Health Stream Literature Summary - Issue 50 - June 2008

Human health risk assessment related to cyanotoxins exposure
Funari, E. and Testai, E. (2008) Critical Reviews in Toxicology, 38(2); 97-125.

This article focuses on evaluating the risk for human health associated with the different sources and routes of exposure to cyanotoxins. These toxins can be classified according to their biological effects on the systems and organs that they affect most strongly including: hepatotoxins, neurotoxins, cytotoxins, irritants and gastrointestinal toxins, and other cyanotoxins whose toxicological or ecotoxicological profile is still only partially known. Each cyanotoxin can be produced by more than one cyanobacterial species; similarly the same species is able to produce more than one toxin. Within a single species, different genotypes occur and some of these possess the genes for production of a given toxin and others do not. Depending on the nature of the toxin and the growth stage, cyanotoxins may be localised both within the cyanobacterial cells and/or dissolved in the water. The highest total amounts of cyanotoxin levels have been found in blooms and scums. When released in the water, cyanotoxins can persist in the environment dependant on the efficiency of degradation. The two cyanotoxins microcystins (MC) and nodularins (NODs) can persist in water for relatively long periods of time ranging from 21 days to 2-3 months, and up to 6 months in dry scum.

Humans may be exposed to cyanotoxins through several routes however the oral route is the most important when consumption of contaminated drinking water or food (including supplements) occurs, or water is ingested during recreational activities. Dermal and inhalation exposure may also occur during recreational, sport or professional activities (i.e. fishing) in infested waters, or domestically when showering. The other possible route of exposure is when water from contaminated superficial water bodies has been used for haemodialysis without adequate purification.

The occurrence of cyanotoxins in drinking water depends on their level in raw surface water and the effectiveness of treatment methods for removing cyanobacteria and cyanotoxins. There may be both acute/short term effects and chronic effects occurring in humans depending on the levels of cyanotoxin in drinking water. Acute/short term effects are associated with consumption of raw waters infested by cyanobacteria or with high cyanotoxin dissolved concentrations in drinking water which may be due to either the breakdown of a natural cyanobacterial bloom or it artificial lysis followed by the failure of water treatment. Acute/short term effects can be prevented with adequate treatments that strongly reduce both cell number (greater than 99%) and dissolved cyanotoxins. Chronic effects are difficult to identify and demonstrate with information from epidemiological studies often scare and inconclusive because cyanotoxins were not proven to be the actual cause of the effects observed but just the most likely one. Even though the epidemiological data is not conclusive, toxicological data can be of benefit for some cyanotoxins at least to evaluate the risk associated with contaminated drinking water consumption. Toxicological data can also be used for defining safe concentrations regarding the acute risk. To manage the possible health problems, some countries have proposed guideline values or adopted mandatory regulatory requirements.

Recreational activities may represent a source of exposure to cyanobacteria and their products via direct contact, inhalation and/or ingestion. Where cyanobacterial blooms are transient, these exposures are not likely to be associated with a chronic risk however in regions where cyanobacterial blooms persist and there are intensive recreation activities, subacute/sub-chronic exposure may become a public health issue. A range of diverse symptoms is associated with exposure to cyanobacteria in recreational settings. Serious illnesses have been reported with symptoms such as severe headache, pneumonia, fever, myalgia, vertigo and blistering in the mouth. Cutaneous effects and symptoms such as rhinitis, conjunctivitis, respiratory symptoms, asthma and urticaria have also been reported. On the basis of anecdotal, epidemiological and toxicological data, it appears that the risk of severe effects for bathers is posed only when cyanobacteria bloom or form scums. The WHO has provided guidelines for preventing the risk from irritating and more severe effects.

There are a number of gaps in the literature and additional efforts are required to describe the patterns of cyanotoxins occurrence and related levels of exposure for the population; to identify possible "new" cyanotoxins; to discover the influence of environmental factors on cyanotoxin production; and to identify repeated-dose toxicity for cyanotoxins other than microcystin-LR, for the derivation of guidance values and regulatory limits.

There are some other specific issues that have not received much attention. Knowledge of the toxicokinetic properties of different cyanotoxins and congeners is required when data is extrapolated from experimental animals to humans during the risk assessment processes. However such information is scant and limited to MCs. There are other susceptibility factors that can modulate the outcome of cyanotoxin exposure in humans including differential exposure (e.g. children drinking a higher water volume in proportion to their body weights) and /or pathological status (e.g. people with injury to liver and kidney, target organs of cyanotoxin action, could be more susceptible than healthy people). Genetic polymorphisms in the human population may affect susceptibility to cyanotoxins. Blooms are often characterised by the presence of a mixture of cyanotoxins and therefore combined exposure represents probably the rule than the exception. Interactions between different cyanotoxins can occur and this needs to be investigated. Also concomitant exposure with other chemicals such as products intended for human health, including drugs, needs to be considered in cases in which interactions are predicted. Another issue that needs more research is the postulated protective action of alcohol consumption on paralytic shellfish poisoning toxicity from saxitoxins.