Insufficient epidemiological data are available to derive a WHO-guideline value or national standards for any of the cyanotoxins. Therefore, the provisional WHO-guideline values or national guideline values (GV) or standards are based on doses that showed no adverse effect in experiments with laboratory animals during many weeks of daily exposure (NOAEL [1]). A TDI (“tolerable daily intake” [2]) is calculated by multiplying the NOAEL with uncertainty factors accounting for the differences between animals and humans as well as for differences in the sensitivity between individuals of the same species (Fig. 1). As for many other substances, a further uncertainty factor is included for lack in knowledge of toxicity over the lifetime of the at-risk organism(s).
Microcystins
For microcystin-LR the World Health Organisation (WHO) applied a total extrapolation/uncertainty factor of 1000 to derive the TDI. The provisional guideline value of the WHO of 1µg/L microcystin-LR has been calculated from the TDI for humans of 60 kg body weight and a consumption of 2 litres of drinking water per day, assuming that 80 % of microcystins are taken up by drinking water.
For other microcystins, no provisional WHO Guideline-values are available, as toxicological data are insufficient for their derivation. Particularly for other frequently occurring microcystins, this is considered unsatisfactory, as often other structural variants contribute the major share of the total microcystins in environmental samples. Some variants show acute toxicity similar to that of Microcystin-LR, others are less toxic. Thus, applying the provisional WHO Guideline-value for Microcystin-LR to all of them is a conservative worst-case approach, but assures a good degree of health protection.
Other toxins
Also, for the derivation of a guideline value for nodularin sufficient toxicological data are lacking. Due to the structural as well as toxicological similarity between nodularins and microcystins, however, the provisional guideline value of microcystin-LR may be used as a first approach.
For cylindrospermopsin a guideline value of 1 µg/L is suggested based on a study of its chronic toxicity and the application of a total uncertainty factor of 1000 as for microcystins. Due to its carcinogenicity, however, a guideline value of 0.1 µg/l for CYN may be more appropriate until unambiguous toxicological data are available (Concept of health-based orientation values, Federal Environmental Agency, Germany). Further toxicological investigations following the OECD protocol are especially needed for the derivation of a WHO guideline value.
Also for the cyanobacterial neurotoxins further toxicological data necessary to derive WHO guideline values. High concentrations causing acute intoxication are rather unlikely in drinking water and data on neurotoxin chronic toxicity are lacking nor does the known mechanisms of action do indicate any; nevertheless, studies are needed to finally clarify the risk due to long-term exposure to these toxins.
The occurrence of other, currently unknown and/or toxicologically not sufficiently assessed cyanobacterial metabolites must be assumed if cyanobacteria proliferate in raw water. However, so far there are no indications that the health hazards posed by these are greater than that those presented by microcystins or cylinrospermopsin. Nevertheless, risk assessment and control should also include exposure to cyanobacterial biomass, rather than relying on the known cyanotoxins alone.
Interpreting Exceedence
Fig. 1: Derivation of the provisional WHO-guideline value for microcystin-LR from animal studies. TDI: Tolerable Daily Intake, NOAEL: No Observed Adverse Effect Level.