Risk assessment neurotoxins

It is obvious from the provisional risk assessment values for microcystins, and, being of the same order of magnitude of mammalian toxicity, similar values may be calculated for the cyanobacterial neurotoxins, that sensitive detection methods are required to detect these low concentrations of toxins. Of the biological methods of detection discussed earlier, the mouse and invertebrate bioassays are not sensitive enough without concentration of water samples, in that they are only able to detect mg of microcystins per litre. Only the immunoassays (ng-/rg 1 and the protein phosphatase inhibition assays (ng O... 

Recently, there has been a growth of interest in the development of in vitro methods for measuring toxic effects of chemicals on the central nervous system. One approach has been to conduct electrophysiological measurements on slices of the hippocampus and other brain tissues (Noraberg 2004, Kohling et al. 2005). An example of this approach is the extracellular recording of evoked potentials from neocortical slices of rodents and humans (Kohling et al. 2005). This method, which employs a three-dimensional microelectrode array, can demonstrate a loss of evoked potential after treatment of brain tissue with the neurotoxin trimethyltin. Apart from the potential of in vitro methods such as this as biomarkers, there is considerable interest in the use of them as alternative methods in the risk assessment of chemicals, a point that will be returned to in Section 16.8. 

Numerous neurotoxic chemicals have been identified. These include pesticides (particularly, but not limited to, organophosphates and carbamates), aliphatic and aromatic hydrocarbons, alcohols, ethers, ketones, heavy metals (including lead, mercury, manganese, and others), and mixtures of these. Hundreds of individual chemicals are established or suspected neurotoxins. The EPA Guidelines for Neurotoxicity Risk Assessment and the Scorecard list of neurotoxicantsl5 contain partial lists of neurotoxic chemicals. The actual number of chemicals with neurotoxic potential has been estimated to range between 3% and 28% of all the approximately 80,000 chemicals in use (2400-22,400) Clearly, the number of mixtures possible is infinite, though little attention has been devoted to the neurotoxic effects of mixtures. 

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