulate preneoplastic colon tumour growth.
In general, the only
treatment available for exposure to the blue green algal toxins is supportive
medical treatment after complete removal from exposure (Chorus 1999). If the exposure was oral, administration of
activated carbon to decrease gut absorption may be efficacious if given within
hours of exposure. Artificial
respiration with exposure to the neurotoxins (such as saxitoxin) should also be
considered (NHMRC 1994). Based on past
outbreaks, monitoring of volume, electrolytes, liver and kidney function should
all be considered in the case of acute gastroenteritis associated with some of
the blue green algal toxins.
Although no specific
treatments exist for the cyanobacterial toxins, Nagata et al (1995) have
created at least 6 monoclonal antibodies (Mabs) to microcystin LR isolated from
Microcystis aeruginosa. These MABs
showed a protective effect on the hepatotoxicity and inhibition of protein phosphatase
of microcystin LR in vitro and in vivo in a dose dependent manner.
Of note, activated
carbon given to experimental animals pre-treatment was not an effective
antidote for preventing effects from subsequent microcystin administration (Mereish 1989, Beasley 1989). Hermansky et al (1991) used a variety of
chemoprotectants in pre treatment prior to exposure of experimental mice to a
lethal dose of microcystin LR (100 ug/kg); phenobarbital (but not the calcium
channel blockers or water soluble anti-oxidants) provided partial protection, while
the hydrophobic anti-oxidants (such as Vitamin E and silymarin), glutathione
active compounds (such as glutathione), and immunosuppressive agents (such as
rifampin and cyclosporin A) provided significant protection if given 48 hours
prior to exposure to microcystin in laboratory animals.
Monitoring
Due to their
significant potential toxicity and the lack of specific treatment modalities
available, the best treatment for the health effects of the blue green algae is
the prevention of exposure to the blue green algal toxins. Therefore, monitoring for these toxins in
surface drinking and recreational waters, as well as other exposure venues, is
crucial in the prevention of human health effects from the blue green algal
toxins (NHMRC 1994, Chorus 1999). For example, recent monitoring studies in
Florida (SJRWMD 2000) of recreational and surface drinking water supplies with
algal blooms, have found 87/167 samples (75 individual water bodies) with
significant levels of toxin producing blue green algae. All of these samples had positive
identification of blue green algal toxins with 80% lethal in mice. Monitoring should include visual monitoring
for blooms, cell counts and identification, and toxin identification and
toxicity testing; other monitoring indices have also been used, including
phosphorus levels in the water, as well as surveillance of health effects in
human and animal populations (Chorus 1999).
Falconer (1994a)
recommended 20,000 cells/ml sampled in the top meter of open water as the
maximum safe level of cyanobacteria in recreational waters. Nevertheless, Falconer warned that if the
bloom is toxic, swallowing or bathing in these waters should be considered
hazardous. Chorus et al (1999) used
data from Pilotto et al (1997) to derive a guideline for acute non-cumulative
health effects resulting in discomfort, not serious health outcomes. Significantly increased odds ratios for eye
irritation, rash and gastrointestinal symptoms were associated with water
contact for more than 1 hour above 5000 cyanobacterial cells/mL and for persons
bathing in water with 5000-20,000 cells/mL.
Pilotto et al (1997) suggested that the current safety threshold for
exposure of 20,000 cells per mL might be too high based on their results.
With monitoring programs, response programs must be established
based on the results of regular monitoring.
