The blue green algae or cyanobacteria represent a diverse group of organisms that produce potent natural toxins. There have been case reports of severe morbidity and mortality in domestic animals through drinking water contaminated by these toxins. Microcystins, in particular, have been associated with acute liver damage and possibly liver cancer in laboratory animals. Although, there has been little epidemiological research on toxin effects in humans, a study by Yu (1995) found an association between primary liver cancer and surface water. Surface water drinking supplies are particularly vulnerable to the growth of these organisms; current US drinking water treatment practices do not monitor or actively treat for blue green algal toxins including the microcystins.
After a monitoring survey in Florida found organisms and microcystins (among other cyanobacterial toxins) in surface water drinking sources, a pilot ecological study was performed using a Geographic Information System (GIS) to evaluate the risk of primary hepatocellular carcinoma (HCC) and proximity to a surface water treatment plant at cancer diagnosis. The study linked all HCC cancers diagnosed in Florida from 1981 to 1998 with environmental databases. A significantly increased risk for HCC with residence within the service area of a surface water treatment plant was found compared to persons living in areas contiguous to the surface water treatment plants.
However, this increased risk was not seen in comparison to persons living in randomly selected ground water treatment service areas or compared to the Florida cumulative incidence rate for the study period, using various comparison and GIS methodologies. Furthermore, these findings must be interpreted in light of significant issues of latency, high population mobility, and the lack of individual exposure information. Nevertheless, the issue of acute and chronic human health effects associated with the consumption of surface waters possibly contaminated by blue green algal toxins merits further investigation.
Primary hepatocellular carcinoma (HCC), a malignant epithelial tumor, is the most prevalent type of liver cancer in the world. It is one of the three leading causes of cancer mortality, accounting for 25 million deaths annually world wide, with a ratio of mortality to incidence of 0.98:1 (London and Pisani). HCC is particularly a problem in the developing countries of the world where 81% of the worlds cases are found ( Parkin and Parkin). For individuals living in developed countries versus developing countries, the age-standardized incidence rates are 7.6/100,000 and 17.9/100,000 for males, and 2.6/100,000 and 6.2/100,000 for females, respectively ( Parkin et al., 1999a). Although, the incidence of HCC is relatively low in the US, it has been increasing (Martin and El). In Florida, since 1981 to 1998, there was a significant increase in the average annual HCC incidence rate ( Shea et al., 2001)). In particular, the average Florida annual HCC incidence rates among male and female hispanics and blacks have been consistently twice the rate of white males and females as standardized rate ratios (SRRs; Shea et al., 2001).
During this time period, the incidence rate in hispanic males (3.29/100,000) approached twice the rate reported in white males (1.82/100,000), while black males (3.86/100,000) had greater than twice the rate of white males; in females, the rates in both hispanic and black females (1.23/100,000 and 1.18/100,000, respectively) were approximately twice those of white females (0.6/100,000). The cyanobacteria or blue green algae are an ancient and ubiquitous family of organisms, many with photosynthetic abilities (Chorus; Carmichael; Falconer and NHMRC). The cyanobacteria frequently are found growing in marine, brackish and fresh waters, including freshwater surface water drinking sources, such as lakes and drinking water reservoirs.
Similar to marine algal blooms, such as red tides, cyanobacteria periodically exhibit significantly increased reproductive rates and total population biomass known as a bloom. The reasons for these cyanobacteria blooms are not completely understood, but most cases are related to the addition of nutrients via runoff ( Philipp; Carmichael and Rapala). Large bloom events are classified as harmful algal blooms if they cause negative environmental impacts such as:
- Organismal mortality (fish, crabs, clams, etc.) due to a significant decrease in the oxygen content in the water via bloom respiration or degradation;
- Loss of submerged aquatic vegetation due to an increased absorption of sunlight that reduces light penetration necessary for maintenance/growth;
- A decrease in ecosystem stability by interfering in food web dynamics by displacing normal phytoplankton species; and
- The production of highly active natural compounds (cyanotoxins) that are known to be toxic or allergenic in nature ( Chorus; NHMRC and Carmichael.)
