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Health Implications of Perchlorate Ingestion
FIGURE 5-1 Committee’s suggested mode-of-action model of perchlorate toxicity in humans. Solid arrows represent outcomes that have been observed in humans during perchlorate exposure. Dashed arrows represent outcomes that have not been clearly demonstrated in humans exposed to perchlorate but that are biologically possible in the absence of adequate compensation. The thyroid response to increased serum TSH and an independent increase in thyroid iodide uptake would raise T3 and T4 production to normal and therefore usually prevent the later steps from occurring.
viewed as adverse” (see EPA 2002a, p. 7-10). The committee, however, does not view transient changes in serum thyroid hormone and TSH concentrations as adverse health effects; it considers them to be biochemical changes that could precede adverse effects. Given its mode-of-action model, the committee concludes that hypothyroidism is the first adverse effect in the mode-of-action model (see Figure 5-2). Any effects downstream of hypothyroidism clearly would be adverse.
EPA developed its risk assessment by using data on effects that it views as adverse. However, the committee does not think that hypothyroidism—the effect that the committee views as adverse—should be used as the basis of a perchlorate risk assessment. It recommends that the key biochemical event be used as the basis of the perchlorate risk assessment. EPA and the committee agree that the key event in the continuum of possible effects of perchlorate exposure is the inhibition of iodide uptake by the thyroid. It is the obligatory initial step in the continuum of possible effects of perchlorate exposure, and thyroid uptake of iodide (as radioiodide) can be measured easily and reliably. Inhibition of iodide uptake by the thyroid clearly is not an adverse effect; however, if it does not occur, there is no progression to