Australia and the UK have attempted to develop such monitoring and
response programs for surface drinking water sources (NHMRC 1994, Jones 1993,
Burch 1993) with alert levels and corresponding responses based on the number
of cyanobacterial cells per ml in routine sampling. For example, Burch et al (1993) and Chorus et al (1999) propose Alert Levels 1 (cells 500-2000
cells/mL or offensive odor or taste), Level 2 (potentially toxic cells
2000-15,000 cells/mL for 2-3 consecutive samples or confirmed toxic bloom,
persistent odor/taste, and obvious bloom), and Level 3 (persistent high numbers
widespread, toxic, cells >15,000 cell/mL for toxic species, persistent
bloom, and only partial success of control measures). Level 1 is associated with increased monitoring; Level 2 results
in media information release and consultation with health authorities as well
as control measures (such as booms, activated carbon); and Level 3 results in
the same actions as Level 2 as well as possible declaration of water as unsafe
for consumption and provision of safe drinking water alternatives after
consultation with health authorities. Subsequent
health surveillance and evaluation may be necessary, especially if exposure is
suspected. Separate guidelines should
be developed for recreational and occupational use of potentially contaminated
surface waters based on the probability and severity of potential health effect
development from exposure to cyanobacterial toxins (Bartram and Rees 1999,
Chorus 1999). In areas of endemic toxic
blue algal blooms, public education and awareness plans should be considered
(Chorus 1999), including issues such as avoidance of occupational and recreational
exposure, description of possible health effects, and warnings that boiling
water will not destroy the cyanobacterial toxins.
In general, the
information available is considered inadequate for the calculation of a
tolerable daily intake (TDI) for the majority of the cyanobacterial toxins
(Chorus 1999). In particular, data are
not available on metabolic disposition, acute and subacute toxicity, repeated
administration, developmental effects, and carcinogenicity and
genotoxicity. In such cases, a TDI can
be derived using the LOAEL or NOAEL divided by appropriate safety and
uncertainty factors, as described in the Addendum to the World Health
Organization Guidelines for Drinking Water Quality (WHO 1998).
A study by Fawell et
al (1994, Chorus 1999) derived a NOAEL of 40 ug/kg body weight per day in a
mice gavage study with a 1000 fold uncertainty factor (intra-species,
inter-species, limitations of database) resulting in a provisional TDI of 0.04
ug/kg body weight per day of microcystin LR.
Falconer (1994a, 1994b) used the following 10 fold safety factors: use
of subchronic data applied to lifetime risk, use of pig data applied to humans,
use of intra-human variation, and tumor promotion risk; therefore he applied a
10,000 overall safety factor. He used
subchronic exposure data in pigs that showed a lowest observed effect level of
280 ug/kg/day, and an assumption of 2 liters water intake per day by a 60 kg
adult. This led him to a provisional
TDI of 0.067ug/kg body weight per day.
The WHO (1998) adopted a provisional guideline (TDI x body weight x
proportion of total daily intake of the contaminant ingested from drinking
water divided by the daily water intake in liters) for microcystin LR of 1.0
ug/L. Special exposure circumstances
(such as dialysis water) may necessitate even stricter control levels (Chorus
1999).
Drinking Water
Barriers that reduce exposure of
drinking water to cyanobacterial blooms at “critical control points” are the
first step in prevention, especially for surface drinking water sources (Chorus
1999, Hitzfeld, 2000). Of note,
algaecides, especially copper sulfate, can be added to water supplies to control
toxic blooms, but acutely this leads to cell lysis and substantial release of
the toxins into the water, as well as the possibility of copper toxicity, thus
exacerbating the potential for health effects (Chorus 1999, Carmichael 1993,
Falconer 1999, NHMRC 1994). Therefore,
removal of intact cells is recommended (Chorus 1999). Activated carbon, chlorination and ozonation in conjunction with
other water treatment practices have all been used in the treatment of drinking
water supplies with potential blue green algal contamination with results varying
based on concentration and time (NHMRC 1994, Jones 1993, Chorus 1999). Chlorine has been found to oxidize
cylindrospermopsin, but not microcystins (Hitzfeld, 2000). The use of activated carbon treatment during
active blooms will decrease but not necessarily eliminate levels of
cyanobacterial toxins in drinking water (Chorus 1999; J Burns SJRWMD, FL,
verbal communication). This is of
particular concern when the toxin is a potential carcinogen, since low level
chronic exposure may predispose to the development of cancer (Chorus 1999,
Carmichael 1993, NHMRC 1994). Changing
drinking water sources to groundwater sources should be explored (Chorus
1999). Future possible treatments
involve ultraviolet light, titanium dioxide and filtration with an ultrafine
membrane to remove whole algal cells Hitzfeld, 2000).