There is a wide spectrum of cyanotoxins (blue green algal toxins) that predominantly affect the nervous, hepatic and dermatologic systems (i.e. neurotoxic, hepatotoxic, and dermatotoxic). 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 liver cells; they damage the liver by altering the cytoskeletal architecture of the hepatocytes (Chorus; Carmichael; NHMRC; Elder; Humpage; Ohtani; MacKintosh and Repavich). In experimental animals, Yu (1995) and others ( Ito and Ueno) have shown that microcystins are promoters, with a possible synergistic effect between microcystins and alflatoxins, for HCC. Yu (1995) and others ( Yu and Yu; Junshi et al., 1990) have studied the possible relationship between the consumption of surface water (pond, ditch, river versus well water or deep well) and an increased risk for primary hepatic cancer in China.
China has an extremely high rate of primary liver cancer, previously associated with hepatitis B and aflatoxin exposures ( Yu and Chorus). However, large epidemiologic studies found not only a significantly increased risk of primary liver cancer in areas of high surface water consumption (standardized incidence ratio, SIR=2.6) compared with areas of non-surface 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 lead to a subsequent decrease in the mortality rate from primary hepatic cancer in one Chinese province; in another province where there was no change in drinking water source, the liver cancer mortality rates continued to increase during the same time period. Monitoring studies using a sensitive enzyme linked immunosorbent assay (ELISA) for microcystins revealed detectable levels of these hepatotoxins, as well as the presence of blue green algae, in the surface waters as opposed to other drinking water sources (Ueno and Falconer).
Recent data suggest that another hepatotoxic cyanobacteria, cylindrospermopsin, may also be associated with tumorigenesis ( Falconer and Humpage, 2001, Humpage et al., 2000). Although, the World Health Organization, (WHO, 1988) adopted a provisional guideline for microcystin-LR in drinking water of 1.0 ?g/l, blue green algae and their toxins are rarely monitored in US surface water drinking supplies. Furthermore, the removal of the organisms and their toxins is difficult and expensive; the use of activated carbon treatment during active blooms will decrease, but not necessarily eliminate, levels of cyanobacterial toxins in drinking water (Chorus and Bartram, 1999). At the present time, the Florida aquifer is the major source for drinking water in the state, however, with Floridas ever increasing population in conjunction with the limitations of the Florida aquifer, the pressure to find alternate sources of high quality drinking water is increasing.
Currently, over 10% of drinking water in Florida is from surface water sources with projected significant increases. Large freshwater surface water bodies are the most easily accessible and can provide substantial volumes of water, however, these water bodies are breeding grounds for toxic cyanobacteria, including the hepatotoxic microcystins and cylindrospermopsins. Recent monitoring studies in Florida (Williams et al., 2001. Williams, C.D., Burns, J., Chapman, A., Flewelling, L., Pawlowicz, M., Carmichael, W., 2001. Assessment of Cyanotoxins. In: Florida's Lakes, Reservoirs, and Rivers. Cyanobacteria Survey Project, Harmful Algal Bloom Task Force, SJRWMD, Palatka, FL.Williams et al., 2001) of recreational and surface water drinking supplies, found that 87/167 (54%) samples, from 75 individual water bodies, contained significant levels of potentially toxic blue green algae, including species that are known to produce microcystins.
Ninety percent of these samples were positively identified as containing blue green algal toxins, with 80% lethality in mice. Among the 18 surface waters serving as water sources for drinking, 12 of the surface water drinking sources tested to date have been found to have toxic blue greens producing microcystins in samples prior to drinking water treatment. Furthermore, samples taken after regular water treatment were found to contain microcystins in the post-treatment drinking water at 7 of the 16 plants, at levels greater than the WHO recommended provisional guideline. In summary, short term and long term health effects have not been thoroughly evaluated in persons with exposure to blue green algae and their toxins (NHMRC, 1994).