The NAS perchlorate review: adverse effects?

Ginsberg and Rice (2005) argued that the regard dose for perchlorate of 00007 mg/kg for day recommended by the National Academy of Sciences (NAS) Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree.

Ginsberg and Rice (2005) based their conclusion upon three points. The first involves the designation of the point of departure as a NOEL (no observ event level) versus a LOAEL (lowest observ adverse issue level). The committee chose as its point of departure a dose of perchlorate (0007 mg/kg by day) that, when given for 14 days to seven normal bring under rules did not cause a statistically significant decrease in the clump mean thyroid iodide uptake (Greet et al. 2002) Accordingly, the committee considered it a NOEL. Ginsberg and Rice (2005) focused upon the fact that only seven subdues were given that dose; they strike one as being to say that attention should be paid single to the results in those bring under rules in whom there was a decrease in thyroid iodide uptake and that the ensues in those in whom there was no decrease or an increase should be ignored. They considered the dose to be a LOAEL because of the decrease in uptake in those not many subjects. It is important to note that a statistically significant decrease of for example, 5% or flat 10% would not be biologically important and, more important, would not be sustained. For example, in another close attention (Braverman et al. 2004), administration of 004 mg/kg by day to normal subjects for 6 month had no consequence on thyroid iodide uptake when measured at 3 and 6 month and no consequence on serum thyroid hormone or thyrotropin concentrations measured monthly [Inspection of Figure 5A in address et al. (2002) suggests that this dose would inhibit thyroid iodide uptake by means of about 25% if measured at 2 weeks.]

The next to the first issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal make submissives for 2 weeks to 6 month In individual study (Brabant et al. 1992) a dose of 92 mg/kg through day for 4 weeks had no result on thyroid function. In occupational studies, doses as high as 05 mg/kg for day had no effect upon thyroid hormone or thyrotropin production in workers. In epidemiologic studies, there were no abnormalities in increase or thyroid function in children expos life-long to 100-120 [micro]g perchlorate for liter of drinking water, or in pregnant women and newborn infants similarly expos Given the choice of a nonadverse consequence (inhibition of iodide uptake by the agency of the thyroid) as the point of departure and the multiple studies in which doses of perchlorate a great deal of higher than 0.007 mg/kg by means of day had no effect upon any aspect of thyroid function, the committee did not apply a database uncertainty factor.

Finally, Ginsberg and Rice (2005) argued that inhibition of thyroid iodide uptake is adverse. That conclusion assumes that any acute inhibition would be sustained, with equal reason thyroid hormone production would decrease. That is not the case. There is remarkable compensation for plane substantial reductions in thyroid iodide uptake and thyroid hormone production. As noted above, make subordinates given 0.04 mg/kg per day for 6 month and 92 mg/kg through day for 4 weeks--doses that certainly would inhibit thyroid iodide uptake for a hardly any weeks--had no decrease in serum thyroid hormone or increase in serum thyrotropin concentrations (the hallmark of flat mild hypothyroidism). Short-term inhibition of thyroid iodide uptake is not an adverse effect; it has no adverse issues because there is rapid compensation mediated through several independent processes. One of these processe is up-regulation of the thyroid sodium-iodide transport combination of parts to form a whole as a result of intrathyroidal iodide deficiency. The next to the first should there be even a true small decrease in thyroid hormone production, is an increase in thyrotropin secretion, resulting in overall stimulation of the thyroid gland. Analyses of the results of any substance on thyroid function must take these compensatory processe into account, particularly the fact that the event of any substance that inhibits thyroid function will diminish with time. sole if all of these mechanisms fail will there be hypothyroidism, the first adverse result in the continuum of issues resulting from perchlorate ingestion. If there is no inhibition of iodide uptake to begin with, there will be no other changes in thyroid function at any time.

We believe that the committee's approveed reference dose of 0.0007 mg/kg through day provides a wide margin of safety for all controls of all ages.

The authors declare they have no competing financial interests.

REFERENCES

Brabant G Bergmann P Kirsch CM Kohrle J Hesch RD yon zur Muhlen A. 1992 Early adaptation of thyrotropin and thyroglobulin secretion to experimentally decreased iodide store in man. Metabolism 4l:1093-1096.

Braverman LE He X Pino s Magnani B, Firek A. 2004 The event of low dose perchlorate upon thyroid function in normal presents [Abstract]. Thyroid 14:691.