THE NAS PERCHLORATE REPORT: UNDERSTANDING THE KEY SCIENTIFIC FINDINGS

The National Academy of Sciences (NAS) Committee to Assess the Health Implications of Perchlorate Ingestion issued its report on January 10. A press release that accompanied the report stated NAS suggests a reference dose for perchlorate that is more than 20 times higher than what U.S. EPA has proposed. It is critical to understand the scientific information behind this conclusion when reviewing and interpreting the report. The highlights below are not intended to be a comprehensive summary of the 192-page report or its conclusions. A complete copy of the NAS report can be viewed at http://lab.nap.edu/nap-cgi/discover.cgi?term=perchlorate&restric;=NAP

NONADVERSE EFFECTS

  • "The committee is recommending using a nonadverse effect rather than an adverse effect as the point of departure for the perchlorate risk assessment. Using a nonadverse effect that is upstream of the adverse effects is a conservative, health protective approach to the perchlorate risk assessment." (p 9)
  • "The committee emphasizes that inhibition of iodide uptake by the thyroid has been the only consistently documented effect of perchlorate exposure in humans." (p 110)
  • "EPA defines changes in serum thyroid hormone and TSH concentrations as adverse effects.." "The committee, however, does not view transient changes in serum thyroid hormone and TSH concentrations as adverse effects, it considers them to be biochemical changes that could precede adverse effects." (p 110)
  • "Inhibition of iodide uptake by the thyroid clearly is not an adverse effect; however, if it does not occur, there is no progression to adverse effects. The committee views its recommendation to use inhibition of iodide uptake by the thyroid as the basis of the perchlorate risk assessment to be the most health protective and scientifically valid approach." (p 111)
  • "The committee recommends using the data from Greer, et al. for derivation of the reference dose." "the study identified a no observed effect level (NOEL) for inhibition of iodide by the thyroid at .007 mg/kg per day." (p 113)
  • "That the no observed effect level (NOEL) value from Greer, et al. (2002) is a health-protective and conservative point of departure is supported by the results of a 4-week study of higher doses in normal subjects (Brabant, et al. 1992) and extensive human and animal data that demonstrates that there will be no progression to adverse effects if no inhibition of iodide uptake occurs." (p 114)
  • "The committee notes that effects downstream of inhibition of iodide uptake by the thyroid have not been clearly demonstrated in any human populations exposed to perchlorate, even at doses as high as 0.5 mg/kg per day." (p 118)

ADVERSE EFFECTS

  • "The committee concludes that the first adverse effect in the continuum would be hypothyroidism." (p 8)
  • ".the perchlorate dose required to cause hypothyroidism in adults would probably be more than 0.40 mg/kg per day, assuming a 70-kg body weight." (p 4, 44) "In pregnant women, infants and children, and people who have a low iodide intake or pre-existing thyroid dysfunction, the dose required to cause a decrease in thyroid hormone production may be lower. However, a dose that does not inhibit thyroid iodide uptake will not affect thyroid function, even in subjects with an abnormal thyroid function or a very low iodide intake." (p 44)
  • "On the basis of the data reviewed, the committee concludes that perchlorate is very unlikely to have toxicologic effects at doses lower than those which would affect thyroid function." (p 99)
  • "However, hypothyroidism should not be used as the basis of the risk assessment. The committee recommends that inhibition of iodide uptake by the thyroid, a nonadverse effect, be used as the point of departure in the perchlorate risk assessment." (p 118,119)

CANCER

  • "The committee concludes that the thyroid tumors ins the (rat) offspring were most likely treatment-related but that thyroid cancer in humans resulting from perchlorate exposure is unlikely because of the hormonally mediated mode of action and species differences (between humans and rats) in thyroid function." (p 7)
  • "The committee notes, however, that on the basis of its understanding of the biology of human and rodent thyroid tumors, it is unlikely that perchlorate poses a risk of thyroid cancer in humans." (p 73)
  • "It is unlikely that perchlorate poses a risk of cancer in humans." (p 95)
  • "Specifically, the development of thyroid tumors as an ultimate result of perchlorate exposures is an unlikely outcome in humans." (p 109)

RATS VS. HUMANS

  • "Most experimental studies in animals designed to characterize the effects of perchlorate exposure have been done in rats. However, rats are much more sensitive to agents that disturb thyroid function than are humans, so the relevance of rat studies in quantitative terms to humans is limited." (p 100)
  • "Humans are much less susceptible than rats to disruption of thyroid function and therefore are not likely to develop thyroid tumors as a result of thyroid exposures." (p 109)
  • "Human or animal data can be used (in deriving a Reference Dose) but human data are preferred when sufficient data are available (EPA 2002b)." (p 112)
  • "For several reasons, the committee does not think that the animal data or the outcomes selected by EPA should be used as the basis of the perchlorate risk assessment." (p 112)
  • "The committee reviewed the human and animal data and found that the human data provided a more reliable point of departure for the risk assessment than the animal data." (p 113)

ADDITIONAL STUDIES

  • "The committee acknowledges that the reference dose (RfD) may need to be adjusted upward or downward on the basis of future research, such as that suggested in this report." "Although the committee found that available data are sufficient to derive a reference dose for perchlorate, new research could provide a more complete understanding of the array of effects of perchlorate, especially regarding the effects of chronic exposure and the effects on sensitive populations." (pp 10-11)
  • See chapter six for full descriptions of additional clinical, toxicology, in vitro and epidemiologic studies suggested (pp 122-131).

SENSITIVE POPULATIONS

  • "In weighing the scientific evidence on perchlorate exposure, the committee emphasized studies with the soundest scientific methods and studies that included biologically sensitive groups, such as pregnant women, fetuses and neonates." (p 50)