Thousands of organic micropollutants and their transformation products occur in water. Although often present at low concentrations, individual compounds contribute to mixture effects. Cell-based bioassays that target health-relevant biological endpoints may therefore complement chemical analysis for water quality assessment. The objective of this study was to evaluate cell-based bioassays for their suitability to benchmark water quality and to assess efficacy of water treatment processes. The selected bioassays cover relevant steps in the toxicity pathways including induction of xenobiotic metabolism, specific and reactive modes of toxic action, activation of adaptive stress response pathways and system responses. Twenty laboratories applied 103 unique in vitro bioassays to a common set of 10 water samples collected in Australia, including wastewater treatment plant effluent, two types of recycled water (reverse osmosis and ozonation/activated carbon filtration), stormwater, surface water, and drinking water. Sixty-five bioassays (63%) showed positive results in at least one sample, typically in wastewater treatment plant effluent, and only five (5%) were positive in the control (ultrapure water). Each water type had a characteristic bioanalytical profile with particular groups of toxicity pathways either consistently responsive or not responsive across test systems. The most responsive health-relevant endpoints were related to xenobiotic metabolism (pregnane X and aryl hydrocarbon receptors), hormone-mediated modes of action (mainly related to the estrogen, glucocorticoid, and antiandrogen activities), reactive modes of action (genotoxicity) and adaptive stress response pathway (oxidative stress response). This study has demonstrated that selected cell-based bioassays are suitable to benchmark water quality and it is recommended to use a purpose-tailored panel of bioassays for routine monitoring.

The toxic alkaloid cylindrospermopsin is produced by a range of cyanobacterial species worldwide. It was first identified in the species Cylindrospermopsis raciborskii from tropical waters, and has since been isolated from four other genera in locations ranging from Israel to Japan. High concentrations of the organisms and toxin have been identified in reservoirs, natural lakes, and rivers in summer in the USA and in Australia. The toxin is a particular problem in drinking water sources as concentrations in the free water are appreciable, so that removal of the filaments during water treatment does not remove the toxin. The toxicity resulting from oral ingestion is seen in the liver, kidneys, stomach, intestine, and white blood cells, with some vascular damage in mice. Gastrointestinal as well as liver injury has been observed in human poisoning. Studies of toxicity in vitro have shown inhibition of protein synthesis. Genotoxicity has also been demonstrated, and there is preliminary evidence for carcinogenicity. A Guideline Value for safe water supply of 1 microg/L has been proposed. Research into toxin measurement techniques and water treatment methods has indicated that effective control measures may be practicable for this toxin in drinking water. Considerably more research is needed to fully define the health risks from this toxin.

Cyanobacterial toxins have caused human poisoning in the Americas, Europe and Australia. There is accumulating evidence that they are present in treated drinking water supplies when cyanobacterial blooms occur in source waters. With increased population pressure and depleted groundwater reserves, surface water is becoming more used as a raw water source, both from rivers and lakes/reservoirs. Additional nutrients in water which arise from sewage discharge, agricultural run-off or storm water result in overabundance of cyanobacteria, described as a ‘water bloom’. The majority of cyanobacterial water-blooms are of toxic species, producing a diversity of toxins. The most important toxins presenting a risk to the human population are the neurotoxic alkaloids (anatoxins and paralytic shellfish poisons), the cyclic peptide hepatotoxins (microcystins) and the cytotoxic alkaloids (cylindrospermopsins). At the present time the only cyanobacteral toxin family that have been internationally assessed for health risk by the WHO are the microcystins, which cause acute liver injury and are active tumour promoters. Based on sub-chronic studies in rodents and pigs, a provisional Guideline Level for drinking water of 1μg/L of microcystin-LR has been determined. This has been adopted in legislation in countries in Europe, South America and Australasia. This may be revised in the light of future teratogenicity, reproductive toxicity and carcinogenicity studies. The other cyanobacterial toxin which has been proposed for detailed health risk assessment is cylindrospermopsin, a cytotoxic compound which has marked genotoxicity, probable mutagenicity, and is a potential carcinogen. This toxin has caused human poisoning from drinking water, and occurs in water supplies in the USA, Europe, Asia, Australia and South America. An initial health risk assessment is presented with a proposed drinking water Guideline Level of 1μg/L. There is a need for both increased monitoring data for toxins in drinking water and epidemiological studies on adverse health effects in exposed populations to clarify the extent of the health risk.

The cyanobacterial toxin cylindrospermopsin (CYN) is a frequent contaminant of freshwaters throughout the world, including those that are sources of drinking water. The first cases of human poisoning attributed to this toxin occurred from a treated drinking water supply in Queensland, Australia, in 1979. The toxin causes extensive damage to the liver, kidneys, spleen, heart, and other organs. It is known to be a potent protein synthesis inhibitor, but there is mounting evidence for genotoxicity and that it metabolizes to even more toxic forms. As part of a risk assessment process leading to a guideline for a safe drinking water level for this toxin, we performed a series of experiments to determine a no-observed-adverse-effect level (NOAEL) for this toxin. In the first trial male mice were exposed to CYN-containing cyanobacterial extract in their drinking water (0-657 microg CYN kg(-1) day(-1)) for 10 weeks. In the second trial mice received purified CYN by daily gavage (0-240 microg CYN kg(-1) day(-1)) for 11 weeks. Body and organ weights were recorded; urine, serum, and hematology analyses were performed; and histopathological examination of tissues was carried out. Body weights were significantly increased at low doses (30 and 60 microg kg(-1) day(-1)) and decreased at high doses (432 and 657 microg kg(-1) day(-1)). Liver and kidney weights were significantly increased at doses of 240 microg kg(-1) day(-1) and 60 microg kg(-1) day(-1), respectively. Serum bilirubin levels were significantly increased and bile acids significantly decreased at doses of 216 microg kg day(-1) and greater. Urine total protein was significantly decreased at doses above 60 microg kg(-1) day(-1). The kidney appeared to be the more sensitive organ to this toxin. If it is assumed that increased organ weights and changes in functional capacity are responses to an underlying toxic effect, then the NOAEL based on this data is 30 microg kg(-1) day(-1), which, with standard calculations and uncertainty factors, provides a proposed guideline safety value of 1 microg/L in drinking water.