Health risks of micropollutants - the need for a new approach.

Micropollutants in water provide a challenge to both science and society. The final consideration is to understand whether they are harmful to human health or to aquatic life and to determine what actions should be taken. The numbers of substances that are being identified requires a new approach to risk assessment and to solving the problem based on proper prioritisation of the needs for more targeted and multidisciplinary research delivering high quality data. The concept of threshold of toxicological concern has been applied to food and could usefully be applied to water. However, this approach also needs to be combined with practical and pragmatic assessments of the behaviour of substances in water and their removal by drinking water treatment. Such an approach provides a bridge from problem identification to problem solving.

Oestrogens and oestrogenic activity in raw and treated water in Severn Trent Water.

Sewage effluent discharged to surface water has been shown to contain human hormones, particularly oestrogens, and synthetic chemicals which may be able to disrupt the endocrine system. Since many surface waters which receive sewage effluent are subsequently used as drinking water sources, it is important to demonstrate that treated drinking water is not contaminated. Oestrogenic activity in rivers and drinking water in the region of Severn Trent Water was studied using a combination of bioassay, to integrate exposure over time, and advanced chemical analysis. There was little or no evidence of substances that were oestrogenic, even in waters receiving significant amounts of sewage effluent. Oestrogenic activity, as measured in the rainbow trout vitellogenin assay, was seen at the Tame/Trent confluence but this activity was relatively weak. There was no activity detected at raw water intakes and no hormones or substances that are oestrogenic were detected in the final drinking water.

The toxicity of cyanobacterial toxins in the mouse: I microcystin-LR.

Blooms of cyanobacteria or blue-green algae are known to have caused poisoning in fish, waterfowl, animals and man. One of the toxins responsible for this is the hepatotoxin microcystin-LR which has been found to occur in blooms present intermittently in sources used for domestic water supplies. Three sets of experiments were undertaken to investigate the acute toxicity of microcystin-LR in mice and rats by the oral and intraperitoneal routes, the potential for effects on foetal development in the mouse, and the effects of repeated oral dosing over 13 weeks in the mouse. The results of this work were as follows: (1) Microcystin-LR is 30-100 times less toxic via oral ingestion than via intraperitoneal injection; (2) Microcystin-LR is not a selective developmental toxicant in the mouse. There was a No Observed Adverse Effect Level (NOAEL) of 600 microg kg(-1) bodyweight per day given on days 6-15 of pregnancy for any form of developmental toxicity; (3) There was a clear NOAEL for tissue damage in the liver of 40 microg kg(-1) bodyweight per day of microcystin-LR. Using this data, a value of 1 microg l(-1) microcystin-LR would be an appropriate guideline value for drinking water.

The toxicity of cyanobacterial toxins in the mouse: II anatoxin-a.

Blooms of cyanobacteria are known to have caused poisoning in fish, waterfowl, animals and man. One of the low molecular weight toxins responsible for this is the neurotoxin anatoxin-a which has been detected in reservoirs used for domestic water supplies. While the acute behaviour of this alkaloid is clear, there is uncertainty regarding the effects on man of ingestion of anatoxin-a at low levels over longer periods. In order to assess this risk, a series of in vitro and in vivo experiments were undertaken to investigate the pharmacology, subacute toxicity, and the teratogenicity of anatoxin-a in the mouse. The results of this work were as follows: (1) Pharmacological screening studies confirmed that anatoxin-a is a potent nicotinic agonist which can produce neuromuscular blockade and death by respiratory arrest. Recovery from a single sub-lethal dose is rapid and complete; (2) Repeated sub-lethal oral administration over 28 days in the mouse did not produce any reliable evidence of treatment-related toxicity; (3) From a preliminary screening study anatoxin-a does not appear to be a developmental toxicant in the mouse. These results indicate that a guideline value for anatoxin-a in drinking water of 1 microg l(-1) would provide an adequate margin of safety.

DNA oxidation by potassium bromate; a direct mechanism or linked to lipid peroxidation?