Recreational Water
The recreational use
of water bodies experiencing an algal bloom is becoming an increasing concern
as intranasal exposure to toxins has been found to be similar to intraperitoneal
exposure (Chorus, 2000). Because
unattractive "scums" and foul smells are not always present during
toxic algal blooms, people, especially children and infants, are at risk of
acute exposure to toxins while swimming, water skiing and even showering or cleaning
with untreated water. Chorus notes that
dogs in particular can consume large quantities of water while playing and
grooming themselves after water contact.
She recommends that organized water events be cancelled when blooms
occur and that people shower with treated water after swimming in water not
known to be safe. Because toxins
degrade naturally after their release, the presence of a known toxin in water
is not necessarily a problem. In fact,
some 75% of all cyanobacteria sampled contain toxins. It is the huge conglomerations of cells that present a concern
for recreational water use, i.e. the formation of large blooms in late summer
and early fall(Chorus 2000).
There is a
possibility of exposure to these toxins also through the consumption of
contaminated food (Prepas 1997, Falconer 1992, Vasconcelos 1999). Microcystin
has been shown to be toxic to a range of zooplankton (Duy et. al., 2000), and
there has been concern that the toxin may accumulate in the bodies of fish
destined for consumption by humans.
For example, based on examination of the gut contents of mussels during
a bloom of Microcystis in Australia,
Falconer et al (1992) concluded that edible mussels should not be collected for
human consumption during a toxic blue green algal bloom. Vasconcelos (1999)
studied fish and shellfish in Portugal, looking particularly for the toxin
microcystin-LR. The author found that
mussels and clams concentrated the toxin in their gut, but seemed unaffected by
the toxin themselves. Both carp and
crayfish were also found to have detectable levels of toxin in their muscle as
well as in the viscera. The fact that
toxin was found in fish not associated with a specific bloom event indicates
that human diets rich in fish and shellfish may pose a threat of chronic low
level exposure.
Use of potentially
contaminated water for irrigation is controversial since not only can the
irrigation aerosol cause potential harm through skin and respiratory contact,
but there is limited evidence that terrestrial plants, including food crops,
can take up microcystins (MacKintosh 1990, Chorus 1999, Codd, 1999). Codd (1999) hypothesized that washing
produce would not be sufficient to remove toxins, but did not in fact evaluate
the effects of any control measures on the contaminated produce.
Cyanobacteria
(particularly Spirulina and Aphanizomenon
flos-aquae) have been used as food and possible therapeutic agent in the
US, Canada, Mexico, and India (NHMRC 1994, Chorus 1999). Although most cyanobacteria species are
nontoxic, the etiology and conditions for toxicity are not well understood, nor
have the health risks and benefits of long term consumption of cyanobacteria
been studied. Gilroy (2000) conducted a
study of commercially sold blue green algae supplements after a documented
bloom in a lake in Oregon where algae is routinely gathered for sale. He found that 85/87 of the samples tested
positive for toxins, most notably microcystins. The toxins were heterogeneously distributed through the products,
indicating a wide variation in consumer exposure. The study concluded that some form of monitoring is needed to
ensure the safety of these products, perhaps encouraging also the use of
cultured algae as opposed to that gathered from the "wild".
In summary, blue
green algae are ubiquitous in surface waters throughout the year in subtropical
climates such as Florida, and they are associated with frequent toxic
blooms. Both occupationally and
recreationally humans can be exposed via dermal and aerosol routes, as well as
through consumption of drinking water and possibly contaminated foods. The human health effects associated with the
blue green algal toxins are predominantly by inference from their known health
effects in a wide variety of organisms, especially neurotoxicity,
hepatotoxicity and tumor promotion.
Short term and long
term health effects have not been thoroughly evaluated in persons with
occupational, recreational and consumption exposure to blue green algae and their
toxins (NHMRC 1994). Countries which do not have adequate supplies of treated
water for their populations are at particular public health risk associated
with blue green algal toxins, as are also children infants and animals. Current drinking water treatment practices
in the US do not regularly monitor, or necessarily remove these toxins from the
drinking water since this would involve extremely expensive measures (J Burns,
SFWMD, verbal communication, Falconer 1989, Volterra 1993, Falconer 1999, Heinze
1999). Even with treatment, low level
chronic exposure to the carcinogenic hepatotoxins are possible in persons
consuming drinking water derived from surface water drinking plants in Florida
and other parts of the US.
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