Improving risk assessment of phytochemicals

There is good evidence to suggest that certain chemicals, other than nutrients, show a J- or U-shaped dose-response relationship at levels of exposure which are lower than those where there is some impairment of the inherent 

For some toxins it is possible to demonstrate an apparent improvement in functional response at levels of exposure which are below a threshold. This effect, which has been termed hormesis , is most effectively demonstrated in the consistently improved longevity of animals whose caloric intake is restricted rather than allowing them to feed ad lib (Tannenbaum, 1942). Clearly in this instance, the observed effects are the result of exposure to a complex mixture of chemicals whose metabolism determines the total amount of energy available to the organism. But it is also possible to show similar effects when single chemicals such as alcohol (Maclure, 1993), or caffeic acid (Lutz et al., 1997) are administered, as well as for more toxic chemicals such as arsenic (Pisciotto and Graziano, 1980) or even tetrachloro-p-dibenzodioxin (TCDD) ( Huff et al., 1994) when administered at very low doses. It is possible that there are toxins that effect a modest, reversible disruption in homeostasis which results in an over-compensation, and that this is the mechanism of the beneficial effect observed. These effects would not be observed in the animal bioassays since to show them it would be necessary to have at least three dose groups below the NOAEL. In addition, the strain of animal used would have to have a very low incidence of disease to show any effect. 

therefore, perfectly feasible to consider that phytochemicals, at the levels present in foods, are capable of showing a similar dose-response. But, in assessing the benefit-risk associated with intake of a specific level in a food, it is important to establish the responses at doses that are below, or slightly above, the plateau region of the dose-response curve. 

Given the problems associated with using standard animal bioassays and doses above the level where hormetic effects might be observed (which 

2 information about the absorption, distribution, target organ and cellular concentrations of the chemical at similar dose levels  

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