Following incubation of calf thymus DNA with potassium bromate (KBrO3) and glutathione (GSH), a statistically significant increase in the concentration of 8-oxodeoxyguanosine (8-oxodG) relative to deoxyguanosine was measured. This was GSH-dependent and was associated with loss of GSH during incubation. In contrast, 8-oxodG was not found to be elevated significantly in either total tissue DNA or mitochondrial DNA isolated from Sprague-Dawley rat kidney perfused in situ with KBrO3 (5 mM) for 15 min or 1 h. There was also no associated increase in the level of renal lipid peroxidation or reduced or oxidised GSH. Following intraperitoneal administration of KBrO3 to Sprague-Dawley rats, a dose of 100 mg/kg (maximum tolerated) gave evidence for oxidative stress in the kidney at 24 h as indicated by a significant increase in lipid peroxidation (P < 0.05) and oxidised GSH (P < 0.05). This was associated with a greater than 2-fold, significant (P < 0.01) increase in the level of 8-oxodG in kidney total DNA and a 57% (not statistically significant) increase in kidney mitochondrial 8-oxodG. Pretreatment of rats with diethylmaleate (DEM) to deplete GSH, elevated the toxicity of 100 mg/kg KBrO3. However, at a dose of 20 mg/kg, no change in any of the parameters indicative of kidney oxidative stress (including indicators of oxidative DNA damage; 8-oxodG or etheno-DNA adducts, which can be produced by lipid peroxides) was seen either with or without DEM pretreatment with the exception of a small but statistically significant (P < 0.05) increase in mitochondrial 8-oxodG when KBrO3 was given following DEM pretreatment. DNA oxidation in the kidney is therefore not inhibited by GSH depletion (contrasting with in vitro findings) and requires a sustained exposure at a near-toxic concentration of KBrO3 which is associated with lipid peroxidation and GSH oxidation. The results do not support a role, in rat kidney, of a direct, GSH-mediated mechanism for KBrO3-induced DNA oxidation as seen in vitro.

Derivation of acceptable concentrations for the protection of aquatic organisms.

Derivation of quality standards to protect aquatic ecosystems demands a minimum set of toxicity data to allow the risk assessor to take some account of: (1) variable responses to toxicants; (2) variable environmental characteristics; (3) interactions between duration of exposure and effects; and (4) ecological significance of impacts. Extrapolation from limited experimental data to predict a concentration protective in diverse ecosystems can employ either statistical models (consistent but rather rigid and may not protect all species) or empirical factors (more flexible and possibly more protective, but require expert judgment in their application). However derived, quality standards must be tailored to the specific conditions of release and environmental fate which influence a chemical's impact in aquatic ecosystems. It must also be recognised that protection of all individuals and even of all aquatic species may not be achievable or necessary to maintain a healthy ecosystem. Some possible future advances in the determination of water quality standards are suggested.

The impact of inorganic chemicals on water quality and health.

Inorganic substances constitute by far the greatest proportion of chemical contaminants in drinking water. They are present in greatest quantity as a consequence of natural processes but several important contaminants are present as a result of man's activities. Some of the most important even come from the plumbing material through which water is passed. Inorganic contaminants are the most important determinands of acceptability to the consumer, affecting taste, colour and scale deposition on pipes and fittings. They are also demonstrably the most important for health, having both beneficial and adverse effects which have been shown in human populations. This is a brief review of some of the most important inorganic constituents of drinking water covering major elements such as hardness and nitrate and more minor constituents in terms of quantity, such as arsenic, selenium and lead.

Assessment of the human risk associated with the presence of carcinogenic compounds in drinking water.

Both organic and inorganic contaminants which have been implicated in causing cancer in man or, more commonly, in laboratory animals can be found in drinking water. Apart from arsenic there are none for which there is convincing epidemiological evidence of a significant risk to man. However environmental epidemiology is fraught with difficulties. There are also difficulties in interpreting laboratory animal data and extrapolating this to the low concentrations found in drinking water although mathematical models can be very useful if used sensibly. There is a danger that the rather extreme public perception of cancer could lead to over regulation of some contaminants in water, possibly with an increase in risk from other hazards such as microbiological contamination.

Identification and assessment of hazardous compounds in drinking water.

The identification of organic chemicals in drinking water and their assessment in terms of potential hazardous effects are two very different but closely associated tasks. In relation to both continuous low-level background contamination and specific, often high-level, contamination due to pollution incidents, the identification of contaminants is a pre-requisite to evaluation of significant hazards. Even in the case of the rapidly developing short-term bio-assays which are applied to water to indicate a potential genotoxic hazard (for example Ames tests), identification of the active chemicals is becoming a major factor in the further assessment of the response. Techniques for the identification of low concentrations of organic chemicals in drinking water have developed remarkably since the early 1970s and methods based upon gas chromatography-mass spectrometry (GC-MS) have revolutionised qualitative analysis of water. Such techniques are limited to "volatile" chemicals and these usually constitute a small fraction of the total organic material in water. However, in recent years there have been promising developments in techniques for "non-volatile" chemicals in water. Such techniques include combined high-performance liquid chromatography-mass spectrometry (HPLC-MS) and a variety of MS methods, involving, for example, field desorption, fast atom bombardment and thermospray ionisation techniques. In the paper identification techniques in general are reviewed and likely future developments outlined. The assessment of hazards associated with chemicals identified in drinking and related waters usually centres upon toxicology - an applied science which involves numerous disciplines. The paper examines the toxicological information needed, the quality and deployment of such information and discusses future research needs. Application of short-term bio-assays to drinking water is a developing area and one which is closely involved with, and to some extent dependent on, powerful methods of identification. Recent developments are discussed.